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.

2015-10-01

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.

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.

Reminiscences of a journeyman scientist: studies of thermoregulation in non-human primates and humans.

Science.gov (United States)

Adair, Eleanor Reed

2008-12-01

After graduating from Mount Holyoke College in 1948 where I majored in experimental psychology I worked at the College for 2 years with the Johns Hopkins Thermophysiological Unit. My graduate work later at the University of Wisconsin, centering on sensory psychology, culminated in my 1955 PhD thesis on human dark adaptation. I continued work in sensory psychology later with Neal Miller at Yale and then moved to the John B. Pierce Foundation--a Yale affiliate--where I began the studies of thermoregulation that constitute the center of my scientific career. Those studies were largely--later wholly--conducted using microwave energy as a thermal load and were thus published in Bioelectromagnetics even as I played an active role in the Bioelectromagnetics Society. In the beginning this work was centered on the responses of Squirrel Monkeys to thermal loads. Later, serving as Senior Scientist at the Air Force Research Laboratory at San Antonio, I completed an extensive analysis of thermal regulation in humans. I consider this work of special note inasmuch as the extraordinary human thermoregulatory ability was surely among the attributes that were paramount in initially separating humans from the other anthropoid primates.

Thermal and metabolic responses of military divers during a 6-hour static dive in cold water.

Science.gov (United States)

Riera, Florence; Horr, Reed; Xu, Xiaojiang; Melin, Bruno; Regnard, Jacques; Bourdon, Lionel

2014-05-01

Human thermal responses during prolonged whole-body immersion in cold water are of interest for the military, especially French SEALS. This study aims at describing the thermo-physiological responses. There were 10 male military divers who were randomly assigned to a full immersion in neutral (34 degrees C), moderately cold (18 degrees C), and cold (10 degrees C) water wearing their operational protective devices (5.5 mm wetsuit with 3.0 mm thick underwear) for 6 h in a static position. Rectal temperature (T(re)) and 14 skin temperatures (T(sk)), blood analysis (stress biomarkers, metabolic substrates), and oxygen consumption (Vo2) were collected. At 34 degrees C, there were no significant modifications of the thermo-physiological responses over time. The most interesting result was that rates of rectal temperature decrease (0.15 +/- 0.02 degrees C x min(-1)) were the same between the two cold stress experimental conditions (at 18 degrees C and 10 degrees C). At the final experiment, rectal temperature was not significantly different between the two cold stress experimental conditions. Mean T(sk) decreased significantly during the first 3 h of immersion and then stabilized at a lower level at 10 degrees C (25.6 +/- 0.8 degrees C) than at 18 degrees C (29.3 +/- 0.9 degrees C). Other results demonstrate that the well-trained subjects developed effective physiological reactions. However, these reactions are consistently too low to counterbalance the heat losses induced by cold temperature conditions and long-duration immersion. This study shows that providing divers with thermal protection is efficient for a long-duration immersion from a medical point of view, but not from an operational one when skin extremities were taken into account.

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.

2015-01-01

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

Thermal sensation and thermophysiological responses with metabolic step-changes

DEFF Research Database (Denmark)

Goto, Tomonobu; Toftum, Jørn; deDear, Richard

2006-01-01

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...... average metabolic rate with varying activity levels, e.g. for the prediction of thermal sensation by steady-state comfort models. The activity during the most recent 5 min should be weighted 65%, during the prior 10-5 min 25% and during the prior 20-10 min 10%....

The effect of the relation between radiation and convection on comfort and energy consumption. Invloed van de verhouding tussen straling en convectie op comfort en energiegebruik; Literatuurstudie

Energy Technology Data Exchange (ETDEWEB)

Vrins, E.; De Haas, F.

1987-10-01

Within the framework of the program 'Local Heating' a literature search was carried out. The search was aimed at the title subject. On the one hand the approach is the thermophysiology of human beings and the indoor climate perception, on the other hand the system and the effect of the system on the indoor climate. The thermophysiology of human beings sets demands to the indoor climate. In what way a system can fulfill these demands and which impact it has on the energy consumption in a certain space are questions for which answers are searched in the literature. Recommendations are formulated to complete lacking knowledge. 28 figs., 6 tabs., 96 refs., 2 apps.

The effect of the relation between radiation and convection on comfort and energy consumption. Invloed van de verhouding tussen straling en convectie op comfort en energiegebruik; Literatuurstudie

Energy Technology Data Exchange (ETDEWEB)

Vrins, E.; De Haas, F.

1987-10-01

Within the framework of the program 'Local Heating' a literature search was carried out. The search was aimed at the title subject. On the one hand the approach is the thermophysiology of human beings and the indoor climate perception, on the other hand the system and the effect of the system on the indoor climate. The thermophysiology of human beings sets demands to the indoor climate. In what way a system can fulfill these demands and which impact it has on the energy consumption in a certain space are questions for which answers are searched in the literature. Recommendations are formulated to complete lacking knowledge. 28 figs., 6 tabs., 96 refs., 2 apps.

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

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.

Urban physics

NARCIS (Netherlands)

Blocken, B.J.E.

2012-01-01

Urban Physics is the multiscale and interdisciplinary research area dealing with physical processes in urban environments that influence our everyday health, comfort and productivity. It involves disciplines ranging from mesoscale meteorology to human thermophysiology. The introductory lecture

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.

Computational estimation of decline in sweating in the elderly from measured body temperatures and sweating for passive heat exposure

International Nuclear Information System (INIS)

Hirata, Akimasa; Nomura, Tomoki; Laakso, Ilkka

2012-01-01

Several studies reported the difference in heat tolerance between younger and older adults, which may be attributable to the decline in the sweating rate. One of the studies suggested a hypothesis that the dominant factor causing the decline in sweating was the decline in thermal sensitivity due to a weaker signal from the periphery to the regulatory centres. However, no quantitative investigation of the skin temperature threshold for activating the sweating has been conducted in previous studies. In this study, we developed a computational code to simulate the time evolution of the temperature variation and sweating in realistic human models under heat exposure, in part by comparing the computational results with measured data from younger and older adults. Based on our computational results, the difference in the threshold temperatures for activating the thermophysiological response, especially for sweating, is examined between older and younger adults. The threshold for activating sweating in older individuals was found to be about 1.5 °C higher than that in younger individuals. However, our computation did not suggest that it was possible to evaluate the central alteration with ageing by comparing the computation with the measurements for passive heat exposure, since the sweating rate is marginally affected by core temperature elevation at least for the scenarios considered here. The computational technique developed herein is useful for understanding the thermophysiological response of older individuals from measured data. (note)

Behavioural responses to human-induced environmental change.

Science.gov (United States)

Tuomainen, Ulla; Candolin, Ulrika

2011-08-01

The initial response of individuals to human-induced environmental change is often behavioural. This can improve the performance of individuals under sudden, large-scale perturbations and maintain viable populations. The response can also give additional time for genetic changes to arise and, hence, facilitate adaptation to new conditions. On the other hand, maladaptive responses, which reduce individual fitness, may occur when individuals encounter conditions that the population has not experienced during its evolutionary history, which can decrease population viability. A growing number of studies find human disturbances to induce behavioural responses, both directly and by altering factors that influence fitness. Common causes of behavioural responses are changes in the transmission of information, the concentration of endocrine disrupters, the availability of resources, the possibility of dispersal, and the abundance of interacting species. Frequent responses are alterations in habitat choice, movements, foraging, social behaviour and reproductive behaviour. Behavioural responses depend on the genetically determined reaction norm of the individuals, which evolves over generations. Populations first respond with individual behavioural plasticity, whereafter changes may arise through innovations and the social transmission of behavioural patterns within and across generations, and, finally, by evolution of the behavioural response over generations. Only a restricted number of species show behavioural adaptations that make them thrive in severely disturbed environments. Hence, rapid human-induced disturbances often decrease the diversity of native species, while facilitating the spread of invasive species with highly plastic behaviours. Consequently, behavioural responses to human-induced environmental change can have profound effects on the distribution, adaptation, speciation and extinction of populations and, hence, on biodiversity. A better understanding of

Human-biometeorological conditions and thermal perception in a Mediterranean coastal park

Science.gov (United States)

Saaroni, Hadas; Pearlmutter, David; Hatuka, Tali

2015-10-01

This study looks at the interrelation of human-biometeorological conditions, physiological thermal stress and subjective thermal perception in the design and use of a new waterfront park in Tel-Aviv, Israel. Our initial assumption was that the park's design would embody a comprehensive response to the area's ever-increasing heat stress and water shortage. However, almost half of it is covered by grass lawns, irrigated with fresh water, while the remaining area is mainly covered with concrete paving, with minimal shading and sparse trees. We hypothesized that stressful thermal conditions would prevail in the park in the summer season and would be expressed in a high discomfort perception of its users. Thermo-physiological stress conditions in a typical summer month were compared with the subjective comfort perceptions of pedestrians surveyed in the park. It was found that even during mid-day hours, the level of thermal stress tends to be relatively mild, owing largely to the strong sea breeze and despite the high intensity of solar radiation. Moreover, it appears that the largely favorable perception of comfort among individuals may also result from socio-cultural aspects related to their satisfaction with the park's aesthetic attractiveness and in fact its very existence. Adaptive planning is proposed for such vulnerable regions, which are expected to experience further aggravation in thermal comfort due to global as well as localized warming trends.

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.

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....

Ovarian response to recombinant human follicle-stimulating hormone

DEFF Research Database (Denmark)

Arce, Joan-Carles; Andersen, Anders Nyboe; Fernández-Sánchez, Manuel

2014-01-01

OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrat......OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH...

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.

Aversive Pavlovian responses affect human instrumental motor performance

Directory of Open Access Journals (Sweden)

Francesco eRigoli

2012-10-01

Full Text Available In neuroscience and psychology, an influential perspective distinguishes between two kinds of behavioural 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 behavioural 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 behaviour, and psychopathology.

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

African Journals Online (AJOL)

This view of the company is often described under the concept of corporate social responsibility. This Paper assesses the nature of corporate social responsibility in Ghana primarily focusing on the mining industry. The Paper outlines the various human rights and mineral rights in Ghana and the effects of mining on human ...

Impact of socially responsible human resources policies on intellectual capital

Directory of Open Access Journals (Sweden)

Jesus Barrena-Martínez

2016-03-01

Full Text Available Purpose: This research focuses on the benefits that social responsibility can report on the area of human resources, examined the impact of a socially responsible configuration of human resource policies and practices in the generation value process for the company, and more specifically in its intellectual capital. Design/methodology/approach: The study performed a regression analysis, testing the individual effects of socially responsible human resource policies on intellectual capital, broken down into three main variables such as human, social and organizational capital. Findings: The results shed light on how the introduction of socially responsible aspects in the management of human resources can facilitate the exchange of knowledge, skills and attitudes human--capital; lead to improvements in communication, trust, cooperation among employees social-capital and, in turn, generates an institutionalized knowledge encoded in the own organizational culture –organizational capital–. Research limitations/implications: The study only provides information from large companies with over 250 employees. Practical implications: There are important implications in the measure of corporate social responsibility concerns in the area of human resources. Social implications: Also important intangible effects on non-economic variables are confirmed, such as intellectual capital. Originality/value: The value of the study lies in its novelty, testing socially responsible configurations of human resources as well as the direct effects of different policies on intellectual capital.

[Bartonellosis. II. Other Bartonella responsible for human diseases].

Science.gov (United States)

Piémont, Y; Heller, R

1999-01-01

In addition to Bartonella henselae, five other Bartonella species were involved in human pathology. As for B. henselae, ectoparasites seem to be responsible for the transmission of most or all these bacterial species. B. bacilliformis is responsible for Carrion's disease that occurs in some valleys of Colombia, Ecuador and Peru. This disease is transmitted by biting of infected sandflies. The bacterial reservoir is constituted by humans only. That disease occurs either as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of the bacterium exist. Trench fever was described during the First World War. This non-lethal disease is constituted of recurrent febrile attacks associated particularly with osseous pains. The causative agent of the disease is B. quintana, transmitted by the body louse. Humans seem to be the reservoir of that bacterium. In some patients, B. quintana can be responsible for endocarditis, bacillary angiomatosis and chronic or recurrent bacteremia. Other human infections due to Bartonella sp. have been described: B. vinsonii, isolated from blood of small rodents, and B. elizabethae, the reservoir of which is currently unknown, can be responsible for endocardites. B. clarridgeiae (isolated from blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat scratch disease. All these bartonelloses are diagnosed by non-standard blood culture or by in vitro DNA amplification or by serological testing. Their treatment requires tetracyclines or chloramphenicol or macrolides.

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…

Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

Science.gov (United States)

Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

2017-06-01

Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Physiological Responses to Acute and Chronic Cold Exposure

Science.gov (United States)

Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

2001-01-01

When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

Biothermal conditions on Mt. Zlatibor based on thermophysiological indices

OpenAIRE

Pecelj Milica; Đorđević Aleksandar; Pecelj Milovan R.; Pecelj-Purković Jelena; Filipović Dejan; Šećerov Velimir

2017-01-01

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...

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…

Simultaneous chromatic and luminance human electroretinogram responses.

Science.gov (United States)

Parry, Neil R A; Murray, Ian J; Panorgias, Athanasios; McKeefry, Declan J; Lee, Barry B; Kremers, Jan

2012-07-01

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

24 CFR 7.14 - Responsibilities of the Office of Human Resources.

Science.gov (United States)

2010-04-01

... Human Resources. 7.14 Section 7.14 Housing and Urban Development Office of the Secretary, Department of... Reprisal Responsibilities § 7.14 Responsibilities of the Office of Human Resources. In accordance with guidelines issued by the Assistant Secretary for Administration, Human Resources Officers shall: (a) Appraise...

Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system.

Science.gov (United States)

Cheng, Liang; Zhang, Zheng; Li, Guangming; Li, Feng; Wang, Li; Zhang, Liguo; Zurawski, Sandra M; Zurawski, Gerard; Levy, Yves; Su, Lishan

2017-10-27

TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro. For example, CpG-A was most efficient to induce IFN-α production in vitro. In contrast, CpG-B, R848 and Poly I:C stimulated much more IFN-α than CpG-A in vivo. Importantly, the human innate immune response to specific TLR-Ls in humanized mice was different from that reported in C57BL/6 mice, but similar to that reported in nonhuman primates. Furthermore, we found that different TLR-Ls distinctively activated and mobilized human plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs) and monocytes in different organs. Finally, we showed that, as adjuvants, CpG-B, R848 and Poly I:C can all enhance antigen specific CD4 + T cell response, while only R848 and Poly I:C induced CD8 + cytotoxic T cells response to a CD40-targeting HIV vaccine in humanized mice, correlated with their ability to activate human mDCs but not pDCs. We conclude that humanized mice serve as a highly relevant model to evaluate and rank the human immunologic effects of novel adjuvants in vivo prior to testing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human rights responsibilities of pharmaceutical companies in relation to access to medicines.

Science.gov (United States)

Lee, Joo-Young; Hunt, Paul

2012-01-01

Although access to medicines is a vital feature of the right to the highest attainable standard of health ("right to health"), almost two billion people lack access to essential medicines, leading to immense avoidable suffering. While the human rights responsibility to provide access to medicines lies mainly with States, pharmaceutical companies also have human rights responsibilities in relation to access to medicines. This article provides an introduction to these responsibilities. It briefly outlines the new UN Guiding Principles on Business and Human Rights and places the human rights responsibilities of pharmaceutical companies in this context. The authors draw from the work of the first UN Special Rapporteur on the right to the highest attainable standard of health, in particular the Human Rights Guidelines for Pharmaceutical Companies in Relation to Access to Medicines that he presented to the UN General Assembly in 2008, and his UN report on GlaxoSmithKline (GSK). While the Guiding Principles on Business and Human Rights are general human rights standards applicable to all business entities, the Human Rights Guidelines for Pharmaceutical Companies consider the specific human rights responsibilities of one sector (pharmaceutical companies) in relation to one area of activity (access to medicines). The article signals the human rights responsibilities of all pharmaceutical companies, with particular attention to patent-holding pharmaceutical companies. Adopting a right-to-health "lens," the article discusses GSK and accountability. The authors argue that human rights should shape pharmaceutical companies' policies, and provide standards in relation to which pharmaceutical companies could, and should, be held accountable. They conclude that it is now crucial to devise independent, accessible, transparent, and effective mechanisms to monitor pharmaceutical companies and hold them publicly accountable for their human rights responsibilities. © 2012 American

[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

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.

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.

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

Human mammary cell lines are extensively used for preclinical safety assessment of insulin analogs. However, it is essentially unknown how mitogenic responses can be optimized in mammary cell-based systems. We developed an insulin mitogenicity assay in MCF-7 human mammary adenocarcinoma cells......, under low serum (0.1% FCS) and phenol red-free conditions, with 3H thymidine incorporation as endpoint. Based on EC50 values determined from 10-fold dilution series, beta-estradiol was the most potent mitogen, followed by human IGF-1, human AspB10 insulin and native human insulin. AspB10 insulin...... 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...

In vivo response of Mesocestoides vogae to human insulin.

Science.gov (United States)

Canclini, L; Esteves, A

2009-02-01

Successful host invasion by parasitic helminths involves detection and appropriate response to a range of host-derived signals. Insulin signal response pathways are ancient and highly-conserved throughout the metazoans. However, very little is known about helminth insulin signalling and the potential role it may play in host-parasite interactions. The response of Mesocestoides vogae (Cestoda: Cyclophyllidea) larvae to human insulin was investigated, focusing on tyrosine-phosphorylation status, glucose content, survival and asexual reproduction rate. Parasite larvae were challenged with different levels of insulin for variable periods. The parameters tested were influenced by human insulin, and suggested a host-parasite molecular dialogue.

How Well Does the Latest Anthropomorphic Test Device Mimic Human Impact Responses?

Science.gov (United States)

Newby, Nate; Somers, Jeff; Caldewll, Erin; Gernhardt, Michael

2014-01-01

One of the goals of the NASA Occupant Protection Group is to understand the human tolerance to dynamic loading. This knowledge has to come through indirect approaches such as existing human response databases, anthropometric test devices (ATD), animal testing, post-­-mortem human subjects, and models. This study investigated the biofidelity of the National Highway Traffic Safety Administration's ATD named the THOR (test device for human occupant restraint). If THOR responds comparably to humans, then it could potentially be used as a human surrogate to help validate space vehicle requirements for occupant protection. The THOR responses to frontal and spinal impacts (ranging from 8 to 12 G with rise times of 40, 70, and 100 ms) were measured and compared to human volunteer responses (95 trials in frontal and 58 in spinal) previously collected by the U. S. Air Force on the same horizontal impact accelerator. The impact acceleration profiles tested are within the expected range of multi-­-purpose crew vehicle (MPCV) landing dynamics. A correlation score was calculated for each THOR to human comparison using CORA (CORrelation and Analysis) software. A two-­-parameter beta distribution model fit was obtained for each dependent variable using maximum likelihood estimation. For frontal impacts, the THOR head x-­-acceleration peak response correlated with the human response at 8 and 10-­-G 100 ms but not 10-­-G 70 ms. The phase lagged the human response. Head z-­-acceleration was not correlated. Chest x-­-acceleration was in phase, had a higher peak response, and was well correlated with lighter subjects (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126 kg). Head x-­-displacement had a leading phase. Several subjects responded with the same peak displacement but the mean of the group was lower. The shoulder x-­-displacement was in phase but had higher peaks than the human response. For spinal impacts, the THOR head x-­-acceleration was not well correlated. Head and

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…

Human Resource Management and Corporate Social Responsibility

OpenAIRE

Bujor Anca Liliana

2012-01-01

The current context of economic development, the transformations that are subject to national and international organizations impose their traditional attitude change in relation to results and performance of current activity. In this context, the Corporate Social Responsibility (CSR) aims to achieve economic success in an ethical manner with respect for people, communities and environment. This article analyses the concept of Corporate Social Responsibility in relation to Human Resources (HR...

Immune responses to implanted human collagen graft in rats

International Nuclear Information System (INIS)

Quteish, D.; Dolby, A.E.

1991-01-01

Immunity to collagen implants may be mediated by cellular and humoral immune responses. To examine the possibility of such immunological reactivity and crossreactivity to collagen, 39 Sprague-Dawley rats (female, 10 weeks old, approximately 250 g wt) were implanted subcutaneously at thigh sites with crosslinked, freeze-dried human placental type I collagen grafts (4x4x2 mm) which had been irradiated (520 Gray) or left untreated. Blood was obtained by intracardiac sampling prior to implantation or from normal rats, and at various times afterwards when the animals were sacrificed. The sera from these animals were examined for circulating antibodies to human, bovine and rat tail (type I) collagens by enzyme-linked immunosorbent assay (ELISA). Also, the lymphoblastogenic responses of spleen lymphocytes from the irradiated collagen-implanted animals were assessed in culture by measuring thymidine uptake with autologous and normal rat sera in the presence of human bovine type I collagens. Implantation of the irradiated and non-irradiated collagen graft in rats led to a significant increase in the level of circulating antibodies to human collagen. Also antibody to bovine and rat tail collagens was detectable in the animals implanted with irradiated collagen grafts but at a lower level than the human collagen. There was a raised lymphoblastogenic response to both human and bovine collagens. The antibody level and lymphoblastogenesis to the tested collagens gradually decreased towards the end of the post-implantation period. (author)

Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure

International Nuclear Information System (INIS)

Laakso, Ilkka; Hirata, Akimasa

2011-01-01

Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters—some of which may be subject to considerable uncertainty—that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg −1 .

Information-integration category learning and the human uncertainty response.

Science.gov (United States)

Paul, Erick J; Boomer, Joseph; Smith, J David; Ashby, F Gregory

2011-04-01

The human response to uncertainty has been well studied in tasks requiring attention and declarative memory systems. However, uncertainty monitoring and control have not been studied in multi-dimensional, information-integration categorization tasks that rely on non-declarative procedural memory. Three experiments are described that investigated the human uncertainty response in such tasks. Experiment 1 showed that following standard categorization training, uncertainty responding was similar in information-integration tasks and rule-based tasks requiring declarative memory. In Experiment 2, however, uncertainty responding in untrained information-integration tasks impaired the ability of many participants to master those tasks. Finally, Experiment 3 showed that the deficit observed in Experiment 2 was not because of the uncertainty response option per se, but rather because the uncertainty response provided participants a mechanism via which to eliminate stimuli that were inconsistent with a simple declarative response strategy. These results are considered in the light of recent models of category learning and metacognition.

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....

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.

Human sexual response.

Science.gov (United States)

Basson, Rosemary

2015-01-01

The human sexual response to sexually arousing stimuli is a motivational incentive-based cycle comprising subjective experience and physiologic changes. Clinical and empirical data support a circular model of overlapping phases of variable order. Brain imaging data of sexual arousal identify areas of cerebral activation and inhibition reflecting a complex network of cognitive, motivational, emotional, and autonomic components. Psychologic and biologic factors influence the brain's appraisal and processing of sexual stimuli to allow or disallow subsequent arousal. The sexual and non-sexual outcomes influence motivation to future sexual intimacy. Variability is marked both between individuals and within a person's sexual life, influenced by multiple factors, including stage of life cycle, mental health, and relationship happiness. Neurologic disease can interrupt the cycle at many points: by limiting motivation, reducing ability to attend to and feel sexual stimuli, and accomplishing the movements needed to stimulate and experience intercourse. Impairments to genital congestion, penile erection, and orgasm may also occur. Disease-associated changes to the interpersonal relationship and self-image plus frequently comorbid depression will tend to lessen motivation and temper the brain's appraisal of sexual stimuli, so precluding arousal. Therapy begins by explaining the sexual response cycle, clarifying the points of interruption in the patient's own cycle so as to guide treatment. © 2015 Elsevier B.V. All rights reserved.

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.

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).

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.

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.

The response of human and rodent cells to hyperthermia

International Nuclear Information System (INIS)

Roizin-Towle, L.; Pirro, J.P.

1991-01-01

Inherent cellular radiosensitivity in vitro has been shown to be a good predictor of human tumor response in vivo. In contrast, the importance of the intrinsic thermosensitivity of normal and neoplastic human cells as a factor in the responsiveness of human tumors to adjuvant hyperthermia has never been analyzed systematically. A comparison of thermal sensitivity and thermo-radiosensitization in four rodent and eight human-derived cell lines was made in vitro. Arrhenius plots indicated that the rodent cells were more sensitive to heat killing than the human, and the break-point was 0.5 degrees C higher for the human than rodent cells. The relationship between thermal sensitivity and the interaction of heat with X rays at low doses was documented by thermal enhancement ratios (TER's). Cells received either a 1 hr exposure to 43 degrees C or a 20 minute treatment at 45 degrees C before exposure to 300 kVp X rays. Thermal enhancement ratios ranged from 1.0 to 2.7 for human cells heated at 43 degrees C and from 2.1 to 5.3 for heat exposures at 45 degrees C. Thermal enhancement ratios for rodent cells were generally 2 to 3 times higher than for human cells, because of the fact that the greater thermosensitivity of rodent cells results in a greater enhancement of radiation damage. Intrinsic thermosensitivity of human cells has relevance to the concept of thermal dose; intrinsic thermo-radiosensitization of a range of different tumor cells is useful in documenting the interactive effects of radiation combined with heat

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…

Human neuronal cell protein responses to Nipah virus infection

Directory of Open Access Journals (Sweden)

Hassan Sharifah

2007-06-01

Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

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.

Exploring Responsibility. Public and Private in Human Rights Protection

OpenAIRE

Bexell, Magdalena

2005-01-01

The theory and practice of international relations are replete with dilemmas related to the distribution of responsibility for human rights protection. Institutionalized notions of public and private empower and shape knowledge of what the spheres of responsibility signify for different kinds of actors. This study examines how the public-private distinction is manifested in controversy concerning the character of corporate social responsibility. The study develops a conceptual framework cente...

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.

Animal and human responses to UVA and UVB

International Nuclear Information System (INIS)

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)

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.

The Socio-ecological Fit of Human Responses to Environmental Degradation: An Integrated Assessment Methodology

Science.gov (United States)

Briassoulis, Helen

2015-12-01

The scientific and policy interest in the human responses to environmental degradation usually focuses on responses sensu stricto and `best practices' that potentially abate degradation in affected areas. The transfer of individual, discrete instruments and `best practices' to different contexts is challenging, however, because socio-ecological systems are complex and environmental degradation is contextual and contingent. To sensibly assess the effectiveness of formal and informal interventions to combat environmental degradation, the paper proposes an integrative, non-reductionist analytic, the `response assemblage', for the study of `responses-in-context,' i.e., products of human decisions to utilize environmental resources to satisfy human needs in socio-ecological systems. Response assemblages are defined as geographically and historically unique, provisional, open, territorial wholes, complex compositions emerging from processes of assembling biophysical and human components, including responses sensu stricto, from affected focal and other socio-ecological systems, to serve human goals, one of which may be combatting environmental degradation. The degree of match among the components, called the socio- ecological fit of the response assemblage, indicates how effectively their contextual and contingent interactions maintain the socio-ecological resilience, promote sustainable development, and secure the continuous provision of ecosystem services in a focal socio-ecological system. The paper presents a conceptual approach to the analysis of the socio-ecological fit of response assemblages and details an integrated assessment methodology synthesizing the resilience, assemblage, and `problem of fit' literature. Lastly, it summarizes the novelty, value, and policy relevance of conceptualizing human responses as response assemblages and of the integrated assessment methodology, reconsiders `best practices' and suggests selected future research directions.

Potent innate immune response to pathogenic leptospira in human whole blood.

Directory of Open Access Journals (Sweden)

Marga G A Goris

Full Text Available BACKGROUND: Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. CONCLUSIONS/SIGNIFICANCE: Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.

Development of BOLD signal hemodynamic responses in the human brain

NARCIS (Netherlands)

Arichi, T.; Varela, M.; Melendez-Calderon, A.; Allievi, A.; Merchant, N.; Tusor, N.; Counsell, S.J.; Burdet, E.; Beckmann, Christian; Edwards, A.D.

2012-01-01

In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing

Legal response to human rights challenges of multinational ...

African Journals Online (AJOL)

Nnamdi Azikiwe University Journal of International Law and Jurisprudence ... Hence, the subject matter of business and human rights is a trending issue at the ... The paper finds that the response is poor and the consequence is the increase in ...

Thermal sensation models: a systematic comparison.

Science.gov (United States)

Koelblen, B; Psikuta, A; Bogdan, A; Annaheim, S; Rossi, R M

2017-05-01

Thermal sensation models, capable of predicting human's perception of thermal surroundings, are commonly used to assess given indoor conditions. These models differ in many aspects, such as the number and type of input conditions, the range of conditions in which the models can be applied, and the complexity of equations. Moreover, the models are associated with various thermal sensation scales. In this study, a systematic comparison of seven existing thermal sensation models has been performed with regard to exposures including various air temperatures, clothing thermal insulation, and metabolic rate values after a careful investigation of the models' range of applicability. Thermo-physiological data needed as input for some of the models were obtained from a mathematical model for human physiological responses. The comparison showed differences between models' predictions for the analyzed conditions, mostly higher than typical intersubject differences in votes. Therefore, it can be concluded that the choice of model strongly influences the assessment of indoor spaces. The issue of comparing different thermal sensation scales has also been discussed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HUMAN RESOURCE MANAGEMENT AND CORPORATE SOCIAL RESPONSIBILITY: A SYSTEMATIC LITERATURE REVIEW

OpenAIRE

FERREIRA, ELİZABETH REAL DE OLIVEIRA – PEDRO; SAUR, IRİNA; AMARAL,

2013-01-01

We perform a systematic literature review on academic papers in Human Resources Management and Corporate Social Responsibility in ISI Current Contents. Based on 117 academic papers from 2001 to date, we perform content analysis in a grounded-theory methodological approach and map the field of Human Resources Management and Corporate Social Responsibility, identifying main schools of thought (invisible colleges) and main players. We see a tendency to increase publications from 2008 onwards. We...

The Socio-ecological Fit of Human Responses to Environmental Degradation: An Integrated Assessment Methodology.

Science.gov (United States)

Briassoulis, Helen

2015-12-01

The scientific and policy interest in the human responses to environmental degradation usually focuses on responses sensu stricto and 'best practices' that potentially abate degradation in affected areas. The transfer of individual, discrete instruments and 'best practices' to different contexts is challenging, however, because socio-ecological systems are complex and environmental degradation is contextual and contingent. To sensibly assess the effectiveness of formal and informal interventions to combat environmental degradation, the paper proposes an integrative, non-reductionist analytic, the 'response assemblage', for the study of 'responses-in-context,' i.e., products of human decisions to utilize environmental resources to satisfy human needs in socio-ecological systems. Response assemblages are defined as geographically and historically unique, provisional, open, territorial wholes, complex compositions emerging from processes of assembling biophysical and human components, including responses sensu stricto, from affected focal and other socio-ecological systems, to serve human goals, one of which may be combatting environmental degradation. The degree of match among the components, called the socio-ecological fit of the response assemblage, indicates how effectively their contextual and contingent interactions maintain the socio-ecological resilience, promote sustainable development, and secure the continuous provision of ecosystem services in a focal socio-ecological system. The paper presents a conceptual approach to the analysis of the socio-ecological fit of response assemblages and details an integrated assessment methodology synthesizing the resilience, assemblage, and 'problem of fit' literature. Lastly, it summarizes the novelty, value, and policy relevance of conceptualizing human responses as response assemblages and of the integrated assessment methodology, reconsiders 'best practices' and suggests selected future research directions.

Functions of pointing by humans, and dogs’ responses, during dog-human play between familiar and unfamiliar players.

Directory of Open Access Journals (Sweden)

Robert W. Mitchell

2018-05-01

Full Text Available Although much research focuses on human index finger pointing to hidden items for dogs in experimental settings, there is little research about human pointing in naturalistic interactions. We examined human pointing to dogs during 62 dog-human play interactions, spanning 4.8 hours of videotape, to determine the functions of human pointing and dogs’ responses to that pointing. Participants were 26 humans and 27 dogs. Humans played with their own dog(s and, almost always, an unfamiliar dog. Seventeen people (16 players and one passerby pointed for 20 dogs a total of 101 times (once with a foot during 26 interactions. Most (49.5% points were toward an object (almost always a ball, to direct attention or action toward the object; 36.6% were to the ground in front of the (almost always familiar pointer, directing the dog to come, and/or drop a ball the dog held, here; 10.9% directed the dog toward the designated player and/or play area; and 3.0% directed the dog to move away from a ball the dog had dropped. Humans almost always pointed such that the dog could see the point (92.1%, and pointed more with their own than with an unfamiliar dog. Dogs responded appropriately (i.e., did what the pointer requested for only 24.7% of the visible points, more often for points to the ground than for points to objects. The proportion of dogs’ appropriate responses to visible points was similar for both familiar (30% and unfamiliar (18% humans. Six dogs who responded appropriately to some points resisted responding appropriately to others. Future research should examine non-object directed uses of pointing with dogs and their responses in naturalistic and experimental settings, and experimentally assess diverse explanations, including resistance, when dogs and other animals fail standard pointing tasks.

Human responses to bright light of different durations.

Science.gov (United States)

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Biomechanical Analysis of Human Abdominal Impact Responses and Injuries through Finite Element Simulations of a Full Human Body Model.

Science.gov (United States)

Ruan, Jesse S; El-Jawahri, Raed; Barbat, Saeed; Prasad, Priya

2005-11-01

Human abdominal response and injury in blunt impacts was investigated through finite element simulations of cadaver tests using a full human body model of an average-sized adult male. The model was validated at various impact speeds by comparing model responses with available experimental cadaver test data in pendulum side impacts and frontal rigid bar impacts from various sources. Results of various abdominal impact simulations are presented in this paper. Model-predicted abdominal dynamic responses such as force-time and force-deflection characteristics, and injury severities, measured by organ pressures, for the simulated impact conditions are presented. Quantitative results such as impact forces, abdominal deflections, internal organ stresses have shown that the abdomen responded differently to left and right side impacts, especially in low speed impact. Results also indicated that the model exhibited speed sensitive response characteristics and the compressibility of the abdomen significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated finite element human body model can be useful for abdominal injury assessment. Internal organ injuries, which are difficult to detect in experimental studies with human cadavers due to the difficulty of instrumentation, may be more easily identified with a validated finite element model through stress-strain analysis.

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

International Responses to Human Protection Crises: Responsibility to Protect and the Emerging Protection Regime*

OpenAIRE

Bellamy, Alex J.

2015-01-01

This essay examines contemporary debates about human protection by the UN Security Council and others in response to major humanitarian crises. It argues that there are clear signs of an emerging international human protection regime in the evolving practice of the Security Council and suggests that this regime is based on an accommodation between different moral accounts of humanitarian intervention. The first section examines some of the legal and moral debates that have arisen with respect...

Connecting Corporate Human Rights Responsibilities and State Obligations under the UN Guiding Principles

DEFF Research Database (Denmark)

Buhmann, Karin

2017-01-01

Taking its point of departure in the UN Guiding Principles on Business and Human Rights (UNGP), this chapter discusses the complementarity between Pillars One on the State Duty to Respect and Pillar Two the Corporate Responsibility to Respect Human Rights. It does this through HRDD and communicat......Taking its point of departure in the UN Guiding Principles on Business and Human Rights (UNGP), this chapter discusses the complementarity between Pillars One on the State Duty to Respect and Pillar Two the Corporate Responsibility to Respect Human Rights. It does this through HRDD...

Oxytocin modulates hemodynamic responses to monetary incentives in humans

Science.gov (United States)

Mickey, Brian J.; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T.; Zubieta, Jon-Kar; Love, Tiffany M.

2016-01-01

Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. Here we examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin’s effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans – even in a non-social context – and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry. PMID:27614896

Oxytocin modulates hemodynamic responses to monetary incentives in humans.

Science.gov (United States)

Mickey, Brian J; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T; Zubieta, Jon-Kar; Love, Tiffany M

2016-12-01

Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.

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.

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.

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.

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.

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

Science.gov (United States)

Gruskin, Sofia; Raad, Zyde

2010-09-28

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.

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

Science.gov (United States)

Ritter, Geralyn S

2010-09-28

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.

Visualization of the human CD4+ T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/γcnull (NOG) mice by retrogenic expression of the human TCR gene

International Nuclear Information System (INIS)

Takahashi, Takeshi; Katano, Ikumi; Ito, Ryoji; Ito, Mamoru

2015-01-01

Highlights: • β-Lactoglobulin (BLG) specific TCR genes were introduced to human HSC by retrovirus. • Human HSC with BLG-specific TCR were transplanted into NOG-HLA-DR4 I-A −/− mice. • BLG-specific TCR induced positive selection of thymocytes. • BLG-specific TCR positive CD4 + T cells mediated immune responses in humanized mice. - Abstract: The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice. To directly monitor immune responses of human CD4 + T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4 + T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic/I-Aβ deficient mice (NOG-DR4/I-A o ). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4 + CD8 − single-positive cells. Adoptive transfer of mature CD4 + T cells expressing the TCR into recipient NOG-DR4/I-A o mice demonstrated that human CD4 + T cells proliferated in response to antigenic stimulation and produced IFN-γ in vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice

Prediction of the human response time with the similarity and quantity of information

International Nuclear Information System (INIS)

Lee, Sungjin; Heo, Gyunyoung; Chang, Soon Heung

2006-01-01

Memory is one of brain processes that are important when trying to understand how people process information. Although a large number of studies have been made on the human performance, little is known about the similarity effect in human performance. The purpose of this paper is to propose and validate the quantitative and predictive model on the human response time in the user interface with the concept of similarity. However, it is not easy to explain the human performance with only similarity or information amount. We are confronted by two difficulties: making the quantitative model on the human response time with the similarity and validating the proposed model by experimental work. We made the quantitative model based on the Hick's law and the law of practice. In addition, we validated the model with various experimental conditions by measuring participants' response time in the environment of computer-based display. Experimental results reveal that the human performance is improved by the user interface's similarity. We think that the proposed model is useful for the user interface design and evaluation phases

Comparison of Human Response against Earthquake and Tsunami

Science.gov (United States)

Arikawa, T.; Güler, H. G.; Yalciner, A. C.

2017-12-01

The evacuation response against the earthquake and tsunamis is very important for the reduction of human damages against tsunami. But it is very difficult to predict the human behavior after shaking of the earthquake. The purpose of this research is to clarify the difference of the human response after the earthquake shock in the difference countries and to consider the relation between the response and the safety feeling, knowledge and education. For the objective of this paper, the questionnaire survey was conducted after the 21st July 2017 Gokova earthquake and tsunami. Then, consider the difference of the human behavior by comparison of that in 2015 Chilean earthquake and tsunami and 2011 Japan earthquake and tsunami. The seismic intensity of the survey points was almost 6 to 7. The contents of the questions include the feeling of shaking, recalling of the tsunami, the behavior after shock and so on. The questionnaire was conducted for more than 20 20 people in 10 areas. The results are the following; 1) Most people felt that it was a strong shake not to stand, 2) All of the questionnaires did not recall the tsunami, 3) Depending on the area, they felt that after the earthquake the beach was safer than being at home. 4) After they saw the sea drawing, they thought that a tsunami would come and ran away. Fig. 1 shows the comparison of the evacuation rate within 10 minutes in 2011 Japan, 2015 Chile and 2017 Turkey.. From the education point of view, education for tsunami is not done much in Turkey. From the protection facilities point of view, the high sea walls are constructed only in Japan. From the warning alert point of view, there is no warning system against tsunamis in the Mediterranean Sea. As a result of this survey, the importance of tsunami education is shown, and evacuation tends to be delayed if dependency on facilities and alarms is too high.

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

Science.gov (United States)

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

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. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

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.

[Autoshaping of a button-push response and eye movement in human subjects].

Science.gov (United States)

Kimura, H; Fukui, I; Inaki, K

1990-12-01

Two experiments were conducted with human subjects to investigate the similarities and differences between animal and human behaviors under autoshaping procedures. In these experiments, light served as CS, and display on TV served as US. Whether the pushing button response or gazing response to CS could be obtained in human subjects under Pavlovian conditioning procedure was examined. In Experiment 1, uninstructed naive subjects were placed in a room containing a push-button and a TV display. Within the experimental sessions, the push-button was lit for 8 s as CS, and then paired with the display of a soft pornographic program on TV for 10 s. The result indicated that the modeling of pushing button promoted the increase of response probability among the subjects. The trials conducted after the rest period indicated an increase of response probability. In Experiment 2, a 4 cm square translucent panel was lit for 20 s as CS, and then paired with the display of a computer graphic picture on TV for 8 s as US. Some subjects started gazing at the CS for several seconds. These results indicated that some subjects could acquire the gazing response under the autoshaping procedure.

Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

Science.gov (United States)

Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

2014-01-01

Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

Immunoglobulin gene usage in the human anti-pathogen response.

Science.gov (United States)

Newkirk, M M; Rioux, J D

1995-09-01

The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

Goal inferences about robot behavior : goal inferences and human response behaviors

NARCIS (Netherlands)

Broers, H.A.T.; Ham, J.R.C.; Broeders, R.; De Silva, P.; Okada, M.

2014-01-01

This explorative research focused on the goal inferences human observers draw based on a robot's behavior, and the extent to which those inferences predict people's behavior in response to that robot. Results show that different robot behaviors cause different response behavior from people.

A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

Science.gov (United States)

Slob, Wout

2015-01-01

Background When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. Objectives We developed a unified framework for probabilistic dose–response assessment. Methods We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose–response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, “effect metrics” can be specified to define “toxicologically equivalent” sizes for this underlying individual response; and d) dose–response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose–response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Results Probabilistically derived exposure limits are based on estimating a “target human dose” (HDMI), which requires risk management–informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%–10% effect sizes. Conclusions Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk

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

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.

Response of Human Skin Equivalents to Sarcoptes scabiei

Science.gov (United States)

MORGAN, MARJORIE S.; ARLIAN, LARRY G.

2010-01-01

Studies have shown that molecules in an extract made from bodies of the ectoparasitic mite, Sarcoptes scabiei De Geer, modulate cytokine secretion from cultured human keratinocytes and fibroblasts. In vivo, in the parasitized skin, these cells interact with each other by contact and cytokine mediators and with the matrix in which they reside. Therefore, these cell types may function differently together than they do separately. In this study, we used a human skin equivalent (HSE) model to investigate the influence of cellular interactions between keratinocytes and fibroblasts when the cells were exposed to active/burrowing scabies mites, mite products, and mite extracts. The HSE consisted of an epidermis of stratified stratum corneum, living keratinocytes, and basal cells above a dermis of fibroblasts in a collagen matrix. HSEs were inoculated on the surface or in the culture medium, and their cytokine secretions on the skin surface and into the culture medium were determined by enzyme-linked immunosorbent assay. Active mites on the surface of the HSE induced secretion of cutaneous T cell-attracting chemokine, thymic stromal lymphopoietin, interleukin (IL)-1α, IL-1β, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, monocyte chemoattractant protein-1, granulocyte/macrophage colony-stimulating factor, and macrophage colony-stimulating factor. The main difference between HSEs and monocultured cells was that the HSEs produced the proinflammatory cytokines IL-1α and IL-1β and their competitive inhibitor IL-1ra, whereas very little of these mediators was previously found for cultured keratinocytes and fibroblasts. It is not clear how the balance between these cytokines influences the overall host response. However, IL-1ra may contribute to the depression of an early cutaneous inflammatory response to scabies in humans. These contrasting results illustrate that cell interactions are important in the host’s response to burrowing scabies mites. PMID:20939384

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.

The potential of a modified physiologically equivalent temperature (mPET) based on local thermal comfort perception in hot and humid regions

Science.gov (United States)

Lin, Tzu-Ping; Yang, Shing-Ru; Chen, Yung-Chang; Matzarakis, Andreas

2018-02-01

Physiologically equivalent temperature (PET) is a thermal index that is widely used in the field of human biometeorology and urban bioclimate. However, it has several limitations, including its poor ability to predict thermo-physiological parameters and its weak response to both clothing insulation and humid conditions. A modified PET (mPET) was therefore developed to address these shortcomings. To determine whether the application of mPET in hot-humid regions is more appropriate than the PET, an analysis of a thermal comfort survey database, containing 2071 questionnaires collected from participants in hot-humid Taiwan, was conducted. The results indicate that the thermal comfort range is similar (26-30 °C) when the mPET and PET are applied as thermal indices to the database. The sensitivity test for vapor pressure and clothing insulation also show that the mPET responds well to the behavior and perceptions of local people in a subtropical climate.

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

Aging augments renal vasoconstrictor response to orthostatic stress in humans.

Science.gov (United States)

Clark, Christine M; Monahan, Kevin D; Drew, Rachel C

2015-12-15

The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP. However, how healthy aging affects the renal vasoconstrictor response to LBNP is unknown. Therefore, 10 young (25 ± 1 yr; means ± SE) and 10 older (66 ± 2 yr) subjects underwent graded LBNP (-15 and -30 mmHg) while beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), arterial BP (Finometer), and heart rate (HR; electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as mean BP/RBFV. All baseline cardiovascular variables were similar between groups, except diastolic BP was higher in older subjects (P aging augments the renal vasoconstrictor response to orthostatic stress in humans. Copyright © 2015 the American Physiological Society.

Human Trafficking And U.S. Government Responses Post-9/11

Science.gov (United States)

2016-09-01

responsibility of anti-trafficking advocates to recognize and support the self - determination and agency of all vulnerable populations and to resist urges...disregard “ self - organization” for “some greater good.”247 Organization pushes sex work closer to a legitimization that Zheng highlights could...environment. The body of human trafficking literature has revealed four common themes: human agency, labor rights, the sex industry, and crime control

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.

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.

Prediction and analysis of human thoracic impact responses and injuries in cadaver impacts using a full human body finite element model.

Science.gov (United States)

Ruan, Jesse; El-Jawahri, Raed; Chai, Li; Barbat, Saeed; Prasad, Priya

2003-10-01

Human thoracic dynamic responses and injuries associated with frontal impact, side impact, and belt loading were investigated and predicted using a complete human body finite element model for an average adult male. The human body model was developed to study the impact biomechanics of a vehicular occupant. Its geometry was based on the Visible Human Project (National Library of Medicine) and the topographies from human body anatomical texts. The data was then scaled to an average adult male according to available biomechanical data from the literature. The model includes details of the head, neck, ribcage, abdomen, thoracic and lumbar spine, internal organs of the chest and abdomen, pelvis, and the upper and lower extremities. The present study is focused on the dynamic response and injuries of the thorax. The model was validated at various impact speeds by comparing predicted responses with available experimental cadaver data in frontal and side pendulum impacts, as well as belt loading. Model responses were compared with similar individual cadaver tests instead of using cadaver corridors because the large differences between the upper and lower bounds of the corridors may confound the model validation. The validated model was then used to study thorax dynamic responses and injuries in various simulated impact conditions. Parameters that could induce injuries such as force, deflection, and stress were computed from model simulations and were compared with previously proposed thoracic injury criteria to assess injury potential for the thorax. It has been shown that the model exhibited speed sensitive impact characteristics, and the compressibility of the internal organs significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated FE human body model could be useful for injury assessment in various cadaveric impacts reported in the literature. Internal organ injuries, which are

Curcumin prevents human dendritic cell response to immune stimulants

International Nuclear Information System (INIS)

Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

2008-01-01

Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14 + monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4 + T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

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.

Transient Genome-Wide Transcriptional Response to Low-Dose Ionizing Radiation In Vivo in Humans

International Nuclear Information System (INIS)

Berglund, Susanne R.; Rocke, David M.; Dai Jian; Schwietert, Chad W.; Santana, Alison; Stern, Robin L.; Lehmann, Joerg; Hartmann Siantar, Christine L.; Goldberg, Zelanna

2008-01-01

Purpose: The in vivo effects of low-dose low linear energy transfer ionizing radiation on healthy human skin are largely unknown. Using a patient-based tissue acquisition protocol, we have performed a series of genomic analyses on the temporal dynamics over a 24-hour period to determine the radiation response after a single exposure of 10 cGy. Methods and Materials: RNA from each patient tissue sample was hybridized to an Affymetrix Human Genome U133 Plus 2.0 array. Data analysis was performed on selected gene groups and pathways. Results: Nineteen gene groups and seven gene pathways that had been shown to be radiation responsive were analyzed. Of these, nine gene groups showed significant transient transcriptional changes in the human tissue samples, which returned to baseline by 24 hours postexposure. Conclusions: Low doses of ionizing radiation on full-thickness human skin produce a definable temporal response out to 24 hours postexposure. Genes involved in DNA and tissue remodeling, cell cycle transition, and inflammation show statistically significant changes in expression, despite variability between patients. These data serve as a reference for the temporal dynamics of ionizing radiation response following low-dose exposure in healthy full-thickness human skin

Characterising the mucosal and systemic immune responses to experimental human hookworm infection.

Directory of Open Access Journals (Sweden)

Soraya Gaze

2012-02-01

Full Text Available The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13 and regulatory (IL-10 and TGF-β response, with some evidence of a Th1 (IFN-γ and IL-2 response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17 response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

Science.gov (United States)

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Responses to Human Bioeffluents at Levels Recommended by Ventilation Standards

DEFF Research Database (Denmark)

Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

2017-01-01

The purpose of this study was to examine whether exposure to human bioeffluents, at the levels recommended by the current ventilation standards, would cause any effects on humans. Ten subjects were exposed in a low-emission stainless-steel climate chamber for 4.25 hours. The outdoor air supply rate...... 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...

The response of human glioblastoma in culture to radiation

International Nuclear Information System (INIS)

Masuda, Koji; Aramaki, Ryoji; Takagi, Tosuke

1980-01-01

Cells from two human glioblastoma multiforme and one mouse glioma were grown in tissue cultures and their X-ray survival curve parameters were determined under oxygenated and hypoxic conditions. These were compared with the survival parameters for mouse fibroblasts (L5) and established cell lines from human carcinoma coli (HeLa S3) irradiated under identical conditions. There was no significant difference in response among the cell lines used. Repair of potentially lethal damage for human glioblastoma and HeLa S3 was assessed by the increase in survival which occurred as the cells were held in density inhibited stationary phase. The magnitude of repair of potentially lethal damage (slope modifying factors) for the glioblastoma and HeLa were 1.9 and 1.1, respectively. (author)

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

OpenAIRE

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 different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From ...

A microculture system for generating haemolytic antibody responses from human tonsillar lymphocytes.

Science.gov (United States)

Booth, R J

1979-01-01

Small numbers of Ficoll-Hypaque purified human tonsillar lymphocytes were stimulated with PWM to produce SRBC-specific PFC in a microculture system. The magnitude of the response varied among different tonsils but was typically between 200 and 1000 PFC/10(6) cells cultured. Little or no response was observed in the absence of PWM. SRBC failed to stimulate a SRBC-specific response and the presence of this antigen in PWM-stimulated cultures depressed the response. The time of the maximum response was inversely related to the number of cells cultured. In addition, the duration of the response was limited by rapid depletion of critical medium requirements and/or build up of inhibitory factors especially when the cell concentration exceeded 5 x 10(5) cells/culture. This effect could be partially overcome by daily feeding of cultures with fresh medium. Fractionation studies indicated a requirement for both T and B cell populations. Constant efficiency of PFC production with respect to cell number could be achieved by the addition of inactivated autologous 'filler' cells. The significance of these results and applicability of the microculture system to a detailed analysis of human antibody responses will be discussed.

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 (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH 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 T FH 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 T FH cell development. Added to T FH 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 T FH 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 T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH 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 T FH 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.

Dynamic gene expression response to altered gravity in human T cells.

Science.gov (United States)

Thiel, Cora S; Hauschild, Swantje; Huge, Andreas; Tauber, Svantje; Lauber, Beatrice A; Polzer, Jennifer; Paulsen, Katrin; Lier, Hartwin; Engelmann, Frank; Schmitz, Burkhard; Schütte, Andreas; Layer, Liliana E; Ullrich, Oliver

2017-07-12

We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. We found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 s and 5 min. The initial response to microgravity involved mostly regulatory RNAs. We identified three gravity-regulated genes which could be cross-validated in both completely independent experiment missions: ATP6V1A/D, a vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain locus participating in V(D)J recombination, and LINC00837, a long intergenic non-protein coding RNA. Due to the extensive and rapid alteration of gene expression associated with regulatory RNAs, we conclude that human cells are equipped with a robust and efficient adaptation potential when challenged with altered gravitational environments.

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

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...... protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle....

Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans

DEFF Research Database (Denmark)

Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph

2005-01-01

Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We...... observed striking CD8+ T-cell responses, which were sustained or even increased over many months after the resolution of acute disease, indicating that CD8+ T cells may play a prominent role in the control of parvovirus B19 and other acute viral infections of humans, including potentially those generated...

Human T-cell responses to oral streptococci in human PBMC-NOD/SCID mice.

Science.gov (United States)

Salam, M A; Nakao, R; Yonezawa, H; Watanabe, H; Senpuku, H

2006-06-01

We investigated cellular and humoral immune responses to oral biofilm bacteria, including Streptococcus mutans, Streptococcus anginosus, Streptococcus sobrinus, and Streptococcus sanguinis, in NOD/SCID mice immunized with human peripheral blood mononuclear cells (hu-PBMC-NOD/SCID mice) to explore the pathogenicity of each of those organisms in dental and oral inflammatory diseases. hu-PBMC-NOD/SCID mice were immunized by intraperitoneal injections with the whole cells of the streptococci once a week for 3 weeks. FACS analyses were used to determine the percentages of various hu-T cell types, as well as intracellular cytokine production of interleukin-4 and interferon-gamma. Serum IgG and IgM antibody levels in response to the streptococci were also determined by enzyme-linked immunosorbent assay. S. anginosus induced a significant amount of the proinflammatory cytokine interferon-gamma in CD4(+) and CD8(+) T cells in comparison with the other streptococci. However, there was no significant differences between the streptococci in interleukin-4 production by CD4(+) and CD8(+) T cells after inoculation. Further, S. mutans significantly induced human anti-S. mutans IgG, IgG(1), IgG(2), and IgM antibodies in comparison with the other organisms. In conclusion, S. anginosus up-regulated Th1 and Tc1 cells, and S. mutans led to increasing levels of their antibodies, which was associated with the induction of Th2 cells. These results may contribute to a better understanding of human lymphocyte interactions to biofilm bacteria, along with their impact on dental and mucosal inflammatory diseases, as well as endocarditis.

Decoding color responses in human visual cortex

International Nuclear Information System (INIS)

Kuriki, Ichiro; Matsumiya, Kazumichi; Shioiri, Satoshi; Nakamura, Shingo; Sun, Pei; Ueno, Kenichi; Tanaka, Keiji; Cheng, Kang

2011-01-01

Color percept is a subjective experience and, in general, it is impossible for other people to tell someone's color percept. The present study demonstrated that the simple image-classification analysis of brain activity obtained by a functional magnetic resonance imaging (fMRI) technique enables to tell which of four colors the subject is looking at. Our results also imply that color information is coded by the responses of hue-selective neurons in human brain, not by the combinations of red-green and blue-yellow hue components. (author)

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.

Visualization of the human CD4{sup +} T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/γc{sup null} (NOG) mice by retrogenic expression of the human TCR gene

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Takeshi, E-mail: takeshi-takahashi@ciea.or.jp; Katano, Ikumi; Ito, Ryoji; Ito, Mamoru

2015-01-02

Highlights: • β-Lactoglobulin (BLG) specific TCR genes were introduced to human HSC by retrovirus. • Human HSC with BLG-specific TCR were transplanted into NOG-HLA-DR4 I-A{sup −/−} mice. • BLG-specific TCR induced positive selection of thymocytes. • BLG-specific TCR positive CD4{sup +} T cells mediated immune responses in humanized mice. - Abstract: The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice. To directly monitor immune responses of human CD4{sup +} T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4{sup +} T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic/I-Aβ deficient mice (NOG-DR4/I-A{sup o}). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4{sup +}CD8{sup −} single-positive cells. Adoptive transfer of mature CD4{sup +} T cells expressing the TCR into recipient NOG-DR4/I-A{sup o} mice demonstrated that human CD4{sup +} T cells proliferated in response to antigenic stimulation and produced IFN-γ in vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice.

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.

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...

Extinction of aversive classically conditioned human sexual response.

Science.gov (United States)

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

2015-04-01

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 extinction phase. Possible resistance to extinction of aversive conditioned sexual responses may have important clinical implications. However, resistance to extinction of aversive conditioned human sexual response has not been studied using extensive extinction trials. This article aims to study resistance to extinction of aversive conditioned sexual responses in sexually functional men and women. A differential conditioning experiment was conducted, with two erotic pictures as conditioned stimulus (CSs) and a painful stimulus as unconditioned stimuli (USs). Only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. Penile circumference and vaginal pulse amplitude were assessed, and ratings of affective value and subjective sexual arousal were obtained. Also, a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. Men and women rated the CS+ more negative as compared with the CS-. During the first trials of the extinction phase, vaginal pulse amplitude was lower in response to the CS+ than in response to the CS-, and on the first extinction trial women rated the CS+ as less sexually arousing. Intriguingly, men did not demonstrate attenuated genital and subjective sexual response. Aversive conditioning, by means of painful stimuli, only affects sexual responses in women, whereas it does not in men. Although conditioned sexual likes and dislikes are relatively persistent, conditioned affect eventually does extinguish. © 2014 International Society for Sexual Medicine.

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...

Response of human and rabbit lymphocytes to low doses of X-rays

International Nuclear Information System (INIS)

Fabry, L.

1982-01-01

The response of human and rabbit lymphocytes to low doses of X-rays was studied by the yields of dicentrics in first division metaphases. For both species, the dose-response curve was best fitted to the linear-quadratic model with a linear component predominating up to 67 and 42 rad respectively for man and rabbit. A calibration curve (5-400 rad) was obtained by combining the present results on man with previous data at higher doses. On the other hand, it appears that, at low doses, the radiosentivity of human lymphocytes is significantly higher than that of rabbit lymphocytes [fr

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 ...

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

Science.gov (United States)

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

Framework for estimating response time data to conduct a seismic human reliability analysis - its feasibility

International Nuclear Information System (INIS)

Park, Jinkyun; Kin, Yochan; Jung, Wondea; Jang, Seung Cheol

2014-01-01

This is because the PSA has been used for several decades as the representative tool to evaluate the safety of NPPs. To this end, it is inevitable to evaluate human error probabilities (HEPs) in conducting important tasks being considered in the PSA framework (i.e., HFEs; human failure events), which are able to significantly affect the safety of NPPs. In addition, it should be emphasized that the provision of a realistic human performance data is an important precondition for calculating HEPs under a seismic condition. Unfortunately, it seems that HRA methods being currently used for calculating HEPs under a seismic event do not properly consider the performance variation of human operators. For this reason, in this paper, a framework to estimate response time data that are critical for calculating HEPs is suggested with respect to a seismic intensity. This paper suggested a systematic framework for estimating response time data that would be one of the most critical for calculating HEPs. Although extensive review of existing literatures is indispensable for identifying response times of human operators who have to conduct a series of tasks prescribed in procedures based on a couple of wrong indications, it is highly expected that response time data for seismic HRA can be properly secured through revisiting response time data collected from diverse situations without concerning a seismic event

Enhancement by platelets of oxygen radical responses of human neutrophils

International Nuclear Information System (INIS)

McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

1986-01-01

When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O- 2 and H 2 O 2 . This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O- 2 generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O- 2 responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

Science.gov (United States)

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Products of neutrophils and eosinophils increase the responsiveness of human isolated bronchial tissue.

Science.gov (United States)

Hallahan, A R; Armour, C L; Black, J L

1990-05-01

This study examines the possibility that products of neutrophils and eosinophils could increase the responsiveness of human isolated bronchial tissue. Neutrophils and eosinophils were isolated from the peripheral blood of healthy volunteers. The cells were incubated with 1 microM calcium ionophore A23187 for 10-15 min then centrifuged, the supernatant collected and stored at -70 degrees C. Human bronchial rings (2-3 mm diameter, 3-4 mm long) were prepared from specimens resected at thoracotomy. The tissues were suspended in organ baths under a 1 g load and changes in tension measured isometrically. Stable contractions to bolus doses of histamine (0.1-10 microM) or to electrical field stimulation (40-100 V, 4-16 Hz, 1 ms for 20 s) were established. Supernatant from 106 neutrophils or 105 eosinophils was then added and tissue responsiveness reassessed. Neutrophil supernatant increased tissue responsiveness to histamine and electrical field stimulation by 54 +/- 17% (n = 5, p less than 0.05) and 18 +/- 7% (n = 6, p less than 0.05), respectively. Eosinophil supernatant increased the histamine response by 60 +/- 23% (n = 8, p less than 0.05) while tissue responsiveness to electrical field stimulation was unchanged (n = 3). Thus, as neutrophils and eosinophils can change the responsiveness of human bronchus in vitro it is possible that they do this in vivo and may not simply be temporally related to the development of bronchial hyperresponsiveness.

cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells.

Directory of Open Access Journals (Sweden)

Jennifer Paijo

2016-04-01

Full Text Available Human cytomegalovirus (HCMV infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING and thus induces antiviral type I interferon (IFN-I responses. We found that plasmacytoid dendritic cells (pDC as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages.

Regulating corporate social and human rights responsibilities at the UN plane

DEFF Research Database (Denmark)

Buhmann, Karin

2009-01-01

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...... 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...

Validation of standard ASTM F2732 and comparison with ISO 11079 with respect to comfort temperature ratings for cold protective clothing.

Science.gov (United States)

Gao, Chuansi; Lin, Li-Yen; Halder, Amitava; Kuklane, Kalev; Holmér, Ingvar

2015-01-01

American standard ASTM F2732 estimates the lowest environmental temperature for thermal comfort for cold weather protective clothing. International standard ISO 11079 serves the same purpose but expresses cold stress in terms of required clothing insulation for a given cold climate. The objective of this study was to validate and compare the temperature ratings using human subject tests at two levels of metabolic rates (2 and 4 MET corresponding to 116.4 and 232.8 W/m(2)). Nine young and healthy male subjects participated in the cold exposure at 3.4 and -30.6 °C. The results showed that both standards predict similar temperature ratings for an intrinsic clothing insulation of 1.89 clo and for 2 MET activity. The predicted temperature rating for 2 MET activity is consistent with test subjects' thermophysiological responses, perceived thermal sensation and thermal comfort. For 4 MET activity, however, the whole body responses were on the cold side, particularly the responses of the extremities. ASTM F2732 is also limited due to its omission and simplification of three climatic variables (air velocity, radiant temperature and relative humidity) and exposure time in the cold which are of practical importance. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

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

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

Directory of Open Access Journals (Sweden)

Talita Rosolen

2016-09-01

Full Text Available 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, social and environmental and strategic human resource management (SHRM in companies operating in Brazil. We also aim to identify whether there is impact of other aspects on this relationship, namely: size, industry and company internationalization level (if national or multinational. Results show evidence that ethical CSR can be associated to SHRM. Environmental CSR showed marginal relation, and social and strategic CSR presented no significant association. Those results emphasize the need to further develop strategic actions of CSR into human resource management in emerging markets. Managers can also benefit from those findings, as it is possible to have a broad view of limitations and opportunities regarding the role played by human resource management in CSR.

Human and animal studies: portals into the whole body and whole population response

Science.gov (United States)

Human and animal studies: portals into the whole body and whole population response Michael C. Madden1 and Brett Winters21US Environmental Protection Agency and 2University of North Carolina Human Studies Facility, Chapel Hill, North Carolina, USA Studies involving collection and...

Human disturbance alters endocrine and immune responses in the Galapagos marine iguana (Amblyrhynchus cristatus).

Science.gov (United States)

French, Susannah S; DeNardo, Dale F; Greives, Timothy J; Strand, Christine R; Demas, Gregory E

2010-11-01

Anthropogenic disturbance is a relevant and widespread facilitator of environmental change and there is clear evidence that it impacts natural populations. While population-level responses to major anthropogenic changes have been well studied, individual physiological responses to mild disturbance can be equally critical to the long-term survival of a species, yet they remain largely unexamined. The current study investigated the impact of seemingly low-level anthropogenic disturbance (ecotourism) on stress responsiveness and specific fitness-related immune measures in different breeding stages of the marine iguana (Amblyrhynchus cristatus). Specifically, we found stress-induced elevations in plasma corticosterone among tourist-exposed populations relative to undisturbed populations. We also found changes in multiple immunological responses associated with stress-related effects of human disturbance, including bacterial killing ability, cutaneous wound healing, and hemolytic complement activity, and the responses varied according to reproductive state. By identifying health-related consequences of human disturbance, this study provides critical insight into the conservation of a well-known species that has a very distinct ecology. The study also broadens the foundation of knowledge needed to understand the global significance of various levels of human disturbance. Copyright © 2010 Elsevier Inc. All rights reserved.

Human disturbance alters endocrine and immune responses in the Galapagos marine iguana (Amblyrhynchus cristatus)

Science.gov (United States)

French, Susannah S; DeNardo, Dale F.; Greives, Timothy J.; Strand, Christine R.; Demas, Gregory E.

2010-01-01

Anthropogenic disturbance is a relevant and widespread facilitator of environmental change and there is clear evidence that it impacts natural populations. While population-level responses to major anthropogenic changes have been well studied, individual physiological responses to mild disturbance can be equally critical to the long-term survival of a species, yet they remain largely unexamined. The current study investigated the impact of seemingly low-level anthropogenic disturbance (ecotourism) on stress responsiveness and specific fitness-related immune measures in different breeding stages of the marine iguana (Amblyrhynchus cristatus). Specifically, we found stress-induced elevations in plasma corticosterone among tourist-exposed populations relative to undisturbed populations. We also found changes in multiple immunological responses associated with stress-related effects of human disturbance, including bacterial killing ability, cutaneous wound healing, and hemolytic complement activity, and the responses varied according to reproductive state. By identifying health-related consequences of human disturbance, this study provides critical insight into the conservation of a well-known species that has a very distinct ecology. The study also broadens the foundation of knowledge needed to understand the global significance of various levels of human disturbance. PMID:20708010

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.

The validity of wireless iButtons® and thermistors for human skin temperature measurement

International Nuclear Information System (INIS)

Smith, A D Harper; Walsh, N P; Crabtree, D R; Bilzon, J L J

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 °C) and were referenced against a certified, mercury thermometer. In the second investigation, eight healthy males completed three randomized trials (ambient temperature = 10 °C, 20 °C and 30 °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 °C for iButtons® and +0.045 °C for thermistors. Upon calibration correction the mean bias for iButtons® and thermistors was not significantly different from zero bias. Interestingly, the typical error of the estimate of iButtons® (0.043 °C) was 1.5 times less than that of thermistors (0.062 °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 °C to 1.356 °C. Mean temperature differences between iButtons® and thermistors during exercise were 0.989 °C (ambient temperature = 10 °C), 0.415 °C (ambient temperature = 20 °C) and 0.318 °C (ambient temperature = 30 °C). Observed

Behavioural responses to human-induced change: Why fishing should not be ignored.

Science.gov (United States)

Diaz Pauli, Beatriz; Sih, Andrew

2017-03-01

Change in behaviour is usually the first response to human-induced environmental change and key for determining whether a species adapts to environmental change or becomes maladapted. Thus, understanding the behavioural response to human-induced changes is crucial in the interplay between ecology, evolution, conservation and management. Yet the behavioural response to fishing activities has been largely ignored. We review studies contrasting how fish behaviour affects catch by passive (e.g., long lines, angling) versus active gears (e.g., trawls, seines). We show that fishing not only targets certain behaviours, but it leads to a multitrait response including behavioural, physiological and life-history traits with population, community and ecosystem consequences. Fisheries-driven change (plastic or evolutionary) of fish behaviour and its correlated traits could impact fish populations well beyond their survival per se , affecting predation risk, foraging behaviour, dispersal, parental care, etc., and hence numerous ecological issues including population dynamics and trophic cascades . In particular, we discuss implications of behavioural responses to fishing for fisheries management and population resilience. More research on these topics, however, is needed to draw general conclusions, and we suggest fruitful directions for future studies.

A DESIGN FRAMEWORK FOR HUMAN EMOTION RECOGNITION USING ELECTROCARDIOGRAM AND SKIN CONDUCTANCE RESPONSE SIGNALS

Directory of Open Access Journals (Sweden)

KHAIRUN NISA’ MINHAD

2017-11-01

Full Text Available Identification of human emotional state while driving a vehicle can help in understanding the human behaviour. Based on this identification, a response system can be developed in order to mitigate the impact that may be resulted from the behavioural changes. However, the adaptation of emotions to the environment at most scenarios is subjective to an individual’s perspective. Many factors, mainly cultural and geography, gender, age, life style and history, level of education and professional status, can affect the detection of human emotional affective states. This work investigated sympathetic responses toward human emotions defined by using electrocardiography (ECG and skin conductance response (SCR signals recorded simultaneously. This work aimed to recognize ECG and SCR patterns of the investigated emotions measured using selected sensor. A pilot study was conducted to evaluate the proposed framework. Initial results demonstrated the importance of suitability of the stimuli used to evoke the emotions and high opportunity for the ECG and SCR signals to be used in the automotive real-time emotion recognition systems.

Magnetogastrographic detection of gastric electrical response activity in humans

International Nuclear Information System (INIS)

Irimia, Andrei; Richards, William O; Bradshaw, L Alan

2006-01-01

The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

THE RESPONSIBILITY OF PROTECTING (R2P HUMAN RIGHTS AND SECURITY COUNCIL

Directory of Open Access Journals (Sweden)

ULDARICIO FIGUEROA PLÁ

2017-12-01

Full Text Available The adoption in 1948 of the Convention on the Prevention and Punishment of the Crime of Genocide seemed to open a new era in the international scenario in which these kind of practices apparently are left in the historic past. Reality has shown us that this international instrument was not enough to face arbitrary measures of some Governments. Nevertheless, genocide actions continuing to be performed, and in order to decrease human suffering, “humanitarian intervention” was thought as a response to the ineffectiveness of the Security Council which also brought along arbitrary actions in its invocation, discrediting it. Before the reiterated calls of the Secretary General of the United Nations to prevent and detain massive violations to human rights, an effort has been made in order to standardizing a type of interventions that can respond to massive violations of human rights. This has been called Responsibility to Protect.

'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

International Nuclear Information System (INIS)

Jetten, Marlon J.A.; Gaj, Stan; Ruiz-Aracama, Ainhoa; Kok, Theo M. de; Delft, Joost H.M. van; Lommen, Arjen; Someren, Eugene P. van; Jennen, Danyel G.J.; Claessen, Sandra M.; Peijnenburg, Ad A.C.M.; Stierum, Rob H.; Kleinjans, Jos C.S.

2012-01-01

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 outperformed

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

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.

Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

International Nuclear Information System (INIS)

Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.; Menon, K.M.

1991-01-01

The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

Human protein status modulates brain reward responses to food cues1–3

NARCIS (Netherlands)

Griffioen-Roose, S.; Smeets, P.A.M.; Heuvel, van den E.M.; Boesveldt, S.; Finlayson, G.; Graaf, de C.

2014-01-01

Background: Protein is indispensable in the human diet, and its intake appears tightly regulated. The role of sensory attributes of foods in protein intake regulation is far from clear. Objective: We investigated the effect of human protein status on neural responses to different food cues with the

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

mEBT: multiple-matching Evidence-based Translator of Murine Genomic Responses for Human Immunity Studies.

Science.gov (United States)

Tae, Donghyun; Seok, Junhee

2018-05-29

In this paper, we introduce multiple-matching Evidence-based Translator (mEBT) to discover genomic responses from murine expression data for human immune studies, which are significant in the given condition of mice and likely have similar responses in the corresponding condition of human. mEBT is evaluated over multiple data sets and shows improved inter-species agreement. mEBT is expected to be useful for research groups who use murine models to study human immunity. http://cdal.korea.ac.kr/mebt/. jseok14@korea.ac.kr. Supplementary data are available at Bioinformatics online.

Enhancement by platelets of oxygen radical responses of human neutrophils

Energy Technology Data Exchange (ETDEWEB)

McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

1986-03-01

When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

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...

Responses of human cells to ZnO nanoparticles: a gene transcription study†

Science.gov (United States)

Moos, Philip J.; Olszewski, Kyle; Honeggar, Matthew; Cassidy, Pamela; Leachman, Sancy; Woessner, David; Cutler, N. Shane; Veranth, John M.

2013-01-01

The gene transcript profile responses to metal oxide nanoparticles was studied using human cell lines derived from the colon and skin tumors. Much of the research on nanoparticle toxicology has focused on models of inhalation and intact skin exposure, and effects of ingestion exposure and application to diseased skin are relatively unknown. Powders of nominally nanosized SiO2, TiO2, ZnO and Fe2O3 were chosen because these substances are widely used in consumer products. The four oxides were evaluated using colon-derived cell lines, RKO and CaCo-2, and ZnO and TiO2 were evaluated further using skin-derived cell lines HaCaT and SK Mel-28. ZnO induced the most notable gene transcription changes, even though this material was applied at the lowest concentration. Nano-sized and conventional ZnO induced similar responses suggesting common mechanisms of action. The results showed neither a non-specific response pattern common to all substances nor synergy of the particles with TNF-α cotreatment. The response to ZnO was not consistent with a pronounced proinflammatory signature, but involved changes in metal metabolism, chaperonin proteins, and protein folding genes. This response was observed in all cell lines when ZnO was in contact with the human cells. When the cells were exposed to soluble Zn, the genes involved in metal metabolism were induced but the genes involved in protein refoldling were unaffected. This provides some of the first data on the effects of commercial metal oxide nanoparticles on human colon-derived and skin-derived cells. PMID:21769377

[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.

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…

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.

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

Quantifying human response capabilities towards tsunami threats at community level

Science.gov (United States)

Post, J.; Mück, M.; Zosseder, K.; Wegscheider, S.; Taubenböck, H.; Strunz, G.; Muhari, A.; Anwar, H. Z.; Birkmann, J.; Gebert, N.

2009-04-01

Decision makers at the community level need detailed information on tsunami risks in their area. Knowledge on potential hazard impact, exposed elements such as people, critical facilities and lifelines, people's coping capacity and recovery potential are crucial to plan precautionary measures for adaptation and to mitigate potential impacts of tsunamis on society and the environment. A crucial point within a people-centred tsunami risk assessment is to quantify the human response capabilities towards tsunami threats. Based on this quantification and spatial representation in maps tsunami affected and safe areas, difficult-to-evacuate areas, evacuation target points and evacuation routes can be assigned and used as an important contribution to e.g. community level evacuation planning. Major component in the quantification of human response capabilities towards tsunami impacts is the factor time. The human response capabilities depend on the estimated time of arrival (ETA) of a tsunami, the time until technical or natural warning signs (ToNW) can be received, the reaction time (RT) of the population (human understanding of a tsunami warning and the decision to take appropriate action), the evacuation time (ET, time people need to reach a safe area) and the actual available response time (RsT = ETA - ToNW - RT). If RsT is larger than ET, people in the respective areas are able to reach a safe area and rescue themselves. Critical areas possess RsT values equal or even smaller ET and hence people whin these areas will be directly affected by a tsunami. Quantifying the factor time is challenging and an attempt to this is presented here. The ETA can be derived by analyzing pre-computed tsunami scenarios for a respective area. For ToNW we assume that the early warning center is able to fulfil the Indonesian presidential decree to issue a warning within 5 minutes. RT is difficult as here human intrinsic factors as educational level, believe, tsunami knowledge and experience

Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

Science.gov (United States)

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

2009-01-01

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 fetus that may have implications for sex-specific programming influences. PMID:19726143

Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans

Directory of Open Access Journals (Sweden)

Line Larry L

2010-03-01

Full Text Available Abstract Background Astaxanthin modulates immune response, inhibits cancer cell growth, reduces bacterial load and gastric inflammation, and protects against UVA-induced oxidative stress in in vitro and rodent models. Similar clinical studies in humans are unavailable. Our objective is to study the action of dietary astaxanthin in modulating immune response, oxidative status and inflammation in young healthy adult female human subjects. Methods Participants (averaged 21.5 yr received 0, 2, or 8 mg astaxanthin (n = 14/diet daily for 8 wk in a randomized double-blind, placebo-controlled study. Immune response was assessed on wk 0, 4 and 8, and tuberculin test performed on wk 8. Results Plasma astaxanthin increased (P helper, Tcytotoxic or natural killer cells. A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8. Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects. There was no difference in TNF and IL-2 concentrations, but plasma IFN-γ and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin. Conclusion Therefore, dietary astaxanthin decreases a DNA damage biomarker and acute phase protein, and enhances immune response in young healthy females.

Human vertical eye movement responses to earth horizontal pitch

Science.gov (United States)

Wall, C. 3rd; Petropoulos, A. E.

1993-01-01

The vertical eye movements in humans produced in response to head-over-heels constant velocity pitch rotation about a horizontal axis resemble those from other species. At 60 degrees/s these are persistent and tend to have non-reversing slow components that are compensatory to the direction of rotation. In most, but not all subjects, the slow component velocity was well characterized by a rapid build-up followed by an exponential decay to a non-zero baseline. Super-imposed was a cyclic or modulation component whose frequency corresponded to the time for one revolution and whose maximum amplitude occurred during a specific head orientation. All response components (exponential decay, baseline and modulation) were larger during pitch backward compared to pitch forward runs. Decay time constants were shorter during the backward runs, thus, unlike left to right yaw axis rotation, pitch responses display significant asymmetries between paired forward and backward runs.

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

OpenAIRE

Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

2017-01-01

Understanding host?enteric virus interactions has been limited by the inability to culture nontransformed small intestinal epithelial cells and to infect animal models with human viruses. We report epithelial responses in human small intestinal enteroid cultures from different individuals following infection with human rotavirus (HRV), a model enteric pathogen. RNA-sequencing and functional assays revealed type III IFN as the dominant transcriptional response that activates interferon-stimula...

Innate Immune Responses of Bat and Human Cells to Filoviruses: Commonalities and Distinctions.

Science.gov (United States)

Kuzmin, Ivan V; Schwarz, Toni M; Ilinykh, Philipp A; Jordan, Ingo; Ksiazek, Thomas G; Sachidanandam, Ravi; Basler, Christopher F; Bukreyev, Alexander

2017-04-15

Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat ( Rousettus aegyptiacus ); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells. The study demonstrated that EBOV and MARV replicate to similar levels in all tested cell lines, indicating that permissiveness for EBOV at cell and organism levels do not necessarily correlate. Filoviruses, particularly MARV, induced a potent innate immune response in rousette cells, which was generally stronger than that in human cells. Both EBOV VP35 and VP24 IID were found to suppress the innate immune response in rousette cells, but only VP35 IID appeared to promote virus replication. Along with IFN-α and IFN-β, IFN-γ was demonstrated to control filovirus infection in bat cells but not in human cells, suggesting host species specificity of the antiviral effect. The antiviral effects of bat IFNs appeared not to correlate with induction of IFN-stimulated genes 54 and 56, which were detected in human cells ectopically expressing bat IFN-α and IFN-β. As bat IFN-γ induced the type I IFN pathway, its antiviral effect is likely to be partially induced via cross talk. IMPORTANCE Bats serve as reservoirs for multiple emerging viruses, including filoviruses, henipaviruses, lyssaviruses, and zoonotic coronaviruses. Although there is no evidence for symptomatic disease caused by either Marburg or Ebola viruses in bats, spillover of these viruses into human populations causes deadly outbreaks. The reason for the lack of symptomatic disease in bats infected with

Corporate Social Responsibility, social contract, corporate personhood and human rights law: Understanding the emerging responsibilities of modern corporations

OpenAIRE

Amao, O

2008-01-01

Copyright @ 2008 Olufemi Amao. The social contract theory has been advanced as a theoretical basis for explaining the emerging practice of Corporate Social Responsibility (CSR) by corporations. Since the 17th century the social contract concept has also been used to justify human rights. The concept is the constitutional foundation of many western states starting with England, US and France. Business ethicists and philosophers have tried to construct and analyse the social responsibility o...

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.

The human intestinal IgA response; burning questions.

Directory of Open Access Journals (Sweden)

Jo eSpencer

2012-05-01

Full Text Available Understanding the cellular and molecular mechanisms that generate the human intestinal IgA response is fundamentally important if effective mucosal vaccination is to be successful and broadly applied. There have been several major advances in this field recently that have allowed us to feel optimistic that this will be achieved. However, there are still many unanswered questions. These questions have been used as a scaffold for this review that considers findings at the current leading edge alongside the many uncertainties in this field.

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

2013-04-01

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 education on immigration issues, and political action toward a more humane immigration reform. Detailed examples of human rights abuses and the WICIR activities described in response to the abuses serve as illustrations of social work advocacy, education, and policy formulation that affect the general public, policymakers, and law enforcement officials.

The thermal environment of the human being on the global scale.

Science.gov (United States)

Jendritzky, Gerd; Tinz, Birger

2009-11-11

The close relationship between human health, performance, well-being and the thermal environment is obvious. Nevertheless, most studies of climate and climate change impacts show amazing shortcomings in the assessment of the environment. Populations living in different climates have different susceptibilities, due to socio-economic reasons, and different customary behavioural adaptations. The global distribution of risks of hazardous thermal exposure has not been analysed before. To produce maps of the baseline and future bioclimate that allows a direct comparison of the differences in the vulnerability of populations to thermal stress across the world. The required climatological data fields are obtained from climate simulations with the global General Circulation Model ECHAM4 in T106-resolution. For the thermo-physiologically relevant assessment of these climate data a complete heat budget model of the human being, the 'Perceived Temperature' procedure has been applied which already comprises adaptation by clothing to a certain degree. Short-term physiological acclimatisation is considered via Health Related Assessment of the Thermal Environment. The global maps 1971-1980 (control run, assumed as baseline climate) show a pattern of thermal stress intensities as frequencies of heat. The heat load for people living in warm-humid climates is the highest. Climate change will lead to clear differences in health-related thermal stress between baseline climate and the future bioclimate 2041-2050 based on the 'business-as-usual' greenhouse gas scenario IS92a. The majority of the world's population will be faced with more frequent and more intense heat strain in spite of an assumed level of acclimatisation. Further adaptation measures are crucial in order to reduce the vulnerability of the populations. This bioclimatology analysis provides a tool for various questions in climate and climate change impact research. Considerations of regional or local scale require climate

Response of the seated human body to whole-body vertical vibration: biodynamic responses to mechanical shocks.

Science.gov (United States)

Zhou, Zhen; Griffin, Michael J

2017-03-01

The biodynamic response of the seated human body has been investigated with 20 males exposed to upward and downward shocks at 13 fundamental frequencies (1-16 Hz) and 18 magnitudes (up to ±8.3 ms -2 ). For 1- and 2- degree-of-freedom models, the stiffness and damping coefficients were obtained by fitting seat acceleration waveforms predicted from the measured force to the measured seat acceleration waveform. Stiffness and damping coefficients were also obtained in the frequency domain with random vibration. The optimum stiffness and damping coefficients varied with the magnitude and the frequency of shocks. With both upward and downward shocks, the resonance frequency of the models decreased from 6.3 to 4 Hz as the vibration dose values of the shocks increased from 0.05 to 2.0 ms -1.75 . The stiffness and damping obtained from responses to shocks were correlated with, and similar to, the stiffness and damping obtained with random vibration. Practitioner Summary: When modelling the dynamic response of the seated human body to vertical acceleration less than 1 g, the relation between force and acceleration can be well represented by a single degree-of-freedom model although the optimum stiffness and damping depend on the magnitude and frequency of sinusoidal, random or shock motion.

The Radiation Dose-Response of the Human Spinal Cord

International Nuclear Information System (INIS)

Schultheiss, Timothy E.

2008-01-01

Purpose: To characterize the radiation dose-response of the human spinal cord. Methods and Materials: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and α/β ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. Results: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The α/β = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. Conclusions: The estimate of α/β is smaller than usually quoted, but values this small were found in some studies. Using α/β = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation

Nonlinear dynamics of cortical responses to color in the human cVEP.

Science.gov (United States)

Nunez, Valerie; Shapley, Robert M; Gordon, James

2017-09-01

The main finding of this paper is that the human visual cortex responds in a very nonlinear manner to the color contrast of pure color patterns. We examined human cortical responses to color checkerboard patterns at many color contrasts, measuring the chromatic visual evoked potential (cVEP) with a dense electrode array. Cortical topography of the cVEPs showed that they were localized near the posterior electrode at position Oz, indicating that the primary cortex (V1) was the major source of responses. The choice of fine spatial patterns as stimuli caused the cVEP response to be driven by double-opponent neurons in V1. The cVEP waveform revealed nonlinear color signal processing in the V1 cortex. The cVEP time-to-peak decreased and the waveform's shape was markedly narrower with increasing cone contrast. Comparison of the linear dynamics of retinal and lateral geniculate nucleus responses with the nonlinear dynamics of the cortical cVEP indicated that the nonlinear dynamics originated in the V1 cortex. The nature of the nonlinearity is a kind of automatic gain control that adjusts cortical dynamics to be faster when color contrast is greater.

Fractional poisson--a simple dose-response model for human norovirus.

Science.gov (United States)

Messner, Michael J; Berger, Philip; Nappier, Sharon P

2014-10-01

This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.

Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells.

Directory of Open Access Journals (Sweden)

Junping Ren

Full Text Available Human metapneumovirus (hMPV is a leading cause of lower respiratory infection in young children, the elderly and immunocompromised patients. Repeated hMPV infections occur throughout life. However, immune evasion mechanisms of hMPV infection are largely unknown. Recently, our group has demonstrated that hMPV M2-2 protein, an important virulence factor, contributes to immune evasion in airway epithelial cells by targeting the mitochondrial antiviral-signaling protein (MAVS. Whether M2-2 regulates the innate immunity in human dendritic cells (DC, an important family of immune cells controlling antigen presenting, is currently unknown. We found that human DC infected with a virus lacking M2-2 protein expression (rhMPV-ΔM2-2 produced higher levels of cytokines, chemokines and IFNs, compared to cells infected with wild-type virus (rhMPV-WT, suggesting that M2-2 protein inhibits innate immunity in human DC. In parallel, we found that myeloid differentiation primary response gene 88 (MyD88, an essential adaptor for Toll-like receptors (TLRs, plays a critical role in inducing immune response of human DC, as downregulation of MyD88 by siRNA blocked the induction of immune regulatory molecules by hMPV. Since M2-2 is a cytoplasmic protein, we investigated whether M2-2 interferes with MyD88-mediated antiviral signaling. We found that indeed M2-2 protein associated with MyD88 and inhibited MyD88-dependent gene transcription. In this study, we also identified the domains of M2-2 responsible for its immune inhibitory function in human DC. In summary, our results demonstrate that M2-2 contributes to hMPV immune evasion by inhibiting MyD88-dependent cellular responses in human DC.

T-dependence of human B lymphocyte proliferative response to mitogens.

Science.gov (United States)

Brochier, J; Samarut, C; Gueho, J P; Revillard, J P

1976-01-01

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.

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

Evaluation of the Effects of Variable Helmet Weight on Human Response During Lateral +Gy Impact

National Research Council Canada - National Science Library

Perry, Chris

2003-01-01

.... A series of tests was conducted by AFRL/HEPA on a horizontal impulse accelerator using human subjects to investigate the effects of helmet inertial properties on human response to short duration...

Human duodenal motor activity in response to acid and different nutrients

NARCIS (Netherlands)

Schwartz, M. P.; Samsom, M.; Smout, A. J.

2001-01-01

Duodenal motor activity in response to intraduodenal infusion of small volumes of acid and nutrients of different chemical composition was studied in 10 healthy humans, using a water-perfused catheter incorporating 20 antropyloroduodenal sideholes. Saline and dextrose did not affect motility. Acid

Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress.

Science.gov (United States)

Kraft, David Christian Evar; Bindslev, Dorth Arenholt; Melsen, Birte; Klein-Nulend, Jenneke

2011-02-01

For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular response via loading-induced flow of interstitial fluid. After surgical removal of ectopically impacted third molars, human dental pulp tissue is an easily accessible and interesting source of cells for mineralized tissue engineering. The aim of this study was to determine whether human dental pulp-derived cells (DPC) are responsive to mechanical loading by pulsating fluid flow (PFF) upon stimulation of mineralization in vitro. Human DPC were incubated with or without mineralization medium containing differentiation factors for 3 weeks. Cells were subjected to 1-h PFF (0.7 ± 0.3 Pa, 5 Hz) and the response was quantified by measuring nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, and gene expression of cyclooxygenase (COX)-1 and COX-2. We found that DPC are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. PFF stimulated NO and PGE₂ production, and up-regulated COX-2 but not COX-1 gene expression. In DPC cultured under mineralizing conditions, the PFF-induced NO, but not PGE₂, production was significantly enhanced. These data suggest that human DPC, like osteogenic cells, acquire responsiveness to pulsating fluid shear stress in mineralizing conditions. Thus DPC might be able to perform bone-like functions during mineralized tissue remodeling in vivo, and therefore provide a promising new tool for mineralized tissue engineering to restore, for example, maxillofacial defects.

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...

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.

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

Science.gov (United States)

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

2013-01-01

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

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.

Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

Science.gov (United States)

Duez, C; Gras-Masse, H; Hammad, H; Akoum, H; Didierlaurent, A; André, C; Tonnel, A B; Pestel, J

2001-01-01

We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.

Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells.

Science.gov (United States)

Prabakar, Kamalaveni R; Domínguez-Bendala, Juan; Molano, R Damaris; Pileggi, Antonello; Villate, Susana; Ricordi, Camillo; Inverardi, Luca

2012-01-01

We sought to assess the potential of human cord blood-derived mesenchymal stem cells (CB-MSCs) to derive insulin-producing, glucose-responsive cells. We show here that differentiation protocols based on stepwise culture conditions initially described for human embryonic stem cells (hESCs) lead to differentiation of cord blood-derived precursors towards a pancreatic endocrine phenotype, as assessed by marker expression and in vitro glucose-regulated insulin secretion. Transplantation of these cells in immune-deficient animals shows human C-peptide production in response to a glucose challenge. These data suggest that human cord blood may be a promising source for regenerative medicine approaches for the treatment of diabetes mellitus.

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.

Statistical methods for analysing responses of wildlife to human disturbance.

Science.gov (United States)

Haiganoush K. Preisler; Alan A. Ager; Michael J. Wisdom

2006-01-01

1. Off-road recreation is increasing rapidly in many areas of the world, and effects on wildlife can be highly detrimental. Consequently, we have developed methods for studying wildlife responses to off-road recreation with the use of new technologies that allow frequent and accurate monitoring of human-wildlife interactions. To illustrate these methods, we studied the...

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

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......Taking its point of departure in the aims of the United Nations, the article discusses challenges to international law making and the UN in the relatively immediate future in view of the increasing role and influence of corporations. This is done addressing challenges posed by globalisation......, in particular with regard to the appropriateness of past and present ideas of duty holders, modes of regulation, and law making, to deliver the aims of the UN; International law making and actors in this process; and a changing character of law and legal regulation, towards deregulation and private regulation...

[The physical therapy undergraduate students' responses to the gross human anatomy subjects].

Science.gov (United States)

Anahara, Reiko; Kawashiro, Yukiko; Matsuno, Yoshiharu; Mori, Chisato; Kohno, Toshihiko

2008-09-01

Instruction in gross human anatomy is one of the important items in the subject for co-medical students of the physical therapist course. The physical therapy undergraduate students are required to have a solid understanding of the structure and formation of the human body. Therefore, their good-understanding of the course on the gross human anatomy and their experience of the gross human anatomy laboratory (observation practice) are acquired to improve their knowledge of the human body. To clarify the student responses to the gross human anatomy course including the gross human anatomy laboratory, several questionnaires were administered to the freshman physical therapy undergraduate student for two years. We found that more than 80% of the students, who felt a negative attitude for gross human anatomy before the course started, had a positive attitude about the gross human anatomy after going through the course. The experience of the gross human anatomy laboratory increased the students' activity of learning and they thought more about the dignity of being human after the course than before viewing. In addition, the results suggested that the multiple experiences of the gross human anatomy course are useful for the physical therapy undergraduate students to improve the quality of their understanding of the human body.

'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

Neural Correlates of the Cortisol Awakening Response in Humans.

Science.gov (United States)

Boehringer, Andreas; Tost, Heike; Haddad, Leila; Lederbogen, Florian; Wüst, Stefan; Schwarz, Emanuel; Meyer-Lindenberg, Andreas

2015-08-01

The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel-based morphometry) magnetic resonance imaging. Across subjects, a smaller CAR was associated with reduced grey matter volume and increased stress-related brain activity in the perigenual ACC, a region which inhibits HPA axis activity during stress that is implicated in risk mechanisms and pathophysiology of stress-related mental diseases. Moreover, functional connectivity between the perigenual ACC and the hypothalamus, the primary controller of HPA axis activity, was associated with the CAR. Our findings provide support for a role of the perigenual ACC in regulating the CAR in humans and may aid future research on the pathophysiology of stress-related illnesses, such as depression, and environmental risk for illnesses such as schizophrenia.

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.

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

Inhibition of EGF processing in responsive and nonresponsive human fibroblasts

International Nuclear Information System (INIS)

Schaudies, R.P.; Wray, H.L.

1988-01-01

We have examined the proteolytic processing of radiolabeled epidermal growth factor (EGF) in EGF growth-responsive human foreskin fibroblasts (HFF) versus EGF nonresponsive human fetal lung fibroblasts (HFL). Previous studies have shown that both cell lines demonstrate similar binding affinities and numbers of binding sites, as well as similar rates of internalization and degradation of the bound, radiolabeled hormone. We have used nondenaturing electrophoresis to compare how these two cell lines process EGF at its carboxy terminus. EGF lacking either one [des-(53)-EGF] or six [des (48-53)-EGF] carboxy terminal amino acids could be distinguished by this method. Chloroquine or leupeptin were added to the incubation system in an attempt to accentuate potential differences in hormonal processing between the responsive and nonresponsive cell lines. In the absence of inhibitors, the responsive and nonresponsive cells generated similar distributions of processed forms of EGF after 30-minutes incubation. However, after 4-hours incubation in the constant presence of 125I-EGF, the electrophoretic profiles of extracted hormone were substantially different. The radiolabel within the responsive cells, as well as that released from them, migrated predominantly at the dye front, indicating complete degradation of EGF. In contrast, the majority of the radiolabel within the nonresponsive cells migrated as partially processed forms of hormone, while the released radiolabel migrated at the dye front. Addition of chloroquine to either cell line inhibited processing of EGF beyond removal of the carboxyl terminal arginine residue. Both intact 125I-EGF, and 125I-EGF lacking the carboxyl terminal arginine were released from chloroquine-treated cells in a ratio equal to that present in the intact cells

Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia

DEFF Research Database (Denmark)

Klausen, T; Christensen, H; Hansen, J M

1996-01-01

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO2 to the hypoxic gas. On separate days, eight healthy male subjects were...

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...

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

Oxidized DNA induces an adaptive response in human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Kostyuk, Svetlana V., E-mail: svet.kostyuk@gmail.com [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Tabakov, Viacheslav J.; Chestkov, Valerij V.; Konkova, Marina S.; Glebova, Kristina V.; Baydakova, Galina V.; Ershova, Elizaveta S.; Izhevskaya, Vera L. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Baranova, Ancha, E-mail: abaranov@gmu.edu [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Center for the Study of Chronic Metabolic Diseases, School of System Biology, George Mason University, Fairfax, VA 22030 (United States); Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

2013-07-15

Highlights: • We describe the effects of gDNAOX on human fibroblasts cultivated in serum withdrawal conditions. • gDNAOX evokes an adaptive response in human fibroblasts. • gDNAOX increases the survival rates in serum starving cell populations. • gDNAOX enhances the survival rates in cell populations irradiated at 1.2 Gy dose. • gDNAOX up-regulates NRF2 and inhibits NF-kappaB-signaling. - Abstract: Cell-free DNA (cfDNA) released from dying cells contains a substantial proportion of oxidized nucleotides, thus, forming cfDNA{sup OX}. The levels of cfDNA{sup OX} are increased in the serum of patients with chronic diseases. Oxidation of DNA turns it into a stress signal. The samples of genomic DNA (gDNA) oxidized by H{sub 2}O{sub 2}in vitro (gDNA{sup OX}) induce effects similar to that of DNA released from damaged cells. Here we describe the effects of gDNA{sup OX} on human fibroblasts cultivated in the stressful conditions of serum withdrawal. In these cells, gDNA{sup OX} evokes an adaptive response that leads to an increase in the rates of survival in serum starving cell populations as well as in populations irradiated at the dose of 1.2 Gy. These effects are not seen in control populations of fibroblasts treated with non-modified gDNA. In particular, the exposure to gDNA{sup OX} leads to a decrease in the expression of the proliferation marker Ki-67 and an increase in levels of PSNA, a decrease in the proportion of subG1- and G2/M cells, a decrease in proportion of cells with double strand breaks (DSBs). Both gDNA{sup OX} and gDNA suppress the expression of DNA sensors TLR9 and AIM2 and up-regulate nuclear factor-erythroid 2 p45-related factor 2 (NRF2), while only gDNA{sup OX} inhibits NF-κB signaling. gDNA{sup OX} is a model for oxidized cfDNA{sup OX} that is released from the dying tumor cells and being carried to the distant organs. The systemic effects of oxidized DNA have to be taken into account when treating tumors. In particular, the damaged DNA

CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic Cell-Mediated CD4 T Cell Responses.

Science.gov (United States)

Wong, Kuan Y; Baron, Rebecca; Seldon, Therese A; Jones, Martina L; Rice, Alison M; Munster, David J

2018-05-15

Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells. Copyright © 2018 by The American Association of Immunologists, Inc.

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

Science.gov (United States)

Ge, Yue; Bruno, Maribel; Haykal-Coates, Najwa; Wallace, Kathleen; Andrews, Debora; Swank, Adam; Winnik, Witold; Ross, Jeffrey A.

2016-01-01

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 and protein response-based biochemical pathways represents a key mechanism through which nickel induces cytotoxicity and carcinogenesis. To identify protein responses and biochemical pathways that are critical to nickel-induced toxicity responses, we measured cytotoxicity and changes in expression and phosphorylation status of 14 critical biochemical pathway regulators in human BEAS-2B cells exposed to four concentrations of nickel using an integrated proteomic approach. A subset of the pathway regulators, including interleukin-6, and JNK, were found to be linearly correlated with cell viability, and may function as molecular determinants of cytotoxic responses of BEAS-2B cells to nickel exposures. In addition, 128 differentially expressed proteins were identified by two dimensional electrophoresis (2-DE) and mass spectrometry. Principal component analysis, hierarchical cluster analyses, and ingenuity signaling pathway analysis (IPA) identified putative nickel toxicity pathways. Some of the proteins and pathways identified have not previously been linked to nickel toxicity. Based on the consistent results obtained from both ELISA and 2-DE proteomic analysis, we propose a core signaling pathway regulating cytotoxic responses of human BEAS-2B cells to nickel exposures, which integrates a small set of proteins involved in glycolysis and gluconeogenesis pathways, apoptosis, protein degradation, and stress responses including inflammation and oxidative stress. PMID:27626938

Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice

Science.gov (United States)

Jaiswal, Smita; Pazoles, Pamela; Woda, Marcia; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

2012-01-01

Dengue is a mosquito-borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD-scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co-transplantation of human fetal thymus and liver tissues into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell-engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice secreted interferon-γ in response to overlapping DENV peptide pools and HLA-A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections. PMID:22384859

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.

Monitoring the Performance of Human and Automated Scores for Spoken Responses

Science.gov (United States)

Wang, Zhen; Zechner, Klaus; Sun, Yu

2018-01-01

As automated scoring systems for spoken responses are increasingly used in language assessments, testing organizations need to analyze their performance, as compared to human raters, across several dimensions, for example, on individual items or based on subgroups of test takers. In addition, there is a need in testing organizations to establish…

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.

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

International Nuclear Information System (INIS)

Rocke, David

2016-01-01

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.

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.

Thermo-responsive human α-elastin self-assembled nanoparticles for protein delivery.

Science.gov (United States)

Kim, Jae Dong; Jung, Youn Jae; Woo, Chang Hee; Choi, Young Chan; Choi, Ji Suk; Cho, Yong Woo

2017-01-01

Self-assembled nanoparticles based on PEGylated human α-elastin were prepared as a potential vehicle for sustained protein delivery. The α-elastin was extracted from human adipose tissue and modified with methoxypolyethyleneglycol (mPEG) to control particle size and enhance the colloidal stability. The PEGylated human α-elastin showed sol-to-particle transition with a lower critical solution temperature (LCST) of 25°C-40°C in aqueous media. The PEGylated human α-elastin nanoparticles (PhENPs) showed a narrow size distribution with an average diameter of 330±33nm and were able to encapsulate significant amounts of insulin and bovine serum albumin (BSA) upon simple mixing at low temperature in water and subsequent heating to physiological temperature. The release profiles of insulin and BSA showed sustained release for 72h. Overall, the thermo-responsive self-assembled PhENPs provide a useful tool for a range of protein delivery and tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2016-04-01

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

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

Science.gov (United States)

Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

2017-01-01

The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine. PMID:28069942

Mucorales spores induce a proinflammatory cytokine response in human mononuclear phagocytes and harbor no rodlet hydrophobins.

Science.gov (United States)

Wurster, Sebastian; Thielen, Vanessa; Weis, Philipp; Walther, Paul; Elias, Johannes; Waaga-Gasser, Ana Maria; Dragan, Mariola; Dandekar, Thomas; Einsele, Hermann; Löffler, Jürgen; Ullmann, Andrew J

2017-11-17

Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and Ascomycota. PBMC, monocytes, and monocyte derived dendritic cells (moDCs) from healthy donors were stimulated with resting and germinated stages of Mucorales and Ascomycota. Cytokine response and expression of activation markers were studied. Both inactivated germ tubes and resting spores of Rhizopus arrhizus and other human pathogenic Mucorales species significantly stimulated mRNA synthesis and secretion of proinflammatory cytokines. Moreover, R. arrhizus spores induced the upregulation of co-stimulatory molecules on moDCs and a specific T-helper cell response. Removal of rodlet hydrophobins by hydrofluoric acid treatment of A. fumigatus conidia resulted in enhanced immunogenicity, whereas the cytokine response of PBMCs to dormant R. arrhizus spores was not influenced by hydrofluoric acid. Scanning electron micrographs of Mucorales spores did not exhibit any morphological correlates of rodlet hydrophobins. Taken together, this study revealed striking differences in the response of human mononuclear cells to resting stages of Ascomycota and Mucorales, which may be explained by absence of an immunoprotective hydrophobin layer in Mucorales spores.

Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

Directory of Open Access Journals (Sweden)

Kai Weng

Full Text Available Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1 as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.

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

DEFF Research Database (Denmark)

Vissing, Kristian; Schjerling, Peter

2014-01-01

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 dir...

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.

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.

Human Response to Emergency Warning

Science.gov (United States)

Sorensen, J.

2009-12-01

Almost every day people evacuate from their homes, businesses or other sites, even ships, in response to actual or predicted threats or hazards. Evacuation is the primary protective action utilized in large-scale emergencies such as hurricanes, floods, tornados, tsunamis, volcanic eruptions, or wildfires. Although often precautionary, protecting human lives by temporally relocating populations before or during times of threat remains a major emergency management strategy. One of the most formidable challenges facing emergency officials is evacuating residents for a fast-moving and largely unpredictable event such as a wildfire or a local tsunami. How to issue effective warnings to those at risk in time for residents to take appropriate action is an on-going problem. To do so, some communities have instituted advanced communications systems that include reverse telephone call-down systems or other alerting systems to notify at-risk residents of imminent threats. This presentation examines the effectiveness of using reverse telephone call-down systems for warning San Diego residents of wildfires in the October of 2007. This is the first systematic study conducted on this topic and is based on interviews with 1200 households in the evacuation areas.

Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer

International Nuclear Information System (INIS)

Barni, S.; Lissoni, P.; Tancini, G.

1986-01-01

While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demostrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation

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.

Response of human fibroblasts to low dose rate gamma irradiation

International Nuclear Information System (INIS)

Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

1984-01-01

Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to γ radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D 0 ) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury

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

The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal.

Science.gov (United States)

Ambagtsheer, Frederike; Weimar, Willem

2016-02-01

Over the years, the trade in human organs has become an object of international concern. Since the 1980s, antiorgan trade initiatives have mainly involved the strengthening of legislative responses. Little attention however is given to nonlegislative responses by law enforcement authorities. The HOTT project is a European Union-funded research project titled "trafficking in human beings for the purpose of organ removal." Its objectives are to increase knowledge, raise awareness, and improve the nonlegislative response to the crime. Its consortium organized a "Writers' Conference" in The Hague, The Netherlands at Europol's Headquarters where a group of 40 experts, consisting of transplant professionals, law enforcement officials, and policy makers, formulated recommendations to improve nonlegislative responses. These recommendations, presented hereafter, address the ethical and legal obligations of health care providers, the protection of persons trafficked for the purpose of organ removal, strengthening cross-border collaboration in criminal cases, and stimulating partnerships between transplant professionals and law enforcement. These recommendations offer ways in which transplant professionals can contribute to improving the nonlegislative response to trafficking in human beings for the purpose of organ removal.

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.

Endurance exercise training increases peripheral vascular response in human fingers.

Science.gov (United States)

Katayama, K; Shimoda, M; Maeda, J; Takemiya, T

1998-10-01

The purpose of this study was to clarify whether peripheral vascular response to alteration of transmural pressure is changed by endurance exercise training. The healthy male subjects (training group; n = 6) performed endurance exercise training that consisted of cycle ergometer exercise 5 d.week-1 and 30 min.d-1 for a period of 8 weeks. Changes in the peripheral vascular response to alteration of transmural pressure in the human finger were measured by a differential digital photoplethysmogram (DeltaDPG) and blood pressure during passive movement of the arm to different vertical hand positions relative to heart level. Following 8 weeks of endurance training, percent changes in DeltaDPG from heart level in the training group increased significantly (mean +/- SD, -48.1 +/- 7. 3 to -58.7 +/- 9.3% at the lowered position, 46.1 +/- 13.4 to 84.6 +/- 8.8% at the elevated position, ppressure, also significantly changed in the training group over the 8 weeks (5.6 +/- 1.3 to 2.7 +/- 1.6 mV. V-1.s-1.mmHg-1 at the lowered position, 30.0 +/- 12.4 to 54.4 +/- 18. 9 mV.V-1.s-1.mmHg-1 at the elevated position ). Maximal oxygen uptake (V.O2 max) was significantly increased in the training group. On the other hand, the control group (n = 6) showed no significant changes in all parameters for 8 weeks. Therefore these results suggest that endurance exercise training induces an increase in peripheral vascular response to alteration of transmural pressure in the human finger.

Characterization of humoral and cellular immune responses in patients with human papilloma virus

International Nuclear Information System (INIS)

Clares Pochet, Maria del Carmen; Ferrer Cosme, Belkis Maria; Dominguez Cardosa, Magda

2012-01-01

A descriptive and cross-sectional study was carried out in 30 females infected with the human papilloma virus, attended in the office of Immunology of the Specialty Polyclinic belonging to 'Saturnino Lora' Provincial Clinical Surgical Teaching Hospital in Santiago de Cuba, from June 2009 to June 2010, in order to characterize them according to immune response. To evaluate the humoral and cellular immune response rosetting assay and quantification of immunoglobulins were used respectively. Women between 25-36 years of age (40 %) infected with this virus, especially those coming from urban areas, prevailed in the series, and a significant decrease of the cellular response as compared to the humoral response was evidenced

A molecular arms race between host innate antiviral response and emerging human coronaviruses.

Science.gov (United States)

Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

2016-02-01

Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Survey of innate immune responses to Burkholderia pseudomallei in human blood identifies a central role for lipopolysaccharide.

Directory of Open Access Journals (Sweden)

Narisara Chantratita

Full Text Available B. pseudomallei is a gram-negative bacterium that causes the tropical infection melioidosis. In northeast Thailand, mortality from melioidosis approaches 40%. As exemplified by the lipopolysaccharide-Toll-like receptor 4 interaction, innate immune responses to invading bacteria are precipitated by activation of host pathogen recognition receptors by pathogen associated molecular patterns. Human melioidosis is characterized by up-regulation of pathogen recognition receptors and pro-inflammatory cytokine release. In contrast to many gram-negative pathogens, however, the lipopolysaccharide of B. pseudomallei is considered only weakly inflammatory. We conducted a study in 300 healthy Thai subjects to investigate the ex vivo human blood response to various bacterial pathogen associated molecular patterns, including lipopolysaccharide from several bacteria, and to two heat-killed B. pseudomallei isolates. We measured cytokine levels after stimulation of fresh whole blood with a panel of stimuli. We found that age, sex, and white blood cell count modulate the innate immune response to B. pseudomallei. We further observed that, in comparison to other stimuli, the innate immune response to B. pseudomallei is most highly correlated with the response to lipopolysaccharide. The magnitude of cytokine responses induced by B. pseudomallei lipopolysaccharide was significantly greater than those induced by lipopolysaccharide from Escherichia coli and comparable to many responses induced by lipopolysaccharide from Salmonella minnesota despite lower amounts of lipid A in the B. pseudomallei lipopolysaccharide preparation. In human monocytes stimulated with B. pseudomallei, addition of polymyxin B or a TLR4/MD-2 neutralizing antibody inhibited the majority of TNF-α production. Challenging existing views, our data indicate that the innate immune response to B. pseudomallei in human blood is largely driven by lipopolysaccharide, and that the response to B

A study on the quantitative model of human response time using the amount and the similarity of information

International Nuclear Information System (INIS)

Lee, Sung Jin

2006-02-01

The mental capacity to retain or recall information, or memory is related to human performance during processing of information. Although a large number of studies have been carried out on human performance, little is known about the similarity effect. The purpose of this study was to propose and validate a quantitative and predictive model on human response time in the user interface with the basic concepts of information amount, similarity and degree of practice. It was difficult to explain human performance by only similarity or information amount. There were two difficulties: constructing a quantitative model on human response time and validating the proposed model by experimental work. A quantitative model based on the Hick's law, the law of practice and similarity theory was developed. The model was validated under various experimental conditions by measuring the participants' response time in the environment of a computer-based display. Human performance was improved by degree of similarity and practice in the user interface. Also we found the age-related human performance which was degraded as he or she was more elder. The proposed model may be useful for training operators who will handle some interfaces and predicting human performance by changing system design

Capturing community context of human response to forest disturbance by insects: a multi-method assessment

Science.gov (United States)

Hua Qin; Courtney G. Flint

2010-01-01

The socioeconomic and environmental features of local places (community context) influence the relationship between humans and their physical environment. In times of environmental disturbance, this community context is expected to influence human perceptual and behavioral responses. Residents from nine Colorado communities experiencing a large outbreak of mountain...

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

International Nuclear Information System (INIS)

Sokolov, Mykyta V.; Panyutin, Irina V.; Panyutin, Igor G.; Neumann, Ronald D.

2011-01-01

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.

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.

Evolution and behavioural responses to human-induced rapid environmental change.

Science.gov (United States)

Sih, Andrew; Ferrari, Maud C O; Harris, David J

2011-03-01

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.

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.

Molecular mechanisms of radioadaptive responses in human lymphoblastoid cells

International Nuclear Information System (INIS)

Kakimoto, Ayana; Taki, Keiko; Nakajima, Tetsuo

2008-01-01

Radioadaptive response is a biodefensive response observed in a variety of mammalian cells and animals where exposure to low dose radiation induces resistance against the subsequent high dose radiation. Elucidation of its mechanisms is important for risk estimation of low dose radiation because the radioadaptive response implies that low dose radiation affects cells/individuals in a different manner from high dose radiation. In the present study, we explored the molecular mechanisms of the radioadaptive response in human lymphoblastoid cells AHH-1 in terms of mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene locus. First we observed that preexposure to the priming dose in the range from 0.02 Gy to 0.2 Gy significantly reduced mutation frequency at HPRT gene locus after irradiation with 3 Gy of X rays. As no significant adaptive response was observed with the priming dose of 0.005 Gy, it was indicated that the lower limit of the priming dose to induce radioadaptive response may be between 0.005 Gy and 0.02 Gy. Second, we examined the effect of 3-amino-benzamide (3AB), an inhibitor of poly(ADP-ribose)polymerase1, which has been reported to inhibit the radioadaptive response in terms of chromosome aberration. However we could observe significant radioadaptive responses in terms of mutation even in the presence of 3AB. These findings suggested that molecular mechanisms of the radioadaptive response in terms of mutation may be different from that for radioadaptive responses in terms of chromosomal aberration, although we could not exclude a possibility that the differential effects of 3AB was due to cell type difference. Finally, by performing a comprehensive analysis of alterations in gene expression using high coverage expression profiling (HiCEP), we could identify 17 genes whose expressions were significantly altered 6 h after irradiation with 0.02 Gy. We also found 17 and 20 genes, the expressions of which were different with or without priming

Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

Science.gov (United States)

Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

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

Leptin regulates dopamine responses to sustained stress in humans.

Science.gov (United States)

Burghardt, Paul R; Love, Tiffany M; Stohler, Christian S; Hodgkinson, Colin; Shen, Pei-Hong; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar

2012-10-31

Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.

Human Responding on Random-Interval Schedules of Response-Cost Punishment: The Role of Reduced Reinforcement Density

Science.gov (United States)

Pietras, Cynthia J.; Brandt, Andrew E.; Searcy, Gabriel D.

2010-01-01

An experiment with adult humans investigated the effects of response-contingent money loss (response-cost punishment) on monetary-reinforced responding. A yoked-control procedure was used to separate the effects on responding of the response-cost contingency from the effects of reduced reinforcement density. Eight adults pressed buttons for money…

Diagnostic and immunological aspects of the antibody response to human cytomegalvirus infection

NARCIS (Netherlands)

Middeldorp, Jaap Michiel

1985-01-01

The studies described in this thesis were initiated with three main aims: First, to develop a practical and sensitive method for serodiagnosis of Human cytomegoal virus ( CMV)-infections and to determine the relative diagnostic value of IgM and IgG antibody responses to distinct CMV-antigens.

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

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

Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts

Science.gov (United States)

Prasad, Raju Y.; Chastain, Paul D.; Nikolaishvili-Feinberg, Nana; Smeester, Lisa M.; Kaufmann, William K.; Fry, Rebecca C.

2013-01-01

The use of nanoparticles in consumer products increases their prevalence in the environment and the potential risk to human health. Although recent studies have shown in vivo and in vitro toxicity of titanium dioxide nanoparticles (nano-TiO2), a more detailed view of the underlying mechanisms of this response needs to be established. Here the effects of nano-TiO2 on the DNA damage response and DNA replication dynamics were investigated in human dermal fibroblasts. Specifically, the relationship between nano-TiO2 and the DNA damage response pathways regulated by ATM/Chk2 and ATR/Chk1 were examined. The results show increased phosphorylation of H2AX, ATM, and Chk2 after exposure. In addition, nano-TiO2 inhibited the overall rate of DNA synthesis and frequency of replicon initiation events in DNA combed fibers. Taken together, these results demonstrate that exposure to nano-TiO2 activates the ATM/Chk2 DNA damage response pathway. PMID:22770119

Indirect effects of human-induced environmental change on offspring production mediated by behavioural responses.

Science.gov (United States)

Candolin, Ulrika; Nieminen, Anne; Nyman, Johanna

2014-01-01

Human-induced rapid environmental changes often cause behavioural alterations in animals. The consequences that these alterations in turn have for the viability of populations are, however, poorly known. We used a population of threespine sticklebacks Gasterosteus aculeatus in the Baltic Sea to investigate the consequences of behavioural responses to human-induced eutrophication for offspring production. The investigated population has been growing during the last decades, and one cause could be increased offspring production. We combined field-based surveys with laboratory-based experiments, and found that an enhanced growth of macroalgae relaxed agonistic interactions among males. This allowed more males to nest, improved hatching success, and increased the number of reproductive cycles that males completed. Thus, the behavioural responses were adaptive at the individual level and increased offspring production. However, a larger proportion of small males of low competitive ability reproduced in dense vegetation. As male size and dominance are heritable, this could influence the genetic composition of the offspring. Together with a higher number of offspring produced, this could influence natural selection and the rate of adaptation to the changing environment. Thus, behavioural responses to a rapid human-induced environmental change can influence offspring production, with potential consequences for population dynamics and evolutionary processes.

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.

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.

The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal

Science.gov (United States)

Ambagtsheer, Frederike; Weimar, Willem

2016-01-01

Abstract Over the years, the trade in human organs has become an object of international concern. Since the 1980s, antiorgan trade initiatives have mainly involved the strengthening of legislative responses. Little attention however is given to nonlegislative responses by law enforcement authorities. The HOTT project is a European Union-funded research project titled “trafficking in human beings for the purpose of organ removal.” Its objectives are to increase knowledge, raise awareness, and improve the nonlegislative response to the crime. Its consortium organized a “Writers' Conference” in The Hague, The Netherlands at Europol's Headquarters where a group of 40 experts, consisting of transplant professionals, law enforcement officials, and policy makers, formulated recommendations to improve nonlegislative responses. These recommendations, presented hereafter, address the ethical and legal obligations of health care providers, the protection of persons trafficked for the purpose of organ removal, strengthening cross-border collaboration in criminal cases, and stimulating partnerships between transplant professionals and law enforcement. These recommendations offer ways in which transplant professionals can contribute to improving the nonlegislative response to trafficking in human beings for the purpose of organ removal. PMID:27500254

Human response to local convective and radiant cooling in a warm environment

DEFF Research Database (Denmark)

Melikov, Arsen Krikor; Krejcirikova, Barbora; Kaczmarczyk, Jan

2013-01-01

The response of 24 human subjects to local convective cooling, radiant cooling, and combined radiant and convective cooling was studied at 28°C and 50% relative humidity. The local cooling devices used were (1) a tabletop cooling fan, (2) personalized ventilation providing a stream of clean air, (3...

Induction of non-responsiveness in human allergen-specific type 2 T helper cells.

Science.gov (United States)

Yssel, H; Fasler, S; Lamb, J; de Vries, J E

1994-12-01

Activation of allergen-reactive human T helper (Th)2 cells in the absence of professional antigen-presenting cells, induces non-responsiveness or anergy in these cells in vitro. This induction of anergy is accompanied by phenotypic modulation and altered cytokine production. Furthermore, peptide-treated Th2 cells fail to provide B-cell help for IgE synthesis. Recent studies indicate that impaired signal transduction via the T-cell receptor may account for the lack of responsiveness to antigenic stimulation. Here, we review present knowledge on the cell biology of non-responsive or anergic Th2 cells.

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 underst......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...

Sulfocerebrosides upregulate liposome uptake in human astrocytes without inducing a proinflammatory response.

Science.gov (United States)

Suesca, Elizabeth; Alejo, Jose Luis; Bolaños, Natalia I; Ocampo, Jackson; Leidy, Chad; González, John M

2013-07-01

Astrocytes are involved in the pathogenesis of demyelinating diseases, where they actively regulate the secretion of proinflammatory factors, and trigger the recruitment of immune cells in the central nervous system (CNS). Antigen presentation of myelin-derived proteins has been shown to trigger astrocyte response, suggesting that astrocytes can directly sense demyelination. However, the direct response of astrocytes to lipid-debris generated during demyelination has not been investigated. The lipid composition of the myelin sheath is distinct, presenting significant amounts of cerebrosides, sulfocerebrosides (SCB), and ceramides. Studies have shown that microglia are activated in the presence of myelin-derived lipids, pointing to the possibility of lipid-induced astrocyte activation. In this study, a human astrocyte cell line was exposed to liposomes enriched in each myelin lipid component. Although liposome uptake was observed for all compositions, astrocytes had augmented uptake for liposomes containing sulfocerebroside (SCB). This enhanced uptake did not modify their expression of human leukocyte antigen (HLA) molecules or secretion of chemokines. This was in contrast to changes observed in astrocyte cells stimulated with IFNγ. Contrary to human monocytes, astrocytes did not internalize beads in the size-range of liposomes, indicating that liposome uptake is lipid specific. Epifluorescence microscopy corroborated that liposome uptake takes place through endocytosis. Soluble SCB were found to partially block uptake of liposomes containing this same lipid. Endocytosis was not decreased when cells were treated with cytochalasin D, but it was decreased by cold temperature incubation. The specific uptake of SCB in the absence of a proinflammatory response indicates that astrocytes may participate in the trafficking and regulation of sulfocerebroside metabolism and homeostasis in the CNS. Copyright © 2013 International Society for Advancement of Cytometry.

The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells

Directory of Open Access Journals (Sweden)

Daniel A. John

2017-09-01

Full Text Available Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100 from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2 production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the Campylobacter species.

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.

Characterization of the early local immune response to Ixodes ricinus tick bites in human skin.

Science.gov (United States)

Glatz, Martin; Means, Terry; Haas, Josef; Steere, Allen C; Müllegger, Robert R

2017-03-01

Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick-bite skin lesions (skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Responsible Mining: A Human Resources Strategy for Mine Development Project

OpenAIRE

Sampathkumar, Sriram (Ram)

2012-01-01

Mining is a global industry. Most mining companies operate internationally, often in remote, challenging environments and consequently frequently have respond to unusual and demanding Human Resource (HR) requirements. It is my opinion that the strategic imperative behind success in mining industry is responsible mining. The purpose of this paper is to examine how an effective HR strategy can be a competitive advantage that contributes to the success of a mining project in the global mining in...

Pupillary Responses to Robotic and Human Emotions: The Uncanny Valley and Media Equation Confirmed

Directory of Open Access Journals (Sweden)

Anne Reuten

2018-05-01

Full Text Available Physiological responses during human–robots interaction are useful alternatives to subjective measures of uncanny feelings for nearly humanlike robots (uncanny valley and comparable emotional responses between humans and robots (media equation. However, no studies have employed the easily accessible measure of pupillometry to confirm the uncanny valley and media equation hypotheses, evidence in favor of the existence of these hypotheses in interaction with emotional robots is scarce, and previous studies have not controlled for low level image statistics across robot appearances. We therefore recorded pupil size of 40 participants that viewed and rated pictures of robotic and human faces that expressed a variety of basic emotions. The robotic faces varied along the dimension of human likeness from cartoonish to humanlike. We strictly controlled for confounding factors by removing backgrounds, hair, and color, and by equalizing low level image statistics. After the presentation phase, participants indicated to what extent the robots appeared uncanny and humanlike, and whether they could imagine social interaction with the robots in real life situations. The results show that robots rated as nearly humanlike scored higher on uncanniness, scored lower on imagined social interaction, evoked weaker pupil dilations, and their emotional expressions were more difficult to recognize. Pupils dilated most strongly to negative expressions and the pattern of pupil responses across emotions was highly similar between robot and human stimuli. These results highlight the usefulness of pupillometry in emotion studies and robot design by confirming the uncanny valley and media equation hypotheses.

Hunted woolly monkeys (Lagothrix poeppigii show threat-sensitive responses to human presence.

Directory of Open Access Journals (Sweden)

Sarah Papworth

Full Text Available Responding only to individuals of a predator species which display threatening behaviour allows prey species to minimise energy expenditure and other costs of predator avoidance, such as disruption of feeding. The threat sensitivity hypothesis predicts such behaviour in prey species. If hunted animals are unable to distinguish dangerous humans from non-dangerous humans, human hunting is likely to have a greater effect on prey populations as all human encounters should lead to predator avoidance, increasing stress and creating opportunity costs for exploited populations. We test the threat sensitivity hypothesis in wild Poeppigi's woolly monkeys (Lagothrix poeppigii in Yasuní National Park, Ecuador, by presenting human models engaging in one of three behaviours "hunting", "gathering" or "researching". These experiments were conducted at two sites with differing hunting pressures. Visibility, movement and vocalisations were recorded and results from two sites showed that groups changed their behaviours after being exposed to humans, and did so in different ways depending on the behaviour of the human model. Results at the site with higher hunting pressure were consistent with predictions based on the threat sensitivity hypothesis. Although results at the site with lower hunting pressure were not consistent with the results at the site with higher hunting pressure, groups at this site also showed differential responses to different human behaviours. These results provide evidence of threat-sensitive predator avoidance in hunted primates, which may allow them to conserve both time and energy when encountering humans which pose no threat.

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.

Frequency response function-based explicit framework for dynamic identification in human-structure systems

Science.gov (United States)

Wei, Xiaojun; Živanović, Stana

2018-05-01

The aim of this paper is to propose a novel theoretical framework for dynamic identification in a structure occupied by a single human. The framework enables the prediction of the dynamics of the human-structure system from the known properties of the individual system components, the identification of human body dynamics from the known dynamics of the empty structure and the human-structure system and the identification of the properties of the structure from the known dynamics of the human and the human-structure system. The novelty of the proposed framework is the provision of closed-form solutions in terms of frequency response functions obtained by curve fitting measured data. The advantages of the framework over existing methods are that there is neither need for nonlinear optimisation nor need for spatial/modal models of the empty structure and the human-structure system. In addition, the second-order perturbation method is employed to quantify the effect of uncertainties in human body dynamics on the dynamic identification of the empty structure and the human-structure system. The explicit formulation makes the method computationally efficient and straightforward to use. A series of numerical examples and experiments are provided to illustrate the working of the method.

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

THE ROLE OF SOCIALLY RESPONSIBLE MARKETING IN THE REPRODUCTION OF THE HUMAN CAPITAL AND REDUCTION OF ITS FIKTIVIZATION PROCESSES

Directory of Open Access Journals (Sweden)

Olena Brintseva

2017-12-01

Full Text Available The urgency of the research. Before the modern person at different stages of reproduction of the human capital, there are many calls and risks that need to be considered and also to adapt to consequences of their action. Target setting. Use of marketing tools is rather a perspective direction of improvement of processes of the human capital reproduction. However, improvement of these processes is promoted by only socially responsible marketing. Uninvestigated parts of general matters defining. Almost unexplored are questions of use of marketing tools in the realization of processes of reproduction of the human capital. The purpose of the paper is to study the use of marketing tools for more effective implementation of reproduction processes of human capital at different stages. The issue of reproduction of human capital is considered in such areas: education, health, and social and labour sphere. Methodology. The paper is based on a critical analysis of scientific researches in the sphere of socially responsible marketing and processes of reproduction of human capital. These issues are researched by Blagov Yu.E., Carroll A., Hrishnova O.A., Kotler P., Lantos J., Lambin J., Libanova E.M., Mishchuk H.Yu., and others. Results. Issues of the human capital reproduction are considered in the following spheres: education, healthcare, and social and labour sphere. It is defined that in modern conditions, social responsibility has to become a basis for the creation of all system of the public relations and cover all stages of reproduction of the human capital. Socially irresponsible marketing leads to the formation, accumulation, and distribution of the fictitious human capital and other its unproductive forms. Practical implications. Now reproduction of the human capital in Ukraine is rather strongly influenced by fiktivization processes connected with the distribution of its unproductive forms. In this context, socially irresponsible marketing of

TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

Directory of Open Access Journals (Sweden)

Lee Adam Wheeler

2016-05-01

Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

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

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

Science.gov (United States)

Sowndhararajan, Kandhasamy; Kim, Songmun

2016-01-01

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

Variable postpartum responsiveness among humans and other primates with "cooperative breeding": A comparative and evolutionary perspective.

Science.gov (United States)

Hrdy, Sarah B

2016-01-01

This article is part of a Special Issue "Parental Care".Until recently, evolutionists reconstructing mother-infant bonding among human ancestors relied on nonhuman primate models characterized by exclusively maternal care, overlooking the highly variable responsiveness exhibited by mothers in species with obligate reliance on allomaternal care and provisioning. It is now increasingly recognized that apes as large-brained, slow maturing, and nutritionally dependent for so long as early humans were, could not have evolved unless "alloparents" (group members other than genetic parents), in addition to parents, had helped mothers to care for and provision offspring, a rearing system known as "cooperative breeding." Here I review situation-dependent maternal responses ranging from highly possessive to permissive, temporarily distancing, rejecting, or infanticidal, documented for a small subset of cooperatively breeding primates. As in many mammals, primate maternal responsiveness is influenced by physical condition, endocrinological priming, prior experience and local environments (especially related to security). But mothers among primates who evolved as cooperative breeders also appear unusually sensitive to cues of social support. In addition to more "sapient" or rational decision-making, humankind's deep history of cooperative breeding must be considered when trying to understand the extremely variable responsiveness of human mothers. Copyright © 2015 Elsevier Inc. All rights reserved.

The Impact of Tipuana tipu Species on Local Human Thermal Comfort Thresholds in Different Urban Canyon Cases in Mediterranean Climates: Lisbon, Portugal

Directory of Open Access Journals (Sweden)

Andre Santos Nouri

2018-01-01

Full Text Available Based upon the case of Lisbon, this article examined the in-situ effects of vegetation upon pedestrian thermal comfort levels. Focussing specifically upon the historic quarter that often witnesses the highest Tamb values and Urban Heat Island (UHI intensities during the summer, the most common urban canyon cases (UCCs were modelled, along with one of the most commonly used vegetative semi-deciduous species found in the city, Tipuana tipu. Based upon a reference point (RP system, the assessments were undertaken through the use of a new version of the SkyHelios model, local obtained Grad values, and the modified physiologically equivalent temperature (mPET index calculated through the human-biometeorological model RayMan. The study identified the in-situ thermo-physiological influences of Tipuana tipu during different periods of the year: (1 during the summer, which revealed considerable reductions of PET/mPET of up to 15.6 °C/11.6 °C during a very hot day (where daily maximum Tamb surpassed 35 °C; and (2 during the winter, which revealed the risks of oversharing as a result of the species keeping its foliage during the winter with reductions of PET/mPET of up to 2.7 °C/2.6 °C. Furthermore, the study utilised the climate tourism/transfer information scheme (CTIS to categorise and facilitate the interpretation of the results.

Response of cultured human airway epithelial cells to X-rays and energetic α-particles

International Nuclear Information System (INIS)

Yang, T.C.; Holley, W.R.; Curtis, S.B.; Gruenert, D.C.; California Univ., San Francisco, CA

1990-01-01

Radon and its progeny, which emit α-particles during decay, may play an important role in inducing human lung cancer. To gain a better understanding of the biological effects of α-particles in human lung we studied the response of cultured human airway epithelial cells to X-rays and monoenergetic helium ions. Experimental results indicated that the radiation response of primary cultures was similar to that for airway epithelial cells that were transformed with a plasmid containing an origin-defective SV40 virus. The RBE for cell inactivation determined by the ratio of D 0 for X-rays to that for 8 MeV helium ions was 1.8-2.2. The cross-section for helium ions, calculated from the D 0 value, was about 24 μm 2 for cells of the primary culture. This cross-section is significantly smaller than the average geometric nuclear area (∼ 180 μm 2 ), suggesting that an average of 7.5 α-particles (8 MeV helium ions) per cell nucleus are needed to induce a lethal lesion. (author)

Data Rights and Responsibilities: A Human Rights Perspective on Data Sharing.

Science.gov (United States)

Harris, Theresa L; Wyndham, Jessica M

2015-07-01

A human-rights-based analysis can be a useful tool for the scientific community and policy makers as they develop codes of conduct, harmonized standards, and national policies for data sharing. The human rights framework provides a shared set of values and norms across borders, defines rights and responsibilities of various actors involved in data sharing, addresses the potential harms as well as the benefits of data sharing, and offers a framework for balancing competing values. The right to enjoy the benefits of scientific progress and its applications offers a particularly helpful lens through which to view data as both a tool of scientific inquiry to which access is vital and as a product of science from which everyone should benefit. © The Author(s) 2015.

Prediction of human population responses to toxic compounds by a collaborative competition.

Science.gov (United States)

Eduati, Federica; Mangravite, Lara M; Wang, Tao; Tang, Hao; Bare, J Christopher; Huang, Ruili; Norman, Thea; Kellen, Mike; Menden, Michael P; Yang, Jichen; Zhan, Xiaowei; Zhong, Rui; Xiao, Guanghua; Xia, Menghang; Abdo, Nour; Kosyk, Oksana; Friend, Stephen; Dearry, Allen; Simeonov, Anton; Tice, Raymond R; Rusyn, Ivan; Wright, Fred A; Stolovitzky, Gustavo; Xie, Yang; Saez-Rodriguez, Julio

2015-09-01

The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal.

Of Hissing Snakes and Angry Voices: Human Infants Are Differentially Responsive to Evolutionary Fear-Relevant Sounds

Science.gov (United States)

Erlich, Nicole; Lipp, Ottmar V.; Slaughter, Virginia

2013-01-01

Adult humans demonstrate differential processing of stimuli that were recurrent threats to safety and survival throughout evolutionary history. Recent studies suggest that differential processing of evolutionarily ancient threats occurs in human infants, leading to the proposal of an inborn mechanism for rapid identification of, and response to,…

The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention.

Science.gov (United States)

Forte, Antonio Elia; Etard, Octave; Reichenbach, Tobias

2017-10-10

Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention.

The Universal Thermal Climate Index UTCI compared to ergonomics standards for assessing the thermal environment.

Science.gov (United States)

Bröde, Peter; Błazejczyk, Krzysztof; Fiala, Dusan; Havenith, George; Holmér, Ingvar; Jendritzky, Gerd; Kuklane, Kalev; Kampmann, Bernhard

2013-01-01

The growing need for valid assessment procedures of the outdoor thermal environment in the fields of public weather services, public health systems, urban planning, tourism & recreation and climate impact research raised the idea to develop the Universal Thermal Climate Index UTCI based on the most recent scientific progress both in thermo-physiology and in heat exchange theory. Following extensive validation of accessible models of human thermoregulation, the advanced multi-node 'Fiala' model was selected to form the basis of UTCI. This model was coupled with an adaptive clothing model which considers clothing habits by the general urban population and behavioral changes in clothing insulation related to actual environmental temperature. UTCI was developed conceptually as an equivalent temperature. Thus, for any combination of air temperature, wind, radiation, and humidity, UTCI is defined as the air temperature in the reference condition which would elicit the same dynamic response of the physiological model. This review analyses the sensitivity of UTCI to humidity and radiation in the heat and to wind in the cold and compares the results with observational studies and internationally standardized assessment procedures. The capabilities, restrictions and potential future extensions of UTCI are discussed.

Indirect detection of an epitope-specific response to HIV-1 gp120 immunization in human subjects.

Directory of Open Access Journals (Sweden)

Evgeny Shmelkov

Full Text Available A specific response of human serum neutralizing antibodies (nAb to a conformational epitope as a result of vaccination of human subjects with the surface envelope glycoprotein (gp120 of HIV-1 has not previously been documented. Here, we used computational analysis to assess the epitope-specific responses of human subjects, which were immunized with recombinant gp120 immunogens in the VAX003 and VAX004 clinical trials. Our computational methodology--a variation of sieve analysis--compares the occurrence of specific nAb targeted conformational 3D epitopes on viruses from infected individuals who received vaccination to the occurrence of matched epitopes in the viruses infecting placebo subjects. We specifically studied seven crystallographically defined nAb targeted conformational epitopes in the V3 loop, an immunogenic region of gp120. Of the six epitopes present in the immunogens and targeted by known monoclonal neutralizing antibodies, only the one targeted by the anti-V3 nAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects compared to the placebo group. This difference occurred only in the VAX003 Thailand cohort. No difference was seen between vaccinated and placebo groups for the occurrence of an epitope that was not present in the immunogen. Thus, it can be theorized that a specific 2219-like human neutralizing antibody immune response to AIDSVAX immunization occurred in the VAX003 cohort, and that this response protected subjects from a narrow subset of HIV-1 viruses circulating in Thailand in the 1990s and bearing the conformational epitope targeted by the neutralizing antibody 2219.

PHYSICAL CAPITAL, HUMAN AND SOCIAL AND RESPONSIBILITY PUBLIC ACCOUNTANT WITH POVERTY

OpenAIRE

Wong Torres, Zelma; Salcedo Guzmán, Luisa Elena

2014-01-01

This article is the result of research carried out in 2010, entitled, physical capital, human and social, and social responsibility of the Certified Public Accountant with Poverty. This article seeks to demonstrate the interest in settlement mechanisms to achieve equity and achieve a development strategy. In this perspective, the article insisted that social policy should be able to influence the structural determinants through which reproduce poverty and inequality, maldistribution of educat...

Lipid content and response to insulin are not invariably linked in human muscle cells

OpenAIRE

Aguer , Céline; Mercier , Jacques; Kitzmann , Magali

2009-01-01

Abstract In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from non-diabetic subjects and type 2 diabetic patients. Myotubes derived from type 2 diabetic patients had a defective response to insulin without showing a signif...

FGF21 and the late adaptive response to starvation in humans.

Science.gov (United States)

Fazeli, Pouneh K; Lun, Mingyue; Kim, Soo M; Bredella, Miriam A; Wright, Spenser; Zhang, Yang; Lee, Hang; Catana, Ciprian; Klibanski, Anne; Patwari, Parth; Steinhauser, Matthew L

2015-11-03

In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.

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...

Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am

International Nuclear Information System (INIS)

DuFrain, R.J.; Littlefield, L.G.; Joiner, E.E.; Frome, E.L.

1979-01-01

Cytogenetic dosimetry estimates to guide treatment of persons internally contaminated with transuranic elements have not previously been possible because appropriate in vitro dose-response curves specifically for alpha particle irradiation of human lymphocytes do not exist. Using well-controlled cytogenetic methods for human lymphocyte culture, an experimentally derived dose-response curve for 241 Am alpha particle (5.49 and 5.44 MeV) radiation of G 0 lymphocytes was generated. Cells were exposed to 43.8, 87.7, 175.3 or 350.6 nCi/ml 241 Am for 1.7 hr giving doses of 0.85, 1.71, 3.42 or 6.84 rad. Based on dicentric chromosome yield, the linear dose-response equation is Y = 4.90(+-0.42) x 10 -2 X, with Y given as dicentrics per cell and X as dose in rads. The study also shows that the two-break asymmetrical exchanges in cells damaged by alpha particle radiation are overdispersed when compared to a Poisson distribution. An example is presented to show how the derived dose-response equation can be used to estimate the radiation dose for a person internally contaminated with an actinide. An experimentally derived RBE value of 118 at 0.85 rad is calculated for the efficiency of 241 Am alpha particle induction of dicentric chromosomes in human G 0 lymphocytes as compared with the efficiency of 60 Co gamma radiation. The maximum theoretical value for the RBE for cytogenetic damage from alpha irradiation was determined to be 278 at 0.1 rad or less which is in marked contrast to previously reported RBE values of approx. 20. (author)

Assessment of body mapping sportswear using a manikin operated in constant temperature mode and thermoregulatory model control mode

Science.gov (United States)

Wang, Faming; Del Ferraro, Simona; Molinaro, Vincenzo; Morrissey, Matthew; Rossi, René

2014-09-01

Regional sweating patterns and body surface temperature differences exist between genders. Traditional sportswear made from one material and/or one fabric structure has a limited ability to provide athletes sufficient local wear comfort. Body mapping sportswear consists of one piece of multiple knit structure fabric or of different fabric pieces that may provide athletes better wear comfort. In this study, the `modular' body mapping sportswear was designed and subsequently assessed on a `Newton' type sweating manikin that operated in both constant temperature mode and thermophysiological model control mode. The performance of the modular body mapping sportswear kit and commercial products were also compared. The results demonstrated that such a modular body mapping sportswear kit can meet multiple wear/thermal comfort requirements in various environmental conditions. All body mapping clothing (BMC) presented limited global thermophysiological benefits for the wearers. Nevertheless, BMC showed evident improvements in adjusting local body heat exchanges and local thermal sensations.

NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans.

Science.gov (United States)

Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; León-Contreras, Juan C; Hernández-Pando, Rogelio; Escobedo, Dante; Torres, Martha; Sada, Eduardo

2012-04-01

A role for the nucleotide-binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL-1β, IL-6, and TNF-α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF-α and IL-6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria-containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Phosphatidylinositol response and proliferation of oxidative enzyme-activated human T lymphocytes: suppression by plasma lipoproteins

International Nuclear Information System (INIS)

Akeson, A.L.; Scupham, D.W.; Harmony, J.A.

1984-01-01

The phosphatidylinositol (PI) response and DNA synthesis of neuraminidase and galactose oxidase (NAGO)-stimulated human T lymphocytes are suppressed by low density lipoproteins (LDL). To understand the mechanism of lymphocyte activation more fully, the PI response and DNA synthesis and suppression of these events by LDL in NAGO-stimulated T lymphocytes were characterized. Between 30 min and 6 hr after NAGO stimulation, there was an increase of 32 Pi incorporation into PI without increased incorporation into the phosphorylated forms of PI or into other phospholipids. DNA synthesis as determined by [ 3 H]thymidine incorporation depended on the lymphocyte-accessory monocyte ratio and total cell density. Optimal stimulation of the PI response and DNA synthesis occurred at the same concentration of neuraminidase and galactose oxidase. While the PI response was only partially suppressed by LDL with optimal suppression at 10 to 20 micrograms of protein/ml, DNA synthesis was completely suppressed although at much higher LDL concentrations, greater than 100 micrograms protein/ml. As monocyte numbers are increased, LDL suppression of DNA synthesis is decreased. The ability of NAGO to stimulate the PI response and DNA synthesis in a similar way, and the suppression of both events by LDL, suggests the PI response is important for lymphocyte activation and proliferation. Stimulation of human T lymphocytes by oxidative mitogens, neuraminidase, and galactose oxidase caused increased phosphatidylinositol metabolism and increased DNA synthesis. Both responses were suppressed by low density lipoproteins

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.

Human rights in global supply chains: Corporate social responsibility and public procurement in the European Union

OpenAIRE

Outhwaite, Opi; Martin-Ortega, Olga

2016-01-01

The global supply chains of multinational enterprises are complex and multi-tiered, often involving many stages of production and spanning several jurisdictions. Important questions remain about how to ensure that human rights are respected in these supply chains, including how multinational enterprises are to exercise the responsibility to respect human rights in their supply chains and the role that can be played by states in protecting human rights outside of their borders. This article fo...

The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response.

Directory of Open Access Journals (Sweden)

Jacky Flipse

Full Text Available Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.

The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response

Science.gov (United States)

Flipse, Jacky; Smit, Jolanda M.

2015-01-01

Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection. PMID:26065421

Autonomous parvoviruses neither stimulate nor are inhibited by the type I interferon response in human normal or cancer cells.

Science.gov (United States)

Paglino, Justin C; Andres, Wells; van den Pol, Anthony N

2014-05-01

Members of the genus Parvovirus are small, nonenveloped single-stranded DNA viruses that are nonpathogenic in humans but have potential utility as cancer therapeutics. Because the innate immune response to parvoviruses has received relatively little attention, we compared the response to parvoviruses to that of several other types of viruses in human cells. In normal human glia, fibroblasts, or melanocytes, vesicular stomatitis virus evoked robust beta interferon (IFN-β) responses. Cytomegalovirus, pseudorabies virus, and Sindbis virus all evoked a 2-log-unit or greater upregulation of IFN-β in glia; in contrast, LuIII and MVMp parvoviruses did not evoke a detectable IFN-β or interferon-stimulated gene (ISG; MX1, oligoadenylate synthetase [OAS], IFIT-1) response in the same cell types. The lack of response raised the question of whether parvoviral infection can be attenuated by IFN; interestingly, we found that IFN did not decrease parvovirus (MVMp, LuIII, and H-1) infectivity in normal human glia, fibroblasts, or melanocytes. The same was true in human cancers, including glioma, sarcoma, and melanoma. Similarly, IFN failed to attenuate transduction by the dependovirus vector adeno-associated virus type 2. Progeny production of parvoviruses was also unimpaired by IFN in both glioma and melanoma, whereas vesicular stomatitis virus replication was blocked. Sarcoma cells with upregulated IFN signaling that show high levels of resistance to other viruses showed strong infection by LuIII. Unlike many other oncolytic viruses, we found no evidence that impairment of innate immunity in cancer cells plays a role in the oncoselectivity of parvoviruses in human cells. Parvoviral resistance to the effects of IFN in cancer cells may constitute an advantage in the virotherapy of some tumors. Understanding the interactions between oncolytic viruses and the innate immune system will facilitate employing these viruses as therapeutic agents in cancer patients. The cancer

Adaptive response to ionizing radiation induced by low doses of gamma rays in human cell lines

International Nuclear Information System (INIS)

Seong, Jinsil; Chang, Ok Suh; Gwi, Eon Kim

1995-01-01

Purpose: The aim of this study was to investigate whether the adaptive response could be induced in human lymphoblastoid cell lines and human tumor cell lines. The time necessary for the expression of the adaptive response was also investigated. Materials and Methods: Three lymphoblastoid cell lines from ataxia telangiectasia (AT) homozygote (GM 1526), AT heterozygote (GM 3382), and normal individual (3402p) and two hepatoma cell lines, Hep G2 and Hep 3B, were used in this study. Experiments were carried out by delivering 0.01 Gy followed by 0.5 Gy of gamma radiation to the exponentially growing cells. The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 to 72 h. In some experiments, 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, was added immediately after the 0.5 Gy exposure. The cultures were fixed 30 min (for the G 2 chromatid) and 6 h (for the S chromatid) after the 0.5 Gy exposure. Metaphase chromosome assay was carried out to score chromatid breaks as an end point. Results: A prior exposure to 0.01 Gy of gamma rays significantly reduced the number of chromatid breaks induced by subsequent higher doses (0.5 Gy) in all the tested cell lines. The magnitude of the adaptive response was similar among the cell lines despite their different radiosensitivities. In the G 2 chromatids, the adaptive response was observed both at short-time intervals, as early as 1 h, and at long-time intervals. In the S chromatids, however, the adaptive response was shown only at long-time intervals. When 3-aminobenzamide was added after the 0.5 Gy, the adaptive responses were abolished in all the experimental groups. Conclusion: The adaptive response was observed in human lymphoblastoid cell lines and hepatoma cell lines. The magnitude of the adaptive response did not seem to be related to the radiosensitivity of the cells. The elimination of the adaptive response with 3

Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study

DEFF Research Database (Denmark)

Nielsen, Kirstine Lykke; Hartvigsen, Merete; Hedemann, Mette Skou

2014-01-01

Background: In nutritional studies, pigs are often used as models for humans because of nutritional and physiologic similarities. However, evidence supporting similar metabolic responses to nutritional interventions is lacking. Objective: The objective was to establish whether pigs and humans...... respond similarly to a nutritional intervention. Using metabolomics, we compared the acute metabolic response to 4 test breads between conventional pigs (growing) and adult human subjects (with the metabolic syndrome). Design: Six catheterized pigs and 15 human subjects were tested in a randomized...... different basal metabolome concentrations in the plasma of pigs and humans. Humans had higher contents of phosphatidylcholines, oleic acid, and carnitine in plasma, possibly reflecting a higher intake of meats and fats. In pigs, betaine, choline, creatinine, tryptophan, and phenylalanine were higher...

Titania-polymeric powder coatings with nano-topography support enhanced human mesenchymal cell responses.

Science.gov (United States)

Mozumder, Mohammad Sayem; Zhu, Jesse; Perinpanayagam, Hiran

2012-10-01

Titanium implant osseointegration is dependent on the cellular response to surface modifications and coatings. Titania-enriched nanocomposite polymeric resin coatings were prepared through the application of advanced ultrafine powder coating technology. Their surfaces were readily modified to create nano-rough (topographies that supported human embryonic palatal mesenchymal cell responses. Energy dispersive x-ray spectroscopy confirmed continuous and homogenous coatings with a similar composition and even distribution of titanium. Scanning electron microscopy (SEM) showed complex micro-topographies, and atomic force microscopy revealed intricate nanofeatures and surface roughness. Cell counts, mitochondrial enzyme activity reduction of yellow 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to dark purple, SEM, and inverted fluorescence microscopy showed a marked increase in cell attachment, spreading, proliferation, and metabolic activity on the nanostructured surfaces. Reverse Transcription- Polymerase Chain Reaction (RT-PCR) analysis showed that type I collagen and Runx2 expression were induced, and Alizarin red staining showed that mineral deposits were abundant in the cell cultures grown on nanosurfaces. This enhancement in human mesenchymal cell attachment, growth, and osteogenesis were attributed to the nanosized surface topographies, roughness, and moderate wetting characteristics of the coatings. Their dimensional similarity to naturally occurring matrix proteins and crystals, coupled with their increased surface area for protein adsorption, may have facilitated the response. Therefore, this application of ultrafine powder coating technology affords highly biocompatible surfaces that can be readily modified to accentuate the cellular response. Copyright © 2012 Wiley Periodicals, Inc.

Activated human nasal epithelial cells modulate specific antibody response against bacterial or viral antigens.

Directory of Open Access Journals (Sweden)

Chiou-Yueh Yeh

Full Text Available Nasal mucosa is an immune responsive organ evidenced by eliciting both specific local secretory IgA and systemic IgG antibody responses with intra-nasal administration of antigens. Nevertheless, the role of nasal epithelial cells in modulating such responses is unclear. Human nasal epithelial cells (hNECs obtained from sinus mucosa of patients with chronic rhinosinusitis were cultured in vitro and firstly were stimulated by Lactococcus lactis bacterium-like particles (BLPs in order to examine their role on antibody production. Secondly, both antigens of immunodominant protein IDG60 from oral Streptococcus mutans and hemagglutinin (HA from influenza virus were tested to evaluate the specific antibody response. Stimulated hNECs by BLPs exhibited a significant increase in the production of interleukin-6 (IL-6, and thymic stromal lymphopoietin (TSLP. Conditioned medium of stimulated hNECs has effects on enhancing the proliferation of CD4+ T cells together with interferon-γ and IL-5 production, increasing the costimulatory molecules on dendritic cells and augmenting the production of IDG60 specific IgA, HA specific IgG, IgA by human peripheral blood lymphocytes. Such production of antigen specific IgG and IgA is significantly counteracted in the presence of IL-6 and TSLP neutralizing antibodies. In conclusion, properly stimulated hNECs may impart immuno-modulatory effects on the antigen-specific antibody response at least through the production of IL-6 and TSLP.

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.

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.

An investigation of human body model morphing for the assessment of abdomen responses to impact against a population of test subjects.

Science.gov (United States)

Beillas, Philippe; Berthet, Fabien

2017-05-29

Human body models have the potential to better describe the human anatomy and variability than dummies. However, data sets available to verify the human response to impact are typically limited in numbers, and they are not size or gender specific. The objective of this study was to investigate the use of model morphing methodologies within that context. In this study, a simple human model scaling methodology was developed to morph two detailed human models (Global Human Body Model Consortium models 50th male, M50, and 5th female, F05) to the dimensions of post mortem human surrogates (PMHS) used in published literature. The methodology was then successfully applied to 52 PMHS tested in 14 impact conditions loading the abdomen. The corresponding 104 simulations were compared to the responses of the PMHS and to the responses of the baseline models without scaling (28 simulations). The responses were analysed using the CORA method and peak values. The results suggest that model scaling leads to an improvement of the predicted force and deflection but has more marginal effects on the predicted abdominal compressions. M50 and F05 models scaled to the same PMHS were also found to have similar external responses, but large differences were found between the two sets of models for the strain energy densities in the liver and the spleen for mid-abdomen impact simulations. These differences, which were attributed to the anatomical differences in the abdomen of the baseline models, highlight the importance of the selection of the impact condition for simulation studies, especially if the organ location is not known in the test. While the methodology could be further improved, it shows the feasibility of using model scaling methodologies to compare human models of different sizes and to evaluate scaling approaches within the context of human model validation.

Characterization of the response chemiluminescence of neutrophils human beings to the hemolysin Escherichia coli alpha

International Nuclear Information System (INIS)

Garcia, J.

2000-01-01

Escherichia coli alpha hemolysin (AH) evoked a luminol-amplified chemiluminescence (CL) response from human polymorphonuclear leukocytes (PMN). Analysis of kinetic parameters of the PMN CL response to AH established similarities with that of PMN to the calcium ionophore A23187. PMN CL responses to both AH and A23187 were equally decreased by preincubating PMN with A63612, a hidroxamic acid derivative and lipooxigenase inhibitor, showing that the CL response to both hemolysin and ionophore share a common mechanism, probably activation of leukotriene synthesis, due to calcium entry into the cells brought about by AH and A23187. In addition, the CL response of PMN to AH was lowered by the hydroxyl radical scavenger dimethyl sulfoxide, further suggesting arachidonate metabolism is involved in CL response. (Author) [es

Extinction produces context inhibition and multiple-context extinction reduces response recovery in human predictive learning.

Science.gov (United States)

Glautier, Steven; Elgueta, Tito; Nelson, James Byron

2013-12-01

Two experiments with human participants were used to investigate recovery of an extinguished learned response after a context change using ABC designs. In an ABC design, the context changes over the three successive stages of acquisition (context A), extinction (context B), and test (context C). In both experiments, we found reduced recovery in groups that had extinction in multiple contexts, and that the extinction contexts acquired inhibitory strength. These results confirm those of previous investigations, that multiple-context extinction can produce less response recovery than single-context extinction, and they also provide new evidence for the involvement of contextual inhibitory processes in extinction in humans. The foregoing results are broadly in line with a protection-from-extinction account of response recovery. Yet, despite the fact that we detected contextual inhibition, predictions based on protection-from-extinction were not fully reliable for the single- and multiple-context group differences that we observed in (1) rates of extinction and (2) the strength of context inhibition. Thus, although evidence was obtained for a protection-from-extinction account of response recovery, this account can not explain all of the data.

Ethics is for human subjects too: participant perspectives on responsibility in health research.

Science.gov (United States)

Cox, Susan M; McDonald, Michael

2013-12-01

Despite the significant literature as well as energy devoted to ethical review of research involving human subjects, little attention has been given to understanding the experiences of those who volunteer as human subjects. Why and how do they decide to participate in research? Is research participation viewed as a form of social responsibility or as a way of obtaining individual benefits? What if anything do research subjects feel they are owed for participation? And what do they feel that they owe the researcher? Drawing on in-depth individual interviews conducted in 2006 and 2007 with 41 subjects who participated in a variety of types of health research in Canada, this paper focuses on subject perspectives on responsibility in research. Highlighting the range of ways that subjects describe their involvement in research and commitments to being a 'good' subject, we present a typology of narratives that sheds new light on the diverse meanings of research participation. These narratives are not mutually exclusive or prescriptive but are presented as ideal types typifying a set of circumstances and values. As such, they collectively illuminate a range of motivations expressed by human subjects as well as potential sources of vulnerability. The typology adds a new dimension to the literature in this area and has significant implications for researchers seeking more human-subject centred approaches to research recruitment and retention, as well as research ethics boards trying to better anticipate the perspectives of prospective participants. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines

International Nuclear Information System (INIS)

Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon

1994-01-01

When cells are exposed to low doses of a mutagenic or clastogenic agents, they often become less sensitive to the effects of a higher does administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher does (50 cGy). The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines. Which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism

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.

Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

Science.gov (United States)

Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

2015-01-01

Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy. Published by Elsevier Ltd.

Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

Directory of Open Access Journals (Sweden)

Devyn D Gilette

2014-04-01

Full Text Available Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity.

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

Science.gov (United States)

Khan, Sitara G.; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R.; Martin, Katherine; Khan, Faisal; O’Gallagher, Kevin; Chowienczyk, Philip J.

2017-01-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. PMID:28646032

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

Science.gov (United States)

Khan, Sitara G; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R; Martin, Katherine; Khan, Faisal; O'Gallagher, Kevin; Chowienczyk, Philip J; Shah, Ajay M

2017-09-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S -methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r 2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. Copyright © 2017 the American Physiological Society.

A Margin-of-Exposure Approach to Assessment of Noncancer Risks of Dioxins Based on Human Exposure and Response Data

OpenAIRE

Aylward, Lesa L.; Goodman, Julie E.; Charnley, Gail; Rhomberg, Lorenz R.

2008-01-01

Background Risk assessment of human environmental exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) and other dioxin-like compounds is complicated by several factors, including limitations in measuring intakes because of the low concentrations of these compounds in foods and the environment and interspecies differences in pharmacokinetics and responses. Objectives We examined the feasibility of relying directly on human studies of exposure and potential responses to...

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...

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...

Impact Response Comparison Between Parametric Human Models and Postmortem Human Subjects with a Wide Range of Obesity Levels.

Science.gov (United States)

Zhang, Kai; Cao, Libo; Wang, Yulong; Hwang, Eunjoo; Reed, Matthew P; Forman, Jason; Hu, Jingwen

2017-10-01

Field data analyses have shown that obesity significantly increases the occupant injury risks in motor vehicle crashes, but the injury assessment tools for people with obesity are largely lacking. The objectives of this study were to use a mesh morphing method to rapidly generate parametric finite element models with a wide range of obesity levels and to evaluate their biofidelity against impact tests using postmortem human subjects (PMHS). Frontal crash tests using three PMHS seated in a vehicle rear seat compartment with body mass index (BMI) from 24 to 40 kg/m 2 were selected. To develop the human models matching the PMHS geometry, statistical models of external body shape, rib cage, pelvis, and femur were applied to predict the target geometry using age, sex, stature, and BMI. A mesh morphing method based on radial basis functions was used to rapidly morph a baseline human model into the target geometry. The model-predicted body excursions and injury measures were compared to the PMHS tests. Comparisons of occupant kinematics and injury measures between the tests and simulations showed reasonable correlations across the wide range of BMI levels. The parametric human models have the capability to account for the obesity effects on the occupant impact responses and injury risks. © 2017 The Obesity Society.

Biological responses of progestogen metabolites in normal and cancerous human breast.

Science.gov (United States)

Pasqualini, Jorge R; Chetrite, Gérard S

2010-12-01

At present, more than 200 progestogen molecules are available, but their biological response is a function of various factors: affinity to progesterone or other receptors, their structure, the target tissues considered, biological response, experimental conditions, dose, method of administration and metabolic transformations. Metabolic transformation is of huge importance because in various biological processes the metabolic product(s) not only control the activity of the maternal hormone but also have an important activity of its own. In this regard, it was observed that the 20-dihydro derivative of the progestogen dydrogesterone (Duphaston®) is significantly more active than the parent compound in inhibiting sulfatase and 17β-hydroxysteroid dehydrogenase in human breast cancer cells. Estrone sulfatase activity is also inhibited by norelgestromin, a norgestimate metabolite. Interesting information was obtained with a similar progestogen, tibolone, which is rapidly metabolized into the active 3α/3β-hydroxy and 4-ene metabolites. All these metabolites can inhibit sulfatase and 17β-hydroxysteroid dehydrogenase and stimulate sulfotransferase in human breast cancer cells. Another attractive aspect is the metabolic transformation of progesterone itself in human breast tissues. In the normal breast progesterone is mainly converted to 4-ene derivatives, whereas in the tumor tissue it is converted mostly to 5α-pregnane derivatives. 20α-Dihydroprogesterone is found mainly in normal breast tissue and possesses antiproliferative properties as well as the ability to act as an anti-aromatase agent. Consequently, this progesterone metabolite could be involved in the control of estradiol production in the normal breast and therefore implicated in one of the multifactorial mechanisms of the breast carcinogenesis process. In conclusion, a better understanding of both natural and synthetic hormone metabolic transformations and their control could potentially provide

A non-invasive, quantitative study of broadband spectral responses in human visual cortex.

Directory of Open Access Journals (Sweden)

Eline R Kupers

Full Text Available Currently, non-invasive methods for studying the human brain do not routinely and reliably measure spike-rate-dependent signals, independent of responses such as hemodynamic coupling (fMRI and subthreshold neuronal synchrony (oscillations and event-related potentials. In contrast, invasive methods-microelectrode recordings and electrocorticography (ECoG-have recently measured broadband power elevation in field potentials (~50-200 Hz as a proxy for locally averaged spike rates. Here, we sought to detect and quantify stimulus-related broadband responses using magnetoencephalography (MEG. Extracranial measurements like MEG and EEG have multiple global noise sources and relatively low signal-to-noise ratios; moreover high frequency artifacts from eye movements can be confounded with stimulus design and mistaken for signals originating from brain activity. For these reasons, we developed an automated denoising technique that helps reveal the broadband signal of interest. Subjects viewed 12-Hz contrast-reversing patterns in the left, right, or bilateral visual field. Sensor time series were separated into evoked (12-Hz amplitude and broadband components (60-150 Hz. In all subjects, denoised broadband responses were reliably measured in sensors over occipital cortex, even in trials without microsaccades. The broadband pattern was stimulus-dependent, with greater power contralateral to the stimulus. Because we obtain reliable broadband estimates with short experiments (~20 minutes, and with sufficient signal-to-noise to distinguish responses to different stimuli, we conclude that MEG broadband signals, denoised with our method, offer a practical, non-invasive means for characterizing spike-rate-dependent neural activity for addressing scientific questions about human brain function.

Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response

Directory of Open Access Journals (Sweden)

Benoit T. Roux

2017-08-01

Full Text Available Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs are novel regulators of immunity, there has been no systematic attempt to identify and characterize the lncRNAs whose expression is changed following the induction of the innate immune response. To address this issue, we have employed next-generation sequencing data to determine the changes in the lncRNA profile in four human (monocytes, macrophages, epithelium, and chondrocytes and four mouse cell types (RAW 264.7 macrophages, bone marrow-derived macrophages, peritoneal macrophages, and splenic dendritic cells following exposure to the pro-inflammatory mediators, lipopolysaccharides (LPS, or interleukin-1β. We show differential expression of 204 human and 210 mouse lncRNAs, with positional analysis demonstrating correlation with immune-related genes. These lncRNAs are predominantly cell-type specific, composed of large regions of repeat sequences, and show poor evolutionary conservation. Comparison within the human and mouse sequences showed less than 1% sequence conservation, although we identified multiple conserved motifs. Of the 204 human lncRNAs, 21 overlapped with syntenic mouse lncRNAs, of which five were differentially expressed in both species. Among these syntenic lncRNA was IL7-AS (antisense, which was induced in multiple cell types and shown to regulate the production of the pro-inflammatory mediator interleukin-6 in both human and mouse cells. In summary, we have identified and characterized those lncRNAs that are differentially expressed following activation of the human and mouse innate immune responses and believe that these catalogs will provide the foundation for the future analysis of the role of lncRNAs in immune and inflammatory responses.

Are drug companies living up to their human rights responsibilities? The perspective of the former United Nations Special Rapporteur (2002-2008.

Directory of Open Access Journals (Sweden)

Paul Hunt

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.

Are drug companies living up to their human rights responsibilities? The perspective of the former United Nations Special Rapporteur (2002-2008).

Science.gov (United States)

Hunt, Paul; Khosla, Rajat

2010-09-28

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.

Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

Directory of Open Access Journals (Sweden)

Govindarajan Kunde R

2011-05-01

Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

[Christian responsibility and experimental medicine. Experiments with and on humans, experiments on animals].

Science.gov (United States)

Grosse, Heinrich W

2002-01-01

The Jewish-Christian convictions that man was created as the image of God founded the "ethics of unavailability" which contrast with the utilitarian "ethics of interests." As man s nature is imperfect according to biblical understanding, those responsible in the field of experimental medicine should counteract all tendencies in society which promote an utopian definition of health and an eugenic mentality (idea of the "perfection of mankind"). Consequently, scientists must reflect their own image of man and the effects of their actions on this image. The goals of experimental medicine must also be examined under the aspect of fairness: do they only benefit a minority in the rich industrial nations? As in research on humans, the ethical evaluation of animal experiments must consider the question of the underlying image of humanity and the responsibility of mankind connected to it. Because of changes in society's values, the validity of traditional anthropocentrism is increasingly questioned. However, this does not affect the view of the special position of man as the bearer of responsibility. Even though there are different biblical statements on the relationship between man and animal, the Christian maxim to minimise violence towards animals can be derived from them. In the case of animal experiments this means: experiments which cause the animals severe suffering must be avoided by waiving the potential gain of knowledge from them. In general: in an ethical discussion on medical experiments using humans or animals, the public must be informed completely and involved effectively. A moratorium must be possible before plans become facts. Thinking about ethical problems in the area of experimental medicine should not be separated from the far-reaching questions about changes in our lifestyle and consumer behaviour.

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

Science.gov (United States)

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

2010-02-15

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

Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice

International Nuclear Information System (INIS)

Zhang Lianzhen; Deng Zhicheng

1993-01-01

The cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice were studied. The results of this study showed that human lymphocytes in vitro and mouse marrow cells in vivo can become adapted to low-level irradiation from 3 H-TdR or exposure to a low dose of X-or γ-irradiation, so that they become less sensitive to the chromosomal damage effects of subsequent exposures. (4 tabs.)

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...

Lessons learned about human stem cell responses to ionizing radiation exposures: a long road still ahead of us.

Science.gov (United States)

Sokolov, Mykyta; Neumann, Ronald

2013-07-29

Human stem cells (hSC) possess several distinct characteristics that set them apart from other cell types. First, hSC are self-renewing, capable of undergoing both asymmetric and symmetric cell divisions. Second, these cells can be coaxed to differentiate into various specialized cell types and, as such, hold great promise for regenerative medicine. Recent progresses in hSC biology fostered the characterization of the responses of hSC to genotoxic stresses, including ionizing radiation (IR). Here, we examine how different types of hSC respond to IR, with a special emphasis on their radiosensitivity, cell cycle, signaling networks, DNA damage response (DDR) and DNA repair. We show that human embryonic stem cells (hESCs) possess unique characteristics in how they react to IR that clearly distinguish these cells from all adult hSC studied thus far. On the other hand, a manifestation of radiation injuries/toxicity in human bodies may depend to a large extent on hSC populating corresponding tissues, such as human mesenchymal stem cells (hMSC), human hematopoietic stem cells (hHSC), neural hSC, intestine hSC, etc. We discuss here that hSC responses to IR differ notably across many types of hSC which may represent the distinct roles these cells play in development, regeneration and/or maintenance of homeostasis.

Myofibrillar proteolysis in response to voluntary or electrically stimulated muscle contractions in humans

DEFF Research Database (Denmark)

Hansen, M; Trappe, T; Crameri, R M

2008-01-01

Knowledge about the effects of exercise on myofibrillar protein breakdown in human subjects is limited. Our purpose was to measure the changes in the degradation of myofibrillar proteins in response to different ways of eliciting muscle contractions using the local interstitial 3-methyl-histidine......Knowledge about the effects of exercise on myofibrillar protein breakdown in human subjects is limited. Our purpose was to measure the changes in the degradation of myofibrillar proteins in response to different ways of eliciting muscle contractions using the local interstitial 3-methyl....... Only after ES did the histochemical stainings show significant disruption of cytoskeletal proteins. Furthermore, intracellular disruption and destroyed Z-lines were markedly more pronounced in ES vs VOL. In conclusion, the local level of interstitial 3-MH in the skeletal muscle was significantly...... enhanced after ES compared with VOL immediately after exercise, while the level of 3-MH did not change in the post-exercise period after VOL. These results indicate that the local myofibrillar breakdown is accelerated after ES associated with severe myofiber damage....

Counter-regulatory hormone responses to spontaneous hypoglycaemia during treatment with insulin Aspart or human soluble insulin

DEFF Research Database (Denmark)

Brock Jacobsen, I; Vind, B F; Korsholm, Lars

2011-01-01

examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed......-regulatory responses regarding growth hormone, glucagon and ghrelin whereas no differences were found in relation to free fatty acid, cortisol, insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins 1 and 2. Treatment with insulin Aspart resulted in well-defined peaks in serum insulin concentrations...... elicited a slightly different physiological response to spontaneous hypoglycaemia compared with human insulin. Keywords hypoglycaemia counter-regulation, insulin Aspart, type 1 diabetes....

Evaluation of on-farm veal calves' responses to unfamiliar humans and potential influencing factors

NARCIS (Netherlands)

Leruste, H.; Bokkers, E.A.M.; Heutinck, L.F.M.; Wolthuis-Fillerup, M.; Werf, van der J.T.N.; Brscic, M.; Cozzi, G.; Engel, B.; Reenen, van C.G.; Lensink, B.J.

2012-01-01

The human–animal relationship is an important component of the welfare of farm animals and for this reason animal responsiveness tests to humans are included in on-farm welfare assessment schemes that provide indicators for this. However, apart from the behaviour of stockpersons towards their

Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems

Directory of Open Access Journals (Sweden)

McDermott Jason E

2011-11-01

Full Text Available Abstract Background Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades. Results In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms. Conclusions This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.

Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.

Science.gov (United States)

Luisier, Raphaëlle; Lempiäinen, Harri; Scherbichler, Nina; Braeuning, Albert; Geissler, Miriam; Dubost, Valerie; Müller, Arne; Scheer, Nico; Chibout, Salah-Dine; Hara, Hisanori; Picard, Frank; Theil, Diethilde; Couttet, Philippe; Vitobello, Antonio; Grenet, Olivier; Grasl-Kraupp, Bettina; Ellinger-Ziegelbauer, Heidrun; Thomson, John P; Meehan, Richard R; Elcombe, Clifford R; Henderson, Colin J; Wolf, C Roland; Schwarz, Michael; Moulin, Pierre; Terranova, Rémi; Moggs, Jonathan G

2014-06-01

The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CAR(KO)-PXR(KO)), double humanized CAR and PXR (CAR(h)-PXR(h)), and wild-type C57BL/6 mice. Wild-type and CAR(h)-PXR(h) mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CAR(KO)-PXR(KO) mouse livers and largely reversible in wild-type and CAR(h)-PXR(h) mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CAR(h)-PXR(h) mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.

Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

Science.gov (United States)

Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

2014-12-01

This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.

Science.gov (United States)

Robertson, Chelsea L; Ishibashi, Kenji; Mandelkern, Mark A; Brown, Amira K; Ghahremani, Dara G; Sabb, Fred; Bilder, Robert; Cannon, Tyrone; Borg, Jacqueline; London, Edythe D

2015-04-15

Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. Copyright © 2015 the authors 0270-6474/15/355990-08$15.00/0.

The influence of value judgments about the existence of free will in prostitution on shaping criminal justice response to human trafficking

OpenAIRE

Ristivojević, Branislav

2015-01-01

Starting from the unbreakable bond that exists between human trafficking and prostitution, the author explores in the paper the issue of the influence of value judgments about the existence of free will in prostitution on shaping criminal justice responses to human trafficking. Two possible answers to this question also create two models of criminal-political responses to human trafficking. The author criticizes the first one, which does not recognize the freedom of will, because besides the ...

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

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.

The human tartrate-resistant acid phosphatase (TRAP): involvement of the hemin responsive elements (HRE) in transcriptional regulation.

Science.gov (United States)

Fleckenstein, E C; Dirks, W G; Drexler, H G

2000-02-01

The biochemical properties and protein structure of the tartrate-resistant acid phosphatase (TRAP), an iron-containing lysosomal glycoprotein in cells of the mononuclear phagocyte system, are well known. In contrast, little is known about the physiology and genic structure of this unique enzyme. In some diseases, like hairy cell leukemia, Gaucher's disease and osteoclastoma, cytochemically detected TRAP expression is used as a disease-associated marker. In order to begin to elucidate the regulation of this gene we generated different deletion constructs of the TRAP 5'-flanking region, placed them upstream of the luciferase reporter gene and assayed them for their ability to direct luciferase expression in human 293 cells. Treatment of these cells with the iron-modulating reagents transferrin and hemin causes opposite effects on the TRAP promoter activity. Two regulatory GAGGC tandem repeat sequences (the hemin responsive elements, HRE) within the 5'-flanking region of the human TRAP gene were identified. Studies with specific HRE-deletion constructs of the human TRAP 5'-flanking region upstream of the luciferase reporter gene document the functionality of these HRE-sequences which are apparently responsible for mediating transcriptional inhibition upon exposure to hemin. In addition to the previously published functional characterization of the murine TRAP HRE motifs, these results provide the first description of a new iron/hemin-responsive transcriptional regulation in the human TRAP gene.

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

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...... 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...... strongly to the corrective response of the stretch reflex in the plantar flexor muscles during walking....

The effects of genetic polymorphism on treatment response of recombinant human growth hormone.

Science.gov (United States)

Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng

2017-12-06

Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Actin-myosin contractility is responsible for the reduced viability of dissociated human embryonic stem cells.

Science.gov (United States)

Chen, Guokai; Hou, Zhonggang; Gulbranson, Daniel R; Thomson, James A

2010-08-06

Human ESCs are the pluripotent precursor of the three embryonic germ layers. Human ESCs exhibit basal-apical polarity, junctional complexes, integrin-dependent matrix adhesion, and E-cadherin-dependent cell-cell adhesion, all characteristics shared by the epiblast epithelium of the intact mammalian embryo. After disruption of epithelial structures, programmed cell death is commonly observed. If individualized human ESCs are prevented from reattaching and forming colonies, their viability is significantly reduced. Here, we show that actin-myosin contraction is a critical effector of the cell death response to human ESC dissociation. Inhibition of myosin heavy chain ATPase, downregulation of myosin heavy chain, and downregulation of myosin light chain all increase survival and cloning efficiency of individualized human ESCs. ROCK inhibition decreases phosphorylation of myosin light chain, suggesting that inhibition of actin-myosin contraction is also the mechanism through which ROCK inhibitors increase cloning efficiency of human ESCs. Copyright 2010 Elsevier Inc. All rights reserved.

Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

Directory of Open Access Journals (Sweden)

Songhua Zhang

Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to 60Co at single fraction

International Nuclear Information System (INIS)

Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de; Leite, M.F.; Goes, A.M.

2005-01-01

Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to 60 Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min -1 rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by 60 Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

Transcriptional Response of Human Cells to Microbeam Irradiation with 2.1 MeV Alpha Particles

Science.gov (United States)

Hellweg, C. E.; Bogner, S.; Spitta, L.; Arenz, A.; Baumstark-Khan, C.; Greif, K. D.; Giesen, U.

Within the next decades an increasing number of human beings in space will be simultaneously exposed to different stimuli especially microgravity and radiation To assess the risks for humans during long-duration space missions the complex interplay of these parameters at the cellular level must be understood Cellular stress protection responses lead to increased transcription of several genes via modulation of transcription factors Activation of the Nuclear Factor kappa B NF- kappa B pathway as a possible anti-apoptotic route represents such an important cellular stress response A screening assay for detection of NF- kappa B-dependent gene activation using the destabilized variant of Enhanced Green Fluorescent Protein d2EGFP as reporter protein had been developed It consists of Human Embryonic Kidney HEK 293 Cells stably transfected with a receptor-reporter-construct carrying d2EGFP under the control of a NF- kappa B response element Clones positive for Tumor Necrosis Factor alpha TNF- alpha inducible d2EGFP expression were selected as cellular reporters Irradiation was performed either with X-rays 150 kV 19 mA at DLR Cologne or with 2 1 MeV alpha particles LET sim 160 keV mu m at PTB Braunschweig After irradiation the following biological endpoints were determined i cell survival via the colony forming ability test ii time-dependent activation of NF- kappa B dependent d2EGFP gene expression using flow cytometry iii quantitative RT-PCR

Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

International Nuclear Information System (INIS)

Tetz, Lauren M.; Cheng, Adrienne A.; Korte, Cassandra S.; Giese, Roger W.; Wang, Poguang; Harris, Craig; Meeker, John D.; Loch-Caruso, Rita

2013-01-01

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

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

Do Quercus ilex woodlands undergo abrupt non-linear functional changes in response to human disturbance along a climatic gradient?

Science.gov (United States)

Bochet, Esther; García-Fayos, Patricio; José Molina, Maria; Moreno de las Heras, Mariano; Espigares, Tíscar; Nicolau, Jose Manuel; Monleon, Vicente

2017-04-01

Theoretical models predict that drylands are particularly prone to suffer critical transitions with abrupt non-linear changes in their structure and functions as a result of the existing complex interactions between climatic fluctuations and human disturbances. However, so far, few studies provide empirical data to validate these models. We aim at determining how holm oak (Quercus ilex) woodlands undergo changes in their functions in response to human disturbance along an aridity gradient (from semi-arid to sub-humid conditions), in eastern Spain. For that purpose, we used (a) remote-sensing estimations of precipitation-use-efficiency (PUE) from enhanced vegetation index (EVI) observations performed in 231x231 m plots of the Moderate Resolution Imaging Spectroradiometer (MODIS); (b) biological and chemical soil parameter determinations (extracellular soil enzyme activity, soil respiration, nutrient cycling processes) from soil sampled in the same plots; (c) vegetation parameter determinations (ratio of functional groups) from vegetation surveys performed in the same plots. We analyzed and compared the shape of the functional change (in terms of PUE and soil and vegetation parameters) in response to human disturbance intensity for our holm oak sites along the aridity gradient. Overall, our results evidenced important differences in the shape of the functional change in response to human disturbance between climatic conditions. Semi-arid areas experienced a more accelerated non-linear decrease with an increasing disturbance intensity than sub-humid ones. The proportion of functional groups (herbaceous vs. woody cover) played a relevant role in the shape of the functional response of the holm oak sites to human disturbance.

Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

International Nuclear Information System (INIS)

Takeda, Kazuyo; Adhikari, Rewati; Yamada, Kenneth M.; Dhawan, Subhash

2015-01-01

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

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.

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.

Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

Directory of Open Access Journals (Sweden)

Derek J. Hanson

2018-06-01

Full Text Available Human herpesvirus (HHV 6 is thought to remain clinically latent in most individuals after primary infection and to reactivate to cause disease in persons with severe immunosuppression. In allogeneic hematopoietic stem cell transplant recipients, reactivation of HHV-6 species B is a considerable cause of morbidity and mortality. HHV-6B reactivation is the most frequent cause of infectious meningoencephalitis in this setting and has been associated with a variety of other complications such as graft rejection and acute graft versus host disease. This has inspired efforts to develop HHV-6-targeted immunotherapies. Basic knowledge of HHV-6-specific adaptive immunity is crucial for these endeavors, but remains incomplete. Many studies have focused on specific HHV-6 antigens extrapolated from research on human cytomegalovirus, a genetically related betaherpesvirus. Challenges to the study of HHV-6-specific T-cell immunity include the very low frequency of HHV-6-specific memory T cells in chronically infected humans, the large genome size of HHV-6, and the lack of an animal model. This review will focus on emerging techniques and methodological improvements that are beginning to overcome these barriers. Population-prevalent antigens are now becoming clear for the CD4+ T-cell response, while definition and ranking of CD8+ T-cell antigens and epitopes is at an earlier stage. This review will discuss current knowledge of the T-cell response to HHV-6, new research approaches, and translation to clinical practice.

Humoral and cell-mediated immune response against human retinal antigens in relation to ocular onchocerciasis

NARCIS (Netherlands)

van der Lelij, A.; Rothova, A.; Stilma, J. S.; Vetter, J. C.; Hoekzema, R.; Kijlstra, A.

1990-01-01

Autoimmune mechanisms are thought to be involved in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. The humoral autoimmune response was determined by measuring serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid binding protein

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.

Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

International Nuclear Information System (INIS)

Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

1991-01-01

Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction.

Science.gov (United States)

Rilling, James K; Demarco, Ashley C; Hackett, Patrick D; Chen, Xu; Gautam, Pritam; Stair, Sabrina; Haroon, Ebrahim; Thompson, Richmond; Ditzen, Beate; Patel, Rajan; Pagnoni, Giuseppe

2014-01-01

Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses

Neurochemical responses to chromatic and achromatic stimuli in the human visual cortex.

Science.gov (United States)

Bednařík, Petr; Tkáč, Ivan; Giove, Federico; Eberly, Lynn E; Deelchand, Dinesh K; Barreto, Felipe R; Mangia, Silvia

2018-02-01

In the present study, we aimed at determining the metabolic responses of the human visual cortex during the presentation of chromatic and achromatic stimuli, known to preferentially activate two separate clusters of neuronal populations (called "blobs" and "interblobs") with distinct sensitivity to color or luminance features. Since blobs and interblobs have different cytochrome-oxidase (COX) content and micro-vascularization level (i.e., different capacities for glucose oxidation), different functional metabolic responses during chromatic vs. achromatic stimuli may be expected. The stimuli were optimized to evoke a similar load of neuronal activation as measured by the bold oxygenation level dependent (BOLD) contrast. Metabolic responses were assessed using functional 1 H MRS at 7 T in 12 subjects. During both chromatic and achromatic stimuli, we observed the typical increases in glutamate and lactate concentration, and decreases in aspartate and glucose concentration, that are indicative of increased glucose oxidation. However, within the detection sensitivity limits, we did not observe any difference between metabolic responses elicited by chromatic and achromatic stimuli. We conclude that the higher energy demands of activated blobs and interblobs are supported by similar increases in oxidative metabolism despite the different capacities of these neuronal populations.

Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

International Nuclear Information System (INIS)

Lesinski, Gregory B; Zimmerer, Jason M; Kreiner, Melanie; Trefry, John; Bill, Matthew A; Young, Gregory S; Becknell, Brian; Carson, William E III

2010-01-01

Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr 701 -phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr 701 -phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation. These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ

Suppression of pro-inflammatory T-cell responses by human mesothelial cells.

Science.gov (United States)

Lin, Chan-Yu; Kift-Morgan, Ann; Moser, Bernhard; Topley, Nicholas; Eberl, Matthias

2013-07-01

Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.

Multi-timescale sediment responses across a human impacted river-estuary system

Science.gov (United States)

Chen, Yining; Chen, Nengwang; Li, Yan; Hong, Huasheng

2018-05-01

Hydrological processes regulating sediment transport from land to sea have been widely studied. However, anthropogenic factors controlling the river flow-sediment regime and subsequent response of the estuary are still poorly understood. Here we conducted a multi-timescale analysis on flow and sediment discharges during the period 1967-2014 for the two tributaries of the Jiulong River in Southeast China. The long-term flow-sediment relationship remained linear in the North River throughout the period, while the linearity showed a remarkable change after 1995 in the West River, largely due to construction of dams and reservoirs in the upland watershed. Over short timescales, rainstorm events caused the changes of suspended sediment concentration (SSC) in the rivers. Regression analysis using synchronous SSC data in a wet season (2009) revealed a delayed response (average 5 days) of the estuary to river input, and a box-model analysis established a quantitative relationship to further describe the response of the estuary to the river sediment input over multiple timescales. The short-term response is determined by both the vertical SSC-salinity changes and the sediment trapping rate in the estuary. However, over the long term, the reduction of riverine sediment yield increased marine sediments trapped into the estuary. The results of this study indicate that human activities (e.g., dams) have substantially altered sediment delivery patterns and river-estuary interactions at multiple timescales.

Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

Science.gov (United States)

Biswas, Sumi; Choudhary, Prateek; Elias, Sean C; Miura, Kazutoyo; Milne, Kathryn H; de Cassan, Simone C; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Osier, Faith H; Hodgson, Susanne H; Duncan, Christopher J A; O'Hara, Geraldine A; Long, Carole A; Hill, Adrian V S; Draper, Simon J

2014-01-01

The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases

Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

Directory of Open Access Journals (Sweden)

Sumi Biswas

Full Text Available The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i ChAd63-MVA immunization, ii immunization and CHMI, and iii primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i total IgG responses before and after CHMI, ii responses to allelic variants of MSP1 and AMA1, iii functional growth inhibitory activity (GIA, iv IgG avidity, and v isotype responses (IgG1-4, IgA and IgM. These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

Additive effects of affective arousal and top-down attention on the event-related brain responses to human bodies.

Science.gov (United States)

Hietanen, Jari K; Kirjavainen, Ilkka; Nummenmaa, Lauri

2014-12-01

The early visual event-related 'N170 response' is sensitive to human body configuration and it is enhanced to nude versus clothed bodies. We tested whether the N170 response as well as later EPN and P3/LPP responses to nude bodies reflect the effect of increased arousal elicited by these stimuli, or top-down allocation of object-based attention to the nude bodies. Participants saw pictures of clothed and nude bodies and faces. In each block, participants were asked to direct their attention towards stimuli from a specified target category while ignoring others. Object-based attention did not modulate the N170 amplitudes towards attended stimuli; instead N170 response was larger to nude bodies compared to stimuli from other categories. Top-down attention and affective arousal had additive effects on the EPN and P3/LPP responses reflecting later processing stages. We conclude that nude human bodies have a privileged status in the visual processing system due to the affective arousal they trigger. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

Science.gov (United States)

Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

2014-09-13

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6

Response of the MG-63 human osteosarcoma cell line grown as multicellular spheroids to neutron irradiation

International Nuclear Information System (INIS)

Kubota, Nobuo; Kakehi, Masae; Matsubara, Shou; Koike, Sachiko; Ando, Koichi.

1993-01-01

Multicellular tumor spheroids are composed of the mixed populations of cells with regard to cell proliferation, nutrition, oxygenation and radiosensitivity. Human osteogenic sarcoma is generally considered clinically radioresistant. However, the in vitro cell survival curves for human osteogenic sarcoma cell lines do not differ from those of other tumor cell lines. In this study, the responses of human osteogenic sarcoma cell line to gamma ray and neutrons were investigated by using spheroid system. The spheroids of the osteogenic sarcoma cell line are considered to be a good in vitro model of radioresistant tumors. The purpose of this study is to measure the response of the spheroids to fast neutron irradiation. MG-63 human osteogenic sarcoma cell line was used for this study. The cell line was cultured in alpha-MEM with supplement. Cell survival was estimated after the trypsinization of spheroids 24 hours after irradiation. The method of measuring spheroid cure is explained. The mean number of surviving cells per spheroid can be obtained from the mean clonogenic number and cell survival curve. The cell survival of MG-63 spheroids exposed to gamma ray and neutrons and the dose effect curves for spheroid cure after irradiation are shown. (K.I.)

Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

Science.gov (United States)

Zhang, Ye; Wu, Honglu

2012-07-01

RESPONSE OF HUMAN PROSTATE CANCER CELLS TO MITOXANTRONE TREATMENT IN SIMULATED MICROGRAVITY ENVIRONMENT Ye Zhang1,2, Christopher Edwards3, and Honglu Wu1 1 NASA-Johnson Space Center, Houston, TX 2 Wyle Integrated Science and Engineering Group, Houston, TX 3 Oregon State University, Corvallis, OR This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on

Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells

NARCIS (Netherlands)

van Hemert, Saskia; Meijerink, Marjolein; Molenaar, Douwe; Bron, Peter A.; de Vos, Paul; Kleerebezem, Michiel; Wells, Jerry M.; Marco, Maria L.

2010-01-01

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

Radiation response of haematopoietic cell lines of human origin

International Nuclear Information System (INIS)

Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.

1986-01-01

Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

Energy Technology Data Exchange (ETDEWEB)

Rocke, David M. [University of California Davis

2013-09-09

During course of this project, we have worked in several areas relevant to low-dose ionizing radiation. Using gene expression to measure biological response, we have examined the response of human skin exposed in-vivo to radation, human skin exposed ex-vivo to radiation, and a human-skin model exposed to radiation. We have learned a great deal about the biological response of human skin to low-dose ionizing radiation.

Contagious yawning, social cognition, and arousal: an investigation of the processes underlying shelter dogs' responses to human yawns.

Science.gov (United States)

Buttner, Alicia Phillips; Strasser, Rosemary

2014-01-01

Studies of contagious yawning have reported inconsistent findings regarding whether dogs exhibit this behavior and whether it is mediated by social-cognitive processes or the result of physiological arousal. We investigated why some dogs yawn in response to human yawns; particularly, whether these dogs are exceptional in their ability to understand human social cues or whether they were more physiologically aroused. Sixty shelter dogs were exposed to yawning and nonyawning control stimuli demonstrated by an unfamiliar human. We took salivary cortisol samples before and after testing to determine the role of arousal in yawn contagion. Dogs were tested on the object-choice task to assess their sensitivity for interpreting human social cues. We found that 12 dogs yawned only in response to human yawns (i.e., appeared to exhibit yawn contagion), though contagious yawning at the population level was not observed. Dogs that exhibited yawn contagion did not perform better on the object-choice task than other dogs, but their cortisol levels remained elevated after exposure to human yawning, whereas other dogs had reduced cortisol levels following yawning stimuli relative to their baseline levels. We interpret these findings as showing that human yawning, when presented in a stressful context, can further influence arousal in dogs, which then causes some to yawn. Although the precise social-cognitive mechanisms that underlie contagious yawning in dogs are still unclear, yawning between humans and dogs may involve some communicative function that is modulated by context and arousal.

[Human milk, immune responses and health effects].

Science.gov (United States)

Løland, Beate Fossum; Baerug, Anne B; Nylander, Gro

2007-09-20

Besides providing optimal nutrition to infants, human milk contains a multitude of immunological components. These components are important for protection against infections and also support the development and maturation of the infant's own immune system. This review focuses on the function of some classical immunocomponents of human milk. Relevant studies are presented that describe health benefits of human milk for the child and of lactation for the mother. Relevant articles were found mainly by searching PubMed. Humoral and cellular components of human milk confer protection against infections in the respiratory--, gastrointestinal--and urinary tract. Human milk also protects premature children from neonatal sepsis and necrotizing enterocolitis. There is evidence that human milk may confer long-term benefits such as lower risk of certain autoimmune diseases, inflammatory bowel disease and probably some malignancies. Human milk possibly affects components of the metabolic syndrome. Recent studies demonstrate long-term health benefits of lactation also for the mother. A reduced incidence of breast cancer is best documented. An increasing number of studies indicate protection against ovarian cancer, rheumatoid arthritis and type II diabetes.

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.

Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation

International Nuclear Information System (INIS)

Zou, Ying; Zhang, Ningzhe; Ellerby, Lisa M.; Davalos, Albert R.; Zeng, Xianmin; Campisi, Judith; Desprez, Pierre-Yves

2012-01-01

Highlights: ► hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. ► Upon irradiation, most hESCs died within 5–7 h. ► Surviving NSCs underwent senescence and displayed features of astrocytes. ► Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. ► 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.

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.

Phenotypic and functional characterization of human memory T cell responses to Burkholderia pseudomallei.

Directory of Open Access Journals (Sweden)

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.

SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

Energy Technology Data Exchange (ETDEWEB)

Yan, D [William Beaumont Hospital, Royal Oak, MI (United States); Chen, S; Krauss, D; Chen, P [Beaumont Health System, Royal Oak, Michigan (United States); Wilson, G [Beaumont Health System, Royal Oak, MI (United States)

2016-06-15

Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function of pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.

The PROGINS polymorphism of the human progesterone receptor diminishes the response to progesterone.

Science.gov (United States)

Romano, Andrea; Delvoux, Bert; Fischer, Dagmar-Christiane; Groothuis, Patrick

2007-02-01

The human progesterone receptor (PR) is a ligand-dependent transcription factor and two isoforms, (PRA and PRB), can be distinguished. PROGINS, a PR polymorphic variant, affects PRA and PRB and acts as a risk-modulating factor in several gynaecological disorders. Little is known about the functional consequences of this variant. Here, we characterise the properties of PROGINS with respect to transcription, mRNA maturation, protein activity and proliferation. PROGINS is characterised by a 320 bp PV/HS-1 Alu insertion in intron G and two point mutations, V660L in exon 4 and H770H (silent substitution) in exon 5. The Alu element contains a half oestrogen-response element/Sp1-binding site (Alu-ERE/Sp1), which acts as an in-cis intronic enhancer leading to increased transcription of the PROGINS allele in response to 17beta-oestradiol. Moreover, Alu insertions in the human genome are frequently methylated. Our data indicate that the PROGINS-Alu does not affect gene transcription due to DNA methylation. However, the Alu element reduced the stability of the PROGINS transcript compared with the CP allele and does not generate splice variants. The amino acid substitution (V600L) in exon 4 leads to differences in PR phosphorylation and degradation in the two PR variants upon ligand binding, most likely as a result of differences in the three-dimensional structures of the two PR variants. As a consequence, the PR-L660 (PROGINS) variant (1) displays decreased transactivation activity in a luciferase reporter system and (2) is less efficient in opposing cell proliferation in hamster ovarian cells expressing human PRA, when compared with the PR-V660 (most common variant). Taken together, our results indicate that the PROGINS variant of PR is less responsive to progestin compared with the most common PR because of (i) reduced amounts of gene transcript and (ii) decreased protein activity.

Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors.

Science.gov (United States)

Viblanc, Vincent A; Smith, Andrew D; Gineste, Benoit; Groscolas, René

2012-07-11

A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism) might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus), breeding on remote and protected islands of the Southern ocean. Using heart rate (HR) as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists) for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches) to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research) which only a few individuals experience each year. Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors

Directory of Open Access Journals (Sweden)

Viblanc Vincent A

2012-07-01

Full Text Available Abstract Background A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Results Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus, breeding on remote and protected islands of the Southern ocean. Using heart rate (HR as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research which only a few individuals experience each year. Conclusions Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

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)

Human antibody and antigen response to IncA antibody of Chlamydia trachomatis.

Science.gov (United States)

Tsai, P Y; Hsu, M C; Huang, C T; Li, S Y

2007-01-01

The high prevalence of C. trachomatis worldwide has underscored the importance of identifying specific immunogenic antigens in facilitating diagnosis as well as vaccine development. The aim of this study is to evaluate IncA antibody and antigen production in natural human infections. Our temporal expression study showed that IncA transcription and protein expression could be detected as early as 4 hours after the start of infection. Antibody responses could be detected in urine and genital swab samples from C. trachomatis-positive patients. It is especially interesting to note that the IncA antigen could be detected in urine. In conclusion, we have identified IncA as an important antigen in human. The potential applicability of the IncA antibody or antigen in the diagnosis as well as to vaccine development for C. trachomatis is also discussed.

A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M. tuberculosis Infected South Africans.

Directory of Open Access Journals (Sweden)

Cecilia S Lindestam Arlehamn

2016-07-01

Full Text Available We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb, in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context of an infection and human population setting. We determined the epitope repertoire of eleven representative Mtb antigens and a large panel of previously defined Mtb epitopes. We estimated that our analytic methods detected 50-75% of the total response in a cohort of 63 individuals. As expected, responses were highly heterogeneous, with responses to a total of 125 epitopes detected. The 66 top epitopes provided 80% coverage of the responses identified in our study. Using a panel of 48 HLA class II-transfected antigen-presenting cells, we determined HLA class II restrictions for 278 epitope/donor recognition events (36% of the total. The majority of epitopes were restricted by multiple HLA alleles, and 380 different epitope/HLA combinations comprised less than 30% of the estimated Mtb-specific response. Our results underline the complexity of human T cell responses at a population level. Efforts to capture and characterize this broad and highly HLA promiscuous Mtb-specific T cell epitope repertoire will require significant peptide multiplexing efforts. We show that a comprehensive "megapool" of Mtb peptides captured a large fraction of the Mtb-specific T cells and can be used to characterize this response.

A Human Resources Perspective on Responsible Corporate Behavior. Case Study: The Multinational Companies in Western Romania

Directory of Open Access Journals (Sweden)

Ciprian Obrad

2018-03-01

Full Text Available This article aims to show the extent to which socially responsible Human Resource Management practices are implemented in multinational companies. As more recent studies highlight, the manner in which companies in Romania presently comprehend the social responsibility of their actions is mostly aimed towards the social component of the outer environment in which they function and less towards their own employees. In Romania, at the moment, there are only a few studies that catalogue the efforts made by companies in order to become more responsible towards their employees, or in other words, studies that present Corporate Social Responsibility (CSR within its relationship with Human Resources Management (HRM. The research method we used for our case study was the semi-structured interview, applied on 32 respondents from the multinational companies carrying out their activities in the automotive sector in western Romania. Our study shows that multinational companies from the automotive sector are aware that CSR effects a series of long-term advantages, either externally—enhancing the company’s reputation and consolidating its brand as employer, its competitive advantage on the market, its media visibility—or internally—fostering an organizational culture that may generate greater engagement from its own employees, and financial advantages.

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.

Lactic acid delays the inflammatory response of human monocytes

International Nuclear Information System (INIS)

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

2015-01-01

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

Forecasting extreme temperature health hazards in Europe

Science.gov (United States)

Di Napoli, Claudia; Pappenberger, Florian; Cloke, Hannah L.

2017-04-01

Extreme hot temperatures, such as those experienced during a heat wave, represent a dangerous meteorological hazard to human health. Heat disorders such as sunstroke are harmful to people of all ages and responsible for excess mortality in the affected areas. In 2003 more than 50,000 people died in western and southern Europe because of a severe and sustained episode of summer heat [1]. Furthermore, according to the Intergovernmental Panel on Climate Change heat waves are expected to get more frequent in the future thus posing an increasing threat to human lives. Developing appropriate tools for extreme hot temperatures prediction is therefore mandatory to increase public preparedness and mitigate heat-induced impacts. A recent study has shown that forecasts of the Universal Thermal Climate Index (UTCI) provide a valid overview of extreme temperature health hazards on a global scale [2]. UTCI is a parameter related to the temperature of the human body and its regulatory responses to the surrounding atmospheric environment. UTCI is calculated using an advanced thermo-physiological model that includes the human heat budget, physiology and clothing. To forecast UTCI the model uses meteorological inputs, such as 2m air temperature, 2m water vapour pressure and wind velocity at body height derived from 10m wind speed, from NWP models. Here we examine the potential of UTCI as an extreme hot temperature prediction tool for the European area. UTCI forecasts calculated using above-mentioned parameters from ECMWF models are presented. The skill in predicting UTCI for medium lead times is also analysed and discussed for implementation to international health-hazard warning systems. This research is supported by the ANYWHERE project (EnhANcing emergencY management and response to extreme WeatHER and climate Events) which is funded by the European Commission's HORIZON2020 programme. [1] Koppe C. et al., Heat waves: risks and responses. World Health Organization. Health and

Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

Science.gov (United States)

Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

2018-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

Modification of nucleotide metabolism in relationship with differentiation and in response to irradiation in human tumour cells

International Nuclear Information System (INIS)

Wei, Shuang

1998-01-01

This research thesis reports the study of the metabolism of nucleotides in human tumour cells. The first part addresses the modifications of nucleotide (more specifically purine) metabolism in relationship with human melanoma cell proliferation and differentiation. The second part addresses the modifications of this metabolism in response to an irradiation in human colon tumour cells. For each part, the author proposes a bibliographic synthesis, and a presentation of studied cells and of methods used to grow cells, and respectively to proliferate and differentiate them or to irradiate them, and then discusses the obtained results [fr

Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells

International Nuclear Information System (INIS)

Sato, Akira; Itoh, Tasuku; Imamichi, Shoji; Kikuhara, Sota; Fujimori, Hiroaki; Hirai, Takahisa; Saito, Soichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Nakamura, Hiroyuki; Suzuki, Minoru

2015-01-01

To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(−) conditions. BNCR mainly induced typical apoptosis in SAS cells 24 h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR. - Highlights: • BNCR in human squamous carcinoma cells caused typical apoptotic features. • BNCR induced fragments of LRMP, in human squamous carcinoma and rat tumor model. • The fragmentation of LRMP could be involved in cellular response to BNCR.

Thermal Response of In Vivo Human Skin to Fractional Radiofrequency Microneedle Device

Directory of Open Access Journals (Sweden)

Woraphong Manuskiatti

2016-01-01

Full Text Available Background. Fractional radiofrequency microneedle system (FRMS is a novel fractional skin resurfacing system. Data on thermal response to this fractional resurfacing technique is limited. Objectives. To investigate histologic response of in vivo human skin to varying energy settings and pulse stacking of a FRMS in dark-skinned subjects. Methods. Two female volunteers who were scheduled for abdominoplasty received treatment with a FRMS with varying energy settings at 6 time periods including 3 months, 1 month, 1 week, 3 days, 1 day, and the time immediately before abdominoplasty. Biopsy specimens were analyzed using hematoxylin and eosin (H&E, Verhoeff-Van Gieson (VVG, colloidal iron, and Fontana-Masson stain. Immunohistochemical study was performed by using Heat Shock Protein 70 (HSP70 antibody and collagen III monoclonal antibody. Results. The average depth of radiofrequency thermal zone (RFTZ ranged from 100 to 300 μm, correlating with energy levels. Columns of cell necrosis and collagen denaturation followed by inflammatory response were initially demonstrated, with subsequent increasing of mucin at 1 and 3 months after treatment. Immunohistochemical study showed positive stain with HSP70. Conclusion. A single treatment with a FRMS using appropriate energy setting induces neocollagenesis. This wound healing response may serve as a mean to improve the appearance of photodamaged skin and atrophic scars.

Differentiation of Inflammation-Responsive Astrocytes from Glial Progenitors Generated from Human Induced Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Renata Santos

2017-06-01

Full Text Available Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1β or tumor necrosis factor α elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1β. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration.

A Histopathologic Study on Pulp Response to Glass Ionomer Cements in Human Teeth

Directory of Open Access Journals (Sweden)

M. Ghavamnasiri

2005-12-01

Full Text Available Statement of Problem: Despite the wide range of new dental materials, there is still a need for biomaterials demonstrating high biocompatibility, antimicrobial effects and ideal mechanical properties.Purpose: The aim of this study was to histologically evaluate the pulpal response to a conventional glass ionomer, a resin modified glass ionomer and a calcium hydroxide in human teeth.Materials and Methods: Fifty five deep class V cavities were prepared in premolars of 31 patients and were divided into 3 groups based on application of the following liners:resin modified glass ionomer (Vivaglass Liner, conventional glass ionomer (ChembondSuperior and calcium hydroxide (Dycal. After applying varnish, teeth were filled with amalgam. Each group was further divided into three subgroups according to time intervals of 7, 30 and 60 days. Teeth were then extracted and their crowns were fixed in formalin. Each sample was assessed microscopically for odontoblastic changes,inflammatory cell infiltration, reactionary dentin formation, remaining dentinal thickness and presence of microorganisms. Statistical analysis including Kruskal Wallis and Mann Whitney was carried out for comparison of mean ranks. (P=0.05.Results: In the Vivaglass Liner group, pulpal response was significantly higher on day 7 as compared to days 30 and 60 (P0.05. There was no correlation between pulpal responses with micro-organisms and remaining dentin thickness (P>0.05.Conclusion: According to the results of this study, light-cured glass ionomer as well as the other tested lining materials were determined to be biologically compatible with vital pulps in deep cavities of sound human teeth.

An Individualized, Perception-Based Protocol to Investigate Human Physiological Responses to Cooling

Science.gov (United States)

Coolbaugh, Crystal L.; Bush, Emily C.; Galenti, Elizabeth S.; Welch, E. Brian; Towse, Theodore F.

2018-01-01

Cold exposure, a known stimulant of the thermogenic effects of brown adipose tissue (BAT), is the most widely used method to study BAT physiology in adult humans. Recently, individualized cooling has been recommended to standardize the physiological cold stress applied across participants, but critical experimental details remain unclear. The purpose of this work was to develop a detailed methodology for an individualized, perception-based protocol to investigate human physiological responses to cooling. Participants were wrapped in two water-circulating blankets and fitted with skin temperature probes to estimate BAT activity and peripheral vasoconstriction. We created a thermoesthesia graphical user interface (tGUI) to continuously record the subject's perception of cooling and shivering status during the cooling protocol. The protocol began with a 15 min thermoneutral phase followed by a series of 10 min cooling phases and concluded when sustained shivering (>1 min duration) occurred. Researchers used perception of cooling feedback (tGUI ratings) to manually adjust and personalize the water temperature at each cooling phase. Blanket water temperatures were recorded continuously during the protocol. Twelve volunteers (ages: 26.2 ± 1.4 years; 25% female) completed a feasibility study to evaluate the proposed protocol. Water temperature, perception of cooling, and shivering varied considerably across participants in response to cooling. Mean clavicle skin temperature, a surrogate measure of BAT activity, decreased (−0.99°C, 95% CI: −1.7 to −0.25°C, P = 0.16) after the cooling protocol, but an increase in supraclavicular skin temperature was observed in 4 participants. A strong positive correlation was also found between thermoesthesia and peripheral vasoconstriction (ρ = 0.84, P < 0.001). The proposed individualized, perception-based protocol therefore has potential to investigate the physiological responses to cold stress applied across populations with

Europe's Shifting Response to HIV/AIDS: From Human Rights to Risk Management.

Science.gov (United States)

Smith, Julia

2016-12-01

Despite a history of championing HIV/AIDS as a human rights issue, and a rhetorical commitment to health as a human right, European states and institutions have shifted from a rights-based response to a risk management approach to HIV/AIDS since the economic recession of 2008. An interdisciplinary perspective is applied to analyze health policy changes at the national, regional, and global levels by drawing on data from key informant interviews, and institutional and civil society documents. It is demonstrated that, in the context of austerity measures, member states such as the UK and Greece reduced commitments to rights associated with HIV/AIDS; at the regional level, the EU failed to develop rights-based approaches to address the vulnerabilities and health care needs of key populations affected by HIV/AIDS, particularly migrants and sex workers; and at the global level, the EU backtracked on commitments to global health and is prioritizing the intellectual property rights of pharmaceutical companies over the human rights of people living with HIV/AIDS. The focus within and from the EU is on containment, efficiency, and cost reduction. The rights of those most affected are no longer prioritized.

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.

Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells.

Science.gov (United States)

Bursomanno, Sara; Beli, Petra; Khan, Asif M; Minocherhomji, Sheroy; Wagner, Sebastian A; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chunaram; Hickson, Ian D; Liu, Ying

2015-01-01

SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology. Copyright © 2014 Elsevier B.V. All rights reserved.

Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI.

Science.gov (United States)

Ferrer-Buitrago, M; Dhaenens, L; Lu, Y; Bonte, D; Vanden Meerschaut, F; De Sutter, P; Leybaert, L; Heindryckx, B

2018-01-10

Can human oocyte calcium analysis predict fertilization success after assisted oocyte activation (AOA) in patients experiencing fertilization failure after ICSI? ICSI-AOA restores the fertilization rate only in patients displaying abnormal Ca2+ oscillations during human oocyte activation. Patients capable of activating mouse oocytes and who showed abnormal Ca2+ profiles after mouse oocyte Ca2+ analysis (M-OCA), have variable responses to ICSI-AOA. It remains unsettled whether human oocyte Ca2+ analysis (H-OCA) would yield an improved accuracy to predict fertilization success after ICSI-AOA. Sperm activation potential was first evaluated by MOAT. Subsequently, Ca2+ oscillatory patterns were determined with sperm from patients showing moderate to normal activation potential based on the capacity of human sperm to generate Ca2+ responses upon microinjection in mouse and human oocytes. Altogether, this study includes a total of 255 mouse and 122 human oocytes. M-OCA was performed with 16 different sperm samples before undergoing ICSI-AOA treatment. H-OCA was performed for 11 patients who finally underwent ICSI-AOA treatment. The diagnostic accuracy to predict fertilization success was calculated based on the response to ICSI-AOA. Patients experiencing low or total failed fertilization after conventional ICSI were included in the study. All participants showed moderate to high rates of activation after MOAT. Metaphase II (MII) oocytes from B6D2F1 mice were used for M-OCA. Control fertile sperm samples were used to obtain a reference Ca2+ oscillation profile elicited in human oocytes. Donated human oocytes, non-suitable for IVF treatments, were collected and vitrified at MII stage for further analysis by H-OCA. M-OCA and H-OCA predicted the response to ICSI-AOA in 8 out of 11 (73%) patients. Compared to M-OCA, H-OCA detected the presence of sperm activation deficiencies with greater sensitivity (75 vs 100%, respectively). ICSI-AOA never showed benefit to overcome

Influence of hydration and experimental length scale on themechanical response of human skin in vivo, using optical coherence tomography

NARCIS (Netherlands)

Hendriks, F.M.; Brokken, D.; Oomens, C.W.J.; Baaijens, F.P.T.

2004-01-01

Human skin is a complex tissue consisting of different layers. To gain better insight into the mechanical behaviour of different skin layers, the mechanical response was studied with experiments of various length scales. Also, the influence of (superficial) hydration on the mechanical response is

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.

Response of the human circadian system to millisecond flashes of light.

Directory of Open Access Journals (Sweden)

Jamie M Zeitzer

Full Text Available Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN, remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7 to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01. These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05 in the electroencephalogram (EEG. Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures.

Proteomic analysis of secreted proteins by human bronchial epithelial cells in response to cadmium toxicity.

Science.gov (United States)