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Sample records for human sensory-evoked responses

  1. Cortical Variability in the Sensory-Evoked Response in Autism

    ERIC Educational Resources Information Center

    Haigh, Sarah M.; Heeger, David J.; Dinstein, Ilan; Minshew, Nancy; Behrmann, Marlene

    2015-01-01

    Previous findings have shown that individuals with autism spectrum disorder (ASD) evince greater intra-individual variability (IIV) in their sensory-evoked fMRI responses compared to typical control participants. We explore the robustness of this finding with a new sample of high-functioning adults with autism. Participants were presented with…

  2. Human sensory-evoked responses differ coincident with either "fusion-memory" or "flash-memory", as shown by stimulus repetition-rate effects

    PubMed Central

    Jewett, Don L; Hart, Toryalai; Larson-Prior, Linda J; Baird, Bill; Olson, Marram; Trumpis, Michael; Makayed, Katherine; Bavafa, Payam

    2006-01-01

    Background: A new method has been used to obtain human sensory evoked-responses whose time-domain waveforms have been undetectable by previous methods. These newly discovered evoked-responses have durations that exceed the time between the stimuli in a continuous stream, thus causing an overlap which, up to now, has prevented their detection. We have named them "A-waves", and added a prefix to show the sensory system from which the responses were obtained (visA-waves, audA-waves, somA-waves). Results: When A-waves were studied as a function of stimulus repetition-rate, it was found that there were systematic differences in waveshape at repetition-rates above and below the psychophysical region in which the sensation of individual stimuli fuse into a continuity. The fusion phenomena is sometimes measured by a "Critical Fusion Frequency", but for this research we can only identify a frequency-region [which we call the STZ (Sensation-Transition Zone)]. Thus, the A-waves above the STZ differed from those below the STZ, as did the sensations. Study of the psychophysical differences in auditory and visual stimuli, as shown in this paper, suggest that different stimulus features are detected, and remembered, at stimulation rates above and below STZ. Conclusion: The results motivate us to speculate that: 1) Stimulus repetition-rates above the STZ generate waveforms which underlie "fusion-memory" whereas rates below the STZ show neuronal processing in which "flash-memory" occurs. 2) These two memories differ in both duration and mechanism, though they may occur in the same cell groups. 3) The differences in neuronal processing may be related to "figure" and "ground" differentiation. We conclude that A-waves provide a novel measure of neural processes that can be detected on the human scalp, and speculate that they may extend clinical applications of evoked response recordings. If A-waves also occur in animals, it is likely that A-waves will provide new methods for

  3. Prematurely Delivered Rats Show Improved Motor Coordination During Sensory-evoked Motor Responses Compared to Age-matched Controls

    PubMed Central

    Roberto, Megan E.; Brumley, Michele R.

    2014-01-01

    The amount of postnatal experience for perinatal rats was manipulated by delivering pups one day early (postconception day 21; PC21) by cesarean delivery and comparing their motor behavior to age-matched controls on PC22 (the typical day of birth). On PC22, pups were tested on multiple measures of motor coordination: leg extension response (LER), facial wiping, contact righting, and fore- and hindlimb stepping. The LER and facial wiping provided measures of synchronous hind- and forelimb coordination, respectively, and were sensory-evoked. Contact righting also was sensory-evoked and provided a measure of axial coordination. Stepping provided a measure of alternated forelimb and hindlimb coordination and was induced with the serotonin receptor agonist quipazine. Pups that were delivered prematurely and spent an additional day in the postnatal environment showed more bilateral limb coordination during expression of the LER and facial wiping, as well as a more mature righting strategy, compared to controls. These findings suggest that experience around the time of birth shapes motor coordination and the expression of species-typical behavior in the developing rat. PMID:24680729

  4. RAT AND HUMAN SENSORY EVOKED POTENTIALS AND THE PREDICTABILITY OF HUMAN NEUROTOXICITY FROM RAT DATA

    EPA Science Inventory

    The development of comprehensive quantitative models as alternatives to risk assessment based on uncertainty factors will require many steps, among them consideration of the relationships between the health endpoints which are measured in laboratory animals and humans. Sensory ev...

  5. Changes in Sensory Evoked Responses Coincide with Rapid Improvement in Speech Identification Performance

    ERIC Educational Resources Information Center

    Alain, Claude; Campeanu, Sandra; Tremblay, Kelly

    2010-01-01

    Perceptual learning is sometimes characterized by rapid improvements in performance within the first hour of training (fast perceptual learning), which may be accompanied by changes in sensory and/or response pathways. Here, we report rapid physiological changes in the human auditory system that coincide with learning during a 1-hour test session…

  6. MDMA (ecstasy) modulates locomotor and prefrontal cortex sensory evoked activity.

    PubMed

    Atkins, Kristal; Burks, Tilithia; Swann, Alan C; Dafny, Nachum

    2009-12-11

    Ingestion of 3, 4-methylenedioxymethamphetamine (MDMA) leads to heightened response to sensory stimulation; thus, MDMA is referred to as "ecstasy" because it produces pleasurable enhancement of such sensation. There have been no electrophysiological studies that report the consequences of MDMA on sensory input. The present study was initiated to study the effects of acute and chronic MDMA on locomotor activity and sensory evoked field potential from freely behaving rats previously implanted with permanent electrodes in the prefrontal cortex (PFC). The main findings of this study are that: (1) acute MDMA augments locomotor behavior and attenuates the incoming sensory input, (2) chronic treatment of MDMA elicits behavioral sensitization, (3) chronic administration of MDMA results in attenuation of the baseline activity of the sensory evoked field potential, and (4) administration of rechallenge MDMA result in enhancement of the PFC sensory evoked field potential. PMID:19769950

  7. USE OF SENSORY EVOKED POTENTIALS IN TOXICOLOGY

    EPA Science Inventory

    The rationale for studying sensory systems as an integral part of neurotoxicological examinations is presented. The role of evoked potentials in assessing brain dysfunction in general and sensory systems in particular is also presented. Four types of sensory evoked potentials (br...

  8. Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites.

    PubMed

    Egger, Robert; Schmitt, Arno C; Wallace, Damian J; Sakmann, Bert; Oberlaender, Marcel; Kerr, Jason N D

    2015-11-10

    Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2-5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism-consistent with the theory of distal dendritic shunting-that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency. PMID:26512104

  9. Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites

    PubMed Central

    Egger, Robert; Schmitt, Arno C.; Wallace, Damian J.; Sakmann, Bert; Oberlaender, Marcel; Kerr, Jason N. D.

    2015-01-01

    Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2–5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism—consistent with the theory of distal dendritic shunting—that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency. PMID:26512104

  10. Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

    PubMed Central

    Duguid, Ian; Branco, Tiago; Chadderton, Paul; Arlt, Charlotte; Powell, Kate; Häusser, Michael

    2015-01-01

    Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses. PMID:26432880

  11. Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex.

    PubMed

    An, Shuming; Kilb, Werner; Luhmann, Heiko J

    2014-08-13

    Self-generated neuronal activity originating from subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neural activity patterns and role of primary motor cortex (M1) in these early movements are still unknown. Combining voltage-sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7% of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts were uncorrelated to movements and these bursts had significantly fewer spikes and shorter burst duration. Focal electrical stimulation of layer V neurons in M1 mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity reliably elicited forepaw movements. We conclude that M1 is already involved in somatosensory information processing during early development. M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Only a fraction of M1 activity transients trigger motor responses directly. We suggest that both spontaneously occurring and sensory-evoked gamma and spindle bursts in M1 contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination. PMID:25122889

  12. Alterations in oropharyngeal sensory evoked potentials (PSEP) with Parkinson's disease.

    PubMed

    Pitts, Teresa; Hegland, Karen Wheeler; Sapienza, Christine M; Bolser, Donald C; Davenport, Paul W

    2016-07-15

    Movement of a food bolus from the oral cavity into the oropharynx activates pharyngeal sensory mechanoreceptors. Using electroencephalography, somatosensory cortical-evoked potentials resulting from oropharyngeal mechanical stimulation (PSEP) have been studied in young healthy individuals. However, limited information is known about changes in processing of oropharyngeal afferent signals with Parkinson's disease (PD). To determine if sensory changes occurred with a mechanical stimulus (air-puff) to the oropharynx, two stimuli (S1-first; S2-s) were delivered 500ms apart. Seven healthy older adults (HOA; 3 male and 4 female; 72.2±6.9 years of age), and thirteen persons diagnosed with idiopathic Parkinson's disease (PD; 11 male and 2 female; 67.2±8.9 years of age) participated. Results demonstrated PSEP P1, N1, and P2 component peaks were identified in all participants, and the N2 peak was present in 17/20 participants. Additionally, the PD participants had a decreased N2 latency and gated the P1, P2, and N2 responses (S2/S1 under 0.6). Compared to the HOAs, the PD participants had greater evidence of gating the P1 and N2 component peaks. These results suggest that persons with PD experience changes in sensory processing of mechanical stimulation of the pharynx to a greater degree than age-matched controls. In conclusion, the altered processing of sensory feedback from the pharynx may contribute to disordered swallow in patients with PD. PMID:27090350

  13. Laminar and Columnar Structure of Sensory-Evoked Multineuronal Spike Sequences in Adult Rat Barrel Cortex In Vivo.

    PubMed

    Reyes-Puerta, Vicente; Sun, Jyh-Jang; Kim, Suam; Kilb, Werner; Luhmann, Heiko J

    2015-08-01

    One of the most relevant questions regarding the function of the nervous system is how sensory information is represented in populations of cortical neurons. Despite its importance, the manner in which sensory-evoked activity propagates across neocortical layers and columns has yet not been fully characterized. In this study, we took advantage of the distinct organization of the rodent barrel cortex and recorded with multielectrode arrays simultaneously from up to 74 neurons localized in several functionally identified layers and columns of anesthetized adult Wistar rats in vivo. The flow of activity within neuronal populations was characterized by temporally precise spike sequences, which were repeatedly evoked by single-whisker stimulation. The majority of the spike sequences representing instantaneous responses were led by a subgroup of putative inhibitory neurons in the principal column at thalamo-recipient layers, thus revealing the presence of feedforward inhibition. However, later spike sequences were mainly led by infragranular excitatory neurons in neighboring columns. Although the starting point of the sequences was anatomically confined, their ending point was rather scattered, suggesting that the population responses are structurally dispersed. Our data show for the first time the simultaneous intra- and intercolumnar processing of information at high temporal resolution. PMID:24518757

  14. Rivalry of homeostatic and sensory-evoked emotions: Dehydration attenuates olfactory disgust and its neural correlates.

    PubMed

    Meier, Lea; Friedrich, Hergen; Federspiel, Andrea; Jann, Kay; Morishima, Yosuke; Landis, Basile Nicolas; Wiest, Roland; Strik, Werner; Dierks, Thomas

    2015-07-01

    Neural correlates have been described for emotions evoked by states of homeostatic imbalance (e.g. thirst, hunger, and breathlessness) and for emotions induced by external sensory stimulation (such as fear and disgust). However, the neurobiological mechanisms of their interaction, when they are experienced simultaneously, are still unknown. We investigated the interaction on the neurobiological and the perceptional level using subjective ratings, serum parameters, and functional magnetic resonance imaging (fMRI) in a situation of emotional rivalry, when both a homeostatic and a sensory-evoked emotion were experienced at the same time. Twenty highly dehydrated male subjects rated a disgusting odor as significantly less repulsive when they were thirsty. On the neurobiological level, we found that this reduction in subjective disgust during thirst was accompanied by a significantly reduced neural activity in the insular cortex, a brain area known to be considerably involved in processing of disgust. Furthermore, during the experience of disgust in the satiated condition, we observed a significant functional connectivity between brain areas responding to the disgusting odor, which was absent during the stimulation in the thirsty condition. These results suggest interference of conflicting emotions: an acute homeostatic imbalance can attenuate the experience of another emotion evoked by the sensory perception of a potentially harmful external agent. This finding offers novel insights with regard to the behavioral relevance of biologically different types of emotions, indicating that some types of emotions are more imperative for behavior than others. As a general principle, this modulatory effect during the conflict of homeostatic and sensory-evoked emotions may function to safeguard survival. PMID:25818686

  15. Peak morphology and scalp topography of the pharyngeal sensory-evoked potential.

    PubMed

    Wheeler-Hegland, Karen; Pitts, Teresa; Davenport, Paul W

    2011-09-01

    The initiation of the pharyngeal stage of swallowing is dependent upon sensory input to the brainstem and cortex. The event-related evoked potential provides a measure of neuronal electrical activity as it relates to a specific stimulus. Air-puff stimulation to the posterior pharyngeal wall produces a sensory-evoked potential (PSEP) waveform. The goal of this study was to characterize the scalp topography and morphology for the component peaks of the PSEP waveform. Twenty-five healthy men and women served as research participants. PSEPs were measured via a 32-electrode cap (10-20 system) connected to SynAmps2 Neuroscan EEG System. Air puffs were delivered directly to the oropharynx using a thin polyethylene tube connected to a flexible laryngoscope. The PSEP waveform is characterized by four early- and mid-latency component peaks: an early positivity (P1) and negativity (N1), followed by a mid-latency positivity (P2) and negativity (N2). The early positive peak P1 is localized bilaterally to the lateral parietal scalp, the N1 medially in the frontoparietal region, and the P2 and N2 with diffuse scalp locations. Somatosensory and premotor regions are possible anatomical correlates of peak locations. Based on the latencies of the peaks, they are likely analogous to somatosensory- and respiratory-related evoked potential peaks. PMID:20890713

  16. Habituation of human limbic neuronal response to sensory stimulation.

    PubMed

    Wilson, C L; Babb, T L; Halgren, E; Wang, M L; Crandall, P H

    1984-04-01

    Hippocampal, parahippocampal gyrus, and amygdalar neuronal responses to visual and acoustic stimuli were analyzed during trains of several hundred stimulus repetitions as part of an investigation of sensory pathways to medial temporal lobe structures in complex-partial epilepsy patients who were being monitored with depth electrodes. Ten percent of more than 500 single and multiple units tested were responsive to simple sensory stimuli. The majority of the responsive units were recorded in the posterior parahippocampal gyrus (HG) during visual stimulation. Although neurons in pes hippocampi (PH; Ammons's horn) were also responsive to photic stimuli, no visually responsive units were found in amygdala. Very few units were responsive to acoustic stimuli, and these were found only in PH and amygdala, and not in HG. Significant trends of increase or decrease in response amplitude during trains of stimuli were found in all acoustically responsive units. Significant trends of visual response amplitude increase or decrease were found in 20% of PH units, and in 44% of HG units. Mean latencies of acoustically responsive units were longer than those of visually responsive units, and latencies of PH sensory units showing decremental response were longer than nondecremental PH units. Rate of response decrement was usually linear for acoustic responses and exponential for visual responses. The response dynamics of medial temporal lobe neurons are compared with those described in the animal limbic system and are related to habituation of human sensory evoked scalp potentials. PMID:6705888

  17. EVALUATION OF SENSORY EVOKED POTENTIALS IN LONG EVANS RATS GESTATIONALLY EXPOSED TO MERCURY (HGO) VAPOR.

    EPA Science Inventory

    Human exposure to mercury vapor (Hg0) has been reported to result in sensory disturbances. Developmental exposure to toxicants may result in long-lasting changes in neural function. This manuscript describes the lack of effect of gestational exposure of Long Evans rats to Hg0 on ...

  18. Quantification of human responses

    NASA Technical Reports Server (NTRS)

    Steinlage, R. C.; Gantner, T. E.; Lim, P. Y. W.

    1992-01-01

    Human perception is a complex phenomenon which is difficult to quantify with instruments. For this reason, large panels of people are often used to elicit and aggregate subjective judgments. Print quality, taste, smell, sound quality of a stereo system, softness, and grading Olympic divers and skaters are some examples of situations where subjective measurements or judgments are paramount. We usually express what is in our mind through language as a medium but languages are limited in available choices of vocabularies, and as a result, our verbalizations are only approximate expressions of what we really have in mind. For lack of better methods to quantify subjective judgments, it is customary to set up a numerical scale such as 1, 2, 3, 4, 5 or 1, 2, 3, ..., 9, 10 for characterizing human responses and subjective judgments with no valid justification except that these scales are easy to understand and convenient to use. But these numerical scales are arbitrary simplifications of the complex human mind; the human mind is not restricted to such simple numerical variations. In fact, human responses and subjective judgments are psychophysical phenomena that are fuzzy entities and therefore difficult to handle by conventional mathematics and probability theory. The fuzzy mathematical approach provides a more realistic insight into understanding and quantifying human responses. This paper presents a method for quantifying human responses and subjective judgments without assuming a pattern of linear or numerical variation for human responses. In particular, quantification and evaluation of linguistic judgments was investigated.

  19. Human vestibular evoked responses.

    PubMed

    Muñoz-Gamboa, C; Jiménez-Cruz, J

    1994-01-01

    The results of an experimental series dedicated to the acquisition of human vestibular evoked responses are presented. In these series, manual stimulation is applied to a normal group of subjects with rotational acceleration impulses. Every stimulus is large in magnitude and very short in duration, producing small head movements of only a few degrees through a specially designed head immobilization helmet. Results correspond to middle latency vestibular evoked responses. PMID:7968862

  20. The startle response and toxicology: Methods, use and interpretation.

    EPA Science Inventory

    The startle response (SR) is a sensory-evoked motor reflex that has been used successfully in toxicology for decades. Advantages of this procedure include: rapidly objective measurement of a defined neural circuit, measurement of habituation of the response, and a high potential ...

  1. Human responses to cold.

    PubMed

    Rintamäki, Hannu

    2007-01-01

    The thermoneutral ambient temperature for naked and resting humans is ca. 27 degrees C. Exposure to cold stimulates cold receptors of the skin which causes cold thermal sensations and stimulation of the sympathetic nervous system. Sympathetic stimulation causes vasoconstriction in skin, arms and legs. Diminished skin and extremity blood flow increases the thermal insulation of superficial tissues more than 300% corresponding to 0.9 clo (0.13 degrees C x m(-2) x W(-1)). With thermoregulatory vasoconstriction/ vasodilatation the body heat balance can be maintained within a range of ca. 4 degrees C, the middle of the range being at ca. 21 degrees C when light clothing is used. Below the thermoneutral zone metabolic heat production (shivering) is stimulated and above the zone starts heat loss by evaporation (sweating). Cold induced vasoconstriction increases blood pressure and viscosity and decreases plasma volume consequently increasing cardiac work. Cold induced hypertensive response can be counteracted by light exercise, while starting heavy work in cold markedly increases blood pressure. Under very cold conditions the sympathetic stimulation opens the anastomoses between arterioles and venules which increases skin temperatures markedly but temporarily, especially in finger tips. Adaptation to cold takes ca. 2 weeks, whereafter the physiological responses to cold are attenuated and cold exposure is subjectively considered less stressful. PMID:17929604

  2. Human sexual response.

    PubMed

    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. PMID:26003236

  3. Human response to aircraft noise

    NASA Technical Reports Server (NTRS)

    Powell, Clemans A.; Fields, James M.

    1991-01-01

    The human auditory system and the perception of sound are discussed. The major concentration is on the annnoyance response and methods for relating the physical characteristics of sound to those psychosociological attributes associated with human response. Results selected from the extensive laboratory and field research conducted on human response to aircraft noise over the past several decades are presented along with discussions of the methodology commonly used in conducting that research. Finally, some of the more common criteria, regulations, and recommended practices for the control or limitation of aircraft noise are examined in light of the research findings on human response.

  4. SENSORY EVOKED POTENTIALS: MEASURES OF NEUROTOXICITY

    EPA Science Inventory

    There is a need for tests of sensory function to be incorporated in laboratory and toxicity testing. t is clear that sensory dysfunction may frequently occur, but go undetected, in standard animal toxicological testing protocols. ensory evoked potential technology can be employed...

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

    ERIC Educational Resources Information Center

    Heron, Michelle; Slaughter, Virginia

    2010-01-01

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

  6. Functional MRI and neural responses in a rat model of Alzheimer’s disease

    PubMed Central

    Sanganahalli, Basavaraju G.; Herman, Peter; Behar, Kevin L.; Blumenfeld, Hal; Rothman, Douglas L.; Hyder, Fahmeed

    2013-01-01

    Based on the hypothesis that brain plaques and tangles can affect cortical functions in Alzheimer's disease (AD) and thus modify functional activity, we investigated functional responses in an AD rat model (called the Samaritan Alzheimer’s rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer’s disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer’s disease. PMID:23648961

  7. Abnormal Population Responses in the Somatosensory Cortex of Alzheimer’s Disease Model Mice

    PubMed Central

    Maatuf, Yossi; Stern, Edward A.; Slovin, Hamutal

    2016-01-01

    Alzheimer’s disease (AD) is the most common form of dementia. One of the neuropathological hallmarks of AD is the accumulation of amyloid-β plaques. Overexpression of human amyloid precursor protein in transgenic mice induces hippocampal and neocortical amyloid-β accumulation and plaque deposition that increases with age. The impact of these effects on neuronal population responses and network activity in sensory cortex is not well understood. We used Voltage Sensitive Dye Imaging, to investigate at high spatial and temporal resolution, the sensory evoked population responses in the barrel cortex of aged transgenic (Tg) mice and of age-matched non-transgenic littermate controls (Ctrl) mice. We found that a whisker deflection evoked abnormal sensory responses in the barrel cortex of Tg mice. The response amplitude and the spatial spread of the cortical responses were significantly larger in Tg than in Ctrl mice. At the network level, spontaneous activity was less synchronized over cortical space than in Ctrl mice, however synchronization during evoked responses induced by whisker deflection did not differ between the two groups. Thus, the presence of elevated Aβ and plaques may alter population responses and disrupts neural synchronization in large-scale networks, leading to abnormalities in sensory processing. PMID:27079783

  8. Abnormal Population Responses in the Somatosensory Cortex of Alzheimer's Disease Model Mice.

    PubMed

    Maatuf, Yossi; Stern, Edward A; Slovin, Hamutal

    2016-01-01

    Alzheimer's disease (AD) is the most common form of dementia. One of the neuropathological hallmarks of AD is the accumulation of amyloid-β plaques. Overexpression of human amyloid precursor protein in transgenic mice induces hippocampal and neocortical amyloid-β accumulation and plaque deposition that increases with age. The impact of these effects on neuronal population responses and network activity in sensory cortex is not well understood. We used Voltage Sensitive Dye Imaging, to investigate at high spatial and temporal resolution, the sensory evoked population responses in the barrel cortex of aged transgenic (Tg) mice and of age-matched non-transgenic littermate controls (Ctrl) mice. We found that a whisker deflection evoked abnormal sensory responses in the barrel cortex of Tg mice. The response amplitude and the spatial spread of the cortical responses were significantly larger in Tg than in Ctrl mice. At the network level, spontaneous activity was less synchronized over cortical space than in Ctrl mice, however synchronization during evoked responses induced by whisker deflection did not differ between the two groups. Thus, the presence of elevated Aβ and plaques may alter population responses and disrupts neural synchronization in large-scale networks, leading to abnormalities in sensory processing. PMID:27079783

  9. Optimal response rates in humans and rats

    PubMed Central

    Freestone, David M.; Balcı, Fuat; Simen, Patrick; Church, Russell M.

    2015-01-01

    The analysis of response rates has been highly influential in psychology, giving rise to many prominent theories of learning. There is, however, growing interest in explaining response rates, not as a global response to associations or value, but as a decision about how to space responses in time. Recently, researchers have shown that humans and mice can time a single response optimally, i.e., in a way that maximizes reward. Here, we use the well-established DRL timing task to show that humans and rats come close to optimizing reinforcement rate, but respond systematically faster than they should. PMID:25706545

  10. Human Sexuality: Responsible Life Choices.

    ERIC Educational Resources Information Center

    Ryder, Verdene; Smith, Peggy B.

    This book provides a complete course in human sexuality. It can also be used to supplement a family living course. Text content provides current information for teaching high school students about sexuality issues. The text offers basic information on growth and development, sexual development, pregnancy, and birth. It explains the sexual decision…

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

    PubMed

    Treves, Adrian; Bonacic, Cristian

    2016-07-01

    Dogs were first domesticated 31 000-41 000 years ago. Humanity has experienced ecological costs and benefits from interactions with dogs and wolves. We propose that humans inherited a dual response of attraction or aversion that expresses itself independently to domestic and wild canids. The dual response has had far-reaching consequences for the ecology and evolution of all three taxa, including today's global 'ecological paw print' of 1 billion dogs and recent eradications of wolves. PMID:27185394

  12. The human auditory evoked response

    NASA Technical Reports Server (NTRS)

    Galambos, R.

    1974-01-01

    Figures are presented of computer-averaged auditory evoked responses (AERs) that point to the existence of a completely endogenous brain event. A series of regular clicks or tones was administered to the ear, and 'odd-balls' of different intensity or frequency respectively were included. Subjects were asked either to ignore the sounds (to read or do something else) or to attend to the stimuli. When they listened and counted the odd-balls, a P3 wave occurred at 300msec after stimulus. When the odd-balls consisted of omitted clicks or tone bursts, a similar response was observed. This could not have come from auditory nerve, but only from cortex. It is evidence of recognition, a conscious process.

  13. The Human Response to Technological Development.

    ERIC Educational Resources Information Center

    Ramey, Luellen

    Technological development and our human potential are two of the greatest challenges facing humankind today. The appropriate response to technological development seems to be to shape it for positive and productive human uses. Just as America once shifted from an agricultural economy to an industrial economy, we are now shifting from an industrial…

  14. ATP responses in human C nociceptors.

    PubMed

    Hilliges, Marita; Weidner, Christian; Schmelz, Martin; Schmidt, Roland; Ørstavik, Kristin; Torebjörk, Erik; Handwerker, Hermann

    2002-07-01

    Microelectrode recordings of impulse activity in nociceptive C fibres were performed in cutaneous fascicles of the peroneal nerve at the knee level in healthy human subjects. Mechano-heat responsive C units (CMH), mechano-insensitive but heat-responsive (CH) as well as mechano-insensitive and heat-insensitive C units (CM(i)H(i)) were identified. A subgroup of the mechano-insensitive units was readily activated by histamine. We studied the responsiveness of these nociceptor classes to injection of 20 microl 5 mM adenosintriphosphate (ATP) using saline injections as control. Because of mechanical distension during injection, which typically activates mechano-responsive C fibres, interest was focused on responsiveness to ATP after withdrawal of the injection needle. Post-injection responses were observed in 17/27 (63%) mechano-responsive units and in 14/22 (64%) mechano-insensitive units. Excitation by ATP occurred in 9/11 CH units and in 5/11 CM(i)H(i) units. ATP responsive units were found both within the histamine-responsive and the histamine-insensitive group of mechano-insensitive fibres. ATP responses appeared with a delay of 0-180 s after completion of injection; responses were most pronounced during the first 1-3 min of activation, and irregular ongoing activity was observed for up to 10 or even 20 min. ATP responses were dose-dependent, concentrations lower than 5 mM gave weaker responses. No heat or mechanical sensitisation was observed in any of the major fibre classes. In conclusion, we have shown that ATP injections at high concentrations activate C-nociceptors in healthy human skin, without preference for mechano-responsive or mechano-insensitive units. ATP did not sensitise human C fibres for mechanical or heat stimuli. We discuss how various mechanisms might contribute to the observed responses to ATP. PMID:12098617

  15. Human cerebral response to animal affective vocalizations

    PubMed Central

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

    2007-01-01

    It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional magnetic resonance imaging in normal participants to measure cerebral activity during auditory stimulation with affectively valenced animal vocalizations, some familiar (cats) and others not (rhesus monkeys). Positively versus negatively valenced vocalizations from cats and monkeys elicited different cerebral responses despite the participants' inability to differentiate the valence of these animal vocalizations by overt behavioural responses. Moreover, the comparison with human non-speech affective vocalizations revealed a common response to the valence in orbitofrontal cortex, a key component on the limbic system. These findings suggest that the neural mechanisms involved in processing human affective vocalizations may be recruited by heterospecific affective vocalizations at an unconscious level, supporting claims of shared emotional systems across species. PMID:18077254

  16. Nanomechanical responses of human hair.

    PubMed

    Samanta, Aniruddha; Bhattacharya, Manjima; Dalui, Srikanta; Acharya, Megha; Das, Pradip Sekhar; Chanda, Dipak Kr; Acharya, Saikat Deb; Sivaraman, Sankar Kalidas; Nath, Shekhar; Mandal, Ashok Kumar; Ghosh, Jiten; Mukhopadhyay, Anoop Kumar

    2016-03-01

    Here we report the first ever studies on nanomechanical properties e.g., nanohardness and Young׳s modulus for human hair of Indian origin. Three types of hair samples e.g., virgin hair samples (VH), bleached hair samples (BH) and Fe-tannin complex colour treated hair samples (FT) with the treatment by a proprietary hair care product are used in the present work. The proprietary hair care product involves a Fe-salt based formulation. The hair samples are characterized by optical microscopy, atomic force microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy (EDAX) genesis line map, EDAX spot mapping, nanoindentation, tensile fracture, and X-ray diffraction techniques. The nanoindentation studies are conducted on the cross-sections of the VH, BH and FT hair samples. The results prove that the nanomechanical properties e.g., nanohardness and Young׳s modulus are sensitive to measurement location e.g., cortex or medulla and presence or absence of the chemical treatment. Additional results obtained from the tensile fracture experiments establish that the trends reflected from the evaluations of the nanomechanical properties are general enough to hold good. Based on these observations a schematic model is developed. The model explains the present results in a qualitative yet satisfactory manner. PMID:26719934

  17. The innate immune response in human tuberculosis

    PubMed Central

    Lerner, Thomas R.; Borel, Sophie

    2015-01-01

    Summary M ycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini‐review, we discuss these host–pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome‐wide association studies). PMID:26135005

  18. The uncertain response in humans and animals

    NASA Technical Reports Server (NTRS)

    Smith, J. D.; Shields, W. E.; Schull, J.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

    1997-01-01

    There has been no comparative psychological study of uncertainty processes. Accordingly, the present experiments asked whether animals, like humans, escape adaptively when they are uncertain. Human and animal observers were given two primary responses in a visual discrimination task, and the opportunity to escape from some trials into easier ones. In one psychophysical task (using a threshold paradigm), humans escaped selectively the difficult trials that left them uncertain of the stimulus. Two rhesus monkeys (Macaca mulatta) also showed this pattern. In a second psychophysical task (using the method of constant stimuli), some humans showed this pattern but one escaped infrequently and nonoptimally. Monkeys showed equivalent individual differences. The data suggest that escapes by humans and monkeys are interesting cognitive analogs and may reflect controlled decisional processes prompted by the perceptual ambiguity at threshold.

  19. Response Acquisition by Humans with Delayed Reinforcement

    ERIC Educational Resources Information Center

    Okouchi, Hiroto

    2009-01-01

    The present experiment examined whether a response class was acquired by humans with delayed reinforcement. Eight white circles were presented on a computer touch screen. If the undergraduates touched two of the eight circles in a specified sequence (i.e., touching first the upper-left circle then the bottom-left circle), then the touches…

  20. Human genetic variability and HIV treatment response.

    PubMed

    Haas, David W

    2006-07-01

    Access to potent antiretroviral medications greatly reduces morbidity and mortality due to HIV/AIDS, but drug toxicity limits treatment success in many individuals. The field of pharmacogenomics strives to understand the influence of human genetic variants in response to medications. Investigators have begun to identify associations among human genetic variants, predisposition to HIV drug toxicities, and likelihood of virologic response. These include associations among abacavir hypersensitivity reactions, HLA type, and hsp70-hom genotypes, and among CYP2B6 polymorphisms, efavirenz pharmacokinetics, and central nervous system symptoms. Pharmacogenomics also holds great promise to suggest novel targets for drug development. The discovery that a naturally occurring, nonfunctional variant of the HIV receptor gene CCR5 protected against HIV infection encouraged the development of CCR5 antagonists. Through continued translational and applied research, pharmacogenomics will ultimately benefit persons living with HIV worldwide by identifying new therapeutic targets and through individualized drug prescribing that is informed by human genetic testing. PMID:16608660

  1. Animal models of human amino acid responses.

    PubMed

    Baker, David H

    2004-06-01

    The principal differences between experimental animals and humans with regard to amino acid responses are 1) growing animals partition most of their amino acid intake to protein accretion, whereas growing children partition most of their intake to maintenance; 2) invasive assessment procedures are common in animals but very limited in humans; and 3) humans can describe how they feel in response to amino acid levels or balances, whereas animals cannot. New (pharmacologic) uses of amino acids have been and are being discovered (e.g., cysteine, arginine, leucine, glutamine), and this makes it imperative that tolerance limits be established. Work with pigs suggests that excessive intake of methionine and tryptophan present the biggest problems, whereas excessive intake of threonine, glutamate, and the branched-chain amino acids seems to be well tolerated. PMID:15173445

  2. Simultaneous chromatic and luminance human electroretinogram responses

    PubMed Central

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

    2012-01-01

    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. PMID:22586211

  3. Seasonality in human cognitive brain responses.

    PubMed

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

    2016-03-15

    Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations. PMID:26858432

  4. Human papillomavirus vaccines--immune responses.

    PubMed

    Stanley, Margaret; Pinto, Ligia A; Trimble, Connie

    2012-11-20

    Prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines are highly effective. The available evidence suggests that neutralising antibody is the mechanism of protection. However, despite the robust humoral response elicited by VLP vaccines, there is no immune correlate, no minimum level of antibody, or any other immune parameter, that predicts protection against infection or disease. The durability of the antibody response and the importance of antibody isotype, affinity and avidity for vaccine effectiveness are discussed. Once infection and disease are established, then cellular immune responses are essential to kill infected cells. These are complex processes and understanding the local mucosal immune response is a prerequisite for the rational design of therapeutic HPV vaccines. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID:23199968

  5. Human freezing in response to affective films.

    PubMed

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

    2014-01-01

    Human freezing has been objectively assessed using a passive picture viewing paradigm as an analog for threat. These results should be replicated for other stimuli in order to determine their stability and generalizability. Affective films are used frequently to elicit affective responses, but it is unknown whether they also elicit freezing-like defense responses. To test whether this is the case, 50 participants watched neutral, pleasant and unpleasant film fragments while standing on a stabilometric platform and wearing a polar band to assess heart rate. Freezing-like responses (indicated by overall reduced body sway and heart rate deceleration) were observed for the unpleasant film only. The unpleasant film also elicited early reduced body sway (1-2 s after stimulus onset). Heart rate and body sway were correlated during the unpleasant film only. The results suggest that ecologically valid stimuli like films are adequate stimuli in evoking defense responses. The results also underscore the importance of including time courses in human experimental research on defense reactions in order to delineate different stages in the defense response. PMID:23805855

  6. Human osteoblast response to PTFE surfaces.

    PubMed

    Walsh, W R; Olmedo, M; Kim, H D; Zou, L; Weiss, A P

    1994-01-01

    Recently, expanded polytetrafluoroethylene (ePTFE, Gortex) vascular grafts have been rolled and used for interpositional arthroplasties of the carpus in the wrist. Little data, however, are available on the response of human osteoblasts to ePTFE. In-vitro cell culture is a useful method to determine initial cell-biomaterial interactions. The present study explores the morphological and mitogenic response of human bone cells cultured on vascular grade ePTFE grafts. The present findings suggest that neither the inner nor the outer surface of ePTFE, in its present form, support osteoblast growth. PTFE may be a suitable material to act as a space filler for carpal bone interpositional arthroplasties. PMID:10150168

  7. Human teeth model using photoacoustic frequency response

    NASA Astrophysics Data System (ADS)

    El-Sharkawy, Yasser H.; El-Sherif, Ashraf F.

    2012-03-01

    In this paper, a novel photo-acoustic technique modality utilizing a frequency- modulated Q-switch Nd:YAG laser at 1064 nm and coherent frequency domain signal processing is introduced for impulse and frequency responses of biological tissues. We present a photoacoustic technique to monitor the temporal behavior of temperature and pressure in an excised sample of human teeth after either a single laser pulse or during multiple laser pulses at pulse repetition frequencies (PRF) from 5 Hz to 100 Hz. Knowledge of the dynamic characteristics of structural elements often means the difference between normal and abnormal tissue. The determination of the resonance characteristics of structures is termed "modal analysis." The results of our study suggest that it is possible to identify the impulse, frequency response and resonance modes of simplified human teeth. This data provided a powerful tool to differentiate between normal and decay teeth.

  8. Skeletal muscle responses to unweighting in humans

    NASA Technical Reports Server (NTRS)

    Dudley, Gary A.

    1991-01-01

    An overview of earth-based studies is presented emphasizing the data on muscular strength and size derived from experiments under simulated microgravity. The studies involve the elimination of weight-bearing responsibility of lower-limb human musculature to simulate the unweighting effects of space travel in the absence of exercise. Reference is given to bedrest and unilateral lower-limb suspension, both of which provide data that demonstrate the decreased strength of the knee extensors of 20-25 percent. The response is related to the decrease in cross-sectional area of the knee extensors which is a direct indication of muscle-fiber atrophy. Most of the effects of unweighting are associated with extensor muscles in the lower limbs and not with postural muscles. Unweighting is concluded to cause significant adaptations in the human neuromuscular system that require further investigation.

  9. Human responses to electricity: A literature review

    NASA Technical Reports Server (NTRS)

    Turner, H. S.

    1972-01-01

    An extensive review of literature on research concerning biomedical sensors is presented for establishing standards for current limiting devices. The physiological and pathological responses of the human, when exposed to electricity are reported including the thresholds: for perception of electricity, pain by electric current, induction of muscular contraction by electric shock, and ventricular fibrillation. The passive electrical properties of cells and tissues are also reported.

  10. DNA repair responses in human skin cells

    SciTech Connect

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.

    1981-07-01

    Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

  11. Human Cytokinome Analysis for Interferon Response

    PubMed Central

    Al-Yahya, Suhad; Mahmoud, Linah; Al-Zoghaibi, Fahad; Al-Tuhami, Abdullah; Amer, Haithem; Almajhdi, Fahad N.; Polyak, Stephen J.

    2015-01-01

    ABSTRACT Cytokines are a group of small secreted proteins that mediate a diverse range of immune and nonimmune responses to inflammatory and microbial stimuli. Only a few of these cytokines mount an antiviral response, including type I, II, and III interferons (IFNs). During viral infections and under inflammatory conditions, a number of cytokines and chemokines are coproduced with IFN; however, no systematic study exists on the interactions of the cytokine repertoire with the IFN response. Here, we performed the largest cytokine and chemokine screen (the human cytokinome, with >240 members) to investigate their modulation of type I and type II IFN responses in a cell line model. We evaluated the cytokine activities in both IFN-stimulated response element (ISRE) and IFN-γ activation sequence (GAS) reporter systems. Several cytokine clusters that augment either or both ISRE- and GAS-mediated responses to IFNs were derived from the screen. We identified novel modulators of IFN response—betacellulin (BTC), interleukin 11 (IL-11), and IL-17F—that caused time-dependent induction of the IFN response. The ability to induce endogenous IFN-β and IFN-stimulated genes varies among these cytokines and was largely dependent on Stat1, as assessed by Stat1 mutant fibroblasts. Certain cytokines appear to augment the IFN-β response through the NF-κB pathway. The novel IFN-like cytokines augmented the antiviral activity of IFN-α against several RNA viruses, including encephalomyocarditis virus, vesicular stomatitis virus, and influenza virus, in susceptible cell lines. Overall, the study represents a large-scale analysis of cytokines for enhancing the IFN response and identified cytokines capable of enhancing Stat1, IFN-induced gene expression, and antiviral activities. IMPORTANCE Innate immunity to viruses is an early defense system to ward off viruses. One mediator is interferon (IFN), which activates a cascade of biochemical events that aim to control the virus life

  12. Responses of the human spleen to exercise.

    PubMed

    Shephard, Roy J

    2016-01-01

    The human spleen shows a decrease in volume of around 40% early during vigorous exercise and in response to other stressful stimuli such as maximal apnoea and the breathing of hypoxic gas mixtures. Contraction seems an active response, mediated by alpha-adrenergic fibres in the splenic nerve. Given the relatively small size of the human spleen, the effect upon physical performance is likely to be small; the augmentation of total blood volume is <2%, and even taking account of other causes of haemoconcentration during vigorous exercise, the increase of haematocrit is <10%. However, one of two studies suggested that the haemoconcentration may be sufficient to cause errors in the traditional method for calculating exercise-induced changes of plasma volume. The spleen also contributes leucocytes and platelets to the general circulation as part of the "fight or flight" reaction to stressors. The mobilisation of leucocytes proceeds more slowly than that of the red cells; it depends not only upon an active contraction of the spleen, but also a modulation of leucocyte adhesion molecules. Splenectomy impairs exercise performance in horses, but human performance data are lacking; overall health effects seem minimal, and many patients live many years after removal of their spleens. PMID:26287390

  13. NASA Medical Response to Human Spacecraft Accidents

    NASA Technical Reports Server (NTRS)

    Patlach, Robert

    2011-01-01

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

  14. Delegating responsibilities in human-robot teams

    NASA Astrophysics Data System (ADS)

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

    2006-05-01

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

  15. Human response to vibration in residential environments.

    PubMed

    Waddington, David C; Woodcock, James; Peris, Eulalia; Condie, Jenna; Sica, Gennaro; Moorhouse, Andrew T; Steele, Andy

    2014-01-01

    This paper presents the main findings of a field survey conducted in the United Kingdom into the human response to vibration in residential environments. The main aim of this study was to derive exposure-response relationships for annoyance due to vibration from environmental sources. The sources of vibration considered in this paper are railway and construction activity. Annoyance data were collected using questionnaires conducted face-to-face with residents in their own homes. Questionnaires were completed with residents exposed to railway induced vibration (N = 931) and vibration from the construction of a light rail system (N = 350). Measurements of vibration were conducted at internal and external positions from which estimates of 24-h vibration exposure were derived for 1073 of the case studies. Sixty different vibration exposure descriptors along with 6 different frequency weightings were assessed as potential predictors of annoyance. Of the exposure descriptors considered, none were found to be a better predictor of annoyance than any other. However, use of relevant frequency weightings was found to improve correlation between vibration exposure and annoyance. A unified exposure-response relationship could not be derived due to differences in response to the two sources so separate relationships are presented for each source. PMID:24437758

  16. Human immune response to Mycobacterium tuberculosis antigens.

    PubMed Central

    Havlir, D V; Wallis, R S; Boom, W H; Daniel, T M; Chervenak, K; Ellner, J J

    1991-01-01

    Little is known about the immunodominant or protective antigens of Mycobacterium tuberculosis in humans. Cell-mediated immunity is necessary for protection, and healthy tuberculin-positive individuals are relatively resistant to exogenous reinfection. We compared the targets of the cell-mediated immune response in healthy tuberculin-positive individuals to those of tuberculosis patients and tuberculin-negative persons. By using T-cell Western blotting (immunoblotting) of nitrocellulose-bound M. tuberculosis culture filtrate, peaks of T-cell blastogenic activity were identified in the healthy tuberculin reactors at 30, 37, 44, 57, 64, 71 and 88 kDa. Three of these fractions (30, 64, and 71 kDa) coincided with previously characterized proteins: antigen 6/alpha antigen, HSP60, and HSP70, respectively. The blastogenic responses to purified M. tuberculosis antigen 6/alpha antigen and BCG HSP60 were assessed. When cultured with purified antigen 6/alpha antigen, lymphocytes of healthy tuberculin reactors demonstrated greater [3H]thymidine incorporation than either healthy tuberculin-negative controls or tuberculous patients (8,113 +/- 1,939 delta cpm versus 645 +/- 425 delta cpm and 1,019 +/- 710 delta cpm, respectively; P less than 0.01). Healthy reactors also responded to HSP60, although to a lesser degree than antigen 6/alpha antigen (4,276 +/- 1,095 delta cpm; P less than 0.05). Partially purified HSP70 bound to nitrocellulose paper elicited a significant lymphocyte blastogenic response in two of six of the tuberculous patients but in none of the eight healthy tuberculin reactors. Lymphocytes of none of five tuberculin-negative controls responded to recombinant antigens at 14 or 19 kDa or to HSP70. Antibody reactivity generally was inversely correlated with blastogenic response: tuberculous sera had high titer antibody to M. tuberculosis culture filtrate in a range from 35 to 180 kDa. This is the first systematic evaluation of the human response to a panel of native

  17. Biomechanical response of the human cervical spine.

    PubMed

    Duma, Stefan M; Kemper, Andrew R; Porta, David J

    2008-01-01

    The purpose of this study was to characterize the biomechanical response of human cervical spine segments in dynamic axial compression. This was accomplished by performing dynamic axial compression tests on human cervical spine segments, C4-T1 and C6-T1, dissected from fresh frozen human male cadavers. The proximal and distal vertebral bodies were fixed to a load cell with a custom aluminum pot and subjected to dynamic compressive loading rates using a servo-hydraulic Material Testing System at a rate of 50 mm/s. The average force and moment at time of structural failure were found to be 3022 +/- 45 N and 46.1 +/-8.1 Nm, respectively, for C4-T1 segments and 6117 +/- 6639 N and 69.5 +/-6.8 Nm, respectively for C6-T1segments. The most severe injury as a result of this testing was compression fractures of the vertebral body. In addition, injuries to the intervertebral discs were only observed in specimens that sustained severe vertebral body fractures. This is consistent with the findings of previous researchers who have reported that intervertebral disc failures do not occur due to single acute loading events without associated severe boney fractures. PMID:19141905

  18. Human responses to augmented virtual scaffolding models.

    PubMed

    Hsiao, Hongwei; Simeonov, Peter; Dotson, Brian; Ammons, Douglas; Kau, Tsui-Ying; Chiou, Sharon

    2005-08-15

    This study investigated the effect of adding real planks, in virtual scaffolding models of elevation, on human performance in a surround-screen virtual reality (SSVR) system. Twenty-four construction workers and 24 inexperienced controls performed walking tasks on real and virtual planks at three virtual heights (0, 6 m, 12 m) and two scaffolding-platform-width conditions (30, 60 cm). Gait patterns, walking instability measurements and cardiovascular reactivity were assessed. The results showed differences in human responses to real vs. virtual planks in walking patterns, instability score and heart-rate inter-beat intervals; it appeared that adding real planks in the SSVR virtual scaffolding model enhanced the quality of SSVR as a human - environment interface research tool. In addition, there were significant differences in performance between construction workers and the control group. The inexperienced participants were more unstable as compared to construction workers. Both groups increased their stride length with repetitions of the task, indicating a possibly confidence- or habit-related learning effect. The practical implications of this study are in the adoption of augmented virtual models of elevated construction environments for injury prevention research, and the development of programme for balance-control training to reduce the risk of falls at elevation before workers enter a construction job. PMID:16253942

  19. Human Papillomaviruses and the Interferon Response

    PubMed Central

    Beglin, Melanie; Melar-New, Marta

    2009-01-01

    Human papillomaviruses (HPV) are small DNA viruses that target stratified keratinocytes for infection. A subset of HPV types infect epithelia in the genital tract and are the causative agents of cervical as well as other anogenital cancers. Interferon treatment of existing genital HPV lesions has had mixed results. While HPV proteins down-regulate the expression of interferon-inducible genes, interferon treatment ultimately induces their high-level transcription after a delay. Cells containing complete HPV genomes that are able to undergo productive replication upon differentiation are sensitive to interferon-induced growth arrest, while cells from high-grade cancers that only express E6 and E7 are resistant. Recent studies indicate this sensitivity is dependent upon the binding of the interferon-inducible factor, p56, to the E1 replication protein. The response to interferon by HPV proteins is complex and results from the action of multiple viral proteins. PMID:19715460

  20. Assessment of neurobehavioral response in humans to low-level volatile organic compound (VOC) sources

    SciTech Connect

    Otto, D.A.

    1991-06-01

    Occupants of sick buildings often complain of CNS symptoms including headache and memory loss, but little objective evidence of neurobehavioral effects exists. Available evidence of neurobehavioral effects of low level VOC exposure representative of new buildings is reviewed. Methods suitable for studying the neurobehavioral effects of low-level VOC exposure--including computerized behavioral tests, balance tests and sensory evoked potentials--are reviewed. The use of computerized behavioral tests in conjunction with symptom questionnaires is recommended for low-level VOC studies.

  1. Cell Culture Assay for Human Noroviruses [response

    SciTech Connect

    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

  2. NASA Medical Response to Human Spacecraft Accidents

    NASA Technical Reports Server (NTRS)

    Patlach, Robert

    2010-01-01

    Manned space flight is risky business. Accidents have occurred and may occur in the future. NASA's manned space flight programs, with all their successes, have had three fatal accidents, one at the launch pad and two in flight. The Apollo fire and the Challenger and Columbia accidents resulted in a loss of seventeen crewmembers. Russia's manned space flight programs have had three fatal accidents, one ground-based and two in flight. These accidents resulted in the loss of five crewmembers. Additionally, manned spacecraft have encountered numerous close calls with potential for disaster. The NASA Johnson Space Center Flight Safety Office has documented more than 70 spacecraft incidents, many of which could have become serious accidents. At the Johnson Space Center (JSC), medical contingency personnel are assigned to a Mishap Investigation Team. The team deploys to the accident site to gather and preserve evidence for the Accident Investigation Board. The JSC Medical Operations Branch has developed a flight surgeon accident response training class to capture the lessons learned from the Columbia accident. This presentation will address the NASA Mishap Investigation Team's medical objectives, planned response, and potential issues that could arise subsequent to a manned spacecraft accident. Educational Objectives are to understand the medical objectives and issues confronting the Mishap Investigation Team medical personnel subsequent to a human space flight accident.

  3. Feasibility of Human Amniotic Fluid Derived Stem Cells in Alleviation of Neuropathic Pain in Chronic Constrictive Injury Nerve Model

    PubMed Central

    Chiang, Chien-Yi; Liu, Shih-An; Sheu, Meei-Ling; Chen, Fu-Chou; Chen, Chun-Jung; Su, Hong-Lin; Pan, Hung-Chuan

    2016-01-01

    Purpose The neurobehavior of neuropathic pain by chronic constriction injury (CCI) of sciatic nerve is very similar to that in humans, and it is accompanied by a profound local inflammation response. In this study, we assess the potentiality of human amniotic fluid derived mesenchymal stem cells (hAFMSCs) for alleviating the neuropathic pain in a chronic constriction nerve injury model. Methods and Methods This neuropathic pain animal model was conducted by four 3–0 chromic gut ligatures loosely ligated around the left sciatic nerve in Sprague—Dawley rats. The intravenous administration of hAFMSCs with 5x105 cells was conducted for three consecutive days. Results The expression IL-1β, TNF-α and synaptophysin in dorsal root ganglion cell culture was remarkably attenuated when co-cultured with hAFMSCs. The significant decrease of PGP 9.5 in the skin after CCI was restored by administration of hAFMSCs. Remarkably increased expression of CD 68 and TNF-α and decreased S-100 and neurofilament expression in injured nerve were rescued by hAFMSCs administration. Increases in synaptophysin and TNF-α over the dorsal root ganglion were attenuated by hAFMSCs. Significant expression of TNF-α and OX-42 over the dorsal spinal cord was substantially attenuated by hAFMSCs. The increased amplitude of sensory evoked potential as well as expression of synaptophysin and TNF-α expression was alleviated by hAFMSCs. Human AFMSCs significantly improved the threshold of mechanical allodynia and thermal hyperalgesia as well as various parameters of CatWalk XT gait analysis. Conclusion Human AFMSCs administration could alleviate the neuropathic pain demonstrated in histomorphological alteration and neurobehavior possibly through the modulation of the inflammatory response. PMID:27441756

  4. Fluorescent antibody responses to adenoviruses in humans.

    PubMed Central

    Ariyawansa, J P; Tobin, J O

    1976-01-01

    Specific IgG, IgA, and IgM immunoglobulin antibody responses to adenovirus infections were studied by the indirect immunofluorescent technique in six pairs of human sera obtained during acute and convalescent phases of the illness. In addition, 70 single specimens of sera showing adenovirus IgG antibody from different age groups from birth to the 60th year of life were titrated for the same antibody to adenovirus types 1, 2, 3, 5, and 7, and 170 serum specimens from the same age groups were screened for specific immunoglobulin antibodies against types 1 and 5. Specific immunoglobulin antibodies lacked type specificity and in acute infections measured heterologous antibody response as well. On the other hand, IgG antibodies detected in single specimens of sera by immunofluorescence correlate with surveys of the isolation of virus from patients and neutralizing antibody studies by other workers. Fluorescent antibodies appeared in all three fractions of the immunoglobulins in acute adenovirus infections. Although this technique may be used in the diagnosis of adenovirus infections there is no advantage compared to complement-fixation testing. However, the use of sera absorbed with group antigen may have a more useful place in serological epidemiology than in diagnostic work. In five pairs of sera obtained during acute and convalescent phases of adenoviral illness and in 70 random single specimens from different age groups, "T" antibodies were detected only in the IgG fraction. The paired sera did not show a significant rise to indicate the usefulness of "T" antibody study in diagnosis. PMID:180061

  5. Fluorescent antibody responses to adenoviruses in humans.

    PubMed

    Ariyawansa, J P; Tobin, J O

    1976-05-01

    Specific IgG, IgA, and IgM immunoglobulin antibody responses to adenovirus infections were studied by the indirect immunofluorescent technique in six pairs of human sera obtained during acute and convalescent phases of the illness. In addition, 70 single specimens of sera showing adenovirus IgG antibody from different age groups from birth to the 60th year of life were titrated for the same antibody to adenovirus types 1, 2, 3, 5, and 7, and 170 serum specimens from the same age groups were screened for specific immunoglobulin antibodies against types 1 and 5. Specific immunoglobulin antibodies lacked type specificity and in acute infections measured heterologous antibody response as well. On the other hand, IgG antibodies detected in single specimens of sera by immunofluorescence correlate with surveys of the isolation of virus from patients and neutralizing antibody studies by other workers. Fluorescent antibodies appeared in all three fractions of the immunoglobulins in acute adenovirus infections. Although this technique may be used in the diagnosis of adenovirus infections there is no advantage compared to complement-fixation testing. However, the use of sera absorbed with group antigen may have a more useful place in serological epidemiology than in diagnostic work. In five pairs of sera obtained during acute and convalescent phases of adenoviral illness and in 70 random single specimens from different age groups, "T" antibodies were detected only in the IgG fraction. The paired sera did not show a significant rise to indicate the usefulness of "T" antibody study in diagnosis. PMID:180061

  6. Acute hemodynamic responses to weightlessness in humans

    NASA Technical Reports Server (NTRS)

    Lathers, C. M.; Charles, J. B.; Elton, K. F.; Holt, T. A.; Mukai, C.; Bennett, B. S.; Bungo, M. W.

    1989-01-01

    As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASA's KC-135 aircraft. Impedance cardiography data were collected over four sets of 8-10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi-supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi-supine posture produced little evidence of a headward fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi-supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headward fluid shift commences in the semi-supine posture before launch. is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours.

  7. Skeletal muscle responses to unloading in humans

    NASA Technical Reports Server (NTRS)

    Dudley, G.; Tesch, P.; Hather, B.; Adams, G.; Buchanan, P.

    1992-01-01

    This study examined the effects of unloading on skeletal muscle structure. Method: Eight subjects walked on crutches for six weeks with a 110 cm elevated sole on the right shoe. This removed weight bearing by the left lower limb. Magnetic resonance imaging of both lower limbs and biopsies of the left m. vastus laterallis (VL) were used to study muscle structure. Results: Unloading decreased (P less than 0.05) muscle cross-sectional areas (CSA) of the knee extensors 16 percent. The knee flexors showed about 1/2 of this response (-7 percent, P less than 0.05). The three vasti muscles each showed decreases (P less than 0.05) of about 15 percent. M. rectus femoris did not change. Mean fiber CSA in VL decreased (P less than 0.05) 14 percent with type 2 and type 1 fibers showing reductions of 15 and 11 percent respectively. The ankle extensors showed a 20 percent decrease (P less than 0.05) in CSA. The reduction for the 'fast' m. gastrocnemius was 27 percent compared to the 18 percent decrease for the 'slow' soleus. Summary: The results suggest that decreases in muscle CSA are determined by the relative change in impact loading history because atrophy was (1) greater in extensor than flexor muscles, (2) at least as great in fast as compared to slow muscles or fibers, and (3) not dependent on single or multi-joint function. They also suggest that the atrophic responses to unloading reported for lower mammals are quantitatively but not qualitatively similar to those of humans.

  8. Acute hemodynamic responses to weightlessness in humans.

    PubMed

    Lathers, C M; Charles, J B; Elton, K F; Holt, T A; Mukai, C; Bennett, B S; Bungo, M W

    1989-07-01

    As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASA's KC-135 aircraft. Impedance cardiography data were collected over four sets of 8-10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi-supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi-supine posture produced little evidence of a headward fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi-supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headward fluid shift commences in the semi-supine posture before launch. is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours. PMID:2760255

  9. Human Cardiovascular Responses to Passive Heat Stress

    PubMed Central

    Crandall, Craig G.; Wilson, Thad E.

    2016-01-01

    Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263

  10. Human cardiovascular responses to passive heat stress.

    PubMed

    Crandall, Craig G; Wilson, Thad E

    2015-01-01

    Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263

  11. Response characteristics of the human torsional vestibuloocular reflex

    NASA Technical Reports Server (NTRS)

    Peterka, Robert J.

    1992-01-01

    The characteristics of the response dynamics of the human torsional vestibuloocular reflex were studied during controlled rotations about an earth-horizontal axis. The results extended the frequency range to 2 Hz and identified the nonlinearity of the amplitude response.

  12. Summary of human responses to ventilation

    SciTech Connect

    Seppanen, Olli A.; Fisk, William J.

    2004-06-01

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

  13. Divergent Mitochondrial Biogenesis Responses in Human Cardiomyopathy

    PubMed Central

    Ahuja, Preeti; Wanagat, Jonathan; Wang, Zhihua; Wang, Yibin; Liem, David A.; Ping, Peipei; Antoshechkin, Igor A.; Margulies, Kenneth B.; MacLellan, W. Robb

    2014-01-01

    Background Mitochondria are key players in the development and progression of heart failure (HF). Mitochondrial (mt) dysfunction leads to diminished energy production and increased cell death contributing to the progression of left ventricular (LV) failure. The fundamental mechanisms that underlie mt dysfunction in HF have not been fully elucidated. Methods and Results To characterize mt morphology, biogenesis and genomic integrity in human HF, we investigated LV tissue from non-failing (NF) hearts and end-stage ischemic (ICM) or dilated (DCM) cardiomyopathic hearts. Although mt dysfunction was present in both types of cardiomyopathy, mt were smaller and increased in number in DCM compared to ICM or NF hearts. Mt volume density and mtDNA copy number was increased by ~2-fold (P<0.001) in DCM hearts in comparison to ICM hearts. These changes were accompanied by an increase in the expression of mtDNA-encoded genes in DCM versus no change in ICM. mtDNA repair and antioxidant genes were reduced in failing hearts suggestive of a defective repair and protection system, which may account for the 4.1-fold increase in mtDNA deletion mutations in DCM (P<0.05 vs NF hearts, P<0.05 vs ICM). Conclusions In DCM, mt dysfunction is associated with mtDNA damage and deletions, which could be a consequence of mutating stress coupled with a PGC-1α-dependent stimulus for mt biogenesis. However, this maladaptive compensatory response contributes to additional oxidative damage. Thus, our findings support further investigations into novel mechanisms and therapeutic strategies for mt dysfunction in DCM. PMID:23589024

  14. The Uncertain Response in Humans and Animals.

    ERIC Educational Resources Information Center

    Smith, J. David; And Others

    1997-01-01

    Compared tendencies of adults and rhesus monkeys to escape adaptively when uncertain. In a visual discrimination task using a threshold paradigm, humans and monkeys escaped trials in which they were uncertain of the stimulus. In a similar task with constant stimuli, some humans escaped adaptively, but one escaped infrequently and non-optimally,…

  15. Very young infants' responses to human and nonhuman primate vocalizations.

    PubMed

    Ferguson, Brock; Perszyk, Danielle R; Waxman, Sandra R

    2014-12-01

    Recent evidence from very young human infants' responses to human and nonhuman primate vocalizations offers new insights - and brings new questions - to the forefront for those who seek to integrate primate-general and human-specific mechanisms of acoustic communication with theories of language acquisition. PMID:25514943

  16. Research at NASA on Human Response to Sonic Booms

    NASA Technical Reports Server (NTRS)

    Sullivan, Brenda M.

    2008-01-01

    NASA used its sonic boom simulator to study human response to shaped sonic booms and concluded that a loudness metric, such as Perceived Level, predicts human reaction to outdoor booms more accurately than overpressure. To investigate the importance of indoor phenomena (rattle, reverberation) under controlled laboratory conditions, NASA is building an "indoor sonic boom simulator." The intention is to develop a psychoacoustic model that describes human response as a function of boom shape (spectrum), boom intensity, reverberation, and varying rattle characteristics.

  17. Human olfactory receptor responses to odorants

    PubMed Central

    Mainland, Joel D; Li, Yun R; Zhou, Ting; Liu, Wen Ling L; Matsunami, Hiroaki

    2015-01-01

    Although the human olfactory system is capable of discriminating a vast number of odors, we do not currently understand what chemical features are encoded by olfactory receptors. In large part this is due to a paucity of data in a search space covering the interactions of hundreds of receptors with billions of odorous molecules. Of the approximately 400 intact human odorant receptors, only 10% have a published ligand. Here we used a heterologous luciferase assay to screen 73 odorants against a clone library of 511 human olfactory receptors. This dataset will allow other researchers to interrogate the combinatorial nature of olfactory coding. PMID:25977809

  18. INTERSUBJECT VARIABILITY IN HUMAN ACUTE OZONE RESPONSIVENESS

    EPA Science Inventory

    Individuals exposed to ozone experience a wide range in the magnitudes of lung function decrements and symptoms produced. hese intersubject differences in response are reproducible over periods of time of at least one year, suggesting that responsiveness to ozone is a characteris...

  19. Animal models of human response to dioxins.

    PubMed Central

    Grassman, J A; Masten, S A; Walker, N J; Lucier, G W

    1998-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. PMID:9599728

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

    PubMed

    Yong, Min Hooi; Ruffman, Ted

    2014-10-01

    Humans respond to an infant crying with an increase in cortisol level and heightened alertness, a response interpreted as emotional contagion, a primitive form of empathy. Previous results are mixed when examining whether dogs might respond similarly to human distress. We examined whether domestic dogs, which have a long history of affiliation with humans, show signs of emotional contagion, testing canine (n=75) and human (n=74) responses to one of three auditory stimuli: a human infant crying, a human infant babbling, and computer-generated "white noise", with the latter two stimuli acting as controls. Cortisol levels in both humans and dogs increased significantly from baseline only after listening to crying. In addition, dogs showed a unique behavioral response to crying, combining submissiveness with alertness. These findings suggest that dogs experience emotional contagion in response to human infant crying and provide the first clear evidence of a primitive form of cross-species empathy. PMID:25452080

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

    PubMed Central

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

    2013-01-01

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

  2. Evolutionary Response to Human Infectious Diseases

    ERIC Educational Resources Information Center

    Armelagos, George J.; Dewey, John R.

    1970-01-01

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

  3. Interethnic variability in human drug responses.

    PubMed

    Evans, D A; McLeod, H L; Pritchard, S; Tariq, M; Mobarek, A

    2001-04-01

    The scientific study of interethnic differences in responses to drugs has been extant for 80 years. Many of these differences have been described at the phenotypic level, and some have been explained by genetic factors. However, it is frequently difficult to disentangle accurately the hereditary and environmental influences in phenotypic comparisons. This is where the recent developments in knowledge of the genes responsible for drug receptors are starting to make a big impact. The beta 2 adrenoceptor is described; it has three genetic polymorphisms. The different genotypes influence responses to agonists such as albuterol (Salbutamol). New gene frequency data including those for Saudi Arabians, Indians, and Africans are shown. The expanding body of knowledge about genetic (and interethnic) variability in drug receptors is likely to be important in clinical medicine. PMID:11259361

  4. Bioethics: New Responsibility for Human Service Administrators.

    ERIC Educational Resources Information Center

    Burke, Rebecca

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

  5. Sex and the nose: human pheromonal responses

    PubMed Central

    Bhutta, Mr Mahmood F

    2007-01-01

    The chemosensory functions of the human nose are underappreciated. Traditional teaching is that the sense of smell detects volatile compounds, which may then allow the identification of substances that may be beneficial or harmful—such as good versus putrefied food. However, increasing evidence from research in other animals suggests that olfaction may serve another and more important purpose, that of mate selection in sexual reproduction; indeed, olfaction may be an essential impetus for evolution. PMID:17541097

  6. Dielectric response of the human tooth dentine

    NASA Astrophysics Data System (ADS)

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

    2005-07-01

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

  7. Compartmentalization of Immune Responses in Human Tuberculosis

    PubMed Central

    Rahman, Sayma; Gudetta, Berhanu; Fink, Joshua; Granath, Anna; Ashenafi, Senait; Aseffa, Abraham; Derbew, Milliard; Svensson, Mattias; Andersson, Jan; Brighenti, Susanna Grundström

    2009-01-01

    Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-γ, tumor necrosis factor-α, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-β and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-β and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control. PMID:19435796

  8. Individual differences in human annoyance response to noise

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

  9. Atmospheric chemistry - Response to human influence

    NASA Technical Reports Server (NTRS)

    Logan, J. A.; Prather, M. J.; Wofsy, S. G.; Mcelroy, M. B.

    1978-01-01

    Global atmospheric chemistry is surveyed, and the agreement of models with observed distribution of gases is considered. The influence of human perturbations due to combustion, agriculture, and chloro-carbon releases is examined with emphasis on ozone. Effects of combustion-related releases of CO on the abundances of other gases as well as possible effects of CO on tropospheric ozone are discussed. Other topics include the contribution of the chlorocarbon industry to stratospheric chloride and the recombination of nitrogen fixed by agriculture and combustion.

  10. Human immune responses and potential for vaccine assessment in humanized mice

    PubMed Central

    Akkina, Ramesh

    2013-01-01

    The new humanized mouse models with a transplanted human immune system have a capacity for de novo multilineage human hematopoiesis and generate T cells, B cells, macrophages, dendritic cells and NK cells. Of the two current leading humanized mouse models, the hu-HSC model is created by human hematopoietic stem cell (HSC) engraftment whereas the BLT mouse model is prepared by cotransplantation of human fetal liver, thymus and HSC. Humoral and cellular immune responses are seen in both models after immunization with antigens or infection with hematotropic pathogens such as EBV, HIV-1 and dengue viruses. While consistent antigen specific IgM production is seen, IgG responses were found to be generally feeble which is attributed to inefficient immunoglobulin class switching. BLT mice permit human HLA restricted T cell responses due to the autologous human thymus contributing to T cell maturation. Use of HLA Class I and II transgenic hu-HSC mice recently demonstrated that the HLA restriction deficiency could be overcome in this model. However, the overall vigor of the immune responses needs further improvement in both the models to approach that of the human. Towards this goal, supplementation with human cytokines and growth factors by transgenesis to improve human cell reconstitution and their homeostatic maintenance are beginning to yield improved mouse strains to create more robust human immune competent mice for immunoprophylaxis studies. PMID:23628166

  11. Dose-Response Relationships in Human Experimental Exposure to Solvents

    PubMed Central

    Iavicoli, Ivo; Carelli, Giovanni; Marinaccio, Alessandro

    2006-01-01

    Previous studies carried out in the field of experimental toxicology have shown evidence of biphasic dose-response relationships for different experimental models, endpoints and chemicals tested. As these studies excluded humans as the experimental model, we have examined the literature of the last three decades in order to verify data concerning human experimental exposure with the aim of highlighting possible biphasic dose-response relationships. The substances used for experimental exposures included hydrocarbons, esters, alcohols, ketones, ethers, glycoethers, halogenated hydrocarbons, and carbon sulphide; the absorption route was inhalation. We did not detect any biphasic dose-response relationship and, in the studies reviewed, our examination revealed major methodological limitations that prevented us making a more detailed examination of experimental data. We concluded that the experimental data available did not allow us to support evidence of biphasic dose-response relationships in human experimental exposure to the above-mentioned chemical substances. PMID:18648639

  12. Response of human skin to esthetic scarification.

    PubMed

    Gabriel, Vincent A; McClellan, Elizabeth A; Scheuermann, Richard H

    2014-11-01

    This study was undertaken to investigate changes in RNA expression in previously healthy adult human skin following thermal injury induced by contact with hot metal that was undertaken as part of esthetic scarification, a body modification practice. Subjects were recruited to have pre-injury skin and serial wound biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1 week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured prior to the use of a whole-genome based bead array platform to describe expression changes in the samples using the pre-injury skin as a comparator. Analysis of the array data was performed using k-means clustering and a hypergeometric probability distribution without replacement and corrections for multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of 10, several clusters of genes were shown to co-cluster together based on Gene Ontology classification with probabilities unlikely to occur by chance alone. OF particular interest were clusters relating to cell cycle, proteinaceous extracellular matrix and keratinization. Given the consistent expression changes at 1 week following injury in the cell cycle cluster, there is an opportunity to intervene early following burn injury to influence scar development. PMID:24582755

  13. Mouse models of human AML accurately predict chemotherapy response

    PubMed Central

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S.; Zhao, Zhen; Rappaport, Amy R.; Luo, Weijun; McCurrach, Mila E.; Yang, Miao-Miao; Dolan, M. Eileen; Kogan, Scott C.; Downing, James R.; Lowe, Scott W.

    2009-01-01

    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients. PMID:19339691

  14. Mouse models of human AML accurately predict chemotherapy response.

    PubMed

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S; Zhao, Zhen; Rappaport, Amy R; Luo, Weijun; McCurrach, Mila E; Yang, Miao-Miao; Dolan, M Eileen; Kogan, Scott C; Downing, James R; Lowe, Scott W

    2009-04-01

    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients. PMID:19339691

  15. Fast response to human voices in autism.

    PubMed

    Lin, I-Fan; Agus, Trevor R; Suied, Clara; Pressnitzer, Daniel; Yamada, Takashi; Komine, Yoko; Kato, Nobumasa; Kashino, Makio

    2016-01-01

    Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level. PMID:27193919

  16. Malaria vaccines and human immune responses.

    PubMed

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. PMID:27262417

  17. Fast response to human voices in autism

    PubMed Central

    Lin, I-Fan; Agus, Trevor R.; Suied, Clara; Pressnitzer, Daniel; Yamada, Takashi; Komine, Yoko; Kato, Nobumasa; Kashino, Makio

    2016-01-01

    Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level. PMID:27193919

  18. Human autonomic responses to blood donation.

    PubMed

    Zöllei, Eva; Paprika, Dóra; Makra, Péter; Gingl, Zoltán; Vezendi, Klára; Rudas, László

    2004-02-27

    In order to characterize autonomic responses to acute volume loss, supine ECG, blood pressure (BP) and uncalibrated breathing signal (UBS) recordings were taken before and after blood donation in 48 healthy volunteers. Time and frequency domain parameters of RR interval (RRI), BP and UBS variability were determined. Baroreflex gain was calculated by the technique of the spontaneous sequences and cross-spectral analysis. The systolic (SAP), diastolic (DAP) and mean BP (MAP) increased after the blood withdrawal. The central frequency of breathing and mean heart rate did not change. RRI variability increased in low frequency band (LF), tended to decrease in high frequency band (HF). Systolic BP variability increased in both frequency bands, but was statistically significant only in the high frequency band. Diastolic BP power increased in both frequencies. From the different baroreflex gain estimates, up sequence BRS and HF alpha index decreased significantly. The phase angle between RRI and systolic blood pressure powers in LF band did not change (-58 +/- 24 degrees and -54 +/- 26 degrees ). In the high frequency range, the phase became more negative (-1 +/- 29 degrees and -17 +/- 32 degrees, p = 0.001). The withdrawal of 350-400 ml blood in 5 min resulted in sympathetic activation, which was reflected in increased systolic, diastolic and mean BP. The increased BP oscillation was a sensitive marker of the minor volume depletion. This was coupled by increased RRI oscillation via baroreflex mechanisms in the LF band. Changes in the RRI and BP oscillations in the HF band showed no similar coupling. That points to the fact that RRI oscillations in this band should not be explained entirely by baroreflex mechanisms. Vagal withdrawal was reflected in decreased root mean square of successive differences (RMSSD), decreased HF RRI power and decreased up sequence BRS. PMID:15046735

  19. Modulation of stimulus contrast on the human pupil orienting response.

    PubMed

    Wang, Chin-An; Munoz, Douglas P

    2014-09-01

    The sudden appearance of a novel stimulus initiates a series of responses to orient the body for appropriate actions, including not only shifts of gaze and attention, but also transient pupil dilation. Modulation of pupil dynamics by stimulus properties is less understood, although its effects on other components of orienting have been extensively explored. Microstimulation of the superior colliculus evoked transient pupil dilation, and the initial component of pupil dilation evoked by microstimulation was similar to that elicited by the presentation of salient sensory stimuli, suggesting a coordinated role of the superior colliculus on this behavior, although evidence in humans is yet to be established. To examine pupil orienting responses in humans, we presented visual stimuli while participants fixated on a central visual spot. Transient pupil dilation in humans was elicited after presentation of a visual stimulus in the periphery. The evoked pupil responses were modulated systematically by stimulus contrast, with faster and larger pupil responses triggered by higher contrast stimuli. The pupil response onset latencies for high contrast stimuli were similar to those produced by the light reflex and significantly faster than the darkness reflex, suggesting that the initial component of pupil dilation is probably mediated by inhibition of the parasympathetic pathway. The contrast modulation was pronounced under different levels of baseline pupil size. Together, our results demonstrate visual contrast modulation on the orienting pupil response in humans. PMID:24911340

  20. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    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.

  1. Exploring human freeze responses to a threat stressor.

    PubMed

    Schmidt, Norman B; Richey, J Anthony; Zvolensky, Michael J; Maner, Jon K

    2008-09-01

    Despite the fundamental nature of tonic immobility in anxiety responses, surprisingly little empirical research has focused on the "freeze" response in humans. The present report evaluated the frequency and predictors of a freeze response in the context of a biological challenge. A nonclinical sample (N=404) underwent a 20-s inhalation of 20% CO(2)/balance O(2). Perceptions of immobility in the context of the challenge were reported in 13% of the sample, compared with 20% reporting a significant desire to flee. Subjective anxiety and panic during the challenge were associated with the freeze response, as were a number of anxiety symptom dimensions. PMID:17880916

  2. Potentiation of specific human in vitro immune responses by the Fc portion of human immunoglobulin.

    PubMed Central

    Morgan, E L; Weigle, W O

    1983-01-01

    Fc fragments derived from a human IgG1 myeloma protein were found to be a potent adjuvant for in vitro human immune responses. The addition of Fc to cultures of human PBL along with SRBC resulted in a pronounced enhancement of the primary in vitro anti-SRBC response. In addition to potentiating the humoral immune response, Fc was also found to augment the tetanus toxoid-induced T cell proliferative response. Augmentation of the immune response is mediated by Fc and not the result of an artifact due to the addition of extraneous protein to culture because neither intact IgG1 nor Fab fragments derived from this myeloma protein possessed any adjuvant properties. The temporal relationship of the administration of antigen and Fc to culture is critical for the potentiation of the immune response. The maximal Fc adjuvant effect was observed when Fc was added with antigen at the beginning of culture. PMID:6603935

  3. Thermodynamic Modeling and Analysis of Human Stress Response

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  4. Improving Emergency Response and Human-Robotic Performance

    SciTech Connect

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

    2007-08-01

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

  5. Effects of cold pressor stress on the human startle response.

    PubMed

    Deuter, Christian E; Kuehl, Linn K; Blumenthal, Terry D; Schulz, André; Oitzl, Melly S; Schachinger, Hartmut

    2012-01-01

    Both emotion and attention are known to influence the startle response. Stress influences emotion and attention, but the impact of stress on the human startle response remains unclear. We used an established physiological stressor, the Cold Pressor Test (CPT), to induce stress in a non-clinical human sample (24 student participants) in a within-subjects design. Autonomic (heart rate and skin conductance) and somatic (eye blink) responses to acoustic startle probes were measured during a pre-stress baseline, during a three minutes stress intervention, and during the subsequent recovery period. Startle skin conductance and heart rate responses were facilitated during stress. Compared to baseline, startle eye blink responses were not affected during the intervention but were diminished afterwards. These data describe a new and unique startle response pattern during stress: facilitation of autonomic stress responses but no such facilitation of somatic startle eye blink responses. The absence of an effect of stress on startle eye blink responsiveness may illustrate the importance of guaranteeing uninterrupted visual input during periods of stress. PMID:23166784

  6. Effects of Cold Pressor Stress on the Human Startle Response

    PubMed Central

    Deuter, Christian E.; Kuehl, Linn K.; Blumenthal, Terry D.; Schulz, André; Oitzl, Melly S.; Schachinger, Hartmut

    2012-01-01

    Both emotion and attention are known to influence the startle response. Stress influences emotion and attention, but the impact of stress on the human startle response remains unclear. We used an established physiological stressor, the Cold Pressor Test (CPT), to induce stress in a non-clinical human sample (24 student participants) in a within-subjects design. Autonomic (heart rate and skin conductance) and somatic (eye blink) responses to acoustic startle probes were measured during a pre-stress baseline, during a three minutes stress intervention, and during the subsequent recovery period. Startle skin conductance and heart rate responses were facilitated during stress. Compared to baseline, startle eye blink responses were not affected during the intervention but were diminished afterwards. These data describe a new and unique startle response pattern during stress: facilitation of autonomic stress responses but no such facilitation of somatic startle eye blink responses. The absence of an effect of stress on startle eye blink responsiveness may illustrate the importance of guaranteeing uninterrupted visual input during periods of stress. PMID:23166784

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

    PubMed

    Piwetz, Sarah; Lundquist, David; Würsig, Bernd

    2015-01-01

    Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. PMID:26555621

  8. [Characteristics of the human cardiovascular system in the human diving response].

    PubMed

    Baranova, T I

    2004-01-01

    Comparative-evolutional research of diving response showed that mechanisms of its expression had much in common in humans and in animals. Firstly, it involves a reflex bradycardia, vasoconstriction of peripheral vessels, and blood flow centralization. But, unlike animals whose diving response has some typical species peculiarities, human diving response is rather diverse. Four types of cardiovascular system response to face submersion were revealed: over-reactive, reactive, paradoxical, and nonreactive. These types were chosen according to the bradycardia character. It is also supposed that the occurrence of individual maximal R--R-interval, while serving as a signal to apnea stopping, is among the reasons of apnea activity limitation. PMID:15143489

  9. Modeling human response errors in synthetic flight simulator domain

    NASA Technical Reports Server (NTRS)

    Ntuen, Celestine A.

    1992-01-01

    This paper presents a control theoretic approach to modeling human response errors (HRE) in the flight simulation domain. The human pilot is modeled as a supervisor of a highly automated system. The synthesis uses the theory of optimal control pilot modeling for integrating the pilot's observation error and the error due to the simulation model (experimental error). Methods for solving the HRE problem are suggested. Experimental verification of the models will be tested in a flight quality handling simulation.

  10. Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells

    PubMed Central

    Huang, Cheng; Kolokoltsova, Olga A.; Yun, Nadezhda E.; Seregin, Alexey V.; Ronca, Shannon; Koma, Takaaki

    2015-01-01

    ABSTRACT The arenavirus family includes several important pathogens that cause severe and sometimes fatal diseases in humans. The highly pathogenic Old World (OW) arenavirus Lassa fever virus (LASV) is the causative agent of Lassa fever (LF) disease in humans. LASV infections in severe cases are generally immunosuppressive without stimulating interferon (IFN) induction, a proinflammatory response, or T cell activation. However, the host innate immune responses to highly pathogenic New World (NW) arenaviruses are not well understood. We have previously shown that the highly pathogenic NW arenavirus, Junin virus (JUNV), induced an IFN response in human A549 cells. Here, we report that Machupo virus (MACV), another highly pathogenic NW arenavirus, also induces an IFN response. Importantly, both pathogenic NW arenaviruses, in contrast to the OW highly pathogenic arenavirus LASV, readily elicited an IFN response in human primary dendritic cells and A549 cells. Coinfection experiments revealed that LASV could potently inhibit MACV-activated IFN responses even at 6 h after MACV infection, while the replication levels of MACV and LASV were not affected by virus coinfection. Our results clearly demonstrated that although all viruses studied herein are highly pathogenic to humans, the host IFN responses toward infections with the NW arenaviruses JUNV and MACV are quite different from responses to infections with the OW arenavirus LASV, a discovery that needs to be further investigated in relevant animal models. This finding might help us better understand various interplays between the host immune system and highly pathogenic arenaviruses as well as distinct mechanisms underlying viral pathogenesis. IMPORTANCE Infections of humans with the highly pathogenic OW LASV are accompanied by potent suppression of interferon or proinflammatory cytokine production. In contrast, infections with the highly pathogenic NW arenavirus JUNV are associated with high levels of IFNs and

  11. Clinical applications of the human brainstem responses to auditory stimuli

    NASA Technical Reports Server (NTRS)

    Galambos, R.; Hecox, K.

    1975-01-01

    A technique utilizing the frequency following response (FFR) (obtained by auditory stimulation, whereby the stimulus frequency and duration are mirror-imaged in the resulting brainwaves) as a clinical tool for hearing disorders in humans of all ages is presented. Various medical studies are discussed to support the clinical value of the technique. The discovery and origin of the FFR and another significant brainstem auditory response involved in studying the eighth nerve is also discussed.

  12. Einstein, social responsibility of physicists and human rights in China

    NASA Astrophysics Data System (ADS)

    Fang, Li-Zhi

    2005-03-01

    Since Einstein first visited Shanghai on 1922, he was deeply and constantly concerned about the cases of injustice, suppression, and human rights abuses in China. The strong sense of social responsibility shown by Einstein is an illustrious role model for Chinese intellectual, especially physicists, who advocate the universal principle of human rights. I will briefly review this history. I will also briefly report what have been done and is doing by Chinese physicists in the long and difficult journey toward democracy and human rights of China.

  13. Response to 'pervasive sequence patents cover the entire human genome'.

    PubMed

    Tu, Shine; Holman, Christopher; Mossoff, Adam; Sichelman, Ted; Risch, Michael; Conteras, Jorge L; Heled, Yaniv; Dolin, Greg; Petherbridge, Lee

    2014-01-01

    A response to Pervasive sequence patents cover the entire human genome by J Rosenfeld and C Mason. Genome Med 2013, 5:27. See related Correspondence by Rosenfeld and Mason, http://genomemedicine.com/content/5/3/27 and related letter by Rosenfeld and Mason, http://genomemedicine.com/content/6/2/15. PMID:25031614

  14. VASCULAR RESPONSE TO TRAFFIC-DERIVED INHALATION IN HUMANS

    EPA Science Inventory

    By coordinating closely with Center Projects 1-3, we will determine whether specific aspects of traffic-derived exposure (primary vs. secondary organics, particulate vs. gases, spark-ignition vs. diesel engine vs. a mixture) enhance the human vascular response to pollutants. W...

  15. Human Response to Aircraft-Noise-Induced Building Vibration

    NASA Technical Reports Server (NTRS)

    Cawthorn, J. M.; Dempsey, T. K.; DeLoach, R.

    1978-01-01

    The effects of noise induced building structure vibration and the rattle of objects on human response to aircraft flyover noise were investigated in a series of studies conducted in both the field and the laboratory. The subjective detection thresholds for vibration and rattle were determined as well as the effect of vibration and rattle upon aircraft noise annoyance.

  16. The response of human and rodent cells to hyperthermia

    SciTech Connect

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

    1991-04-01

    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.

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

    Barabási, Albert-László

    2011-01-01

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

  19. Aging affects the cardiovascular responses to cold stress in humans

    PubMed Central

    Hess, Kari L.; Wilson, Thad E.; Sauder, Charity L.; Gao, Zhaohui; Ray, Chester A.

    2009-01-01

    Cardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger [25 ± 1 (SE) yr old] and 12 older (65 ± 2 yr old) adults. We found that superficial skin cooling elicited an increase in blood pressure from resting levels (pressor response; P < 0.05) in younger and older adults. However, the magnitude of this pressor response (systolic and mean blood pressure) was more than twofold higher in older adults (P < 0.05 vs. younger adults). The magnitude of the pressor response was similar at peripheral (brachial) and central (estimated in the aorta) measurement sites. Regression analysis revealed that aortic pulse wave velocity, a measure of central arterial stiffness obtained before cooling, was the best predictor of the increased pressor response to superficial skin cooling in older adults, explaining ∼63% of its variability. These results indicate that there is a greater pressor response to non-internal body temperature-reducing cold stress with age in humans that may be mediated by increased levels of central arterial stiffness. PMID:19679742

  20. The effects of response cost and response restriction on a multiple-response repertoire with humans

    PubMed Central

    Crosbie, John

    1993-01-01

    In two experiments a multiple-response repertoire of four free-operant responses was developed with university students as subjects using monetary gain as reinforcement. Following baseline, one of the responses was reduced either by making monetary loss contingent upon it (response cost) or by removing it from the repertoire (response restriction). In Experiment 1 a multielement baseline design was employed in which baseline and restriction or response-cost contingencies alternated semirandomly every 3 minutes. In Experiment 2 a reversal design was employed (i.e., baseline, restriction or response cost, then baseline), and each response required a different amount of effort. Both experiments had the following results: (a) The target response decreased substantially; (b) most nontarget responses increased, and the rest remained near their baseline levels; and (c) no support was found for Dunham's hierarchical, most frequent follower, or greatest temporal similarity rules. For several subjects, the least probable responses during baseline increased most, and the most probable responses increased least. Furthermore, in Experiment 2, responses with the lowest frequency of reinforcement increased most (for all 7 subjects), and those with the greatest frequency of reinforcement increased least (for 5 subjects). PMID:16812683

  1. Anticipating Human Activities Using Object Affordances for Reactive Robotic Response.

    PubMed

    Koppula, Hema S; Saxena, Ashutosh

    2016-01-01

    An important aspect of human perception is anticipation, which we use extensively in our day-to-day activities when interacting with other humans as well as with our surroundings. Anticipating which activities will a human do next (and how) can enable an assistive robot to plan ahead for reactive responses. Furthermore, anticipation can even improve the detection accuracy of past activities. The challenge, however, is two-fold: We need to capture the rich context for modeling the activities and object affordances, and we need to anticipate the distribution over a large space of future human activities. In this work, we represent each possible future using an anticipatory temporal conditional random field (ATCRF) that models the rich spatial-temporal relations through object affordances. We then consider each ATCRF as a particle and represent the distribution over the potential futures using a set of particles. In extensive evaluation on CAD-120 human activity RGB-D dataset, we first show that anticipation improves the state-of-the-art detection results. We then show that for new subjects (not seen in the training set), we obtain an activity anticipation accuracy (defined as whether one of top three predictions actually happened) of 84.1, 74.4 and 62.2 percent for an anticipation time of 1, 3 and 10 seconds respectively. Finally, we also show a robot using our algorithm for performing a few reactive responses. PMID:26656575

  2. Eyes open versus eyes closed - Effect on human rotational responses

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    The effect of eyelid closure on the response to rotational vestibular stimulation was assessed by evaluating 16 normal human subjects with both earth vertical axis (EVA) and earth horizontal axis (EHA) yaw rotations with either eyes closed (EC) or eyes open in the dark (EOD). Results indicated that for EVA rotation, the subjects' responses were of larger magnitude and less variable with EOD than with EC. However, for EHA rotation, responses were of larger magnitude and equally variable with EC as compared to EOD. Data also indicated that the quality of the EHA response with EC was altered because eyelid closure influenced the amount of periodic gaze. It is concluded that eyelid closure has an effect upon both canalocular and otolithocular reflexes and it is suggested that both EVA and EHA rotational testing be performed with EOD rather than with EC.

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

    ERIC Educational Resources Information Center

    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…

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

    NASA Astrophysics Data System (ADS)

    Allison, Edward H.; Bassett, Hannah R.

    2015-11-01

    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.

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

    PubMed

    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. PMID:26564848

  6. Reproducibility of the vascular response to heating in human skin.

    PubMed

    Savage, M V; Brengelmann, G L

    1994-04-01

    Blood flow in human skin increases enormously in response to direct heating. If local skin temperature is held above 42 degrees C, blood flow eventually stabilizes at a level beyond which other influences, barring change in blood pressure, can produce no further increase. If this maximal level is a reproducible characteristic of an individual's cutaneous vasculature, it could be useful in comparing individuals; for example, in their response to hyperthermia. Our experiments were carried out to discover whether the maximal response of the vasculature of the skin of the forearm can be reproduced within reasonable limits and, also, to clarify the time course of the response. We used water sprayed over the surface of the forearms of 10 subjects to hold skin temperature above 42 degrees C for 60 min. During the last 10 min of heating, forearm blood flow (via venous occlusion plethysmography) was stable, at a level ranging from 16 to 38 ml.min-1.100 ml-1. This level, normalized to a blood pressure of 100 mmHg, was reproduced in a given individual on four or five occasions, with an average coefficient of variation of 10%. The response was 77 +/- 11% (SD) complete after 20 min of heating. Elapsed time at 90% of the final value was 35 +/- 9 (SD) min. We conclude that the maximal forearm blood flow response to local heating is a reproducible characteristic of the cutaneous vasculature with potential utility in the scaling of responses between and within individuals. PMID:8045857

  7. Immune responses in humans after 60 days of confinement

    NASA Technical Reports Server (NTRS)

    Schmitt, D. A.; Peres, C.; Sonnenfeld, G.; Tkackzuk, J.; Arquier, M.; Mauco, G.; Ohayon, E.

    1995-01-01

    A confinement experiment in a normobaric diving chamber was undertaken to better understand the effect of confinement and isolation on human psychology and physiology. Pre- and postconfinement blood samples were obtained from four test subjects and control donors to analyze immune responses. No modification in the levels of CD2+, CD3+, CD4+, CD8+, CD19+, and CD56+ cells was observed after confinement. Mitogen-induced T-lymphocyte proliferation and interleukin-2 receptor expression were not altered significantly. Whole blood interferon-alpha and gamma-induction and plasma cortisol levels were also unchanged, as was natural killer cell activity. These data suggest that in humans, no specific components of the immune response are affected by a 2-month isolation and confinement of a small group.

  8. Curcumin prevents human dendritic cell response to immune stimulants

    SciTech Connect

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

    2008-09-26

    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{sup +} 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{sup +} 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.

  9. Brain connectivity reflects human aesthetic responses to music.

    PubMed

    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. PMID:26966157

  10. Curcumin prevents human dendritic cell response to immune stimulants

    PubMed Central

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

    2012-01-01

    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 naïve 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. PMID:18639521

  11. Effects of Control Stick Parameters on Human Controller Response

    NASA Technical Reports Server (NTRS)

    Repperger, D. W.; Levinson, W. H.

    1984-01-01

    A fixed base laboratory tracking study was conducted to determine the effects of stick displacement and stick force characteristics on human tracking performance. Three different levels of control stick force/displacement characteristics and stick electrical gain were varied to observe their influence on RMS (Root Mean Square) tracking error and RMS control activity (stick output). The results indicated that both RMS tracking error and RMS control activity were influenced by the three different levels of control stick force/displacement characteristics and stick electrical gain. The human neuromotor time constant was affected by the electrical control gain of the stick while the spring stiffness of the stick influenced the time delay characteristics of the human response behavior.

  12. Biomechanical impact response of the human chin and manubrium.

    PubMed

    Stammen, Jason A; Bolte, John H; Shaw, Joshua

    2012-03-01

    Chin-to-chest impact commonly occurs in frontal crash simulations with restrained anthropomorphic test devices (ATDs) in non-airbag situations. This study investigated the biofidelity of this contact by evaluating the impact response of both the chin and manubrium of adult post-mortem human subjects (PMHSs). The adult PMHS data were scaled to a 10-year-old (YO) human size and then compared with the Hybrid III 10YO child (HIII-10C) ATD response with the same test configurations. For both the chin and manubrium, the responses of the scaled PMHS had different characteristics than the HIII-10C ATD responses. Elevated energy impact tests to the PMHS mandible provided a mean injury tolerance value for chin impact force. Chin contact forces in the HIII-10C ATD were calculated in previously conducted HYGE sled crash simulation tests, and these contact forces were strongly correlated with the Head Injury Criterion (HIC(36 ms)). The mean injurious force from the PMHS tests corresponded to a HIC(36 ms) value that would predict an elevated injury risk if it is assumed that fractures of the chin and skull are similarly correlated with HIC(36 ms). Given the rarity of same occupant-induced chin injury in booster-seated occupants in real crash data and the disparity in chin and manubrium stiffnesses between scaled PMHS and HIII-10C ATD, the data from this study can be made use of to improve biofidelity of chin-to-manubrium contact in ATDs. PMID:21971966

  13. Human genes in TB infection: their role in immune response.

    PubMed

    Lykouras, D; Sampsonas, F; Kaparianos, A; Karkoulias, K; Tsoukalas, G; Spiropoulos, K

    2008-03-01

    Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and T-helper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving. PMID:18507196

  14. Modulation of the host response in human schistosomiasis

    PubMed Central

    Hofstetter, M.; Poindexter, R. W.; Ruiz-Tiben, E.; Ottesen, E. A.

    1982-01-01

    Mechanisms for modulating the host's immune response in human Schistosomiasis mansoni have been described for delayed hypersensitivity responsiveness and antibody production. Since clinical symptoms of immediate hypersensitivity (i.e. allergic reactivity) are rare in schistosomiasis despite the presence of parasite-specific immunoglobulin E, circulating parasite antigen, and normal numbers of basophils and mast cells in infected patients, it seemed likely that there was host modulation of immediate hypersensitivity responsiveness as well. Using an in vitro basophil histamine release assay we have shown that basophils from fifteen patients with S. mansoni infections are sensitized with schistosome-specific immunoglobulin E and will release histamine in an antigen-dose-dependent manner when challenged with a soluble adult worm antigen. This histamine release was suppressed by autologus, but not normal serum. Fractionation of the serum over staphylococcal protein A and antigen affinity columns identified an immunoglobulin G parasite-specific `blocking antibody', analogous to blocking antibodies elicited during immunotherapy of atopic patients, as being responsible for the modulation of this immediate hypersensitivity responsiveness in vitro. Blocking antibody specificity varied from patient to patient, an observation suggesting that different allergens were being recognized by different individuals. These studies demonstrate that in addition to the immunoregulatory mechanisms previously described in patients with schistosome infections, there is host modulation of immediate hypersensitivity responsiveness that appears to involve specific immunoglobulin G blocking antibodies. PMID:6179857

  15. Human striatal responses to monetary reward depend on saliency.

    PubMed

    Zink, Caroline F; Pagnoni, Giuseppe; Martin-Skurski, Megan E; Chappelow, Jonathan C; Berns, Gregory S

    2004-05-13

    While the striatum has been implicated in reward processing, an alternative view contends that the striatum processes salient events in general. Using fMRI, we investigated human striatal responses to monetary reward while modulating the saliency surrounding its receipt. Money was maximally salient when its receipt depended on a correct response (active) and minimally salient when its receipt was completely independent of the task (passive). The saliency manipulation was confirmed by skin conductance responses and subjective ratings of the stimuli. Significant caudate and nucleus accumbens activations occurred following the active compared to passive money. Such activations were attributed to saliency rather than the motor requirement associated with the active money because striatal activations were not observed when the money was replaced by inconsequential, nonrewarding stimuli. The present study provides evidence that the striatum's role in reward processing is dependent on the saliency associated with reward, rather than value or hedonic feelings. PMID:15134646

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

    PubMed

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

    2012-04-01

    Several authors have argued that criminal behavior is generally caused by neurobiological deficits. This assumption not only questions the concept of free will and a person's responsibility for his or her own actions but also the principle of guilt in criminal law. When critically examining the current state of research, it becomes apparent that the results are not sufficient to support the existence of a universally valid neurobiological causality of criminal behavior. Moreover, the assumption of total neurobiological determination of human behavior and the impossibility of individual responsibility are characterized by both faulty empiricism and methodical misconceptions. The principle of relative determinism and the analysis of the offender's behavior at the time of the offense thus remain the central and cogent approach to the assessment of criminal responsibility. PMID:21362643

  17. Human vertical eye movement responses to earth horizontal pitch

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

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

    2016-01-01

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

  19. Neural responses to perceiving suffering in humans and animals.

    PubMed

    Franklin, Robert G; Nelson, Anthony J; Baker, Michelle; Beeney, Joseph E; Vescio, Theresa K; Lenz-Watson, Aurora; Adams, Reginald B

    2013-01-01

    The human ability to perceive and understand others' suffering is critical to reinforcing and maintaining our social bonds. What is not clear, however, is the extent to which this generalizes to nonhuman entities. Anecdotal evidence indicates that people may engage in empathy-like processes when observing suffering nonhuman entities, but psychological research suggests that we more readily empathize with those to whom we are closer and more similar. In this research, we examined neural responses in participants while they were presented with pictures of human versus dog suffering. We found that viewing human and animal suffering led to large overlapping regions of activation previously implicated in empathic responding to suffering, including the anterior cingulate gyrus and anterior insula. Direct comparisons of viewing human and animal suffering also revealed differences such that human suffering yielded significantly greater medial prefrontal activation, consistent with high-level theory of mind, whereas animal suffering yielded significantly greater parietal and inferior frontal activation, consistent with more semantic evaluation and perceptual simulation. PMID:23405957

  20. Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations

    PubMed Central

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

    2016-01-01

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

  1. Antibody Response to Cryptococcus neoformans Proteins in Rodents and Humans

    PubMed Central

    Chen, Lin-Chi; Goldman, David L.; Doering, Tamara L.; Pirofski, Liise-anne; Casadevall, Arturo

    1999-01-01

    The prevalence and specificity of serum antibodies to Cryptococcus neoformans proteins was studied in mice and rats with experimental infection, in individuals with or without a history of potential laboratory exposure to C. neoformans, human immunodeficiency virus (HIV)-positive individuals who developed cryptococcosis, in matched samples from HIV-positive individuals who did not develop cryptococcosis, and in HIV-negative individuals. Rodents had little or no serum antibody reactive with C. neoformans proteins prior to infection. The intensity and specificity of the rodent antibody response were dependent on the species, the mouse strain, and the viability of the inoculum. All humans had serum antibodies reactive with C. neoformans proteins regardless of the potential exposure, the HIV infection status, or the subsequent development of cryptococcosis. Our results indicate (i) a high prevalence of antibodies reactive with C. neoformans proteins in the sera of rodents after cryptococcal infection and in humans with or without HIV infection; (ii) qualitative and quantitative differences in the antibody profiles of HIV-positive individuals; and (iii) similarities and differences between humans, mice, and rats with respect to the specificity of the antibodies reactive with C. neoformans proteins. The results are consistent with the view that C. neoformans infections are common in human populations, and the results have implications for the development of vaccination strategies against cryptococcosis. PMID:10225877

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  3. Titanium surface hydrophilicity modulates the human macrophage inflammatory cytokine response.

    PubMed

    Alfarsi, Mohammed A; Hamlet, Stephen M; Ivanovski, Saso

    2014-01-01

    Increased titanium surface hydrophilicity has been shown to accelerate dental implant osseointegration. Macrophages are important in the early inflammatory response to surgical implant placement and influence the subsequent healing response. This study investigated the modulatory effect of a hydrophilic titanium surface on the inflammatory cytokine expression profile in a human macrophage cell line (THP-1). Genes for 84 cytokines, chemokines, and their receptors were analyzed following exposure to (1) polished (SMO), (2) micro-rough sand blasted, acid etched (SLA), and (3) hydrophilic-modified SLA (modSLA) titanium surfaces for 1 and 3 days. By day 3, the SLA surface elicited a pro-inflammatory response compared to the SMO surface with statistically significant up-regulation of 16 genes [Tumor necrosis factor (TNF) Interleukin (IL)-1β, Chemokine (C-C motif) ligand (CCL)-1, 2, 3, 4, 18, 19, and 20, Chemokine (C-X-C motif) ligand (CXCL)-1, 5, 8 and 12, Chemokine (C-C motif) receptor (CCR)-7, Lymphotoxin-beta (LTB), and Leukotriene B4 receptor (LTB4R)]. This effect was countered by the modSLA surface, which down-regulated the expression of 10 genes (TNF, IL-1α and β, CCL-1, 3, 19 and 20, CXCL-1 and 8, and IL-1 receptor type 1), while two were up-regulated (osteopontin and CCR5) compared to the SLA surface. These cytokine gene expression changes were confirmed by decreased levels of corresponding protein secretion in response to modSLA compared to SLA. These results show that a hydrophilic titanium surface can modulate human macrophage pro-inflammatory cytokine gene expression and protein secretion. An attenuated pro-inflammatory response may be an important molecular mechanism for faster and/or improved wound healing. PMID:23595995

  4. Immediate response to resistive loading in anesthetized humans.

    PubMed

    Zin, W A; Behrakis, P K; Luijendijk, S C; Higgs, B D; Baydur, A; Böddener, A; Milic-Emili, J

    1986-02-01

    In eight spontaneously breathing anesthetized subjects (halothane: approximately 1 minimal alveolar concn; 70% N2O-30% O2), we determined 1) the inspiratory driving pressure by analysis of the pressure developed at the airway opening (Poao) during inspiratory efforts against airways occluded at end expiration; 2) the active inspiratory impedance; and 3) the immediate (first loaded breath) response to added inspiratory resistive loads (delta R). Based on these data we made model predictions of the immediate tidal volume response to delta R. Such predictions closely fitted the experimental results. The present investigation indicates that 1) in halothane-anesthetized humans the shape of the Poao wave differs from that in anesthetized animals, 2) the immediate response to delta R is not associated with appreciable changes in intensity, shape, and timing of inspiratory neural drive but depends mainly on intrinsic (nonneural) mechanisms; 3) the flow-dependent resistance of endotracheal tubes must be taken into account in studies dealing with increased neuromuscular drive in intubated subjects; and 4) in anesthetized humans Poao reflects the driving pressure available to produce the breathing movements. PMID:3949656

  5. Development of BOLD signal hemodynamic responses in the human brain

    PubMed Central

    Arichi, Tomoki; Fagiolo, Gianlorenzo; Varela, Marta; Melendez-Calderon, Alejandro; Allievi, Alessandro; Merchant, Nazakat; Tusor, Nora; Counsell, Serena J.; Burdet, Etienne; Beckmann, Christian F.; Edwards, A. David

    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 populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the Blood Oxygen Level Dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41 + 1 weeks), and 10 preterm infants (median PMA 34 + 4 weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond. PMID:22776460

  6. Thermophysiological responses to hyperthermic drugs: extrapolating from rodent to human.

    PubMed

    Gordon, Christopher J

    2007-01-01

    This chapter focuses on the effects of hyperthermia on drug and chemical toxicity. In general, hyperthermia exacerbates the toxicity of many types of drugs and environmental toxicants. Using rodents to model the potential responses of humans to hyperthermic drugs is hampered by the unique differences in thermoregulatory ability and body mass. Because of their relatively large surface area:mass ratio, ambient temperature has a more profound influence on the potential hyperthermic effect of a drug in rodents. The relative increase in heat production (i.e., as a percentage of their basal metabolic rate) required to raise core temperature by 1 degrees C will increase with a decrease in body mass. The thermoregulatory response to methylenedioxymethamphetamine (MDMA) is used to illustrate the differences in thermoregulatory responses of rats and humans to a hyperthermic drug. Overall, the interaction between ambient temperature and drug-induced changes in body temperature is critical in the evaluation of hyperthermic-induced toxicity in rodent models. PMID:17645915

  7. Skeletal muscle responses to lower limb suspension in humans

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  8. Human mesangial cells resist glycoxidative stress through an antioxidant response.

    PubMed

    Nitti, Mariapaola; Furfaro, Anna Lisa; Patriarca, Stefania; Balbis, Emanuela; Domenicotti, Cinzia; Cottalasso, Damiano; Pronzato, Maria Adelaide; Marinari, Umberto Maria; Traverso, Nicola

    2011-02-01

    The generation of advanced glycation end-products (AGE), the interaction with their receptors, the generation of reactive oxygen species, and the modulation of intracellular redox equilibrium are believed to be the main factors causing alterations of mesangial cell physiology leading to diabetic nephropathy. Normal human primary mesangial cells were exposed to glycoxidative stress by culture in high glucose (HG) or treatment with AGE for up to 6 days. In both cases only a moderate generation of reactive oxygen species and production of HNE-protein adducts were induced while protein nitrotyrosination was not affected. Moreover, HG and AGE caused a significant antioxidant response, confirmed by the induction of heme oxygenase 1 and the consumption of vitamin E. Glutathione was decreased only by HG. Mesangial cell proliferation and viability were slightly affected by HG and AGE. Furthermore, both treatments failed to influence TGF-ß1 and MCP-1 secretion and to modulate RAGE and collagen IV expression. We believe that normal human mesangial cells can resist glycoxidative stress by the observed antioxidant response. These results support the concept that mesangial cells are only partly responsible for the onset and progression of diabetic nephropathy and that the role of other cell types, such as podocytes and endothelial cells, should be taken into consideration. PMID:21152865

  9. Quantifying human response capabilities towards tsunami threats at community level

    NASA Astrophysics Data System (ADS)

    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

  10. Transcriptional profiling of vaccine‐induced immune responses in humans and non‐human primates

    PubMed Central

    Wang, I‐Ming; Bett, Andrew J.; Cristescu, Razvan; Loboda, Andrey; ter Meulen, Jan

    2012-01-01

    Summary There is an urgent need for pre‐clinical and clinical biomarkers predictive of vaccine immunogenicity, efficacy and safety to reduce the risks and costs associated with vaccine development. Results emerging from immunoprofiling studies in non‐human primates and humans demonstrate clearly that (i) type and duration of immune memory are largely determined by the magnitude and complexity of the innate immune signals and (ii) genetic signatures highly predictive of B‐cell and T‐cell responses can be identified for specific vaccines. For vaccines with similar composition, e.g. live attenuated viral vaccines, these signatures share common patterns. Signatures predictive of vaccine efficacy have been identified in a few experimental challenge studies. This review aims to give an overview of the current literature on immunoprofiling studies in humans and also presents some of our own data on profiling of licensed and experimental vaccines in non‐human primates. PMID:22103427

  11. Human responses to bright light of different durations

    PubMed Central

    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

    2012-01-01

    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 (<3 lux), and were then randomized for exposure to a bright 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. PMID:22526883

  12. Analysis of proposed criteria for human response to vibration

    NASA Technical Reports Server (NTRS)

    Janeway, R. N.

    1975-01-01

    The development of criteria for human vibration response is reviewed, including the evolution of the ISO standard 2631. The document is analyzed to show why its application to vehicle ride evaluation is strongly opposed. Alternative vertical horizontal limits for comfort are recommended in the ground vehicle ride frequency range above 1 Hz. These values are derived by correlating the absorbed power findings of Pradko and Lee with other established criteria. Special emphasis is placed on working limits in the frequency range of 1 to 10 Hz since this is the most significant area in ground vehicle ride evaluation.

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  14. Detecting Blood Flow Response to Stimulation of the Human Eye

    PubMed Central

    Pechauer, Alex D.; Huang, David; Jia, Yali

    2015-01-01

    Retinal blood supply is tightly regulated under a variety of hemodynamic considerations in order to satisfy a high metabolic need and maintain both vessel structure and function. Simulation of the human eye can induce hemodynamics alterations, and attempt to assess the vascular reactivity response has been well documented in the scientific literature. Advancements in noninvasive imaging technologies have led to the characterization of magnitude and time course in retinal blood flow response to stimuli. This allowed for a better understanding of the mechanism in which blood flow is regulated, as well as identifying functional impairments in the diseased eye. Clinically, the ability to detect retinal blood flow reactivity during stimulation of the eye offers potential for the detection, differentiation, and diagnosis of diseases. PMID:26504775

  15. The Effect of Music on the Human Stress Response

    PubMed Central

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

    2013-01-01

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

  16. Human immunodeficiency virus type 1 infection of human macrophages modulates the cytokine response to Pneumocystis carinii.

    PubMed Central

    Kandil, O; Fishman, J A; Koziel, H; Pinkston, P; Rose, R M; Remold, H G

    1994-01-01

    The present studies examined production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 by human monocyte-derived macrophages exposed to Pneumocystis carinii in vitro and the impact of concurrent macrophage infection with human immunodeficiency virus type 1 (HIV-1) on these cytokine responses. Macrophages were infected with the HIV-1 BaL monocytotropic strain for 10 to 14 days and then exposed to P. carinii. At various times following P. carinii treatment, culture supernatants were harvested to assess the cytokine profile. Addition of P. carinii to HIV-uninfected macrophages resulted in augmented production of IL-6, TNF-alpha, and IL-1 beta protein. By contrast, in HIV-infected macrophages exposed to P. carinii, only the release of IL-6 was increased compared with that for HIV-uninfected macrophages, while the levels of TNF-alpha and IL-1 beta decreased. This altered response was confirmed at the molecular level for TNF-alpha mRNA. Preventing physical contact between P. carinii and macrophages by a membrane filter inhibited all cytokine release. Substituting P. carinii with a preparation of P. carinii 95- to 115-kDa major membrane glycoprotein A yielded a response similar to that obtained by addition of intact P. carinii. These results suggest that HIV-1 infection of human macrophages modulates cytokine responses to P. carinii. Images PMID:8300221

  17. HIV-1 increases TLR responses in human primary astrocytes

    PubMed Central

    Serramía, M Jesús; Muñoz-Fernández, M Ángeles; Álvarez, Susana

    2015-01-01

    Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis. They provide trophic support to neurons and are immune cells with key roles during states-of-inflammation. The potential for production of proinflammatory cytokines and its consequences has been studied in the context of HIV-1 infection of normal human astrocytes (NHA). NHA express TLR3, TLR4, and TLR5. TLR3 ligation induced the strongest proinflammatory polarizing response, characterized by generation of high levels of TNF-α, IL-6, and IL-8. HIV-1 increased the transient production of key inflammatory mediators, and exposure to LPS of HIV-1-infected cells increased significantly the cytokine secretion. We confirmed that it is necessary viral gene expression from the moment of pretreatment with antiretrovirals inhibited totally HIV-1-induced TLR response. The higher response to LPS from HIV-1-infected cells did not correlate with TLR4 or MyD88 increased expression. LPS responsiveness of infected cells parallels MHC class II expression, but not CD14. HIV-1-infected NHA present increased sensitivity to the proinflammatory effects of LPS. If this phenomenon occurs in vivo, it will contribute to the immunopathogenesis of this disease and may ultimately offer novel targets for immunomodulatory therapy. PMID:26671458

  18. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    PubMed

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. PMID:26924539

  19. Behavioral Responses Associated with a Human-Mediated Predator Shelter

    PubMed Central

    Shannon, Graeme; Cordes, Line S.; Hardy, Amanda R.; Angeloni, Lisa M.; Crooks, Kevin R.

    2014-01-01

    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. PMID:24718624

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

    PubMed

    Shannon, Graeme; Cordes, Line S; Hardy, Amanda R; Angeloni, Lisa M; Crooks, Kevin R

    2014-01-01

    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. PMID:24718624

  1. Are children with autism more responsive to animated characters? A study of interactions with humans and human-controlled avatars.

    PubMed

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

    2014-10-01

    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 cartoon characters who sought social responses. We found superior gestural and verbal responses to the therapist; intermediate response levels to the avatar and the actor; and poorest responses to the cartoon characters, although attention was equivalent across conditions. These results suggest that even avatars that provide live, responsive interactions are not superior to human therapists in eliciting verbal and non-verbal communication from children with autism in this age range. PMID:24859047

  2. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules

    PubMed Central

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

    2015-01-01

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

  3. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity

    PubMed Central

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  4. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.

    PubMed

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin; Henriques-Normark, Birgitta; Olliver, Marie

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  5. Oxidative stress responses in the human fungal pathogen, Candida albicans.

    PubMed

    Dantas, Alessandra da Silva; 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

  6. Response of the human pupil to geometrically changed light stimuli

    NASA Astrophysics Data System (ADS)

    Kesseler, Wolfgang

    2000-06-01

    Models of the human pupil response have been widely investigated. Yet, besides the well known model for the pupil diameter as a function of light intensity and some studies on the influence of wavelength, a model for the dependence of the pupil diameter on the geometry of an observed image is still missing. This paper describes an experimental setup to study the influence of the geometry of a light distribution stimulating the human eye and its pupil. Moreover, experimental results of the human pupil response as a function of the time and of geometric parameters of the stimulating field are presented. To measure the behavior of the pupil, a test person is positioned in front of a back-side illuminated diffusing pane. This pane approximates a Lambert-radiator. The illuminated area is adjustable to different circular aperture sizes. While varying both size and intensity, the pupil response of a test person is observed by an infrared CCD- camera. Electronic image processing is used to determine the diameter of the captured pupil in the image. The first step is to convert the gray-scale image into a binary image with an optimized threshold. Then, the two dimensional image is reduced to a one-dimensional column-image by collecting and adding all pixels of each row (parallel projection). This step enables a very effective frequency-domain analysis (Fourier transform) leading to the detection of the pupil diameter. The actual setup is able to process ten images per second with a resolution of 0.2 mm. Short-time effects of the pupil diameter can therefore be observed as well as long-time effects. It was found that previous results regarding the pupil diameter as function of the light intensity were confirmed. This indicates that the automatic system works well and the psycho-physical experiments are conducted reasonably. However, as a new result, it was found that the pupil response seems to be dependent on the aperture size of the stimulating field.

  7. Glucocorticoids boost stimulus-response memory formation in humans.

    PubMed

    Guenzel, Friederike M; Wolf, Oliver T; Schwabe, Lars

    2014-07-01

    Stress affects memory beyond hippocampus-dependent spatial or episodic memory processes. In particular, stress may influence also striatum-dependent stimulus-response (S-R) memory processes. Rodent studies point to an important role of glucocorticoids in the modulation of S-R memory. However, whether glucocorticoids influence S-R memory processes in humans is still unknown. Therefore, we examined in the current experiment the impact of glucocorticoids on the formation of S-R memories in humans. For this purpose, healthy men and women received either hydrocortisone or a placebo 45 min before completing an S-R association learning task and an S-R navigation task. In addition, participants performed also a virtual spatial navigation task and a spatial navigation task in a real environment. Memory of all four learning tasks was tested one week later. Our data showed that hydrocortisone before learning enhanced memory of the S-R association learning task. Moreover, hydrocortisone enhanced the memory of the virtual spatial navigation task, mainly in women. Memory performance in the other tasks remained unaffected by hydrocortisone. These findings provide first evidence that glucocorticoids may facilitate S-R memory formation processes in humans. PMID:24845173

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Carotid baroreflex responsiveness in heat-stressed humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.

    2000-01-01

    The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.

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

    PubMed

    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. PMID:27413170

  11. The Radiation Dose-Response of the Human Spinal Cord

    SciTech Connect

    Schultheiss, Timothy E.

    2008-08-01

    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 {alpha}/{beta} 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 {alpha}/{beta} = 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 {alpha}/{beta} is smaller than usually quoted, but values this small were found in some studies. Using {alpha}/{beta} = 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.

  12. Glucocorticoids enhance the in vivo migratory response of human monocytes.

    PubMed

    Yeager, Mark P; Pioli, Patricia A; Collins, Jane; Barr, Fiona; Metzler, Sara; Sites, Brian D; Guyre, Paul M

    2016-05-01

    Glucocorticoids (GCs) are best known for their potent anti-inflammatory effects. However, an emerging model for glucocorticoid (GC) regulation of in vivo inflammation also includes a delayed, preparatory effect that manifests as enhanced inflammation following exposure to an inflammatory stimulus. When GCs are transiently elevated in vivo following exposure to a stressful event, this model proposes that a subsequent period of increased inflammatory responsiveness is adaptive because it enhances resistance to a subsequent stressor. In the present study, we examined the migratory response of human monocytes/macrophages following transient in vivo exposure to stress-associated concentrations of cortisol. Participants were administered cortisol for 6h to elevate in vivo cortisol levels to approximate those observed during major systemic stress. Monocytes in peripheral blood and macrophages in sterile inflammatory tissue (skin blisters) were studied before and after exposure to cortisol or placebo. We found that exposure to cortisol induced transient upregulation of monocyte mRNA for CCR2, the receptor for monocyte chemotactic protein-1 (MCP-1/CCL2) as well as for the chemokine receptor CX3CR1. At the same time, mRNA for the transcription factor IκBα was decreased. Monocyte surface expression of CCR2 but not CX3CR1 increased in the first 24h after cortisol exposure. Transient exposure to cortisol also led to an increased number of macrophages and neutrophils in fluid derived from a sterile inflammatory site in vivo. These findings suggest that the delayed, pro-inflammatory effects of cortisol on the human inflammatory responses may include enhanced localization of effector cells at sites of in vivo inflammation. PMID:26790757

  13. Different vasodilator responses of human arms and legs

    PubMed Central

    Newcomer, Sean C; Leuenberger, Urs A; Hogeman, Cynthia S; Handly, Brian D; Proctor, David N

    2004-01-01

    Forearm vascular responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators have been thoroughly characterized in humans. While the forearm is a well-established experimental model for studying human vascular function, it is of limited consequence to systemic cardiovascular control owing to its small muscle mass and blood flow requirements. In the present study we determined whether these responses could be generalized to the leg. Based upon blood pressure differences between the leg and arm during upright posture, we hypothesized that the responsiveness to endothelium-dependent vasodilators would be greater in the forearm than the leg. Brachial and femoral artery blood flow (Q, ultrasound Doppler) at rest and during intra-arterial infusions of endothelium-dependent (acetylcholine and substance P) and -independent (sodium nitroprusside) vasodilators were measured in eight healthy men (22–27 years old). Resting blood flows in the forearm before infusion of acetylcholine, substance P or sodium nitroprusside were 25 ± 4, 30 ± 7 and 29 ± 5 ml min−1, respectively, and in the leg were 370 ± 32, 409 ± 62 and 330 ± 30 ml min−1, respectively. At the highest infusion rate of acetylcholine (16 μg (100 ml tissue)−1 min−1) there was a greater (P < 0.05) increase in Q to the forearm (1864 ± 476%) than to the leg (569 ± 86%). Similarly, at the highest infusion rate of substance P (125 pg (100 ml tissue)−1 min−1) there was a greater (P < 0.05) increase in Q to the forearm (911 ± 286%) than to the leg (243 ± 58%). The responses to sodium nitroprusside (1 μg (100 ml tissue)−1 min−1) were also greater (P < 0.05) in the forearm (925 ± 164%) than in the leg (326 ± 65%). These data indicate that vascular responses to both endothelium-dependent and -independent vasodilator agents are blunted in the leg compared to the forearm. PMID:14990681

  14. Leukocyte Responsiveness to Exercise in Individuals Positive for Human Cytomegalovirus.

    PubMed

    Wilson, J N; Navalta, J W

    2016-05-01

    Human cytomegalovirus (HCMV) infects 50% of adults in the United States. HCMV can become a cause for concern in individuals who have a compromised immune system, which may occur after high-intensity exercise. The purpose of this preliminary study was to characterize the lymphocyte, monocyte, and neutrophil responses to exercise in HCMV+individuals. Participants were either positive (HCMV +) or negative (HCMV-) for HCMV. Participants visited the laboratory on 3 separate occasions: HCMV screening, 100% VO2max test, and 80% VO2max run. Mixed-model factorial ANOVA procedures with repeated measures on sampling condition were performed on absolute and relative circulating lymphocytes, monocytes, and neutrophils. Significant main effects for time for both absolute and relative values were seen for all leukocyte subsets regardless of virus status. Significant differences for absolute and relative values were seen between sampling conditions for all leukocyte subsets. We report for the first time that HCMV status does not affect circulating neutrophil responses to high-intensity exercise, though exercise-induced neutrocytosis is seen during the post-exercise and 60 min post-exercise sampling conditions, regardless of HCMV status. There is no HCMV effect on circulating monocyte responses to exercise, though exercise-induced monocytosis was seen during the post-exercise sampling condition regardless of HCMV status. PMID:26837931

  15. Overview of NASA human response to sonic boom program

    NASA Technical Reports Server (NTRS)

    Shepherd, Kevin P.

    1992-01-01

    For some routes the ability to fly at supersonic speeds over land as well as over water would greatly enhance the time benefit to the passenger. It would also increase the productivity and economic viability of the aircraft. There are no reliable guidelines which can be used to determine a sonic boom exposure which would be acceptable for overland supersonic flight. In addition to the peak pressure of the sonic boom, the detailed shape of the signature will also influence the perception, and therefore the community response, to sonic boom exposures. Initially, the program aims to develop the capability to predict human response to individual sonic booms. This will enable a quantitative assessment of the benefit of 'low boom' aircraft configurations and will also serve to guide the design of the aircraft and its operating conditions. This capability will form the foundation of studies to determine the relationship between sonic boom exposure and community response. Only then will it be possible to assess the feasibility of acceptable overland supersonic flight.

  16. Human discomfort response to noise combined with vertical vibration

    NASA Technical Reports Server (NTRS)

    Leatherwood, J. D.

    1979-01-01

    An experimental investigation was conducted (1) to determine the effects of combined environmental noise and vertical vibration upon human subjective discomfort response, (2) to develop a model for the prediction of passenger discomfort response to the combined environment, and (3) to develop a set of noise-vibration curves for use as criteria in ride quality design. Subjects were exposed to parametric combinations of noise and vibrations through the use of a realistic laboratory simulator. Results indicated that accurate prediction of passenger ride comfort requires knowledge of both the level and frequency content of the noise and vibration components of a ride environment as well as knowledge of the interactive effects of combined noise and vibration. A design tool in the form of an empirical model of passenger discomfort response to combined noise and vertical vibration was developed and illustrated by several computational examples. Finally, a set of noise-vibration criteria curves were generated to illustrate the fundamental design trade-off possible between passenger discomfort and the noise-vibration levels that produce the discomfort.

  17. CD46-induced human Tregs enhance B cell responses

    PubMed Central

    Fuchs, Anja; Atkinson, John P.; Fremeaux-Bacchi, Veronique; Kemper, Claudia

    2010-01-01

    Summary Regulatory CD4+ T cells (Tregs) are important modulators of the immune response. Different types of Tregs have been identified based on whether they are thymically derived (natural Tregs) or induced in the periphery (adaptive Tregs). We recently reported on an adaptive Treg phenotype that can be induced by the concomitant stimulation of human CD4+ T cells through CD3 and the membrane complement regulator CD46. These complement-induced Treg cells (cTreg) potently inhibit bystander T cell proliferation through high-level secretion of IL-10. In addition, cTreg express granzyme B and exhibit cytotoxic effects towards activated effector T cells. Here we analyzed the effect of cTreg on B cell functions in a co-culture system. We found that cTreg enhance B cell antibody production. This B cell support is dependent on cell/cell contact as well as cTreg-derived IL-10. In addition, we show that T cells from a CD46-deficient patient are not capable of promoting B cell responses, whereas CD46-deficient B cells have no intrinsic defect in Ig production. This finding may relate to a subset of CD46-deficient patients who present with common variable immunodeficiency (CVID). Thus, the lack of cTreg function in optimizing B cell responses could explain why some CD46-deficient patients develop CVID. PMID:19784949

  18. Protective and pathologic immune responses in human tegumentary leishmaniasis.

    PubMed

    Carvalho, Lucas P; Passos, Sara; Schriefer, Albert; Carvalho, Edgar M

    2012-01-01

    Studies in the recent years have advanced the knowledge of how host and parasite factors contribute to the pathogenesis of human tegumentary leishmaniasis. Polymorphism within populations of Leishmania from the same species has been documented; indicating that infection with different strains may lead to distinct clinical pictures and can also interfere in the response to treatment. Moreover, detection of parasite genetic tags for the precise identification of strains will improve diagnostics and therapy against leishmaniasis. On the host side, while a predominant Th1 type immune response is important to control parasite growth, it does not eradicate Leishmania and, in some cases, does not prevent parasite dissemination. Evidence has accumulated showing the participation of CD4(+) and CD8(+) T cells, as well as macrophages, in the pathology associated with L. braziliensis, L. guayanensis, and L. major infection. The discovery that a large percentage of individuals that are infected with Leishmania do not develop disease will help to understand how the host controls Leishmania infection. As these individuals have a weaker type 1 immune response than patients with cutaneous leishmaniasis, it is possible that control of parasite replication in these individuals is dependent, predominantly, on innate immunity, and studies addressing the ability of neutrophils, macrophages, and NK cells to kill Leishmania should be emphasized. PMID:23060880

  19. Colonic secretory effect in response to enteral feeding in humans.

    PubMed Central

    Bowling, T E; Raimundo, A H; Grimble, G K; Silk, D B

    1994-01-01

    Diarrhoea complicating enteral feeding is a common clinical problem affecting up to 25% of patients. Its pathogenesis remains unknown. A new technique of human in vivo segmental colonic perfusion was used to investigate colonic water and electrolyte movement in response to enteral feeding. Four groups of studies were performed in which low and high load polymeric enteral diet infusions were undertaken, either intragastrically or intraduodenally (n = 6 each group). Net absorption of sodium, chloride, and water occurred during fasting throughout the colon in all groups. There was a significant net secretion of sodium, chloride, and water in the ascending colon during low load (sodium: -42 mmol/h; 95% confidence limits -52 to -19, Chloride: -18 mmol/h; -50 to +16, water: -174 ml/h; -348 to -30) and high load (sodium: -24 mmol/h; -60 to +8, chloride: -18 mmol/h; -31 to +16, water: -120 ml/h; -246 to +6) gastric feeding, and during high load duodenal feeding (sodium: -12 mmol/h; -22 to -6, chloride; -6 mmol/h; -16 to +3, water: -72 ml/h; -144 to -6). Net secretion persisted in the distal colon only during high load gastric feeding. In the other three groups there was a net absorption in the distal colon. This study identified a significant colonic secretory response to enteral feeding, which is related to the site and load of the diet infusion. This response may play an important part in the pathogenesis of enteral feeding related diarrhoea. PMID:7829011

  20. Unconditioned responses and functional fear networks in human classical conditioning

    PubMed Central

    Linnman, Clas; Rougemont-Bücking, Ansgar; Beucke, Jan Carl; Zeffiro, Thomas A; Milad, Mohammed R

    2011-01-01

    Human imaging studies examining fear conditioning have mainly focused on the neural responses to conditioned cues. In contrast, the neural basis of the unconditioned response and the mechanisms by which fear modulates inter-regional functional coupling have received limited attention. We examined the neural responses to an unconditioned stimulus using a partial-reinforcement fear conditioning paradigm and functional MRI. The analysis focused on: (1) the effects of an unconditioned stimulus (an electric shock) that was either expected and actually delivered, or expected but not delivered, and (2) on how related brain activity changed across conditioning trials, and (3) how shock expectation influenced inter-regional coupling within the fear network. We found that: (1) the delivery of the shock engaged the red nucleus, amygdale, dorsal striatum, insula, somatosensory and cingulate cortices, (2) when the shock was expected but not delivered, only the red nucleus, the anterior insular and dorsal anterior cingulate cortices showed activity increases that were sustained across trials, and (3) psycho-physiological interaction analysis demonstrated that fear led to increased red nucleus coupling to insula but decreased hippocampus coupling to the red nucleus, thalamus and cerebellum. The hippocampus and the anterior insula may serve as hubs facilitating the switch between engagement of a defensive immediate fear network and a resting network. PMID:21377494

  1. Unconditioned responses and functional fear networks in human classical conditioning.

    PubMed

    Linnman, Clas; Rougemont-Bücking, Ansgar; Beucke, Jan Carl; Zeffiro, Thomas A; Milad, Mohammed R

    2011-08-01

    Human imaging studies examining fear conditioning have mainly focused on the neural responses to conditioned cues. In contrast, the neural basis of the unconditioned response and the mechanisms by which fear modulates inter-regional functional coupling have received limited attention. We examined the neural responses to an unconditioned stimulus using a partial-reinforcement fear conditioning paradigm and functional MRI. The analysis focused on: (1) the effects of an unconditioned stimulus (an electric shock) that was either expected and actually delivered, or expected but not delivered, and (2) on how related brain activity changed across conditioning trials, and (3) how shock expectation influenced inter-regional coupling within the fear network. We found that: (1) the delivery of the shock engaged the red nucleus, amygdale, dorsal striatum, insula, somatosensory and cingulate cortices, (2) when the shock was expected but not delivered, only the red nucleus, the anterior insular and dorsal anterior cingulate cortices showed activity increases that were sustained across trials, and (3) psycho-physiological interaction analysis demonstrated that fear led to increased red nucleus coupling to insula but decreased hippocampus coupling to the red nucleus, thalamus and cerebellum. The hippocampus and the anterior insula may serve as hubs facilitating the switch between engagement of a defensive immediate fear network and a resting network. PMID:21377494

  2. Our Professional Responsibilities Relative to Human-Animal Interactions

    PubMed Central

    Bustad, L. K.; Hines, L.

    1984-01-01

    An interesting area with great potential for benefiting and enriching the lives and conditions of people and animals is opening to us in research, service and teaching. By working with colleagues in other disciplines, we can develop new and creative ways to realize the great promise inherent in people-animal interactions properly studied and utilized. Veterinarians who understand that a strong human-companion animal bond can augment people's mental and physical states will help develop sound and effective companion animal programs for individuals who are lonely or handicapped and for persons in the school systems of the community, as well as its hospices, nursing and convalescent homes, prisons and other institutions. Children experiencing the deep satisfaction of interacting with animals while young will more likely become responsible pet owners and advocates as adults. The image of the profession is enhanced when children and adults see veterinarians as concerned teachers and compassionate health professionals. We as professionals will be required not only to update our knowledge and skills, but to acquire new knowledge in fields of animal and human behavior, psychology and sociology. We are needed on interdisciplinary research teams to study human-animal interactions. We will also be asked to commit time and personal energies in community programs, sometimes with no remuneration. But if skilled health professionals like veterinarians do not take the lead in establishing sound, long-term companion animal programs in their own communities, everyone will suffer including the animals. How we, as individual professionals, respond will be an important reflection of our compassion and our humanity. PMID:17422458

  3. Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.

    PubMed Central

    Alp, N J; Allport, T D; Van Zanten, J; Rodgers, B; Sissons, J G; Borysiewicz, L K

    1991-01-01

    Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known about responses against this protein by CD4+ T cells, which may be important as direct effector cells or helper cells for antibody and CD8+ responses. Proliferative-T-cell responses to HCMV IE1 were studied in normal seropositive subjects. Peripheral blood mononuclear cells from 85% of seropositive subjects proliferated in response to HCMV from infected fibroblasts, and of these, 73% responded to recombinant baculovirus IE1. Responding cells were predominantly CD3+ CD4+. IE1 antigen preparations, including baculovirus recombinant protein, transfected rat cell nuclei, and synthetic peptides, induced IE1-specific T-cell lines which cross-reacted between the preparations. The fine specificity of these IE1-specific T-cell lines was studied by using overlapping synthetic peptides encompassing the entire sequence of the IE1 protein. The regions of the IE1 molecule recognized were identified and these varied between individuals, possibly reflecting differences in major histocompatibility complex (MHC) class II haplotype. In one subject, the peptide specificities of proliferative and MHC class I-restricted cytotoxic determinants on IE1 were spatially distinct. Thus, no single immunodominant T-cell determinant within HCMV IE1 was identified, suggesting that multiple peptides or a region of the 72-kDa IE1 protein would be required to induce specific T-cell responses in humans. PMID:1714519

  4. The fractional viscoelastic response of human breast tissue cells

    NASA Astrophysics Data System (ADS)

    Carmichael, B.; Babahosseini, H.; Mahmoodi, S. N.; Agah, M.

    2015-07-01

    The mechanical response of a living cell is notoriously complicated. The complex, heterogeneous characteristics of cellular structure introduce difficulties that simple linear models of viscoelasticity cannot overcome, particularly at deep indentation depths. Herein, a nano-scale stress-relaxation analysis performed with an atomic force microscope reveals that isolated human breast cells do not exhibit simple exponential relaxation capable of being modeled by the standard linear solid (SLS) model. Therefore, this work proposes the application of the fractional Zener (FZ) model of viscoelasticity to extract mechanical parameters from the entire relaxation response, improving upon existing physical techniques to probe isolated cells. The FZ model introduces a new parameter that describes the fractional time-derivative dependence of the response. The results show an exceptional increase in conformance to the experimental data compared to that predicted by the SLS model, and the order of the fractional derivative (α) is remarkably homogeneous across the populations, with a median value of 0.48 ± 0.06 for the malignant population and 0.51 ± 0.07 for the benign. The cells’ responses exhibit power-law behavior and complexity not associated with simple relaxation (SLS, α = 1) that supports the application of a fractional model. The distributions of some of the FZ parameters also preserve the distinction between the malignant and benign sample populations seen from the linear model and previous results while including the contribution of fast-relaxation behavior. The resulting viscosity, measured by a composite relaxation time, exhibits considerably less dispersion due to residual error than the distribution generated by the linear model and therefore serves as a more powerful marker for cell differentiation.

  5. Acute electrophysiological responses of bradykinin-stimulated human fibroblasts.

    PubMed

    Estacion, M

    1991-05-01

    1. Acute responses to bradykinin in human dermal fibroblasts were studied at 20-24 degrees C using both the patch-clamp technique to monitor ion currents and Fura-2 fluorescence to monitor [Ca2+]i. 2. During subconfluent culture, human dermal fibroblasts can express a diversity of ion channels as described in the preceding paper. 3. When GTP (1 mM) was included in the pipette solution, two additional ion channel populations were transiently augmented in response to bradykinin stimulation. 4. The first is a component of outwardly rectifying current which reached maximal induction within 10-15 s after bradykinin addition (1 microM) and then decayed back to near baseline over 60 s. 5. Ion substitution experiments combined with tail current analysis indicate that the outward current is carried predominantly by K+. 6. Video imaging of single-cell Fura-2 fluorescence from both intact cells and patch-clamped cells showed temporal correlation of the K+ current modulation and the Ca2+ transients in response to bradykinin stimulation. 7. The calcium ionophore, ionomycin, caused both an increase in intracellular calcium and the augmentation of the outward K+ current. The amount of additional K+ current was correlated with [Ca2+]i levels and could be elicited even without the presence of GTP in the pipette. 8. Apamin, a blocker of Ca(2+)-activated K+ channels, inhibited (at 1 microM) the ionomycin-induced modulation of K+ current. 9. In addition, an inward current was transiently induced in response to bradykinin. This current was strictly dependent on the presence of GTP in the pipette solution. This current showed little voltage dependence, as evidenced by a linear current vs. voltage relation, and a reversal potential near but measurably more positive than 0 mV. 10. This current could be decoupled from the Ca2+ transient and be irreversibly induced by including GTP gamma S (100 microM) in the pipette solution. 11. Ion substitution experiments show that this is a non

  6. Bone sarcoma in humans induced by radium: A threshold response?

    SciTech Connect

    Rowland, R.E.

    1996-08-01

    The radium 226 and radium 228 have induced malignancies in the skeleton (primarily bone sarcomas) of humans. They have also induced carcinomas in the paranasal sinuses and mastoid air cells. There is no evidence that any leukemias or any other solid cancers have been induced by internally deposited radium. This paper discuses a study conducted on the dial painter population. This study made a concerted effort to verify, for each of the measured radium cases, the published values of the skeletal dose and the initial intake of radium. These were derived from body content measurements made some 40 years after the radium intake. Corrections to the assumed radium retention function resulted in a considerable number of dose changes. These changes have changed the shape of the dose response function. It now appears that the induction of bone sarcomas is a threshold process.

  7. Helicobacter hepaticus Induces an Inflammatory Response in Primary Human Hepatocytes

    PubMed Central

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W. R.; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter spp. on human liver cells, resulting in an inflammatory response with increased synthesis of inflammatory mediators and consecutive monocyte activation. PMID:24932686

  8. Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition.

    PubMed

    Mitchell, W Kyle; Wilkinson, Daniel J; Phillips, Bethan E; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J

    2016-07-01

    Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle "quality" decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies. PMID:27422520

  9. Medial olivocochlear efferent reflex inhibition of human cochlear nerve responses.

    PubMed

    Lichtenhan, J T; Wilson, U S; Hancock, K E; Guinan, J J

    2016-03-01

    Inhibition of cochlear amplifier gain by the medial olivocochlear (MOC) efferent system has several putative roles: aiding listening in noise, protection against damage from acoustic overexposure, and slowing age-induced hearing loss. The human MOC reflex has been studied almost exclusively by measuring changes in otoacoustic emissions. However, to help understand how the MOC system influences what we hear, it is important to have measurements of the MOC effect on the total output of the organ of Corti, i.e., on cochlear nerve responses that couple sounds to the brain. In this work we measured the inhibition produced by the MOC reflex on the amplitude of cochlear nerve compound action potentials (CAPs) in response to moderate level (52-60 dB peSPL) clicks from five, young, normal hearing, awake, alert, human adults. MOC activity was elicited by 65 dB SPL, contralateral broadband noise (CAS). Using tympanic membrane electrodes, approximately 10 h of data collection were needed from each subject to yield reliable measurements of the MOC reflex inhibition on CAP amplitudes from one click level. The CAS produced a 16% reduction of CAP amplitude, equivalent to a 1.98 dB effective attenuation (averaged over five subjects). Based on previous reports of efferent effects as functions of level and frequency, it is possible that much larger effective attenuations would be observed at lower sound levels or with clicks of higher frequency content. For a preliminary comparison, we also measured MOC reflex inhibition of DPOAEs evoked from the same ears with f2's near 4 kHz. The resulting effective attenuations on DPOAEs were, on average, less than half the effective attenuations on CAPs. PMID:26364824

  10. Airway epithelial cell response to human metapneumovirus infection

    SciTech Connect

    Bao, X.; Liu, T.; Spetch, L.; Kolli, D.; Garofalo, R.P.; Casola, A.

    2007-11-10

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-{kappa}B, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immunomodulatory mediators.

  11. AIRWAY EPITHELIAL CELL RESPONSE TO HUMAN METAPNEUMOVIRUS INFECTION

    PubMed Central

    X, Bao; T, Liu; L, Spetch; D, Kolli; R.P, Garofalo; A, Casola

    2007-01-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-κB, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immuno-modulatory mediators. PMID:17655903

  12. The osmotic response of human erythrocytes and the membrane cytoskeleton.

    PubMed

    Heubusch, P; Jung, C Y; Green, F A

    1985-02-01

    The volumes of human erythrocytes suspended in solutions of varying concentrations of sodium chloride and sucrose were measured by a Coulter Channelyzer Model H4 with appropriate corrections. The cells showed greatly restricted volume changes at osmolarities between 200-700 mOsm. At osmolarities outside this limit, on the other hand, the cells showed nonrestricted volume changes following essentially the predictions of an ideal osmometer. This unexpected volume response was not spuriously due to changes in shape or to a changing orientation of the cells as they traversed the aperture. The restricted volume change observed was abolished when the cells had previously been treated with diamide or had been heated for 60 minutes at 50 degrees C, conditions that are known to disturb the spectrin-actin network. The possibility must be considered that the osmotic behavior of human erythrocytes may be nonideal and that this nonideal behavior is primarily due to mechanical restriction provided by the spectrin-actin network of the membrane cytoskeleton. PMID:3918046

  13. Lactic acid delays the inflammatory response of human monocytes

    SciTech Connect

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

    2015-02-13

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

  14. Comparison of Biodynamic Responses in Standing and Seated Human Bodies

    NASA Astrophysics Data System (ADS)

    MATSUMOTO, Y.; GRIFFIN, M. J.

    2000-12-01

    The dynamic responses of the human body in a standing position and in a sitting position have been compared. The apparent mass and transmissibilities to the head, six locations along the spine, and the pelvis were measured with eight male subjects exposed to vertical whole-body vibration. In both postures, the principal resonance in the apparent mass occurred in the range 5-6 Hz, with slightly higher frequencies and lower apparent mass in the standing posture. There was greater transmission of vertical vibration to the pelvis and the lower spine and greater relative motion within the lower spine in the standing posture than in the sitting posture at the principal resonance and at higher frequencies. Transmissibilities from the supporting surface (floor or seat) to the thoracic region had similar magnitudes for both standing and sitting subjects. The lumbar spine has less lordosis and may be more compressed and less flexible in the sitting posture than in the standing posture. This may have reduced the relative motions between lumbar vertebrae and both the supporting vibrating surface and the other vertebrae in the sitting posture. The characteristics of the vibration transmitted to the pelvis may have differed in the two postures due to different transmission paths. Increased forward rotation of the pelvis in the standing posture may have caused the differences in responses of the pelvis and the lower spine that were observed between the two postures.

  15. Analysis of human postural responses to recoverable falls

    NASA Technical Reports Server (NTRS)

    Bortolami, S. B.; DiZio, P.; Rabin, E.; Lackner, J. R.

    2003-01-01

    We studied the kinematics and kinetics of human postural responses to "recoverable falls." To induce brief falling we used a Hold and Release (H&R) paradigm. Standing subjects actively resisted a force applied to their sternum. When this force was quickly released they were suddenly off balance. For a brief period, approximately 125 ms, until restoring forces were generated to shift the center of foot pressure in front of the center of mass, the body was in a forward fall acted on by gravity and ground support forces. We were able to describe the whole-body postural behavior following release using a multilink inverted pendulum model in a regime of "small oscillations." A three-segment model incorporating upper body, upper leg, and lower leg, with active stiffness and damping at the joints was fully adequate to fit the kinematic data from all conditions. The significance of our findings is that in situations involving recoverable falls or loss of balance the earliest responses are likely dependent on actively-tuned, reflexive mechanisms yielding stiffness and damping modulation of the joints. We demonstrate that haptic cues from index fingertip contact with a stationary surface lead to a significantly smaller angular displacement of the torso and a more rapid recovery of balance. Our H&R paradigm and associated model provide a quantifiable approach to studying recovery from potential falling in normal and clinical subjects.

  16. Responsiveness of human varicose saphenous veins to vasoactive agents

    PubMed Central

    Brunner, Friedrich; Hoffmann, Christine; Schuller-Petrovic, Sanja

    2001-01-01

    Aims To test in vitro the constrictor and relaxation responsiveness of variously diseased segments of human saphenous vein from patients with varicose vein disease. Methods The vein segments were derived (i) from the inguinal saphenous vein (valvularly incompetent and slightly dilated; tissue A); (ii) from the distal end of the lower leg just above the medial ankle (competent; tissue B); (iii) from a tributary to the long saphenous vein just below the knee (dilated, incompetent and overtly varicose; tissue C). The contractile responses were tested with phenylephrine (an α-adrenergic receptor agonist) and aescin, a clinically used phlebotonic drug derived from horse chestnut extract. Relaxant responses were tested with acetylcholine and sodium nitroprusside. Results Both contractile agents contracted vein segments from the inguinal and ankle area with similar potency and efficacy, but were virtually without effect in the overtly varicose segments from the calf. EC50 values (molar concentration of the agonist that produces 50% of the maximum effect) in tissues A and B were 2.9 ± 0.3 and 2.5 ± 0.5 µmol l−1 (phenylephrine) and 9.4 ± 1.0 and 15.9 ± 2.5 µmol l−1 (aescin); the corresponding maximum effects (maximum effect, percent of KCl-induced contraction) were 76 ± 3 and 70 ± 4% (phenylephrine) and 70 ± 2 and 71 ± 3% (aescin) (P = NS in both cases for A vs B). In tissue C, the maximum effects were 5 ± 5% (phenylephrine) and 10 ± 7% (aescin) of KCl-induced contraction (not significantly different from zero). Acetylcholine-induced relaxation was similar for vein segments from locations A and B, whereas sodium nitroprusside was more effective in tissue B than A. Conclusions These findings support the notion that abnormalities within the venous wall affect venous smooth muscle contractility. Since competent and incompetent clinically normal vessels show normal contractile responses, whereas varicose vessels are not responsive to vasoactive drugs, it is

  17. Human arm posture prediction in response to isometric endpoint forces.

    PubMed

    Davoudabadi Farahani, Saeed; Andersen, Michael Skipper; de Zee, Mark; Rasmussen, John

    2015-11-26

    The ability to predict the musculoskeletal response to external loads has multiple applications for the design of machines with a human interface and for the prediction of outcomes of musculoskeletal interventions. In this study, we applied an inverse-inverse dynamics technique to investigate its ability to predict arm posture in response to isometric hand forces. For each subject, we made a three-dimensional musculoskeletal model using the AnyBody Modelling System (AMS). Then, we had each subject-specific model hold a weight anteriorly to the right shoulder joint at a distance of half of the arm length. We selected the glenohumeral abduction angle (GHAA) as the only free parameter. Subsequently, we used inverse-inverse dynamics to find the optimal GHAA that minimised a performance criterion with physiological constraints. In this study, we investigated the performance of two different objective functions: summation of squared muscle activity (SSMA) and summation of squared normalised joint torques (SSNJT). To validate the simulation results, arm posture responses to different isometric downward hand forces were measured for six healthy male subjects. Five trials were performed for each loading condition. The results showed that, with an increase in hand load, there was a reduced GHAA in all subjects. Another interesting finding was that self-selected postures for lighter tasks varied more than postures for heavier tasks for all subjects. To understand this, we investigated the curvature of the objective function as a function of the load and observed an increased curvature with increased load. This may explain the reduced intra-subject variations observed for increasing loads. PMID:26482735

  18. Human Response to Simulated Low-Intensity Sonic Booms

    NASA Technical Reports Server (NTRS)

    Sullivan, Brenda M.

    2004-01-01

    NASA's High Speed Research (HSR ) program in the 1990s was intended to develop a technology base for a future High-Speed Civil Transport (HSCT). As part of this program, the NASA Langley Research Center sonic boom simulator (SBS) was built and used for a series of tests on subjective response to sonic booms. At the end of the HSR program, an HSCT was deemed impractical, but since then interest in supersonic flight has reawakened, this time focusing on a smaller aircraft suitable for a business jet. To respond to this interest, the Langley sonic boom simulator has been refurbished. The upgraded computer-controlled playback system is based on an SGI O2 computer, in place of the previous DEC MicroVAX. As the frequency response of the booth is not flat, an equalization filter is required. Because of the changes made during the renovation (new loudspeakers), the previous equalization filter no longer performed as well as before, so a new equalization filter has been designed. Booms to be presented in the booth are preprocessed using the filter. When the preprocessed signals are presented into the booth and measured with a microphone, the results are very similar to the intended shapes. Signals with short rise times and sharp "corners" are observed to have a small amount of "ringing" in the response. During the HSR program a considerable number of subjective tests were completed in the SBS. A summary of that research is given in Leatherwood et al. (Individual reports are available at http://techreports.larc.nasa.gov/ltrs/ltrs.html.) Topics of study included shaped sonic booms, asymmetrical booms, realistic (recorded) boom waveforms, indoor and outdoor booms shapes, among other factors. One conclusion of that research was that a loudness metric, like the Stevens Perceived Level (PL), predicted human reaction much more accurately than overpressure or unweighted sound pressure level. Structural vibration and rattle were not included in these studies.

  19. Clinical iron deficiency disturbs normal human responses to hypoxia

    PubMed Central

    Frise, Matthew C.; Cheng, Hung-Yuan; Nickol, Annabel H.; Curtis, M. Kate; Pollard, Karen A.; Roberts, David J.; Ratcliffe, Peter J.; Dorrington, Keith L.; Robbins, Peter A.

    2016-01-01

    BACKGROUND. Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. METHODS. We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography. RESULTS. Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7–9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, –8.3 to –0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups. CONCLUSION. Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01847352). FUNDING. M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was

  20. IMMEDIATE HUMAN PULP RESPONSE TO ETHANOL-WET BONDING TECHNIQUE

    PubMed Central

    Scheffel, Débora Lopes Salles; Sacono, Nancy Tomoko; Ribeiro, Ana Paula Dias; Soares, Diana Gabriela; Basso, Fernanda Gonçalves; Pashley, David Henry; Costa, Carlos Alberto de Souza; Hebling, Josimeri

    2016-01-01

    Objective To evaluate the short-term response of human pulps to ethanol-wet bonding technique associated with an etch-and-rinse adhesive system. Methods Deep class V cavities were prepared on the buccal surface of 17 sound premolars scheduled for extraction for orthodontics. The teeth were assigned into three groups: Ethanol-wet bonding (G1), water-wet bonding (G2) and calcium hydroxide (G3, control). Two teeth were used as intact control. After acid-etching, the cavities from G1 were filled with 100% ethanol for 60s and blot-dried before the application of Single Bond 2. In G2, the cavities were filled with distilled water for 60s previously to adhesive application and in G3, the cavity floor was lined with calcium hydroxide before etching and bonding. All cavities were restored with resin composite. The teeth were extracted 48h after the clinical procedures. From each tooth 6 μm-thick serial sections were obtained and stained with hematoxylin and eosin (H/E) and Masson's trichrome. Bacteria microleakage was assessed using Brown & Brenn. All sections were blindly evaluated and scored for five histological features. Results Mean remaining dentin thickness was 463±65μm (G1); 425±184μm (G2); and 348±194μm (G3). Similar pulp reactions followed ethanol- or water-wet bonding techniques. Slight inflammatory responses and disruption of the odontoblast layer related to the cavity floor were seen in all groups. Stained bacteria were not detected in any cavities. Normal pulp tissue was observed in G3 except for one case. Conclusions After 48 h, ethanol-wet bonding technique applied on deep cavities prepared in vital teeth does not increase pulpal damage compared to water-wet bonding technique. Clinical significance Ethanol-wet bonding has been considered an experimental technique that may increase resin-dentin bond durability. This study reported the in vivo response of human pulp tissue when 100% ethanol was applied previously to an etch-and-rinse simplified adhesive

  1. Multiprocessing computer system for sensory evoked potentials and EEG spectral analysis for clinical neurophysiology laboratory.

    PubMed

    Steben, J D; Streletz, L J; Fariello, R G

    1985-12-01

    A general-purpose minicomputer has been adapted and interfaced for the averaging and analysis of clinical evoked potentials and for compressed spectral arrays (CSA) of the routine EEG. In the first 2 years of operation, over 1,000 routine clinical studies of visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) have been performed with it, as well as over 100 CSAs and a variety of special and research studies. The CSA modality gives comparative frequency-domain pictures of left and right hemisphere power. An attached graphics terminal gives a live cumulative display of the EP and CSA. In addition, the system has automated and comprehensive physician-interactive graphics analysis and report generation capabilities. The reports are finalized versions used in the patient's chart, minimizing clerical efforts. PMID:3841553

  2. Activated human neutrophil response to perfluorocarbon nanobubbles: oxygen-dependent and -independent cytotoxic responses.

    PubMed

    Hwang, Tsong-Long; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Li-Jia; Fang, Jia-You

    2011-06-10

    Nanobubbles, a type of nanoparticles with acoustically active properties, are being utilized as diagnostic and therapeutic nanoparticles to better understand, detect, and treat human diseases. The objective of this work was to prepare different nanobubble formulations and investigate their physicochemical characteristics and toxic responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated human neutrophils. The nanobubbles were prepared using perfluoropentane and coconut oil as the respective core and shell, with soybean phosphatidylcholine (SPC) and/or cationic surfactants as the interfacial layers. The cytotoxic effect of the nanobubbles on neutrophils was determined by extracellular O₂(.)⁻ release, intracellular reactive oxygen species (ROS), lactate dehydrogenase (LDH), and elastase release. Particle sizes of the nanobubbles with different percentages of perfluorocarbon, oil, and surfactants in ranged 186-432 nm. The nanobubbles were demonstrated to inhibit the generation of superoxide and intracellular ROS. The cytotoxicity of nanobubbles may be mainly associated with membrane damage, as indicated by the high LDH leakage. Systems with Forestall (FE), a cationic surfactant, or higher SPC contents exhibited the greatest LDH release by 3-fold compared to the control. The further addition of an oil component reduced the cytotoxicity induced by the nanobubbles. Exposure to most of the nanobubble formulations upregulated elastase release by activated neutrophils. Contrary to this result, stearylamine (SA)-containing systems slightly but significantly suppressed elastase release. FE and SA in a free form caused stronger responses by neutrophils than when they were incorporated into nanobubbles. In summary, exposure to nanobubbles resulted in a formulation-dependent toxicity toward human neutrophils that was associated with both oxygen-dependent and -independent pathways. Clinicians should therefore exercise caution when using nanobubbles in patients

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

    PubMed

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

    2014-05-01

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

  4. Response of human cells to desiccation: comparison with hyperosmotic stress response

    PubMed Central

    Huang, Zebo; Tunnacliffe, Alan

    2004-01-01

    Increasing interest in anhydrobiosis (‘life without water’) has prompted the use of mammalian cells as a model in which candidate adaptations suspected of conferring desiccation tolerance can be tested. Despite this, there is no information on whether mammalian cells are able to sense and respond to desiccation. We have therefore examined the effect of desiccation on stress signalling pathways and on genes which are proposed to be expressed in response to water loss through osmotic stress. Depending on the severity of the drying regime, human cells survived for at least 24 h. Both SAPK/JNK and p38 mitogen-activated protein kinases (MAPKs) were activated within 30 min by desiccation as well as by all osmotica tested, and therefore MAPK pathways probably play an important role in both responses. Gene induction profiles differed under the two stress conditions, however: quantitative polymerase chain reaction (PCR) experiments showed that AR, BGT-1 and SMIT, which encode proteins governing organic osmolyte accumulation, were induced by hypersalinity but not by desiccation. This was surprising, since these genes have been proposed to be regulated by ionic strength and cell volume, both of which should be significantly affected in drying cells. Further investigation demonstrated that AR, BGT-1 and SMIT expression was dependent on the nature of the osmolyte. This suggests that their regulation involves factors other than intracellular ionic strength and cell volume changes, consistent with the lack of induction by desiccation. Our results show for the first time that human cells react rapidly to desiccation by MAPK activation, and that the response partially overlaps with that to hyperosmotic stress. PMID:15146043

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

    PubMed Central

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

    2013-01-01

    Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity and accelerated reproduction, both based on the idea of predictive adaptive responses (PARs). According to external PAR hypotheses, early-life adversity provides a ‘weather forecast’ of the environmental conditions into which the individual will mature, and it is adaptive for the individual to develop an appropriate phenotype for this anticipated environment. In internal PAR hypotheses, early-life adversity has a lasting negative impact on the individual's somatic state, such that her health is likely to fail more rapidly as she gets older, and there is an advantage to adjusting her reproductive schedule accordingly. We use a model of fluctuating environments to derive evolveability conditions for acceleration of reproductive timing in response to early-life adversity in a long-lived organism. For acceleration to evolve via the external PAR process, early-life cues must have a high degree of validity and the level of annual autocorrelation in the individual's environment must be almost perfect. For acceleration to evolve via the internal PAR process requires that early-life experience must determine a significant fraction of the variance in survival prospects in adulthood. The two processes are not mutually exclusive, and mechanisms for calibrating reproductive timing on the basis of early experience could evolve through a combination of the predictive value of early-life adversity for the later environment and its negative impact on somatic state. PMID:23843395

  6. Human thermal physiological and psychological responses under different heating environments.

    PubMed

    Wang, Zhaojun; Ning, Haoran; Ji, Yuchen; Hou, Juan; He, Yanan

    2015-08-01

    Anecdotal evidence suggests that many residents of severely cold areas of China who use floor heating (FH) systems feel warmer but drier compared to those using radiant heating (RH) systems. However, this phenomenon has not been verified experimentally. In order to validate the empirical hypothesis, and research the differences of human physiological and psychological responses in these two asymmetrical heating environments, an experiment was designed to mimic FH and RH systems. The subjects participating in the experiment were volunteer college-students. During the experiment, the indoor air temperature, air speed, relative humidity, globe temperature, and inner surface temperatures were measured, and subjects' heart rate, blood pressure and skin temperatures were recorded. The subjects were required to fill in questionnaires about their thermal responses during testing. The results showed that the subjects' skin temperatures, heart rate and blood pressure were significantly affected by the type of heating environment. Ankle temperature had greatest impact on overall thermal comfort relative to other body parts, and a slightly cool FH condition was the most pleasurable environment for sedentary subjects. The overall thermal sensation, comfort and acceptability of FH were higher than that of RH. However, the subjects of FH felt drier than that of RH, although the relative humidity in FH environments was higher than that of the RH environment. In future environmental design, the thermal comfort of the ankles should be scrutinized, and a FH cool condition is recommended as the most comfortable thermal environment for office workers. Consequently, large amounts of heating energy could be saved in this area in the winter. The results of this study may lead to more efficient energy use for office or home heating systems. PMID:26267512

  7. Acute hypoxemia in humans enhances the neutrophil inflammatory response.

    PubMed

    Tamura, Douglas Y; Moore, Ernest E; Partrick, David A; Johnson, Jeffrey L; Offner, Patrick J; Silliman, Christopher C

    2002-04-01

    The neutrophil (PMN) is regarded as a key component in the hyperinflammatory response known as the systemic inflammatory response syndrome. Acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF) are related to the severity of this hyperinflammation. ICU patients who are at highest risk of developing MOF may have acute hypoxic events that complicate their hospital course. This study was undertaken to evaluate the effects of acute hypoxia and subsequent hypoxemia on circulating PMNs in human volunteers. Healthy subjects were exposed to a changing O2/N2 mixture until their O2 saturation (SaO2) reached a level of 68% saturation. These subjects were then exposed to room air and then returned to their baseline SaO2. PMNs were isolated from pre- and post-hypoxemic arterial blood samples and were then either stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or PMA alone, or they were primed with L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF) followed by fMLP activation. Reactive oxygen species generation as measured by superoxide anion production was enhanced in primed PMNs after hypoxemia. Protease degranulation as measured by elastase release was enhanced in both quiescent PMNs and primed PMNs after fMLP activation following the hypoxemic event. Adhesion molecule upregulation as measured by CD11b/CD18, however, was not significantly changed after hypoxemia. Apoptosis of quiescent PMNs was delayed after the hypoxemic event. TNFalpha, IL-1, IL-6, and IL-8 cytokine levels were unchanged following hypoxemia. These results indicate that relevant acute hypoxemic events observed in the clinical setting enhance several PMN cytotoxic functions and suggest that a transient hypoxemic insult may promote hyperinflammation. PMID:11954825

  8. Analysis of Human Innate Immune Responses to PRINT Fabricated Nanoparticles with Cross Validation Using a Humanized Mouse Model

    PubMed Central

    Robbins, GR; Roberts, RA; Guo, H; Reuter, K; Shen, T; Sempowski, GD; McKinnon, Karen P.; Su, L; DeSimone, JM; Ting, JP

    2015-01-01

    Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14+ monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells (hu-PBMC) suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor do they induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14+ monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity. PMID:25596079

  9. Proteomic analysis of human osteoprogenitor response to disordered nanotopography

    PubMed Central

    Kantawong, Fahsai; Burchmore, Richard; Gadegaard, Nikolaj; Oreffo, Richard O. C.; Dalby, Matthew J.

    2009-01-01

    Previous studies have shown that microgroove-initiated contact guidance can induce bone formation in osteoprogenitor cells (OPGs) and produce changes in the cell proteome. For proteomic analysis, differential in-gel electrophoresis (DIGE) can be used as a powerful diagnostic method to provide comparable data between the proteomic profiles of cells cultured in different conditions. This study focuses on the response of OPGs to a novel nanoscale pit topography with osteoinductive properties compared with planar controls. Disordered near-square nanopits with 120 nm diameter and 100 nm depth with an average 300 nm centre-to-centre spacing (300 nm spaced pits in square pattern, but with ±50 nm disorder) were fabricated on 1×1 cm2 polycaprolactone sheets. Human OPGs were seeded onto the test materials. DIGE analysis revealed changes in the expression of a number of distinct proteins, including upregulation of actin isoforms, beta-galectin1, vimentin and procollagen-proline, 2-oxoglutarate 4-dioxygenase and prolyl 4-hydroxylase. Downregulation of enolase, caldesmon, zyxin, GRASP55, Hsp70 (BiP/GRP78), RNH1, cathepsin D and Hsp27 was also observed. The differences in cell morphology and mineralization are also reported using histochemical techniques. PMID:19068473

  10. Diurnal variations in the human host response to endotoxin.

    PubMed

    Pollmächer, T; Mullington, J; Korth, C; Schreiber, W; Hermann, D; Orth, A; Galanos, C; Holsboer, F

    1996-11-01

    To investigate diurnal variations in the host response to endotoxin, Salmonella abortus equi endotoxin (0.8 ng/kg) was given intravenously to healthy men in a placebo-controlled design at 0900 or 1900 h. The time course of rectal temperature and the plasma levels of tumor necrosis factor- alpha (TNF-alpha), interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), and cortisol were monitored for 11 h following the injections. The time of day did not affect the endotoxin-induced increase in plasma TNF-alpha or IL-6. However, subjects who received endotoxin in the evening, when endogenous glucocorticoid levels were low, showed about twice the increases in rectal temperature and plasma ACTH and cortisol levels as those who received endotoxin in the morning, when endogenous glucocorticoid levels were high. These results demonstrate diurnal variations in the human susceptibility to endotoxin that may be due to a suppression of the biologic effects of TNF-alpha and IL-6 by endogenous glucocorticoids. PMID:8896506

  11. Hsp60 response in experimental and human temporal lobe epilepsy

    PubMed Central

    Gammazza, Antonella Marino; Colangeli, Roberto; Orban, Gergely; Pierucci, Massimo; Di Gennaro, Giancarlo; Bello, Margherita Lo; D'Aniello, Alfredo; Bucchieri, Fabio; Pomara, Cristoforo; Valentino, Mario; Muscat, Richard; Benigno, Arcangelo; Zummo, Giovanni; de Macario, Everly Conway; Cappello, Francesco; Di Giovanni, Giuseppe; Macario, Alberto J. L.

    2015-01-01

    The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management. PMID:25801186

  12. Eicosanoid generation and responsiveness of human lymphatics in hyperlipoproteinemia.

    PubMed

    Oguogho, A; Kaliman, J; Sinzinger, H

    2000-01-01

    In this work, the oxidation injury in hyperlipoproteinemia (HLP) was determined by measuring the isoprostane 8-epi-prostaglandin (PG) F2alpha in human lymphatics, lymph fluid, plasma, serum and urine. Lymphatics from 6 patients with HLP generated less PGI2 and contained more 8-epi-PGF2alpha as compared to 6 normolipemics without risk factors. Likewise, plasma (29.3 vs 19.7 pg/ml), lymph fluid (137.3 vs 65.3 pg/ml), serum (286.7 vs 204.1 pg/ml) and urinary (360.8 vs 241.0 pg/mg creatinine) values of 8-epi-PGF2alpha in HLP (as compared to normolipemics) were significantly elevated. Lymphatics from HLP showed an enhanced contractile response, less 14C-arachidonic acid conversion to PGI2 and less PGI2-formation upon various stimuli compared to normolipemics of comparable age. These findings indicate that HLP-induced oxidation injury, resulting in an altered (iso-)eicosanoid production and function, may also significantly affect (patho-) physiology of lymphathics. PMID:10765978

  13. Unfolded protein response in Gaucher disease: from human to Drosophila

    PubMed Central

    2013-01-01

    Background In Gaucher disease (GD), resulting from mutations in the GBA gene, mutant β-glucocerebrosidase (GCase) molecules are recognized as misfolded in the endoplasmic reticulum (ER). They are retrotranslocated to the cytoplasm, where they are ubiquitinated and undergo proteasomal degradation in a process known as the ER Associated Degradation (ERAD). We have shown in the past that the degree of ERAD of mutant GCase correlates with GD severity. Persistent presence of mutant, misfolded protein molecules in the ER leads to ER stress and evokes the unfolded protein response (UPR). Methods We investigated the presence of UPR in several GD models, using molecular and behavioral assays. Results Our results show the existence of UPR in skin fibroblasts from GD patients and carriers of GD mutations. We could recapitulate UPR in two different Drosophila models for carriers of GD mutations: flies heterozygous for the endogenous mutant GBA orthologs and flies expressing the human N370S or L444P mutant GCase variants. We encountered early death in both fly models, indicating the deleterious effect of mutant GCase during development. The double heterozygous flies, and the transgenic flies, expressing mutant GCase in dopaminergic/serotonergic cells developed locomotion deficit. Conclusion Our results strongly suggest that mutant GCase induces the UPR in GD patients as well as in carriers of GD mutations and leads to development of locomotion deficit in flies heterozygous for GD mutations. PMID:24020503

  14. Assessing large-scale wildlife responses to human infrastructure development.

    PubMed

    Torres, Aurora; Jaeger, Jochen A G; Alonso, Juan Carlos

    2016-07-26

    Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future. PMID:27402749

  15. In vitro response of human fibroblasts to commercially pure titanium.

    PubMed

    Mostardi, R A; Meerbaum, S O; Kovacik, M W; Gradisar, I A

    1999-10-01

    The generation of metal particles through surface wear of prosthetic joints has been associated with biological reactions that may lead to prosthetic component loosening. The role of the macrophage in these reactions has been studied extensively, but that of the fibroblast has not. The few fibroblast studies that there have been have shown that particles of several metals, with sizes over a wide range, can promote cytokine release and may cause cell necrosis. The intent of this study was to determine if there are metal particle exposure threshold levels that result in morphological changes and cell necrosis of fibroblasts in peri-articular tissues. Retrieved human fibroblasts (superior medial plica) were cultured in standard fashion and then were exposed to various particle dosages of commercially pure Titanium (cpTi). Cell morphological changes and necrosis were observed to occur when the total mass of the particle dosage exceeded a threshold level. These data imply that these cell responses occur at threshold levels of wear particle exposure. PMID:10400881

  16. Studying the immune response to human viral infections using zebrafish

    PubMed Central

    Goody, Michelle F.; Sullivan, Con; Kim, Carol H.

    2014-01-01

    Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish. PMID:24718256

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

    NASA Technical Reports Server (NTRS)

    Sundaresan, A.; Pellis, N. R.

    2005-01-01

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

  18. Response of human macrophages to wound matrices in vitro.

    PubMed

    Witherel, Claire E; Graney, Pamela L; Freytes, Donald O; Weingarten, Michael S; Spiller, Kara L

    2016-05-01

    Chronic wounds remain a major burden to the global healthcare system. Myriad wound matrices are commercially available but their mechanisms of action are poorly understood. Recent studies have shown that macrophages are highly influenced by their microenvironment, but it is not known how different biomaterials affect this interaction. Here, it was hypothesized that human macrophages respond differently to changes in biomaterial properties in vitro with respect to phenotype, including pro-inflammatory M1, anti-inflammatory M2a, known for facilitating extracellular matrix deposition and proliferation, and M2c, which has recently been associated with tissue remodeling. Using multiple donors, it was found that collagen scaffolds cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) promoted the least inflammatory phenotype in primary human macrophages compared with scaffolds cross-linked with formaldehyde or glutaraldehyde. Importantly, gene expression analysis trends were largely conserved between donors, especially TNFa (M1), CCL22 (M2a), and MRC1 (M2a). Then the response of primary and THP1 monocyte-derived macrophages to four commercially available wound matrices were compared-Integra Dermal Regeneration Template (Integra), PriMatrix Dermal Repair Scaffold (PriMatrix), AlloMend Acellular Dermal Matrix (AlloMend), and Oasis Wound Matrix (Oasis). Gene expression trends were different between primary and THP1 monocyte-derived macrophages for all six genes analyzed in this study. Finally, the behavior of primary macrophages cultured onto the wound matrices over time was analyzed. Integra and Oasis caused down-regulation of M2a markers CCL22 and TIMP3. PriMatrix caused up-regulation of TNFa (M1) and CD163 (M2c) and down-regulation of CCL22 and TIMP3 (both M2a). AlloMend caused up-regulation in CD163 (M2c). Lastly, Oasis promoted the largest increase in the combinatorial M1/M2 score, defined as the sum of M1 genes divided by

  19. Not quite human: infrahumanization in response to collective responsibility for intergroup killing.

    PubMed

    Castano, Emanuele; Giner-Sorolla, Roger

    2006-05-01

    The present research examines how awareness of violence perpetrated against an out-group by one's in-group can intensify the infrahumanization of the out-group, as measured by a reduced tendency to accord uniquely human emotions to out-groups. Across 3 experiments that used different in-groups (humans, British, White Americans) and out-groups (aliens, Australian Aborigines, and Native Americans), when participants were made aware of the in-group's mass killing of the out-group, they infrahumanized the victims more. The perception of collective responsibility, not just the knowledge that the out-group members had died in great numbers, was shown to be necessary for this effect. Infrahumanization also occurred concurrently with increased collective guilt but was unrelated to it. It is proposed that infrahumanization may be a strategy for people to reestablish psychological equanimity when confronted with a self-threatening situation and that such a strategy may occur concomitantly with other strategies, such as providing reparations to the out-group. PMID:16737374

  20. Biphasic Response of Ciprofloxacin in Human Fibroblast Cell Cultures

    PubMed Central

    Hincal, Filiz; Gürbay, Aylin; Favier, Alain

    2003-01-01

    To investigate the possibility of the involvement of an oxidative stress induction in the mechanism of the cytotoxic effect of quinolone antibiotics, we examined the viability of human fibroblast cells exposed to ciprofloxacin (CPFX), and measured the levels of lipid peroxidation (LP), glutathione (GSH), and the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX). The data showed that the effect of CPFX on the viability of cells, as determined by neutral red uptake assay, was time-dependent, and the dose-response relation was biphasic. Cytotoxicity was not observed in the concentration range 5–150 mg/l CPFX when the cells were incubated for 24 h. In contrast, lower concentrations (5 and 12.5 mg/l) of CPFX increased the cell growth in all incubation periods tested. Marked decreases in the viability of fibroblasts were observed at concentrations 50 and 75 mg/l, and ≥50 mg/l, following 48 and 72 h exposure, respectively (p < 0.05). However, when the cells were exposed to > 75 mg/l CPFX for 48 h, no cytotoxicity was observed. By exposing fibroblast cultures to 75 mg/l CPFX for 48 h, an induction of LP enhancement and a marked decrease in intracellular GSH were observed. Vitamin E pretreatment of the cells lowered the level of LP, increased the total GSH content, and provided significant protection against CPFX-induced cytotoxicity. The biphasic effect of CPFX possibly resulted from the complex dose-dependent relationships between reactive oxygen species (ROS), cell proliferation, and cell viability. It was previously reported, in fact, for several cell models that ROS exert a biphasic effect on cell growth. Furthermore, cultured fibroblasts release their own free radicals, and the inhibition of endogenous ROS inhibits the fibroblast cell proliferation, whereas the effect of exogenous ROS is biphasic. PMID:19330132

  1. Escherichia coli ghosts promote innate immune responses in human keratinocytes.

    PubMed

    Abtin, Arby; Kudela, Pavol; Mayr, Ulrike Beate; Koller, Verena Juliana; Mildner, Michael; Tschachler, Erwin; Lubitz, Werner

    2010-09-10

    Bacterial ghosts (BGs) as non-living bacterial envelopes devoid of cytoplasmic content with preserved and intact inner and outer membrane structures of their living counterparts have been used to study the ability of their surface components for the induction of antimicrobial peptides and pro-inflammatory cytokines in human primary keratinocytes (KCs). Quantitative real-time PCR analysis revealed that incubation of KCs with BGs generated from wild-type Escherichia coli induced the mRNA expression of antimicrobial psoriasin (S100A7c) in a BGs particle concentration-dependent manner. Using immunoblot analysis we showed that BGs generated from the flagellin-deficient (ΔFliC) E. coli strain NK9375 were as effective as its isogenic wild-type (wt) E. coli strain NK9373 to induce psoriasin expression when normalized to BG particles being taken up by KCs. However, results obtained from endocytic activity of KCs reflect that internalization of BGs is greatly dependent on the presence of flagellin on the surface of BGs. Moreover, BGs derived from wt E. coli NK9373 strongly induced the release of the pro-inflammatory cytokines IL-6 and IL-8, compared to ΔFliC E. coli NK9375 BGs. Taken together, obtained data demonstrate that non-living BGs possessing all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat have the capacity to induce the expression of innate immune modulators and that these responses are partially dependent on the presence of flagellin. PMID:20696136

  2. Radiation response of cultured human cells is unaffected by Johrei.

    PubMed

    Hall, Zach; Luu, Tri; Moore, Dan; Yount, Garret

    2007-06-01

    Johrei has been credited with healing thousands from radiation wounds after the Hiroshima and Nagasaki bombs in 1945. This alternative medical therapy is becoming increasingly popular in the United States, as are other Energy Medicine modalities that purport to influence a universal healing energy. Human brain cells were cultured and exposed to increasing doses of ionizing radiation. Experienced Johrei practitioners directed healing intentionality toward the cells for 30 min from a distance of 20 cm and the fate of the cells was observed by computerized time-lapse microscopy. Cell death and cell divisions were tallied every 30 min before, during and after Johrei treatment for a total of 22.5 h. An equal number of control experiments were conducted in which cells were irradiated but did not receive Johrei treatment. Samples were assigned to treatment conditions randomly and data analysis was conducted in a blinded fashion. Radiation exposure decreased the rate of cell division (cell cycle arrest) in a dose-dependent manner. Division rates were estimated for each 30 min and averaged over 8 independent experiments (4 control and 4 with Johrei treatment) for each of 4 doses of X-rays (0, 2, 4 and 8 Gy). Because few cell deaths were observed, pooled data from the entire observation period were used to estimate death rates. Analysis of variance did not reveal any significant differences on division rate or death rate between treatment groups. Only radiation dose was statistically significant. We found no indication that the radiation response of cultured cells is affected by Johrei treatment. PMID:17549235

  3. Cue Set Stimulation as a Factor in Human Response Generation.

    ERIC Educational Resources Information Center

    Petelle, John L.

    The hypotheses that there will be a significant difference (1) in the number of responses generated according to economic issues, (2) in the number of responses generated according to social issues, (3) in the number of responses generated between the category of economic issues and the category of social issues, (4) in cue ranking by response…

  4. The human rights responsibilities of multinational tobacco companies

    PubMed Central

    Crow, M

    2005-01-01

    This article explores various strategies which could be used to hold the tobacco industry accountable for human rights violations precipitated by its conduct. First, a brief overview of the international human rights regime and the tobacco related jurisprudence issued by human rights treaty bodies is provided. The article then explains how tobacco control advocates could promote more systematic consideration of governments' tobacco related human rights violations by reconceptualising the Framework Convention on Tobacco Control in the language of rights. The feasibility of using the existing human rights framework to target the tobacco industry directly is analysed with the conclusion that this approach has serious limitations. Emerging human rights norms, which have greater potential to affect the industry's conduct, are presented. Finally, given the questionable authoritativeness of these norms, alternative ways that they could be employed to hold tobacco companies accountable for the rights related consequences of their activities are proposed. PMID:16046696

  5. A Study on the Impact of Fatigue on Human Raters When Scoring Speaking Responses

    ERIC Educational Resources Information Center

    Ling, Guangming; Mollaun, Pamela; Xi, Xiaoming

    2014-01-01

    The scoring of constructed responses may introduce construct-irrelevant factors to a test score and affect its validity and fairness. Fatigue is one of the factors that could negatively affect human performance in general, yet little is known about its effects on a human rater's scoring quality on constructed responses. In this study, we…

  6. Development of the dose-response relationship for human toxoplasma gondii infection associated with meat consumption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States.A substantial portion of human T. gondii infections may be acquired through the consumption of meats. The dose-response relationship for human exposure...

  7. 24 CFR 7.14 - Responsibilities of the Office of Human Resources.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... CFR part 1614; (7) An explanation of the recourse available where noncompliance by the Department is... 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...

  8. 24 CFR 7.14 - Responsibilities of the Office of Human Resources.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... CFR part 1614; (7) An explanation of the recourse available where noncompliance by the Department is... 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...

  9. 24 CFR 7.14 - Responsibilities of the Office of Human Resources.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... CFR part 1614; (7) An explanation of the recourse available where noncompliance by the Department is... 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...

  10. 24 CFR 7.14 - Responsibilities of the Office of Human Resources.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... CFR part 1614; (7) An explanation of the recourse available where noncompliance by the Department is... 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...

  11. Initial description of a quantitative, cross-species (chimpanzee-human) social responsiveness measure

    PubMed Central

    Marrus, Natasha; Faughn, Carley; Shuman, Jeremy; Petersen, Steve; Constantino, John; Povinelli, Daniel; Pruett, John R.

    2011-01-01

    Objective Comparative studies of social responsiveness, an ability that is impaired in autistic spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. Method We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimp SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n=29) with the Chimp SRS and typical and autistic spectrum disorder (ASD) human children (n=20) with the XSRS. Results The Chimp SRS demonstrated strong inter-rater reliability at the three sites (ranges for individual ICCs: .534–.866 and mean ICCs: .851–.970). As has been observed in humans, exploratory principal components analysis of Chimp SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r=.976, p=.001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. Conclusion Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) humans and chimpanzees. PMID:21515200

  12. Elastin sequences trigger transient proinflammatory responses by human dermal fibroblasts

    PubMed Central

    Almine, Jessica F.; Wise, Steven G.; Hiob, Matti; Singh, Neeraj Kumar; Tiwari, Krishna Kumar; Vali, Shireen; Abbasi, Taher; Weiss, Anthony S.

    2013-01-01

    of elastin as a result of dermal damage leads to rapid chemokine up-regulation by fibroblasts that is quenched when exposed elastin is removed by MMP-12.—Almine, J. F., Wise, S. G., Hiob, M., Kumar Singh, N. K., Tiwari, K. K., Vali, S., Abbasi, T., and Weiss, A. S. Elastin sequences trigger transient proinflammatory responses by human dermal fibroblasts. PMID:23671273

  13. Comparison of Hybrid-III and postmortem human surrogate response to simulated underbody blast loading.

    PubMed

    Bailey, Ann Marie; Christopher, John J; Salzar, Robert S; Brozoski, Frederick

    2015-05-01

    Response of the human body to high-rate vertical loading, such as military vehicle underbody blast (UBB), is not well understood because of the chaotic nature of such events. The purpose of this research was to compare the response of postmortem human surrogates (PMHS) and the Hybrid-III anthropomorphic test device (ATD) to simulated UBB loading ranging from 100 to 860 g seat and floor acceleration. Data from 13 whole body PMHS tests were used to create response corridors for vertical loading conditions for the pelvis, T1, head, femur, and tibia; these responses were compared to Hybrid-III responses under matched loading conditions. PMID:25751733

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

    PubMed

    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. PMID:22789042

  15. Divergence of human and nonhuman primate lymphocyte responses to bacterial superantigens.

    PubMed

    Bavari, S; Hunt, R E; Ulrich, R G

    1995-09-01

    We compared T cell responses of human, rhesus monkey (Macaca mulatta), and chimpanzee (Pan troglodytes) to four bacterial superantigens. When lymphocytes were cultured in media supplemented with species-specific sera, chimpanzee T cells were stimulated by lower doses of staphylococcal enterotoxin (SE) A and toxic shock syndrome toxin 1 (TSST1) than were human T cells, while chimpanzee responses to SEB and SEC1 were nearly equivalent to the human response. Interestingly, rhesus lymphocytes responded to 10,000 times lower amounts of SEA, SEB, and SEC1 and to 100 times lower concentrations of TSST1 than human cells. The greater sensitivity of rhesus T cells to these toxins was not a result of differences in class II binding affinities and was only partly attributable to the presence of anti-SE and TSST1 antibodies in human serum. These results suggest that rhesus T lymphocytes are more sensitive toward these bacterial superantigens than human T cells. PMID:7554446

  16. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  17. Experimental quantification of the tactile spatial responsivity of human cornea.

    PubMed

    Beiderman, Yevgeny; Belkin, Michael; Rotenstreich, Ygal; Zalevsky, Zeev

    2015-01-01

    We present the first experimental quantification of the tactile spatial responsivity of the cornea and we teach a subject to recognize spatial tactile shapes that are stimulated on their cornea. PMID:26158088

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

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro- reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venotis Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 q 1.71, -4.36 q 1.38, and -2.56 q 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulnionary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  19. Mycobacterial infection induces a specific human innate immune response

    PubMed Central

    Blischak, John D.; Tailleux, Ludovic; Mitrano, Amy; Barreiro, Luis B.; Gilad, Yoav

    2015-01-01

    The innate immune system provides the first response to infection and is now recognized to be partially pathogen-specific. Mycobacterium tuberculosis (MTB) is able to subvert the innate immune response and survive inside macrophages. Curiously, only 5–10% of otherwise healthy individuals infected with MTB develop active tuberculosis (TB). We do not yet understand the genetic basis underlying this individual-specific susceptibility. Moreover, we still do not know which properties of the innate immune response are specific to MTB infection. To identify immune responses that are specific to MTB, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied their transcriptional response. We identified a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. This subset includes genes involved in phagosome maturation, superoxide production, response to vitamin D, macrophage chemotaxis, and sialic acid synthesis. We suggest that genetic variants that affect the function or regulation of these genes should be considered candidate loci for explaining TB susceptibility. PMID:26586179

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

    ERIC Educational Resources Information Center

    Robinson, Adam M., Jr.

    2010-01-01

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

  1. Prokineticin 1 Induces Inflammatory Response in Human Myometrium

    PubMed Central

    Gorowiec, Marta R.; Catalano, Rob D.; Norman, Jane E.; Denison, Fiona C.; Jabbour, Henry N.

    2011-01-01

    The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1β, chemokine C-C motif ligand 3, and colony-stimulating factor 3. In addition, we demonstrate that PROK1 increases the expression of chemokine C-C motif ligand 20, IL-6, IL-8, prostaglandin synthase 2, and prostaglandin E2 and F2α secretion. The treatment of myometrial explants with 100 ng/mL of lipopolysaccharide up-regulates the expression of PROK1, PROK1 receptor, and inflammatory mediators. The infection of myometrial explants with lentiviral microRNA targeting PROK1, preceding treatment with lipopolysaccharide, reduces the expression of inflammatory genes. We propose that PROK1 is a novel inflammatory mediator that can contribute to the onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. PMID:21983634

  2. The response of single human cells to zero-gravity

    NASA Technical Reports Server (NTRS)

    Montgomery, P. O., Jr.; Cook, J. E.; Reynolds, R. C.; Paul, J. S.; Hayflick, L.; Stock, D.; Shulz, W. W.; Kimzey, S. L.; Thirolf, R. G.; Rogers, T.

    1977-01-01

    Microscopic and histochemical evaluations of human embrionic lung cells after exposure to zero-gravity are reported. Growth curves, DNA microspectrophotometry, phase microscopy, and ultrastructural studies of fixed cells revealed no effects on the cultures. Minor unexplained differences have been found in biochemical constituents of the samples.

  3. Calculation of Inertial Parameters to Find Dynamic Human Response

    NASA Astrophysics Data System (ADS)

    Shaibani, Saami J.

    2004-03-01

    A number of authenticated models of the human body have been produced during decades of research, and yet deficient substitutes continue to be concocted. Recent examples of the latter sadly include: (a) if human = water and potato = water, then human = potato; (b) pancreas = hot dog; and, (c) spine = plastic pipe. Omission of any suitable use of biology in these cases makes the inadequacies involved all the more unacceptable. The unduly simplistic nature seen there is contrasted with the correct procedures documented in this paper. Particular attention is paid here to the fields of anatomy and anthropometry, and the unique challenges[1] associated with pediatric cases are also discussed. The results of this study show that the naivety in the flawed examples above and elsewhere is completely unjustified, even for first-order speculations. The importance of first-hand clinical experience is explained as an essential component in the determination of accurate biomechanical data for human kinematics. 1. Bull. Am. Phys. Soc., 44, 273 (1999).

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

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  5. Decoding and reconstructing color from responses in human visual cortex

    PubMed Central

    Brouwer, Gijs Joost; Heeger, David J.

    2009-01-01

    How is color represented by spatially distributed patterns of activity in visual cortex? Functional magnetic resonance imaging (fMRI) responses to several stimulus colors were analyzed with multivariate techniques: conventional pattern classification, a forward model of idealized color tuning, and principal component analysis (PCA). Stimulus color was accurately decoded from activity in V1, V2, V3, V4, VO1 but not LO1, LO2, V3A/B or MT+. The conventional classifier and forward model yielded similar accuracies, but the forward model (unlike the classifier) also reliably reconstructed novel stimulus colors not used to train (specify parameters of) the model. The mean responses, averaged across voxels in each visual area, were not reliably distinguishable for the different stimulus colors. Hence, each stimulus color was associated with a unique spatially distributed pattern of activity, presumably reflecting the color-selectivity of cortical neurons. In a complementary PCA analysis, a color space was derived from the covariation, across voxels, in the responses to different colors. In V4 and VO1, the first two principal component scores (main source of variation) of the responses revealed a progression through perceptual color space, with perceptually similar colors evoking the most similar responses. This was not the case for any of the other visual cortical areas, including V1, even though decoding was most accurate in V1. This dissociation implies a transformation from the color representation in V1 to reflect perceptual color space in V4 and VO1. PMID:19890009

  6. DNA damage response induced by HZE particles in human cells

    NASA Astrophysics Data System (ADS)

    Chen, David; Aroumougame, Asaithamby

    Convincing evidences indicate that high-linear energy transfer (LET) ionizing radiation (IR) induced complex DNA lesions are more difficult to repair than isolated DNA lesions induced by low-LET IR; this has been associated with the increased RBE for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in high energy charged-particle irradiated human cells. We have employed an in situ method to directly monitor induction and repair of clustered DNA lesions at the single-cell level. We showed, consistent with biophysical modeling, that the kinetics of loss of clustered DNA lesions was substantially compromised in human fibroblasts. The unique spatial distribution of different types of DNA lesions within the clustered damages determined the cellular ability to repair these damages. Importantly, examination of metaphase cells derived from HZE particle irradiated cells revealed that the extent of chromosome aberrations directly correlated with the levels of unrepaired clustered DNA lesions. In addition, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We found that complex DNA lesions induced by HZE particles were even more difficult to be repaired in organotypic 3D culture, resulting enhanced cell killing and chromosome aberrations. Our data suggest that DNA repair capability in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis. As the organotypic 3D model mimics human lung, it opens up new experimental approaches to explore the effect of radiation in vivo and will have important implications for evaluating radiation risk in human tissues.

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

    PubMed Central

    Slack, Daniel L.; Burnstein, Marcus J.; Errett, Lee; Bonneau, Daniel; Latter, David; Rotstein, Ori D.; Bolz, Steffen-Sebastian; Lidington, Darcy; Voigtlaender-Bolz, Julia

    2015-01-01

    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. PMID:26367262

  8. Computations of uncertainty mediate acute stress responses in humans

    PubMed Central

    de Berker, Archy O.; Rutledge, Robb B.; Mathys, Christoph; Marshall, Louise; Cross, Gemma F.; Dolan, Raymond J.; Bestmann, Sven

    2016-01-01

    The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function. PMID:27020312

  9. Sympathetic responses to head-down rotations in humans.

    PubMed

    Hume, K M; Ray, C A

    1999-06-01

    Muscle sympathetic nerve activity (MSNA) increases with head-down neck flexion (HDNF). The present study had three aims: 1) to examine sympathetic and vascular responses to two different magnitudes of HDNF; 2) to examine these same responses during prolonged HDNF; and 3) to determine the influence of nonspecific pressure receptors in the head on MSNA. The first experiment tested responses to two static head positions in the vertical axis [HDNF and intermediate HDNF (I-HDNF; approximately 50% of HDNF)]. MSNA increased above baseline during both I-HDNF and HDNF (from 219 +/- 36 to 301 +/- 47 and from 238 +/- 42 to 356 +/- 59 units/min, respectively; P < 0.01). Calf blood flow (CBF) decreased and calf vascular resistance increased during both I-HDNF and HDNF (P < 0.01). Both the increase in MSNA and the decrease in CBF were linearly related to the magnitude of the downward head rotations (P < 0.01). The second experiment tested responses during prolonged HDNF. MSNA increased (from 223 +/- 63 to 315 +/- 79 units/min; P < 0.01) and CBF decreased (from 3.2 +/- 0.4 to 2.6 +/- 0.04 ml. 100 ml-1. min-1; P < 0.01) at the onset of HDNF. These responses were maintained throughout the 30-min period. Mean arterial blood pressure gradually increased during the 30 min of HDNF (from 94 +/- 4 to 105 +/- 3 mmHg; P < 0.01). In a third experiment, head-down neck extension was performed with subjects in the supine position. Unlike HDNF, head-down neck extension did not affect MSNA. The results from these studies demonstrate that MSNA: 1) increases in magnitude as the degree of HDNF increases; 2) remains elevated above baseline during prolonged HDNF; and 3) responses during HDNF are not associated with nonspecific receptors in the head activated by increases in cerebral pressure. PMID:10368363

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

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

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

  11. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study.

    PubMed

    Goutianos, Georgios; Tzioura, Aikaterini; Kyparos, Antonios; Paschalis, Vassilis; Margaritelis, Nikos V; Veskoukis, Aristidis S; Zafeiridis, Andreas; Dipla, Konstantina; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2015-02-01

    Animal models are widely used in biology and the findings of animal research are traditionally projected to humans. However, recent publications have raised concerns with regard to what extent animals and humans respond similar to physiological stimuli. Original data on direct in vivo comparison between animals and humans are scarce and no study has addressed this issue after exercise. We aimed to compare side by side in the same experimental setup rat and human responses to an acute exercise bout of matched intensity and duration. Rats and humans ran on a treadmill at 86% of maximal velocity until exhaustion. Pre and post exercise we measured 30 blood chemistry parameters, which evaluate iron status, lipid profile, glucose regulation, protein metabolism, liver, and renal function. ANOVA indicated that almost all biochemical parameters followed a similar alteration pattern post exercise in rats and humans. In fact, there were only 2/30 significant species × exercise interactions (in testosterone and globulins), indicating different responses to exercise between rats and humans. On the contrary, the main effect of exercise was significant in 15/30 parameters and marginally nonsignificant in other two parameters (copper, P = 0.060 and apolipoprotein B, P = 0.058). Our major finding is that the rat adequately mimics human responses to exercise in those basic blood biochemical parameters reported here. The physiological resemblance of rat and human blood responses after exercise to exhaustion on a treadmill indicates that the use of blood chemistry in rats for exercise physiology research is justified. PMID:25677548

  12. The Academic Librarian's Human Resources Handbook. Employer Rights and Responsibilities.

    ERIC Educational Resources Information Center

    Baldwin, David A.

    This handbook offers "how to" guidance on library management and provides a single source for laws, regulations, executive orders, guidelines, and court decisions on employee and employer rights and responsibilities. Detailed information is provided on: recruiting and selecting personnel; the employment relationship; wages and hours; employee…

  13. RELATIONSHIP BETWEEN DELIVERED OZONE DOSE AND FUNCTIONAL RESPONSES IN HUMANS

    EPA Science Inventory

    The relationship between delivered ozone dose and variability of pulmonary function response to ozone was investigated in 20 young, healthy non-smoking male volunteers. he subjects were exposed to 0.4 ppm ozone for one hour during which they walked on a treadmill at a speed and i...

  14. Factors influencing the response to chemotherapy in human cystic echinococcosis.

    PubMed Central

    Todorov, T.; Mechkov, G.; Vutova, K.; Georgiev, P.; Lazarova, I.; Tonchev, Z.; Nedelkov, G.

    1992-01-01

    As the effectiveness of mebendazole and albendazole in patients with echinococcosis has been found to vary, we investigated some of the factors likely to be responsible. A total of 79 patients who were treated with mebendazole (44 patients) or albendazole (35 patients) were included in the study. Evaluation of the treatment results was based on the changes in cyst morphology, as evidenced by the results of X-ray radiography, sonography, and computed tomography, and on analysis of the findings in relation to parasitic and drug factors. The response of cysts according to their site did not vary much, with the exception of the poor response of bone cysts. A more important factor seems to be cyst size, since the treatment was more efficacious against smaller and younger cysts. The presence of daughter cysts should be regarded as an unfavourable factor for treatment response. Cyst multiplicity did not present insurmountable difficulties, provided the cysts were small and a prolonged course of therapy was undergone. The choice of drug used for the therapy was important, with the results supporting the advantage of albendazole. In planning the chemotherapy of hydatid disease, factors such as cyst condition and drug used should therefore be taken into consideration. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1638663

  15. Human Operant Learning under Concurrent Reinforcement of Response Variability

    ERIC Educational Resources Information Center

    Maes, J. H. R.; van der Goot, M.

    2006-01-01

    This study asked whether the concurrent reinforcement of behavioral variability facilitates learning to emit a difficult target response. Sixty students repeatedly pressed sequences of keys, with an originally infrequently occurring target sequence consistently being followed by positive feedback. Three conditions differed in the feedback given to…

  16. Gravitational effects on human cardiovascular responses to isometric muscle contractions

    NASA Astrophysics Data System (ADS)

    Bonde-Petersen, Flemmig; Suzuki, Yoji; Sadamoto, Tomoko

    Isometric exercise induces profound cardiovascular adaptations increasing mean arterial pressure and heart rate. We investigated effects of simulated +Gz and -Gz respectively on the central and peripheral cardiovascular system. Sustained handgrip exercise was performed at 40% of maximum for 2 minutes in five subjects. This maneuver increased mean arterial pressure by 40-45 mm Hg both during head out water immersion which simulates weightlessness, as well as bedrest during -25, 0, and +25 degrees tilt from the horizontal. Lower body negative pressure (-60 mm Hg for 10 min) attenuated the response to handgrip exercise to 30 mm Hg. It also increased the heart rate minimally by about 20 beats per minute while the water immersion, as well as head up, head down and horizontal bedrest showed increments of about 50 beats per min. It was concluded that the response to isometric contraction is mediated through the high pressure baroreceptors, because similar responses were seen during stresses producing a wide variation in central venous pressure. During lower body negative pressure the increased sympathetic nervous activity itself increased resting heart rate and mean arterial pressure. The responses to static exercise were, therefore, weaker.

  17. Effects of flavonoids on human lymphocyte proliferative responses

    SciTech Connect

    Mookerjee, B.K.; Lee, T.P.; Logue, G.P.; Lippes, H.A.; Middleton, E.

    1986-01-01

    Flavonoids reversibly inhibit lymphocyte proliferative responses to phytomitogens, soluble antigens and phorbol esters by blocking an early event or events that follow stimulation. Quercetin and tangeretin inhibit thymidine transport in stimulated lymphocytes. These flavonoids reversibly inhibit antigen processing by monocytes and inhibit the expression of class II histocompatibility (DR) antigens in PBM cells.

  18. Measuring Human Performance within Computer Security Incident Response Teams

    SciTech Connect

    McClain, Jonathan T.; Silva, Austin Ray; Avina, Glory Emmanuel; Forsythe, James C.

    2015-09-01

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

  19. Physiology and relevance of human adaptive thermogenesis response.

    PubMed

    Celi, Francesco S; Le, Trang N; Ni, Bin

    2015-05-01

    In homoeothermic organisms, the preservation of core temperature represents a primal function, and its costs in terms of energy expenditure can be considerable. In modern humans, the endogenous thermoregulation mechanisms have been replaced by clothing and environmental control, and the maintenance of thermoneutrality has been successfully achieved by manipulation of the micro- and macroenvironment. The rediscovery of the presence and activity of brown adipose tissue in adult humans has renewed the interest on adaptive thermogenesis (AT) as a means to facilitate weight loss and improve carbohydrate metabolism. The aim of this review is to describe the recent advancements in the study of this function, and to assess the potential and limitations of exploiting AT for environmental/behavioral, and pharmacological interventions. PMID:25869212

  20. The response of single human cells to zero gravity

    NASA Technical Reports Server (NTRS)

    Montgomery, P. O., Jr.; Cook, J. E.; Reynolds, R. C.; Paul, J. S.; Hayflick, L.; Stock, D.; Schulz, W. W.; Kimzey, S. L.; Thirolf, R. G.; Rogers, T.

    1974-01-01

    The SO15 experiment was designed to extend observations of the effects of zero-gravity to living human cells during and subsequent to a 59-day flight on Skylab 3. A strain of diploid human embryonic lung cells, WI-38, was chosen for this purpose. The studies were concerned with observations designed to detect the effects of zero-gravity on cell growth rates and on cell structure as observed by light microscopy, transmission and scanning electron microscopy and histochemistry. Studies of the effects of zero-gravity on the cell function and the cell cycle were performed by time lapse motion picture photography and microspectrophotometry. Subsequent study of the returned living cells included karotyping, G- and C-banding, and analyses of the culture media used. Some of the living cells returned were banked by deep freeze techniques for possible future experiments.

  1. Human skeletal muscle responses to spaceflight and possible countermeasures

    NASA Technical Reports Server (NTRS)

    Gollnick, Philip D.; Edgerton, V. Reggie; Saltin, Bengt

    1990-01-01

    The current status of knowledge concerning the effects of unweighting skeletal muscle is summarized. The results of both ground-based and space-based animal studies are reviewed which show that there is rapid loss in muscle mass, primarily in slow-twitch muscle, of the rat during unweighting of muscle. There is also a shift in the myosin isoforms with muscles such that slow-twitch muscles take on many of the characteristics of fast-twitch muscles. Ground-based studies in human suggest that programs of electrical stimulation can be developed to simulate normal muscular contractions. Attempts to develop countermeasures to the adverse effects of space travel on muscular functions in humans have not been successful to date.

  2. The science of human security: a response from political science.

    PubMed

    Roberts, David

    2008-01-01

    The concept of human security has developed in significance in the last decade to the point that its meaning and validity is hotly contested in the field of international relations, security, and development studies. A key consideration relates to its ambiguity at best and its amorphousness at worst. Medical scholarship proposes approaches that may render more meaningful the concept. However, collaboration and co-operation between political scientists and medical practitioners offers even greater potential to this vital programme. The latter offer the technical and methodological skills and approaches lacking in political science, whilst the former develop political frameworks to shift the causal focus towards human, institutional and structural agency in mass avoidable global civilian mortality. PMID:18456988

  3. Human response to house vibrations caused by sonic booms or air blasts.

    PubMed

    Schomer, P D

    1978-07-01

    Descriptions of the effects of sonic booms of air blasts by observers in buildings have included such statements as "noticeable vibrations" in addition to phrases such as "the house rattles," "the windows rattle," or "bric-à-brac rattles." Analysis of studies of human response to vibrations, vibration complaints in the Toronto area, special tests by Kryter at Edwards Air Force Base, and laboratory studies of human response to sonic booms show that perceived vibration is not normally a factor that contributes significantly to human response to airborne, large-amplitude impulse noise. Rather, human response is solely the result of the impulse noise itself and of audible noise due to induced radiation from vibrating surfaces. PMID:711997

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

    ERIC Educational Resources Information Center

    Kihlman, Tor

    1988-01-01

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

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

    PubMed Central

    Kam, Tae-Eui; Mannion, Damien J.; Lee, Seong-Whan; Doerschner, Katja; Kersten, Daniel J.

    2015-01-01

    Determining the compositional properties of surfaces in the environment is an important visual capacity. One such property is specular reflectance, which encompasses the range from matte to shiny surfaces. Visual estimation of specular reflectance can be informed by characteristic motion profiles; a surface with a specular reflectance that is difficult to determine while static can be confidently disambiguated when set in motion. Here, we used fMRI to trace the sensitivity of human visual cortex to such motion cues, both with and without photometric cues to specular reflectance. Participants viewed rotating blob-like objects that were rendered as images (photometric) or dots (kinematic) with either matte-consistent or shiny-consistent specular reflectance profiles. We were unable to identify any areas in low and mid-level human visual cortex that responded preferentially to surface specular reflectance from motion. However, univariate and multivariate analyses identified several visual areas; V1, V2, V3, V3A/B, and hMT+, capable of differentiating shiny from matte surface flows. These results indicate that the machinery for extracting kinematic cues is present in human visual cortex, but the areas involved in integrating such information with the photometric cues necessary for surface specular reflectance remain unclear. PMID:26539100

  6. A Study of the Characteristics of Human-Pilot Control Response to Simulated Aircraft Lateral Motions

    NASA Technical Reports Server (NTRS)

    Cheatham, Donald C

    1954-01-01

    Report presents the results of studies made in an attempt to provide information on the control operations of the human pilot. These studies included an investigation of the ability of pilots to control simulated unstable yawing oscillations, a study of the basic characteristics of human-pilot control response, and a study to determine whether and to what extent pilot control response can be represented in an analytical form.

  7. Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines.

    PubMed

    Good, Michael F; Hawkes, Michael T; Yanow, Stephanie K

    2015-11-01

    Malaria vaccine development is hampered by the lack of small animal models that recapitulate human immune responses to Plasmodium falciparum. We review the burgeoning literature on humanized mice for P. falciparum infection, including challenges in engraftment of human immune cells, hepatocytes, and erythrocytes. Recent advances in immune-compromised mouse models and stem cell technology have already enabled proof of concept that the entire parasite life cycle can be sustained in a murine model and that adaptive human immune responses to several parasite stages can be measured. Nonetheless, optimization is needed to achieve a reproducible and relevant murine model for malaria vaccine development. This review is focused on the complexities of T cell development in a mouse humanized with both a lymphoid system and hepatocytes. An understanding of this will facilitate the use of humanized mice in the development of liver-stage vaccines. PMID:26458783

  8. Biomechanical response of human liver in tensile loading.

    PubMed

    Kemper, Andrew R; Santago, Anthony C; Stitzel, Joel D; Sparks, Jessica L; Duma, Stefan M

    2010-01-01

    Motor vehicle collisions commonly result in serious life threatening liver injuries. Although finite element models are becoming an integral tool in the reduction of automotive related liver injuries, the establishment of accurate material models and tissue level tolerance values is critical for accurate injury risk assessment. This study presents a total of 51 tension tests performed on human liver parenchyma at various loading rates in order to characterize the viscoelastic and failure properties of human liver. Standard dog-bone coupons were obtained from fresh human livers and tested within 48 hours of death. Each coupon was tested once to failure at one of four loading rates (0.008 s(-1), 0.089 s(-1), 0.871 s(-1), and 9.477 s(-1)) to investigate the effects of rate dependence. Load and acceleration data were obtained from each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that liver parenchyma is rate dependent, with higher rate tests giving higher failure stresses and lower failure strains. The failure strains for all tests ranged from 11% to 54% and the failure stresses ranged from 7 kPa to 95 kPa. This study provides novel biomechanical data that can be used in the development of both rate dependent material models and tissue level tolerance values critical for the validation of finite element models used to assess injury risk in automobile collisions. PMID:21050588

  9. Biomechanical Response of Human Liver in Tensile Loading

    PubMed Central

    Kemper, Andrew R.; Santago, Anthony C.; Stitzel, Joel D.; Sparks, Jessica L.; Duma, Stefan M.

    2010-01-01

    Motor vehicle collisions commonly result in serious life threatening liver injuries. Although finite element models are becoming an integral tool in the reduction of automotive related liver injuries, the establishment of accurate material models and tissue level tolerance values is critical for accurate injury risk assessment. This study presents a total of 51 tension tests performed on human liver parenchyma at various loading rates in order to characterize the viscoelastic and failure properties of human liver. Standard dog-bone coupons were obtained from fresh human livers and tested within 48 hours of death. Each coupon was tested once to failure at one of four loading rates (0.008 s–1, 0.089 s–1, 0.871 s–1, and 9.477 s–1) to investigate the effects of rate dependence. Load and acceleration data were obtained from each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that liver parenchyma is rate dependent, with higher rate tests giving higher failure stresses and lower failure strains. The failure strains for all tests ranged from 11% to 54% and the failure stresses ranged from 7 kPa to 95 kPa. This study provides novel biomechanical data that can be used in the development of both rate dependent material models and tissue level tolerance values critical for the validation of finite element models used to assess injury risk in automobile collisions. PMID:21050588

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

    EPA Science Inventory

    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 ...

  11. EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN MACROPHAGE RESPONSIVENESS TO LIPOPOLYSACCHARIDE

    EPA Science Inventory

    EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN MACROPHAGE RESPONSIVENESS TO LIPOPOLYSACCHARIDE
    S. Mundandhara1 and M.C. Madden2, 1UNC Center for Environmental Medicine, Asthma, and Lung Biology, 2US EPA, NHEERL, Human Studies Division, Chapel Hill, NC, USA

    Epidemiologica...

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

    EPA Science Inventory

    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...

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID

  15. The commerce of human body parts: an Eastern Orthodox response.

    PubMed

    Reardon, P H

    2000-08-01

    The Orthodox Church teaches that the bodies of those in Christ are to be regarded as sanctified by the hearing of the Word and faithful participation in the Sacraments, most particularly the Holy Eucharist; because of the indwelling of the Holy Spirit the consecrated bodies of Christians do not belong to them but to Christ; with respect to the indwelling Holy Spirit there is no difference between the bodies of Christians before and after death; whether before or after death, the Christian body is also to receive the same veneration; and notwithstanding the physical corruptions that the body endures by reason of death, there remains a strict continuity between the body in which the Christian dies and the body in which the Christian will rise again. That is to say, it is the very same reality that is sown in corruption and will be raised in incorruption. Given such consideration, the notion of "selling" and integral part of a human being is simply outside the realm of rational comprehension. Indeed, it is profoundly repugnant to those Orthodox Christian sentiments that are formed and nourished by the Church's sacramental teaching and liturgical worship. One does not sell or purchase that which has been consecrated in those solemn ways that the Church consecrates the human body. PMID:12171078

  16. Portrait of transcriptional responses to ultraviolet and ionizing radiation in human cells

    PubMed Central

    Rieger, Kerri E.; Chu, Gilbert

    2004-01-01

    To understand the human response to DNA damage, we used microarrays to measure transcriptional responses of 10 000 genes to ionizing radiation (IR) and ultraviolet radiation (UV). To identify bona fide responses, we used cell lines from 15 individuals and a rigorous statistical method, Significance Analysis of Microarrays (SAM). By exploring how sample number affects SAM, we rendered a portrait of the human damage response with a degree of accuracy unmatched by previous studies. By showing how SAM can be used to estimate the total number of responsive genes, we discovered that 24% of all genes respond to IR and 32% respond to UV, although most responses were less than 2-fold. Many genes were involved in known damage-response pathways for cell cycling and proliferation, apoptosis, DNA repair or the stress response. However, the majority of genes were involved in unexpected pathways, with functions in signal transduction, RNA binding and editing, protein synthesis and degradation, energy metabolism, metabolism of macromolecular precursors, cell structure and adhesion, vesicle transport, or lysosomal metabolism. Although these functions were not previously associated with the damage response in mammals, many were conserved in yeast. These insights reveal new directions for studying the human response to DNA damage. PMID:15356296

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

    PubMed

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

    2009-10-01

    Recent findings have demonstrated that women might be more reactive than men to viewing painful stimuli (vicarious response to pain), and therefore more empathic [Han, S., Fan, Y., & Mao, L. (2008). Gender difference in empathy for pain: An electrophysiological investigation. Brain Research, 1196, 85-93]. We investigated whether the two sexes differed in their cerebral responses to affective pictures portraying humans in different positive or negative contexts compared to natural or urban scenarios. 440 IAPS slides were presented to 24 Italian students (12 women and 12 men). Half the pictures displayed humans while the remaining scenes lacked visible persons. ERPs were recorded from 128 electrodes and swLORETA (standardized weighted Low-Resolution Electromagnetic Tomography) source reconstruction was performed. Occipital P115 was greater in response to persons than to scenes and was affected by the emotional valence of the human pictures. This suggests that processing of biologically relevant stimuli is prioritized. Orbitofrontal N2 was greater in response to positive than negative human pictures in women but not in men, and not to scenes. A late positivity (LP) to suffering humans far exceeded the response to negative scenes in women but not in men. In both sexes, the contrast suffering-minus-happy humans revealed a difference in the activation of the occipito/temporal, right occipital (BA19), bilateral parahippocampal, left dorsal prefrontal cortex (DPFC) and left amygdala. However, increased right amygdala and right frontal area activities were observed only in women. The humans-minus-scenes contrast revealed a difference in the activation of the middle occipital gyrus (MOG) in men, and of the left inferior parietal (BA40), left superior temporal gyrus (STG, BA38) and right cingulate (BA31) in women (270-290 ms). These data indicate a sex-related difference in the brain response to humans, possibly supporting human empathy. PMID:19061906

  18. Translational control of human neutrophil responses by MNK1.

    PubMed

    Fortin, Carl F; Mayer, Thomas Z; Cloutier, Alexandre; McDonald, Patrick P

    2013-10-01

    A growing number of inflammatory and immune processes in vivo have been shown to be influenced by neutrophil-derived cytokines. Whereas the underlying transcriptional mechanisms are increasingly well understood, the translational regulation of this neutrophil response remains largely unexplored. Here, we show that the MNK1, which participates in translational control in several cell types, is activated in response to physiological neutrophil agonists (LPS, TNF-α) in the cytoplasmic and nuclear compartments. With the use of various pharmacological inhibitors, we found that MNK1 activation takes place downstream of the TAK1-p38 MAPK axis in neutrophils, whereas the MEK/ERK, JNK, PI3K, and PKC pathways are not involved. Pharmacological blockade of MNK1, as well as overexpression experiments, established that cytokine protein synthesis (but not gene expression) is under the control of MNK1 in neutrophils. Likewise, MNK1 inhibition reversed the antiapoptotic effect of LPS and TNF-α in neutrophils, and this was accompanied by a decreased expression of the antiapoptotic protein Mcl-1. Thus, MNK1 appears to be an important regulator of neutrophil responses. Although MNK1 inhibition did not affect protein recruitment to mRNA caps, it decreased the phosphorylation of molecules implicated in translation initiation control, such as S6K, S6, and hyperphosphorylated 4E-BP1. These molecular targets of MNK1 are shared with those of PI3K in neutrophils, and accordingly, MNK1 inhibition partially impaired the belated PI3K/Akt activation elicited by LPS or TNF in these cells. Given the importance of neutrophils and their products in numerous chronic inflammatory disorders, MNK1 could represent an attractive therapeutic target. PMID:23401599

  19. Evolution and Ontogeny of Stress Response to Social Challenges in the Human Child

    ERIC Educational Resources Information Center

    Flinn, Mark V.

    2006-01-01

    The stress response systems of the human child are highly sensitive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Two…

  20. Responses to human intruders by birds nesting in colonies: Experimental results and management guidelines

    USGS Publications Warehouse

    Erwin, R.M.

    1989-01-01

    Colonies of nesting wading birds and seabirds were studied at coastal sites in Virginia and North Carolina to determine distances at which birds flushed in response to human intrusion. There were few statistically significant relationships between flushing distances and colony size. Similarly, there were few differences between responses during incubation compared to post-hatching periods.

  1. Evaluation of human response to structural vibrations induced by sonic booms

    NASA Technical Reports Server (NTRS)

    Sutherland, Louis C.; Czech, J.

    1992-01-01

    The topic is addressed of building vibration response to sonic boom and the evaluation of the associated human response to this vibration. An attempt is made to reexamine some of the issues addressed previously and to offer fresh insight that may assist in reassessing the potential impact of sonic boom over populated areas. Human response to vibration is reviewed first and a new human vibration response criterion curve is developed as a function of frequency. The difference between response to steady state versus impulsive vibration is addressed and a 'vibration exposure' or 'vibration energy' descriptor is suggested as one possible way to evaluate duration effects on response to transient vibration from sonic booms. New data on the acoustic signature of rattling objects are presented along with a review of existing data on the occurrence of rattle. Structural response to sonic boom is reviewed and a new descriptor, 'Acceleration Exposure Level' is suggested which can be easily determined from the Fourier Spectrum of a sonic boom. A preliminary assessment of potential impact from sonic booms is provided in terms of human response to vibration and detection of rattle based on a synthesis of the preceding material.

  2. THE EFFECT OF OZONE ON HUMAN IMMUNITY: IN VITRO RESPONSIVENESS OF LYMPHOCYTES TO PHYTOHEMMAGGLUTININ

    EPA Science Inventory

    Peripheral blood lymphocytes from 20 human subjects exposed to 784 micrograms cu m ozone for 4 hours, and from 11 subjects exposed to clean air for the same length of time were studied for in vitro responsiveness to phytohemagglutinin (PHA). Thymus-derived (T) lymphocyte response...

  3. Grassroots responsiveness to human rights abuse: history of the Washtenaw Interfaith Coalition for Immigrant Rights.

    PubMed

    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. PMID:23724575

  4. Diverting Attention Suppresses Human Amygdala Responses to Faces

    PubMed Central

    Morawetz, Carmen; Baudewig, Juergen; Treue, Stefan; Dechent, Peter

    2010-01-01

    Recent neuroimaging studies disagree as to whether the processing of emotion-laden visual stimuli is dependent upon the availability of attentional resources or entirely capacity-free. Two main factors have been proposed to be responsible for the discrepancies: the differences in the perceptual attentional demands of the tasks used to divert attentional resources from emotional stimuli and the spatial location of the affective stimuli in the visual field. To date, no neuroimaging report addressed these two issues in the same set of subjects. Therefore, the aim of the study was to investigate the effects of high and low attentional load as well as different stimulus locations on face processing in the amygdala using functional magnetic resonance imaging to provide further evidence for one of the two opposing theories. We were able for the first time to directly test the interaction of attentional load and spatial location. The results revealed a strong attenuation of amygdala activity when the attentional load was high. The eccentricity of the emotional stimuli did not affect responses in the amygdala and no interaction effect between attentional load and spatial location was found. We conclude that the processing of emotional stimuli in the amygdala is strongly dependent on the availability of attentional resources without a preferred processing of stimuli presented in the periphery and provide firm evidence for the concept of the attentional load theory of emotional processing in the amygdala. PMID:21160563

  5. The molecular basis for uv response of cultured human cells

    SciTech Connect

    Karin, M.

    1991-01-01

    During the past year we have analyzed the mechanism by which UV and H{sub 2}O{sub 2} increase the activity of AP-1 in HeLa cells. AP-1 is a dimeric protein complex composed of the fos and jun gene products. After UV irradiation of HeLa cells (or exposure to H{sub 2}O{sub 2}) expression of the c-jun gene rapidly increases at least 50-fold. This induction occurs through the previously identified AP-1 site in the c-jun promoter. This positive autoregulation is mediated by AP-1 complexes that are composed mostly of cJun. cJun is a phosphoprotein that undergoes complex changes in its phosphorylation state following exposure to phorbol esters, growth factors or transforming oncogenes. We show that UV irradiation causes increases in the phosphorylation of cJun. We have been trying to determine the common signal by which DNA damaging agents lead to activation of the UV response. We present evidence that oxidative stress may serve as a signal for AP-1 induction during the UV response. We are also trying to purify and characterize UVIC, a factor secreted from UV damaged cells which protects non-irradiated cells from damage. We have identified UVIC as a 17 kDa polypeptide that retains radioprotective activity after SDS-PAGE and renaturation. We are currently scaling up the isolation and purification process. 4 refs. (MHB)

  6. The molecular basis for uv response of cultured human cells

    SciTech Connect

    Karin, M.

    1991-12-01

    During the past year we have analyzed the mechanism by which UV and H{sub 2}O{sub 2} increase the activity of AP-1 in HeLa cells. AP-1 is a dimeric protein complex composed of the fos and jun gene products. After UV irradiation of HeLa cells (or exposure to H{sub 2}O{sub 2}) expression of the c-jun gene rapidly increases at least 50-fold. This induction occurs through the previously identified AP-1 site in the c-jun promoter. This positive autoregulation is mediated by AP-1 complexes that are composed mostly of cJun. cJun is a phosphoprotein that undergoes complex changes in its phosphorylation state following exposure to phorbol esters, growth factors or transforming oncogenes. We show that UV irradiation causes increases in the phosphorylation of cJun. We have been trying to determine the common signal by which DNA damaging agents lead to activation of the UV response. We present evidence that oxidative stress may serve as a signal for AP-1 induction during the UV response. We are also trying to purify and characterize UVIC, a factor secreted from UV damaged cells which protects non-irradiated cells from damage. We have identified UVIC as a 17 kDa polypeptide that retains radioprotective activity after SDS-PAGE and renaturation. We are currently scaling up the isolation and purification process. 4 refs. (MHB)

  7. Abrupt rise of new machine ecology beyond human response time

    PubMed Central

    Johnson, Neil; Zhao, Guannan; Hunsader, Eric; Qi, Hong; Johnson, Nicholas; Meng, Jing; Tivnan, Brian

    2013-01-01

    Society's techno-social systems are becoming ever faster and more computer-orientated. However, far from simply generating faster versions of existing behaviour, we show that this speed-up can generate a new behavioural regime as humans lose the ability to intervene in real time. Analyzing millisecond-scale data for the world's largest and most powerful techno-social system, the global financial market, we uncover an abrupt transition to a new all-machine phase characterized by large numbers of subsecond extreme events. The proliferation of these subsecond events shows an intriguing correlation with the onset of the system-wide financial collapse in 2008. Our findings are consistent with an emerging ecology of competitive machines featuring ‘crowds' of predatory algorithms, and highlight the need for a new scientific theory of subsecond financial phenomena. PMID:24022120

  8. The response of single human cells to zero gravity

    NASA Technical Reports Server (NTRS)

    Montgomery, P. O., Jr.; Cook, J. E.; Reynolds, R. C.; Paul, J. S.; Hayflick, L.; Schulz, W. W.; Stock, D.; Kinzey, S.; Rogers, T.; Campbell, D.

    1975-01-01

    Twenty separate cultures of Wistar-38 human embryonic lung cells were exposed to a zero-gravity environment on Skylab for periods of time ranging from one to 59 days. Duplicate cultures were run concurrently as ground controls. Ten cultures were fixed on board the satellite during the first 12 days of flight. Growth curves, DNA microspectrophotometry, phase microscopy, and ultrastructural studies of the fixed cells revealed no effects of a zero-gravity environment on the ten cultures. Two cultures were photographed with phase time lapse cinematography during the first 27 days of flight. No differences were found in mitotic index, cell cycle, and migration between the flight and control cells. Eight cultures were returned to earth in an incubated state. Karyotyping and chromosome banding tests show no differences between the flight and control cells.

  9. Biomechanical response of human spleen in tensile loading.

    PubMed

    Kemper, Andrew R; Santago, Anthony C; Stitzel, Joel D; Sparks, Jessica L; Duma, Stefan M

    2012-01-10

    Blunt splenic injuries are most frequently caused as a result of motor vehicle collisions and are associated with high mortality rates. In order to accurately assess the risk of automotive related spleen injuries using tools such as finite element models, tissue level tolerance values and suitable material models must be developed and validated based on appropriate biomechanical data. This study presents a total of 41 tension tests performed on spleen parenchyma coupons and 29 tension tests performed on spleen capsule/parenchyma coupons. Standard dog-bone coupons were obtained from fresh human spleen and tested within 48 h of death. Each coupon was tested once to failure at one of the four loading rates to investigate the effects of rate dependence. Load and acceleration data were obtained at each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that both the spleen parenchyma and the capsule are rate dependent, with higher loading rates yielding higher failure stresses and lower failure strains. The results also show that the failure stress of the splenic capsule is significantly greater than that of the underlying parenchyma. Overall, this study provides novel biomechanical data that demonstrate the rate dependent tissue level tolerance values of human spleen tissue in tensile loading, which can aid in the improvement of finite element models used to assess injury risk in blunt trauma. PMID:22078273

  10. Strain-Related Differences in the Immune Response: Relevance to Human Stroke.

    PubMed

    Becker, Kyra J

    2016-08-01

    There are significant differences in the immune response and in the susceptibility to autoimmune diseases among rodent strains. It would thus be expected that the contribution of the immune response to cerebral ischemic injury would also differ among rodent strains. More importantly, there are significant differences between the immune responses of rodents and humans. All of these factors are likely to impact the successful translation of immunomodulatory therapies from experimental rodent models to patients with stroke. PMID:26860504

  11. Investigating Coastal Processes Responsible for Large-Scale Shoreline Responses to Human Shoreline Stabilization

    NASA Astrophysics Data System (ADS)

    Slott, J. M.; Murray, A. B.; Ashton, A. D.

    2006-12-01

    Human shoreline stabilization practices, such as beach nourishment (i.e. placing sand on an eroding beach), have become more prevalent as erosion threatens coastal communities. On sandy shorelines, recent experiments with a numerical model of shoreline change (Slott, et al., in press) indicate that moderate shifts in storminess patterns, one possible outcome of global warming, may accelerate the rate at which shorelines erode or accrete, by altering the angular distribution of approaching waves (the `wave climate'). Accelerated erosion would undoubtedly place greater demands on stabilization. Scientists and coastal engineers have typically only considered the site-specific consequences of shoreline stabilization; here we explore the coastal processes responsible for large-scale (10's kms) and long-term (decades) effects using a numerical model developed by Ashton, et al. (2001). In this numerical model, waves breaking at oblique angles drive a flux of sediment along the shoreline, where gradients in this flux can shape the coastline into surprisingly complex forms (e.g. cuspate-capes found on the Carolina coast). Wave "shadowing" plays a major role in shoreline evolution, whereby coastline features may block incoming waves from reaching distant parts. In this work, we include beach nourishment in the Ashton, et al. (2001) model. Using a cuspate-cape shoreline as our initial model condition, we conducted pairs of experiments and varied the wave-climate forcing across each pair, each representing different storminess scenarios. Here we report on one scenario featuring increased extra-tropical storm influence. For each experiment-pair we ran a control experiment with no shoreline stabilization and a second where a beach nourishment project stabilized a cape tip. By comparing the results of these two parallel runs, we isolate the tendency of the shoreline to migrate landward or seaward along the domain due solely to beach nourishment. Significant effects from beach

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

    PubMed

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

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation. PMID:26555860

  13. Scale dependent behavioral responses to human development by a large predator, the puma.

    PubMed

    Wilmers, Christopher C; Wang, Yiwei; Nickel, Barry; Houghtaling, Paul; Shakeri, Yasaman; Allen, Maximilian L; Kermish-Wells, Joe; Yovovich, Veronica; Williams, Terrie

    2013-01-01

    The spatial scale at which organisms respond to human activity can affect both ecological function and conservation planning. Yet little is known regarding the spatial scale at which distinct behaviors related to reproduction and survival are impacted by human interference. Here we provide a novel approach to estimating the spatial scale at which a top predator, the puma (Puma concolor), responds to human development when it is moving, feeding, communicating, and denning. We find that reproductive behaviors (communication and denning) require at least a 4× larger buffer from human development than non-reproductive behaviors (movement and feeding). In addition, pumas give a wider berth to types of human development that provide a more consistent source of human interference (neighborhoods) than they do to those in which human presence is more intermittent (arterial roads with speeds >35 mph). Neighborhoods were a deterrent to pumas regardless of behavior, while arterial roads only deterred pumas when they were communicating and denning. Female pumas were less deterred by human development than males, but they showed larger variation in their responses overall. Our behaviorally explicit approach to modeling animal response to human activity can be used as a novel tool to assess habitat quality, identify wildlife corridors, and mitigate human-wildlife conflict. PMID:23613732

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  15. Human holistic and energetic responses following a tornado.

    PubMed

    Slater, Victoria E

    2004-03-01

    After an F-4 tornado destroyed a large section of our town, I gave 50 complementary energy treatments to tornado victims. I discovered that the same energetic, physical, emotional, mental, and spiritual disruption occurred in people directly and indirectly exposed to the tornado, and that the damage did not repair spontaneously over time. This article describes the energetic damage people sustained from the tornado and their physical, mental, emotional, and spiritual responses. It also describes the energetic treatment that effectively eliminated the trauma, returning the tornado victim to a stable state. The article concludes with clinical and research implications and relates the treatment of the tornado victims to holistic nursing. The treatment holds promise for victims of posttraumatic stress disorder. PMID:15035243

  16. Human response to vibroacoustic environments of space vehicles

    NASA Astrophysics Data System (ADS)

    Willshire, K. F.

    1984-10-01

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

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

    PubMed

    Ahola-Launonen, Johanna

    2016-04-01

    This article discusses the suggestion of having the notion of solidarity as the foundational value for welfare scheme reforms. Solidarity is an emerging concept in bioethical deliberations emphasizing the need for value-oriented discussion in revising healthcare structures, and the notion has been contrasted with liberal justice and rights. I suggest that this contrast is unnecessary, flawed, and potentially counterproductive. As necessary as the sense of solidarity is in a society, it is an insufficient concept to secure the goals related to social responsibility. The discussion on solidarity is also based on a questionable sense of nostalgia. Furthermore, solidarity and liberal justice share essential objectives concerning welfare schemes; therefore, the question arises whether the proper comparison should in the first place be within justice and solidarity. PMID:26957443

  18. Human response to vibroacoustic environments of space vehicles

    NASA Technical Reports Server (NTRS)

    Willshire, K. F.

    1984-01-01

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

  19. Human immune responses to Schistosoma mansoni vaccine candidate antigens.

    PubMed

    Ribeiro de Jesus, A; Araújo, I; Bacellar, O; Magalhães, A; Pearce, E; Harn, D; Strand, M; Carvalho, E M

    2000-05-01

    To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n = 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP- and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-gamma levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3- and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio = 11.2 [95% confidence interval, 2.7 to 45.8]). PMID:10768975

  20. The Human Sympathetic Nervous System Response to Spaceflight

    NASA Technical Reports Server (NTRS)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

    2003-01-01

    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  1. Evaluation of human response to structural vibration induced by sonic boom

    NASA Technical Reports Server (NTRS)

    Sutherland, L. C.; Czech, J.

    1992-01-01

    This paper addresses the topic of building vibration response to sonic boom and the evaluation of the associated human response to this vibration. The paper reexamines some of the issues addressed in the previous extensive coverage of the topic, primarily by NASA, and attempts to offer a fresh viewpoint for some of the problems that may assist in reassessing the potential impact of sonic boom over populated areas. The topics addressed are: (1) human response to vibration; (2) criteria for, and acoustic signature of rattle; (3) structural response to shaped booms, including definition of two new descriptors for assessing the structural response to sonic boom; and (4) a detailed review of the previous NASA/FAA Sonic Boom Test Program involving structural response measurements at Edwards AFB and an initial estimate of structural response to sonic booms from possible high speed civil transport configurations. Finally, these estimated vibration responses are shown to be substantially greater than the human response and rattle criteria developed earlier.

  2. Active muscle response using feedback control of a finite element human arm model.

    PubMed

    Östh, Jonas; Brolin, Karin; Happee, Riender

    2012-01-01

    Mathematical human body models (HBMs) are important research tools that are used to study the human response in car crash situations. Development of automotive safety systems requires the implementation of active muscle response in HBM, as novel safety systems also interact with vehicle occupants in the pre-crash phase. In this study, active muscle response was implemented using feedback control of a nonlinear muscle model in the right upper extremity of a finite element (FE) HBM. Hill-type line muscle elements were added, and the active and passive properties were assessed. Volunteer tests with low impact loading resulting in elbow flexion motions were performed. Simulations of posture maintenance in a gravity field and the volunteer tests were successfully conducted. It was concluded that feedback control of a nonlinear musculoskeletal model can be used to obtain posture maintenance and human-like reflexive responses in an FE HBM. PMID:21294008

  3. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

    PubMed

    Madden, Lauran; Juhas, Mark; Kraus, William E; Truskey, George A; Bursac, Nenad

    2015-01-01

    Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders. PMID:25575180

  4. Olfactory Responses of Southern House Mosquito, Culex quinquefasciatus, to Human Odorants.

    PubMed

    Ye, Zi; Liu, Feng; Liu, Nannan

    2016-06-01

    Mosquito control is essential to protect humans from mosquito-borne diseases. The host recognition between mosquitoes and humans is achieved by the mosquito olfactory system. Antennal sensilla, which house olfactory receptor neurons, are responsible for detecting chemical cues from hosts. To deepen our understanding of the mechanisms involved in the host seeking behavior of mosquitoes, we conducted an electrophysiological study to investigate the response profile of each type of antennal sensilla to human odorants using single sensillum recording. In this study, more than 100 human odorants have been applied as stimuli to 5 morphological types of sensilla, long sharp trichoid (LST), short sharp trichoid (SST), short blunt trichoid I (SBTI), short blunt trichoid II (SBTII), and grooved peg (GP). Different types of sensilla present distinctive response profiles to the human odorants tested. In particular, SST, SBTI, and SBTII sensilla responded to more than 1 category of human odorants, while GP and LST were narrowly tuned to amines and methyl nonanoate, respectively. The dose-dependent patterns and odorant-specific/chemical structure-specific temporal dynamics of SBTI and SBTII antennal sensilla to human odorants had been further detected. Taken together, our study provides the new information on the olfactory physiology of Culex quinquefasciatus (Diptera: Culicidae) to human odorants, leading to a better understanding of mosquito-host recognition and being important for future development of new reagents in the mosquito control. PMID:26969630

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

    PubMed Central

    Kulish, Vladimir V.

    2015-01-01

    Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy. PMID:26089955

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

    PubMed Central

    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. PMID:27293597

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

    PubMed

    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. PMID:27293597

  8. Initial In Vitro Investigation of the Human Immune Response to Corneal Cells from Genetically Engineered Pigs

    PubMed Central

    Koike, Naoko; Long, Cassandra; Piluek, Jordan; Roh, Danny S.; SundarRaj, Nirmala; Funderburgh, James L.; Mizuguchi, Yoshiaki; Isse, Kumiko; Phelps, Carol J.; Ball, Suyapa F.; Ayares, David L.; Cooper, David K. C.

    2011-01-01

    Purpose. To compare the in vitro human humoral and cellular immune responses to wild-type (WT) pig corneal endothelial cells (pCECs) with those to pig aortic endothelial cells (pAECs). These responses were further compared with CECs from genetically engineered pigs (α1,3-galactosyltransferase gene-knockout [GTKO] pigs and pigs expressing a human complement-regulatory protein [CD46]) and human donors. Methods. The expression of Galα1,3Gal (Gal), swine leukocyte antigen (SLA) class I and class II on pCECs and pAECs, with or without activation by porcine IFN-γ, was tested by flow cytometry. Pooled human serum was used to measure IgM/IgG binding to and complement-dependent cytotoxicity (CDC) to cells from WT, GTKO, and GTKO/CD46 pigs. The human CD4+ T-cell response to cells from WT, GTKO, GTKO/CD46 pigs and human was tested by mixed lymphocyte reaction (MLR). Results. There was a lower level of expression of the Gal antigen and of SLA class I and II on the WT pCECs than on the WT pAECs, resulting in less antibody binding and reduced human CD4+ T-cell proliferation. However, lysis of the WT pCECs was equivalent to that of the pAECs, suggesting more susceptibility to injury. There were significantly weaker humoral and cellular responses to the pCECs from GTKO/CD46 pigs compared with the WT pCECs, although the cellular response to the GTKO/CD46 pCECs was greater than to the human CECs. Conclusions. These data provide the first report of in vitro investigations of CECs from genetically engineered pigs and suggest that pig corneas may provide an acceptable alternative to human corneas for clinical transplantation. PMID:21596821

  9. Tubulin acetylation: responsible enzymes, biological functions and human diseases.

    PubMed

    Li, Lin; Yang, Xiang-Jiao

    2015-11-01

    Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function. PMID:26227334

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

    NASA Technical Reports Server (NTRS)

    Moore, Berrien, III; Melillo, Jerry

    1994-01-01

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

  11. The human brain response to dental pain relief.

    PubMed

    Meier, M L; Widmayer, S; Abazi, J; Brügger, M; Lukic, N; Lüchinger, R; Ettlin, D A

    2015-05-01

    Local anesthesia has made dental treatment more comfortable since 1884, but little is known about associated brain mechanisms. Functional magnetic resonance imaging is a modern neuroimaging tool widely used for investigating human brain activity related to sensory perceptions, including pain. Most brain regions that respond to experimental noxious stimuli have recently been found to react not only to nociception alone, but also to visual, auditory, and other stimuli. Thus, presumed functional attributions have come under scrutiny regarding selective pain processing in the brain. Evidently, innovative approaches are warranted to identify cerebral regions that are nociceptive specific. In this study, we aimed at circumventing known methodological confounders by applying a novel paradigm in 14 volunteers: rather than varying the intensity and thus the salience of painful stimuli, we applied repetitive noxious dental stimuli at constant intensity to the left mandibular canine. During the functional magnetic resonance imaging paradigm, we suppressed the nociceptive barrage by a mental nerve block. Brain activity before and after injection of 4% articaine was compared intraindividually on a group level. Dental pain extinction was observed to correspond to activity reduction in a discrete region of the left posterior insular cortex. These results confirm previous reports demonstrating that direct electrical stimulation of this brain region-but not of others-evokes bodily pain sensations. Hence, our investigation adds further evidence to the notion that the posterior insula plays a unique role in nociceptive processing. PMID:25691071

  12. Lipolytic response to glucose infusion in human subjects

    SciTech Connect

    Wolfe, R.R.; Peters, E.J.

    1987-02-01

    The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and (1- TC)palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg x min , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg x min , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg x min infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  14. Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans

    PubMed Central

    Schnarr, Kara; Carter, Timothy F.; Gillis, Daniel; Webber, Colin; Dayes, Ian; Dolling, Joanna A.; Gulenchyn, Karen; Boreham, Douglas R.

    2015-01-01

    The biological effects of exposure to radioactive fluorodeoxyglucose (18F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo 18F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of 18F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of 18F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual’s radiation response. In summary, the results of this study indicate18F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures. PMID:26740810

  15. Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis.

    PubMed Central

    Elkhalifa, M Y; Ghalib, H W; Dafa'Alla, T; Williams, J F

    1991-01-01

    Characterization of in vitro lymphocyte responsiveness was performed on selected groups of onchocerciasis patients from Sudan and Sierra Leone. These patients manifested a very broad range of clinical signs and showed widely divergent parasite infection intensities. Lymphocyte proliferative responses to soluble Onchocerca volvulus antigen (sAg) were poor in infected persons; mitogen and PPD responses were maintained in the normal range in one group of patients from southwestern Sudan, but were profoundly depressed in a group from N.E. Sudan. Proliferative responses and interferon-gamma (INF-gamma) secretion were very significantly depressed in the presence of live microfilariae of O. volvulus or secretions/excretions (S/E) from microfilariae (mf) or from female, but not male, adult parasites. Lymphocyte responses were maintained near normal when exogenous IL-2 was added to these cultures. The results indicate that O. volvulus infection and its clinical consequences are not consistently associated with systemic deficits in immune responsiveness. However, suppression of lymphocyte reactivity by mf and S/E in vitro suggests that direct parasite intervention in host cell responses could be taking place in vivo, perhaps at the local microenvironment level; mediated by effects on cytokine production. PMID:1747951

  16. Implicit learning and generalization of stretch response modulation in humans.

    PubMed

    Turpin, Nicolas A; Levin, Mindy F; Feldman, Anatol G

    2016-06-01

    Adaptation of neural responses to repeated muscle stretching likely represents implicit learning to minimize muscle resistance to perturbations. To test this hypothesis, the forearm was placed on a horizontal manipulandum. Elbow flexors or extensors compensated an external load and were stretched by 20° or 70° rotations. Participants were instructed not to intervene by intentionally modifying the muscle resistance elicited by stretching. In addition to phasic stretch reflexes (SRs), muscle stretching was associated with inhibitory periods (IPs) in the ongoing muscle activity starting at minimal latencies of ∼35 ms. The SR amplitude decreased dramatically across 5-12 trials and was not restored after a resting period of 3-5 min, despite the increase in stretch amplitude from 20° to 70°, but IPs remained present. When SRs were suppressed, stretching of originally nonstretched, antagonist muscles initiated after the rest period showed immediate SR suppression while IPs remained present in the first and subsequent trials. Adaptation to muscle stretching thus includes features characteristic of implicit learning such as memory consolidation and generalization. Adaptation may be achieved by central shifts in the threshold positions at which muscles begin to be activated. Shifts are thought to be prepared in advance and triggered with stretch onset. Threshold position resetting provides a comprehensive explanation of the results in the broader context of the control of posture, movement, and motor learning in the healthy and damaged nervous system. PMID:27052586

  17. Response of intracerebral human glioblastoma xenografts to multifraction radiation exposures

    SciTech Connect

    Ozawa, Tomoko; Faddegon, Bruce A.; Hu, Lily J.; Bollen, Andrew W.; Lamborn, Kathleen R.; Deen, Dennis F. . E-mail: ddeen@itsa.ucsf.edu

    2006-09-01

    Purpose: We investigated the effects of fractionated radiation treatments on the life spans of athymic rats bearing intracerebral brain tumors. Methods and Materials: U-251 MG or U-87 MG human glioblastoma cells were implanted into the brains of athymic rats, and the resulting tumors were irradiated once daily with various doses of ionizing radiation for 5 consecutive days or for 10 days with a 2-day break after Day 5. Results: Five daily doses of 1 and 1.5 Gy, and 10 doses of 0.75 and 1 Gy, cured some U-251 MG tumors. However, five daily doses of 0.5 Gy increased the survival time of animals bearing U-251 MG tumors 5 days without curing any animals of their tumors. Ten doses of 0.3 Gy given over 2 weeks extended the lifespan of the host animals 9 days without curing any animals. For U-87 MG tumors, 5 daily doses of 3 Gy produced an increased lifespan of 8 days without curing any animals, and 10 doses of 1 Gy prolonged lifespan 5.5 days without curing any animals. The differences in extension of life span between the 5- and 10-fraction protocols were minor for either tumor type. Conclusion: The finding that the U-251 MG tumors are more sensitive than U-87 MG tumors, despite the fact that U-251 MG tumors contain many more hypoxic cells than U-87 MG tumors, suggests the intrinsic cellular radiosensitivities of these cell lines are more important than hypoxia in determining their in vivo radiosensitivities.

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

    NASA Technical Reports Server (NTRS)

    Newby, N.; Somers, J. T.; Caldwell, E.; Gernhardt, M.

    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 chest z-acceleration was in phase

  19. Plasma atriopeptin response to prolonged cycling in humans.

    PubMed

    Perrault, H; Cantin, M; Thibault, G; Brisson, G R; Brisson, G; Beland, M

    1991-03-01

    The exercise-induced increase in plasma atriopeptin (ANP) has been related to exercise intensity. The independent effect of duration on the ANP response to dynamic exercise remains incompletely documented. The purpose of this study was to describe the time course of plasma ANP concentration during a 90-min cycling exercise protocol and to examine this in light of concurrent variations in plasma arginine vasopressin (AVP), aldosterone (ALD), and catecholamine (norepinephrine and epinephrine) concentrations as well as plasma renin activity (PRA). Seven male and four female healthy college students (23 +/- 2 yr) completed a prolonged exercise protocol on a cycle ergometer at an intensity of 67% of maximal O2 uptake. Venous blood was sampled through an indwelling catheter at rest, after 15, 30, 45, 60, and 90 min of exercise, and after 30 min of passive upright recovery. Results (means +/- SE) indicate an increase in ANP from rest (22 +/- 2.6 pg/ml) at 15 min of exercise (45.3 +/- 7.4 pg/ml) with a further increase at 30 min (59.4 +/- 9.8 pg/ml) and a leveling-off thereafter until completion of the exercise protocol (51.7 +/- 10.7 pg/ml). In plasma ALD and PRA, a significant increase was found from rest (ALD, 21.4 +/- 6.4 ng/dl), PRA, 2.5 +/- 0.5 ng.ml-1.h-1 after 30 min of cycling, which continued to increase until completion of the exercise (ALD 46.6 +/- 8.7 ng/dl, PRA 9.5 +/- 0.9 ng.ml-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1827790

  20. Plasma matrix metalloproteinase-9 response to downhill running in humans.

    PubMed

    Welsh, M C; Allen, D L; Byrnes, W C

    2014-05-01

    Matrix metalloproteinase-9 is a proteolytic enzyme capable of degrading proteins of the muscle extracellular matrix. Systemic levels of MMP-9 or its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), have the potential to serve as blood markers of exercise-induced muscle damage. The purpose of this study was to determine if an eccentrically-dominated task, downhill running (DHR), produces changes in plasma MMP-9 or TIMP-1 and examine the relationship between MMP-9/TIMP-1 levels and indirect indicators of muscle damage. Subjects were sedentary (SED, n=12) or had a history of concentrically-biased training (CON, n=9). MMP-9 and TIMP-1 were measured before (Pre-Ex), immediately after (Post-Ex), and 1-, 2-, 4-, and 7-days post-DHR (-10°), and compared to discomfort ratings, creatine kinase activity and strength loss. At 1-day Post-Ex, discomfort increased (5.6 ± 7.8 to 45.5 ± 19.9 mm; 0-100 mm scale), strength decreased (-6.9 ± 1.6%) and CK increased (162.9 ± 177.2%). MMP-9 was modestly but significantly increased at Post-Ex in both CONC and SED (32.7 ± 33.6%) and at 4-days in SED (66.9 ± 88.1%), Individual responses were variable, however. There were no correlations between MMPs and discomfort ratings, plasma CK or strength. While plasma MMP-9 changes may be detectable in the systemic circulation after DHR, they are small and do not correspond to other markers of damage. PMID:24048912

  1. Differential neural responses to humans vs. robots: an event-related potential study.

    PubMed

    Hirai, Masahiro; Hiraki, Kazuo

    2007-08-24

    Do we perceive humanoid robots as human beings? Recent neuroimaging studies have reported similarity in the neural processing of human and robot actions in the superior temporal sulcus area but a differential neural response in the premotor area. These studies suggest that the neural activity of the occipitotemporal region would not be affected by appearance information. Unlike those studies, in this study, by using the inversion effect as an index, we demonstrated for the first time that the appearance information of a presented action affects neural responses in the occipitotemporal region. In event-related potential (ERP) studies, the inversion effect is the phenomenon whereby an upright face- and body-sensitive ERP component in the occipitotemporal region is enhanced and delayed up to 200 ms in response to an inverted face and body, but not to an inverted object. We used three kinds of walking animation with different appearance information (human, robot, and point-light) as well as inverted stimuli of each appearance. The anatomical structure and walking speed of the presented stimuli were all identical. The results showed that the inversion effect occurred in the right occipitotemporal region only in response to human appearance, and not robotic and point-light appearances. That is, the amplitude of the inverted condition of human appearance was significantly larger than that of the upright condition only. Our results, which are contrary to other recent neuroimaging studies, suggested that appearance information affects the neural response in the occipitotemporal region. PMID:17658496

  2. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study

    PubMed Central

    Goutianos, Georgios; Tzioura, Aikaterini; Kyparos, Antonios; Paschalis, Vassilis; Margaritelis, Nikos V; Veskoukis, Aristidis S; Zafeiridis, Andreas; Dipla, Konstantina; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2015-01-01

    Animal models are widely used in biology and the findings of animal research are traditionally projected to humans. However, recent publications have raised concerns with regard to what extent animals and humans respond similar to physiological stimuli. Original data on direct in vivo comparison between animals and humans are scarce and no study has addressed this issue after exercise. We aimed to compare side by side in the same experimental setup rat and human responses to an acute exercise bout of matched intensity and duration. Rats and humans ran on a treadmill at 86% of maximal velocity until exhaustion. Pre and post exercise we measured 30 blood chemistry parameters, which evaluate iron status, lipid profile, glucose regulation, protein metabolism, liver, and renal function. ANOVA indicated that almost all biochemical parameters followed a similar alteration pattern post exercise in rats and humans. In fact, there were only 2/30 significant species × exercise interactions (in testosterone and globulins), indicating different responses to exercise between rats and humans. On the contrary, the main effect of exercise was significant in 15/30 parameters and marginally nonsignificant in other two parameters (copper, P = 0.060 and apolipoprotein B, P = 0.058). Our major finding is that the rat adequately mimics human responses to exercise in those basic blood biochemical parameters reported here. The physiological resemblance of rat and human blood responses after exercise to exhaustion on a treadmill indicates that the use of blood chemistry in rats for exercise physiology research is justified. PMID:25677548

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

    PubMed

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

    2011-01-01

    Optic flow is one of the most important sources of information for enabling human navigation through the world. A striking finding from single-cell studies in monkeys is the rapid saturation of response of MT/MST areas with the density of optic flow type motion information. These results are reflected psychophysically in human perception in the saturation of motion aftereffects. We began by comparing responses to natural optic flow scenes in human visual brain areas to responses to the same scenes with inverted contrast (photo negative). This changes scene familiarity while preserving local motion signals. This manipulation had no effect; however, the response was only correlated with the density of local motion (calculated by a motion correlation model) in V1, not in MT/MST. To further investigate this, we manipulated the visible proportion of natural dynamic scenes and found that areas MT and MST did not increase in response over a 16-fold increase in the amount of information presented, i.e., response had saturated. This makes sense in light of the sparseness of motion information in natural scenes, suggesting that the human brain is well adapted to exploit a small amount of dynamic signal and extract information important for survival. PMID:21908713

  4. Characterization of the Inflammasome in Human Kupffer Cells in Response to Synthetic Agonists and Pathogens.

    PubMed

    Zannetti, Claudia; Roblot, Guillaume; Charrier, Emily; Ainouze, Michelle; Tout, Issam; Briat, François; Isorce, Nathalie; Faure-Dupuy, Suzanne; Michelet, Maud; Marotel, Marie; Kati, Semra; Schulz, Thomas F; Rivoire, Michel; Traverse-Glehen, Alexandra; Luangsay, Souphalone; Alatiff, Omran; Henry, Thomas; Walzer, Thierry; Durantel, David; Hasan, Uzma

    2016-07-01

    The liver is the largest gland in the human body and functions as an innate immune organ. Liver macrophages called Kupffer cells (KC) constitute the largest group of macrophages in the human body. Innate immune responses involving KC represent the first line of defense against pathogens in the liver. Human monocyte-derived macrophages have been used to characterize inflammasome responses that lead to the release of the proinflammatory cytokines IL-1β and IL-18, but it has not yet been determined whether human KC contain functional inflammasomes. We show, to our knowledge for the first time, that KC express genes and proteins that make up several different inflammasome complexes. Moreover, activation of KC in response to the absent in melanoma 2 (AIM2) inflammasome led to the production of IL-1β and IL-18, which activated IL-8 transcription and hepatic NK cell activity, respectively. Other inflammasome responses were also activated in response to selected bacteria and viruses. However, hepatitis B virus inhibited the AIM2 inflammasome by reducing the mRNA stability of IFN regulatory factor 7, which regulated AIM2 transcription. These data demonstrate the production of IL-1β and IL-18 in KC, suggesting that KC contain functional inflammasomes that could be important players in the innate immune response following certain infections of the liver. We think our findings could potentially aid therapeutic approaches against chronic liver diseases that activate the inflammasome. PMID:27226092

  5. Are Drug Companies Living Up to Their Human Rights Responsibilities? Moving Toward Assessment

    PubMed Central

    Gruskin, Sofia; Raad, Zyde

    2010-01-01

    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. PMID:20927356

  6. Magnetic and electrical responses of the human brain to texture-defined form and to textons.

    PubMed

    Regan, D; He, P

    1995-09-01

    1. We searched for a neurophysical correlate of preattentive texture discrimination by recording magnetic and electric evoked responses from the human brain during the first few hundred milliseconds following the presentation of texture-defined (TD) checkerboard form. The only two textons that changed when the TD checkerboard appeared or disappeared were the local orientation and line termination textons. (Textons are conspicuous local features within a texture pattern). 2. Our evidence that the magnetic response to TD form cannot be explained in terms of responses to the two associated textons is as follows: 1) by dissociating the two responses we showed that the magnetic response to TD form is almost entirely independent of the magnetic response to the local orientation texton; 2) a further distinction between the two responses is that their distributions over the head are different; and 3) the magnetic response to TD form differs from the magnetic response to the line termination texton in both distribution over the head and waveform. We conclude that this evidence identifies the existence of a brain response correlate of preattentive texture discrimination. 3. We also recorded brain responses to luminance-defined (LD) checkerboard form. Our grounds for concluding that magnetic brain responses to the onset of checkerboard form are generated by different and independent neural systems for TD and LD form are as follows: 1) magnetic responses to the onset of TD form and LD form had different distributions over the skull, had different waveforms, and depended differently on check size; and 2) the waveform of the response to superimposed TD and LD checks closely approximated the linear sum of responses to TD checks and LD checks alone. 4. One possible explanation for the observed differences between the magnetic and electric evoked responses is that responses to both onset and offset of TD form predominantly involve neurons aligned parallel to the skull, whereas that

  7. Alpha 1A-adrenoceptor-mediated contractile responses of the human vas deferens.

    PubMed Central

    Furukawa, K.; Rosario, D. J.; Smith, D. J.; Chapple, C. R.; Uchiyama, T.; Chess-Williams, R.

    1995-01-01

    1. The predominant alpha 1-adrenoceptor mediating contractions of the human vas deferens has been characterised in vitro by use of subtype selective antagonists. 2. Responses of human epididymal vas deferens were obtained to phenylephrine in the presence of amine uptake inhibitors and propranolol. The effects of the alpha 1-adrenoceptor antagonists, 5-methylurapidil, oxymetazoline, WB4101, prazosin and chloroethylclonidine were examined and also the L-type calcium channel blocker, nifedipine. 3. 5-Methylurapidil, WB4101, oxymetazoline and prazosin acted as competitive antagonists of the responses to phenylephrine, yielding pA2 values of 8.8, 9.2, 7.7 and 8.8 respectively. All four antagonists produced Schild plots with slopes similar to unity and maximum responses to phenylephrine were not altered in the presence of any of the antagonists. 4. Tamsulosin (1 nM) caused rightward shifts of phenylephrine concentration-response curves yielding an apparent pKB value of 10.0. However, maximum responses were also reduced by 51% with this concentration of antagonist. 5. Incubation of tissues with chloroethylclonidine (100 microM for 40 min) failed to alter responses significantly but the presence of nifedipine (1 microM) reduced maximum responses to phenylephrine by 32%. 6. The high affinity of 5-methylurapidil, oxymetazoline and WB4101, together with the failure of chloroethylclonidine to antagonize responses, indicate that the predominant alpha 1-adrenoceptor mediating contraction of the human vas deferens has the characteristics previously described for the pharmacologically-defined alpha 1A-adrenoceptor. The data are also consistent with those described for the cloned alpha 1c-adrenoceptor subtype thereby supporting the hypothesis that the two receptors are identical. The human vas deferens therefore represents a readily accessible preparation for functional studies of the human alpha 1A-adrenoceptor. PMID:8564226

  8. Who is Responsible for Human Suffering due to Earthquakes?

    NASA Astrophysics Data System (ADS)

    Wyss, M.

    2012-12-01

    A court in L'Aquila, Italy, convicted seven to six years in prison and a combined fine of two million Euros for not following their "obligation to avoid death, injury and damage, or at least to minimize them," as the prosecution alleged. These men lose their jobs and pensions, and are banned from holding public office. Meanwhile, the town of L'Aquila is teeming with furious citizens, who are preparing additional civil suits against the defendants, whom they hold responsible for the deaths of their loved ones, killed by collapsing buildings during the magnitude 6.3 earthquake of April 6, 2009. Before this shock, an earthquake swarm had scared the inhabitants for several weeks. To calm the population, the vice-director of the Department of Civil Protection (DCP) called a meeting of the Italian Commission of Great Risks (CGR) in L'Aquila to assess the situation on March 31. One hour before this meeting, the vice-director stated in a TV interview that the seismic situation in L'Aquila was "certainly normal" and posed "no danger" and he added that "the scientific community continues to assure me that, to the contrary, it's a favorable situation because of the continuous discharge of energy." This statement is untrue in two ways. Firstly, small earthquakes do not release enough strain energy to reduce the potential for a large shock, and secondly no seismologist would make such a statement because we know it is not true. However, the population clung to the idea: "the more tremors, the less danger". People who lost relatives allege that they would have left their homes, had they not been falsely assured of their safety. The court treated all seven alike, although they had very different functions and obligations. Two were leaders in DCP, four were members of the CGR, and one was a seismology expert, who brought the latest seismic data. The minutes of the meeting show that none of the experts said anything wrong. They all stated that the probability of a main shock to

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

    ERIC Educational Resources Information Center

    Murithi, Tim

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Lemberger, Matthew E.

    2012-01-01

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

  11. Electrophysiological CNS-processes related to associative learning in humans.

    PubMed

    Christoffersen, Gert R J; Schachtman, Todd R

    2016-01-01

    The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. PMID:26367470

  12. Toward data-to-decision sensing environments to assess human intent from responses to stimuli

    NASA Astrophysics Data System (ADS)

    Kothari, Cartik R.; Russomanno, David J.; Sartain, Ronald B.; Frankel, Ronald

    2012-06-01

    Remote detection of harmful intent is necessary for eective and appropriate countermeasures and will reduce risks to life and property. Trained human observers and sensor systems typically use facial expressions, gaits, gestures, perspiration, and a number of other observable characteristics as possible indicators of harmful intent with mixed results. It is proposed that responses of human subjects to external stimuli can be used as additional indicators of harmful intent in surveillance contexts. A variety of alerting stimuli, possible responses to the stimuli, features to be sensed by sensors, and the utility of these sensed features as indicators of harmful intent are discussed in this paper. An ontology-based data-to-decision framework for assessing human intent, which would leverage the formal representations of the alerting stimuli, as well as the variety of possible responses, is proposed in the context of Semantic Web infrastructure.

  13. At a crossroads: human DNA tumor viruses and the host DNA damage response.

    PubMed

    Nikitin, Pavel A; Luftig, Micah A

    2011-07-01

    Human DNA tumor viruses induce host cell proliferation in order to establish the necessary cellular milieu to replicate viral DNA. The consequence of such viral-programmed induction of proliferation coupled with the introduction of foreign replicating DNA structures makes these viruses particularly sensitive to the host DNA damage response machinery. In fact, sensors of DNA damage are often activated and modulated by DNA tumor viruses in both latent and lytic infection. This article focuses on the role of the DNA damage response during the life cycle of human DNA tumor viruses, with a particular emphasis on recent advances in our understanding of the role of the DNA damage response in EBV, Kaposi's sarcoma-associated herpesvirus and human papillomavirus infection. PMID:21927617

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

    PubMed Central

    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

  15. Functionally relevant responses to human facial expressions of emotion in the domestic horse (Equus caballus).

    PubMed

    Smith, Amy Victoria; Proops, Leanne; Grounds, Kate; Wathan, Jennifer; McComb, Karen

    2016-02-01

    Whether non-human animals can recognize human signals, including emotions, has both scientific and applied importance, and is particularly relevant for domesticated species. This study presents the first evidence of horses' abilities to spontaneously discriminate between positive (happy) and negative (angry) human facial expressions in photographs. Our results showed that the angry faces induced responses indicative of a functional understanding of the stimuli: horses displayed a left-gaze bias (a lateralization generally associated with stimuli perceived as negative) and a quicker increase in heart rate (HR) towards these photographs. Such lateralized responses towards human emotion have previously only been documented in dogs, and effects of facial expressions on HR have not been shown in any heterospecific studies. Alongside the insights that these findings provide into interspecific communication, they raise interesting questions about the generality and adaptiveness of emotional expression and perception across species. PMID:26864784

  16. Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.

    PubMed

    Reese, Tiffany A; Bi, Kevin; Kambal, Amal; Filali-Mouhim, Ali; Beura, Lalit K; Bürger, Matheus C; Pulendran, Bali; Sekaly, Rafick-Pierre; Jameson, Stephen C; Masopust, David; Haining, W Nicholas; Virgin, Herbert W

    2016-05-11

    Immune responses differ between laboratory mice and humans. Chronic infection with viruses and parasites are common in humans, but are absent in laboratory mice, and thus represent potential contributors to inter-species differences in immunity. To test this, we sequentially infected laboratory mice with herpesviruses, influenza, and an intestinal helminth and compared their blood immune signatures to mock-infected mice before and after vaccination against yellow fever virus (YFV-17D). Sequential infection altered pre- and post-vaccination gene expression, cytokines, and antibodies in blood. Sequential pathogen exposure induced gene signatures that recapitulated those seen in blood from pet store-raised versus laboratory mice, and adult versus cord blood in humans. Therefore, basal and vaccine-induced murine immune responses are altered by infection with agents common outside of barrier facilities. This raises the possibility that we can improve mouse models of vaccination and immunity by selective microbial exposure of laboratory animals to mimic that of humans. PMID:27107939

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. Cyclic dinucleotides modulate human T-cell response through monocyte cell death.

    PubMed

    Tosolini, Marie; Pont, Frédéric; Verhoeyen, Els; Fournié, Jean-Jacques

    2015-12-01

    Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c-di-AMP and cGAMP, two adenosine-based cyclic dinucleotides, activated T lymphocytes in an unusual manner through monocyte cell death. c-di-AMP and cGAMP induced the selective apoptosis of human monocytes, and T lymphocytes were activated by the direct contact with these dying monocytes. The ensuing T-cell response comprised cell-cycle exit, phenotypic maturation into effector memory cells and proliferation arrest, but not cell death. This quiescence was transient since T cells remained fully responsive to further restimulation. Together, our results depict a novel activation pattern for human T lymphocytes: a transient quiescence induced by c-di-AMP- or cGAMP-primed apoptotic monocytes. PMID:26460927

  20. Cultured human airway epithelial cells (calu-3): a model of human respiratory function, structure, and inflammatory responses.

    PubMed

    Zhu, Yan; Chidekel, Aaron; Shaffer, Thomas H

    2010-01-01

    This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compared with Beractant and control, and perfluorocarbons also protect against hyperoxia-induced airway epithelial cell injury. The Calu-3 cell preparation is a sensitive and efficient preclinical model to study human respiratory processes and diseases related to oxygen- and ventilator-induced lung injury. PMID:20948883

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

    PubMed

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

    2015-06-01

    Almécija and colleagues claim that we apply a simplified understanding of bone functional adaptation and that our results of human-like hand use in Australopithecus africanus are not novel. We argue that our results speak to actual behavior, rather than potential behaviors, and our functional interpretation is well supported by our methodological approach, comparative sample, and previous experimental data. PMID:26045429

  2. Complexity of the primary genetic response to mitogenic activation of human T cells

    SciTech Connect

    Zipfel, P.F.; Siebenlist, U. ); Irving, S.G.; Kelly, K. )

    1989-03-01

    The authors describe the isolation and characterization of more than 60 novel cDNA clones that constitute part of the immediate genetic response to resting human peripheral blood T cells after mitogen activation. This primary response was highly complex, both in the absolute number of inducible genes and in the diversity of regulation. Although most of the genes expressed in activated T cells were shared with the activation response of normal human fibroblasts, a significant number were more restricted in tissue specificity and thus likely encode or effect the differentiated functions of activated T cells. The activatable genes could be further differentiated on the basis of kinetics of induction, response to cycloheximide, and sensitivity to the immunosuppressive drug cylcosporin A. It is of note that cyclosporin A inhibited the expression of more than 10 inducible genes, which suggests that this drug has a broad genetic mechanism of action.

  3. Complexity of the primary genetic response to mitogenic activation of human T cells.

    PubMed Central

    Zipfel, P F; Irving, S G; Kelly, K; Siebenlist, U

    1989-01-01

    We describe the isolation and characterization of more than 60 novel cDNA clones that constitute part of the immediate genetic response to resting human peripheral blood T cells after mitogen activation. This primary response was highly complex, both in the absolute number of inducible genes and in the diversity of regulation. Although most of the genes expressed in activated T cells were shared with the activation response of normal human fibroblasts, a significant number were more restricted in tissue specificity and thus likely encode or effect the differentiated functions of activated T cells. The activatable genes could be further differentiated on the basis of kinetics of induction, response to cycloheximide, and sensitivity to the immunosuppressive drug cyclosporin A. It is of note that cyclosporin A inhibited the expression of more than 10 inducible genes, which suggests that this drug has a broad genetic mechanism of action. Images PMID:2498643

  4. Expression Profiling of LPS Responsive miRNA in Primary Human Macrophages

    PubMed Central

    Naqvi, Afsar Raza; Zhong, Sheng; Dang, Hong; Fordham, Jezrom B; Nares, Salvador; Khan, Asma

    2016-01-01

    microRNAs (miRNAs) have emerged as important regulators of the innate and adaptive immune response. The purpose of the present study was to interrogate miRNA profiles of primary human macrophages challenged with bacterial lipopolysaccharide (LPS) with focus on expression kinetics. We employed Nanostring platform to precisely characterize the changes in miRNA expression following different doses and durations of LPS exposure. Differentially expressed miRNAs were identified in response to LPS challenge with convergent and divergent expression profiles. Pathway analysis of LPS-responsive miRNAs revealed regulation of biological processes linked to key cell signaling (including PIK3-Akt, MAP kinase, ErbB) and pathogen response pathways. Our data provide a comprehensive miRNA profiling of human primary macrophages treated with LPS. These results show that bacterial Toll like receptor (TLR) ligands can temporally modulate macrophage miRNA expression. PMID:27307950

  5. Device for rapid quantification of human carotid baroreceptor-cardiac reflex responses

    NASA Technical Reports Server (NTRS)

    Sprenkle, J. M.; Eckberg, D. L.; Goble, R. L.; Schelhorn, J. J.; Halliday, H. C.

    1986-01-01

    A new device has been designed, constructed, and evaluated to characterize the human carotid baroreceptor-cardiac reflex response relation rapidly. This system was designed for study of reflex responses of astronauts before, during, and after space travel. The system comprises a new tightly sealing silicon rubber neck chamber, a stepping motor-driven electrodeposited nickel bellows pressure system, capable of delivering sequential R-wave-triggered neck chamber pressure changes between +40 and -65 mmHg, and a microprocessor-based electronics system for control of pressure steps and analysis and display of responses. This new system provokes classic sigmoid baroreceptor-cardiac reflex responses with threshold, linear, and saturation ranges in most human volunteers during one held expiration.

  6. Differential response to bacteria, and TOLLIP expression, in the human respiratory tract

    PubMed Central

    Moncayo-Nieto, Olga Lucia; Wilkinson, Thomas S; Brittan, Mairi; McHugh, Brian J; Jones, Richard O; Conway Morris, Andrew; Walker, William S; Davidson, Donald J; Simpson, A John

    2014-01-01

    Objectives The observation that pathogenic bacteria are commonly tolerated in the human nose, yet drive florid inflammation in the lung, is poorly understood, partly due to limited availability of primary human cells from each location. We compared responses to bacterial virulence factors in primary human nasal and alveolar cells, and characterised the distribution of Toll-interacting protein (TOLLIP; an inhibitor of Toll-like receptor (TLR) signalling) in the human respiratory tract. Methods Primary cells were isolated from nasal brushings and lung tissue taken from patients undergoing pulmonary resection. Cells were exposed to lipopolysaccharide, lipoteichoic acid, peptidoglycan, CpG-C DNA or tumour necrosis factor (TNF). Cytokines were measured in cell supernatants. TOLLIP was characterised using quantitative real-time PCR and immunofluorescence. Results In primary alveolar, but not primary nasal, cells peptidoglycan significantly increased secretion of interleukin (IL)-1β, IL-6, IL-8, IL-10 and TNF. TLR2 expression was significantly higher in alveolar cells and correlated with IL-8 production. TOLLIP expression was significantly greater in nasal cells. Conclusion In conclusion, primary human alveolar epithelial cells are significantly more responsive to peptidoglycan than primary nasal epithelial cells. This may partly be explained by differential TLR2 expression. TOLLIP is expressed widely in the human respiratory tract, and may contribute to the regulation of inflammatory responses. PMID:25478190

  7. Color responses and their adaptation in human superior colliculus and lateral geniculate nucleus.

    PubMed

    Chang, Dorita H F; Hess, Robert F; Mullen, Kathy T

    2016-09-01

    We use an fMRI adaptation paradigm to explore the selectivity of human responses in the lateral geniculate nucleus (LGN) and superior colliculus (SC) to red-green color and achromatic contrast. We measured responses to red-green (RG) and achromatic (ACH) high contrast sinewave counter-phasing rings with and without adaptation, within a block design. The signal for the RG test stimulus was reduced following both RG and ACH adaptation, whereas the signal for the ACH test was unaffected by either adaptor. These results provide compelling evidence that the human LGN and SC have significant capacity for color adaptation. Since in the LGN red-green responses are mediated by P cells, these findings are in contrast to earlier neurophysiological data from non-human primates that have shown weak or no contrast adaptation in the P pathway. Cross-adaptation of the red-green color response by achromatic contrast suggests unselective response adaptation and points to a dual role for P cells in responding to both color and achromatic contrast. We further show that subcortical adaptation is not restricted to the geniculostriate system, but is also present in the superior colliculus (SC), an oculomotor region that until recently, has been thought to be color-blind. Our data show that the human SC not only responds to red-green color contrast, but like the LGN, shows reliable but unselective adaptation. PMID:27150230

  8. Interindividual variation in response to xenobiotic exposure established in precision-cut human liver slices.

    PubMed

    Jetten, Marlon J A; Claessen, Sandra M; Dejong, Cornelis H C; Lahoz, Agustin; Castell, José V; van Delft, Joost H M; Kleinjans, Jos C S

    2014-09-01

    Large differences in toxicity responses occur within the human population. In this study we evaluate whether interindividual variation in baseline enzyme activity (EA)/gene expression (GE) levels in liver predispose for the variation in toxicity responses by assessing dose-response relationships for several prototypical hepatotoxicants. Baseline levels of cytochrome-P450 (CYP) GE/EA were measured in precision-cut human liver slices. Slices (n=4-5/compound) were exposed to a dose-range of acetaminophen, aflatoxin B1, benzo(α) pyrene or 2-nitrofluorene. Interindividual variation in induced genotoxicity (COMET-assay and CDKN1A/p21 GE) and cytotoxicity (lactate dehydrogenase-leakage), combined with NQO1- and GSTM1-induced GE-responses for oxidative stress and GE-responses of several CYPs was evaluated. The benchmark dose-approach was applied as a tool to model exposure responses on an individual level. Variation in baseline CYP levels, both GE and EA, can explain variation in compound exposure-responses on an individual level. Network analyses enable the definition of key parameters influencing interindividual variation after compound exposure. For 2-nitrofluorene, this analysis suggests involvement of CYP1B1 in the metabolism of this compound, which represents a novel finding. In this study, GSTM1 which is known to be highly polymorphic within the human population, but so far could not be linked to toxicity in acetaminophen-poisoned patients, is suggested to cause interindividual variability in acetaminophen-metabolism, dependent on the individual's gene expression-responses of CYP-enzymes. This study demonstrates that using interindividual variation within network modelling provides a source for the definition of essential and even new parameters involved in compound-related metabolism. This information might enable ways to make more quantitative estimates of human risks. PMID:24949552

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

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  10. Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

    NASA Technical Reports Server (NTRS)

    Cajochen, C.; Zeitzer, J. M.; Czeisler, C. A.; Dijk, D. J.

    2000-01-01

    Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to <3 lux for several hours. Light exerted an acute alerting response as assessed by a reduction in the incidence of slow-eye movements, a reduction of EEG activity in the theta-alpha frequencies (power density in the 5-9 Hz range) as well as a reduction in self-reported sleepiness. This alerting response was positively correlated with the degree of melatonin suppression by light. In accordance with the dose response function for circadian resetting and melatonin suppression, the responses of all three indices of alertness to variations in illuminance were consistent with a logistic dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

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

    PubMed Central

    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. PMID:27227066

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

    PubMed

    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. PMID:27227066

  13. Source analysis of magnetic field responses from the human auditory cortex elicited by short speech sounds.

    PubMed

    Kuriki, S; Okita, Y; Hirata, Y

    1995-01-01

    We made a detailed source analysis of the magnetic field responses that were elicited in the human brain by different monosyllabic speech sounds, including vowel, plosive, fricative, and nasal speech. Recordings of the magnetic field responses from a lateral area of the left hemisphere of human subjects were made using a multichannel SQUID magnetometer, having 37 field-sensing coils. A single source of the equivalent current dipole of the field was estimated from the spatial distribution of the evoked responses. The estimated sources of an N1m wave occurring at about 100 ms after the stimulus onset of different monosyllables were located close to each other within a 10-mm-sided cube in the three-dimensional space of the brain. Those sources registered on the magnetic resonance images indicated a restricted area in the auditory cortex, including Heschl's gyri in the superior temporal plane. In the spatiotemporal domain the sources exhibited apparent movements, among which anterior shift with latency increase on the anteroposterior axis and inferior shift on the inferosuperior axis were common in the responses to all monosyllables. However, selective movements that depended on the type of consonants were observed on the mediolateral axis; the sources of plosive and fricative responses shifted laterally with latency increase, but the source of the vowel response shifted medially. These spatiotemporal movements of the sources are discussed in terms of dynamic excitation of the cortical neurons in multiple areas of the human auditory cortex. PMID:7621933

  14. Adapting to the human world: dogs' responsiveness to our social cues.

    PubMed

    Reid, Pamela J

    2009-03-01

    Dogs are more skilful than a host of other species at tasks which require they respond to human communicative gestures in order to locate hidden food. Four basic interpretations for this proficiency surface from distilling the research findings. One possibility is that dogs simply have more opportunity than other species to learn to be responsive to human social cues. A different analysis suggests that the domestication process provided an opening for dogs to apply general cognitive problem-solving skills to a novel social niche. Some researchers go beyond this account and propose that dogs' co-evolution with humans equipped them with a theory of mind for social exchanges. Finally, a more prudent approach suggests that sensitivity to the behaviours of both humans and conspecifics would be particularly advantageous for a social scavenger like the dog. A predisposition to attend to human actions allows for rapid early learning of the association between gestures and the availability of food. PMID:19056474

  15. Responses to Vocalizations and Auditory Controls in the Human Newborn Brain

    PubMed Central

    Cristia, Alejandrina; Minagawa, Yasuyo; Dupoux, Emmanuel

    2014-01-01

    In the adult brain, speech can recruit a brain network that is overlapping with, but not identical to, that involved in perceiving non-linguistic vocalizations. Using the same stimuli that had been presented to human 4-month-olds and adults, as well as adult macaques, we sought to shed light on the cortical networks engaged when human newborns process diverse vocalization types. Near infrared spectroscopy was used to register the response of 40 newborns' perisylvian regions when stimulated with speech, human and macaque emotional vocalizations, as well as auditory controls where the formant structure was destroyed but the long-term spectrum was retained. Left fronto-temporal and parietal regions were significantly activated in the comparison of stimulation versus rest, with unclear selectivity in cortical activation. These results for the newborn brain are qualitatively and quantitatively compared with previous work on newborns, older human infants, adult humans, and adult macaques reported in previous work. PMID:25517997

  16. Responses of human MG-63 osteosarcoma cell line and human osteoblast-like cells to pulsed electromagnetic fields.

    PubMed

    Sollazzo, V; Traina, G C; DeMattei, M; Pellati, A; Pezzetti, F; Caruso, A

    1997-01-01

    We have studied the effects of low-energy, low-frequency pulsed electromagnetic fields (PEMF) on cell proliferation, in both human osteoblast-like cells obtained from bone specimens and in human MG-63 osteosarcoma cell line. Assessment of osteoblastic phenotype was performed both by immunolabeling with antiosteonectin antibody and by verifying the presence of parathyroid hormone receptors. The cells were placed in multiwell plates and set in a tissue culture incubator between a pair of Helmholtz coils powered by a pulse generator (1.3 ms, 75 Hz) for different periods of time. [3H]Thymidine incorporation was used to evaluate cell proliferation. Since it had previously been observed that the osteoblast proliferative response to PEMF exposure may also be conditioned by the presence of serum in the medium, experiments were carried out at different serum concentrations. [3H]Thymidine incorporation increases in osteoblast-like cells, when they are exposed to PEMF in the presence of 10% fetal calf serum (FCS). The greatest effect is observed after 24 hours of PEMF exposure. No effects on cell proliferation are observed when osteoblast-like cells are exposed to PEMF in the presence of 0.5% FCS or in a serum-free medium. On the other hand, PEMF-exposed MG-63 cells show increased cell proliferation either at 10% FCS, 0.5% FCS and in serum-free medium. Nevertheless, the maximum effect of PEMF exposure on MG-63 cell proliferation depends on the percentage of FCS in the medium. The higher the FCS concentration, the faster the proliferative response to PEMF exposure. Our results show that, although MG-63 cells display some similarity with human bone cells, their responses to PEMF's exposure are quite different from that observed in normal human bone cells. PMID:9383242

  17. Hunted Woolly Monkeys (Lagothrix poeppigii) Show Threat-Sensitive Responses to Human Presence

    PubMed Central

    Papworth, Sarah; Milner-Gulland, E. J.; Slocombe, Katie

    2013-01-01

    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. PMID:23614003

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

    PubMed

    Papworth, Sarah; Milner-Gulland, E J; Slocombe, Katie

    2013-01-01

    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. PMID:23614003

  19. Potent Innate Immune Response to Pathogenic Leptospira in Human Whole Blood

    PubMed Central

    Hartskeerl, Rudy A.; van Gorp, Eric C. M.; Schuller, Simone; Monahan, Avril M.; Nally, Jarlath E.; van der Poll, Tom; van 't Veer, Cornelis

    2011-01-01

    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. PMID:21483834

  20. Development of an Ex Vivo Tissue Platform To Study the Human Lung Response to Coxiella burnetii.

    PubMed

    Graham, Joseph G; Winchell, Caylin G; Kurten, Richard C; Voth, Daniel E

    2016-05-01

    Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute debilitating flu-like illness that can also present as chronic endocarditis. Disease typically occurs following inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In human cells, C. burnetii generates a replication niche termed the parasitophorous vacuole (PV) by directing fusion with autophagosomes and lysosomes. C. burnetii requires this lysosomal environment for replication and uses a Dot/Icm type IV secretion system to generate the large PV. However, we do not understand how C. burnetii evades the intracellular immune surveillance that triggers an inflammatory response. We recently characterized human alveolar macrophage (hAM) infection in vitro and found that avirulent C. burnetii triggers sustained interleukin-1β (IL-1β) production. Here, we evaluated infection of ex vivo human lung tissue, defining a valuable approach for characterizing C. burnetii interactions with a human host. Within whole lung tissue, C. burnetii preferentially replicated in hAMs. Additionally, IL-1β production correlated with formation of an apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)-dependent inflammasome in response to infection. We also assessed potential activation of a human-specific noncanonical inflammasome and found that caspase-4 and caspase-5 are processed during infection. Interestingly, although inflammasome activation is closely linked to pyroptosis, lytic cell death did not occur following C. burnetii-triggered inflammasome activation, indicating an atypical response after intracellular detection. Together, these studies provide a novel platform for studying the human innate immune response to C. burnetii. PMID:26902725

  1. Human and laboratory rodent low response to alcohol: Is better consilience possible?

    PubMed Central

    Crabbe, John C.; Bell, Richard L.; Ehlers, Cindy L.

    2010-01-01

    If people are brought into the laboratory and given alcohol, there are pronounced differences among individuals in many responses to the drug. Some participants in alcohol challenge protocols show a cluster of “low level of responses to alcohol,” determined by observing post-drinking related changes in subjective, motor and physiological effects at a given dose level. Those individuals characterized as having low Level of Response (LR) to alcohol have been shown to be at increased risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship between low LR and AD appears to be in part genetic. LR to alcohol is an area where achieving greater consilience between the human and rodent phenotypes would seem to be highly likely. However, despite extensive data from both human and rodent studies, few attempts have been made to evaluate the human and animal data systematically in order to understand which aspects of LR appear to be most directly comparable across species and thus the most promising for further study. We review four general aspects of LR that could be compared between humans and laboratory animals: 1) behavioral measures of subjective intoxication; 2) body sway; 3) endocrine responses; and 4) stimulant, autonomic and electrophysiological responses. None of these aspects of LR provide completely face-valid direct comparisons across species. Nevertheless, one of the most replicated findings in humans is the low subjective response, but, as it may reflect either aversively-valenced and/or positively-valenced responses to alcohol as usually assessed, it is unclear which rodent responses are analogous. Stimulated heart rate appears to be consistent in animal and human studies, although at-risk subjects appear to be more, rather than less sensitive to alcohol using this measure. The hormone and electrophysiological data offer strong possibilities of understanding the neurobiological mechanisms, but the rodent data in particular are rather

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

    PubMed Central

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

    2010-01-01

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

  3. Sonic boom (human response and atmospheric effects) outdoor-to-indoor response to minimized sonic booms

    NASA Technical Reports Server (NTRS)

    Brown, David; Sutherland, Louis C.

    1992-01-01

    The preferred descriptor to define the spectral content of sonic booms is the Sound Exposure Spectrum Level, LE(f). This descriptor represents the spectral content of the basic noise descriptors used for describing any single event--the Sound Exposure Level, LE. The latter is equal to ten times the logarithms, to the base ten, of the integral, over the duration of the event, of the square of the instantaneous acoustic pressure, divided by the square of the reference pressure, 20 micro-Pa. When applied to the evaluation of community response to sonic booms, it is customary to use the so-called C-Weighted Sound Exposure Level, LCE, for which the frequency content of the instantaneous acoustic pressure is modified by the C-Weighting curve.

  4. Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses

    NASA Technical Reports Server (NTRS)

    Fritsch, Janice M.; Charles, John B.; Bennett, Barbara S.; Jones, Michele M.; Eckberg, Dwain L.

    1992-01-01

    The effect of a spaceflight on the vagally mediated baroreceptor-cardiac reflex responses of humans were investigated by measuring the responses (provoked by neck pressure changes) in supine position and the heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day long Space Shuttle missions. The results showed that exposures to spaceflight resulted in reduced baseline levels of the vagal-cardiac outflow and the vagally mediated responses to changes of the arterial baroreceptor input and that these changes contribute to postflight reductions of astronauts' ability to maintain standing arterial pressures.

  5. Positive human contact on the first day of life alters the piglet's behavioural response to humans and husbandry practices.

    PubMed

    Muns, Ramon; Rault, Jean-Loup; Hemsworth, Paul

    2015-11-01

    This experiment examined the effects of positive human contact at suckling on the first day of life on the behavioural and physiological responses of piglets to both humans and routine husbandry procedures. Forty litters from multiparous sows were randomly allocated to one of two treatments: Control (CC, minimal human interaction with day-old piglets) or Positive Contact (PC, human talking and caressing piglets during 6 suckling bouts on their first day of life, day 1). In each litter, 2 males and 2 females were randomly selected and their behavioural responses to tail docking (day 2), and to an experimenter (day 35) were studied. Escape behaviour at tail docking was assessed according to intensity (on a scale from 0 to 4 representing no movement to high intensity movement) and duration (on a scale from 0 to 3 representing no movement to continuous movement). At day 15 of age, a human approach and avoidance test was performed on focal piglets and at day 15, escape behaviour to capture before and after testing was recorded again. Blood samples for cortisol analysis were obtained from the focal piglets 30 min after tail docking and 1 h after weaning. Escape behaviour to tail docking of the PC piglets was of shorter duration than that of the CC piglets (P = 0.05). There was a tendency for the escape behaviour both before and after testing at day 15 to be of a lower intensity (P = 0.11 and P = 0.06, respectively) and a shorter duration (P = 0.06 and P = 0.08, respectively) in the PC piglets. There was a tendency for PC piglets to have higher cortisol concentrations after tail docking than the CC piglets (P = 0.07). Male piglets had higher cortisol concentrations after tail docking and after weaning than female piglets (P = 0.02 and P = 0.03). The results indicate that Positive Contact treatment reduced the duration of escape behaviour of piglets to tail docking. The role of classical conditioning, habituation and developmental changes in the observed effects of the

  6. Learning Agreements and Socially Responsible Approaches to Professional and Human Resource Development in the United Kingdom

    ERIC Educational Resources Information Center

    Wallis, Emma

    2008-01-01

    This article draws upon original qualitative data to present an initial assessment of the significance of learning agreements for the development of socially responsible approaches to professional and human resource development within the workplace. The article suggests that the adoption of a partnership-based approach to learning is more…

  7. EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN ALVEOLAR MACROPHAGE RESPONSIVENESS TO LIPOPOLYSACCHARIDE

    EPA Science Inventory

    Effects of diesel exhaust particles on human alveolar macrophage responsiveness to lipopolysaccharide
    S. Mundandhara1 , S. Becker2 and M. Madden2, 1UNC Center for Environmental Medicine, Asthma, and Lung Biology, 2US EPA, NHEERL, HSD, Chapel Hill, NC, US

    Epidemiological...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  10. OZONE-INDUCED RESPIRATORY SYMPTOMS AND LUNG FUNCTION DECREMENTS IN HUMANS: EXPOSURE-RESPONSE MODELS

    EPA Science Inventory

    Short duration exposure to ozone (<8 hr) is known to result in lung function decrements and respiratory symptoms in humans. The magnitudes of these responses are functions of ozone concentration (C), activity level measured by minute ventilation (Ve), duration of exposure (T), a...

  11. 24 CFR 7.14 - Responsibilities of the Office of Human Resources.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Responsibilities of the Office of Human Resources. 7.14 Section 7.14 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development EQUAL EMPLOYMENT OPPORTUNITY; POLICY, PROCEDURES AND PROGRAMS Equal Employment Opportunity Without Regard to...

  12. Comparative capture rate responses of mosquito vectors to light trap and human landing collection methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Capture rate responses of female Aedes albopictus Skuse, Anopheles quadrimaculatus Say, Culex nigripalpus Theobald, Culex quinquefasciatus Say, and Ochlerotatus triseriatus (Wiedemann) to CDC-type light trap (LT) and human landing (HL) collection methods were observed and evaluated for congruency wi...

  13. A Comparison of Human and Computer Marking of Short Free-Text Student Responses

    ERIC Educational Resources Information Center

    Butcher, Philip G.; Jordan, Sally E.

    2010-01-01

    The computer marking of short-answer free-text responses of around a sentence in length has been found to be at least as good as that of six human markers. The marking accuracy of three separate computerised systems has been compared, one system (Intelligent Assessment Technologies FreeText Author) is based on computational linguistics whilst two…

  14. Psychological impact of the animal-human bond in disaster preparedness and response.

    PubMed

    Hall, Molly J; Ng, Anthony; Ursano, Robert J; Holloway, Harry; Fullerton, Carol; Casper, Jacob

    2004-11-01

    The authors present an overview of the impact of the animal-human bond on disaster management and highlight the need to further examine the relationship of animals and humans in disaster response. The human connection to animals influences compliance with individual and community evacuation plans. Search and rescue teams with canine units confront physical and emotional demands that affect both handler and animal. The culling of animal populations on a scale such as occurred during the recent foot-and-mouth epidemic in the United Kingdom affects every member of rural society. Livestock farmers and their families endure enormous emotional losses, and veterinarians and government officials who must implement these programs suffer as well. A familiarity with and understanding of these issues is important for psychiatrists and other mental health professionals who are involved in disaster preparedness and response. PMID:15583518

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

    NASA Astrophysics Data System (ADS)

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

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

  16. Uncertain responses by humans and rhesus monkeys (Macaca mulatta) in a psychophysical same-different task

    NASA Technical Reports Server (NTRS)

    Shields, W. E.; Smith, J. D.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

    1997-01-01

    The authors asked whether animals, like humans, use an uncertain response adaptively to escape indeterminate stimulus relations. Humans and monkeys were placed in a same-different task, known to be challenging for animals. Its difficulty was increased further by reducing the size of the stimulus differences, thereby making many same and different trials difficult to tell apart. Monkeys do escape selectively from these threshold trials, even while coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their response strategies on short time scales according to the local task conditions. Signal-detection and optimality analyses confirm the similarity of humans' and animals' performances. Whereas associative interpretations account poorly for these results, an intuitive uncertainty construct does so easily. The authors discuss the cognitive processes that allow uncertainty's adaptive use and recommend further comparative studies of metacognition.

  17. Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines

    PubMed Central

    Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina; Athale, Shruti; Xue, Yaming; Yu, Chun I; Metang, Patrick; Cheruku, Abhilasha; Berthier, Isabelle; Gayet, Ingrid; Wang, Yuanyuan; Ohouo, Marina; Snipes, LuAnn; Xu, Hui; Obermoser, Gerlinde; Blankenship, Derek; Oh, Sangkon; Ramilo, Octavio; Chaussabel, Damien; Banchereau, Jacques; Palucka, Karolina; Pascual, Virginia

    2014-01-01

    The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines. PMID:25335753

  18. In vitro depression of human lymphocyte mitogen response (phytohaemagglutinin) by asbestos fibres.

    PubMed Central

    Barbers, R G; Shih, W W; Saxon, A

    1982-01-01

    Asbestosis is a fibrotic lung disease associated with chronic inhalation of asbestos dust. The response of peripheral blood mononuclear cells (PBM) to phytohaemagglutinin (PHA) in asbestosis patients has been reported to be impaired, suggesting a disturbance in the cell-mediated response of chronically exposed individuals. We demonstrated that PHA responses of normal PBM are also depressed when exposed to various forms of asbestos fibres in vitro. Furthermore, we showed the primary effect of the fibres to be on lymphoid (non-adherent) populations rather than monocytes (adherent cells). Exposure as brief as 1 hr affected the subsequent PHA response of the cells. This effect did not appear to involve suppressor cell activation nor was it mediated by soluble factors. Our findings therefore offer an explanation for the alterations in the cellular immune response observed in humans as a result of lymphoid cells coming into transient contact with inhaled asbestos fibres residing in the lung. Images Fig. 6 PMID:7116687

  19. The effect of adherent and phagocytic cells on human lymphocyte PHA responsiveness.

    PubMed

    Potter, M R; Moore, M

    1977-01-01

    The effect of small numbers of adherent and phagocytic cells on the human peripheral blood lymphocyte response to PHA was examined by depleting these cells from lymphocyte preparations. Lymphocyte preparations obtained by centrifugation on Ficoll--Triosil, which contained on average 85% lymphocytes, responded well to PHA. Depletion of cells adhering to nylon fibre, giving a population containing on average 95% lymphocytes, resulted in a considerably reduced response. Depletion of cells that adhered to plastic or ingested iron powder to give populations containing on average 90% lymphocytes, also reduced the PHA response, but to a lesser extent. Reduction in PHA responsiveness correlated with increasing lymphocyte purity. The responsiveness of nylon-column-filtered cells could be restored by adding a small number of cells from a monocyte-rich population. PMID:300303

  20. Human single-neuron responses at the threshold of conscious recognition

    PubMed Central

    Quiroga, R. Quian; Mukamel, R.; Isham, E. A.; Malach, R.; Fried, I.

    2008-01-01

    We studied the responses of single neurons in the human medial temporal lobe while subjects viewed familiar faces, animals, and landmarks. By progressively shortening the duration of stimulus presentation, coupled with backward masking, we show two striking properties of these neurons. (i) Their responses are not statistically different for the 33-ms, 66-ms, and 132-ms stimulus durations, and only for the 264-ms presentations there is a significantly higher firing. (ii) These responses follow conscious perception, as indicated by the subjects' recognition report. Remarkably, when recognized, a single snapshot as brief as 33 ms was sufficient to trigger strong single-unit responses far outlasting stimulus presentation. These results suggest that neurons in the medial temporal lobe can reflect conscious recognition by “all-or-none” responses. PMID:18299568

  1. Immature Responses to GABA in Fragile X Neurons Derived from Human Embryonic Stem Cells

    PubMed Central

    Telias, Michael; Segal, Menahem; Ben-Yosef, Dalit

    2016-01-01

    Fragile X Syndrome (FXS) is the most common form of inherited cognitive disability. However, functional deficiencies in FX neurons have been described so far almost exclusively in animal models. In a recent study we found several functional deficits in FX neurons differentiated in-vitro from human embryonic stem cells (hESCs), including their inability to fire repetitive action potentials, and their lack of synaptic activity. Here, we investigated the responses of such neurons to pulse application of the neurotransmitter GABA. We found two distinct types of responses to GABA and sensitivity to the GABA-A receptor antagonist bicuculline; type 1 (mature) characterized by non-desensitized responses to GABA as well as a high sensitivity to bicuculline, and type 2 (immature) which are desensitized to GABA and insensitive to bicuculline. Type 1 responses were age-dependent and dominant in mature WT neurons. In contrast, FX neurons expressed primarily type 2 phenotype. Expression analysis of GABA-A receptor subunits demonstrated that this bias in human FX neurons was associated with a significant alteration in the expression pattern of the GABA-A receptor subunits α2 and β2. Our results indicate that FMRP may play a role in the development of the GABAergic synapse during neurogenesis. This is the first demonstration of the lack of a mature response to GABA in human FX neurons and may explain the inappropriate synaptic functions in FXS. PMID:27242433

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

    PubMed

    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. PMID:20708010

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

    PubMed Central

    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

  4. Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge.

    PubMed

    Kudielka, Brigitte M; Hellhammer, D H; Wüst, Stefan

    2009-01-01

    Stress and stress-related health impairments are major problems in human life and elucidating the biological pathways linking stress and disease is of substantial importance. However, the identification of mechanisms underlying a dysregulation of major components of the stress response system is, particularly in humans, a very challenging task. Salivary cortisol responses to diverse acute challenge paradigms show large intra- and interindividual variability. In order to uncover mechanisms mediating stress-related disorders and to potentially develop new therapeutic strategies, an extensive phenotyping of HPA axis stress responses is essential. Such a research agenda depends on substantial knowledge of moderating and intervening variables that affect cortisol responses to different stressors and stimuli. The aim of this report is, therefore, to provide a comprehensive summary of important determinants of, in particular, human salivary cortisol responses to different kinds of laboratory stimuli including acute psychosocial stress as well as pharmacological provocation procedures. This overview demonstrates the role of age and gender, endogenous and exogenous sex steroid levels, pregnancy, lactation and breast-feeding, smoking, coffee and alcohol consumption as well as dietary energy supply in salivary cortisol responses to acute stress. Furthermore, it briefly summarizes current knowledge of the role of genetic factors and methodological issues in terms of habituation to repeated psychosocial stress exposures and time of testing as well as psychological factors, that have been shown to be associated with salivary cortisol responses like early life experiences, social factors, psychological interventions, personality as well as acute subjective-psychological stress responses and finally states of chronic stress and psychopathology. PMID:19041187

  5. The gradual vocal responses to human-provoked discomfort in farmed silver foxes

    PubMed Central

    Gogoleva, Svetlana S.; Volodina, Elena V.; Kharlamova, Anastasia V.; Trut, Lyudmila N.

    2012-01-01

    Vocal indicators of welfare have proven their use for many farmed and zoo animals and may be applied to farmed silver foxes as these animals display high vocal activity toward humans. Farmed silver foxes were selected mainly for fur, size, and litter sizes, but not for attitudes to people, so they are fearful of humans and have short-term welfare problems in their proximity. With a human approach test, we designed here the steady increase and decrease of fox–human distance and registered vocal responses of 25 farmed silver foxes. We analyzed the features of vocalizations produced by the foxes at different fox–human distances, assuming that changes in vocal responses reflect the degrees of human-related discomfort. For revealing the discomfort-related vocal traits in farmed silver foxes, we proposed and tested the algorithm of “joint calls,” equally applicable for analysis of all calls independently on their structure, either tonal or noisy. We discuss that the increase in proportion of time spent vocalizing and the shift of call energy toward higher frequencies may be integral vocal characteristics of short-term welfare problems in farmed silver foxes and probably in other captive mammals. PMID:22865950

  6. Utilization of the human louse genome to study insecticide resistance and innate immune response

    PubMed Central

    Clark, J. Marshall; Yoon, Kyong Sup; Kim, Ju Hyeon; Lee, Si Hyeock; Pittendrigh, Barry R.

    2015-01-01

    Since sequencing the human body louse genome, substantial advances have occurred in the utilization of the information gathered from louse genomes and transcriptomes. Comparatively, the body louse genome contains far fewer genes involved in environmental response, such as xenobiotic detoxification and innate immune response. Additionally, the body louse maintains a primary bacterial endosymbiont, Candidatus Riesia pediculicola, and a number of bacterial pathogens that it vectors, which have genomes that are also reduced in size. Thus, human louse genomes offer unique information and tools for use in advancing our understanding of coevolution among vectors, endosymbionts and pathogens. In this review, we summarize the current literature on the extent of pediculicide resistance, the availability of new pediculicides and information establishing this organism as an efficient model to study how xenobiotic metabolism, which is involved in insecticide resistance, is induced and how insects modify their innate immune response upon bacterial challenge resulting in enhanced vector competence. PMID:25987230

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

    PubMed

    Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

    2016-04-01

    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. PMID:27058035

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

    PubMed Central

    Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

    2016-01-01

    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. PMID:27058035

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

    SciTech Connect

    Switalla, S.; Lauenstein, L.; Prenzler, F.; Knothe, S.; Foerster, C.; Fieguth, H.-G.; Pfennig, O.; Schaumann, F.; Martin, C.; Guzman, C.A.; Ebensen, T.; Mueller, 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-1{beta}, MIP-1{beta}, and IL-10 in viable PCLS. Stimulation of lung tissue with BPPcysMPEG, however, induced a differential response. While LPS upregulated IFN-{gamma}, 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-1{beta}, and IFN-{gamma}. 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.

  10. Induction of human papillomavirus type 16-specific immunologic responses in a normal and an human papillomavirus-infected populations

    PubMed Central

    Cheng, Wen-Fang; Lee, Chien-Nan; Su, Yi-Ning; Chang, Ming-Cheng; Hsiao, Wen-Chun; Chen, Chi-An; Hsieh, Chang-Yao

    2005-01-01

    Human papillomavirus (HPV) infection, especially with the oncogenic genotypes, is the most important risk factor for developing cervical cancer. We focused on generating HPV16 E7-specific cytotoxic CD8+ T lymphocytes and evaluating HPV16 E7-specific immune responses in HPV16-infected and uninfected populations. Peripheral blood mononuclear cells (PBMCs) were first collected from an uninfected group with an human lymphocyte antigen (HLA) A2 haplotype (four volunteers). Mature monocyte-derived dendritic cells (DCs) were generated from the PBMCs and pulsed with one of two HLA-A2-restricted E7 peptides, aa 11–20 [YMLDLQPETT] and aa 86–93 [TLGIVCPI], as antigen presenting cells. The autologous naïve or cultured PBMCs were then cultured with peptide-pulsed DCs to detect the HPV16 E7-specific immune responses by a variety of techniques such as enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) assay and cytotoxic T lymphocyte assay. Interferon-γ (IFN-γ) from E7-specific cytotoxic CD8+ T lymphocytes stimulated with the respective peptide was detected by ELISA. Using ELISPOT analysis, a marked increase in the number of IFN-γ-secreting CD8+ E7-specific lymphocytes was observed following peptide stimulation. Cultured CD8+ T lymphocytes were highly cytotoxic against the CaSki cells. PBMCs were then colleted from an HPV16-infected population of the HLA-A2 haplotype, including four persons of HPV16 infection only, four with cervical intraepithelial neoplasia (CIN) lesions, and four cervical cancer patients. We then compared the immunologic responses to E7 between HPV16-infected and uninfected populations by ELISA and ELISPOT assay. The E7-specific immunologic responses of the HPV16-infected populations were significantly higher than those of the uninfected population. In addition, persons with an HPV16 infection only or those with CIN lesions generated higher E7-specific immunologic responses than cervical cancer patients. Our results

  11. Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

    PubMed Central

    Tabb, Michelle M; Kholodovych, Vladyslav; Grün, Felix; Zhou, Changcheng; Welsh, William J; Blumberg, Bruce

    2004-01-01

    Polychlorinated biphenyls (PCBs) are a family of persistent organic contaminants suspected to cause adverse effects in wildlife and humans. In rodents, PCBs bind to the aryl hydrocarbon (AhR) and pregnane X receptors (PXR) inducing the expression of catabolic cytochrome p450 enzymes of the CYP1A and 3A families. We found that certain highly chlorinated PCBs are potent activators of rodent PXR but antagonize its human ortholog, the steroid and xenobiotic receptor (SXR), inhibiting target gene induction. Thus, exposure to PCBs may blunt the human xenobiotic response, inhibiting the detoxification of steroids, bioactive dietary compounds, and xenobiotics normally mediated by SXR. The antagonistic PCBs are among the most stable and abundant in human tissues. These findings have important implications for understanding the biologic effects of PCB exposure and the use of animal models to predict the attendant risk. PMID:14754570

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

    PubMed

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

    2016-01-01

    In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein expression as well as protein synthesis rate. Further the (14)C bomb-pulse method has provided data on long-term tissue turnover in human tendon. Non-invasive techniques allow measurement of tendon metabolism (positron emission tomography (PET)), tendon morphology (magnetic resonance imaging (MRI)), and tendon mechanical properties (ultrasonography combined with force measurement during movement). Finally, 3D cell cultures of human tendon cells provide the opportunity to investigate cell-matrix interactions in response to various interventions. PMID:27535251

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

    PubMed

    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. PMID:26537863

  14. Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans

    PubMed Central

    Foster, Glen E; Brugniaux, Julien V; Pialoux, Vincent; Duggan, Cailean T C; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

    2009-01-01

    Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir = 45.0 mmHg) alternating with 2 min of normoxia (peak = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg (P < 0.01), nitric oxide derivatives were reduced by 55% (P < 0.05), the pressor response to acute hypoxia increased (P < 0.01), and the cerebral vascular resistance response to hypoxia increased (P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA. PMID:19417094

  15. Human colon carcinogenesis is associated with increased interleukin-17-driven inflammatory responses

    PubMed Central

    Xie, Zhaohui; Qu, Yine; Leng, Yanli; Sun, Wenxiu; Ma, Siqi; Wei, Jingbo; Hu, Jiangong; Zhang, Xiaolan

    2015-01-01

    Inflammation is known to contribute to carcinogenesis in human colorectal cancer. Proinflammatory cytokine interleukin-17 (IL-17 or IL-17A) has been shown to play a critical role in colon carcinogenesis in mouse models. However, few studies have investigated IL-17A in human colon tissues. In the present study, we assessed IL-17-driven inflammatory responses in 17 cases of human colon adenocarcinomas, 16 cases of human normal colon tissues adjacent to the resected colon adenocarcinomas, ten cases of human ulcerative colitis tissues from biopsies, and eight cases of human colon polyps diagnosed as benign adenomas. We found that human colon adenocarcinomas contained the highest levels of IL-17A cytokine, which was significantly higher than the IL-17A levels in the adenomas, ulcerative colitis, and normal colon tissues (P<0.01). The levels of IL-17 receptor A (IL-17RA) were also the highest in human colon adenocarcinomas, followed by adenomas and ulcerative colitis. The increased levels of IL-17A and IL-17RA were accompanied with increased IL-17-driven inflammatory responses, including activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) pathways, increase in expression of matrix metalloproteinase (MMP)9, MMP7, MMP2, B-cell lymphoma (Bcl-2), and cyclin D1, decrease in Bcl-2-associated X protein (BAX) expression, and increase in vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) expression that were associated with increased angiogenesis. These findings suggest that IL-17 and its signaling pathways appear as promising new targets in the design and development of drugs for cancer prevention and treatment, particularly in colorectal cancer. PMID:25834404

  16. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  17. Age and Skeletal Sites Affect BMP-2 Responsiveness of Human Bone Marrow Stromal Cells

    PubMed Central

    Osyczka, Anna M.; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O.

    2010-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be partly due to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  18. Functional Analysis of the Human Antibody Response to Meningococcal Factor H Binding Protein

    PubMed Central

    Beernink, Peter T.; Giuntini, Serena; Costa, Isabella; Lucas, Alexander H.

    2015-01-01

    ABSTRACT Two licensed serogroup B meningococcal vaccines contain factor H binding protein (FHbp). The antigen specifically binds human FH, which downregulates complement. In wild-type mice whose mouse FH does not bind to FHbp vaccines, the serum anti-FHbp antibody response inhibited binding of human FH to FHbp. The inhibition was important for eliciting broad anti-FHbp serum bactericidal activity. In human FH transgenic mice and some nonhuman primates, FHbp was able to form a complex with FH and FHbp vaccination elicited anti-FHbp antibodies that did not inhibit FH binding. To investigate the human anti-FHbp repertoire, we cloned immunoglobulin heavy- and light-chain-variable-region genes of individual B cells from three adults immunized with FHbp vaccines and generated 10 sequence-distinct native anti-FHbp antibody fragments (Fabs). All 10 Fabs bound to live meningococci; only 1 slightly inhibited binding of human FH, while 4 enhanced FH binding. Affinity-purified anti-FHbp antibody from serum of a fourth immunized adult also enhanced binding of human FH to live meningococcal bacteria. Despite the bound FH, the affinity-purified serum anti-FHbp antibodies elicited human complement-mediated bactericidal activity that was amplified by the alternative pathway. The lack of FH inhibition by the human anti-FHbp Fabs and serum antibodies suggests that binding of human FH to the vaccine antigen skews the anti-FHbp antibody repertoire to epitopes outside the FH-binding site. Mutant FHbp vaccines with decreased FH binding may represent a means to redirect the human antibody repertoire to epitopes within the FH binding site, which can inhibit FH binding and, potentially, increase safety and protective activity. PMID:26106082

  19. Use of postmortem human subjects to describe injury responses and tolerances.

    PubMed

    Yoganandan, Narayan; Stemper, Brian D; Pintar, Frank A; Maiman, Dennis J

    2011-04-01

    Traumatic injuries from blunt, penetrating, and blast events expose the human body to unintentional and intentional external mechanical loads. To mitigate trauma and develop safety-engineered devices for clinical and bioengineering applications, it is critical to delineate the structural load-bearing anatomy and biomechanics of the various components of the human body. This article presents advances made in the understanding of the injury responses and tolerances through experiments conducted using intact or segmented tissues from postmortem human subjects (PMHS), and a considerable majority of data for the presentation has been extracted from studies conducted at the Institutions of the authors. The role of the PMHS model for studying traumatic injuries to the head and face, vertebral column (cervical, thoracic and lumbar spines), thorax, abdomen, pelvis, and lower extremities is discussed. Different impact loading scenarios, likely responsible for the initial trauma causation, are considered in the analysis and determination of the human response to injury. Clinical advances made using the PMHS model are discussed. This includes vertebral stabilization system evaluations secondary to traumatic injuries to the spinal column. The critical importance of using data from the PMHS model in developing validated computational models for advancing crashworthiness research, occupant safety in motor vehicle crashes, medical devices, and safety-engineering applications is highlighted. PMID:21433078

  20. Human Neoplasms Elicit Multiple Specific Immune Responses in the Autologous Host

    NASA Astrophysics Data System (ADS)

    Sahin, Ugur; Tureci, Ozlem; Schmitt, Holger; Cochlovius, Bjorn; Johannes, Thomas; Schmits, Rudolf; Stenner, Frank; Luo, Guorong; Schobert, Ingrid; Pfreundschuh, Michael

    1995-12-01

    Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

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

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  2. Evaluation of Mechanical Response of Human Palm to Small Impact Force

    NASA Astrophysics Data System (ADS)

    Ito, Hitomi; Fujii, Yusaku

    Method of measuring mechanical characteristics of human palm against small impact force is proposed. Medical doctors qualitatively evaluate the mechanical characteristics of the human body by manipulation and percussion. In the field of bioengineering, accurate quantitative analysis of the mechanical characteristics of the human body is required. In this paper, the mechanical characteristics of a human palm against small impact force are determined by means of the Levitation Mass Method (LMM). The LMM is a method for accurately measuring varying forces without the use of force transducers. Mechanical characteristics of a human palm were measured with high accuracy by means of an instrument based on the LMM. In the measurement, the mass, that is a moving part of an aerostatic linear bearing (a hydrostatic linear air bearing, an externally pressurized air bearing), is made to collide with a human palm under test. During the collision measurement, only the Doppler shift frequency of the laser light reflecting on the mass is highly accurately measured using an optical interferometer. The velocity, position, acceleration and inertial force of the mass are calculated from the measured time-varying Doppler shift. The mechanical response of a human palm against small impact loading is also characterized from the measured data.

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

    PubMed Central

    Lemon, Christian H.

    2015-01-01

    Introduction This mini-review discusses some of the parallels between rodent neurophysiological and human psychophysical data concerning temperature effects on sweet taste. Methods and Purpose “Sweet” is an innately rewarding taste sensation that is associated in part with foods that contain calories in the form of sugars. Humans and other mammals can show unconditioned preference for select sweet stimuli. Such preference is poised to influence diet selection and, in turn, nutritional status, which underscores the importance of delineating the physiological mechanisms for sweet taste with respect to their influence on human health. Advances in our knowledge of the biology of sweet taste in humans have arisen in part through studies on mechanisms of gustatory processing in rodent models. Along this line, recent work has revealed there are operational parallels in neural systems for sweet taste between mice and humans, as indexed by similarities in the effects of temperature on central neurophysiological and psychophysical responses to sucrose in these species. Such association strengthens the postulate that rodents can serve as effective models of particular mechanisms of appetitive taste processing. Data supporting this link are discussed here, as are rodent and human data that shed light on relationships between mechanisms for sweet taste and ingestive disorders, such as alcohol abuse. Results and Conclusions Rodent models have utility for understanding mechanisms of taste processing that may pertain to human flavor perception. Importantly, there are limitations to generalizing data from rodents, albeit parallels across species do exist. PMID:26388965

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

    PubMed

    Güntekin, Bahar; Başar, Erol

    2016-05-01

    In the last decade, the brain's oscillatory responses have invaded the literature. The studies on delta (0.5-3.5Hz) oscillatory responses in humans upon application of cognitive paradigms showed that delta oscillations are related to cognitive processes, mainly in decision making and attentional processes. The present manuscript comprehensively reviews the studies on delta oscillatory responses upon cognitive stimulation in healthy subjects and in different pathologies, namely Alzheimer's disease, Mild Cognitive Impairment (MCI), bipolar disorder, schizophrenia and alcoholism. Further delta oscillatory response upon presentation of faces, facial expressions, and affective pictures are reviewed. The relationship between pre-stimulus delta activity and post-stimulus evoked and event-related responses and/or oscillations is discussed. Cross-frequency couplings of delta oscillations with higher frequency windows are also included in the review. The conclusion of this review includes several important remarks, including that delta oscillatory responses are involved in cognitive and emotional processes. A decrease of delta oscillatory responses could be a general electrophysiological marker for cognitive dysfunction (Alzheimer's disease, MCI, bipolar disorder, schizophrenia and alcoholism). The pre-stimulus activity (phase or amplitude changes in delta activity) has an effect on post-stimulus EEG responses. PMID:25660301

  5. Statistics of single unit responses in the human medial temporal lobe: A sparse and overdispersed code

    NASA Astrophysics Data System (ADS)

    Magyar, Andrew

    The recent discovery of cells that respond to purely conceptual features of the environment (particular people, landmarks, objects, etc) in the human medial temporal lobe (MTL), has raised many questions about the nature of the neural code in humans. The goal of this dissertation is to develop a novel statistical method based upon maximum likelihood regression which will then be applied to these experiments in order to produce a quantitative description of the coding properties of the human MTL. In general, the method is applicable to any experiments in which a sequence of stimuli are presented to an organism while the binary responses of a large number of cells are recorded in parallel. The central concept underlying the approach is the total probability that a neuron responds to a random stimulus, called the neuronal sparsity. The model then estimates the distribution of response probabilities across the population of cells. Applying the method to single-unit recordings from the human medial temporal lobe, estimates of the sparsity distributions are acquired in four regions: the hippocampus, the entorhinal cortex, the amygdala, and the parahippocampal cortex. The resulting distributions are found to be sparse (large fraction of cells with a low response probability) and highly non-uniform, with a large proportion of ultra-sparse neurons that possess a very low response probability, and a smaller population of cells which respond much more frequently. Rammifications of the results are discussed in relation to the sparse coding hypothesis, and comparisons are made between the statistics of the human medial temporal lobe cells and place cells observed in the rodent hippocampus.

  6. Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice.

    PubMed

    Chalouhi, Nohra; Starke, Robert M; Correa, Tatiana; Jabbour, Pascal M; Zanaty, Mario; Brown, Robert D; Torner, James C; Hasan, David M

    2016-08-01

    We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin. PMID:27296993

  7. The human P-glycoprotein transporter enhances the type I interferon response to Listeria monocytogenes infection.

    PubMed

    Sigal, Nadejda; Kaplan Zeevi, Millie; Weinstein, Shiri; Peer, Dan; Herskovits, Anat A

    2015-06-01

    Human multidrug efflux transporters are known for their ability to extrude antibiotics and toxic compounds out of cells, yet accumulating data indicate they have additional functions in diverse physiological processes not related to drug efflux. Here, we show that the human multidrug transporter P-glycoprotein (P-gp) (also named MDR1 and ABCB1) is transcriptionally induced in the monocytic cell line THP-1 upon infection with the human intracellular bacterial pathogen Listeria monocytogenes. Notably, we found that P-gp is important for full activation of the type I interferon response elicited against L. monocytogenes bacteria. Both inhibition of P-gp function by verapamil and inhibition of its transcription using mRNA silencing led to a reduction in the magnitude of the type I response in infected cells. This function of P-gp was specific to type I interferon cytokines elicited against cytosolic replicating bacteria and was not observed in response to cyclic di-AMP (c-di-AMP), a molecule that was shown to be secreted by L. monocytogenes during infection and to trigger type I interferons. Moreover, P-gp was not involved in activation of other proinflammatory cytokines, such as those triggered by vacuolar-restricted L. monocytogenes or lipopolysaccharide (LPS). Taken together, these findings demonstrate a role for P-gp in proper development of an innate immune response against intracellular pathogens, highlighting the complexity in employing therapeutic strategies that involve inhibition of multidrug resistance (MDR) efflux pumps. PMID:25824830

  8. The Human P-Glycoprotein Transporter Enhances the Type I Interferon Response to Listeria monocytogenes Infection

    PubMed Central

    Sigal, Nadejda; Kaplan Zeevi, Millie; Weinstein, Shiri; Peer, Dan

    2015-01-01

    Human multidrug efflux transporters are known for their ability to extrude antibiotics and toxic compounds out of cells, yet accumulating data indicate they have additional functions in diverse physiological processes not related to drug efflux. Here, we show that the human multidrug transporter P-glycoprotein (P-gp) (also named MDR1 and ABCB1) is transcriptionally induced in the monocytic cell line THP-1 upon infection with the human intracellular bacterial pathogen Listeria monocytogenes. Notably, we found that P-gp is important for full activation of the type I interferon response elicited against L. monocytogenes bacteria. Both inhibition of P-gp function by verapamil and inhibition of its transcription using mRNA silencing led to a reduction in the magnitude of the type I response in infected cells. This function of P-gp was specific to type I interferon cytokines elicited against cytosolic replicating bacteria and was not observed in response to cyclic di-AMP (c-di-AMP), a molecule that was shown to be secreted by L. monocytogenes during infection and to trigger type I interferons. Moreover, P-gp was not involved in activation of other proinflammatory cytokines, such as those triggered by vacuolar-restricted L. monocytogenes or lipopolysaccharide (LPS). Taken together, these findings demonstrate a role for P-gp in proper development of an innate immune response against intracellular pathogens, highlighting the complexity in employing therapeutic strategies that involve inhibition of multidrug resistance (MDR) efflux pumps. PMID:25824830

  9. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs

    PubMed Central

    Madden, Lauran; Juhas, Mark; Kraus, William E; Truskey, George A; Bursac, Nenad

    2015-01-01

    Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues (‘myobundles’) using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7+ cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04885.001 PMID:25575180

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

    PubMed

    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. PMID:26518662

  11. Modeling human vestibular responses during eccentric rotation and off vertical axis rotation

    NASA Technical Reports Server (NTRS)

    Merfeld, D. M.; Paloski, W. H. (Principal Investigator)

    1995-01-01

    A mathematical model has been developed to help explain human multi-sensory interactions. The most important constituent of the model is the hypothesis that the nervous system incorporates knowledge of sensory dynamics into an "internal model" of these dynamics. This internal model allows the nervous system to integrate the sensory information from many different sensors into a coherent estimate of self-motion. The essence of the model is unchanged from a previously published model of monkey eye movement responses; only a few variables have been adjusted to yield the prediction of human responses. During eccentric rotation, the model predicts that the axis of eye rotation shifts slightly toward alignment with gravito-inertial force. The model also predicts that the time course of the perception of tilt following the acceleration phase of eccentric rotation is much slower than that during deceleration. During off vertical axis rotation (OVAR) the model predicts a small horizontal bias along with small horizontal, vertical, and torsional oscillations. Following OVAR stimulation, when stopped right- or left-side down, a small vertical component is predicted that decays with the horizontal post-rotatory response. All of the predictions are consistent with measurements of human responses.

  12. Modeling human vestibular responses during eccentric rotation and off vertical axis rotation.

    PubMed

    Merfeld, D M

    1995-01-01

    A mathematical model has been developed to help explain human multi-sensory interactions. The most important constituent of the model is the hypothesis that the nervous system incorporates knowledge of sensory dynamics into an "internal model" of these dynamics. This internal model allows the nervous system to integrate the sensory information from many different sensors into a coherent estimate of self-motion. The essence of the model is unchanged from a previously published model of monkey eye movement responses; only a few variables have been adjusted to yield the prediction of human responses. During eccentric rotation, the model predicts that the axis of eye rotation shifts slightly toward alignment with gravito-inertial force. The model also predicts that the time course of the perception of tilt following the acceleration phase of eccentric rotation is much slower than that during deceleration. During off vertical axis rotation (OVAR) the model predicts a small horizontal bias along with small horizontal, vertical, and torsional oscillations. Following OVAR stimulation, when stopped right- or left-side down, a small vertical component is predicted that decays with the horizontal post-rotatory response. All of the predictions are consistent with measurements of human responses. PMID:8749160

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

    PubMed

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

    2011-11-17

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

  14. Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo

    PubMed Central

    Troost, Freddy J; van Baarlen, Peter; Lindsey, Patrick; Kodde, Andrea; de Vos, Willem M; Kleerebezem, Michiel; Brummer, Robert-Jan M

    2008-01-01

    Background There is limited knowledge on the extent and dynamics of the mucosal response to commensal and probiotic species in the human intestinal lumen. This study aimed to identify the acute, time-dependent responses of intestinal mucosa to commensal Lactobacillus plantarum WCFS1 in vivo in two placebo-controlled human intervention studies in healthy volunteers. Transcriptional changes in duodenal mucosa upon continuous intraduodenal infusion of L. plantarum WCFS1 for one- and six h, respectively, were studied using oro- and nasogastric intubations with dedicated orogastric catheters and tissue sampling by standard flexible gastroduodenoscopy. Results One- and six-h exposure of small intestinal mucosa to L. plantarum WCFS1 induced differential expression of 669 and 424 gene reporters, respectively. While short-term exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and cell cycle progression, cells switched to a more proliferative phase after prolonged exposure with an overall expression profile characterized by upregulation of genes involved in lipid metabolism, cellular growth and development. Cell death and immune responses were triggered, but cell death-executing genes or inflammatory signals were not expressed. Proteome analysis showed differential expression of several proteins. Only the microsomal protein 'microsomal triglyceride transfer protein' was regulated on both the transcriptional and the protein level in all subjects. Conclusion Overall, this study showed that intestinal exposure to L. plantarum WCFS1 induced consistent, time-dependent transcriptional responses in healthy intestinal mucosa. This extensive exploration of the human response to L. plantarum WCFS1 could eventually provide molecular support for specific or probiotic activity of this strain or species, and exemplifies the strength of the applied technology to identify the potential bio-activity of microbes in the human intestine. PMID:18681965

  15. Normalizing and scaling of data to derive human response corridors from impact tests.

    PubMed

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

    2014-06-01

    It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed. PMID:24726322

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

    PubMed

    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. PMID:16894493

  17. Mathematical modeling of human cardiovascular system for simulation of orthostatic response

    NASA Technical Reports Server (NTRS)

    Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

    1992-01-01

    This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

  18. Mathematical modeling of human cardiovascular system for simulation of orthostatic response.

    PubMed

    Melchior, F M; Srinivasan, R S; Charles, J B

    1992-06-01

    This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system. PMID:1621848

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

    PubMed Central

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

    2015-01-01

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

  20. Some early uses of evoked brain responses in investigations of human visual function.

    PubMed

    Regan, D

    2009-05-01

    In the context of the technical possibilities of the time, this paper describes early attempts to employ visual-evoked potentials (VEPs) as a tool for investigating human visual function, focussing on the contributions of Henk Spekreijse and his colleagues. The topics covered are as follows: attempts to distinguish between true pattern-specific VEPs and the effects of responses to changes in local luminance; retinal rivalry and interocular sustained suppression; the implications of VEPs elicited by equiluminant chromatic patterns; VEPs specific to real and apparent motion; stereo VEPs; identification of a visual-auditory convergence area in the human brain. PMID:18304602

  1. Expression profiling of human epidermal keratinocyte response following 1-minute JP-8 exposure.

    PubMed

    Chou, Chi-Chung; Yang, Jen-Hung; Chen, San-Duo; Monteiro-Riviere, Nancy A; Li, Han-Ni; Chen, Jeremy J W

    2006-01-01

    The cDNA microarray analysis of 9600 expressed sequence tags was performed to examine the gene expression changes in human epidermal keratinocytes after 1-minute JP-8 exposure; 151 genes were identified as JP-8 responsive and classified into 8 clusters by self organization map. Genes involved in basal transcription and translations were up-regulated, whereas genes related to DNA repair, metabolism, and keratin were mostly down-regulated. Genes encoded for growth factors, apoptosis, signal transduction, and adhesion were also altered. These results indicated that human keratinocyte responds to a single dose of JP-8 insult and revealed several cellular processes previously not associated with jet fuel exposure. PMID:16835149

  2. Biology of human skin transplanted to the nude mouse: I. Response to agents which modify epidermal proliferation.

    PubMed

    Krueger, G G; Shelby, J

    1981-06-01

    To accept human skin transplanted to the congenitally athymic (nude) mouse as a system to study human skin and its physiologic and pathologic states, it must be demonstrated that skin so maintained retains its function as a biologic unit. We have found that responses of grafted human skin and nude mouse skin to various agents differ. This difference in response has been utilized to assess barrier function and proliferative capacity of human skin grafts. Human skin grafts undergo a proliferative response when 10 ng of the tumor promoter, 12-O-tetradecanoyl phorbol 13-acetate (TPA) is applied. Nudes do not respond to this dose. Increasing the dose to 100 ng of TPA evokes a response in both. However, only in the human skin grafts can this response be blocked with betamethasone valerate (BV). In that human skin grafts do not take on their hosts' responsiveness, and the response of domestic pig skin to these agents before and after grafting is identical, the conclusion is reached that human skin appears to retain its inherent biologic unit function. The data also demonstrate some of the potential of this system to study kinetics of the epidermis of human skin. PMID:7017014

  3. Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

    PubMed Central

    Bershad, Anya K.; Jaffe, Jerome H.; Childs, Emma; de Wit, Harriet

    2014-01-01

    Preclinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the effects of buprenorphine, a μ-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N = 48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs. PMID:25544740

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

    PubMed Central

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

    2013-01-01

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

  5. Computer prediction of human thermoregulatory and temperature responses to a wide range of environmental conditions

    NASA Astrophysics Data System (ADS)

    Fiala, D.; Lomas, K. J.; Stohrer, M.

    A mathematical model for predicting human thermal and regulatory responses in cold, cool, neutral, warm, and hot environments has been developed and validated. The multi-segmental passive system, which models the dynamic heat transport within the body and the heat exchange between body parts and the environment, is discussed elsewhere. This paper is concerned with the development of the active system, which simulates the regulatory responses of shivering, sweating, and peripheral vasomotion of unacclimatised subjects. Following a comprehensive literature review, 26 independent experiments were selected that were designed to provoke each of these responses in different circumstances. Regression analysis revealed that skin and head core temperature affect regulatory responses in a non-linear fashion. A further signal, i.e. the rate of change of the mean skin temperature weighted by the skin temperature error signal, was identified as governing the dynamics of thermoregulatory processes in the cold. Verification and validation work was carried out using experimental data obtained from 90 exposures covering a range of steady and transient ambient temperatures between 5°C and 50°C and exercise intensities between 46 W/m2 and 600 W/m2. Good general agreement with measured data was obtained for regulatory responses, internal temperatures, and the mean and local skin temperatures of unacclimatised humans for the whole spectrum of climatic conditions and for different activity levels.

  6. Computer prediction of human thermoregulatory and temperature responses to a wide range of environmental conditions.

    PubMed

    Fiala, D; Lomas, K J; Stohrer, M

    2001-09-01

    A mathematical model for predicting human thermal and regulatory responses in cold, cool, neutral, warm, and hot environments has been developed and validated. The multi-segmental passive system, which models the dynamic heat transport within the body and the heat exchange between body parts and the environment, is discussed elsewhere. This paper is concerned with the development of the active system, which simulates the regulatory responses of shivering, sweating, and peripheral vasomotion of unacclimatised subjects. Following a comprehensive literature review, 26 independent experiments were selected that were designed to provoke each of these responses in different circumstances. Regression analysis revealed that skin and head core temperature affect regulatory responses in a nonlinear fashion. A further signal, i.e. the rate of change of the mean skin temperature weighted by the skin temperature error signal, was identified as governing the dynamics of thermoregulatory processes in the cold. Verification and validation work was carried out using experimental data obtained from 90 exposures covering a range of steady and transient ambient temperatures between 5 degrees C and 50 degrees C and exercise intensities between 46 W/m2 and 600 W/m2. Good general agreement with measured data was obtained for regulatory responses, internal temperatures, and the mean and local skin temperatures of unacclimatised humans for the whole spectrum of climatic conditions and for different activity levels. PMID:11594634

  7. Neural processing of gravitoinertial cues in humans. III. Modeling tilt and translation responses.

    PubMed

    Merfeld, D M; Zupan, L H

    2002-02-01

    All linear accelerometers measure gravitoinertial force, which is the sum of gravitational force (tilt) and inertial force due to linear acceleration (translation). Neural strategies must exist to elicit tilt and translation responses from this ambiguous cue. To investigate these neural processes, we developed a model of human responses and simulated a number of motion paradigms used to investigate this tilt/translation ambiguity. In this model, the separation of GIF into neural estimates of gravity and linear acceleration is accomplished via an internal model made up of three principal components: 1) the influence of rotational cues (e.g., semicircular canals) on the neural representation of gravity, 2) the resolution of gravitoinertial force into neural representations of gravity and linear acceleration, and 3) the neural representation of the dynamics of the semicircular canals. By combining these simple hypotheses within the internal model framework, the model mimics human responses to a number of different paradigms, ranging from simple paradigms, like roll tilt, to complex paradigms, like postrotational tilt and centrifugation. It is important to note that the exact same mechanisms can explain responses induced by simple movements as well as by more complex paradigms; no additional elements or hypotheses are needed to match the data obtained during more complex paradigms. Therefore these modeled response characteristics are consistent with available data and with the hypothesis that the nervous system uses internal models to estimate tilt and translation in the presence of ambiguous sensory cues. PMID:11826049

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

    NASA Technical Reports Server (NTRS)

    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.

  9. Human T cell responses to Japanese encephalitis virus in health and disease.

    PubMed

    Turtle, Lance; Bali, Tanushka; Buxton, Gemma; Chib, Savita; Chan, Sajesh; Soni, Mohammed; Hussain, Mohammed; Isenman, Heather; Fadnis, Prachi; Venkataswamy, Manjunatha M; Satishkumar, Vishali; Lewthwaite, Penny; Kurioka, Ayako; Krishna, Srinivasa; Shankar, M Veera; Ahmed, Riyaz; Begum, Ashia; Ravi, Vasanthapuram; Desai, Anita; Yoksan, Sutee; Fernandez, Stefan; Willberg, Christian B; Kloverpris, Henrik N; Conlon, Christopher; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

    2016-06-27

    Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus. PMID:27242166

  10. Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts

    NASA Astrophysics Data System (ADS)

    Harder, Samantha J.; Isabelle, Martin; Devorkin, Lindsay; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G.; Lum, Julian J.; Jirasek, Andrew

    2016-02-01

    External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.

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

    PubMed Central

    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

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

    PubMed

    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

  13. Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response.

    PubMed

    Gardiner, Sheila M; March, Julie E; Kemp, Philip A; Bennett, Terence

    2004-10-01

    A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg(-1)) in conscious, male, Sprague-Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0-5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30-120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred. Pretreatment with indomethacin or N(G) nitro-l-arginine methylester (l-NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and l-NAME together prevented all haemodynamic responses to hUII. Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol. In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation. Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs. One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid- or prostanoid- and NO-mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia). PMID:15339862

  14. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves.

    PubMed

    Funato, Tetsuro; Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-05-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  15. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves

    PubMed Central

    Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-01-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  16. Fucose-binding Lotus tetragonolobus lectin binds to human polymorphonuclear leukocytes and induces a chemotactic response.

    PubMed

    VanEpps, D E; Tung, K S

    1977-09-01

    Fucose-binding L. tetragonolobus lectin to the surface of human polymorphonuclear leukocytes (PMN) and induces a chemotactic response. Both surface binding and chemotaxis are inhibited by free fucose but not by fructose, mannose, or galactose. The lectin-binding sites on PMN are unrelated to the A, B, or O blood group antigen. Utilization of this lectin should be a useful tool in isolating PMN membrane components and in analyzing the mechanism of neutrophil chemotaxis. PMID:330752

  17. Psychophysical relationships characterizing human response to whole-body sinusoidal vertical vibration

    NASA Technical Reports Server (NTRS)

    Leatherwood, J. D.; Dempsey, T. K.

    1976-01-01

    An experimental investigation determined that the psychophysical relationships between subjective discomfort evaluations to vibratory stimuli and subjective evaluations of the intensity of vibratory stimuli can be expressed in a linear fashion. Furthermore, significant differences were found to exist between discomfort and intensity subjective response for several but not all discrete frequencies investigated. The implication of these results is that ride quality criteria based upon subjective evaluation of vibration intensity should be applied cautiously in the development of criteria for human comfort.

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

    PubMed Central

    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

  19. Animal models and their importance to human physiological responses in microgravity

    NASA Technical Reports Server (NTRS)

    Tipton, C. M.

    1996-01-01

    Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

  20. Stress responses to DNA damaging agents in the human colon carcinoma cell line, RKO.

    PubMed

    Beard, S E; Capaldi, S R; Gee, P

    1996-11-01

    DNA damage results from a wide variety of external agents such as chemicals and radiation. The consequences of exposure to agents that damage DNA have been traditionally studied from the perspective of cell survival and mutagenesis. Mutations are late endpoints of DNA damage. Cells respond to the earlier stages of DNA damage by inducing the expression of several genes, including those specific of the nature of the lesion. These early transcriptional responses are likely to predetermine the later fate of the damaged cell. Genes activated during this early response include those involved in DNA repair, replication, and growth control. We are interested in the transcriptional mechanisms by which cells respond to DNA damaging agents. To facilitate the measurement of gene induction, we used seven different reporter constructs integrated stably into the RKO cell line derived from a human colon carcinoma. These constructs were derived from promoters and/or response elements isolated from genes associated with DNA damage responses in human cells, and were fused to the bacterial reporter gene, choramphenicol acetyl transferase (CAT). The cell lines generated in this manner contain the promoters and/or response elements representing DNA polymerase beta, p53, gadd (growth arrest and DNA damage) 45 and 153, c-fos, TPA response element, and tissue-type plasminogen activator. These recombinant cell lines were assembled in a 96-well microtiter plate permitting their simultaneous exposure to compounds and subsequent CAT protein measurement. This assembly has been designated the CAT-Tox (D) assay. These cell lines were exposed to different classes of DNA damaging agents including those which covalently join bases to form dimers (e.g., UVC irradiation), generate DNA adducts by alkylation (e.g., methylmethane sulfonate [MMS], ethylmethane sulfonate [EMS], N-methyl-N-nitro-N-nitrosoguanine [MNNG], dimethylnitrosamine [DMN]), cross-link DNA (e.g., mitomycin C), and inhibit DNA

  1. Regulation of Pulmonary and Systemic Bacterial Lipopolysaccharide Responses in Transgenic Mice Expressing Human Elafin

    PubMed Central

    Sallenave, J.-M.; Cunningham, G. A.; James, R. M.; McLachlan, G.; Haslett, C.

    2003-01-01

    The control of lung inflammation is of paramount importance in a variety of acute pathologies, such as pneumonia, the acute respiratory distress syndrome, and sepsis. It is becoming increasingly apparent that local innate immune responses in the lung are negatively influenced by systemic inflammation. This is thought to be due to a local deficit in cytokine responses by alveolar macrophages and neutrophils following systemic bacterial infection and the development of a septic response. Recently, using an adenovirus-based strategy which overexpresses the human elastase inhibitor elafin locally in the lung, we showed that elafin is able to prime lung innate immune responses. In this study, we generated a novel transgenic mouse strain expressing human elafin and studied its response to bacterial lipopolysaccharide (LPS) when the LPS was administered locally in the lungs and systemically. When LPS was delivered to the lungs, we found that mice expressing elafin had lower serum-to-bronchoalveolar lavage ratios of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein 2, and monocyte chemoattractant protein 1, than wild-type mice. There was a concomitant increase in inflammatory cell influx, showing that there was potential priming of innate responses in the lungs. When LPS was given systemically, the mice expressing elafin had reduced levels of serum TNF-α compared to the levels in wild-type mice. These results indicate that elafin may have a dual function, promoting up-regulation of local lung innate immunity while simultaneously down-regulating potentially unwanted systemic inflammatory responses in the circulation. PMID:12819058

  2. Regulation of pulmonary and systemic bacterial lipopolysaccharide responses in transgenic mice expressing human elafin.

    PubMed

    Sallenave, J-M; Cunningham, G A; James, R M; McLachlan, G; Haslett, C

    2003-07-01

    The control of lung inflammation is of paramount importance in a variety of acute pathologies, such as pneumonia, the acute respiratory distress syndrome, and sepsis. It is becoming increasingly apparent that local innate immune responses in the lung are negatively influenced by systemic inflammation. This is thought to be due to a local deficit in cytokine responses by alveolar macrophages and neutrophils following systemic bacterial infection and the development of a septic response. Recently, using an adenovirus-based strategy which overexpresses the human elastase inhibitor elafin locally in the lung, we showed that elafin is able to prime lung innate immune responses. In this study, we generated a novel transgenic mouse strain expressing human elafin and studied its response to bacterial lipopolysaccharide (LPS) when the LPS was administered locally in the lungs and systemically. When LPS was delivered to the lungs, we found that mice expressing elafin had lower serum-to-bronchoalveolar lavage ratios of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), macrophage inflammatory protein 2, and monocyte chemoattractant protein 1, than wild-type mice. There was a concomitant increase in inflammatory cell influx, showing that there was potential priming of innate responses in the lungs. When LPS was given systemically, the mice expressing elafin had reduced levels of serum TNF-alpha compared to the levels in wild-type mice. These results indicate that elafin may have a dual function, promoting up-regulation of local lung innate immunity while simultaneously down-regulating potentially unwanted systemic inflammatory responses in the circulation. PMID:12819058

  3. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils

    PubMed Central

    Lee, Cheng-Yuk; Thompson III, George R.; Hastey, Christine J.; Hodge, Gregory C.; Lunetta, Jennine M.; Pappagianis, Demosthenes; Heinrich, Volkmar

    2015-01-01

    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. PMID:26070210

  4. Oregonin reduces lipid accumulation and proinflammatory responses in primary human macrophages.

    PubMed

    Lundqvist, Annika; Magnusson, Lisa U; Ullström, Christina; Krasilnikova, Jelena; Telysheva, Galina; Dizhbite, Tatjana; Hultén, Lillemor Mattsson

    2015-03-13

    Inflammation in the vascular wall is important for the development of atherosclerosis. We have previously shown that inflammatory macrophages are more abundant in human atherosclerotic lesions than in healthy arteries. Activated macrophages produce reactive oxygen species (ROS) that promote local inflammation in atherosclerotic lesions. Here, we investigated the role of oregonin, a diarylheptanoid, on proinflammatory responses in primary human macrophages and found that oregonin decreased cellular lipid accumulation and proinflammatory cytokine secretion. We also found that oregonin decreased ROS production in macrophages. Additionally, we observed that treatment of lipopolysaccharide-exposed macrophages with oregonin significantly induced the expression of antioxidant-related genes, including Heme oxygenase-1 and NADPH dehydrogenase quinone 1. In summary, we have shown that oregonin reduces lipid accumulation, inflammation and ROS production in primary human macrophages, indicating that oregonin has anti-inflammatory bioactivities. PMID:25686497

  5. Learning of anticipatory responses in single neurons of the human medial temporal lobe

    PubMed Central

    Reddy, Leila; Poncet, Marlene; Self, Matthew W.; Peters, Judith C.; Douw, Linda; van Dellen, Edwin; Claus, Steven; Reijneveld, Jaap C.; Baayen, Johannes C.; Roelfsema, Pieter R.

    2015-01-01

    Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL. PMID:26449885

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

    PubMed Central

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

    2016-01-01

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

  7. Melatonin shifts human circadian rhythms according to a phase-response curve.

    PubMed

    Lewy, A J; Ahmed, S; Jackson, J M; Sack, R L

    1992-10-01

    A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle. PMID:1394610

  8. Ingested Human Insulin Inhibits the Mosquito NF-κB-Dependent Immune Response to Plasmodium falciparum

    PubMed Central

    Corby-Harris, Vanessa; Green, Gabriel P.; Smithers, Hannah M.; Cheung, Kong W.; Riehle, Michael A.; Luckhart, Shirley

    2012-01-01

    We showed previously that ingested human insulin activates the insulin/IGF-1 signaling pathway in Anopheles stephensi and increases the susceptibility of these mosquitoes to Plasmodium falciparum. In other organisms, insulin can alter immune responsiveness through regulation of NF-κB transcription factors, critical elements for innate immunity that are also central to mosquito immunity. We show here that insulin signaling decreased expression of NF-κB-regulated immune genes in mosquito cells stimulated with either bacterial or malarial soluble products. Further, human insulin suppressed mosquito immunity through sustained phosphatidylinositol 3-kinase activation, since inhibition of this pathway led to decreased parasite development in the mosquito. Together, these data demonstrate that activation of the insulin/IGF-1 signaling pathway by ingested human insulin can alter NF-κB-dependent immunity, and ultimately the susceptibility, of mosquitoes to P. falciparum. PMID:22473605

  9. Human Visual Cortex Responses to Rapid Cone and Melanopsin-Directed Flicker

    PubMed Central

    Spitschan, Manuel; Datta, Ritobrato; Stern, Andrew M.

    2016-01-01

    Signals from cones are recombined in postreceptoral channels [luminance, L + M; red-green, L − M; blue-yellow, S − (L + M)]. The melanopsin-containing retinal ganglion cells are also active at daytime light levels and recent psychophysical results suggest that melanopsin contributes to conscious vision in humans. Here, we measured BOLD fMRI responses to spectral modulations that separately targeted the postreceptoral cone channels and melanopsin. Responses to spatially uniform (27.5° field size, central 5° obscured) flicker at 0.5, 1, 2, 4, 8, 16, 32, and 64 Hz were recorded from areas V1, V2/V3, motion-sensitive area MT, and the lateral occipital complex. In V1 and V2/V3, higher temporal sensitivity was observed to L + M + S (16 Hz) compared with L − M flicker (8 Hz), consistent with psychophysical findings. Area MT was most sensitive to rapid (32 Hz) flicker of either L + M + S or L − M. We found S cone responses only in areas V1 and V2/V3 (peak frequency: 4–8 Hz). In addition, we studied an L + M modulation and found responses that were effectively identical at all temporal frequencies to those recorded for the L + M + S modulation. Finally, we measured the cortical response to melanopsin-directed flicker and compared this response with control modulations that addressed stimulus imprecision and the possibility of stimulation of cones in the shadow of retinal blood vessels (penumbral cones). For our stimulus conditions, melanopsin flicker did not elicit a cortical response exceeding that of the control modulations. We note that failure to control for penumbral cone stimulation could be mistaken for a melanopsin response. SIGNIFICANCE STATEMENT The retina contains cone photoreceptors and ganglion cells that contain the photopigment melanopsin. Cones provide brightness and color signals to visual cortex. Melanopsin influences circadian rhythm and the pupil, but its contribution to cortex and perception is less clear. We measured the response of human

  10. Long-term human response to uncertain environmental conditions in the Andes

    PubMed Central

    Dillehay, Tom D.; Kolata, Alan L.

    2004-01-01

    Human interaction with the physical environment has increasingly transformed Earth-system processes. Reciprocally, climate anomalies and other processes of environmental change of natural and anthropogenic origin have been affecting, and often disrupting, societies throughout history. Transient impact events, despite their brevity, can have significant long-term impact on society, particularly if they occur in the context of ongoing, protracted environmental change. Major climate events can affect human activities in critical conjunctures that shape particular trajectories of social development. Here we report variable human responses to major environmental events in the Andes with a particular emphasis on the period from anno Domini 500–1500 on the desert north coast of Perú. We show that preindustrial agrarian societies implemented distinct forms of anticipatory response to environmental change and uncertainty. We conclude that innovations in production strategies and agricultural infrastructures in these indigenous societies reflect differential social response to both transient (El Niño–Southern Oscillation events) and protracted (desertification) environmental change. PMID:15024122

  11. Growth function for human response to large-amplitude impulse noise.

    PubMed

    Schomer, P D

    1978-12-01

    The U. S. Environmental Protection Agency has proposed the use of C-weighted day/night level for the assessment of impulse noise such as the noise resulting from sonic boom, blast noise (artillery, armor, demolition, etc.) and other large-amplitude impulse sources. One remaining question pertaining to the use of C-weighting has been the growth function for human response to impulse noise. This question arises because work by Kryter and by Young using peak values and/or small amplitudes exhibited growth functions of 6--7dB for a doubling of annoyance, while the growth function for human response to common sources (planes, vehicles, etc.) increases by about 10 dB for a doubling of annoyance. Kyter's and Young's data are reanalyzed herein by using C-weighting and by including only large-amplitude data. This reanalysis results in a growth function for human response to impulse noise which increases by about 10 dB for a doubling of annoyance. This equality of growth function between common A-weighted noise and C-weighted impulse noise further supports the use of C-weighted day/night level for assessment of sonic boom, blast noise, or other large-amplitude impulse noises having similar spectral content. PMID:739098

  12. Thalamic Responses to Nociceptive-Specific Input in Humans: Functional Dichotomies and Thalamo-Cortical Connectivity.

    PubMed

    Bastuji, Hélène; Frot, Maud; Mazza, Stéphanie; Perchet, Caroline; Magnin, Michel; Garcia-Larrea, Luis

    2016-06-01

    While nociceptive cortical activation is now well characterized in humans, understanding of the nociceptive thalamus remains largely fragmentary. We used laser stimuli and intracerebral electrodes in 17 human subjects to record nociceptive-specific field responses in 4 human thalamic nuclei and a number of cortical areas. Three nuclei known to receive spinothalamic (STT) projections in primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central lateral [CL]) exhibited responses with similar latency, indicating their parallel activation by nociceptive afferents. Phase coherence analysis, however, revealed major differences in their functional connectivity: while VPL and PuA drove a limited set of cortical targets, CL activities were synchronized with a large network including temporal, parietal, and frontal areas. Our data suggest that STT afferents reach simultaneously a set of lateral and medial thalamic regions unconstrained by traditional nuclear borders. The broad pattern of associated cortical networks suggests that a single nociceptive volley is able to trigger the sensory, cognitive, and emotional activities that underlie the complex pain experience. The medial pulvinar, an associative nucleus devoid of STT input, exhibited delayed responses suggesting its dependence on descending cortico-thalamic projections. Its widespread cortical connectivity suggests a role in synchronizing parietal, temporal, and frontal activities, hence contributing to the access of noxious input to conscious awareness. PMID:25994963

  13. Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans

    PubMed Central

    Locher, Chrystèle; Raux, Mathieu; Fiamma, Marie-Noelle; Morélot-Panzini, Capucine; Zelter, Marc; Derenne, Jean-Philippe; Similowski, Thomas; Straus, Christian

    2006-01-01

    Background Breathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation. Results Six healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH2O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20: -0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs. Conclusion Inspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans. PMID:16875504

  14. Genetic selection for modulators of a retinoic-acid-responsive reporter in human cells.

    PubMed Central

    Richards, Burt; Karpilow, Jon; Dunn, Christine; Peterson, Isaac; Maxfield, Andrew; Zharkikh, Ludmilla; Abedi, Majid; Hurlburt, Anthony; Hardman, Joshua; Hsu, Forrest; Li, Wenhua; Rebentisch, Matthew; Sandrock, Robert; Sandrock, Tanya; Kamb, Alexander; Teng, David H-F

    2003-01-01

    We used a genetic screening methodology, a human cell line bearing a retinoic-acid-responsive enhanced GFP reporter, and a flow sorter to recover dominant modulators of reporter expression. Four inducers and three suppressors that were fused to the C terminus of a protein scaffold for stability were isolated and their mechanisms of action studied. Mutagenesis experiments indicated that six of these dominant agents exerted their effects at the protein level. The single cDNA coding fragment that was isolated comprised the central 64-amino-acid section of human cyclophilin B, which contained its peptidyl-prolyl isomerase domain; this cyclophilin fragment repressed expression of the retinoic-acid-responsive reporter. The remaining clones encoded peptides shorter than 30 amino acids unrelated to known gene open reading frames. Genetic epistasis studies between the strongest inducer, R3, and a dominant-negative mutant of RARalpha suggest that the two factors function in the same pathway. Transcript microarray analyses suggest that R3 induced a subset of the retinoid-responsive genes in melanoma cells. Finally, yeast two-hybrid assays and co-immunoprecipitation studies of human cell extracts identified PAT1 as a protein that interacts with R3. PMID:12663543

  15. Orientation Selectivity of Motion-Boundary Responses in Human Visual Cortex

    PubMed Central

    Heeger, David J.; Landy, Michael S.

    2010-01-01

    Motion boundaries (local changes in visual motion direction) arise naturally when objects move relative to an observer. In human visual cortex, neuroimaging studies have identified a region (the kinetic occipital area [KO]) that responds more strongly to motion-boundary stimuli than to transparent-motion stimuli. However, some functional magnetic resonance imaging (fMRI) studies suggest that KO may encompass multiple visual areas and single-unit studies in macaque visual cortex have identified neurons selective for motion-boundary orientation in areas V2, V3, and V4, implying that motion-boundary selectivity may not be restricted to a single area. It is not known whether fMRI responses to motion boundaries are selective for motion-boundary orientation, as would be expected if these responses reflected the population activity of motion-boundary–selective neurons. We used an event-related fMRI adaptation protocol to measure orientation-selective responses to motion boundaries in human visual cortex. On each trial, we measured the response to a probe stimulus presented after an adapter stimulus (a vertical or horizontal motion-boundary grating). The probe stimulus was either a motion-boundary grating oriented parallel or orthogonal to the adapter stimulus or a transparent-motion stimulus. Orientation-selective adaptation for motion boundaries—smaller responses for trials in which test and adapter stimuli were parallel to each other—was observed in multiple extrastriate visual areas. The strongest adaptation, relative to the unadapted responses, was found in V3A, V3B, LO1, LO2, and V7. Most of the visual areas that exhibited orientation-selective adaptation in our data also showed response preference for motion boundaries over transparent motion, indicating that most of the human visual areas previously shown to respond to motion boundaries are also selective for motion-boundary orientation. These results suggest that neurons selective for motion

  16. Specific responses of human hippocampal neurons are associated with better memory.

    PubMed

    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. PMID:26240357

  17. Specific responses of human hippocampal neurons are associated with better memory

    PubMed Central

    Suthana, Nanthia A.; Parikshak, Neelroop N.; Ekstrom, Arne D.; Ison, Matias J.; Knowlton, Barbara J.; Bookheimer, Susan Y.; Fried, Itzhak

    2015-01-01

    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. PMID:26240357

  18. CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses

    PubMed Central

    Hammitzsch, Ariane; Tallant, Cynthia; Fedorov, Oleg; O’Mahony, Alison; Brennan, Paul E.; Hay, Duncan A.; Martinez, Fernando O.; Al-Mossawi, M. Hussein; de Wit, Jelle; Vecellio, Matteo; Wells, Christopher; Wordsworth, Paul; Müller, Susanne; Knapp, Stefan; Bowness, Paul

    2015-01-01

    Th17 responses are critical to a variety of human autoimmune diseases, and therapeutic targeting with monoclonal antibodies against IL-17 and IL-23 has shown considerable promise. Here, we report data to support selective bromodomain blockade of the transcriptional coactivators CBP (CREB binding protein) and p300 as an alternative approach to inhibit human Th17 responses. We show that CBP30 has marked molecular specificity for the bromodomains of CBP and p300, compared with 43 other bromodomains. In unbiased cellular testing on a diverse panel of cultured primary human cells, CBP30 reduced immune cell production of IL-17A and other proinflammatory cytokines. CBP30 also inhibited IL-17A secretion by Th17 cells from healthy donors and patients with ankylosing spondylitis and psoriatic arthritis. Transcriptional profiling of human T cells after CBP30 treatment showed a much more restricted effect on gene expression than that observed with the pan-BET (bromo and extraterminal domain protein family) bromodomain inhibitor JQ1. This selective targeting of the CBP/p300 bromodomain by CBP30 will potentially lead to fewer side effects than with the broadly acting epigenetic inhibitors currently in clinical trials. PMID:26261308

  19. Minimal changes in heart rate of incubating American Oystercatchers (Haematopus palliatus) in response to human activity

    USGS Publications Warehouse

    Borneman, Tracy E.; Rose, Eli T.; Simons, Theodore R.

    2014-01-01

    An organism's heart rate is commonly used as an indicator of physiological stress due to environmental stimuli. We used heart rate to monitor the physiological response of American Oystercatchers (Haematopus palliatus) to human activity in their nesting environment. We placed artificial eggs with embedded microphones in 42 oystercatcher nests to record the heart rate of incubating oystercatchers continuously for up to 27 days. We used continuous video and audio recordings collected simultaneously at the nests to relate physiological response of birds (heart rate) to various types of human activity. We observed military and civilian aircraft, off-road vehicles, and pedestrians around nests. With the exception of high-speed, low-altitude military overflights, we found little evidence that oystercatcher heart rates were influenced by most types of human activity. The low-altitude flights were the only human activity to significantly increase average heart rates of incubating oystercatchers (12% above baseline). Although statistically significant, we do not consider the increase in heart rate during high-speed, low-altitude military overflights to be of biological significance. This noninvasive technique may be appropriate for other studies of stress in nesting birds.

  20. Hypoxia attenuates anti-Aspergillus fumigatus immune responses initiated by human dendritic cells.

    PubMed

    Fliesser, Mirjam; Wallstein, Marion; Kurzai, Oliver; Einsele, Hermann; Löffler, Jürgen

    2016-08-01

    Aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (IPA), a life-threatening infection in immunocompromised patients. During the course of IPA, localised areas of tissue hypoxia occur. Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of hypoxia on the human anti-A. fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated in vitro with germ tubes of A. fumigatus under normoxia or hypoxia (1% O2 ), followed by analysis of DC viability, maturation and cytokine release. While DC viability was unaffected, hypoxia attenuated cytokine release from DCs and maturation of DCs upon stimulation with A. fumigatus. These data suggest that hypoxia at the site of A. fumigatus infection inhibits full activation and function of human DCs. Thereby, this study identified hypoxia as a crucial immune-modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients. PMID:27005862

  1. Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: proof of principle.

    PubMed

    Schwartz, Maria A K; Lieske, John C; Kumar, Vivek; Farell-Baril, Gerard; Miller, Virginia M

    2008-01-01

    Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcification. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium. PMID:18686783

  2. Species-Specific Responses of Carnivores to Human-Induced Landscape Changes in Central Argentina

    PubMed Central

    Caruso, Nicolás; Lucherini, Mauro; Fortin, Daniel; Casanave, Emma B.

    2016-01-01

    The role that mammalian carnivores play in ecosystems can be deeply altered by human-driven habitat disturbance. While most carnivore species are negatively affected, the impact of habitat changes is expected to depend on their ecological flexibility. We aimed to identify key factors affecting the habitat use by four sympatric carnivore species in landscapes of central Argentina. Camera trapping surveys were carried out at 49 sites from 2011 to 2013. Each site was characterized by 12 habitat attributes, including human disturbance and fragmentation. Four landscape gradients were created from Principal Component Analysis and their influence on species-specific habitat use was studied using Generalized Linear Models. We recorded 74 events of Conepatus chinga, 546 of Pseudalopex gymnocercus, 193 of Leopardus geoffroyi and 45 of Puma concolor. We found that the gradient describing sites away from urban settlements and with low levels of disturbance had the strongest influence. L. geoffroyi was the only species responding significantly to the four gradients and showing a positive response to modified habitats, which could be favored by the low level of persecution by humans. P. concolor made stronger use of most preserved sites with low proportion of cropland, even though the species also used sites with an intermediate level of fragmentation. A more flexible use of space was found for C. chinga and P. gymnocercus. Our results demonstrate that the impact of human activities spans across this guild of carnivores and that species-specific responses appear to be mediated by ecological and behavioral attributes. PMID:26950300

  3. The pyrimidin analogue cyclopentenyl cytosine induces alloantigen-specific non-responsiveness of human T lymphocytes

    PubMed Central

    Nikolaeva, N; Bemelman, F J; Yong, S-L; Verschuur, A; van Lier, R A W; ten Berge, I J M

    2008-01-01

    Cyclopentenyl cytosine (CPEC) has been shown to induce apoptosis in human T lymphoblastic cell lines and T cells from leukaemia patients. In this study we have addressed the question of whether CPEC is able to decrease proliferation and effector functions of human alloresponsive T lymphocytes and induce T cell anergy. The proliferative capacity of human peripheral blood mononuclear cells in response to allogeneic stimulation was measured by 5,6-carboxy-succinimidyl-diacetate-fluorescein-ester staining. Flow cytometric analysis was performed using surface CD4, CD8, CD25, CD103 and intracellular perforin, granzyme A, granzyme B, caspase-3 and forkhead box P3 (FoxP3) markers. The in vivo immunosuppressive capacity was tested in a murine skin graft model. Addition of CPEC at a concentration of 20 nM strongly decreased the expansion and cytotoxicity of alloreactive T cells. Specific restimulation in the absence of CPEC showed that the cells became anergic. The drug induced caspase-dependent apoptosis of alloreactive T lymphocytes. Finally, CPEC increased the percentage of CD25high FoxP3+ CD4+ and CD103+ CD8+ T cells, and potentiated the effect of rapamycin in increasing the numbers of alloreactive regulatory T cells. Treatment with CPEC of CBA/CA mice transplanted with B10/Br skin grafts significantly prolonged graft survival. We conclude that CPEC inhibits proliferation and cytotoxicity of human alloreactive T cells and induces alloantigen non-responsiveness in vitro. PMID:18062797

  4. Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.

    PubMed

    Jubb, Alasdair W; Young, Robert S; Hume, David A; Bickmore, Wendy A

    2016-01-15

    Phenotypic differences between individuals and species are controlled in part through differences in expression of a relatively conserved set of genes. Genes expressed in the immune system are subject to especially powerful selection. We have investigated the evolution of both gene expression and candidate enhancers in human and mouse macrophages exposed to glucocorticoid (GC), a regulator of innate immunity and an important therapeutic agent. Our analyses revealed a very limited overlap in the repertoire of genes responsive to GC in human and mouse macrophages. Peaks of inducible binding of the GC receptor (GR) detected by chromatin immunoprecipitation-Seq correlated with induction, but not repression, of target genes in both species, occurred at distal regulatory sites not promoters, and were strongly enriched for the consensus GR-binding motif. Turnover of GR binding between mice and humans was associated with gain and loss of the motif. There was no detectable signal of positive selection at species-specific GR binding sites, but clear evidence of purifying selection at the small number of conserved sites. We conclude that enhancer divergence underlies the difference in transcriptional activation after GC treatment between mouse and human macrophages. Only the shared inducible loci show evidence of selection, and therefore these loci may be important for the subset of responses to GC that is shared between species. PMID:26663721

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

    PubMed Central

    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

  6. Bacillus anthracis’ lethal toxin induces broad transcriptional responses in human peripheral monocytes

    PubMed Central

    2012-01-01

    Background Anthrax lethal toxin (LT), produced by the Gram-positive bacterium Bacillus anthracis, is a highly effective zinc dependent metalloprotease that cleaves the N-terminus of mitogen-activated protein kinase kinases (MAPKK or MEKs) and is known to play a role in impairing the host immune system during an inhalation anthrax infection. Here, we present the transcriptional responses of LT treated human monocytes in order to further elucidate the mechanisms of LT inhibition on the host immune system. Results Western Blot analysis demonstrated cleavage of endogenous MEK1 and MEK3 when human monocytes were treated with 500 ng/mL LT for four hours, proving their susceptibility to anthrax lethal toxin. Furthermore, staining with annexin V and propidium iodide revealed that LT treatment did not induce human peripheral monocyte apoptosis or necrosis. Using Affymetrix Human Genome U133 Plus 2.0 Arrays, we identified over 820 probe sets differentially regulated after LT treatment at the p <0.001 significance level, interrupting the normal transduction of over 60 known pathways. As expected, the MAPKK signaling pathway was most drastically affected by LT, but numerous genes outside the well-recognized pathways were also influenced by LT including the IL-18 signaling pathway, Toll-like receptor pathway and the IFN alpha signaling pathway. Multiple genes involved in actin regulation, signal transduction, transcriptional regulation and cytokine signaling were identified after treatment with anthrax LT. Conclusion We conclude LT directly targets human peripheral monocytes and causes multiple aberrant gene responses that would be expected to be associated with defects in human monocyte’s normal signaling transduction pathways and function. This study provides further insights into the mechanisms associated with the host immune system collapse during an anthrax infection, and suggests that anthrax LT may have additional downstream targets outside the well-known MAPK

  7. Comparison of Head-Neck Responses in Frontal Impacts Using Restrained Human Surrogates

    PubMed Central

    Yoganandan, Narayan; Pintar, Frank A.; Schlick, Michael; Moore, Jason; Maiman, Dennis J.

    2011-01-01

    The objective of the study was to evaluate the head and neck kinetics of three-point belted Hybrid III dummy and Test Device for Human Occupant Restraint (THOR) in frontal impacts, and compare their responses with data from post mortem human subjects (PMHS). Surrogates were placed on a buck, capable of accommodating different anthropometry with similar initial positioning. Duplicate tests were conducted at low, medium, and high (3.6, 6.9, and 15.8 m/s) velocities. Upper and lower neck forces and moments were determined from load cell measures and its locations with respect to the ends of the neck. Head excursion-time responses were more repeatable in the Hybrid III dummy than the THOR dummy. Hybrid III dummy response was more rigid in the sagittal plane. Peak THOR motions were closer to PMHS. Based on times of occurrences of peak excursions, THOR was closer to PMHS at all velocities, while Hybrid III dummy showed biofidelity at the medium and high velocities. Controlled positioning and testing with different surrogates provide an evaluation of inter-subject responses. THOR was more likely to “get the head where and when it needs to be” in frontal impacts. With the importance of testing at lower speeds due to recent recognition of real-world injuries, these data suggest that THOR may be an optimal dummy for frontal impacts. Comparisons of head-neck kinetic data with PMHS are valuable in frontal impact injury assessments. PMID:22105395

  8. Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights.

    PubMed

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Fuentes-Duculan, Judilyn; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; Correa da Rosa, Joel; Cueto, Inna; Mitsui, Hiroshi; Krueger, James G

    2014-10-01

    Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune-modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3-day (peak) and 14-day (resolution) time points using immune markers, reverse-transcriptase-PCR (RT-PCR), and gene array approaches. A peak response showed modulation of ∼7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T cells and mature (DC-lysosome-associated membrane glycoprotein positive (DC-LAMP+)) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T cell-derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ∼1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest that the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin. PMID:24751728

  9. Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights

    PubMed Central

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Fuentes-Duculan, Judilyn; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; da Rosa, Joel Correa; Cueto, Inna; Mitsui, Hiroshi; Krueger, James G.

    2014-01-01

    Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3 day (peak) and 14 day (resolution) timepoints using immune markers, RT-PCR and gene array approaches. A peak response showed modulation of ~7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T-cells and mature (DC-LAMP+) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T-cell derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ~1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin. PMID:24751728

  10. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    PubMed

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

  11. TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

    PubMed Central

    McClure, Ryan; Massari, Paola

    2014-01-01

    Toll-like receptor (TLR) signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in human being 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. PMID:25161655

  12. Investigating the functionality of an OCT4-short response element in human induced pluripotent stem cells

    PubMed Central

    Vega-Crespo, Agustin; Truong, Brian; Hermann, Kip J; Awe, Jason P; Chang, Katherine M; Lee, Patrick C; Schoenberg, Benjamen E; Wu, Lily; Byrne, James A; Lipshutz, Gerald S

    2016-01-01

    Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics. PMID:27500178

  13. Opportunistic pathogen Candida albicans elicits a temporal response in primary human mast cells

    PubMed Central

    Lopes, José Pedro; Stylianou, Marios; Nilsson, Gunnar; Urban, Constantin F.

    2015-01-01

    Immunosuppressed patients are frequently afflicted with severe mycoses caused by opportunistic fungal pathogens. Besides being a commensal, colonizing predominantly skin and mucosal surfaces, Candida albicans is the most common human fungal pathogen. Mast cells are present in tissues prone to fungal colonization being expectedly among the first immune cells to get into contact with C. albicans. However, mast cell-fungus interaction remains a neglected area of study. Here we show that human mast cells mounted specific responses towards C. albicans. Collectively, mast cell responses included the launch of initial, intermediate and late phase components determined by the secretion of granular proteins and cytokines. Initially mast cells reduced fungal viability and occasionally internalized yeasts. C. albicans could evade ingestion by intracellular growth leading to cellular death. Furthermore, secreted factors in the supernatants of infected cells recruited neutrophils, but not monocytes. Late stages were marked by the release of cytokines that are known to be anti-inflammatory suggesting a modulation of initial responses. C. albicans-infected mast cells formed extracellular DNA traps, which ensnared but did not kill the fungus. Our results suggest that mast cells serve as tissue sentinels modulating antifungal immune responses during C. albicans infection. Consequently, these findings open new doors for understanding fungal pathogenicity. PMID:26192381

  14. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

    PubMed Central

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-01-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

  15. Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status

    PubMed Central

    Mirzayans, Razmik; Andrais, Bonnie; Scott, April; Wang, Ying W.; Murray, David

    2013-01-01

    Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation). Most of these responses result in loss of colony-forming ability in the clonogenic survival assay. However, not all modes of so-called clonogenic cell “death” are necessarily advantageous for therapeutic outcome in cancer radiotherapy. For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence. Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities. Herein we review the current knowledge on the roles that the p53 and p21WAF1 tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation. In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation. This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents. PMID:24232458

  16. Interactions between glutamate, dopamine, and the neuronal signature of response inhibition in the human striatum.

    PubMed

    Lorenz, Robert C; Gleich, Tobias; Buchert, Ralph; Schlagenhauf, Florian; Kühn, Simone; Gallinat, Jürgen

    2015-10-01

    Response inhibition is a basic mechanism in cognitive control and dysfunctional in major psychiatric disorders. The neuronal mechanisms are in part driven by dopamine in the striatum. Animal data suggest a regulatory role of glutamate on the level of the striatum. We used a trimodal imaging procedure of the human striatum including F18-DOPA positron emission tomography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging of a stop signal task. We investigated dopamine synthesis capacity and glutamate concentration in vivo and their relation to functional properties of response inhibition. A mediation analysis revealed a significant positive association between dopamine synthesis capacity and inhibition-related neural activity in the caudate nucleus. This relationship was significantly mediated by striatal glutamate concentration. Furthermore, stop signal reaction time was inversely related to striatal activity during inhibition. The data show, for the first time in humans, an interaction between dopamine, glutamate, and the neural signature of response inhibition in the striatum. This finding stresses the importance of the dopamine-glutamate interaction for behavior and may facilitate the understanding of psychiatric disorders characterized by impaired response inhibition. PMID:26177932

  17. Mathematical modeling provides kinetic details of the human immune response to vaccination

    PubMed Central

    Le, Dustin; Miller, Joseph D.; Ganusov, Vitaly V.

    2015-01-01

    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. PMID:25621280

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

    PubMed

    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 (<100 nm) surface nano-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. PMID:22619111

  19. Response of the seated human body to whole-body vertical vibration: biodynamic responses to sinusoidal and random vibration.

    PubMed

    Zhou, Zhen; Griffin, Michael J

    2014-01-01

    The dependence of biodynamic responses of the seated human body on the frequency, magnitude and waveform of vertical vibration has been studied in 20 males and 20 females. With sinusoidal vibration (13 frequencies from 1 to 16 Hz) at five magnitudes (0.1-1.6 ms(-2) r.m.s.) and with random vibration (1-16 Hz) at the same magnitudes, the apparent mass of the body was similar with random and sinusoidal vibration of the same overall magnitude. With increasing magnitude of vibration, the stiffness and damping of a model fitted to the apparent mass reduced and the resonance frequency decreased (from 6.5 to 4.5 Hz). Male and female subjects had similar apparent mass (after adjusting for subject weight) and a similar principal resonance frequency with both random and sinusoidal vibration. The change in biodynamic response with increasing vibration magnitude depends on the frequency of the vibration excitation, but is similar with sinusoidal and random excitation. PMID:24730687

  20. Local modulation of human brain responses by circadian rhythmicity and sleep debt.

    PubMed

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

    2016-08-12

    Human performance is modulated by circadian rhythmicity and homeostatic sleep pressure. Whether and how this interaction is represented at the regional brain level has not been established. We quantified changes in brain responses to a sustained-attention task during 13 functional magnetic resonance imaging sessions scheduled across the circadian cycle, during 42 hours of wakefulness and after recovery sleep, in 33 healthy participants. Cortical responses showed significant circadian rhythmicity, the phase of which varied across brain regions. Cortical responses also significantly decreased with accrued sleep debt. Subcortical areas exhibited primarily a circadian modulation that closely followed the melatonin profile. These findings expand our understanding of the mechanisms involved in maintaining cognition during the day and its deterioration during sleep deprivation and circadian misalignment. PMID:27516598

  1. Cancer risk assessment: Optimizing human health through linear dose-response models.

    PubMed

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C

    2015-07-01

    This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot". PMID:25916915

  2. Human antibody response to dengue virus: implications for dengue vaccine design.

    PubMed

    Moi, Meng Ling; Takasaki, Tomohiko; Kurane, Ichiro

    2016-01-01

    Dengue, a global health threat, is a leading cause of morbidity and mortality in most tropical and subtropical countries. Dengue can range from asymptomatic, relatively mild dengue fever to severe and life-threatening dengue hemorrhagic fever. Disease severity and outcome is largely associated with the host immune response. Several candidate vaccines in clinical trials appear promising as effective measures for dengue disease control. Vaccine development has been hampered by safety and efficacy issues, driven by a lack of understanding of the host immune response. This review focuses on recent research findings on the dengue host immune response, particularly in humans, and the relevance of these findings to challenges in vaccine development. PMID:27398060

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

    SciTech Connect

    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.

    2012-03-15

    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 outperformed

  4. Lipoproteins are Major Targets of the Polyclonal Human T-cell Response to M. tuberculosis1

    PubMed Central

    Seshadri, Chetan; Turner, Marie T.; Lewinsohn, David M.; Moody, D. Branch; Van Rhijn, Ildiko

    2012-01-01

    Most vaccines and basic studies of T cell epitopes in M. tuberculosis emphasize water soluble proteins that are secreted into the extracellular space and presented in the context of MHC Class II. Much less is known about the role of antigens retained within the cell wall. We used polyclonal T cells from infected humans to probe for responses to immunodominant antigens in the M. tuberculosis cell wall. We found that the magnitude of response to secreted or cell wall intrinsic compounds was similar among healthy controls, patients with latent tuberculosis, and patients with active tuberculosis. Individual responses to secreted antigens and cell wall extract were strongly correlated (r2=0.495, p=0.001), suggesting that T cells responding to cell wall and secreted antigens are present at similar frequency. Surprisingly, T cell stimulatory factors intrinsic to the cell wall partition into organic solvents; however, these responses are not explained by CD1-mediated presentation of lipids. Instead, we find that molecules soluble in organic solvents are dependent upon MHC Class II and recognized by IFN-γ secreting CD4+ T cells. We reasoned that MHC Class II dependent antigens extracting into lipid mixtures might be found among triacylated lipoproteins present in mycobacteria. We used M. tuberculosis lacking prolipoprotein signal peptidase A (lspA), an enzyme required for lipoprotein synthesis, to demonstrate loss of polyclonal T cell responses. Our results demonstrate the use of bacterial genetics to identify lipoproteins as an unexpected and immunodominant class of cell wall-associated antigens targeted by the polyclonal human T cell response to M. tuberculosis. PMID:23197260

  5. Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays.

    PubMed

    Cocorocchio, Marco; Ives, Robert; Clapham, David; Andrews, Paul L R; Williams, Robin S B

    2016-01-01

    Treatment compliance is reduced when pharmaceutical compounds have a bitter taste and this is particularly marked for paediatric medications. Identification of bitter taste liability during drug discovery utilises the rat in vivo brief access taste aversion (BATA) test which apart from animal use is time consuming with limited throughput. We investigated the suitability of using a simple, non-animal model, the amoeba Dictyostelium discoideum to investigate taste-related responses and particularly identification of compounds with a bitter taste liability. The effect of taste-related compounds on Dictyostelium behaviour following acute exposure (15 minutes) was monitored. Dictyostelium did not respond to salty, sour, umami or sweet tasting compounds, however, cells rapidly responded to bitter tastants. Using time-lapse photography and computer-generated quantification to monitor changes in cell membrane movement, we developed an assay to assess the response of Dict