Glucocorticoid programming of neuroimmune function.

PubMed

Walker, David J; Spencer, Karen A

2018-01-15

Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Clinical-Physiological Considerations in Patients Undergoing Staged Palliation for a Functionally Single Ventricle.

PubMed

Penny, Daniel J; Krishnamurthy, Rajesh

2016-08-01

The objectives of this review are to discuss the pathophysiology of the circulation with a functionally univentricular heart, with a focus on the unique physiologic characteristics, which provide the underpinnings for the management of these complex patients. MEDLINE and PubMed. The circulation of the patient with a functionally univentricular heart displays unique physiologic characteristics, which are quite different from those of the normal biventricular circulation. There are profound differences within the heart itself in terms of ventricular function, interventricular interactions, and myocardial architecture, which are likely to have significant implications for the efficiency of ventricular ejection and metabolism. The coupling between the systemic ventricle and the aorta also displays unique features. The 3D orientation of the Fontan anastomosis itself can profoundly impact cardiac output, although the "portal" pulmonary arterial bed is a crucial determinant of overall cardiovascular function. As a result, disease-specific approaches to improve cardiovascular function are required at all stages during the care of these complex patients.

Comparative study on the toxic effects of red tide flagellates Heterocapsa circularisquama and Chattonella marina on the short-necked clam (Ruditapes philippinarum).

PubMed

Kim, Daekyung; Choi, Kwang-Sik; Hong, Hyun-Ki; Jiang, Zedong; Zou, Yanan; Choi, Kyu-Sung; Yamasaki, Yasuhiro; Matsuyama, Yukihiko; Yamaguchi, Kenichi; Oda, Tatsuya

2011-01-01

Heterocapsa circularisquama showed much higher toxic effects on short-necked clams than Chattonella marina. Clams exposed to H. circularisquama exhibited morphological changes concomitant with an accumulation of mucus-like substances in the gills, a profound reduction in filtration activity, and lysosomal destabilization in hemocytes. Chattonella marina was less effective than H. circularisquama, and Heterocapsa triquetra was almost harmless in all these criteria. These results suggest that H. circularisquama exerted its lethal effect on short-necked clams through gill tissue damage and subsequent induction of physiological stress.

Physiological Sociology. Endocrine Correlates of Status Behaviors,

DTIC Science & Technology

1975-01-01

affiliative bonding. One psychiatric illness which manifests itself in social structural relationships in a profound was is sociopathic behavior. By the...very nature of the sociopathic individual, persons with the disorder display altered social behavior (Robins, 1966). The question as to whether such...Oxford: Oxford University Press, 1971. Goldman, H., Lindner, L., Dinitz, S., and Allen, H. The simple sociopath : Physiologic and sociologic

[Physiology in Relation to Anesthesia Practice: Preface and Comments].

PubMed

Yamada, Yoshitsugu

2016-05-01

It has been long recognized that anesthesia practice is profoundly based in physiology. With the advance of the technology of imaging, measurement and information, a serious gap has emerged between anesthesia mainly handling gross systemic parameters and molecular physiology. One of the main reasons is the lack of establishment of integration approach. This special series of reviews deals with systems physiology covering respiratory, cardiovascular, and nervous systems. It also includes metabolism, and fluid, acid-base, and electrolyte balance. Each review focuses on several physiological concepts in each area, explaining current understanding and limits of the concepts based on the new findings. They reaffirm the importance of applying physiological inference in anesthesia practice and underscore the needs of advancement of systems physiology.

Thermoregulatory responses to environmental toxicants: The interaction of thermal stress and toxicant exposure

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

Leon, Lisa R.

2008-11-15

Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment. These physiological responses may exacerbate chemical toxicity due to increased permeability of the skin, which facilitates the cutaneous absorption of many environmental toxicants. The core temperature responses that aremore » elicited in response to high ambient temperatures, toxicant exposure or both can also have a profound impact on the ability of an organism to survive the insult. In small rodents, the thermoregulatory response to thermal stress and many environmental toxicants (such as organophosphate compounds) is often biphasic in nature, consisting initially of a regulated reduction in core temperature (i.e., hypothermia) followed by fever. Hypothermia is an important thermoregulatory survival strategy that is used by small rodents to diminish the effect of severe environmental insults on tissue homeostasis. The protective effect of hypothermia is realized by its effects on chemical toxicity as molecular and cellular processes, such as lipid peroxidation and the formation of reactive oxygen species, are minimized at reduced core temperatures. The beneficial effects of fever are unknown under these conditions. Perspective is provided on the applicability of data obtained in rodent models to the human condition.« less

Behavioral and physiological consequences of enrichment loss in rats

PubMed Central

Smith, Brittany L.; Lyons, Carey E; Correa, Fernanda Guilhaume; Benoit, Stephen C.; Myers, Brent; Solomon, Matia B.; Herman, James P.

2017-01-01

Significant loss produces the highest degree of stress and compromised well-being in humans. Current rodent models of stress involve the application of physically or psychologically aversive stimuli, but do not address the concept of loss. We developed a rodent model for significant loss, involving removal of long-term access to a rewarding enriched environment. Our results indicate that removal from environmental enrichment produces a profound behavioral and physiological phenotype with depression-like qualities, including helplessness behavior, hypothalamo-pituitary-adrenocortical axis dysregulation and overeating. Importantly, this enrichment removal phenotype was prevented by antidepressant treatment. Furthermore, the effects of enrichment removal do not occur following relief from chronic stress and are not duplicated by loss of exercise or social contact. PMID:28012292

The tell-tale: what do heart rate; skin temperature and skin conductance reveal about emotions of people with severe and profound intellectual disabilities?

PubMed

Vos, Pieter; De Cock, Paul; Munde, Vera; Petry, Katja; Van Den Noortgate, Wim; Maes, Bea

2012-01-01

Identifying emotions in people with severe and profound intellectual disabilities is a difficult challenge. Since self-reports are not available, behaviour is the most used source of information. Given the limitations and caveats associated with using behaviour as the sole source of information about their emotions, it is important to supplement behavioural information with information from another source. As it is accepted that emotions consist of language, behaviour and physiology, in this article we investigated if physiology could give information about the emotions of people with severe and profound intellectual disabilities. To this aim we tested hypotheses derived from the motivational model of Bradley, Codispoti, Cuthbert, and Lang (2001) about the relation between heart rate and the valence of emotions and between heart rate, skin conductance and skin temperature and behavioural expressions of emotions of people with severe and profound intellectual disability. We presented 27 participants with 4 staff-selected negative and 4 staff-selected positive stimuli. The situations were videotaped and their heart rate, skin conductance and skin temperature was measured. Each behaviour of the participant was coded using the observational method developed by Petry and Maes (2006). As hypothesized, we found a lower heart rate when participants were presented with negative stimuli than when they were presented with positive stimuli in the first 6s of stimuli presentation. Their skin temperature was higher for the expression of low intensity negative emotions compared to the expression of low intensity positive emotions. The results suggest that, as with people without disability, heart rate and skin temperature can give information about the emotions of persons with severe and profound ID. Copyright © 2012 Elsevier Ltd. All rights reserved.

Metabolite Adjustments in Drought Tolerant and Sensitive Soybean Genotypes in Response to Water Stress

PubMed Central

Silvente, Sonia; Sobolev, Anatoly P.; Lara, Miguel

2012-01-01

Soybean (Glycine max L.) is an important source of protein for human and animal nutrition, as well as a major source of vegetable oil. The soybean crop requires adequate water all through its growth period to attain its yield potential, and the lack of soil moisture at critical stages of growth profoundly impacts the productivity. In this study, utilizing 1H NMR-based metabolite analysis combined with the physiological studies we assessed the effects of short-term water stress on overall growth, nitrogen fixation, ureide and proline dynamics, as well as metabolic changes in drought tolerant (NA5009RG) and sensitive (DM50048) genotypes of soybean in order to elucidate metabolite adjustments in relation to the physiological responses in the nitrogen-fixing plants towards water limitation. The results of our analysis demonstrated critical differences in physiological responses between these two genotypes, and identified the metabolic pathways that are affected by short-term water limitation in soybean plants. Metabolic changes in response to drought conditions highlighted pools of metabolites that play a role in the adjustment of metabolism and physiology of the soybean varieties to meet drought effects. PMID:22685583

Interactions between Artificial Gravity, the Affected Physiological Systems, and Nutrition

NASA Technical Reports Server (NTRS)

Heer, Martina; Baecker, Nathalie; Zwart, Sara; Smith, Scott

2006-01-01

Malnutrition, either by insufficient supply of some nutrients or by overfeeding, has a profound effect on the health of an organism. Therefore, optimal nutrition is a necessity in normal gravity on Earth, in microgravity, and when applying artificial gravity to the human system. Reduced physical activity, such as observed in microgravity or bed rest, has an effect on many physiological systems, such as the cardiovascular, musculoskeletal, immune, and body fluids regulation systems. There is currently no countermeasure that is effective to counteract both the cardiovascular and musculoskeletal deconditioning when applied for a short duration (see Chapter 1). Artificial gravity therefore seems the simplest physiological approach to keep these systems intact. The application of intermittent daily dose of artificial gravity by means of centrifugation has often been proposed as a potential countermeasure against the physiological deconditioning induced by spaceflight. However, neither the optimal gravity level, nor its optimal duration of exposure have been enough studied to recommend a validated, effective, and efficient artificial gravity application. As discussed in previous chapters, artificial gravity has a very high potential to counteract any changes caused by reduced physical activity. The nutrient supply, which ideally should match the actual needs, will interact with these changes and therefore has also to be taken into account. This chapter reviews the potential interactions between these nutrients (energy intake, vitamins, minerals) and the other physiological systems affected by artificial gravity generated by an on-board short-radius centrifuge.

Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research

PubMed Central

Baker, David G.

1998-01-01

Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Frequently, these organisms cause no overt signs of disease. However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. While the number and prevalence of these pathogens have declined considerably, many still turn up in laboratory animals and represent unwanted variables in research. Investigators using mice, rats, and rabbits in biomedical experimentation should be aware of the profound effects that many of these agents can have on research. PMID:9564563

Effects of alcohol on the endocrine system.

PubMed

Rachdaoui, Nadia; Sarkar, Dipak K

2013-09-01

Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine, and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiologic and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease, and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. Copyright © 2013 Elsevier Inc. All rights reserved.

Behavioral treatment of chronic aerophagia.

PubMed

Barrett, R P; McGonigle, J J; Ackles, P K; Burkhart, J E

1987-05-01

Effects of various behavioral interventions on stereotyped aerophagic responding by a profoundly mentally retarded, 5-year-old girl were assessed. Aerophagic responding was defined as air swallowing with extreme stomach protrusion, followed by breath-holding. Observations of air swallowing, as well as physiologic measurements related to heart rate and respiratory patterns, were recorded across both baseline and treatment phases of the study. Multiple behavioral interventions were assessed within a laboratory setting using an alternating treatment design format, with the most effective treatment systematically extended to additional settings. Results indicated that a behavior modification treatment package was effective in suppressing the high frequency of this rare stereotyped act to near-zero rates.

Monitoring and Correcting Autonomic Function Aboard Mir: NASA Technology Used in Space and on Earth to Facilitate Adaptation

NASA Technical Reports Server (NTRS)

Cowings, P.; Toscano, W.; Taylor, B.; DeRoshia, C.; Kornilova, L.; Koslovskaya, I.; Miller, N.

1999-01-01

The broad objective of the research was to study individual characteristics of human adaptation to long duration spaceflight and possibilities of their correction using autonomic conditioning. The changes in autonomic state during adaptation to microgravity can have profound effects on the operational efficiency of crewmembers and may result in debilitating biomedical symptoms. Ground-based and inflight experiment results showed that certain responses of autonomic nervous system were correlated with, or consistently preceded, reports of performance decrements or the symptoms. Autogenic-Feedback-Training Exercise (AFTE) is a physiological conditioning method that has been used to train people to voluntary control several of their own physiological responses. The specific objectives were: 1) To study human autonomic nervous system (ANS) responses to sustained exposure to microgravity; 2) To study human behavior/performance changes related to physiology; 3) To evaluate the effectiveness of preflight autonomic conditioning (AFTE) for facilitating adaptation to space and readaptation to Earth; and 4) To archive these data for the NASA Life Sciences Data Archive and thereby make this information available to the international scientific community.

Oxytocin and bone

PubMed Central

Sun, Li; Zaidi, Mone; Zallone, Alberta

2014-01-01

One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR−/− mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

Coping with thermal challenges: physiological adaptations to environmental temperatures.

PubMed

Tattersall, Glenn J; Sinclair, Brent J; Withers, Philip C; Fields, Peter A; Seebacher, Frank; Cooper, Christine E; Maloney, Shane K

2012-07-01

Temperature profoundly influences physiological responses in animals, primarily due to the effects on biochemical reaction rates. Since physiological responses are often exemplified by their rate dependency (e.g., rate of blood flow, rate of metabolism, rate of heat production, and rate of ion pumping), the study of temperature adaptations has a long history in comparative and evolutionary physiology. Animals may either defend a fairly constant temperature by recruiting biochemical mechanisms of heat production and utilizing physiological responses geared toward modifying heat loss and heat gain from the environment, or utilize biochemical modifications to allow for physiological adjustments to temperature. Biochemical adaptations to temperature involve alterations in protein structure that compromise the effects of increased temperatures on improving catalytic enzyme function with the detrimental influences of higher temperature on protein stability. Temperature has acted to shape the responses of animal proteins in manners that generally preserve turnover rates at animals' normal, or optimal, body temperatures. Physiological responses to cold and warmth differ depending on whether animals maintain elevated body temperatures (endothermic) or exhibit minimal internal heat production (ectothermic). In both cases, however, these mechanisms involve regulated neural and hormonal over heat flow to the body or heat flow within the body. Examples of biochemical responses to temperature in endotherms involve metabolic uncoupling mechanisms that decrease metabolic efficiency with the outcome of producing heat, whereas ectothermic adaptations to temperature are best exemplified by the numerous mechanisms that allow for the tolerance or avoidance of ice crystal formation at temperatures below 0°C. 2012 American Physiological Society. Compr Physiol 2:2037-2061, 2012.

Physiological correlates of mental workload

NASA Technical Reports Server (NTRS)

Zacharias, G. L.

1980-01-01

A literature review was conducted to assess the basis of and techniques for physiological assessment of mental workload. The study findings reviewed had shortcomings involving one or more of the following basic problems: (1) physiologic arousal can be easily driven by nonworkload factors, confounding any proposed metric; (2) the profound absence of underlying physiologic models has promulgated a multiplicity of seemingly arbitrary signal processing techniques; (3) the unspecified multidimensional nature of physiological "state" has given rise to a broad spectrum of competing noncommensurate metrics; and (4) the lack of an adequate definition of workload compels physiologic correlations to suffer either from the vagueness of implicit workload measures or from the variance of explicit subjective assessments. Using specific studies as examples, two basic signal processing/data reduction techniques in current use, time and ensemble averaging are discussed.

Long-Term Effects of Environmental Endocrine Disruptors on Reproductive Physiology and Behavior

PubMed Central

Patisaul, Heather B.; Adewale, Heather B.

2009-01-01

It is well established that, over the course of development, hormones shape the vertebrate brain such that sex specific physiology and behaviors emerge. Much of this occurs in discrete developmental windows that span gestation through the prenatal period, although it is now becoming clear that at least some of this process continues through puberty. Perturbation of this developmental progression can permanently alter the capacity for reproductive success. Wildlife studies have revealed that exposure to endocrine disrupting compounds (EDCs), either naturally occurring or man made, can profoundly alter reproductive physiology and ultimately impact entire populations. Laboratory studies in rodents and other species have elucidated some of the mechanisms by which this occurs and strongly indicate that humans are also vulnerable to disruption. Use of hormonally active compounds in human medicine has also unfortunately revealed that the developing fetus can be exposed to and affected by endocrine disruptors, and that it might take decades for adverse effects to manifest. Research within the field of environmental endocrine disruption has also contributed to the general understanding of how early life experiences can alter reproductive physiology and behavior through non-genomic, epigenetic mechanisms such as DNA methylation and histone acetylation. These types of effects have the potential to impact future generations if the germ line is affected. This review provides an overview of how exposure to EDCs, particularly those that interfere with estrogen action, impacts reproductive physiology and behaviors in vertebrates. PMID:19587848

Mechanisms of weight loss, diabetes control and changes in food choices after gastrointestinal surgery.

PubMed

Papamargaritis, Dimitrios; Panteliou, Eleftheria; Miras, Alexander D; le Roux, Carel W

2012-12-01

The long-term effects of lifestyle changes, diet and medical therapy on obesity are limited. Bariatric surgery is the most effective long-term treatment with the greatest chances for amelioration of obesity-associated complications, including type 2 diabetes mellitus (T2DM). There is increasing evidence in the literature that bariatric operations have a profound effect on human physiology, by reducing hunger, increasing satiety, paradoxically increasing energy expenditure, and even promoting healthy food preferences. Some of these operations improve glucose homeostasis in patients with T2DM independently of weight loss. Changes in the gut hormone levels of glucagon-like peptide 1, peptide YY and ghrelin have been proposed as some of the mediators implicated in changing physiology. The aim of this review is to critically explore the current knowledge on the putative mechanisms of the change in weight and improvement in T2DM glycaemic control after the most commonly performed bariatric operations.

Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

PubMed Central

Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

2014-01-01

Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

A Microbial Perspective on the Grand Challenges in Comparative Animal Physiology

PubMed Central

2018-01-01

ABSTRACT Interactions with microbial communities can have profound influences on animal physiology, thereby impacting animal performance and fitness. Therefore, it is important to understand the diversity and nature of host-microbe interactions in various animal groups (invertebrates, fish, amphibians, reptiles, birds, and mammals). In this perspective, I discuss how the field of host-microbe interactions can be used to address topics that have been identified as grand challenges in comparative animal physiology: (i) horizontal integration of physiological processes across organisms, (ii) vertical integration of physiological processes across organizational levels within organisms, and (iii) temporal integration of physiological processes during evolutionary change. Addressing these challenges will require the use of a variety of animal models and the development of systems approaches that can integrate large, multiomic data sets from both microbial communities and animal hosts. Integrating host-microbe interactions into the established field of comparative physiology represents an exciting frontier for both fields. PMID:29556549

[Sports and pregnancy].

PubMed

Emonts, P; Thoumsin, H; Foidart, J M

2001-04-01

Pregnant women consult often their obstetricians for counselling about their way of living. Particularly answering questions concerning physical activity and sports during pregnancy require a profound knowledge on the physiological adaptations of pregnancy and, on the other hand, on performance and sports physiology. On the basis of the current state of research, physical exercise and sport are to be recommended during pregnancy so long as women are aware of potential dangers and contraindications. Maternal benefits and fetal benefits have today been demonstrated.

Drosophila development, physiology, behavior, and lifespan are influenced by altered dietary composition

PubMed Central

Ormerod, Kiel G.; LePine, Olivia K.; Abbineni, Prabhodh S.; Bridgeman, Justin M.; Mercier, A. Joffre; Tattersall, Glenn J.

2017-01-01

ABSTRACT Diet profoundly influences the behavior of animals across many phyla. Despite this, most laboratories using model organisms, such as Drosophila, use multiple, different, commercial or custom-made media for rearing their animals. In addition to measuring growth, fecundity and longevity, we used several behavioral and physiological assays to determine if and how altering food media influence wild-type (Canton S) Drosophila melanogaster, at larval, pupal, and adult stages. Comparing 2 commonly used commercial food media we observed several key developmental and morphological differences. Third-instar larvae and pupae developmental timing, body weight and size, and even lifespan significantly differed between the 2 diets, and some of these differences persisted into adulthood. Diet was also found to produce significantly different thermal preference, locomotory capacity for geotaxis, feeding rates, and lower muscle response to hormonal stimulation. There were no differences, however, in adult thermal preferences, in the number or viability of eggs laid, or in olfactory learning and memory between the diets. We characterized the composition of the 2 diets and found particularly significant differences in cholesterol and (phospho)lipids between them. Notably, diacylglycerol (DAG) concentrations vary substantially between the 2 diets, and may contribute to key phenotypic differences, including lifespan. Overall, the data confirm that 2 different diets can profoundly influence the behavior, physiology, morphology and development of wild-type Drosophila, with greater behavioral and physiologic differences occurring during the larval stages. PMID:28277941

How sleep and wakefulness influence circadian rhythmicity: effects of insufficient and mistimed sleep on the animal and human transcriptome.

PubMed

Archer, Simon N; Oster, Henrik

2015-10-01

The mammalian circadian system is a multi-oscillator, hierarchically organised system where a central pacemaker synchronises behavioural, physiological and gene expression rhythms in peripheral tissues. Epidemiological studies show that disruption of this internal synchronisation by short sleep and shift work is associated with adverse health outcomes through mechanisms that remain to be elucidated. Here, we review recent animal and human studies demonstrating the profound effects of insufficient and mistimed sleep on the rhythms of gene expression in central and peripheral tissues. In mice, sleep restriction leads to an ~80% reduction in circadian transcripts in the brain and profound disruption of the liver transcriptome. In humans, sleep restriction leads to a 1.9% reduction in circadian transcripts in whole blood, and when sleep is displaced to the daytime, 97% of rhythmic genes become arrhythmic and one-third of all genes show changes in temporal expression profiles. These changes in mice and humans include a significant reduction in the circadian regulation of transcription and translation and core clock genes in the periphery, while at the same time rhythms within the suprachiasmatic nucleus are not disrupted. Although the physiological mediators of these sleep disruption effects on the transcriptome have not been established, altered food intake, changes in hormones such as cortisol, and changes in body and brain temperature may play important roles. Processes and molecular pathways associated with these disruptions include metabolism, immune function, inflammatory and stress responses, and point to the molecular mechanisms underlying the established adverse health outcomes associated with short sleep duration and shift work, such as metabolic syndrome and cancer. © 2015 European Sleep Research Society.

Physiological performance of warm-adapted marine ectotherms: Thermal limits of mitochondrial energy transduction efficiency.

PubMed

Martinez, Eloy; Hendricks, Eric; Menze, Michael A; Torres, Joseph J

2016-01-01

Thermal regimes in aquatic systems have profound implications for the physiology of ectotherms. In particular, the effect of elevated temperatures on mitochondrial energy transduction in tropical and subtropical teleosts may have profound consequences on organismal performance and population viability. Upper and lower whole-organism critical temperatures for teleosts suggest that subtropical and tropical species are not susceptible to the warming trends associated with climate change, but sub-lethal effects on energy transduction efficiency and population dynamics remain unclear. The goal of the present study was to compare the thermal sensitivity of processes associated with mitochondrial energy transduction in liver mitochondria from the striped mojarra (Eugerres plumieri), the whitemouth croaker (Micropogonias furnieri) and the palometa (Trachinotus goodei), to those of the subtropical pinfish (Lagodon rhomboides) and the blue runner (Caranx crysos). Mitochondrial function was assayed at temperatures ranging from 10 to 40°C and results obtained for both tropical and subtropical species showed a reduction in the energy transduction efficiency of the oxidative phosphorylation (OXPHOS) system in most species studied at temperatures below whole-organism critical temperature thresholds. Our results show a loss of coupling between O2 consumption and ATP production before the onset of the critical thermal maxima, indicating that elevated temperature may severely impact the yield of ATP production per carbon unit oxidized. As warming trends are projected for tropical regions, increasing water temperatures in tropical estuaries and coral reefs could impact long-term growth and reproductive performance in tropical organisms, which are already close to their upper thermal limit. Copyright © 2015 Elsevier Inc. All rights reserved.

Alterations in physiology and anatomy during pregnancy.

PubMed

Tan, Eng Kien; Tan, Eng Loy

2013-12-01

Pregnant women undergo profound anatomical and physiological changes so that they can cope with the increased physical and metabolic demands of their pregnancies. The cardiovascular, respiratory, haematological, renal, gastrointestinal and endocrine systems all undergo important physiological alterations and adaptations needed to allow development of the fetus and to allow the mother and fetus to survive the demands of childbirth. Such alterations in anatomy and physiology may cause difficulties in interpreting signs, symptoms, and biochemical investigations, making the clinical assessment of a pregnant woman inevitably confusing but challenging. Understanding these changes is important for every practicing obstetrician, as the pathological deviations from the normal physiological alterations may not be clear-cut until an adverse outcome has resulted. Only with a sound knowledge of the physiology and anatomy changes can the care of an obstetric parturient be safely optimized for a better maternal and fetal outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

Loss of thermal refugia near equatorial range limits.

PubMed

Lima, Fernando P; Gomes, Filipa; Seabra, Rui; Wethey, David S; Seabra, Maria I; Cruz, Teresa; Santos, António M; Hilbish, Thomas J

2016-01-01

This study examines the importance of thermal refugia along the majority of the geographical range of a key intertidal species (Patella vulgata Linnaeus, 1758) on the Atlantic coast of Europe. We asked whether differences between sun-exposed and shaded microhabitats were responsible for differences in physiological stress and ecological performance and examined the availability of refugia near equatorial range limits. Thermal differences between sun-exposed and shaded microhabitats are consistently associated with differences in physiological performance, and the frequency of occurrence of high temperatures is most probably limiting the maximum population densities supported at any given place. Topographical complexity provides thermal refugia throughout most of the distribution range, although towards the equatorial edges the magnitude of the amelioration provided by shaded microhabitats is largely reduced. Importantly, the limiting effects of temperature, rather than being related to latitude, seem to be tightly associated with microsite variability, which therefore is likely to have profound effects on the way local populations (and consequently species) respond to climatic changes. © 2015 John Wiley & Sons Ltd.

Biphasic Effect of Melanocortin Agonists on Metabolic Rate and Body Temperature

PubMed Central

Lute, Beth; Jou, William; Lateef, Dalya M.; Goldgof, Margalit; Xiao, Cuiying; Piñol, Ramón A.; Kravitz, Alexxai V.; Miller, Nicole R.; Huang, Yuning George; Girardet, Clemence; Butler, Andrew A.; Gavrilova, Oksana; Reitman, Marc L.

2014-01-01

Summary The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses. Intraperitoneal administration of the nonselective melanocortin agonist MTII causes a melanocortin-4 receptor (Mc4r) mediated hypermetabolism/hyperthermia. This is preceded by a profound, transient hypometabolism/hypothermia that is preserved in mice lacking any one of Mc1r, Mc3r, Mc4r, or Mc5r. Three other melanocortin agonists also caused hypothermia, which is actively achieved via seeking a cool environment, vasodilation, and inhibition of brown adipose tissue thermogenesis. These results suggest that the hypometabolic/hypothermic effect of MTII is not due to a failure of thermoregulation. The hypometabolism/hypothermia was prevented by dopamine antagonists and MTII selectively activated arcuate nucleus dopaminergic neurons; these neurons may contribute to the hypometabolism/hypothermia. We propose that the hypometabolism/hypothermia is a regulated response, potentially beneficial during extreme physiologic stress. PMID:24981835

Multiscale Evaluation of Thermal Dependence in the Glucocorticoid Response of Vertebrates.

PubMed

Jessop, Tim S; Lane, Meagan L; Teasdale, Luisa; Stuart-Fox, Devi; Wilson, Robbie S; Careau, Vincent; Moore, Ignacio T

2016-09-01

Environmental temperature has profound effects on animal physiology, ecology, and evolution. Glucocorticoid (GC) hormones, through effects on phenotypic performance and life history, provide fundamental vertebrate physiological adaptations to environmental variation, yet we lack a comprehensive understanding of how temperature influences GC regulation in vertebrates. Using field studies and meta- and comparative phylogenetic analyses, we investigated how acute change and broadscale variation in temperature correlated with baseline and stress-induced GC levels. Glucocorticoid levels were found to be temperature and taxon dependent, but generally, vertebrates exhibited strong positive correlations with acute changes in temperature. Furthermore, reptile baseline, bird baseline, and capture stress-induced GC levels to some extent covaried with broadscale environmental temperature. Thus, vertebrate GC function appears clearly thermally influenced. However, we caution that lack of detailed knowledge of thermal plasticity, heritability, and the basis for strong phylogenetic signal in GC responses limits our current understanding of the role of GC hormones in species' responses to current and future climate variation.

Olfactory regulation of the sexual behavior and reproductive physiology of the laboratory mouse: effects and neural mechanisms.

PubMed

Kelliher, Kevin R; Wersinger, Scott R

2009-01-01

In many species, chemical compounds emitted by conspecifics exert profound effects on reproductive physiology and sexual behavior. This is particularly true in the mouse, where such cues advance and delay puberty, suppress and facilitate estrous cycles, and cause the early termination of pregnancy. They also facilitate sexual behavior and inform mate selection. The mouse has a rich and complex repertoire of social behaviors. The technologies of molecular genetics are well developed in the mouse. Gene expression can be experimentally manipulated in the mouse relatively easily and in a time- and tissue-specific manner. Thus, the mouse is an excellent model in which to investigate the genetic, neural, and hormonal bases by which chemical compounds released by other mice affect physiology and behavior. These chemical cues are detected and processed by the olfactory system and other specialized but less well characterized sensory organs. The sensory information reaches brain regions that regulate hormone levels as well as those that are involved in behavior and alters the function of these brain regions. The effects of these chemical compounds have important implications for the laboratory animal facility as well as for researchers. We begin with an overview of the basic structure and function of the olfactory system and of the connections among brain regions that receive olfactory stimuli. We discuss the effects of chemosensory cues on the behavior and physiology of the organism along with what is known about the neural and hormonal mechanisms underlying these effects. We also describe some of the implications for the laboratory animal facility.

Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions.

PubMed

Liester, Mitchell B; Prickett, James I

2012-01-01

Ayahuasca is a medicinal plant mixture utilized by indigenous peoples throughout the Amazon River basin for healing purposes. The "vine of the soul" or "vine of death," as it is known in South America, contains a combination of monoamine oxidase inhibitors and N,N-dimethyltryptamine (DMT). When ingested together, these medicines produce profound alterations in consciousness. Increasingly, ayahuasca is being utilized to treat addictions. However, the mechanism of action by which ayahuasca treats addictions remains unclear. We offer four hypotheses to explain possible biochemical, physiological, psychological, and transcendent mechanisms by which ayahuasca may exert its anti-addiction effects.

Xenobiotic metabolism in the fourth dimension: PARtners in time.

PubMed

Green, Carla B; Takahashi, Joseph S

2006-07-01

A significant portion of the transcriptome in mammals, including the PAR bZIP transcription factors DBP, HLF, and TEF, is under circadian clock control. In this issue of Cell Metabolism, Gachon and colleagues (Gachon et al., 2006) show that disruption of these three genes in mice alters gene expression patterns of many proteins involved in drug metabolism and in liver and kidney responses to xenobiotic agents. Triple mutant mice have severe physiological deficits, including increased hypersensitivity to xenobiotic agents and premature aging, highlighting the profound effect the circadian clock has on this important response system.

Can we HIIT cancer if we attack inflammation?

PubMed

Papadopoulos, Efthymios; Santa Mina, Daniel

2018-01-01

Physical exercise offers numerous health-related benefits to individuals with cancer. Epidemiologic research has primarily been concerned with conventional exercise training that aligns with the recommendations of 150 min of moderate to vigorous physical activity per week. These recommendations are safe and effective at improving physical and psychosocial outcomes. Given the extensive evidence for generalized physical activity, researchers have begun to explore novel training regimens that may provide additional health benefits and/or improved adherence. Specifically, exercise at higher intensities may offer more or different benefits than conventional training approaches with potentially profound effects on the tumor microenvironment. This commentary focuses on the physiological effects of high-intensity interval training, also known as "HIIT," and its potential antineoplastic properties.

Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival

PubMed Central

Khacho, Mireille; Tarabay, Michelle; Patten, David; Khacho, Pamela; MacLaurin, Jason G.; Guadagno, Jennifer; Bergeron, Richard; Cregan, Sean P.; Harper, Mary-Ellen; Park, David S.; Slack, Ruth S.

2014-01-01

Sustained cellular function and viability of high-energy demanding post-mitotic cells rely on the continuous supply of ATP. The utilization of mitochondrial oxidative phosphorylation for efficient ATP generation is a function of oxygen levels. As such, oxygen deprivation, in physiological or pathological settings, has profound effects on cell metabolism and survival. Here we show that mild extracellular acidosis, a physiological consequence of anaerobic metabolism, can reprogramme the mitochondrial metabolic pathway to preserve efficient ATP production regardless of oxygen levels. Acidosis initiates a rapid and reversible homeostatic programme that restructures mitochondria, by regulating mitochondrial dynamics and cristae architecture, to reconfigure mitochondrial efficiency, maintain mitochondrial function and cell survival. Preventing mitochondrial remodelling results in mitochondrial dysfunction, fragmentation and cell death. Our findings challenge the notion that oxygen availability is a key limiting factor in oxidative metabolism and brings forth the concept that mitochondrial morphology can dictate the bioenergetic status of post-mitotic cells. PMID:24686499

Multiple Functions of Endocannabinoid Signaling in the Brain

PubMed Central

Katona, István; Freund, Tamás F.

2014-01-01

Despite being regarded as a hippie science for decades, cannabinoid research has finally found its well-deserved position in mainstream neuroscience. A series of groundbreaking discoveries revealed that endocannabinoid molecules are as widespread and important as conventional neurotransmitters like glutamate or GABA, yet act in profoundly unconventional ways. We aim to illustrate how uncovering the molecular, anatomical and physiological characteristics of endocannabinoid signaling revealed new mechanistic insights into several fundamental phenomena in synaptic physiology. First, we summarize unexpected advances in the molecular complexity of biogenesis and inactivation of the two endocannabinoids, anandamide and 2-arachidonoylglycerol. Then we show how these new metabolic routes are integrated into well-known intracellular signaling pathways. These endocannabinoid-producing signalosomes operate in phasic and tonic modes thereby differentially governing homeostatic, short-term and long-term synaptic plasticity throughout the brain. Finally, we discuss how cell type- and synapse-specific refinement of endocannabinoid signaling may explain the characteristic behavioral effects of cannabinoids. PMID:22524785

Regulation of Coronary Blood Flow

PubMed Central

Goodwill, Adam G.; Dick, Gregory M.; Kiel, Alexander M.; Tune, Johnathan D.

2018-01-01

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. PMID:28333376

Challenges of Developing Communicative Interaction in Individuals with Congenital Profound Intellectual and Multiple Disabilities

ERIC Educational Resources Information Center

Blain-Moraes, Stefanie; Chau, Tom

2012-01-01

Background: Physiological responses have been used in individuals with acquired disability to enable communicative interaction without motor movement. This study explored four autonomic nervous system (ANS) signals--electrodermal activity, skin temperature, cardiac patterns and respiratory patterns--to enable interaction with individuals born with…

Adolescents with Psychopathic Traits Report Reductions in Physiological Responses to Fear

ERIC Educational Resources Information Center

Marsh, Abigail A.; Finger, Elizabeth C.; Schechter, Julia C.; Jurkowitz, Ilana T. N.; Reid, Marguerite E.; Blair, R. J. R.

2011-01-01

Background: Psychopathy is characterized by profound affective deficits, including shallow affect and reduced empathy. Recent research suggests that these deficits may apply particularly to negative emotions, or to certain negative emotions such as fear. Despite increased focus on the cognitive and neural underpinnings of psychopathy, little is…

Thermal and cardiovascular strain imposed by motorcycle protective clothing under Australian summer conditions.

PubMed

de Rome, Liz; Taylor, Elizabeth A; Croft, Rodney J; Brown, Julie; Fitzharris, Michael; Taylor, Nigel A S

2016-04-01

Motorcycle protective clothing can be uncomfortably hot during summer, and this experiment was designed to evaluate the physiological significance of that burden. Twelve males participated in four, 90-min trials (cycling 30 W) across three environments (25, 30, 35 °C [all 40% relative humidity]). Clothing was modified between full and minimal injury protection. Both ensembles were tested at 25 °C, with only the more protective ensemble investigated at 30 and 35 °C. At 35 °C, auditory canal temperature rose at 0.02 °C min(-1) (SD 0.005), deviating from all other trials (p < 0.05). The thresholds for moderate (>38.5 °C) and profound hyperthermia (>40.0 °C) were predicted to occur within 105 min (SD 20.6) and 180 min (SD 33.0), respectively. Profound hyperthermia might eventuate in ~10 h at 30 °C, but should not occur at 25 °C. These outcomes demonstrate a need to enhance the heat dissipation capabilities of motorcycle clothing designed for summer use in hot climates, but without compromising impact protection. Practitioner's Summary: Motorcycle protective clothing can be uncomfortably hot during summer. This experiment was designed to evaluate the physiological significance of this burden across climatic states. In the heat, moderate (>38.5 °C) and profound hyperthermia (>40.0 °C) were predicted to occur within 105 and 180 min, respectively.

The evaluation and management of female sexual dysfunction.

PubMed

Dawson, Melissa L; Shah, Nima M; Rinko, Rebecca C; Veselis, Clinton; Whitmore, Kristene E

2017-12-01

Female sexual dysfunction has complex physiologic and psychological components that require a detailed screening, history, and physical examination. Our goal in this review is to provide family physicians with insights and practical advice to help screen, diagnose, and treat female sexual dysfunction, which can have a profound impact on patients' most intimate relationships.

Nosema parasitism in honey bees (Apis mellifera) impacts olfactory learning and memory and neurochemistry

USDA-ARS?s Scientific Manuscript database

Nosema sp. is an internal parasite of the honey bee, Apis mellifera, and one of the leading contributors to colony losses worldwide. This parasite is found in the honey bee midgut, and has profound consequences on the host’s physiology. There are reports that Nosema sp. impairs foraging performance ...

Effects of Perinatal Polychlorinated Biphenyls on Adult Female Rat Reproduction: Development, Reproductive Physiology, and Second Generational Effects

PubMed Central

Steinberg, Rebecca M.; Walker, Deena M.; Juenger, Thomas E.; Woller, Michael J.; Gore, Andrea C.

2009-01-01

Perinatal exposures to endocrine-disrupting chemicals such as polychlorinated biphenyls (PCBs) can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally-exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture Aroclor (A) 1221 (0, 0.1, 1 or 10 mg/kg) on embryonic days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed towards females. In the F1 generation, additional effects were found including a significant alteration of serum luteinizing hormone (LH) in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been perinatally exposed to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared to F2 decendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant consequences on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans. PMID:18305224

Individual boldness traits influenced by temperature in male Siamese fighting fish.

PubMed

Forsatkar, Mohammad Navid; Nematollahi, Mohammad Ali; Biro, Peter A; Beckmann, Christa

2016-10-15

Temperature has profound effects on physiology of ectothermic animals. However, the effects on temperature variation on behavioral traits are poorly studied in contrast to physiological endpoints. This may be important as even small differences in temperatures have large effects on physiological rates including overall metabolism, and behavior is known to be linked to metabolism at least in part. The primary aim of this study was to determine the effects of ambient temperature on boldness responses of a species of fish commonly used in behavioral experiments, the Siamese fighting fish (Betta splendens). At 26°C, subjects were first examined for baseline behaviors over three days, using three different (but complementary) 'open field' type assays tested in a fixed order. Those same fish were next exposed to either the same temperature (26°C) or a higher temperature (30°C) for 10days, and then the same behavioral assays were repeated. Those individuals exposed to increased temperatures reduced their latency to leave the release area (area I), spent more time in area III (farthest from release area), and were more active overall; together we infer these behaviors to reflect an increase in general 'boldness' with increased temperature. Our results add to a limited number of studies of temperature effects on behavioral tendencies in ectotherms that are evident even after some considerable acclimation. From a methodological perspective, our results indicate careful temperature control is needed when studying behavior in this and other species of fish. Copyright © 2016 Elsevier Inc. All rights reserved.

Variable effects of arbuscular mycorrhizal fungal inoculation on physiological and molecular measures of root and stomatal conductance of diverse Medicago truncatula accessions.

PubMed

Watts-Williams, Stephanie J; Cavagnaro, Timothy R; Tyerman, Stephen D

2018-06-22

Association with arbuscular mycorrhizal fungi (AMF) can impact on plant water relations; mycorrhizal plants can exhibit increased stomatal conductance (g s ) and root hydraulic conductance (normalised to root dry weight, L o ), and altered expression of aquaporins (AQP). Many factors regulate such responses, however, plant intraspecific diversity effects have yet to be explored. Twenty geographically diverse accessions of Medicago truncatula were inoculated with the AMF Funneliformis mosseae or mock-inoculated, and grown under well-watered conditions. Biomass, g s , shoot nutrient concentrations and mycorrhizal colonisation were measured in all accessions, and L o and gene expression in five accessions. The diverse accessions varied in physiology and gene expression; some accessions were also larger or had higher g s when colonised by F. mosseae. In the five accessions, L o was higher in two accessions when colonised by AMF, and also maintained within a much smaller range than the mock-inoculated plants. Expression of MtPIP1 correlated with both g s and L o , and when plants were more than 3% colonised, mycorrhizal colonisation correlated with L o . Accession and AMF treatments had profound effects on M. truncatula, including several measures of plant water relations. Correlations between response variables, especially between molecular and physiological variables, across genotypes, highlight the findings of this study. This article is protected by copyright. All rights reserved.

Effect of Light and Melatonin and other Melatonin Receptor Agonists on Human Circadian Physiology

PubMed Central

Emens, Jonathan S.

2015-01-01

Synopsis Circadian (body clock) timing has a profound influence on mental health, physical health, and health behaviors. This review focuses on how light, melatonin and other melatonin receptor agonist drugs can be used to shift circadian timing in patients with misaligned circadian rhythms. A brief overview of the human circadian system is provided, followed by a discussion of patient characteristics and safety considerations that can influence the treatment of choice. The important features of light treatment, light avoidance, exogenous melatonin and other melatonin receptor agonists are reviewed, along with some of the practical aspects of light and melatonin treatment. PMID:26568121

Oxytocin during Development: Possible Organizational Effects on Behavior.

PubMed

Miller, Travis V; Caldwell, Heather K

2015-01-01

Oxytocin (Oxt) is a neurohormone known for its physiological roles associated with lactation and parturition in mammals. Oxt can also profoundly influence mammalian social behaviors such as affiliative, parental, and aggressive behaviors. While the acute effects of Oxt signaling on adult behavior have been heavily researched in many species, including humans, the developmental effects of Oxt on the brain and behavior are just beginning to be explored. There is evidence that Oxt in early postnatal and peripubertal development, and perhaps during prenatal life, affects adult behavior by altering neural structure and function. However, the specific mechanisms by which this occurs remain unknown. Thus, this review will detail what is known about how developmental Oxt impacts behavior as well as explore the specific neurochemicals and neural substrates that are important to these behaviors.

Anesthesia in Experimental Stroke Research

PubMed Central

Hoffmann, Ulrike; Sheng, Huaxin; Ayata, Cenk; Warner, David S.

2016-01-01

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke. PMID:27534542

The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes.

PubMed

Seeley, Randy J; Chambers, Adam P; Sandoval, Darleen A

2015-03-03

Bariatric surgical procedures such as vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most potent treatments available to produce sustained reductions in body weight and improvements in glucose regulation. While traditionally these effects are attributed to mechanical aspects of these procedures, such as restriction and malabsorption, a growing body of evidence from mouse models of these procedures points to physiological changes that mediate the potent effects of these surgeries. In particular, there are similar changes in gut hormone secretion, bile acid levels, and composition after both of these procedures. Moreover, loss of function of the nuclear bile acid receptor (FXR) greatly diminishes the effects of VSG. Both VSG and RYGB are linked to profound changes in the gut microbiome that also mediate at least some of these surgical effects. We hypothesize that surgical rearrangement of the gastrointestinal tract results in enteroplasticity caused by the high rate of nutrient presentation and altered pH in the small intestine that contribute to these physiological effects. Identifying the molecular underpinnings of these procedures provides new opportunities to understand the relationship of the gastrointestinal tract to obesity and diabetes as well as new therapeutic strategies to harness the effectiveness of surgery with less-invasive approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

An investigation into the preservation of microbial cell banks for α-amylase production during 5 l fed-batch Bacillus licheniformis fermentations.

PubMed

Hancocks, Nichola H; Thomas, Colin R; Stocks, Stuart M; Hewitt, Christopher J

2010-10-01

Fluorescent staining techniques were used for a systematic examination of methods used to cryopreserve microbial cell banks. The aim of cryopreservation here is to ensure subsequent reproducible fermentation performance rather than just post thaw viability. Bacillus licheniformis cell physiology post-thaw is dependent on the cryopreservant (either Tween 80, glycerol or dimethyl sulphoxide) and whilst this had a profound effect on the length of the lag phase, during subsequent 5 l fed-batch fermentations, it had little effect on maximum specific growth rate, final biomass concentration or α-amylase activity. Tween 80 not only protected the cells during freezing but also helped them recover post-thaw resulting in shorter process times.

Induction of diapause and seasonal morphs in butterflies and other insects: knowns, unknowns and the challenge of integration

PubMed Central

Nylin, Sören

2013-01-01

The ‘choice’ of whether to enter diapause or to develop directly has profound effects on the life histories of insects, and may thus have cascading consequences such as seasonal morphs and other less obvious forms of seasonal plasticity. Present knowledge of the control of diapause and seasonal morphs at the physiological and molecular levels is briefly reviewed. Examples, mainly derived from personal research (primarily on butterflies), are given as a starting point with the aim of outlining areas of research that are still poorly understood. These include: the role of the direction of change in photoperiod; the role of factors such as temperature and diet in modifying the photoperiodic responses; and the role of sex, parental effects and sex linkage on photoperiodic control. More generally, there is still a limited understanding of how external cues and physiological pathways regulating various traits are interconnected via gene action to form a co-adapted complete phenotype that is adaptive in the wild despite environmental fluctuation and change. PMID:23894219

Sodium nitrite: the "cure" for nitric oxide insufficiency.

PubMed

Parthasarathy, Deepa K; Bryan, Nathan S

2012-11-01

This process of "curing" food is a long practice that dates back thousands of years long before refrigeration or food safety regulations. Today food safety and mass manufacturing are dependent upon safe and effective means to cure and preserve foods including meats. Nitrite remains the most effective curing agent to prevent food spoilage and bacterial contamination. Despite decades of rigorous research on its safety and efficacy as a curing agent, it is still regarded by many as a toxic undesirable food additive. However, research within the biomedical science community has revealed enormous therapeutic benefits of nitrite that is currently being developed as novel therapies for conditions associated with nitric oxide (NO) insufficiency. Much of the same biochemistry that has been understood for decades in the meat industry has been rediscovered in human physiology. This review will highlight the fundamental biochemistry of nitrite in human physiology and highlight the risk benefit evaluation surrounding nitrite in food and meat products. Foods or diets enriched with nitrite can have profound positive health benefits. Copyright © 2012 Elsevier Ltd. All rights reserved.

Physiologic basis for understanding quantitative dehydration assessment.

PubMed

Cheuvront, Samuel N; Kenefick, Robert W; Charkoudian, Nisha; Sawka, Michael N

2013-03-01

Dehydration (body water deficit) is a physiologic state that can have profound implications for human health and performance. Unfortunately, dehydration can be difficult to assess, and there is no single, universal gold standard for decision making. In this article, we review the physiologic basis for understanding quantitative dehydration assessment. We highlight how phenomenologic interpretations of dehydration depend critically on the type (dehydration compared with volume depletion) and magnitude (moderate compared with severe) of dehydration, which in turn influence the osmotic (plasma osmolality) and blood volume-dependent compensatory thresholds for antidiuretic and thirst responses. In particular, we review new findings regarding the biological variation in osmotic responses to dehydration and discuss how this variation can help provide a quantitative and clinically relevant link between the physiology and phenomenology of dehydration. Practical measures with empirical thresholds are provided as a starting point for improving the practice of dehydration assessment.

What does not kill them makes them stronger: larval environment and infectious dose alter mosquito potential to transmit filarial worms.

PubMed

Breaux, Jennifer A; Schumacher, Molly K; Juliano, Steven A

2014-07-07

For organisms with complex life cycles, larval environments can modify adult phenotypes. For mosquitoes and other vectors, when physiological impacts of stressors acting on larvae carry over into the adult stage they may interact with infectious dose of a vector-borne pathogen, producing a range of phenotypes for vector potential. Investigation of impacts of a common source of stress, larval crowding and intraspecific competition, on adult vector interactions with pathogens may increase our understanding of the dynamics of pathogen transmission by mosquito vectors. Using Aedes aegypti and the nematode parasite Brugia pahangi, we demonstrate dose dependency of fitness effects of B. pahangi infection on the mosquito, as well as interactions between competitive stress among larvae and infectious dose for resulting adults that affect the physiological and functional ability of mosquitoes to act as vectors. Contrary to results from studies on mosquito-arbovirus interactions, our results suggest that adults from crowded larvae may limit infection better than do adults from uncrowded controls, and that mosquitoes from high-quality larval environments are more physiologically and functionally capable vectors of B. pahangi. Our results provide another example of how the larval environment can have profound effects on vector potential of resulting adults. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Development and Application of a Virtual Screening Protocol for the Identification of Multitarget Fragments.

PubMed

Bottegoni, Giovanni; Veronesi, Marina; Bisignano, Paola; Kacker, Puneet; Favia, Angelo D; Cavalli, Andrea

2016-06-20

In this study, we report on a virtual ligand screening protocol optimized to identify fragments endowed with activity at multiple targets. Thanks to this protocol, we were able to identify a fragment that displays activity in the low-micromolar range at both β-secretase 1 (BACE-1) and glycogen synthase kinase 3β (GSK-3β). These two structurally and physiologically unrelated enzymes likely contribute, through different pathways, to the onset of Alzheimer's disease (AD). Therefore, their simultaneous inhibition holds great potential in exerting a profound effect on AD. In perspective, the strategy outlined herein can be adapted to other target combinations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neuroendocrine Consequences of Androgen Excess in Female Rodents

PubMed Central

Foecking, Eileen M.; McDevitt, Melissa A.; Acosta-Martínez, Maricedes; Horton, Teresa H.; Levine, Jon E.

2008-01-01

Androgens exert significant organizational and activational effects on the nervous system and behavior. Despite the fact that female mammals generally produce low levels of androgens, relative to the male of the same species, increasing evidence suggests that androgens can exert profound effects on the normal physiology and behavior of females during fetal, neonatal, and adult stages of life. This review examines the effects of exposure to androgens at three stages of development – as an adult, during early postnatal life and as a fetus, on reproductive hormone secretions in female rats. We examine the effects of androgen exposure both as a model of neuroendocrine sexual differentiation and with respect to the role androgens play in the normal female. We then discuss the hypothesis that androgens may cause epigenetic modification of estrogen target genes in the brain. Finally we consider the clinical consequences of excess androgen exposure in women. PMID:18374922

The arcuate nucleus and NPY contribute to the antitumorigenic effect of calorie restriction

PubMed Central

Minor, Robin K.; López, Miguel; Younts, Caitlin M.; Jones, Bruce; Pearson, Kevin J.; Anson, R. Michael; Diéguez, Carlos; de Cabo, Rafael

2011-01-01

Summary Calorie restriction (CR) is known to have profound effects on tumor incidence. A typical consequence of CR is hunger, and we hypothesized that the neuroendocrine response to CR might in part mediate CR's antitumor effects. We tested CR under appetite suppression using two models: neuropeptide Y (NPY) knockout mice and monosodium glutamate (MSG)-injected mice. While CR was protective in control mice challenged with a two-stage skin carcinogenesis model, papilloma development was neither delayed nor reduced by CR in the MSG-treated and NPY knockout mice. Adiponectin levels were also not increased by CR in the appetite-suppressed mice. We propose that some of CR’s beneficial effects cannot be separated from those imposed on appetite, and that NPY neurons in the arcuate nucleus of the hypothalamus (ARC) are involved in the translation of reduced intake to downstream physiological and functional benefits. PMID:21385308

Maternal cardiac metabolism in pregnancy

PubMed Central

Liu, Laura X.; Arany, Zolt

2014-01-01

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

Are there Race-Dependent Endothelial Cell Responses to Exercise?

PubMed Central

Brown, Michael D.; Feairheller, Deborah L.

2013-01-01

African Americans have endothelial dysfunction which likely contributes to their high prevalence of hypertension. Endothelial cell responses to stimuli could play a role in the development of endothelial dysfunction and hypertension. High physiological levels of vascular laminar shear stress can profoundly alter endothelial cell phenotype. It is not known whether there are race-dependent endothelial cell responses to laminar shear stress. PMID:23262464

[Thyroid and pregnancy].

PubMed

Iwen, K A; Lehnert, H

2018-05-17

During pregnancy thyroid hormones have profound effects on embryonal/fetal development and maternal health. Therefore, thyroid gland disorders should be immediately diagnosed and adequately treated. Pregnancy-specific physiological alterations during pregnancy cause changes in the reference interval for thyroid-stimulating hormone levels and trimester-specific thresholds must be taken into account. This article summarizes the most important diagnostic and therapeutic aspects before, during and after pregnancy. With reference to the period prior to pregnancy, the article discusses iodide supplementation, preconceptional examination of thyroid gland metabolism and the importance of thyroid gland functional disorders for fertility and fulfilling the desire to have children. With a view to the period during pregnancy, the effect of hypothyroxinemia, hypothyroidism, and hyperthyroidism as well as the effects of their treatment on the development of the child are explained. Finally, a description is given of what must be paid attention to in the breast-feeding period and in postpartum thyroiditis.

Neuroendocrine regulation of somatic growth in fishes.

PubMed

Dai, XiangYan; Zhang, Wei; Zhuo, ZiJian; He, JiangYan; Yin, Zhan

2015-02-01

Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

Humor, laughter, learning, and health! A brief review.

PubMed

Savage, Brandon M; Lujan, Heidi L; Thipparthi, Raghavendar R; DiCarlo, Stephen E

2017-09-01

Human emotions, such as anxiety, depression, fear, joy, and laughter, profoundly affect psychological and physiological processes. These emotions form a set of basic, evolved functions that are shared by all humans. Laughter is part of a universal language of basic emotions that all humans recognize. Health care providers and educators may utilize the power of laughter to improve health and enhance teaching and learning. This is an important consideration because teaching is not just about content: it is also about forming relationships and strengthening human connections. In this context, when used effectively, humor is documented to build relationships and enhance performance. Specifically, humor improves student performance by attracting and sustaining attention, reducing anxiety, enhancing participation, and increasing motivation. Moreover, humor stimulates multiple physiological systems that decrease levels of stress hormones, such as cortisol and epinephrine, and increase the activation of the mesolimbic dopaminergic reward system. To achieve these benefits, it is important to use humor that is relevant to the course content and not disparaging toward others. Self-effacing humor illustrates to students that the teacher is comfortable making mistakes and sharing these experiences with the classroom. In this brief review, we discuss the history and relationship between humor, laughing, learning, and health with an emphasis on the powerful, universal language of laughter. Copyright © 2017 the American Physiological Society.

Caring for the infant of a diabetic mother.

PubMed

Hatfield, Linda; Schwoebel, Ann; Lynyak, Corinne

2011-01-01

In the United States, approximately 100,000 infants are born to diabetic mothers each year. If diabetes in pregnancy is uncontrolled, the diversity of resulting health problems can have a profound effect on the embryo, the fetus, and the neonate. These infants are at risk for a multitude of physiologic, metabolic, and congenital complications such as macrosomia, asphyxia, respiratory distress, hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia and hyperviscosity, cardiomegaly, and central nervous system disruption. Preconception control of glucose metabolism throughout the trajectory of a woman's pregnancy is a significant factor in decreasing the adverse impact of diabetes on the fetus and newborn. Meticulous attention to neonatal glucose levels, thorough physical examination, and precise diagnosis are prerequisites to appropriate care for the neonate.

Behavioural effect of low-dose BPA on male zebrafish: Tuning of male mating competition and female mating preference during courtship process.

PubMed

Li, Xiang; Guo, Jia-Yu; Li, Xu; Zhou, Hai-Jun; Zhang, Shu-Hui; Liu, Xiao-Dong; Chen, Dong-Yan; Fang, Yong-Chun; Feng, Xi-Zeng

2017-02-01

The ubiquity of environmental pollution by endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) is progressively considered as a major threat to aquatic ecosystems worldwide. Numerous toxicological studies have proved that BPA are hazardous to aquatic environment, along with alterations in the development and physiology of aquatic vertebrates. However, generally, there is a paucity in knowledge of behavioural and physiological effects of BPA with low concentration, for example, 0.22 nM (50 ng/L) and 2.2 nM (500 ng/L). Here we show that treatment of adult male zebrafish (Danio rerio) with 7 weeks low-dose (0.22 nM-2.2 nM) BPA, resulted in alteration in histological structure of testis tissue and abnormality in expression levels of genes involved in testicular steroidogenesis. Furthermore, low-dose BPA treatment decreased the male locomotion during courtship; and was associated with less courtship behaviours to female but more aggressive behaviours to mating competitor. Interestingly, during the courtship test, we observed that female preferred control male to male under low-dose BPA exposure. Subsequently, we found that the ability of female to chose optimal mating male through socially mutual interaction and dynamics of male zebrafish, which was based on visual discrimination. In sum, our results shed light on the potential behavioural and physiological effect of low-dose BPA exposure on courtship behaviours of zebrafish, which could exert profound consequences on natural zebrafish populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options.

PubMed

Konturek, Peter C; Brzozowski, T; Konturek, S J

2011-12-01

Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress-induced condition in the upper GI tract, the diagnostic testing includes mainly blood tests and gastroscopy to rule out GERD and peptic ulcer disease. The therapy for these conditions is mainly based on the inhibition of gastric acid by proton pump inhibitors and eradication of Helicobacter pylori-infection. Additionally, melatonin an important mediator of brain gut axis has been shown to exhibit important protective effects against stress-induced lesions in the gastrointestinal tract. Finally, probiotics may profoundly affect the brain-gut interactions ("microbiome-gut-brain axis") and attenuate the development of stress-induced disorders in both the upper and lower gastrointestinal tract. Further studies on the brain-gut axis are needed to open new therapeutic avenues in the future.

Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine.

PubMed

Selen Alpergin, Ebru S; Bolandnazar, Zeinab; Sabatini, Martina; Rogowski, Michael; Chiellini, Grazia; Zucchi, Riccardo; Assadi-Porter, Fariba M

2017-01-01

Complex diseases such as polycystic ovary syndrome (PCOS) are associated with intricate pathophysiological, hormonal, and metabolic feedbacks that make their early diagnosis challenging, thus increasing the prevalence risks for obesity, cardiovascular, and fatty liver diseases. To explore the crosstalk between endocrine and lipid metabolic pathways, we administered 3-iodothyronamine (T1AM), a natural analog of thyroid hormone, in a mouse model of PCOS and analyzed plasma and tissue extracts using multidisciplinary omics and biochemical approaches. T1AM administration induces a profound tissue-specific antilipogenic effect in liver and muscle by lowering gene expression of key regulators of lipid metabolism, PTP1B and PLIN2, significantly increasing metabolites (glucogenic, amino acids, carnitine, and citrate) levels, while enhancing protection against oxidative stress. In contrast, T1AM has an opposing effect on the regulation of estrogenic pathways in the ovary by upregulating STAR, CYP11A1, and CYP17A1. Biochemical measurements provide further evidence of significant reduction in liver cholesterol and triglycerides in post-T1AM treatment. Our results shed light onto tissue-specific metabolic vs. hormonal pathway interactions, thus illuminating the intricacies within the pathophysiology of PCOS This study opens up new avenues to design drugs for targeted therapeutics to improve quality of life in complex metabolic diseases. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Animal-Microbial Symbioses in Changing Environments

PubMed Central

Carey, Hannah V.; Duddleston, Khrystyne N.

2014-01-01

The environments in which animals have evolved and live have profound effects on all aspects of their biology. Predictable rhythmic changes in the physical environment are arguably among the most important forces shaping the evolution of behavior and physiology of animals, and to anticipate and prepare for these predictable changes animals have evolved biological clocks. Unpredictable changes in the physical environment have important impacts on animal biology as well. The ability of animals to cope with and survive unpredictable perturbations depends on phenotypic plasticity and/or microevolution. From the time metazoans first evolved from their protistan ancestors they have lived in close association with a diverse array of microbes that have influenced, in some way, all aspects of the evolution of animal structure, function and behavior. Yet, few studies have addressed whether daily or seasonal rhythms may affect, or be affected by, an animal’s microbial symbionts. This survey highlights how biologists interested in the ecological and evolutionary physiology of animals whose lifestyles are influenced by environmental cycles may benefit from considering whether symbiotic microbes have shaped the features they study. PMID:25086977

Mechanisms of alveolar fibrosis after acute lung injury.

PubMed

Marinelli, W A; Henke, C A; Harmon, K R; Hertz, M I; Bitterman, P B

1990-12-01

In patients who die after severe acute lung injury, a dramatic fibroproliferative response occurs within the alveolar air space, interstitium, and microvessels. Profound shunt physiology, dead space ventilation, and pulmonary hypertension are the physiologic consequences of this fibroproliferative response. The anatomic pattern of the response is unique within each alveolar compartment. For example, the air space is obliterated by granulation tissue, with replicating mesenchymal cells, their connective tissue products, and an expanding network of intra-alveolar capillaries. In contrast, the vascular fibroproliferative response is dominated by mesenchymal cell replication and connective tissue deposition within the walls of microvessels. Despite the unique anatomic features of these fibroproliferative processes, the regulatory signals involved are likely to be similar. Although our current understanding of the signals regulating the fibroproliferative response to acute lung injury is limited, inferences can be made from in vitro studies of mesenchymal cell behavior and several better understood fibroproliferative processes, including wound healing and chronic fibrotic lung diseases. As clinicians, our future ability to enhance effective lung repair will likely utilize therapeutic strategies specifically targeted to the signals that regulate the fibroproliferative process within the alveolar microenvironment.

Reelin protects against amyloid β toxicity in vivo

PubMed Central

Lane-Donovan, Courtney; Philips, Gary T.; Wasser, Catherine R.; Durakoglugil, Murat S.; Masiulis, Irene; Upadhaya, Ajeet; Pohlkamp, Theresa; Coskun, Cagil; Kotti, Tiina; Steller, Laura; Hammer, Robert E.; Frotscher, Michael; Bock, Hans H.; Herz, Joachim

2015-01-01

Alzheimer's disease (AD) is a currently incurable neurodegenerative disorder and the most common form of dementia in people over the age of 65. The predominant genetic risk factor for AD is the ε4 allele encoding apolipoprotein E (ApoE4). The secreted glycoprotein Reelin, which is a physiological ligand for the multifunctional ApoE receptors Apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr), enhances synaptic plasticity. We have previously shown that the presence of ApoE4 renders neurons unresponsive to Reelin by impairing the recycling of the receptors, thereby decreasing its protective effects against amyloid β (Aβ) oligomer-induced synaptic toxicity in vitro. Here, we show that when Reelin was knocked out in adult mice, these mice behaved normally without overt learning or memory deficits. However, they were strikingly sensitive to amyloid-induced synaptic suppression, and had profound memory and learning disabilities at very low amounts of amyloid deposition. Our findings highlight the physiological importance of Reelin in protecting the brain against Aβ-induced synaptic dysfunction and memory impairment. PMID:26152694

Early Life Stress, Mood, and Anxiety Disorders.

PubMed

Syed, Shariful A; Nemeroff, Charles B

2017-02-01

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

Widespread seasonal gene expression reveals annual differences in human immunity and physiology

PubMed Central

Dopico, Xaquin Castro; Evangelou, Marina; Ferreira, Ricardo C.; Guo, Hui; Pekalski, Marcin L.; Smyth, Deborah J.; Cooper, Nicholas; Burren, Oliver S.; Fulford, Anthony J.; Hennig, Branwen J.; Prentice, Andrew M.; Ziegler, Anette-G.; Bonifacio, Ezio; Wallace, Chris; Todd, John A.

2015-01-01

Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease. PMID:25965853

The emergence of Nervennahrung: Nerves, mind and metabolism in the long eighteenth century.

PubMed

Stahnisch, Frank W

2012-06-01

Morphological assumptions concerning the form, structure and internal life of the brain and nervous system profoundly influenced contemporary physiological concepts about nerve actions throughout the 'long eighteenth century'. This article investigates some early theories of mind and metabolism. In a bottom-up fashion, it asks how eighteenth-century theories regarding the physiological actions of the body organs shaped the conceptions of the structure of the brain and nervous tissue themselves. These proposed that a healthy Nervennahrung (the German word for 'nerve nutrition', which might be rendered as brain food in modern English), not only guaranteed the integrity and stability of neuronal structures in the body, but also explained the complex texture of the brain and spinal cord in physiological terms. Eighteenth-century nerve theories already embodied a Leitmotiv of neurology and brain psychiatry from the later nineteenth century: 'Without phosphorus there is no thought!' Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of Animal Venoms and Toxins on Hallmarks of Cancer

PubMed Central

Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

2016-01-01

Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

Daidzein and its Effects on Brain.

PubMed

Ahmed, Touqeer; Javed, Sana; Tariq, Ameema; Budzyńska, Barbara; D'Onofrio, Grazia; Daglia, Maria; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad

2017-01-01

Among naturally occurring isoflavones, soy isoflavones are an important class with various biological activities. Due to their phytoestrogenic structure, their effects on the brain are profound thus making the neurobiological effects of these compounds an active area of research. One such compound is daidzein, which has been reported to affect various neurobiological regulatory mechanisms such as behavior, cognition, growth, development and reproduction. These effects are mainly elicited through the interaction of daidzein with different signaling molecules and receptors, thereby offering neuroprotection. In addition, daidzein has also been reported to possess activities against various neuropathological conditions mainly by its interaction with the cerebrovascular system. This review focuses on providing a comprehensive account on the bioavailability and metabolism of daidzein in vivo, and discusses its activities and mechanisms of action in detail, in both physiological and pathological conditions. In addition, the effects of daidzein on other disorders have also been examined briefly in this article. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A vascular mechanism to explain thermally mediated variations in deep-body cooling rates during the immersion of profoundly hyperthermic individuals.

PubMed

Caldwell, Joanne N; van den Heuvel, Anne M J; Kerry, Pete; Clark, Mitchell J; Peoples, Gregory E; Taylor, Nigel A S

2018-04-01

What is the central question of this study? Does the cold-water immersion (14°C) of profoundly hyperthermic individuals induce reductions in cutaneous and limb blood flow of sufficient magnitude to impair heat loss relative to the size of the thermal gradient? What is the main finding and its importance? The temperate-water cooling (26°C) of profoundly hyperthermic individuals was found to be rapid and reproducible. A vascular mechanism accounted for that outcome, with temperature-dependent differences in cutaneous and limb blood flows observed during cooling. Decisions relating to cooling strategies must be based upon deep-body temperature measurements that have response dynamics consistent with the urgency for cooling. Physiologically trivial time differences for cooling the intrathoracic viscera of hyperthermic individuals have been reported between cold- and temperate-water immersion treatments. One explanation for that observation is reduced convective heat delivery to the skin during cold immersion, and this study was designed to test both the validity of that observation, and its underlying hypothesis. Eight healthy men participated in four head-out water immersions: two when normothermic, and two after exercise-induced, moderate-to-profound hyperthermia. Two water temperatures were used within each thermal state: temperate (26°C) and cold (14°C). Tissue temperatures were measured at three deep-body sites (oesophagus, auditory canal and rectum) and eight skin surfaces, with cutaneous vascular responses simultaneously evaluated from both forearms (laser-Doppler flowmetry and venous-occlusion plethysmography). During the cold immersion of normothermic individuals, oesophageal temperature decreased relative to baseline (-0.31°C over 20 min; P < 0.05), whilst rectal temperature increased (0.20°C; P < 0.05). When rendered hyperthermic, oesophageal (-0.75°C) and rectal temperatures decreased (-0.05°C) during the transition period (<8.5 min, mostly in air at 22°C), with the former dropping to 37.5°C only 54 s faster when immersed in cold rather than in temperate water (P < 0.05). Minimal cutaneous vasoconstriction occurred during either normothermic immersion, whereas pronounced constriction was evident during both immersions when subjects were hyperthermic, with the colder water eliciting a greater vascular response (P < 0.05). It was concluded that the rapid intrathoracic cooling of asymptomatic, hyperthermic individuals in temperate water was a reproducible phenomenon, with slower than expected cooling in cold water brought about by stronger cutaneous vasoconstriction that reduced convective heat delivery to the periphery. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

PubMed

Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

2016-01-01

The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Greco-Roman Stone Disease

NASA Astrophysics Data System (ADS)

Moran, Michael E.; Ruzhansky, Katherine

2008-09-01

Greek and Roman thought had a profound influence upon Western medical practice. From the fall of the Greek civilization to the fall of the Roman, remarkable progress of our understanding of human anatomy and physiology occurred. Here we review the attempts of Greek and Roman thinkers to develop the first understanding of the pathophysiology of urolithiasis, its epidemiology, differential diagnosis of renal versus bladder stones, medications for both colic and prevention, the role of familial syndromes, and dietary management.

Concepts in hypoxia reborn

PubMed Central

2010-01-01

The human fetus develops in a profoundly hypoxic environment. Thus, the foundations of our physiology are built in the most hypoxic conditions that we are ever likely to experience: the womb. This magnitude of exposure to hypoxia in utero is rarely experienced in adult life, with few exceptions, including severe pathophysiology in critical illness and environmental hypobaric hypoxia at high altitude. Indeed, the lowest recorded levels of arterial oxygen in adult humans are similar to those of a fetus and were recorded just below the highest attainable elevation on the Earth's surface: the summit of Mount Everest. We propose that the hypoxic intrauterine environment exerts a profound effect on human tolerance to hypoxia. Cellular mechanisms that facilitate fetal well-being may be amenable to manipulation in adults to promote survival advantage in severe hypoxemic stress. Many of these mechanisms act to modify the process of oxygen consumption rather than oxygen delivery in order to maintain adequate tissue oxygenation. The successful activation of such processes may provide a new chapter in the clinical management of hypoxemia. Thus, strategies employed to endure the relative hypoxia in utero may provide insights for the management of severe hypoxemia in adult life and ventures to high altitude may yield clues to the means by which to investigate those strategies. PMID:20727228

Fluid and electrolyte control in simulated and actual spaceflight

NASA Technical Reports Server (NTRS)

Leach, C. S.; Johnson, P. C., Jr.

1985-01-01

Effects of microgravity on body fluid distribution and electrolyte and hormonal levels of astronauts have been studied since the early manned space missions. Bedrested subjects have been used as controls to separate effects of microgravity from those of hypokinesia. These investigations have led to documentation of the physiological effects of spaceflight and to a unified theory of response to microgravity. During flight, crewmembers have decreased thirst and a net loss of body water, sodium, and potassium. These changes seem to be initiated by passive transfer of extracellular fluid resulting in increased central venous pressure (CVP), to which the homeostatic mechanisms respond. A new equilibrium state is maintained during flight; it does not change in response to negative calcium and nitrogen balances during flight. On reexposure to gravity, profound water and salt retention occurs to replete extracellular fluid. Attempts to avoid cardiac deconditioning by repleting water and salt before leaving microgravity have somewhat ameliorated postural hypotension but have had little effect on CVP, cardiac chamber size or electrolyte dynamics.

Testicular cancer: a review.

PubMed

Hawkins, C; Miaskowski, C

1996-09-01

To describe the pathophysiologic mechanisms, histologic and clinical staging, diagnosis, and medical and nursing management of testicular cancer. Published studies, review articles, and Physician Data Query database. Testicular cancer is a complex disease resulting from transformation of gonadal tissues. The pathophysiologic mechanisms involve damage to tissue in utero and after birth. Orchiectomy is the treatment of choice for early-stage disease. Orchiectomy can have profound physiologic and psychological consequences for young males. Subsequent chemotherapy and radiation therapy also may have severe side effects including azoospermia, bone marrow suppression, nephrotoxicity, and pulmonary toxicity. Early detection of this disease results in improved patient outcomes. Patients treated with radical inguinal orchiectomy and radiation therapy have fewer long-term side effects and toxicities than patients who require more extensive surgery and chemotherapy. Nursing care must focus not only on relieving the patient's physical symptoms but on helping him deal with the psychosexual issues associated with the disease and its treatment.

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice*

PubMed Central

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D.; Kelley, David E.; Myers, Robert W.; Li, Cai

2016-01-01

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2NI) and R531G (AMPKγ2RG), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2NI or AMPKγ2RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2NI or AMPKγ2RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2NI and AMPKγ2RG, respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2NI or AMPKγ2RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2WT mice, AMPKγ2NI and AMPKγ2RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2RG but not AMPKγ2NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2NI and AMPKγ2RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. PMID:27621313

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice.

PubMed

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D; Kelley, David E; Myers, Robert W; Li, Cai; Guan, Hong-Ping

2016-11-04

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2 NI ) and R531G (AMPKγ2 RG ), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2 NI or AMPKγ2 RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2 NI or AMPKγ2 RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2 NI and AMPKγ2 RG , respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2 NI or AMPKγ2 RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2 WT mice, AMPKγ2 NI and AMPKγ2 RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2 RG but not AMPKγ2 NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2 NI and AMPKγ2 RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2 RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Relationship between Legionella pneumophila and Acanthamoeba polyphaga: Physiological status and susceptibility to chemical inactivation

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

Barker, J.; Farrell, I.; Brown, M.R.W.

1992-08-01

Survival studies were conducted on Legionella pneumophila cells that had been grown intracellulary in Acanthamoeba polyphaga and then exposed to polyhexamethylene biguanide (PHMB), benzisothiazolone (BIT), and 5-chloro-N-methylisothiazolone (CMIT). Susceptibilities were also determined for L. pneumophila grown under iron-sufficient and iron-depleted conditions. BIT was relatively ineffective against cells to PHMB and CMIT. The activities of all three biocides were greatly reduced against L. pneumophila grown in amoebae. PHMB (1 [times] MIC) gave 99.99% reductions in viability for cultures grown in broth within 6 h and no detectable survivors at 24 h but only 90 and 99.9% killing at 6 h andmore » 24 h, respectively, for cells grown in amoebae. The antimicrobial properties of the three biocides against A. polyphaga were also determined. The majority of amoebae recovered from BIT treatment, but few, if any, survived CMIT treatment or exposure of PHMB. This study not only shows the profound effect that intra-amoebal growth has on the physiological status and antimicrobial susceptibility of L. pneumophila but also reveals PHMB to be a potential biocide for effective water treatment. In this respect, PHMB has significant activity, below its recommended use concentrations, against both the host amoeba and L. pneumophila.« less

Nitric oxide: a multitasked signaling gas in plants.

PubMed

Domingos, Patricia; Prado, Ana Margarida; Wong, Aloysius; Gehring, Christoph; Feijo, Jose A

2015-04-01

Nitric oxide (NO) is a gaseous reactive oxygen species (ROS) that has evolved as a signaling hormone in many physiological processes in animals. In plants it has been demonstrated to be a crucial regulator of development, acting as a signaling molecule present at each step of the plant life cycle. NO has also been implicated as a signal in biotic and abiotic responses of plants to the environment. Remarkably, despite this plethora of effects and functional relationships, the fundamental knowledge of NO production, sensing, and transduction in plants remains largely unknown or inadequately characterized. In this review we cover the current understanding of NO production, perception, and action in different physiological scenarios. We especially address the issues of enzymatic and chemical generation of NO in plants, NO sensing and downstream signaling, namely the putative cGMP and Ca(2+) pathways, ion-channel activity modulation, gene expression regulation, and the interface with other ROS, which can have a profound effect on both NO accumulation and function. We also focus on the importance of NO in cell-cell communication during developmental processes and sexual reproduction, namely in pollen tube guidance and embryo sac fertilization, pathogen defense, and responses to abiotic stress. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Effects of Heat Stress on Construction Labor Productivity in Hong Kong: A Case Study of Rebar Workers.

PubMed

Yi, Wen; Chan, Albert P C

2017-09-12

Global warming is bringing more frequent and severe heat waves, and the result will be serious for vulnerable populations such as construction workers. Excessive heat stress has profound effects on physiological responses, which cause occupational injuries, fatalities and low productivity. Construction workers are particularly affected by heat stress, because of the body heat production caused by physically demanding tasks, and hot and humid working conditions. Field studies were conducted between August and September 2016 at two construction training grounds in Hong Kong. Onsite wet-bulb globe temperature (WBGT), workers' heart rate (HR), and labor productivity were measured and monitored. Based on the 378 data sets of synchronized environmental, physiological, construction labor productivity (CLP), and personal variables, a CLP-heat stress model was established. It was found that WBGT, percentage of maximum HR, age, work duration, and alcohol drinking habits were determining factors for predicting the CLP (adjusted R ² = 0.68, p < 0.05). The model revealed that heat stress reduces CLP, with the percentage of direct work time decreasing by 0.33% when the WBGT increased by 1 °C. The findings in this study extend the existing practice notes by providing scientific data that may be of benefit to the industry in producing solid guidelines for working in hot weather.

Stress hormones predict a host superspreader phenotype in the West Nile virus system

USGS Publications Warehouse

Gervasi, Stephanie; Burgan, Sarah; Hofmeister, Erik K.; Unnasch, Thomas R.; Martin, Lynn B.

2017-01-01

Glucocorticoid stress hormones, such as corticosterone (CORT), have profound effects on the behaviour and physiology of organisms, and thus have the potential to alter host competence and the contributions of individuals to population- and community-level pathogen dynamics. For example, CORT could alter the rate of contacts among hosts, pathogens and vectors through its widespread effects on host metabolism and activity levels. CORT could also affect the intensity and duration of pathogen shedding and risk of host mortality during infection. We experimentally manipulated songbird CORT, asking how CORT affected behavioural and physiological responses to a standardized West Nile virus (WNV) challenge. Although all birds became infected after exposure to the virus, only birds with elevated CORT had viral loads at or above the infectious threshold. Moreover, though the rate of mortality was faster in birds with elevated CORT compared with controls, most hosts with elevated CORT survived past the day of peak infectiousness. CORT concentrations just prior to inoculation with WNV and anti-inflammatory cytokine concentrations following viral exposure were predictive of individual duration of infectiousness and the ability to maintain physical performance during infection (i.e. tolerance), revealing putative biomarkers of competence. Collectively, our results suggest that glucocorticoid stress hormones could directly and indirectly mediate the spread of pathogens.

Effects of increased levels of atmospheric CO2 and high temperatures on rice growth and quality

PubMed Central

Waqas, Muhammad Ahmed; Wang, Song-he; Xiong, Xiang-yang; Wan, Yun-fan

2017-01-01

The increased atmospheric temperatures resulting from the increased concentration of atmospheric carbon dioxide (CO2) have had a profound influence on global rice production. China serves as an important area for producing and consuming rice. Therefore, exploring the effects of the simultaneously rising levels of atmospheric CO2 and temperatures on rice growth and quality in the future is very important. The present study was designed to measure the most important aspects of variation for rice-related physiological, ecological and quality indices in different growing periods under a simultaneous increase of CO2 and temperature, through simulation experiments in climate-controlled growth chambers, with southern rice as the study object. The results indicated that the ecological indices, rice phenology, and leaf area would decrease under a simultaneous increase of CO2 and temperature. For the physiological indices, Malondialdehyde (MDA) levels increased significantly in the seedling period. However, it showed the trend of increase and subsequent decrease in the heading and filling periods. In addition, the decomposition of soluble protein (SP) and soluble sugar (SS) accelerated in filling period. The rice quality index of the Head Rice Rate showed the decreasing trend and subsequent increase, but the Chalky Rice Rate and Protein Content indices gradually decreased while the Gel Consistency gradually increased. PMID:29145420

Effects of Heat Stress on Construction Labor Productivity in Hong Kong: A Case Study of Rebar Workers

PubMed Central

Chan, Albert P. C.

2017-01-01

Global warming is bringing more frequent and severe heat waves, and the result will be serious for vulnerable populations such as construction workers. Excessive heat stress has profound effects on physiological responses, which cause occupational injuries, fatalities and low productivity. Construction workers are particularly affected by heat stress, because of the body heat production caused by physically demanding tasks, and hot and humid working conditions. Field studies were conducted between August and September 2016 at two construction training grounds in Hong Kong. Onsite wet-bulb globe temperature (WBGT), workers’ heart rate (HR), and labor productivity were measured and monitored. Based on the 378 data sets of synchronized environmental, physiological, construction labor productivity (CLP), and personal variables, a CLP-heat stress model was established. It was found that WBGT, percentage of maximum HR, age, work duration, and alcohol drinking habits were determining factors for predicting the CLP (adjusted R2 = 0.68, p < 0.05). The model revealed that heat stress reduces CLP, with the percentage of direct work time decreasing by 0.33% when the WBGT increased by 1 °C. The findings in this study extend the existing practice notes by providing scientific data that may be of benefit to the industry in producing solid guidelines for working in hot weather. PMID:28895899

Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

PubMed Central

Piérard, Gérald E.; Humbert, Philippe; Berardesca, Enzo; Gaspard, Ulysse; Hermanns-Lê, Trinh; Piérard-Franchimont, Claudine

2013-01-01

Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral) and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin. PMID:24455744

Physiological and biochemical changes associated with acute experimental dehydration in the desert adapted mouse, Peromyscus eremicus.

PubMed

Kordonowy, Lauren; Lombardo, Kaelina D; Green, Hannah L; Dawson, Molly D; Bolton, Evice A; LaCourse, Sarah; MacManes, Matthew D

2017-03-01

Characterizing traits critical for adaptation to a given environment is an important first step in understanding how phenotypes evolve. How animals adapt to the extreme heat and aridity commonplace to deserts is an exceptionally interesting example of these processes, and has been the focus of study for decades. In contrast to those studies, where experiments are conducted on either wild animals or captive animals held in non-desert conditions, the study described here leverages a unique environmental chamber that replicates desert conditions for captive Peromyscus eremicus (cactus mouse). Here, we establish baseline values for daily water intake and for serum electrolytes, as well as the response of these variables to acute experimental dehydration. In brief, P   eremicus daily water intake is very low. Its serum electrolytes are distinct from many previously studied animals, and its response to acute dehydration is profound, though not suggestive of renal impairment, which is atypical of mammals. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Ocean acidification causes ecosystem shifts via altered competitive interactions

NASA Astrophysics Data System (ADS)

Kroeker, Kristy J.; Micheli, Fiorenza; Gambi, Maria Cristina

2013-02-01

Ocean acidification represents a pervasive environmental change that is predicted to affect a wide range of species, yet our understanding of the emergent ecosystem impacts is very limited. Many studies report detrimental effects of acidification on single species in lab studies, especially those with calcareous shells or skeletons. Observational studies using naturally acidified ecosystems have shown profound shifts away from such calcareous species, and there has been an assumption that direct impacts of acidification on sensitive species drive most ecosystem responses. We tested an alternative hypothesis that species interactions attenuate or amplify the direct effects of acidification on individual species. Here, we show that altered competitive dynamics between calcareous species and fleshy seaweeds drive significant ecosystem shifts in acidified conditions. Although calcareous species recruited and grew at similar rates in ambient and low pH conditions during early successional stages, they were rapidly overgrown by fleshy seaweeds later in succession in low pH conditions. The altered competitive dynamics between calcareous species and fleshy seaweeds is probably the combined result of decreased growth rates of calcareous species, increased growth rates of fleshy seaweeds, and/or altered grazing rates. Phase shifts towards ecosystems dominated by fleshy seaweed are common in many marine ecosystems, and our results suggest that changes in the competitive balance between these groups represent a key leverage point through which the physiological responses of individual species to acidification could indirectly lead to profound ecosystem changes in an acidified ocean.

Chronic Corticosterone Treatment During Adolescence Has Significant Effects on Metabolism and Skeletal Development in Male C57BL6/N Mice.

PubMed

Kinlein, Scott A; Shahanoor, Ziasmin; Romeo, Russell D; Karatsoreos, Ilia N

2017-07-01

Glucocorticoids are potent modulators of metabolic and behavioral function. Their role as mediators in the "stress response" is well known, but arguably their primary physiological function is in the regulation of cellular and organismal metabolism. Disruption of normal glucocorticoid function is linked to metabolic disease, such as Cushing syndrome. Glucocorticoids are also elevated in many forms of obesity, suggesting that there are bidirectional effects of these potent hormones on metabolism and metabolic function. Adolescence is a time of rapid physical growth, and disruptions during this critical time likely have important implications for adult function. The hypothalamic-pituitary-adrenal axis continues to mature during this period, as do tissues that respond to glucocorticoids. In this work, we investigate how chronic noninvasive exposure to corticosterone affects metabolic outcomes (body weight, body composition, insulin, and glucose homeostasis), as well as changes in bone density in both adult and adolescent male mice. Specifically, we report a different pattern of metabolic effects in adolescent mice compared with adults, as well as an altered trajectory of recovery in adolescents and adults. Together, these data indicate the profound influence that adolescent development has on the metabolic outcomes of chronic corticosterone exposure, and describe a tractable model for understanding the short- and long-term impacts of hypercortisolemic states on physiological and neurobehavioral functions. Copyright © 2017 Endocrine Society.

Acid-Sensing Ion Channel Pharmacology, Past, Present, and Future ….

PubMed

Rash, Lachlan D

2017-01-01

pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally. Acid-sensing ion channels (ASICs) are primary pH sensors in mammals and are expressed widely in neuronal and nonneuronal cells. There are six main subtypes of ASICs in rodents that can form homo- or heteromeric channels resulting in many potential combinations. ASICs are present and activated under all of the conditions mentioned earlier, suggesting that they play an important role in how cells respond to acidosis. Compared to many other ion channel families, ASICs were relatively recently discovered-1997-and there is a substantial lack of potent, subtype-selective ligands that can be used to elucidate their structural and functional properties. In this chapter I cover the history of ASIC channel pharmacology, which began before the proteins were even identified, and describe the current arsenal of tools available, their limitations, and take a glance into the future to predict from where new tools are likely to emerge. © 2017 Elsevier Inc. All rights reserved.

Extreme endurance flights by landbirds crossing the Pacific Ocean: Ecological corridor rather than barrier?

USGS Publications Warehouse

Gill, Robert E.; Tibbitts, T.L.; Douglas, David C.; Handel, Colleen M.; Mulcahy, D.M.; Gottschalck, J.C.; Warnock, N.; McCaffery, B.J.; Battley, Phil F.; Piersma, Theunis

2009-01-01

Mountain ranges, deserts, ice fields and oceans generally act as barriers to the movement of land-dependent animals, often profoundly shaping migration routes. We used satellite telemetry to track the southward flights of bar-tailed godwits (Limosa lapponica baueri), shorebirds whose breeding and non-breeding areas are separated by the vast central Pacific Ocean. Seven females with surgically implanted transmitters flew non-stop 8117-11680km (10153??1043 s.d.) directly across the Pacific Ocean; two males with external transmitters flew non-stop along the same corridor for 7008-7390km. Flight duration ranged from 6.0 to 9.4 days (7.8??1.3 s.d.) for birds with implants and 5.0 to 6.6 days for birds with externally attached transmitters. These extraordinary non-stop flights establish new extremes for avian flight performance, have profound implications for understanding the physiological capabilities of vertebrates and how birds navigate, and challenge current physiological paradigms on topics such as sleep, dehydration and phenotypic flexibility. Predicted changes in climatic systems may affect survival rates if weather conditions at their departure hub or along the migration corridor should change. We propose that this transoceanic route may function as an ecological corridor rather than a barrier, providing a wind-assisted passage relatively free of pathogens and predators. ?? 2008 The Royal Society.

Extreme endurance flights by landbirds crossing the Pacific Ocean: ecological corridor rather than barrier?

PubMed Central

Gill, Robert E.; Tibbitts, T. Lee; Douglas, David C.; Handel, Colleen M.; Mulcahy, Daniel M.; Gottschalck, Jon C.; Warnock, Nils; McCaffery, Brian J.; Battley, Philip F.; Piersma, Theunis

2008-01-01

Mountain ranges, deserts, ice fields and oceans generally act as barriers to the movement of land-dependent animals, often profoundly shaping migration routes. We used satellite telemetry to track the southward flights of bar-tailed godwits (Limosa lapponica baueri), shorebirds whose breeding and non-breeding areas are separated by the vast central Pacific Ocean. Seven females with surgically implanted transmitters flew non-stop 8117–11 680 km (10 153±1043 s.d.) directly across the Pacific Ocean; two males with external transmitters flew non-stop along the same corridor for 7008–7390 km. Flight duration ranged from 6.0 to 9.4 days (7.8±1.3 s.d.) for birds with implants and 5.0 to 6.6 days for birds with externally attached transmitters. These extraordinary non-stop flights establish new extremes for avian flight performance, have profound implications for understanding the physiological capabilities of vertebrates and how birds navigate, and challenge current physiological paradigms on topics such as sleep, dehydration and phenotypic flexibility. Predicted changes in climatic systems may affect survival rates if weather conditions at their departure hub or along the migration corridor should change. We propose that this transoceanic route may function as an ecological corridor rather than a barrier, providing a wind-assisted passage relatively free of pathogens and predators. PMID:18974033

Arbuscular mycorrhizal symbiosis can mitigate the negative effects of night warming on physiological traits of Medicago truncatula L.

PubMed

Hu, Yajun; Wu, Songlin; Sun, Yuqing; Li, Tao; Zhang, Xin; Chen, Caiyan; Lin, Ge; Chen, Baodong

2015-02-01

Elevated night temperature, one of the main climate warming scenarios, can have profound effects on plant growth and metabolism. However, little attention has been paid to the potential role of mycorrhizal associations in plant responses to night warming, although it is well known that symbiotic fungi can protect host plants against various environmental stresses. In the present study, physiological traits of Medicago truncatula L. in association with the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis were investigated under simulated night warming. A constant increase in night temperature of 1.53 °C significantly reduced plant shoot and root biomass, flower and seed number, leaf sugar concentration, and shoot Zn and root P concentrations. However, the AM association essentially mitigated these negative effects of night warming by improving plant growth, especially through increased root biomass, root to shoot ratio, and shoot Zn and root P concentrations. A significant interaction was observed between R. irregularis inoculation and night warming in influencing both root sucrose concentration and expression of sucrose synthase (SusS) genes, suggesting that AM symbiosis and increased night temperature jointly regulated plant sugar metabolism. Night warming stimulated AM fungal colonization but did not influence arbuscule abundance, symbiosis-related plant or fungal gene expression, or growth of extraradical mycelium, indicating little effect of night warming on the development or functioning of AM symbiosis. These findings highlight the importance of mycorrhizal symbiosis in assisting plant resilience to climate warming.

Effect of calcitonin on gastrointestinal regulatory peptides in man.

PubMed

Stevenson, J C; Adrian, T E; Christofides, N D; Bloom, S R

1985-05-01

A major physiological role of calcitonin in humans appears to be regulation of skeletal turnover. It has been suggested that another function of calcitonin is to prevent post-prandial rises in calcium, particularly in animals, but the importance of such a function in man remains to be determined. Although it is known that calcitonin has an inhibitory effect on the secretion of gastrin and insulin, its actions on other gut and pancreatic hormones have not previously been studied. To investigate interrelations between calcitonin and gastrointestinal regulatory peptides, 0.5 mg synthetic human calcitonin was administered to 10 fasting patients. No changes in the plasma concentrations of glucose, somatostatin, neurotensin, enteroglucagon, vasoactive intestinal polypeptide or bombesin were observed. In contrast, profound falls in the circulating levels of gastrin, insulin and pancreatic glucagon were seen, reaching a maximum shortly after the peak of plasma calcitonin concentration. Marked changes were also observed in the levels of motilin, pancreatic polypeptide and, to a lesser extent, gastric inhibitory polypeptide, but the maximal falls occurred about 40 min later, coinciding with a significant fall in serum calcium. It is possible that the effect of calcitonin on these hormones was direct, perhaps receptor-mediated. The falls in levels of motilin and pancreatic polypeptide could have been further enhanced by changes in extracellular calcium ion concentrations. Whether any of these effects of calcitonin occur physiologically remains to be determined. However, these findings suggest new therapeutic possibilities for calcitonin.

Co-regulation of Primary Mouse Hepatocyte Viability and Function by Oxygen and Matrix

PubMed Central

Buck, Lorenna D.; Inman, S. Walker; Rusyn, Ivan; Griffith, Linda G.

2014-01-01

Although oxygen and extracellular matrix cues both influence differentiation state and metabolic function of primary rat and human hepatocytes, relatively little is known about how these factors together regulate behaviors of primary mouse hepatocytes in culture. To determine the effects of pericellular oxygen tension on hepatocellular function, we employed 2 methods of altering oxygen concentration in the local cellular microenvironment of cells cultured in the presence or absence of an extracellular matrix (Matrigel) supplement. By systematically altering medium depth and gas phase oxygen tension, we created multiple oxygen regimes (hypoxic, normoxic, and hyperoxic) and measured the local oxygen concentrations in the pericellular environment using custom-designed oxygen microprobes. From these measurements of oxygen concentrations, we derived values of oxygen consumption rates under a spectrum of environmental contexts, thus providing the first reported estimates of these values for primary mouse hepatocytes. Oxygen tension and matrix microenvironment were found to synergistically regulate hepatocellular survival and function as assessed using quantitative image analysis for cells stained with vital dyes, and assessment of secretion of albumin. Hepatocellular viability was affected only at strongly hypoxic conditions. Surprisingly, albumin secretion rates were greatest at a moderately supra-physiological oxygen concentration, and this effect was mitigated at still greater supra-physiological concentrations. Matrigel enhanced the effects of oxygen on retention of function. This study underscores the importance of carefully controlling cell density, medium depth and gas phase oxygen, as the effects of these parameters on local pericellular oxygen tension and subsequent hepatocellular function are profound. PMID:24222008

EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness

PubMed Central

2014-01-01

Background Almost 90% of all cases of congenital, non-syndromic, severe to profound inherited deafness display an autosomal recessive mode of transmission (DFNB forms). To date, 47 causal DFNB genes have been identified, but many others remain to be discovered. We report the study of two siblings born to consanguineous Algerian parents and affected by isolated, profound congenital deafness. Method Whole-exome sequencing was carried out on these patients after a failure to identify mutations in the DFNB genes frequently involved. Results A biallelic nonsense mutation, c.88C > T (p.Gln30*), was identified in EPS8 that encodes epidermal growth factor receptor pathway substrate 8, a 822 amino-acid protein involved in actin dynamics. This mutation predicts a truncated inactive protein or no protein at all. The mutation was also present, in the heterozygous state, in one clinically unaffected sibling and in both unaffected parents, and was absent from the other two unaffected siblings. It was not found in 120 Algerian normal hearing control individuals or in the Exome Variant Server database. EPS8 is an F-actin capping and bundling protein. Mutant mice lacking EPS8 (Eps8−/− mice), which is present in the hair bundle, the sensory antenna of the auditory sensory cells that operate the mechano-electrical transduction, are also profoundly deaf and have abnormally short hair bundle stereocilia. Conclusion This new DFNB form is likely to arise from abnormal hair bundles resulting in compromised detection of physiological sound pressures. PMID:24741995

Inducible Knockout of the Cyclin-Dependent Kinase 5 Activator p35 Alters Hippocampal Spatial Coding and Neuronal Excitability

PubMed Central

Kamiki, Eriko; Boehringer, Roman; Polygalov, Denis; Ohshima, Toshio; McHugh, Thomas J.

2018-01-01

p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice. PMID:29867369

Bodily illusions in health and disease: physiological and clinical perspectives and the concept of a cortical 'body matrix'.

PubMed

Moseley, G Lorimer; Gallace, Alberto; Spence, Charles

2012-01-01

Illusions that induce a feeling of ownership over an artificial body or body-part have been used to explore the complex relationships that exist between the brain's representation of the body and the integrity of the body itself. Here we discuss recent findings in both healthy volunteers and clinical populations that highlight the robust relationship that exists between a person's sense of ownership over a body part, cortical processing of tactile input from that body part, and its physiological regulation. We propose that a network of multisensory and homeostatic brain areas may be responsible for maintaining a 'body-matrix'. That is, a dynamic neural representation that not only extends beyond the body surface to integrate both somatotopic and peripersonal sensory data, but also integrates body-centred spatial sensory data. The existence of such a 'body-matrix' allows our brain to adapt to even profound anatomical and configurational changes to our body. It also plays an important role in maintaining homeostatic control over the body. Its alteration can be seen to have both deleterious and beneficial effects in various clinical populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Pulmonary rehabilitation after total laryngectomy using a heat and moisture exchanger (HME)].

PubMed

Lorenz, K J; Maier, H

2009-08-01

A complete removal of the larynx has profound consequences for a patient. Since laryngectomy involves the separation of the upper airway from the lower airway, it not only implies a loss of the voice organ but also leads to chronic lung problems such as increased coughing, mucus production and expectoration. In addition, laryngectomees complain of fatigue, sleeping problems, a reduced sense of smell and taste, and a loss of social contact. A heat and moisture exchanger (HME) cassette can replace a function of the upper airway which consists in conditioning inspired air. It can improve pulmonary symptoms in three ways. 1. An HME cassette heats and moisturises inhaled air and thus creates nearly physiological conditions in the region of the deep airway. 2. The use of an HME cassette leads to an increase in breathing resistance, thereby reducing dynamic airway compression and improving lung ventilation. 3. An HME cassette acts as a filter and removes larger particles from incoming air. This review examines the current understanding of lung physiology after laryngectomy and assesses the effects of HME cassettes on the conditioning of respiratory air, lung function and psychosocial problems. Georg Thieme Verlag KG Stuttgart, New York.

Hyperoxia reduces insulin release and induces mitochondrial dysfunction with possible implications for hyperoxic treatment of neonates.

PubMed

Hals, Ingrid; Ohki, Tsuyoshi; Singh, Rinku; Ma, Zuheng; Björklund, Anneli; Balasuriya, Chandima; Scholz, Hanne; Grill, Valdemar

2017-10-01

We previously showed that hyperoxia in vitro negatively affects beta cells of the rat. Here, we tested for possible clinical significance as well as mitochondrial interactions by hyperoxia, using human islets (function and viability), INS-1 832/13 cells (mitochondrial metabolism), and mouse neonates (effects in vivo). Lastly, we assessed relevant parameters in a cohort of individuals born preterm and then exposed to hyperoxia. Human islets and INS-1 832/13 cells were exposed to 24 h of hyperoxia (90-92% oxygen). Mouse neonates were subjected to 5 days of continuous hyperoxia. Individuals born preterm were evaluated in terms of glucose homeostasis and beta cell function by HbA1c and the HOMA2 formula. In human islets, hyperoxia significantly reduced glucose-stimulated insulin secretion by 42.2 ± 5.3% and viability assessed by MTT by 22.5 ± 5.4%. Hyperoxia down-regulated mitochondrial complex II by 21 ± 5% and upregulated complex III by 26 ± 10.1% and complex IV by 37 ± 10.6%. Partly similar effects on mitochondrial complexes were found in hyperoxia-exposed INS-1 832/13 cells. Exposure to hyperoxia swiftly reduced oxygen consumption in these cells and increased mitochondrial uncoupling. Hyperoxia transiently but significantly reduced insulin release in mouse neonates. Individuals born preterm displayed higher HbA1c versus controls, as well as insulin resistance. Thus, hyperoxia exerts negative effects in vitro on human beta cells and results indicate inhibitory effects on insulin secretion in vivo in mouse neonates. Negative effects may be lessened by the demonstrated swift and profound mitochondrial adaptability. Our findings open the possibility that hyperoxia could negatively affect beta cells of preterm human neonates. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Local Adaptation to Altitude Underlies Divergent Thermal Physiology in Tropical Killifishes of the Genus Aphyosemion

PubMed Central

McKenzie, David J.; Estivales, Guillan; Svendsen, Jon C.; Steffensen, John F.; Agnèse, Jean-François

2013-01-01

In watersheds of equatorial West Africa, monophyletic groups of killifish species (genus Aphyosemion) occur in discrete altitudinal ranges, low altitude species (LA, sea level to ∼350 m) or high altitude species (HA, 350 to 900 m). We investigated the hypothesis that local adaptation to altitude by the LA and HA species would be revealed as divergent effects of temperature on their physiological energetics. Two species from each group (mass ∼350 mg) were acclimated to 19, 25 and 28°C, with 19 and 28°C estimated to be outside the thermal envelope for LA or HA, respectively, in the wild. Wild-caught animals (F0 generation) were compared with animals raised in captivity at 25°C (F1 generation) to investigate the contribution of adaptation versus plasticity. Temperature significantly increased routine metabolic rate in all groups and generations. However, LA and HA species differed in the effects of temperature on their ability to process a meal. At 25°C, the specific dynamic action (SDA) response was completed within 8 h in all groups, but acclimation to temperatures beyond the thermal envelope caused profound declines in SDA performance. At 19°C, the LA required ∼14 h to complete the SDA, whereas the HA required only ∼7 h. The opposite effect was observed at 28°C. This effect was evident in both F0 and F1. Reaction norms for effects of temperature on SDA therefore revealed a trade-off, with superior performance at warmer temperatures by LA being associated with inferior performance at cooler temperatures, and vice-versa in HA. The data indicate that divergent physiological responses to temperature in the LA and HA species reflect local adaptation to the thermal regime in their habitat, and that local adaptation to one thermal environment trades off against performance in another. PMID:23349857

Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior

PubMed Central

Lowry, C.A.; Hollis, J.H.; de Vries, A.; Pan, B.; Brunet, L.R.; Hunt, J.R.F.; Paton, J.F.R.; van Kampen, E.; Knight, D.M.; Evans, A.K.; Rook, G.A.W.; Lightman, S.L.

2007-01-01

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes. PMID:17367941

Local adaptation to altitude underlies divergent thermal physiology in tropical killifishes of the genus Aphyosemion.

PubMed

McKenzie, David J; Estivales, Guillan; Svendsen, Jon C; Steffensen, John F; Agnèse, Jean-François

2013-01-01

In watersheds of equatorial West Africa, monophyletic groups of killifish species (genus Aphyosemion) occur in discrete altitudinal ranges, low altitude species (LA, sea level to ∼350 m) or high altitude species (HA, 350 to 900 m). We investigated the hypothesis that local adaptation to altitude by the LA and HA species would be revealed as divergent effects of temperature on their physiological energetics. Two species from each group (mass ∼350 mg) were acclimated to 19, 25 and 28°C, with 19 and 28°C estimated to be outside the thermal envelope for LA or HA, respectively, in the wild. Wild-caught animals (F0 generation) were compared with animals raised in captivity at 25°C (F1 generation) to investigate the contribution of adaptation versus plasticity. Temperature significantly increased routine metabolic rate in all groups and generations. However, LA and HA species differed in the effects of temperature on their ability to process a meal. At 25°C, the specific dynamic action (SDA) response was completed within 8 h in all groups, but acclimation to temperatures beyond the thermal envelope caused profound declines in SDA performance. At 19°C, the LA required ∼14 h to complete the SDA, whereas the HA required only ∼7 h. The opposite effect was observed at 28°C. This effect was evident in both F0 and F1. Reaction norms for effects of temperature on SDA therefore revealed a trade-off, with superior performance at warmer temperatures by LA being associated with inferior performance at cooler temperatures, and vice-versa in HA. The data indicate that divergent physiological responses to temperature in the LA and HA species reflect local adaptation to the thermal regime in their habitat, and that local adaptation to one thermal environment trades off against performance in another.

Cell-Extracellular Matrix Mechanobiology: Forceful Tools and Emerging Needs for Basic and Translational Research.

PubMed

Holle, Andrew W; Young, Jennifer L; Van Vliet, Krystyn J; Kamm, Roger D; Discher, Dennis; Janmey, Paul; Spatz, Joachim P; Saif, Taher

2018-01-10

Extracellular biophysical cues have a profound influence on a wide range of cell behaviors, including growth, motility, differentiation, apoptosis, gene expression, adhesion, and signal transduction. Cells not only respond to definitively mechanical cues from the extracellular matrix (ECM) but can also sometimes alter the mechanical properties of the matrix and hence influence subsequent matrix-based cues in both physiological and pathological processes. Interactions between cells and materials in vitro can modify cell phenotype and ECM structure, whether intentionally or inadvertently. Interactions between cell and matrix mechanics in vivo are of particular importance in a wide variety of disorders, including cancer, central nervous system injury, fibrotic diseases, and myocardial infarction. Both the in vitro and in vivo effects of this coupling between mechanics and biology hold important implications for clinical applications.

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain.

PubMed

Grinevich, Valery; Knobloch-Bollmann, H Sophie; Eliava, Marina; Busnelli, Marta; Chini, Bice

2016-02-01

Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Expression of AmGR10 of the Gustatory Receptor Family in Honey Bee Is Correlated with Nursing Behavior.

PubMed

Paerhati, Yisilahaiti; Ishiguro, Shinichi; Ueda-Matsuo, Risa; Yang, Ping; Yamashita, Tetsuro; Ito, Kikukatsu; Maekawa, Hideaki; Tani, Hiroko; Suzuki, Koichi

2015-01-01

We investigated the association between the expression of a gene encoding gustatory receptor (G10) and division of labor in the honey bee, Apis mellifera. Among 10 GR genes encoding proteins 15% ~ 99% amino acid identity in the honey bee, we found that AmGR10 with 99% identity is involved in nursing or brood care. Expression of AmGR10 was restricted to organs of the hypopharyngeal gland, brain, and ovary in the nurse bee phase. Members of an extended nursing caste under natural conditions continued to express this gene. RNAi knockdown of AmGR10 accelerated the transition to foraging. Our findings demonstrate that this one gene has profound effects on the division of labor associated with the development and physiology of honeybee society.

Repeated, but Not Acute, Stress Suppresses Inflammatory Plasma Extravasation

NASA Astrophysics Data System (ADS)

Strausbaugh, Holly J.; Dallman, Mary F.; Levine, Jon D.

1999-12-01

Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.

Music listening as a means of stress reduction in daily life.

PubMed

Linnemann, Alexandra; Ditzen, Beate; Strahler, Jana; Doerr, Johanna M; Nater, Urs M

2015-10-01

The relation between music listening and stress is inconsistently reported across studies, with the major part of studies being set in experimental settings. Furthermore, the psychobiological mechanisms for a potential stress-reducing effect remain unclear. We examined the potential stress-reducing effect of music listening in everyday life using both subjective and objective indicators of stress. Fifty-five healthy university students were examined in an ambulatory assessment study, both during a regular term week (five days) and during an examination week (five days). Participants rated their current music-listening behavior and perceived stress levels four times per day, and a sub-sample (n = 25) additionally provided saliva samples for the later analysis of cortisol and alpha-amylase on two consecutive days during both weeks. Results revealed that mere music listening was effective in reducing subjective stress levels (p = 0.010). The most profound effects were found when 'relaxation' was stated as the reason for music listening, with subsequent decreases in subjective stress levels (p ≤ 0.001) and lower cortisol concentrations (p ≤ 0.001). Alpha-amylase varied as a function of the arousal of the selected music, with energizing music increasing and relaxing music decreasing alpha-amylase activity (p = 0.025). These findings suggest that music listening can be considered a means of stress reduction in daily life, especially if it is listened to for the reason of relaxation. Furthermore, these results shed light on the physiological mechanisms underlying the stress-reducing effect of music, with music listening differentially affecting the physiological stress systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implications of the stability behavior of zinc oxide nanoparticles for toxicological studies

NASA Astrophysics Data System (ADS)

Meißner, Tobias; Oelschlägel, Kathrin; Potthoff, Annegret

2014-08-01

The increasing use of zinc oxide (ZnO) nanoparticles in sunscreens and other cosmetic products demands a risk assessment that has to be done in toxicological studies. Such investigations require profound knowledge of the behavior of ZnO in cell culture media. The current study was performed to get well-dispersed suspensions of a hydrophilic (ZnO-hydro) and a lipophilic coated (ZnO-lipo) ZnO nanomaterial for use in in vitro tests. Therefore, systematic tests were carried out with common dispersants (phosphate, lecithin, proteins) to elucidate chemical and physical changes of ZnO nanoparticles in water and physiological solutions (PBS, DMEM). Non-physiological stock suspensions were prepared using ultrasonication. Time-dependent changes of pH, conductivity, zeta potential, particle size and dissolution were recorded. Secondly, the stock suspensions were added to physiological media with or without albumin (BSA) or serum (FBS), to examine characteristics such as agglomeration and dissolution. Stable stock suspensions were obtained using phosphate as natural and physiological electrostatic stabilizing agent. Lecithin proved to be an effective wetting agent for ZnO-lipo. Although the particle size remained constant, the suspension changed over time. The pH increased as a result of ZnO dissolution and formation of zinc phosphate complexes. The behavior of ZnO in physiological media was found to depend strongly on the additives used. Applying only phosphate as additive, ZnO-hydro agglomerated within minutes. In the presence of lecithin or BSA/serum, agglomeration was inhibited. ZnO dissolution was higher under physiological conditions than in the stock suspension. Serum especially promoted this process. Using body-related dispersants (phosphate, lecithin) non-agglomerating stock suspensions of hydrophilic and lipophilic ZnO were prepared as a prerequisite to perform meaningful toxicological investigation. Both nanomaterials showed a non-negligible dissolution behavior that strongly depended on the surrounding conditions. Agglomeration of ZnO particles in physiological media is a complex function of particle coating, used dispersants and serum proteins if supplemented. The present study gives a clear guideline how to prepare and handle suspensions with ZnO for in vitro testing and allows the correlation between the chemical-physical particles behavior with findings from toxicological tests.

Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

PubMed

Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean

2015-08-01

The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements. © 2015 Wiley Periodicals, Inc.

High Intracellular Chloride Slows the Decay of Glycinergic Currents

PubMed Central

Pitt, Samantha J.; Sivilotti, Lucia G.; Beato, Marco

2009-01-01

The time course of currents mediated by native and recombinant glycine receptors was examined with a combination of rapid agonist applications to outside-out patches and single-channel recording. The deactivation time constant of currents evoked by brief, saturating pulses of glycine is profoundly affected by the chloride concentration on the intracellular side of the cell membrane. Deactivation was threefold slower when intracellular chloride was increased from a low level (10 mm), similar to that observed in living mature neurons, to 131 mm (“symmetrical” chloride, often used in pipette internal solutions). Single-channel analysis revealed that high chloride has its greatest effect on the channel closing rate, slowing it by a factor of 2 compared with the value we estimated in the cell-attached mode (in which the channels are at physiological intracellular chloride concentrations). The same effect of chloride was observed when glycinergic evoked synaptic currents were recorded from juvenile rat spinal motoneurons in vitro, because the decay time constant was reduced from ∼7ms to ∼3 ms when cells were dialyzed with 10 mm chloride intracellular recording solution. Our results indicate that the time course of glycinergic synaptic inhibition in intact neurons is much faster than is estimated by measurements in symmetrical chloride and can be modulated by changes in intracellular chloride concentration in the range that can occur in physiological or pathological conditions. PMID:18987182

The effects of iPod and text-messaging use on driver distraction: a bio-behavioral analysis.

PubMed

Mouloua, M; Ahern, A; Quevedo, A; Jaramillo, D; Rinalducci, E; Smither, J; Alberti, P; Brill, C

2012-01-01

This study was designed to empirically examine the effects of iPod device and text-messaging activities on driver distraction. Sixty participants were asked to perform a driving simulation task while searching for songs using an iPod device or text messaging. Driving errors as measured by lane deviations were recorded and analyzed as a function of the distracters. Physiological measures (EEG) were also recorded during the driving phases in order to measure participant levels of cortical arousal. It was hypothesized that iPod use and text messaging would result in a profound effect on driving ability. The results showed a significant effect of iPod use and text-messaging on driving performance. Increased numbers of driving errors were recorded during the iPod and text-messaging phases than the pre- and post-allocation phases. Higher levels of Theta activity were also observed during the iPod and Text-messaging phase than the pre- and post-allocation phases. Implications for in-vehicle systems design, training, and safety are also discussed.

Severe to profound hearing impairment: quality of life, psychosocial consequences and audiological rehabilitation.

PubMed

Carlsson, Per-Inge; Hjaldahl, Jennie; Magnuson, Anders; Ternevall, Elisabeth; Edén, Margareta; Skagerstrand, Åsa; Jönsson, Radi

2015-01-01

To study the quality of life (QoL) and psychosocial consequences in terms of sick leave and audiological rehabilitation given to patients with severe to profound hearing impairment. A retrospective study of data on 2319 patients with severe to profound hearing impairment in The Swedish Quality Register of Otorhinolaryngology, followed by a posted questionnaire including The Hospital Anxiety and Depression Scale (HADS). The results indicate greater levels of anxiety and depression among patients with severe or profound hearing impairment than in the general population, and annoying tinnitus and vertigo had strong negative effects on QoL. The proportion of sick leave differed between the studied dimensions in the study. The proportion of patients who received extended audiological rehabilitation was 38% in the present study. Treatment focused on anxiety, depression, tinnitus and vertigo must be given early in the rehabilitation process in patients with severe or profound hearing impairment. Because sick leave differs greatly within this group of patients, collaboration with the regional Social Insurance Agency is crucial part of the rehabilitation. The study also shows that presently, only a small proportion of patients in Sweden with severe to profound hearing impairment receive extended audiological rehabilitation. Implications for Rehabilitation Greater levels of anxiety and depression have been found among patients with severe or profound hearing impairment than in the general population, and annoying tinnitus and vertigo have strong negative effects on QoL in this group of patients. Only a small proportion of patients with severe to profound hearing impairment receive extended audiological rehabilitation today, including medical, technical and psychosocial efforts. Extended audiological rehabilitation focused on anxiety, depression, tinnitus and vertigo must be given, together with technical rehabilitation, early in the rehabilitation process in patients with severe or profound hearing impairment.

Psychophysiology of Spaceflight and Aviation

NASA Technical Reports Server (NTRS)

Cowings, Patricia; Toscano, William

2013-01-01

In space, the absence of gravity alone causes unique physiological stress. Significant biomedical changes, across multiple organ systems, such as body fluid redistribution, diminished musculoskeletal strength, changes in cardiac function and sensorimotor control have been reported. The time course of development of these disorders and severity of symptoms experienced by individuals varies widely. Space motion sickness (SMS) is an example of maladaptation to microgravity, which occurs early in the mission and can have profound effects on physical health and crew performance. Disturbances in sleep quality, perception, emotional equilibrium and mood have also been reported, with impact to health and performance varying widely across individuals. And lastly, post-flight orthostatic intolerance, low blood pressure experienced after returning to Earth, is also of serious concern. Both the Russian and American space programs have a varied list of human errors and mistakes, which adversely impacted mission goals. Continued probability of human exposure to microgravity for extended time periods provides a rationale for the study of the effects of stress. The primary focus of this research group is directed toward examining individual differences in: (a) prediction of susceptibility to these disorders, (b) assessment of symptom severity, (c) evaluation of the effectiveness of countermeasures, and (d) developing and testing a physiological training method, Autogenic-Feedback Training Exercise (AFTE) as a countermeasure with multiple applications. The present paper reports on the results of a series of human flight experiments with AFTE aboard the Space Shuttle and Mir Space Station, and during emergency flight scenarios on Earth.

Interactions between Artificial Gravity, Affected Physiological Systems, and Nutrition

NASA Technical Reports Server (NTRS)

Heer, Martina; Baecker, Natalie; Zwart, Sara; Smith, Scott M.

2007-01-01

Malnutrition, either by insufficient supply of some nutrients or by overfeeding has a profound effect on the health of an organism. Therefore, optimal nutrition is mandatory on Earth (1 g), in microgravity and also when applying artificial gravity to the human system. Immobilization like in microgravity or bed rest also has a profound effect on different physiological systems, like body fluid regulation, the cardiovascular, the musculoskeletal, the immunological system and others. Up to now there is no countermeasure available which is effective to counteract cardiovascular deconditioning (rf. Chapter 5) together with maintenance of the musculoskeletal system in a rather short period of time. Gravity seems therefore to be one of the main stimuli to keep these systems and application of certain duration of artificial gravity per day by centrifugation has often been proposed as a very potential countermeasure against the weakening of the physiological systems. Up to now, neither optimal intensity nor optimal length of application of artificial gravity has been studied sufficiently to recommend a certain, effective and efficient protocol. However, as shown in chapter 5 on cardiovascular system, in chapter 6 on the neuromuscular system and chapter 7 (bone and connective system) artificial gravity has a very high potential to counteract any degradation caused by immobilization. But, nutrient supply -which ideally should match the actual needs- will interact with these changes and therefore has also to be taken into account. It is well known that astronauts beside the Skylab missions- were and are still not optimally nourished during their stay in space (Bourland et al. 2000;Heer et al. 1995;Heer et al. 2000b;Smith et al. 1997;Smith & Lane 1999;Smith et al. 2001;Smith et al. 2005). It has also been described anecdotally that astronauts have lower appetites. One possible explanation could be altered taste and smell sensations during space flight, although in some early space flights no significant changes were found (Heidelbaugh et al. 1968;Watt et al. 1985). However, data from a recent head-down bed rest study showed significant decrease in smell sensation (Enck et al. unpublished data) suggesting that fluid shifts might have an impact. If this holds true and which has to be validated in further studies, this seems to play an important role for lowered food intake causing insufficient energy intake and subsequently insufficient supply of most of the macro- and micronutrients. Other nutrients are taken in excess, for example sodium. As it is very well known from daily food consumption especially premanufactured food with high salt content seems to be more palatable than that with low salt content. Salt also functions as preservation which is very important taking into account the space food system limitations (i.e., lack of refrigerators and freezers). The preference for food with high salt intake by astronauts might therefore very likely be caused by altered smell and taste sensations in microgravity.

Physiological State Influences the Social Interactions of Two Honeybee Nest Mates

PubMed Central

Wright, Geraldine A.; Lillvis, Joshua L.; Bray, Helen J.; Mustard, Julie A.

2012-01-01

Physiological state profoundly influences the expression of the behaviour of individuals and can affect social interactions between animals. How physiological state influences food sharing and social behaviour in social insects is poorly understood. Here, we examined the social interactions and food sharing behaviour of honeybees with the aim of developing the honeybee as a model for understanding how an individual's state influences its social interactions. The state of individual honeybees was manipulated by either starving donor bees or feeding them sucrose or low doses of ethanol to examine how a change in hunger or inebriation state affected the social behaviours exhibited by two closely-related nestmates. Using a lab-based assay for measuring individual motor behaviour and social behaviour, we found that behaviours such as antennation, willingness to engage in trophallaxis, and mandible opening were affected by both hunger and ethanol intoxication. Inebriated bees were more likely to exhibit mandible opening, which may represent a form of aggression, than bees fed sucrose alone. However, intoxicated bees were as willing to engage in trophallaxis as the sucrose-fed bees. The effects of ethanol on social behaviors were dose-dependent, with higher doses of ethanol producing larger effects on behaviour. Hungry donor bees, on the other hand, were more likely to engage in begging for food and less likely to antennate and to display mandible opening. We also found that when nestmates received food from donors previously fed ethanol, they began to display evidence of inebriation, indicating that ethanol can be retained in the crop for several hours and that it can be transferred between honeybee nestmates during trophallaxis. PMID:22427864

Comparing the long-term retention of a physiology course for medical students with the traditional and problem-based learning.

PubMed

Pourshanazari, A A; Roohbakhsh, A; Khazaei, M; Tajadini, H

2013-03-01

The rapid improvements in medical sciences and the ever-increasing related data, however, require novel methods of instruction. One such method, which has been given less than due attention in Iran, is problem-based learning (PBL). In this study, we aimed to evaluate the impact of study skills and the PBL methods on short and long-term retention of information provided for medical students in the course of respiratory physiology and compare it with traditional learning method. In this study, 39 medical students from Medical School of Kerman University of Medical Sciences, Kerman, Iran (2006-2010) were enrolled in the study and allocated randomly in three equal groups (13 in each group). All groups underwent a pre-test to be assessed for their basic information regarding respiratory physiology. Two groups were instructed using the traditional method, and one group used PBL. Among the two groups of the traditional method, one was instructed about study skills and the other was not. Once the PBL group took the study skill workshop, they were aided by tutors for their education. In the final term test, those students who had learned study skills and were instructed with the traditional method scored higher compared to other groups (p < 0.05). However, in the 1 year (p < 0.05) and 4 year (p < 0.01) interval examinations, the PBL group achieved significantly higher scores. Despite the fact that PBL had no positive effect on the final term exam of our students, it yielded a more profound and retained understanding of the subject course. Moreover, considering the positive effect of study skills on long-term student scores, we recommend students to receive instructions regarding the appropriate study skills when initiated into universities.

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract.

PubMed

Mimee, Andrea; Ferguson, Alastair V

2015-04-15

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. Copyright © 2015 the American Physiological Society.

Dietary tributyrin, an HDAC inhibitor, promotes muscle growth through enhanced terminal differentiation of satellite cells.

PubMed

Murray, Robert L; Zhang, Wei; Iwaniuk, Marie; Grilli, Ester; Stahl, Chad H

2018-05-01

Muscle growth and repair rely on two main mechanisms - myonuclear accretion and subsequent protein accumulation. Altering the ability of muscle resident stem cells (satellite cells) to progress through their myogenic lineage can have a profound effect on lifetime muscle growth and repair. The use of the histone deacetylase (HDAC) inhibitor, butyrate, has had positive outcomes on the in vitro promotion of satellite cell myogenesis. In animal models, the use of butyrate has had promising results in treating myopathic conditions as well as improving growth efficiency, but the impact of dietary butyrate on satellite cells and muscle growth has not been elucidated. We investigated the impact of tributyrin, a butyrate prodrug, on satellite cell activity and muscle growth in a piglet model. Satellite cells from tributyrin-treated piglets had altered myogenic potential, and piglets receiving tributyrin had a ~40% increase in DNA:protein ratio after 21 days, indicating the potential for enhanced muscle growth. To assess muscle growth potential, piglets were supplemented tributyrin (0.5%) during either the neonatal phase (d1-d21) and/or the nursery phase (d21-d58) in a 2 × 2 factorial design. Piglets who received tributyrin during the neonatal phase had improved growth performance at the end of the study and had a ~10% larger loin eye area and muscle fiber cross-sectional area. Tributyrin treatment in the nursery phase alone did not have a significant effect on muscle growth or feed efficiency. These findings suggest that tributyrin is a potent promoter of muscle growth via altered satellite cell myogenesis. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Emotional and aesthetic antecedents and consequences of music-induced thrills.

PubMed

Konecni, Vladimir J; Wanic, Rebekah A; Brown, Amber

2007-01-01

The significance of music-induced thrills or chills was explored in 3 experiments (N= 223). Specifically, the ability of antecedent (priming) stimuli in different modalities and aesthetic domains (national anthems, stories, architectural objects, paintings) to increase the participants' thrills responsiveness to music by Rachmaninoff and Haydn was examined. In addition, the differential effects of having or not having experienced thrills on the participants' subsequent willingness to donate blood, and on their mood and self-concept, were tested. It was found that while the antecedent stimuli in different modalities could themselves induce thrills in a predictable manner, these priming stimuli, and the thrills they elicited, had relatively weak effects on the thrills subsequently induced by the Rachmaninoff and Haydn pieces. The measures of altruism, self-concept, and mood were not affected by either the antecedent variables or the thrills experience. Thrills may often accompany profound aesthetic experiences and provide their physiological underpinning, yet themselves be of limited psychological significance.

Personal reflections on the multichannel cochlear implant and a view of the future.

PubMed

Clark, Graeme M

2008-01-01

The multichannel cochlear implant is the first neural prosthesis to effectively and safely bring electronic technology into a direct physiological relation with the central nervous system and human consciousness. It is also the first cochlear implant to give speech understanding to tens of thousands of persons with profound deafness and spoken language to children born deaf in more than 80 countries. In so doing, it is the first major advance in research and technology to help deaf children communicate since Sign Language of the Deaf was developed at the Paris deaf school (L'Institut National de Jeunes Sourds de Paris) >200 years ago. Furthermore, biomedical research has been fundamental for ensuring that the multielectrode implant is safe as well as effective. More recent research has also shown that bilateral implants confer the benefits of binaural hearing. Future research using nanotechnology should see high-fidelity sound received, which would help deaf persons communicate in noise and enjoy music. Research should also lead to implants in ears with useful hearing.

Effects of Alcohol on the Endocrine System

PubMed Central

Rachdaoui, Nadia; Sarkar, Dipak K.

2013-01-01

Synopsis The endocrine system ensures a proper communication between various organs of the body to maintain a constant internal environment. The endocrine system also plays an essential role in enabling the body to respond and appropriately cope with changes in the internal or external environments, such as respond to stress and injury. These functions of the endocrine system to maintain body homeostasis are aided by its communication with the nervous system, immune system and body’s circadian mechanism. Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiological and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. PMID:24011889

Measurement tools for mental health problems and mental well-being in people with severe or profound intellectual disabilities: A systematic review.

PubMed

Flynn, Samantha; Vereenooghe, Leen; Hastings, Richard P; Adams, Dawn; Cooper, Sally-Ann; Gore, Nick; Hatton, Chris; Hood, Kerry; Jahoda, Andrew; Langdon, Peter E; McNamara, Rachel; Oliver, Chris; Roy, Ashok; Totsika, Vasiliki; Waite, Jane

2017-11-01

Mental health problems affect people with intellectual disabilities (ID) at rates similar to or in excess of the non-ID population. People with severe ID are likely to have persistent mental health problems. In this systematic review (PROSPERO 2015:CRD42015024469), we identify and evaluate the methodological quality of available measures of mental health problems or well-being in individuals with severe or profound ID. Electronic searches of ten databases identified relevant publications. Two reviewers independently reviewed titles and abstracts of retrieved records (n=41,232) and full-text articles (n=573). Data were extracted and the quality of included papers was appraised. Thirty-two papers reporting on 12 measures were included. Nine measures addressed a broad spectrum of mental health problems, and were largely observational. One physiological measure of well-being was included. The Aberrant Behavior Checklist, Diagnostic Assessment for the Severely Handicapped Scale-II and Mood, Interest and Pleasure Questionnaire are reliable measures in this population. However, the psychometric properties of six other measures were only considered within a single study - indicating a lack of research replication. Few mental health measures are available for people with severe or profound ID, particularly lacking are tools measuring well-being. Assessment methods that do not rely on proxy reports should be explored further. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

PubMed

Moran-Ramos, Sofia; He, Xuan; Chin, Elizabeth L; Tovar, Armando R; Torres, Nimbe; Slupsky, Carolyn M; Raybould, Helen E

2017-01-01

Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats

PubMed Central

Moran-Ramos, Sofia; He, Xuan; Chin, Elizabeth L.; Tovar, Armando R.; Torres, Nimbe; Slupsky, Carolyn M.; Raybould, Helen E.

2017-01-01

Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism. PMID:28196086

Co-regulation of primary mouse hepatocyte viability and function by oxygen and matrix.

PubMed

Buck, Lorenna D; Inman, S Walker; Rusyn, Ivan; Griffith, Linda G

2014-05-01

Although oxygen and extracellular matrix cues both influence differentiation state and metabolic function of primary rat and human hepatocytes, relatively little is known about how these factors together regulate behaviors of primary mouse hepatocytes in culture. To determine the effects of pericellular oxygen tension on hepatocellular function, we employed two methods of altering oxygen concentration in the local cellular microenvironment of cells cultured in the presence or absence of an extracellular matrix (Matrigel) supplement. By systematically altering medium depth and gas phase oxygen tension, we created multiple oxygen regimes (hypoxic, normoxic, and hyperoxic) and measured the local oxygen concentrations in the pericellular environment using custom-designed oxygen microprobes. From these measurements of oxygen concentrations, we derived values of oxygen consumption rates under a spectrum of environmental contexts, thus providing the first reported estimates of these values for primary mouse hepatocytes. Oxygen tension and matrix microenvironment were found to synergistically regulate hepatocellular survival and function as assessed using quantitative image analysis for cells stained with vital dyes, and assessment of secretion of albumin. Hepatocellular viability was affected only at strongly hypoxic conditions. Surprisingly, albumin secretion rates were greatest at a moderately supra-physiological oxygen concentration, and this effect was mitigated at still greater supra-physiological concentrations. Matrigel enhanced the effects of oxygen on retention of function. This study underscores the importance of carefully controlling cell density, medium depth, and gas phase oxygen, as the effects of these parameters on local pericellular oxygen tension and subsequent hepatocellular function are profound. © 2014 Wiley Periodicals, Inc.

Exposure to Acetylcholinesterase Inhibitors Alters the Physiology and Motor Function of Honeybees

PubMed Central

Williamson, Sally M.; Moffat, Christopher; Gomersall, Martha A. E.; Saranzewa, Nastja; Connolly, Christopher N.; Wright, Geraldine A.

2013-01-01

Cholinergic signaling is fundamental to neuromuscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signaling can alter the behavior of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioral sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioral effects on honeybees of exposure to a selection of pesticides that target cholinergic signaling by inhibiting acetylcholinesterase (AChE). To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behavior continuously for 15 min. At a 10 nM concentration, all the AChE inhibitors caused similar effects on behavior, notably increased grooming activity and changes in the frequency of bouts of behavior such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behavior, and a 1 μM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the four compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil) or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee AChE inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behavior that could lead to reduced survival. PMID:23386834

Exposure to acetylcholinesterase inhibitors alters the physiology and motor function of honeybees.

PubMed

Williamson, Sally M; Moffat, Christopher; Gomersall, Martha A E; Saranzewa, Nastja; Connolly, Christopher N; Wright, Geraldine A

2013-01-01

Cholinergic signaling is fundamental to neuromuscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signaling can alter the behavior of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioral sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioral effects on honeybees of exposure to a selection of pesticides that target cholinergic signaling by inhibiting acetylcholinesterase (AChE). To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behavior continuously for 15 min. At a 10 nM concentration, all the AChE inhibitors caused similar effects on behavior, notably increased grooming activity and changes in the frequency of bouts of behavior such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behavior, and a 1 μM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the four compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil) or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee AChE inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behavior that could lead to reduced survival.

Differential effects of two phospholipase D inhibitors, 1-butanol and N-acylethanolamine, on in vivo cytoskeletal organization and Arabidopsis seedling growth.

PubMed

Motes, Christy M; Pechter, Priit; Yoo, Cheol Min; Wang, Yuh-Shuh; Chapman, Kent D; Blancaflor, Elison B

2005-12-01

Plant development is regulated by numerous chemicals derived from a multitude of metabolic pathways. However, we know very little about the biological effects and functions of many of these metabolites in the cell. N-Acylethanolamines (NAEs) are a group of lipid mediators that play important roles in mammalian physiology. Despite the intriguing similarities between animals and plants in NAE metabolism and perception, not much is known about the precise function of these metabolites in plant physiology. In plants, NAEs have been shown to inhibit phospholipase Dalpha (PLDalpha) activity, interfere with abscisic acid-induced stomatal closure, and retard Arabidopsis seedling development. 1-Butanol, an antagonist of PLD-dependent phosphatidic acid production, was reported to induce defects in Arabidopsis seedling development that were somewhat similar to effects induced by elevated levels of NAE. This raised the possibility that the impact of NAE on seedling growth could be mediated in part via its influence on PLD activity. To begin to address this possibility, we conducted a detailed, comparative analysis of the effects of 1-butanol and N-lauroylethanolamine (NAE 12:0) on Arabidopsis root cell division, in vivo cytoskeletal organization, seed germination, and seedling growth. Although both NAE 12:0 and 1-butanol induced profound cytoskeletal and morphological alterations in seedlings, there were distinct differences in their overall effects. 1-Butanol induced more pronounced modifications in cytoskeletal organization, seedling growth, and cell division at concentrations severalfold higher than NAE 12:0. We propose that these compounds mediate their differential effects on cellular organization and seedling growth, in part through the differential modulation of specific PLD isoforms.

["Psychologus nemo, nisi Physiologus"--Johannes Müller and perspectives of médecine philosophique: a discovery from University's Archive].

PubMed

Scharbert, Gerhard

2010-01-01

Taking Johannes Müller's still little examined school education in then French Koblenz at its starting point, this paper argues that Miiller's pre-academic training in the applied sciences as well as in the old languages--which Müller saw as a basic essential for the philosophically educated naturalist--had a profound impact on the scientific-philosophical views he put forward in his Dissertatio inauguralis physiologica sistens commentarios de phoronomia animalium published in 1822. The Dissertatio was influenced, in particular, by the work of Pierre-Jean-Georges Cabanis (1757-1808) and can be read as a physiological application of French Enlightenment sensualist philosophy. It shows that Müller already at early moment took up decisive impulses from revolutionary France. Also, a traditional mistake is shown to have falsified a fundamental aspect of this earliest work already with lasting effect.

Food Intake and Eating Behavior After Bariatric Surgery.

PubMed

Al-Najim, Werd; Docherty, Neil G; le Roux, Carel W

2018-07-01

Obesity is an escalating global chronic disease. Bariatric surgery is a very efficacious treatment for obesity and its comorbidities. Alterations to gastrointestinal anatomy during bariatric surgery result in neurological and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut microbiota, which coalesce to exert a profound influence on eating behavior. A thorough understanding of the mechanisms underlying eating behavior is essential in the management of patients after bariatric surgery. Studies investigating candidate mechanisms have expanded dramatically in the last decade. Herein we review the proposed mechanisms governing changes in eating behavior, food intake, and body weight after bariatric surgery. Additive or synergistic effects of both conditioned and unconditioned factors likely account for the complete picture of changes in eating behavior. Considered application of strategies designed to support the underlying principles governing changes in eating behavior holds promise as a means of optimizing responses to surgery and long-term outcomes.

Diversity in arrestin function.

PubMed

Kendall, Ryan T; Luttrell, Louis M

2009-09-01

The termination of heptahelical receptor signaling is a multilevel process coordinated, in large part, by members of the arrestin family of proteins. Arrestin binding to agonist-occupied receptors promotes desensitization by interrupting receptor-G protein coupling, while simultaneously recruiting machinery for receptor endocytosis, vesicular trafficking, and receptor fate determination. By simultaneously binding other proteins, arrestins also act as ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein 'signalsome' complexes. Arrestin-binding thus 'switches' receptors from a transient G protein-coupled state to a persistent arrestin-coupled state that continues to signal as the receptor transits intracellular compartments. While it is clear that signalsome assembly has profound effects on the duration and spatial characteristics of heptahelical receptor signals, the physiologic functions of this novel signaling mechanism are poorly understood. Growing evidence suggests that signalsomes regulate such diverse processes as endocytosis and exocytosis, cell migration, survival, and contractility.

Optogenetic Tools for Subcellular Applications in Neuroscience.

PubMed

Rost, Benjamin R; Schneider-Warme, Franziska; Schmitz, Dietmar; Hegemann, Peter

2017-11-01

The ability to study cellular physiology using photosensitive, genetically encoded molecules has profoundly transformed neuroscience. The modern optogenetic toolbox includes fluorescent sensors to visualize signaling events in living cells and optogenetic actuators enabling manipulation of numerous cellular activities. Most optogenetic tools are not targeted to specific subcellular compartments but are localized with limited discrimination throughout the cell. Therefore, optogenetic activation often does not reflect context-dependent effects of highly localized intracellular signaling events. Subcellular targeting is required to achieve more specific optogenetic readouts and photomanipulation. Here we first provide a detailed overview of the available optogenetic tools with a focus on optogenetic actuators. Second, we review established strategies for targeting these tools to specific subcellular compartments. Finally, we discuss useful tools and targeting strategies that are currently missing from the optogenetics repertoire and provide suggestions for novel subcellular optogenetic applications. Copyright © 2017 Elsevier Inc. All rights reserved.

The sleep needs of adolescents.

PubMed

Kelman, B B

1999-08-01

The amount of sleep affects the way adolescents perform, feel, think, learn, and remember. Significant physiological and social changes have profound effects on adolescents' sleeping patterns. Lack of sleep increases the possibility of increased daytime sleepiness, which may result in a tragic automobile or work accident. Other consequences of sleep deprivation include poor school performance, heightened risk of drug and alcohol use, increased irritability, and aggressive behavior, all of which can interfere with relationships with classmates, parents, and teachers. The purpose of this paper is to explore the literature concerning what is known about why adolescents need more sleep and why adolescents do not obtain enough sleep. Nursing interventions targeting adolescents, parents, teachers, schools, and employers are included. If adolescents understand and learn to improve their sleep patterns while they are young, they may have improved sleep habits in adulthood. Teaching adolescents about the importance of sleep is an important task for school nurses.

The importance of interactions among nutrition, seasonality and socio-sexual factors in the development of hormone-free methods for controlling fertility.

PubMed

Scaramuzzi, R J; Martin, G B

2008-07-01

Around the world, consumers are demanding animal products that are produced to agreed standards for human health, environmental management and animal welfare. This has led to the development in Australia of the concept of 'clean, green and ethical' (CGE) animal production based on the manipulation of nutrition ('focus feeding') and the application of phenomena, such as the 'male effect', to provide 'natural' methods for managing small ruminant production systems. With respect to the management of fertility, CGE involves utilization of the inherited responses of animals to environmental factors to manipulate their reproductive processes. The successful development and implementation of this new generation of management tools depends on a thorough yet holistic understanding of the interactions among environmental factors and the ways these interactions affect reproductive physiology and behaviour of the animal. For sheep and goats, a central aspect of CGE management is the way in which ovarian function is affected by three major factors (nutrition, photoperiod and socio-sexual signals) and by interactions among them. Nutrition can exert two profound yet contrasting types of effect on ovarian activity: (i) the complete inhibition of reproduction by undernutrition through the hypothalamic mechanism that controls ovulation and (ii) the enhancement of fecundity by nutritional supplementation, through a direct ovarian mechanism, in females that are already ovulating. A similarly profound control over ovarian function in female sheep and goats is exerted by the well-known endocrine responses to photoperiod (seasonality) and to male socio-sexual signals. The 'male effect' already has a long history as a valuable technique for inducing a synchronized fertile ovulation during seasonal and post-partum anoestrus in sheep and goats. Importantly, experimentation has shown that these three major environmental factors interact, synergistically and antagonistically, but the precise nature of these interactions and their significance to reproductive outcomes are not well understood. Most research to date has been with small ruminants but CGE principles can be applied to any species in a managed environment. For example, a male effect has been reported for lactating cattle and, in the horse, the pattern of seasonality of oestrus can be altered by nutrition. Well-fed mares have a longer breeding season and some animals become non-seasonal. Similar observations have been reported for sheep and goats. By working towards a holistic perspective of the physiology, nutrition, genetics and behaviour of our animals, we will be able to formulate ways to manipulate the animals' environment that will improve management, productivity and profitability and, simultaneously, promote a CGE industry.

The medial prefrontal cortex: coordinator of autonomic, neuroendocrine and behavioural responses to stress.

PubMed

McKlveen, J M; Myers, B; Herman, J P

2015-06-01

Responding to real or potential threats in the environment requires the coordination of autonomic, neuroendocrine and behavioural processes to promote adaptation and survival. These diverging systems necessitate input from the limbic forebrain to integrate and modulate functional output in accordance with contextual demand. In the present review, we discuss the potential role of the medial prefrontal cortex (mPFC) as a coordinator of behavioural and physiological stress responses across multiple temporal and contextual domains. Furthermore, we highlight converging evidence from rodent and human research indicating the necessity of the mPFC for modulating physiological energetic systems to mobilise or limit energetic resources as needed to ultimately promote behavioural adaptation in the face of stress. We review the literature indicating that glucocorticoids act as one of the primary messengers in the reallocation of energetic resources having profound effects locally within the mPFC, as well as shaping how the mPFC acts within a network of brain structures to modulate responses to stress. Finally, we discuss how both rodent and human studies point toward a critical role of the mPFC in the coordination of anticipatory responses to stress and why this distinction is an important one to make in stress neurobiology. © 2015 British Society for Neuroendocrinology.

FEV manoeuvre induced changes in breath VOC compositions: an unconventional view on lung function tests

NASA Astrophysics Data System (ADS)

Sukul, Pritam; Schubert, Jochen K.; Oertel, Peter; Kamysek, Svend; Taunk, Khushman; Trefz, Phillip; Miekisch, Wolfram

2016-06-01

Breath volatile organic compound (VOC) analysis can open a non-invasive window onto pathological and metabolic processes in the body. Decades of clinical breath-gas analysis have revealed that changes in exhaled VOC concentrations are important rather than disease specific biomarkers. As physiological parameters, such as respiratory rate or cardiac output, have profound effects on exhaled VOCs, here we investigated VOC exhalation under respiratory manoeuvres. Breath VOCs were monitored by means of real-time mass-spectrometry during conventional FEV manoeuvres in 50 healthy humans. Simultaneously, we measured respiratory and hemodynamic parameters noninvasively. Tidal volume and minute ventilation increased by 292 and 171% during the manoeuvre. FEV manoeuvre induced substance specific changes in VOC concentrations. pET-CO2 and alveolar isoprene increased by 6 and 21% during maximum exhalation. Then they decreased by 18 and 37% at forced expiration mirroring cardiac output. Acetone concentrations rose by 4.5% despite increasing minute ventilation. Blood-borne furan and dimethyl-sulphide mimicked isoprene profile. Exogenous acetonitrile, sulphides, and most aliphatic and aromatic VOCs changed minimally. Reliable breath tests must avoid forced breathing. As isoprene exhalations mirrored FEV performances, endogenous VOCs might assure quality of lung function tests. Analysis of exhaled VOC concentrations can provide additional information on physiology of respiration and gas exchange.

The G protein-coupled estrogen receptor GPER in health and disease

PubMed Central

Prossnitz, Eric R.; Barton, Matthias

2012-01-01

Estrogens mediate profound effects throughout the body, and regulate physiological and pathological processes in both women and men. The decreased incidence of many diseases in premenopausal women is attributed to the presence of 17β-estradiol, the predominant and most potent endogenous estrogen. In addition to endogenous estrogens, however, several manmade and plant-derived molecules also exhibit estrogenic activity. Traditionally, the actions of 17β-estradiol are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ, which function as ligand-activated transcription factors. However, 17β-estradiol also mediates rapid signaling events via pathways that involve transmembrane ERs, such as G-protein-coupled ER 1, (GPER, formerly known as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling and transcriptional regulation. With the discovery of GPER-selective ligands that can selectively modulate GPER function in cell experiments and preclinical studies, and the use of GPER-knockout mice, many more potential roles for GPER are currently being elucidated. This Review highlights the physiological roles of GPER in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer. GPER is emerging as a novel therapeutic target and prognostic indicator for these diseases. PMID:21844907

Diverse Microbiota Identified in Whole Intact Nest Chambers of the Red Mason Bee Osmia bicornis (Linnaeus 1758)

PubMed Central

Keller, Alexander; Grimmer, Gudrun; Steffan-Dewenter, Ingolf

2013-01-01

Microbial activity is known to have profound impact on bee ecology and physiology, both by beneficial and pathogenic effects. Most information about such associations is available for colony-building organisms, and especially the honey bee. There, active manipulations through worker bees result in a restricted diversity of microbes present within the colony environment. Microbial diversity in solitary bee nests remains unstudied, although their larvae face a very different situation compared with social bees by growing up in isolated compartments. Here, we assessed the microbiota present in nests and pre-adults of Osmia bicornis, the red mason bee, by culture-independent pyrosequencing. We found high bacterial diversity not comparable with honey bee colonies. We identified a variety of bacteria potentially with positive or negative interactions for bee larvae. However, most of the other diverse bacteria present in the nests seem to originate from environmental sources through incorporated nest building material and stored pollen. This diversity of microorganisms may cause severe larval mortality and require specific physiological or symbiotic adaptations against microbial threats. They may however also profit from such a diverse environment through gain of mutualistic partners. We conclude that further studies of microbiota interaction in solitary bees will improve the understanding of fitness components and populations dynamics. PMID:24205188

The G-protein-coupled estrogen receptor GPER in health and disease.

PubMed

Prossnitz, Eric R; Barton, Matthias

2011-08-16

Estrogens mediate profound effects throughout the body and regulate physiological and pathological processes in both women and men. The low prevalence of many diseases in premenopausal women is attributed to the presence of 17β-estradiol, the predominant and most potent endogenous estrogen. In addition to endogenous estrogens, several man-made and plant-derived molecules, such as bisphenol A and genistein, also exhibit estrogenic activity. Traditionally, the actions of 17β-estradiol are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ, which function as ligand-activated transcription factors. However, 17β-estradiol also mediates rapid signaling events via pathways that involve transmembrane ERs, such as G-protein-coupled ER 1 (GPER; formerly known as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling and transcriptional regulation. With the discovery of GPER-selective ligands that can selectively modulate GPER function in vitro and in preclinical studies and with the use of Gper knockout mice, many more potential roles for GPER are being elucidated. This Review highlights the physiological roles of GPER in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer, for which GPER is emerging as a novel therapeutic target and prognostic indicator.

A review of the serotonin transporter and prenatal cortisol in the development of autism spectrum disorders

PubMed Central

2013-01-01

The diagnosis of autism spectrum disorder (ASD) during early childhood has a profound effect not only on young children but on their families. Aside from the physical and behavioural issues that need to be dealt with, there are significant emotional and financial costs associated with living with someone diagnosed with ASD. Understanding how autism occurs will assist in preparing families to deal with ASD, if not preventing or lessening its occurrence. Serotonin plays a vital role in the development of the brain during the prenatal and postnatal periods, yet very little is known about the serotonergic systems that affect children with ASD. This review seeks to provide an understanding of the biochemistry and physiological actions of serotonin and its termination of action through the serotonin reuptake transporter (SERT). Epidemiological studies investigating prenatal conditions that can increase the risk of ASD describe a number of factors which elevate plasma cortisol levels causing such symptoms during pregnancy such as hypertension, gestational diabetes and depression. Because cortisol plays an important role in driving dysregulation of serotonergic signalling through elevating SERT production in the developing brain, it is also necessary to investigate the physiological functions of cortisol, its action during gestation and metabolic syndromes. PMID:24103554

Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

PubMed

Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

2012-06-07

Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.

DYNAMICS OF ACRIDINE ORANGE-CELL INTERACTION

PubMed Central

Robbins, Elliott; Marcus, Philip I.

1963-01-01

The in vitro localization of acridine orange (AO) in living cells was monitored by means of fluorescence microscopy, quantitative cell viability studies, and photofluorimetric measurements following dye-cell interaction. The parameters, pH, time, dye concentration, and the metabolic state of the cell were found to exert a profound influence on the time course and distribution of staining. The parameters studied are mutually interdependent, and intracellular dye localization may be predictably altered by their appropriate manipulation. Conditions are defined whereby two morphologically distinct but physiologically interrelated reactions, namely, acridine orange particle (AOP) formation and cytoplasmic reddening (CR) may be caused, prevented, reversed, or modified. These results are explained in terms of the facilitation or inhibition of an intracytoplasmic dye-segregating mechanism, in turn affected by the rate of dye ingress and the physiological state of the cell. Whereas the accumulation of AO in AOP is compatible with cell viability, the appearance of CR is correlated with cell death. It is pointed out that meaningful interpretation of vital staining requires precise regulation of many parameters in the extracellular milieu. A scheme of cell compartmentalization with respect to AO is proposed to satisfactorily account for the effects of environmental variations on the distribution and ultimate fate of intracellular dye. The AOP are viewed as normally present acid phosphatase-positive multivesicular bodies. PMID:14079487

Diverse microbiota identified in whole intact nest chambers of the red mason bee Osmia bicornis (Linnaeus 1758).

PubMed

Keller, Alexander; Grimmer, Gudrun; Steffan-Dewenter, Ingolf

2013-01-01

Microbial activity is known to have profound impact on bee ecology and physiology, both by beneficial and pathogenic effects. Most information about such associations is available for colony-building organisms, and especially the honey bee. There, active manipulations through worker bees result in a restricted diversity of microbes present within the colony environment. Microbial diversity in solitary bee nests remains unstudied, although their larvae face a very different situation compared with social bees by growing up in isolated compartments. Here, we assessed the microbiota present in nests and pre-adults of Osmia bicornis, the red mason bee, by culture-independent pyrosequencing. We found high bacterial diversity not comparable with honey bee colonies. We identified a variety of bacteria potentially with positive or negative interactions for bee larvae. However, most of the other diverse bacteria present in the nests seem to originate from environmental sources through incorporated nest building material and stored pollen. This diversity of microorganisms may cause severe larval mortality and require specific physiological or symbiotic adaptations against microbial threats. They may however also profit from such a diverse environment through gain of mutualistic partners. We conclude that further studies of microbiota interaction in solitary bees will improve the understanding of fitness components and populations dynamics.

Global metabolic impacts of recent climate warming.

PubMed

Dillon, Michael E; Wang, George; Huey, Raymond B

2010-10-07

Documented shifts in geographical ranges, seasonal phenology, community interactions, genetics and extinctions have been attributed to recent global warming. Many such biotic shifts have been detected at mid- to high latitudes in the Northern Hemisphere-a latitudinal pattern that is expected because warming is fastest in these regions. In contrast, shifts in tropical regions are expected to be less marked because warming is less pronounced there. However, biotic impacts of warming are mediated through physiology, and metabolic rate, which is a fundamental measure of physiological activity and ecological impact, increases exponentially rather than linearly with temperature in ectotherms. Therefore, tropical ectotherms (with warm baseline temperatures) should experience larger absolute shifts in metabolic rate than the magnitude of tropical temperature change itself would suggest, but the impact of climate warming on metabolic rate has never been quantified on a global scale. Here we show that estimated changes in terrestrial metabolic rates in the tropics are large, are equivalent in magnitude to those in the north temperate-zone regions, and are in fact far greater than those in the Arctic, even though tropical temperature change has been relatively small. Because of temperature's nonlinear effects on metabolism, tropical organisms, which constitute much of Earth's biodiversity, should be profoundly affected by recent and projected climate warming.

FEV manoeuvre induced changes in breath VOC compositions: an unconventional view on lung function tests

PubMed Central

Sukul, Pritam; Schubert, Jochen K.; Oertel, Peter; Kamysek, Svend; Taunk, Khushman; Trefz, Phillip; Miekisch, Wolfram

2016-01-01

Breath volatile organic compound (VOC) analysis can open a non-invasive window onto pathological and metabolic processes in the body. Decades of clinical breath-gas analysis have revealed that changes in exhaled VOC concentrations are important rather than disease specific biomarkers. As physiological parameters, such as respiratory rate or cardiac output, have profound effects on exhaled VOCs, here we investigated VOC exhalation under respiratory manoeuvres. Breath VOCs were monitored by means of real-time mass-spectrometry during conventional FEV manoeuvres in 50 healthy humans. Simultaneously, we measured respiratory and hemodynamic parameters noninvasively. Tidal volume and minute ventilation increased by 292 and 171% during the manoeuvre. FEV manoeuvre induced substance specific changes in VOC concentrations. pET-CO2 and alveolar isoprene increased by 6 and 21% during maximum exhalation. Then they decreased by 18 and 37% at forced expiration mirroring cardiac output. Acetone concentrations rose by 4.5% despite increasing minute ventilation. Blood-borne furan and dimethyl-sulphide mimicked isoprene profile. Exogenous acetonitrile, sulphides, and most aliphatic and aromatic VOCs changed minimally. Reliable breath tests must avoid forced breathing. As isoprene exhalations mirrored FEV performances, endogenous VOCs might assure quality of lung function tests. Analysis of exhaled VOC concentrations can provide additional information on physiology of respiration and gas exchange. PMID:27311826

microRNA-200b as a Switch for Inducible Adult Angiogenesis.

PubMed

Sinha, Mithun; Ghatak, Subhadip; Roy, Sashwati; Sen, Chandan K

2015-05-10

Angiogenesis is the process by which new blood vessels develop from a pre-existing vascular system. It is required for physiological processes such as developmental biology and wound healing. Angiogenesis also plays a crucial role in pathological conditions such as tumor progression. The underlying importance of angiogenesis necessitates a highly regulated process. Recent works have demonstrated that the process of angiogenesis is regulated by small noncoding RNA molecules called microRNAs (miRs). These miRs, collectively referred to as angiomiRs, have been reported to have a profound effect on the process of angiogenesis by acting as either pro-angiogenic or anti-angiogenic regulators. In this review, we will discuss the role of miR-200b as a regulator of angiogenesis. Once the process of angiogenesis is complete, anti-angiogenic miR-200b has been reported to provide necessary braking. Downregulation of miR-200b has been reported across various tumor types, as deregulated angiogenesis is necessary for tumor development. Transient downregulation of miR-200b in wounds drives wound angiogenesis. New insights and understanding of the molecular mechanism of regulation of angiogenesis by miR-200b has opened new avenues of possible therapeutic interventions to treat angiogenesis-related patho-physiological conditions. Antioxid. Redox Signal. 22, 1257-1272.

ω-3 polyunsaturated fatty acids direct differentiation of the membrane phenotype in mesenchymal stem cells to potentiate osteogenesis

PubMed Central

Levental, Kandice R.; Surma, Michal A.; Skinkle, Allison D.; Lorent, Joseph H.; Zhou, Yong; Klose, Christian; Chang, Jeffrey T.; Hancock, John F.; Levental, Ilya

2017-01-01

Mammalian cells produce hundreds of dynamically regulated lipid species that are actively turned over and trafficked to produce functional membranes. These lipid repertoires are susceptible to perturbations from dietary sources, with potentially profound physiological consequences. However, neither the lipid repertoires of various cellular membranes, their modulation by dietary fats, nor their effects on cellular phenotypes have been widely explored. We report that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts or adipocytes results in extensive remodeling of the plasma membrane (PM), producing cell-specific membrane compositions and biophysical properties. The distinct features of osteoblast PMs enabled rational engineering of membrane phenotypes to modulate differentiation in MSCs. Specifically, supplementation with docosahexaenoic acid (DHA), a lipid component characteristic of osteoblast membranes, induced broad lipidomic remodeling in MSCs that reproduced compositional and structural aspects of the osteoblastic PM phenotype. The PM changes induced by DHA supplementation potentiated osteogenic differentiation of MSCs concurrent with enhanced Akt activation at the PM. These observations prompt a model wherein the DHA-induced lipidome leads to more stable membrane microdomains, which serve to increase Akt activity and thereby enhance osteogenic differentiation. More broadly, our investigations suggest a general mechanism by which dietary fats affect cellular physiology through remodeling of membrane lipidomes, biophysical properties, and signaling. PMID:29134198

Thalamic synaptic transmission of sensory information modulated by synergistic interaction of adenosine and serotonin.

PubMed

Yang, Ya-Chin; Hu, Chun-Chang; Huang, Chen-Syuan; Chou, Pei-Yu

2014-03-01

The thalamic synapses relay peripheral sensory information to the cortex, and constitute an important part of the thalamocortical network that generates oscillatory activities responsible for different vigilance (sleep and wakefulness) states. However, the modulation of thalamic synaptic transmission by potential sleep regulators, especially by combination of regulators in physiological scenarios, is not fully characterized. We found that somnogen adenosine itself acts similar to wake-promoting serotonin, both decreasing synaptic strength as well as short-term depression, at the retinothalamic synapse. We then combined the two modulators considering the coexistence of them in the hypnagogic (sleep-onset) state. Adenosine plus serotonin results in robust synergistic inhibition of synaptic strength and dramatic transformation of short-term synaptic depression to facilitation. These synaptic effects are not achievable with a single modulator, and are consistent with a high signal-to-noise ratio but a low level of signal transmission through the thalamus appropriate for slow-wave sleep. This study for the first time demonstrates that the sleep-regulatory modulators may work differently when present in combination than present singly in terms of shaping information flow in the thalamocortical network. The major synaptic characters such as the strength and short-term plasticity can be profoundly altered by combination of modulators based on physiological considerations. © 2013 International Society for Neurochemistry.

A Grounded Theory of Effective Reading by Profoundly Deaf Adults

ERIC Educational Resources Information Center

Silvestri, Julia; Wang, Ye

2018-01-01

The purpose of the study was to uncover and describe psycholinguistic and sociocognitive factors facilitating effective reading by signing adults who are profoundly deaf and do not use hearing technology. The sample comprised four groups, each consisting of 15 adults, for a total of 60 participants. The four groups were "deaf…

Iron deficiency beyond erythropoiesis: should we be concerned?

PubMed

Musallam, Khaled M; Taher, Ali T

2018-01-01

To consider the key implications of iron deficiency for biochemical and physiological functions beyond erythropoiesis. PubMed was searched for relevant journal articles published up to August 2017. Anemia is the most well-recognized consequence of persisting iron deficiency, but various other unfavorable consequences can develop either before or concurrently with anemia. Mitochondrial function can be profoundly disturbed since iron is a cofactor for heme-containing enzymes and non-heme iron-containing enzymes in the mitochondrial electron transport chain. Biosynthesis of heme and iron-sulfur clusters in the mitochondria is inhibited, disrupting synthesis of compounds such as hemoglobin, myoglobin, cytochromes and nitric oxide synthase. The physiological consequences include fatigue, lethargy, and dyspnea; conversely, iron repletion in iron-deficient individuals has been shown to improve exercise capacity. The myocardium, with its high energy demands, is particularly at risk from the effects of iron deficiency. Randomized trials have found striking improvements in disease severity in anemic but also non-anemic chronic heart failure patients with iron deficiency after iron therapy. In vitro and pre-clinical studies have demonstrated that iron is required by numerous enzymes involved in DNA replication and repair, and for normal cell cycle regulation. Iron is also critical for immune cell growth, proliferation, and differentiation, and for specific cell-mediated effector pathways. Observational studies have shown that iron-deficient individuals have defective immune function, particularly T-cell immunity, but more evidence is required. Pre-clinical models have demonstrated abnormal myelogenesis, brain cell metabolism, neurotransmission, and hippocampal formation in iron-deficient neonates and young animals. In humans, iron deficiency anemia is associated with poorer cognitive and motor skills. However, the impact of iron deficiency without anemia is less clear. The widespread cellular and physiological effects of iron deficiency highlight the need for early detection and treatment of iron deficiency, both to ameliorate these non-erythropoietic effects, and to avoid progression to iron deficiency anemia.

Circadian rhythms, time-restricted feeding, and healthy aging.

PubMed

Manoogian, Emily N C; Panda, Satchidananda

2017-10-01

Circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function, and behavior. These endogenous rhythms dampen with age and thus compromise temporal coordination. Feeding-fasting patterns are an external cue that profoundly influence the robustness of daily biological rhythms. Erratic eating patterns can disrupt the temporal coordination of metabolism and physiology leading to chronic diseases that are also characteristic of aging. However, sustaining a robust feeding-fasting cycle, even without altering nutrition quality or quantity, can prevent or reverse these chronic diseases in experimental models. In humans, epidemiological studies have shown erratic eating patterns increase the risk of disease, whereas sustained feeding-fasting cycles, or prolonged overnight fasting, is correlated with protection from breast cancer. Therefore, optimizing the timing of external cues with defined eating patterns can sustain a robust circadian clock, which may prevent disease and improve prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Cardiovascular health and fitness after stroke.

PubMed

Ivey, F M; Macko, R F; Ryan, A S; Hafer-Macko, C E

2005-01-01

Stroke patients have profound cardiovascular and muscular deconditioning, with metabolic fitness levels that are about half those found in age-matched sedentary controls. Physical deconditioning, along with elevated energy demands of hemiparetic gait, define a detrimental combination termed diminished physiological fitness reserve that can greatly limit that can greatly limit performance of activities of daily living. The physiological features that underlie worsening metabolic fitness in the chronic phase of stroke include gross muscular atrophy, altered muscle molecular phenotype, increased intramuscular area fat, elevated tissue inflammatory markers, and diminished peripheral blood flow dynamics. Epidemiological evidence further suggests that the reduced cardiovascular fitness and secondary biological changes in muscle may propagate components of the metabolic syndrome, conferring added morbidity and mortality risk. This article reviews some of the consequences of poor fitness in chronic stroke and the potential biological underpinnings that support a rationale for more aggressive approaches to exercise therapy in this population.

Traffic noise causes physiological stress and impairs breeding migration behaviour in frogs

PubMed Central

Tennessen, Jennifer B.; Parks, Susan E.; Langkilde, Tracy

2014-01-01

Human-generated noise has profoundly changed natural soundscapes in aquatic and terrestrial ecosystems, imposing novel pressures on ecological processes. Despite interest in identifying the ecological consequences of these altered soundscapes, little is known about the sublethal impacts on wildlife population health and individual fitness. We present evidence that noise induces a physiological stress response in an amphibian and impairs mate attraction in the natural environment. Traffic noise increased levels of a stress-relevant glucocorticoid hormone (corticosterone) in female wood frogs (Lithobates sylvaticus) and impaired female travel towards a male breeding chorus in the field, providing insight into the sublethal consequences of acoustic habitat loss. Given that prolonged elevated levels of corticosterone can have deleterious consequences on survival and reproduction and that impaired mate attraction can impact population persistence, our results suggest a novel pathway by which human activities may be imposing population-level impacts on globally declining amphibians. PMID:27293653

Traffic noise causes physiological stress and impairs breeding migration behaviour in frogs.

PubMed

Tennessen, Jennifer B; Parks, Susan E; Langkilde, Tracy

2014-01-01

Human-generated noise has profoundly changed natural soundscapes in aquatic and terrestrial ecosystems, imposing novel pressures on ecological processes. Despite interest in identifying the ecological consequences of these altered soundscapes, little is known about the sublethal impacts on wildlife population health and individual fitness. We present evidence that noise induces a physiological stress response in an amphibian and impairs mate attraction in the natural environment. Traffic noise increased levels of a stress-relevant glucocorticoid hormone (corticosterone) in female wood frogs (Lithobates sylvaticus) and impaired female travel towards a male breeding chorus in the field, providing insight into the sublethal consequences of acoustic habitat loss. Given that prolonged elevated levels of corticosterone can have deleterious consequences on survival and reproduction and that impaired mate attraction can impact population persistence, our results suggest a novel pathway by which human activities may be imposing population-level impacts on globally declining amphibians.

Sex steroids and the GH axis: Implications for the management of hypopituitarism.

PubMed

Birzniece, Vita; Ho, Ken K Y

2017-02-01

Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism. Copyright © 2017 Elsevier Ltd. All rights reserved.

The health effects of economic insecurity.

PubMed Central

Catalano, R

1991-01-01

BACKGROUND. Interest in the health and behavioral effects of economic insecurity appears to vary with the performance of the economy. The current recession in the United States and Western Europe and growing unemployment in Eastern Europe make it timely to analytically review the recent research concerned with the health effects of economic contraction. METHODS. The research concerned with the health and behavioral effects of economic insecurity is organized by dependent variable and method. Rules for determining which effects are supported by strong and which by weak evidence are developed and applied to the literature. RESULTS. Evidence for effects on symptoms of psychological distress, seeking help for psychological distress, and nonspecific physiological illness is strong. Evidence for effects on suicide, child abuse, adverse birth outcomes, and heart disease is characterized as weak or sufficiently controversial to warrant skepticism. CONCLUSIONS. The health effects of economic security are undoubtedly mediated by economic policies. Estimating the effect of policy alternatives on the incidence of various outcomes is, however, very difficult given the current state of the research. The effect of rising unemployment on health in Eastern Europe cannot, moreover, be estimated from existing research. Effects estimated from Western economies probably do not generalize to situations in which the meaning of economic insecurity is conditioned by profound social and political reforms. PMID:1951825

A comparison of the effects of four therapy procedures on concentration and responsiveness in people with profound learning disabilities.

PubMed

Lindsay, W R; Pitcaithly, D; Geelen, N; Buntin, L; Broxholme, S; Ashby, M

1997-06-01

This paper is an investigation into the efficacy of four therapeutic treatment procedures increasingly used with people with profound learning disabilities: snoezelen, hand massage/aromatherapy, relaxation, and active therapy (a bouncy castle). In particular, the effects of these procedures on concentration and responsiveness were examined. Eight subjects with profound learning disabilities took part in the study and each subject received each of the treatments. To assess the effects of the treatments, simple concentration tasks were administered and the subjects' responsiveness to each treatment was rated by independent observers. The results suggest that both snoezelen and relaxation had a positive effect on concentration and seemed to be the most enjoyable therapies for clients, whereas hand massage/aromatherapy and active therapy had no or even negative effects on concentration and appeared less enjoyable.

Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

PubMed

Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

2017-10-01

In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.

Normalizing the environment recapitulates adult human immune traits in laboratory mice.

PubMed

Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

2016-04-28

Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

Brain local and regional neuroglial alterations in Alzheimer's Disease: cell types, responses and implications.

PubMed

Toledano, Adolfo; Álvarez, María-Isabel; Toledano-Díaz, Adolfo; Merino, José-Joaquín; Rodríguez, José Julio

2016-01-01

From birth to death, neurons are dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. Three families have been classically considered within the CNS: astroglia, oligodendroglia and microglia. Many types/subtypes (including NGR2+ cells), with a wide variety of physiological and pathological effects on neurons, have been described using morphological and immunocytochemical criteria. Glio-glial, glio-neuronal and neuro-glial cell signaling and gliotransmission are phenomena that are essential to support brain functions. Morphofunctional changes resulting from the plasticity of all the glial cell types parallel the plastic neuronal changes that optimize the functionality of neuronal circuits. Moreover, neuroglia possesses the ability to adopt a reactive status (gliosis) in which, generally, new functions arise to improve and restore if needed the neural functionality. All these features make neuroglial cells elements of paramount importance when attempting to explain any physiological or pathological processes in the CNS, because they are involved in both, neuroprotection/neurorepair and neurodegeneration. There exist diverse and profound, regional and local, neuroglial changes in all involutive processes (physiological and pathological aging; neurodegenerative disorders, including Alzheimer ´s disease -AD-), but today, the exact meaning of such modifications (the modifications of the different neuroglial types, in time and place), is not well understood. In this review we consider the different neuroglial cells and their responses in order to understand the possible role they fulfill in pathogenesis, diagnosis and treatment (preventive or palliative) of AD. The existence of differentiated and/or concurrent pathogenic and neuro-protective/neuro-restorative astroglial and microglial responses is highlighted.

Two years of combined high-intensity physical training and heat acclimatization affect lymphocyte and serum HSP70 in purebred military working dogs.

PubMed

Bruchim, Yaron; Aroch, Itamar; Eliav, Ady; Abbas, Atallah; Frank, Ilan; Kelmer, Efrat; Codner, Carolina; Segev, Gilad; Epstein, Yoram; Horowitz, Michal

2014-07-15

Military working dogs in hot countries undergo exercise training at high ambient temperatures for at least 9 mo annually. Physiological adaptations to these harsh conditions have been extensively studied; however, studies focusing on the underlying molecular adaptations are limited. In the current study, military working dogs were chosen as a model to examine the effects of superimposing endurance exercise on seasonal acclimatization to environmental heat stress. The lymphocyte HSP70 profile and extracellular HSP70 were studied in tandem with physiological performance in the dogs from their recruitment for the following 2 yr. Aerobic power and heat shock proteins were measured at the end of each summer, with physical performance tests (PPTs) in an acclimatized room (22°C). The study shows that together with a profound enhancement of aerobic power and physical performance, hsp72 mRNA induction immediately post-PPT and 45 min later, progressively increased throughout the study period (relative change in median lymphocyte hsp72 mRNA first PPT, 4.22 and 12.82; second PPT, 17.19 and 109.05, respectively), whereas induction of HSP72 protein was stable. These responses suggest that cellular/molecular adaptive tools for maintaining HSP72 homeostasis exist. There was also a significant rise in basal and peak median optical density extracellular HSP at the end of each exercise test (first PPT, 0.13 and 0.15; second PPT, 1.04 and 1.52, respectively). The relationship between these enhancements and improved aerobic power capacity is not yet fully understood. Copyright © 2014 the American Physiological Society.

Physiological Ranges of Matrix Rigidity Modulate Primary Mouse Hepatocyte Function In Part Through Hepatocyte Nuclear Factor 4 Alpha

PubMed Central

Desai, Seema S.; Tung, Jason C.; Zhou, Vivian X.; Grenert, James P.; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M.; Chang, Tammy T.

2016-01-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of hepatic-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150Pa and increased to 1–6kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α) whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase (FAK). In addition, blockade of the Rho/Rho-associated protein kinase (ROCK) pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/ROCK pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. PMID:26755329

Impacts of particulate matter pollution on plants: Implications for environmental biomonitoring.

PubMed

Rai, Prabhat Kumar

2016-07-01

Air pollution is one of the serious problems world is facing in recent Anthropocene era of rapid industrialization and urbanization. Specifically particulate matter (PM) pollution represents a threat to both the environment and human health. The changed ambient environment due to the PM pollutant in urban areas has exerted a profound influence on the morphological, biochemical and physiological status of plants and its responses. Taking into account the characteristics of the vegetation (wide distribution, greater contact area etc.) it turns out to be an effective indicator of the overall impact of PM pollution and harmful effects of PM pollution on vegetation have been reviewed in the present paper, covering an extensive span of 1960 to March 2016. The present review critically describes the impact of PM pollution and its constituents (e.g. heavy metals and poly-aromatic hydrocarbons) on the morphological attributes such as leaf area, leaf number, stomata structure, flowering, growth and reproduction as well as biochemical parameters such as pigment content, enzymes, ascorbic acid, protein, sugar and physiological aspect such as pH and Relative water content. Further, the paper provides a brief overview on the impact of PM on biodiversity and climate change. Moreover, the review emphasizes the genotoxic impacts of PM on plants. Finally, on the basis of such studies tolerant plants as potent biomonitors with high Air Pollution Tolerance Index (APTI) and Air Pollution Index (API) can be screened and may be recommended for green belt development. Copyright © 2016 Elsevier Inc. All rights reserved.

Routine habitat change: a source of unrecognized transient alteration of intestinal microbiota in laboratory mice.

PubMed

Ma, Betty W; Bokulich, Nicholas A; Castillo, Patricia A; Kananurak, Anchasa; Underwood, Mark A; Mills, David A; Bevins, Charles L

2012-01-01

The mammalian intestine harbors a vast, complex and dynamic microbial population, which has profound effects on host nutrition, intestinal function and immune response, as well as influence on physiology outside of the alimentary tract. Imbalance in the composition of the dense colonizing bacterial population can increase susceptibility to various acute and chronic diseases. Valuable insights on the association of the microbiota with disease critically depend on investigation of mouse models. Like in humans, the microbial community in the mouse intestine is relatively stable and resilient, yet can be influenced by environmental factors. An often-overlooked variable in research is basic animal husbandry, which can potentially alter mouse physiology and experimental outcomes. This study examined the effects of common husbandry practices, including food and bedding alterations, as well as facility and cage changes, on the gut microbiota over a short time course of five days using three culture-independent techniques, quantitative PCR, terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). This study detected a substantial transient alteration in microbiota after the common practice of a short cross-campus facility transfer, but found no comparable alterations in microbiota within 5 days of switches in common laboratory food or bedding, or following an isolated cage change in mice acclimated to their housing facility. Our results highlight the importance of an acclimation period following even simple transfer of mice between campus facilities, and highlights that occult changes in microbiota should be considered when imposing husbandry variables on laboratory animals.

Nuclear Receptors in Bone Physiology and Diseases

PubMed Central

Youn, Min-Young; Inoue, Kazuki; Takada, Ichiro; Kouzmenko, Alexander; Kato, Shigeaki

2013-01-01

During the last decade, our view on the skeleton as a mere solid physical support structure has been transformed, as bone emerged as a dynamic, constantly remodeling tissue with systemic regulatory functions including those of an endocrine organ. Reflecting this remarkable functional complexity, distinct classes of humoral and intracellular regulatory factors have been shown to control vital processes in the bone. Among these regulators, nuclear receptors (NRs) play fundamental roles in bone development, growth, and maintenance. NRs are DNA-binding transcription factors that act as intracellular transducers of the respective ligand signaling pathways through modulation of expression of specific sets of cognate target genes. Aberrant NR signaling caused by receptor or ligand deficiency may profoundly affect bone health and compromise skeletal functions. Ligand dependency of NR action underlies a major strategy of therapeutic intervention to correct aberrant NR signaling, and significant efforts have been made to design novel synthetic NR ligands with enhanced beneficial properties and reduced potential negative side effects. As an example, estrogen deficiency causes bone loss and leads to development of osteoporosis, the most prevalent skeletal disorder in postmenopausal women. Since administration of natural estrogens for the treatment of osteoporosis often associates with undesirable side effects, several synthetic estrogen receptor ligands have been developed with higher therapeutic efficacy and specificity. This review presents current progress in our understanding of the roles of various nuclear receptor-mediated signaling pathways in bone physiology and disease, and in development of advanced NR ligands for treatment of common skeletal disorders. PMID:23589826

Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

PubMed Central

Saupe, E. E.; Hendricks, J. R.; Portell, R. W.; Dowsett, H. J.; Haywood, A.; Hunter, S. J.; Lieberman, B. S.

2014-01-01

In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species' physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species' environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species' upper and lower thermal tolerances are constrained across this interval. We find that these species' environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and future warming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species' present-day environmental requirements to future climatic landscapes to assess conservation risks. PMID:25297868

Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

USGS Publications Warehouse

Saupe, E.E.; Hendricks, J.R.; Portell, R.W.; Dowsett, Harry J.; Haywood, A. M.; Hunter, S.J.; Lieberman, B.S.

2014-01-01

In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species' physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species' environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species' upper and lower thermal tolerances are constrained across this interval. We find that these species' environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and future warming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species' present-day environmental requirements to future climatic landscapes to assess conservation risks.

The effects of poly-unsaturated fatty acids on the physiology of hibernation in a South American marsupial, Dromiciops gliroides.

PubMed

Contreras, Carolina; Franco, Marcela; Place, Ned J; Nespolo, Roberto F

2014-11-01

Many mammals hibernate, which is a profound lethargic state of several weeks or months during winter, that represents a transitory episode of hetherothermy. As with other cases of dormancy, the main benefit of hibernation seems to be energy saving. However, the depth and duration of torpor can be experimentally modified by the composition of food, especially by fattyacid composition. In eutherians, diets rich in unsaturated fatty acids (i.e., fatty acids with at least one double bond) lengthen torpor, reduce metabolism and permit hibernation at lower temperatures. Here we studied whether diets varying in fatty acid composition have an effect on the physiology of hibernation in a South American marsupial, Dromiciops gliroides. We designed a factorial experiment where thermal acclimation (two levels: natural versus constant temperature) was combined with diet acclimation: saturated (i.e., diets with high concentration of saturated fatty acids) versus unsaturated (i.e., diets with high concentration of unsaturated fatty acids). We measured energy metabolism in active and torpid individuals, as well as torpor duration, and a suite of 12 blood biochemical parameters. After a cafeteria test, we found that D. gliroides did not show any preference for a given diet. Also, we did not find effects of diet on body temperature during torpor, or its duration. However, saturated diets, combined with high temperatures provoked a disproportionate increase in fat utilization, leading to body mass reduction. Those animals were more active, and metabolized more fats than those fed with a high proportion of unsaturated fatty acids (="unsaturated diets"). These results contrast with previous studies, which showed a significant effect of fatty acid composition of diets on food preferences and torpor patterns in mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of hydration state and energy balance on innate immunity of a desert reptile.

PubMed

Moeller, Karla T; Butler, Michael W; Denardo, Dale F

2013-05-04

Immune function is a vital physiological process that is often suppressed during times of resource scarcity due to investments in other physiological systems. While energy is the typical currency that has been examined in such trade-offs, limitations of other resources may similarly lead to trade-offs that affect immune function. Specifically, water is a critical resource with profound implications for organismal ecology, yet its availability can fluctuate at local, regional, and even global levels. Despite this, the effect of osmotic state on immune function has received little attention. Using agglutination and lysis assays as measures of an organism's plasma concentration of natural antibodies and capacity for foreign cell destruction, respectively, we tested the independent effects of osmotic state, digestive state, and energy balance on innate immune function in free-ranging and laboratory populations of the Gila monster, Heloderma suspectum. This desert-dwelling lizard experiences dehydration and energy resource fluctuations on a seasonal basis. Dehydration was expected to decrease innate immune function, yet we found that dehydration increased lysis and agglutination abilities in both lab and field studies, a relationship that was not simply an effect of an increased concentration of immune molecules. Laboratory-based differences in digestive state were not associated with lysis or agglutination metrics, although in our field population, a loss of fat stores was correlated with an increase in lysis. Depending on the life history of an organism, osmotic state may have a greater influence on immune function than energy availability. Thus, consideration of osmotic state as a factor influencing immune function will likely improve our understanding of ecoimmunology and the disease dynamics of a wide range of species.

The effect of hydration state and energy balance on innate immunity of a desert reptile

PubMed Central

2013-01-01

Introduction Immune function is a vital physiological process that is often suppressed during times of resource scarcity due to investments in other physiological systems. While energy is the typical currency that has been examined in such trade-offs, limitations of other resources may similarly lead to trade-offs that affect immune function. Specifically, water is a critical resource with profound implications for organismal ecology, yet its availability can fluctuate at local, regional, and even global levels. Despite this, the effect of osmotic state on immune function has received little attention. Results Using agglutination and lysis assays as measures of an organism’s plasma concentration of natural antibodies and capacity for foreign cell destruction, respectively, we tested the independent effects of osmotic state, digestive state, and energy balance on innate immune function in free-ranging and laboratory populations of the Gila monster, Heloderma suspectum. This desert-dwelling lizard experiences dehydration and energy resource fluctuations on a seasonal basis. Dehydration was expected to decrease innate immune function, yet we found that dehydration increased lysis and agglutination abilities in both lab and field studies, a relationship that was not simply an effect of an increased concentration of immune molecules. Laboratory-based differences in digestive state were not associated with lysis or agglutination metrics, although in our field population, a loss of fat stores was correlated with an increase in lysis. Conclusions Depending on the life history of an organism, osmotic state may have a greater influence on immune function than energy availability. Thus, consideration of osmotic state as a factor influencing immune function will likely improve our understanding of ecoimmunology and the disease dynamics of a wide range of species. PMID:23642164

The Effectiveness of a Constant Time Delay Procedure on Teaching Lifetime Sport Skills to Adolescents with Severe to Profound Intellectual Disabilities.

ERIC Educational Resources Information Center

Zhang, Jiabei; And Others

1995-01-01

A constant time delay (CTD) procedure was used to teach four adolescents with severe/profound intellectual disabilities to perform bowling, throwing, and putting. Results indicated that the adolescents could be effectively taught gross motor lifetime sport skills with the CTD procedure and that verbal description plus physical assistance could be…

Fast, Power-Rich Space Transportation Key to Human Space Exploration and Survival

NASA Astrophysics Data System (ADS)

Chang-Diaz, F.

2002-01-01

above the rest: Physiological debilitation, radiation sickness and psychological stress. Many counter-measures are presently being considered to ameliorate these difficulties; however, in the long run, two important new developments are required: abundant space power and advanced propulsion. Recent initiatives are beginning to focus on these long-term issues. As a result, important technologies currently in the conceptual realm are now being considered for rapid test and deployment. This presentation discusses the promises and the challenges of the new approaches and the profound impact they will have on our capability to survive and explore our new human frontier.

Failure of perception of hypocapnia: physiological and clinical implications.

PubMed Central

King, J C; Rosen, S D; Nixon, P G

1990-01-01

Hyperventilation causes hypocapnia and respiratory alkalosis and thereby predisposes to coronary vasoconstriction and cardiac arrhythmia. Diagnostic methods for use between episodes have not been established. In this study of 100 patients and 25 control subjects the resting end-tidal PCO2 (Pet CO2) levels and the results of a forced hyperventilation test did not show a significant difference between the groups. However the patients hyperventilated more profoundly in response to emotional stimulation, and were less aware of inappropriate breathing and hypocapnia. It is suggested that these differences should be accommodated in cardiac rehabilitation. PMID:2125316

An overview of the domestication and impact of the Salmonella mobilome.

PubMed

Mebrhatu, Mehari Tesfazgi; Cenens, William; Aertsen, Abram

2014-02-01

Salmonella spp. are accountable for a large fraction of the global infectious disease burden, with most of their infections being food- or water-borne. The phenotypic features and adaptive potential of Salmonella spp. appear to be driven to a large extent by mobile or laterally acquired genetic elements. A better understanding of the conduct and diversification of these important pathogens consequently requires a more profound insight into the different mechanisms by which these pivotal elements establish themselves in the cell and affect its behavior. This review, therefore, provides an overview of the physiological impact and domestication of the Salmonella mobilome.

Achieving profound anesthesia using the intraosseous technique.

PubMed

Coury, K A

1997-10-01

The intraosseous technique has been described as a useful adjunct to primary anesthetic administration. It has several advantages (Table 3) over other supplemental techniques in that it is relatively simple to implement into routine practice, it affords fast, predictable results, and it is relatively painless. The technique has been shown to be very successful in achieving profound pulpal anesthesia when administered as a supplement to the inferior alveolar nerve block and is effective in achieving profound anesthesia in irreversibly inflamed teeth, especially mandibular molars.

Effects of ambient stimuli on measures of behavioral state and microswitch use in adults with profound multiple impairments.

PubMed

Murphy, Kathleen M; Saunders, Muriel D; Saunders, Richard R; Olswang, Lesley B

2004-01-01

The effects of different types and amounts of environmental stimuli (visual and auditory) on microswitch use and behavioral states of three individuals with profound multiple impairments were examined. The individual's switch use and behavioral states were measured under three setting conditions: natural stimuli (typical visual and auditory stimuli in a recreational situation), reduced visual stimuli, and reduced visual and auditory stimuli. Results demonstrated differential switch use in all participants with the varying environmental setting conditions. No consistent effects were observed in behavioral state related to environmental condition. Predominant behavioral state scores and switch use did not systematically covary with any participant. Results suggest the importance of considering environmental stimuli in relationship to switch use when working with individuals with profound multiple impairments.

Laminar shear stress regulates endothelial kinin B1 receptor expression and function: potential implication in atherogenesis

PubMed Central

Duchene, Johan; Cayla, Cécile; Vessillier, Sandrine; Scotland, Ramona; Yamashiro, Kazuo; Lecomte, Florence; Syed, Irfan; Vo, Phuong; Marrelli, Alessandra; Pitzalis, Costantino; Cipollone, Francesco; Schanstra, Joost; Bascands, Jean-Loup; Hobbs, Adrian J; Perretti, Mauro; Ahluwalia, Amrita

2009-01-01

OBJECTIVE The pro-inflammatory phenotype induced by low laminar shear stress (LSS) is implicated in atherogenesis. The kinin B1 receptor (B1R), known to be induced by inflammatory stimuli, exerts many pro-inflammatory effects including vasodilatation and leukocyte recruitment. We investigated whether low LSS is a stimulus for endothelial B1R expression and function. METHODS AND RESULTS Human and mouse atherosclerotic plaques expressed high level of B1R mRNA and protein. In addition, B1R expression was upregulated in the aortic arch (low LSS region) of ApoE-/- mice fed a high fat diet compared to vascular regions of high LSS and animals fed normal chow. Of interest, a greater expression of B1R was noticed in endothelial cells from regions of low LSS in aortic arch of ApoE-/- mice. B1R was also upregulated in human umbilical vein endothelial cells (HUVEC) exposed to low LSS (0-2dyn/cm2) compared to physiological LSS (6-10dyn/cm2): an effect similarly evident in murine vascular tissue perfused ex vivo. Functionally, B1R activation increased prostaglandin and CXCL5 expression in cells exposed to low, but not physiological, LSS. IL-1β and ox-LDL induced B1R expression and function in HUVECs, a response substantially enhanced under low LSS conditions and inhibited by blockade of NFκB activation. CONCLUSION Herein, we show that LSS is a major determinant of functional B1R expression in endothelium. Furthermore, whilst physiological high LSS is a powerful repressor of this inflammatory receptor, low LSS at sites of atheroma are associated with substantial upregulation, identifying this receptor as a potential therapeutic target. CONDENSED ABSTRACT Low laminar shear stress (LSS) underlies the pro-inflammatory processes in atherogenesis. Herein, we demonstrate that whilst physiological LSS represses inflammatory kinin B1 receptor (B1R) expression/function, low atherogenic LSS is associated with profound upregulation of both in atherosclerosis in both humans and animal models, highlighting B1R as an exciting potential therapeutic target. PMID:19661485

Does Aggressive Phototherapy Increase Mortality while Decreasing Profound Impairment among the Smallest and Sickest Newborns?

PubMed Central

Tyson, Jon E; Pedroza, Claudia; Langer, John; Green, Charles; Morris, Brenda; Stevenson, David; Van Meurs, Krisa P.; Oh, William; Phelps, Dale; O’Shea, Michael; McDavid, Georgia E.; Grisby, Cathy; Higgins, Rose

2013-01-01

Objective Aggressive phototherapy (AgPT) is widely used and assumed to be safe and effective for even the most immature infants. We assessed whether the benefits and hazards for the smallest and sickest infants differed from those for other extremely low birth weight (ELBW; (≤1000 g) infants in our Neonatal Research Network trial, the only large trial of AgPT. Study Design ELBW infants (n=1974) were randomized to AgPT or conservative phototherapy at age 12–36 hours. The effect of AgPT on outcomes (death; impairment; profound impairment; death or impairment [primary outcome], and death or profound impairment) at 18–22 months corrected age was related to BW stratum (501–750 g; 751–1000 g) and baseline severity of illness using multilevel regression equations. The probability of benefit and of harm was directly assessed with Bayesian analyses. Results Baseline illness severity was well characterized using mechanical ventilation and FiO2 at 24 hours age. Among mechanically ventilated infants ≤750 g BW (n =684), a reduction in impairment and in profound impairment was offset by higher mortality (p for interaction <0.05) with no significant effect on composite outcomes. Conservative Bayesian analyses of this subgroup identified a 99% (posterior) probability that AgPT increased mortality, a 97% probability that AgPT reduced impairment, and a 99% probability that AgPT reduced profound impairment. Conclusions Findings from the only large trial of AgPT suggest that AgPT may increase mortality while reducing impairment and profound impairment among the smallest and sickest infants. New approaches to reduce their serum bilirubin need development and rigorous testing. PMID:22652561

The Metronome of Symbiosis: Interactions Between Microbes and the Host Circadian Clock.

PubMed

Heath-Heckman, Elizabeth A C

2016-11-01

The entrainment of circadian rhythms, physiological cycles with a period of about 24 h, is regulated by a variety of mechanisms, including nonvisual photoreception. While circadian rhythms have been shown to be integral to many processes in multicellular organisms, including immune regulation, the effect of circadian rhythms on symbiosis, or host-microbe interactions, has only recently begun to be studied. This review summarizes recent work in the interactions of both pathogenic and mutualistic associations with host and symbiont circadian rhythms, focusing specifically on three mutualistic systems in which this phenomenon has been best studied. One important theme taken from these studies is the fact that mutualisms are profoundly affected by the circadian rhythms of the host, but that the microbial symbionts in these associations can, in turn, manipulate host rhythms. The interplay between circadian rhythms and symbiosis is a promising new field with effects that should be kept in mind when designing future studies across biology. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

ALCOHOL AND THE PREFRONTAL CORTEX

PubMed Central

Abernathy, Kenneth; Chandler, L. Judson; Woodward, John J.

2013-01-01

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. PMID:20813246

Epidemiology, natural history, and management of urinary tract infections in pregnancy.

PubMed

Andriole, V T; Patterson, T F

1991-03-01

The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic UTIs in women with bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic UTI and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery.

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures.

PubMed

Potter, Gregory D M; Skene, Debra J; Arendt, Josephine; Cade, Janet E; Grant, Peter J; Hardie, Laura J

2016-12-01

Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, the Oprm1 (-/-) Mouse.

PubMed

Garbugino, Luciana; Centofante, Eleonora; D'Amato, Francesca R

2016-01-01

Environmental enrichment has been proven to have positive effects on both behavioral and physiological phenotypes in rodent models of mental and neurodevelopmental disorders. In this study, we used mice lacking the µ-opioid receptor gene (Oprm1 (-/-)), which has been shown to have deficits in social competence and communication, to assess the hypothesis that early enrichment can ameliorate sociability during development and adulthood. Due to the immaturity of sensory-motor capabilities of young pups, we chose as environmental stimulation a second lactating female, who provided extra maternal care and stimulation from birth. The results show that double mothering normalized the abnormal response to maternal separation in Oprm1 (-/-) pups and increased social motivation in juveniles and adult knockout mice. Additionally, we observed that Oprm1 (-/-) mice act as less attractive social partners than wild types, which suggests that social motivation can be modulated by the stimulus employed. This experiment supports previous findings suggesting that early social environmental stimulation has profound and long-term beneficial effects, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases.

An enteric virus can replace the beneficial function of commensal bacteria

PubMed Central

Kernbauer, Elisabeth; Ding, Yi; Cadwell, Ken

2014-01-01

Intestinal microbial communities have profound effects on host physiology1. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined2,3. Here, we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germfree or antibiotics-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells (ILCs) observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signaling. Consistent with this observation, the IFNα receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of antibiotics-treatment in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity akin to commensal bacteria. PMID:25409145

PEG-chitosan hydrogel with tunable stiffness for study of drug response of breast cancer cells

PubMed Central

Chang, Fei-Chien; Tsao, Ching-Ting; Lin, Anqi; Zhang, Mengying; Levengood, Sheeny Lan; Zhang, Miqin

2016-01-01

Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defined stiffness is invaluable for studying the interactions of cells with their biophysical microenvironment in vitro. We demonstrate a methoxypolyethylene glycol (mPEG)-modified chitosan hydrogel network where hydrogel stiffness can be easily modulated under physiological conditions by adjusting the degree of mPEG grafting onto chitosan (PEGylation). We show that the storage modulus of the hydrogel increases as PEGylation decreases and the gels exhibit instant self-recovery after deformation. Breast cancer cells cultured on the stiffest hydrogels adopt a more malignant phenotype with increased resistance to doxorubicin as compared with cells cultured on tissue culture polystyrene or Matrigel. This work demonstrates the utility of mPEG-modified chitosan hydrogel, with tunable mechanical properties, as an improved replacement of conventional culture system for in vitro characterization of breast cancer cell phenotype and evaluation of cancer therapies. PMID:27595012

Multi-Sensory Rooms: Comparing Effects of the Snoezelen and the Stimulus Preference Environment on the Behavior of Adults with Profound Mental Retardation

ERIC Educational Resources Information Center

Fava, Leonardo; Strauss, Kristin

2010-01-01

The present study examined whether Snoezelen and Stimulus Preference environments have differential effects on disruptive and pro-social behaviors in adults with profound mental retardation and autism. In N = 27 adults these target behaviors were recorded for a total of 20 sessions using both multi-sensory rooms. Three comparison groups were…

Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners.

PubMed

Griffiths, Colin; Smith, Martine

2016-03-01

People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the methodological approach that was used to achieve this. In this qualitative study, two dyads consisting of a person with severe or profound intellectual and multiple disability and a teacher or carer were filmed as they engaged in school-based activities. Two 1-hour videotapes were transcribed and analysed using grounded theory. Attuning was identified within the theory proposed here as a central process that calibrates and regulates communication. Attuning is conceptualized as a bidirectional, dyadic communication process. Understanding this process may support more effective communication between people with severe or profound intellectual and multiple disability and their interaction partners. © 2015 John Wiley & Sons Ltd.

Fosfomycin residues in colostrum: Impact on morpho-physiology and microbiology of suckling piglets.

PubMed

Fernández Paggi, M B; Martínez, G; Diéguez, S N; Pérez Gaudio, D S; Decundo, J M; Riccio, M B; Amanto, F A; Tapia, M O; Soraci, A L

2018-06-01

Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms for the treatment of a wide variety of bacterial infections. In this study, the elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of this antibiotic on the microbiota and intestinal morpho-physiology of suckling piglets were analyzed. The average amount of fosfomycin eliminated in colostrum (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85 μg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The elimination profile of fosfomycin concentrations in colostrum occurs at a time of profound changes in the morpho-physiology of the gastrointestinal tract of the piglet. However, the studied concentrations did not produce imbalances on the microbiota or on the morpho-physiology of the gastrointestinal tract of the piglet. Concentrations of fosfomycin were maintained in the mammary gland above the MIC for more than 8 hr for pathogenic bacteria of productive importance. This would indicate that fosfomycin may be considered safe for the specific treatment of bacterial infectious processes in sows during the peri- and postpartum period. This first study with disodium fosfomycin stimulates awareness in the proper use of antimicrobials at farrowing. © 2018 John Wiley & Sons Ltd.

Circadian clocks in symbiotic corals: the duet between Symbiodinium algae and their coral host.

PubMed

Sorek, Michal; Díaz-Almeyda, Erika M; Medina, Mónica; Levy, Oren

2014-04-01

To date, the association and synchronization between two organismal circadian clocks ticking in parallel as part of a meta-organism (termed a symbiotic association), have rarely been investigated. Reef-building corals exhibit complex rhythmic responses to diurnal, lunar, and annual changes. Understanding circadian, circatidal, and annual regulation in reef-building corals is complicated by the presence of photosynthetic endosymbionts, which have a profound physiochemical influence on the intracellular environment. How corals tune their animal-based clock machinery to respond to external cues while simultaneously responding to internal physiological changes imposed by the symbiont, is not clear. There is insufficient molecular or physiological evidence of the existence of a circadian pacemaker that controls the metabolism, photosynthesis, synchronized mass spawning, and calcification processes in symbiotic corals. In this review, we present current knowledge regarding the animal pacemaker and the symbiotic-algal pacemaker. We examine the evidence from behavioral, physiological, molecular, and evolutionary perspectives. We explain why symbiotic corals are an interesting model with which to study the complexities and evolution of the metazoan circadian clock. We also provide evidence of why the chronobiology of corals is fundamental and extremely important for explaining the biology, physiology, and metabolism of coral reefs. A deeper understanding of these complex issues can help explain coral mass spawning, one of the earth's greatest and most mysterious behavioral phenomena. Copyright © 2014 Elsevier B.V. All rights reserved.

The behavioural and physiological strategies of bird and reptile embryos in response to unpredictable variation in nest temperature.

PubMed

Du, Wei-Guo; Shine, Richard

2015-02-01

Temperature profoundly affects the rate and trajectory of embryonic development, and thermal extremes can be fatal. In viviparous species, maternal behaviour and physiology can buffer the embryo from thermal fluctuations; but in oviparous animals (like most reptiles and all birds), an embryo is likely to encounter unpredictable periods when incubation temperatures are unfavourable. Thus, we might expect natural selection to have favoured traits that enable embryos to maintain development despite those fluctuations. Our review of recent research identifies three main routes that embryos use in this way. Extreme temperatures (i) can be avoided (e.g. by accelerating hatching, by moving within the egg, by cooling the egg by enhanced rates of evaporation, or by hysteresis in rates of heating versus cooling); (ii) can be tolerated (e.g. by entering diapause, by producing heat-shock proteins, or by changing oxygen use); or (iii) the embryo can adjust its physiology and/or developmental trajectory in ways that reduce the fitness penalties of unfavourable thermal conditions (e.g. by acclimating, by exploiting brief windows of favourable conditions, or by producing the hatchling phenotype best suited to those incubation conditions). Embryos are not simply passive victims of ambient conditions. Like free-living stages of the life cycle, embryos exhibit behavioural and physiological plasticity that enables them to deal with unpredictable abiotic challenges. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

Seasonal variations in the physiological stress response to discrete bouts of aerial exposure in the little skate, Leucoraja erinacea.

PubMed

Cicia, Angela M; Schlenker, Lela S; Sulikowski, James A; Mandelman, John W

2012-06-01

Aerial exposure and acute thermal stress have been shown to elicit profound physiological disruptions in obligate water-breathing teleosts. However, no study has investigated these responses in an elasmobranch. To address this, venous blood samples were collected and evaluated from little skates (Leucoraja erinacea) subjected to discrete aerial exposure durations (0, 15, and 50 min) coupled with differing abrupt thermal changes (gradient between seawater and air; winter: ΔT=-3 °C; summer: ΔT=+9 °C) in two distinct laboratory studies. In general, blood acid-base properties (e.g. decline in pH; elevation in PCO(2)) and select metabolites (elevated whole-blood lactate) and electrolytes (elevated plasma K(+)) were significantly disrupted by aerial exposure, and were most disturbed after skates were exposed to air for 50 min. However, the magnitude of the blood acid-base perturbations, metabolic contribution to the resulting blood acidosis, elevations to ionic and metabolic parameters, and delayed mortality were more extreme during the summer study, suggesting that acute thermal stress exacerbates the physiological impairments associated with aerial exposure in little skates. Conversely, a reduced thermal gradient (from seawater to air) may attenuate the magnitude of metabolic and ionic perturbations, resulting in a high physiological threshold for coping with extended aerial exposure. Copyright © 2011 Elsevier Inc. All rights reserved.

Slow motion in films and video clips: Music influences perceived duration and emotion, autonomic physiological activation and pupillary responses.

PubMed

Wöllner, Clemens; Hammerschmidt, David; Albrecht, Henning

2018-01-01

Slow motion scenes are ubiquitous in screen-based audiovisual media and are typically accompanied by emotional music. The strong effects of slow motion on observers are hypothetically related to heightened emotional states in which time seems to pass more slowly. These states are simulated in films and video clips, and seem to resemble such experiences in daily life. The current study investigated time perception and emotional response to media clips containing decelerated human motion, with or without music using psychometric and psychophysiological testing methods. Participants were presented with slow-motion scenes taken from commercial films, ballet and sports footage, as well as the same scenes converted to real-time. Results reveal that slow-motion scenes, compared to adapted real-time scenes, led to systematic underestimations of duration, lower perceived arousal but higher valence, lower respiration rates and smaller pupillary diameters. The presence of music compared to visual-only presentations strongly affected results in terms of higher accuracy in duration estimates, higher perceived arousal and valence, higher physiological activation and larger pupillary diameters, indicating higher arousal. Video genre affected responses in addition. These findings suggest that perceiving slow motion is not related to states of high arousal, but rather affects cognitive dimensions of perceived time and valence. Music influences these experiences profoundly, thus strengthening the impact of stretched time in audiovisual media.

Identification and characterisation of isoprene-degrading bacteria in an estuarine environment.

PubMed

Johnston, Antonia; Crombie, Andrew T; El Khawand, Myriam; Sims, Leanne; Whited, Gregg M; McGenity, Terry J; Colin Murrell, J

2017-09-01

Approximately one-third of volatile organic compounds (VOCs) emitted to the atmosphere consists of isoprene, originating from the terrestrial and marine biosphere, with a profound effect on atmospheric chemistry. However, isoprene provides an abundant and largely unexplored source of carbon and energy for microbes. The potential for isoprene degradation in marine and estuarine samples from the Colne Estuary, UK, was investigated using DNA-Stable Isotope Probing (DNA-SIP). Analysis at two timepoints showed the development of communities dominated by Actinobacteria including members of the genera Mycobacterium, Rhodococcus, Microbacterium and Gordonia. Representative isolates, capable of growth on isoprene as sole carbon and energy source, were obtained from marine and estuarine locations, and isoprene-degrading strains of Gordonia and Mycobacterium were characterised physiologically and their genomes were sequenced. Genes predicted to be required for isoprene metabolism, including four-component isoprene monooxygenases (IsoMO), were identified and compared with previously characterised examples. Transcriptional and activity assays of strains growing on isoprene or alternative carbon sources showed that growth on isoprene is an inducible trait requiring a specific IsoMO. This study is the first to identify active isoprene degraders in estuarine and marine environments using DNA-SIP and to characterise marine isoprene-degrading bacteria at the physiological and molecular level. © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

microRNA–200b as a Switch for Inducible Adult Angiogenesis

PubMed Central

Sinha, Mithun; Ghatak, Subhadip; Roy, Sashwati

2015-01-01

Abstract Significance: Angiogenesis is the process by which new blood vessels develop from a pre-existing vascular system. It is required for physiological processes such as developmental biology and wound healing. Angiogenesis also plays a crucial role in pathological conditions such as tumor progression. The underlying importance of angiogenesis necessitates a highly regulated process. Recent Advances: Recent works have demonstrated that the process of angiogenesis is regulated by small noncoding RNA molecules called microRNAs (miRs). These miRs, collectively referred to as angiomiRs, have been reported to have a profound effect on the process of angiogenesis by acting as either pro-angiogenic or anti-angiogenic regulators. Critical Issues: In this review, we will discuss the role of miR-200b as a regulator of angiogenesis. Once the process of angiogenesis is complete, anti-angiogenic miR-200b has been reported to provide necessary braking. Downregulation of miR-200b has been reported across various tumor types, as deregulated angiogenesis is necessary for tumor development. Transient downregulation of miR-200b in wounds drives wound angiogenesis. Future Directions: New insights and understanding of the molecular mechanism of regulation of angiogenesis by miR-200b has opened new avenues of possible therapeutic interventions to treat angiogenesis-related patho-physiological conditions. Antioxid. Redox Signal. 22, 1257–1272. PMID:25761972

The ecological and physiological responses of the microbial community from a semiarid soil to hydrocarbon contamination and its bioremediation using compost amendment.

PubMed

Bastida, F; Jehmlich, N; Lima, K; Morris, B E L; Richnow, H H; Hernández, T; von Bergen, M; García, C

2016-03-01

The linkage between phylogenetic and functional processes may provide profound insights into the effects of hydrocarbon contamination and biodegradation processes in high-diversity environments. Here, the impacts of petroleum contamination and the bioremediation potential of compost amendment, as enhancer of the microbial activity in semiarid soils, were evaluated in a model experiment. The analysis of phospholipid fatty-acids (PLFAs) and metaproteomics allowed the study of biomass, phylogenetic and physiological responses of the microbial community in polluted semiarid soils. Petroleum pollution induced an increase of proteobacterial proteins during the contamination, while the relative abundance of Rhizobiales lowered in comparison to the non-contaminated soil. Despite only 0.55% of the metaproteome of the compost-treated soil was involved in biodegradation processes, the addition of compost promoted the removal of polycyclic aromatic hydrocarbons (PAHs) and alkanes up to 88% after 50 days. However, natural biodegradation of hydrocarbons was not significant in soils without compost. Compost-assisted bioremediation was mainly driven by Sphingomonadales and uncultured bacteria that showed an increased abundance of catabolic enzymes such as catechol 2,3-dioxygenases, cis-dihydrodiol dehydrogenase and 2-hydroxymuconic semialdehyde. For the first time, metaproteomics revealed the functional and phylogenetic relationships of petroleum contamination in soil and the microbial key players involved in the compost-assisted bioremediation. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of traffic noise on tree frog stress levels, immunity, and color signaling.

PubMed

Troïanowski, Mathieu; Mondy, Nathalie; Dumet, Adeline; Arcanjo, Caroline; Lengagne, Thierry

2017-10-01

During the last decade, many studies have focused on the detrimental effects of noise pollution on acoustic communication. Surprisingly, although it is known that noise exposure strongly influences health in humans, studies on wildlife remain scarce. In order to gain insight into the consequences of traffic noise exposure, we experimentally manipulated traffic noise exposure as well as the endocrine status of animals to investigate physiological and phenotypic consequences of noise pollution in an anuran species. We showed that noise exposure increased stress hormone level and induced an immunosuppressive effect. In addition, both traffic noise exposure and stress hormone application negatively impacted H. arborea vocal sac coloration. Moreover, our results suggest profound changes in sexual selection processes because the best quality males with initial attractive vocal sac coloration were the most impacted by noise. Hence, our study suggests that the recent increases in anthropogenic noise worldwide might affect a broader range of animal species than previously thought, because of alteration of visual signals and immunity. Generalizing these results to other taxa is crucial for the conservation of biodiversity in an increasingly noisy world. © 2017 Society for Conservation Biology.

Social Influences on Neurobiology and Behavior: Epigenetic Effects During Development

PubMed Central

Curley, JP; Jensen, CL; Mashoodh, R; Champagne, FA

2010-01-01

The quality of the social environment can have profound influences on the development and activity of neural systems with implications for numerous behavioral and physiological responses, including the expression of emotionality. Though social experiences occurring early in development may be particularly influential on the developing brain, there is continued plasticity within these neural circuits amongst juveniles and into early adulthood. In this review, we explore the evidence derived from studies in rodents which illustrates the social modulation during development of neural systems, with a particular emphasis on those systems in which a long-term effect is observed. One possible explanation for the persistence of dynamic changes in these systems in response to the environment is the involvement of epigenetic mechanisms, and here we discuss recent studies which support the role of these mechanisms in mediating the link between social experiences, gene expression, neurobiological changes, and behavioral variation. This literature raises critical questions about the interaction between neural systems, the concordance between neural and behavioral changes, sexual dimorphism in effects, the importance of considering individual differences in response to the social environment, and the potential of an epigenetic perspective in advancing our understanding of the pathways leading to variations in mental health. PMID:20650569

Effect of correction of aberration dynamics on chaos in human ocular accommodation.

PubMed

Hampson, Karen M; Cufflin, Matthew P; Mallen, Edward A H

2013-11-15

We used adaptive optics to determine the effect of monochromatic aberration dynamics on the level of chaos in the accommodation control system. Four participants viewed a stationary target while the dynamics of their aberrations were either left uncorrected, defocus was corrected, or all aberrations except defocus were corrected. Chaos theory analysis was used to discern changes in the accommodative microfluctuations. We found a statistically significant reduction in the chaotic nature of the accommodation microfluctuations during correction of defocus, but not when all aberrations except defocus were corrected. The Lyapunov exponent decreased from 0.71 ± 0.07 D/s (baseline) to 0.55 ± 0.03 D/s (correction of defocus fluctuations). As the reduction of chaos in physiological signals is indicative of stress to the system, the results indicate that for the participants included in this study, fluctuations in defocus have a more profound effect than those of the other aberrations. There were no changes in the power spectrum between experimental conditions. Hence chaos theory analysis is a more subtle marker of changes in the accommodation control system and will be of value in the study of myopia onset and progression.

The False-Friend Effect in Three Profoundly Deaf Learners of French: Disentangling Morphology, Phonology and Orthography

ERIC Educational Resources Information Center

Janke, Vikki; Kolokonte, Marina

2015-01-01

Three profoundly deaf individuals undertook a low-frequency backward lexical translation task (French/English), where morphological structure was manipulated and orthographic distance between test items was measured. Conditions included monomorphemic items (simplex), polymorphemic items (complex), items whose French morphological structure…

Physiological Regulation of Stomatal Conductance in Boreal Forest Species: Do Species Differ and Does it Matter?

NASA Astrophysics Data System (ADS)

Berry, J. A.; Wolf, A.; Vygodskaya, N. N.

2004-12-01

Measurements of energy and water balance over Boreal forest ecosystems have generally shown very large ratios of sensible heat flux to latent heat flux (Bowen ratio) - especially on fine summer days. This strong control on evaporation at the plant scale can restrict precipitation and effect hydrometeorlogy at the regional scale. The large Bowen ratio is, in part, explained by the low maximum stomatal conductance of Boreal forest tree species and is probably related to their very low photosynthetic capacity. However, mid-day conductance can be much lower than expected on this basis and reflects the additional effect of a dynamic feedback system between stomatal conductance and the properties of the atmospheric boundary layer. Low stomatal conductance leads to a large sensible heat flux which, in turn, leads to a deeper, warmer and dryer atmospheric boundary layer and to a greater evaporative demand on the plant, causing the stomata close still more. Predicting the response of this non-linear system presents a major challenge. Physiological studies conducted in the Canadian Boreal forest show very large differences in the tendency of species to experience mid day stomatal closure. Jack pine was found to be quite susceptible while black spruce the most resistant to mid day stomatal closure. These species had very similar photosynthetic capacity (Vmax) and Ball-Berry stomatal sensitivity coefficients. Jack pine was, however, more sensitive to inhibition of photosynthesis by elevated temperatures and, as a consequence, stomata closed as temperature and the vapor pressure deficit increased during mid day. In contrast, black spruce was much less effected. These differences could have profound implications for simulating regional scale hydrometeorology over large areas dominated by monospecific stands in the NEESPI domain.

The effects of experimentally induced hyperthyroidism on the diving physiology of harbor seals (Phoca vitulina)

PubMed Central

Weingartner, Gundula M.; Thornton, Sheila J.; Andrews, Russel D.; Enstipp, Manfred R.; Barts, Agnieszka D.; Hochachka, Peter W.

2012-01-01

Many phocid seals are expert divers that remain submerged longer than expected based on estimates of oxygen storage and utilization. This discrepancy is most likely due to an overestimation of diving metabolic rate. During diving, a selective redistribution of blood flow occurs, which may result in reduced metabolism in the hypoperfused tissues and a possible decline in whole-body metabolism to below the resting level (hypometabolism). Thyroid hormones are crucial in regulation of energy metabolism in vertebrates and therefore their control might be an important part of achieving a hypometabolic state during diving. To investigate the effect of thyroid hormones on diving physiology of phocid seals, we measured oxygen consumption, heart rate, and post-dive lactate concentrations in five harbor seals (Phoca vitulina) conducting 5 min dives on command, in both euthyroid and experimentally induced hyperthyroid states. Oxygen consumption during diving was significantly reduced (by 25%) in both euthyroid and hyperthyroid states, confirming that metabolic rate during diving falls below resting levels. Hyperthyroidism increased oxygen consumption (by 7–8%) when resting in water and during diving, compared with the euthyroid state, illustrating the marked effect of thyroid hormones on metabolic rate. Consequently, post-dive lactate concentrations were significantly increased in the hyperthyroid state, suggesting that the greater oxygen consumption rates forced seals to make increased use of anaerobic metabolic pathways. During diving, hyperthyroid seals also exhibited a more profound decline in heart rate than seals in the euthyroid state, indicating that these seals were pushed toward their aerobic limit and required a more pronounced cardiovascular response. Our results demonstrate the powerful role of thyroid hormones in metabolic regulation and support the hypothesis that thyroid hormones play a role in modulating the at-sea metabolism of phocid seals. PMID:23060807

Long-term effects of chronic light pollution on seasonal functions of European blackbirds (Turdus merula).

PubMed

Dominoni, Davide M; Quetting, Michael; Partecke, Jesko

2013-01-01

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems.

Use of antiarrhythmic drugs in elderly patients.

PubMed

Lee, Hon-Chi; Tl Huang, Kristin; Shen, Win-Kuang

2011-09-01

Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intracellular Ca(2+) overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhythmics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology, disease processes, and medication regimen.

Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.

PubMed

Desai, Seema S; Tung, Jason C; Zhou, Vivian X; Grenert, James P; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M; Chang, Tammy T

2016-07-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275). © 2016 by the American Association for the Study of Liver Diseases.

Oligodendrocyte ablation affects the coordinated interaction between granule and Purkinje neurons during cerebellum development

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

Collin, Ludovic; Doretto, Sandrine; Department of Psychiatry and Human Behavior, University of California Irvine, 3226 Gillespie Neuroscience Research Facility, Irvine CA 92697

2007-08-01

Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS) classically known to be devoted to the formation of myelin sheaths around most axons of the vertebrate brain. We have addressed the role of these cells during cerebellar development, by ablating OLs in vivo. Previous analyses had indicated that OL ablation during the first six postnatal days results into a striking cerebellar phenotype, whose major features are a strong reduction of granule neurons and aberrant Purkinje cells development. These two cell types are highly interconnected during cerebellar development through the production of molecules that help their proliferation, differentiationmore » and maintenance. In this article, we present data showing that OL ablation has major effects on the physiology of Purkinje (PC) and granule cells (GC). In particular, OL ablation results into a reduction of sonic hedgehog (Shh), Brain Derived Neurotrophic Factor (BDNF), and Reelin (Rln) expression. These results indicate that absence of OLs profoundly alters the normal cerebellar developmental program.« less

Biocrusts in the context of global change

USGS Publications Warehouse

Reed, Sasha C.; Maestre, Fernando T.; Ochoa-Hueso, Raul; Kuske, Cheryl; Darrouzet-Nardi, Anthony N.; Darby, Brian; Sinsabaugh, Bob; Oliver, Mel; Sancho, Leo; Belnap, Jayne

2016-01-01

A wide range of studies show global environmental change will profoundly affect the structure, function, and dynamics of terrestrial ecosystems. The research synthesized here underscores that biocrust communities are also likely to respond significantly to global change drivers, with a large potential for modification to their abundance, composition, and function. We examine how elevated atmospheric CO2 concentrations, climate change (increased temperature and altered precipitation), and nitrogen deposition affect biocrusts and the ecosystems they inhabit. We integrate experimental and observational data, as well as physiological, community ecology, and biogeochemical perspectives. Taken together, these data highlight the potential for biocrust organisms to respond dramatically to environmental change and show how changes to biocrust community composition translate into effects on ecosystem function (e.g., carbon and nutrient cycling, soil stability, energy balance). Due to the importance of biocrusts in regulating dryland ecosystem processes and the potential for large modifications to biocrust communities, an improved understanding and predictive capacity regarding biocrust responses to environmental change are of scientific and societal relevance.

Dietary nitrate and nitrite: Benefits, risks, and evolving perceptions.

PubMed

Bedale, Wendy; Sindelar, Jeffrey J; Milkowski, Andrew L

2016-10-01

Consumers have an illogical relationship with nitrite (and its precursor, nitrate) in food. Despite a long history of use, nitrite was nearly banned from use in foods in the 1970s due to health concerns related to the potential for carcinogenic nitrosamine formation. Changes in meat processing methods reduced those potential risks, and nitrite continued to be used in foods. Since then, two opposing movements continue to shape how consumers view dietary nitrate and nitrite. The discovery of the profound physiological importance of nitric oxide led to the realization that dietary nitrate contributes significantly to the nitrogen reservoir for nitric oxide formation. Numerous clinical studies have also demonstrated beneficial effects from dietary nitrate consumption, especially in vascular and metabolic health. However, the latest wave of consumer sentiment against food additives, the clean-label movement, has renewed consumer fear and avoidance of preservatives, including nitrite. Education is necessary but may not be sufficient to resolve this disconnect in consumer perception. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroendocrine changes upon exposure to predator odors.

PubMed

Hegab, Ibrahim M; Wei, Wanhong

2014-05-28

Predator odors are non-intrusive and naturalistic stressors of high ethological relevance in animals. Upon exposure to a predator or its associated cues, robust physiological and molecular anti-predator defensive strategies are elicited thereby allowing prey species to recognize, avoid and defend against a possible predation threat. In this review, we will discuss the nature of neuroendocrine stress responses upon exposure to predator odors. Predator odors can have a profound effect on the endocrine system, including activation of the hypothalamic-pituitary-adrenal axis, and induction of stress hormones such as corticosterone and adrenocorticotropic hormone. On a neural level, short-term exposure to predator odors leads to induction of the c-fos gene, while induction of ΔFosB in a different brain region is detected under chronic predation stress. Future research should aim to elucidate the relationships between neuroendocrine and behavioral outputs to gage the different levels of anti-predator responses in prey species. Copyright © 2014 Elsevier Inc. All rights reserved.

Surgical Models of Roux-en-Y Gastric Bypass Surgery and Sleeve Gastrectomy in Rats and Mice

PubMed Central

Bruinsma, Bote G.; Uygun, Korkut; Yarmush, Martin L.; Saeidi, Nima

2015-01-01

Bariatric surgery is the only definitive solution currently available for the present obesity pandemic. These operations typically involve reconfiguration of gastrointestinal tract anatomy and impose profound metabolic and physiological benefits, such as substantially reducing body weight and ameliorating type II diabetes. Therefore, animal models of these surgeries offer unique and exciting opportunities to delineate the underlying mechanisms that contribute to the resolution of obesity and diabetes. Here we describe a standardized procedure for mouse and rat models of Roux-en-Y gastric bypass (80–90 minutes operative time) and sleeve gastrectomy (30–45 minutes operative time), which, to a high degree resemble operations in human. We also provide detailed protocols for both pre- and post-operative techniques that ensure a high success rate in the operations. These protocols provide the opportunity to mechanistically investigate the systemic effects of the surgical interventions, such as regulation of body weight, glucose homeostasis, and gut microbiome. PMID:25719268

Differentiation and Glucocorticoid Regulated Apopto-Phagocytic Gene Expression Patterns in Human Macrophages. Role of Mertk in Enhanced Phagocytosis

PubMed Central

Zahuczky, Gábor; Kristóf, Endre; Majai, Gyöngyike; Fésüs, László

2011-01-01

The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk. PMID:21731712

Peatmoss (Sphagnum) diversification associated with Miocene Northern Hemisphere climatic cooling?

PubMed

Shaw, A Jonathan; Devos, Nicolas; Cox, Cymon J; Boles, Sandra B; Shaw, Blanka; Buchanan, Alex M; Cave, Lynette; Seppelt, Rodney

2010-06-01

Global climate changes sometimes spark biological radiations that can feed back to effect significant ecological impacts. Northern Hemisphere peatlands dominated by living and dead peatmosses (Sphagnum) harbor almost 30% of the global soil carbon pool and have functioned as a net carbon sink throughout the Holocene, and probably since the late Tertiary. Before that time, northern latitudes were dominated by tropical and temperate plant groups and ecosystems. Phylogenetic analyses of mosses (phylum Bryophyta) based on nucleotide sequences from the plastid, mitochondrial, and nuclear genomes indicate that most species of Sphagnum are of recent origin (ca. <20 Ma). Sphagnum species are not only well-adapted to boreal peatlands, they create the conditions that promote development of peatlands. The recent radiation that gave rise to extant diversity of peatmosses is temporally associated with Miocene climatic cooling in the Northern Hemisphere. The evolution of Sphagnum has had profound influences on global biogeochemistry because of the unique biochemical, physiological, and morphological features of these plants, both while alive and after death. 2010 Elsevier Inc. All rights reserved.

Weighed down by stigma: How weight-based social identity threat contributes to weight gain and poor health

PubMed Central

Hunger, Jeffrey M.; Major, Brenda; Blodorn, Alison; Miller, Carol T.

2015-01-01

Weight stigma is pervasive, and a number of scholars argue that this profound stigma contributes to the negative effects of weight on psychological and physical health. Some lay individuals and health professionals assume that stigmatizing weight can actually motivate healthier behaviors and promote weight loss. However, as we review, weight stigma is consistently associated with poorer mental and physical health outcomes. In this article we propose a social identity threat model elucidating how weight stigma contributes to weight gain and poorer mental and physical health among overweight individuals. We propose that weight-based social identity threat increases physiological stress, undermines self-regulation, compromises psychological health, and increases the motivation to avoid stigmatizing domains (e.g., the gym) and escape the stigma by engaging in unhealthy weight loss behaviors. Given the prevalence of overweight and obesity in the US, weight stigma thus has the potential to undermine the health and wellbeing of millions of Americans. PMID:29225670

Aggregate size and structure determination of nanomaterials in physiological media: importance of dynamic evolution

NASA Astrophysics Data System (ADS)

Afrooz, A. R. M. Nabiul; Hussain, Saber M.; Saleh, Navid B.

2014-12-01

Most in vitro nanotoxicological assays are performed after 24 h exposure. However, in determining size and shape effect of nanoparticles in toxicity assays, initial characterization data are generally used to describe experimental outcome. The dynamic size and structure of aggregates are typically ignored in these studies. This brief communication reports dynamic evolution of aggregation characteristics of gold nanoparticles. The study finds that gradual increase in aggregate size of gold nanospheres (AuNS) occurs up to 6 h duration; beyond this time period, the aggregation process deviates from gradual to a more abrupt behavior as large networks are formed. Results of the study also show that aggregated clusters possess unique structural conformation depending on nominal diameter of the nanoparticles. The differences in fractal dimensions of the AuNS samples likely occurred due to geometric differences, causing larger packing propensities for smaller sized particles. Both such observations can have profound influence on dosimetry for in vitro nanotoxicity analyses.

Detection, significance, and therapy of bacteriuria in pregnancy. Update in the managed health care era.

PubMed

Patterson, T F; Andriole, V T

1997-09-01

Profound physiologic and anatomic changes of the urinary tract during pregnancy contribute to the increased risk for symptomatic urinary tract infection in women with bacteriuria. Asymptomatic bacteriuria is the major risk factor for developing symptomatic UTIs during pregnancy and may be associated with adverse effects on maternal and fetal health. Because most symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All pregnant women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy should be given to women with bacteriuria and clearance of bacteriuria should be documented after therapy is complete. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a urologic evaluation after delivery.

Food-producing animals and their health in relation to human health

PubMed Central

Téllez, Guillermo; Lauková, Andrea; Latorre, Juan D.; Hernandez-Velasco, Xochitl; Hargis, Billy M.; Callaway, Todd

2015-01-01

The fields of immunology, microbiology, and nutrition converge in an astonishing way. Dietary ingredients have a profound effect on the composition of the gut microflora, which in turn regulates the physiology of metazoans. As such, nutritional components of the diet are of critical importance not only for meeting the nutrient requirements of the host, but also for the microbiome. During their coevolution, bacterial microbiota has established multiple mechanisms to influence the eukaryotic host, generally in a beneficial fashion. The microbiome encrypts a variety of metabolic functions that complements the physiology of their hosts. Over a century ago Eli Metchnikoff proposed the revolutionary idea to consume viable bacteria to promote health by modulating the intestinal microflora. The idea is more applicable now than ever, since bacterial antimicrobial resistance has become a serious worldwide problem both in medical and agricultural fields. The impending ban of antibiotics in animal feed due to the current concern over the spread of antibiotic resistance genes makes a compelling case for the development of alternative prophylactics. Nutritional approaches to counteract the debilitating effects of stress and infection may provide producers with useful alternatives to antibiotics. Improving the disease resistance of animals grown without antibiotics will benefit the animals’ health, welfare, and production efficiency, and is also a key strategy in the effort to improve the microbiological safe status of animal-derived food products (e.g. by poultry, rabbits, ruminants, or pigs). This review presents some of the alternatives currently used in food-producing animals to influence their health in relation to human health. PMID:25651994

Routine Habitat Change: A Source of Unrecognized Transient Alteration of Intestinal Microbiota in Laboratory Mice

PubMed Central

Ma, Betty W.; Bokulich, Nicholas A.; Castillo, Patricia A.; Kananurak, Anchasa; Underwood, Mark A.; Mills, David A.; Bevins, Charles L.

2012-01-01

The mammalian intestine harbors a vast, complex and dynamic microbial population, which has profound effects on host nutrition, intestinal function and immune response, as well as influence on physiology outside of the alimentary tract. Imbalance in the composition of the dense colonizing bacterial population can increase susceptibility to various acute and chronic diseases. Valuable insights on the association of the microbiota with disease critically depend on investigation of mouse models. Like in humans, the microbial community in the mouse intestine is relatively stable and resilient, yet can be influenced by environmental factors. An often-overlooked variable in research is basic animal husbandry, which can potentially alter mouse physiology and experimental outcomes. This study examined the effects of common husbandry practices, including food and bedding alterations, as well as facility and cage changes, on the gut microbiota over a short time course of five days using three culture-independent techniques, quantitative PCR, terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). This study detected a substantial transient alteration in microbiota after the common practice of a short cross-campus facility transfer, but found no comparable alterations in microbiota within 5 days of switches in common laboratory food or bedding, or following an isolated cage change in mice acclimated to their housing facility. Our results highlight the importance of an acclimation period following even simple transfer of mice between campus facilities, and highlights that occult changes in microbiota should be considered when imposing husbandry variables on laboratory animals. PMID:23082164

Host-Microbe Interactions in Microgravity: Assessment and Implications

PubMed Central

Foster, Jamie S.; Wheeler, Raymond M.; Pamphile, Regine

2014-01-01

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes. PMID:25370197

β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions.

PubMed

Zhu, Lu; Almaça, Joana; Dadi, Prasanna K; Hong, Hao; Sakamoto, Wataru; Rossi, Mario; Lee, Regina J; Vierra, Nicholas C; Lu, Huiyan; Cui, Yinghong; McMillin, Sara M; Perry, Nicole A; Gurevich, Vsevolod V; Lee, Amy; Kuo, Bryan; Leapman, Richard D; Matschinsky, Franz M; Doliba, Nicolai M; Urs, Nikhil M; Caron, Marc G; Jacobson, David A; Caicedo, Alejandro; Wess, Jürgen

2017-02-01

β-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the β-arrestin-2 gene, barr2, in β-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function.

Host-microbe interactions in microgravity: assessment and implications.

PubMed

Foster, Jamie S; Wheeler, Raymond M; Pamphile, Regine

2014-05-26

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes.

Sex Differences in Human Fatigability: Mechanisms and Insight to Physiological Responses

PubMed Central

Hunter, Sandra K.

2014-01-01

Sex-related differences in physiology and anatomy are responsible for profound differences in neuromuscular performance and fatigability between men and women. Women are usually less fatigable than men for similar intensity isometric fatiguing contractions. This sex difference in fatigability, however, is task specific because different neuromuscular sites will be stressed when the requirements of the task are altered, and the stress on these sites can differ for men and women. Task variables that can alter the sex difference in fatigue include the type, intensity and speed of contraction, the muscle group assessed, and the environmental conditions. Physiological mechanisms that are responsible for sex-based differences in fatigability may include activation of the motor neuron pool from cortical and subcortical regions, synaptic inputs to the motor neuron pool via activation of metabolically-sensitive small afferent fibres in the muscle, muscle perfusion, and skeletal muscle metabolism and fibre type properties. Non-physiological factors such as the sex bias of studying more males than females in human and animal experiments can also mask a true understanding of the magnitude and mechanisms of sex-based differences in physiology and fatigability. Despite recent developments, there is a tremendous lack of understanding of sex differences in neuromuscular function and fatigability, the prevailing mechanisms and the functional consequences. This review emphasises the need to understand sex-based differences in fatigability in order to shed light on the benefits and limitations that fatigability can exert for men and women during daily tasks, exercise performance, training and rehabilitation in both health and disease. PMID:24433272

Exploring the Homeostatic and Sensory Roles of the Immune System.

PubMed

Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

2016-01-01

Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.

Enemies of Ethics Equals Environmental Exodus, Part 2.

PubMed

Ramsey, Suzanne

2015-01-01

Bullying and mobbing in the workplace have accelerated at alarming rates around the world in the past decade. Health care workers, nurses, managers, physicians, and owners of organizations, sometimes choose unethical methodology as a means to obtain personal and/or organizational goals. The consequences of these unethical decisions have a profound impact on the victim, bystanders, the organization, as well as the nursing profession. As a result, victims (nurses) often suffer from physiological and psychological distress, posttraumatic stress disorder, suicide, and erosion of professional confidence; patient's quality of care is undermined; nurses exit the profession; and organizations suffer from decreased morale, decline in productivity, financial loss, and a tarnished reputation.

An acoustic analysis of laughter produced by congenitally deaf and normally hearing college students.

PubMed

Makagon, Maja M; Funayama, E Sumie; Owren, Michael J

2008-07-01

Relatively few empirical data are available concerning the role of auditory experience in nonverbal human vocal behavior, such as laughter production. This study compared the acoustic properties of laughter in 19 congenitally, bilaterally, and profoundly deaf college students and in 23 normally hearing control participants. Analyses focused on degree of voicing, mouth position, air-flow direction, temporal features, relative amplitude, fundamental frequency, and formant frequencies. Results showed that laughter produced by the deaf participants was fundamentally similar to that produced by the normally hearing individuals, which in turn was consistent with previously reported findings. Finding comparable acoustic properties in the sounds produced by deaf and hearing vocalizers confirms the presumption that laughter is importantly grounded in human biology, and that auditory experience with this vocalization is not necessary for it to emerge in species-typical form. Some differences were found between the laughter of deaf and hearing groups; the most important being that the deaf participants produced lower-amplitude and longer-duration laughs. These discrepancies are likely due to a combination of the physiological and social factors that routinely affect profoundly deaf individuals, including low overall rates of vocal fold use and pressure from the hearing world to suppress spontaneous vocalizations.

Music Training for Severely and Profoundly Retarded Individuals.

ERIC Educational Resources Information Center

Kesler, Buford; Richmond, Bert O.

Investigated were the effects of sex, ability and training method on the musical instrument playing ability of 16 institutionalized severely and profoundly retarded persons ages 7 to 20 years. Ss were randomly assigned to one of four treatment groups, and the time required to reach criterion playing a familiar tune was recorded. Data indicated…

The Effects of Governing Board Configuration on Profound Organizational Change in Hospitals

ERIC Educational Resources Information Center

Alexander, Jeffrey A.; Ye, Yining; Lee, Shoou-Yih D.; Weiner, Bryan J.

2006-01-01

This study extends the literature on governing boards and organizational change by examining how governing board configurations have influenced profound organizational change in U.S. hospitals, and the conditions under which such change occurs. Hospitals governed by boards that more closely resembled a corporate governance model were more likely…

School-Wide Positive Behavior Support for Individuals with Severe and Profound Disabilities

ERIC Educational Resources Information Center

Judge, Brittany A.

2015-01-01

One of the greatest challenges for alternative schools is to develop effective training programs for students with severe and profound developmental disabilities. School-wide positive behavior support (SWPBS) has been shown to decrease problematic behaviors in alternative schools and self-contained settings yet little is known about how effective…

Self-Injurious Behavior in People with Profound Intellectual Disabilities: A Meta-Analysis of Single-Case Studies

ERIC Educational Resources Information Center

Denis, Jo; Van den Noortgate, Wim; Maes, Bea

2011-01-01

The limitations people with profound intellectual disabilities experience in functioning contribute to a vulnerability to self-injurious behavior. Since this problem behavior has important negative consequences for people concerned, examining the effectiveness of treatments is important. In the current meta-analysis, single-case studies…

Vagus Nerve Stimulation Applied with a Rapid Cycle Has More Profound Influence on Hippocampal Electrophysiology Than a Standard Cycle.

PubMed

Larsen, Lars E; Wadman, Wytse J; Marinazzo, Daniele; van Mierlo, Pieter; Delbeke, Jean; Daelemans, Sofie; Sprengers, Mathieu; Thyrion, Lisa; Van Lysebettens, Wouter; Carrette, Evelien; Boon, Paul; Vonck, Kristl; Raedt, Robrecht

2016-07-01

Although vagus nerve stimulation (VNS) is widely used, therapeutic mechanisms and optimal stimulation parameters remain elusive. In the present study, we investigated the effect of VNS on hippocampal field activity and compared the efficiency of different VNS paradigms. Hippocampal electroencephalography (EEG) and perforant path dentate field-evoked potentials were acquired before and during VNS in freely moving rats, using 2 VNS duty cycles: a rapid cycle (7 s on, 18 s off) and standard cycle (30 s on, 300 s off) and various output currents. VNS modulated the evoked potentials, reduced total power of the hippocampal EEG, and slowed the theta rhythm. In the hippocampal EEG, theta (4-8 Hz) and high gamma (75-150 Hz) activity displayed strong phase amplitude coupling that was reduced by VNS. Rapid-cycle VNS had a greater effect than standard-cycle VNS on all outcome measures. Using rapid cycle VNS, a maximal effect on EEG parameters was found at 300 μA, beyond which effects saturated. The findings suggest that rapid-cycle VNS produces a more robust outcome than standard cycle VNS and support already existing preclinical evidence that relatively low output currents are sufficient to produce changes in brain physiology and thus likely also therapeutic efficacy.

The Effects of Hallucinogens on Gene Expression.

PubMed

Martin, David A; Nichols, Charles D

2018-01-01

The classic serotonergic hallucinogens, or psychedelics, have the ability to profoundly alter perception and behavior. These can include visual distortions, hallucinations, detachment from reality, and mystical experiences. Some psychedelics, like LSD, are able to produce these effects with remarkably low doses of drug. Others, like psilocybin, have recently been demonstrated to have significant clinical efficacy in the treatment of depression, anxiety, and addiction that persist for at least several months after only a single therapeutic session. How does this occur? Much work has recently been published from imaging studies showing that psychedelics alter brain network connectivity. They facilitate a disintegration of the default mode network, producing a hyperconnectivity between brain regions that allow centers that do not normally communicate with each other to do so. The immediate and acute effects on both behaviors and network connectivity are likely mediated by effector pathways downstream of serotonin 5-HT2A receptor activation. These acute molecular processes also influence gene expression changes, which likely influence synaptic plasticity and facilitate more long-term changes in brain neurochemistry ultimately underlying the therapeutic efficacy of a single administration to achieve long-lasting effects. In this review, we summarize what is currently known about the molecular genetic responses to psychedelics within the brain and discuss how gene expression changes may contribute to altered cellular physiology and behaviors.

Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

PubMed

Bottaccioli, Anna Giulia; Bottaccioli, Francesco; Minelli, Andrea

2018-05-15

In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases. © 2018 New York Academy of Sciences.

Improving the Functional Utility and Effectiveness of Classroom Services for Students with Profound Multiple Handicaps.

ERIC Educational Resources Information Center

Green, Carolyn W.; And Others

1986-01-01

A staff supervision and classroom management program to increase involvement in functional task activities (e.g., self-help, leisure, social/communication) was implemented in three classes serving 19 students (ages 11-36) with profound mental and physical handicaps. Large increases in functional task involvement and smaller increases in student…

Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners

ERIC Educational Resources Information Center

Griffiths, Colin; Smith, Martine

2016-01-01

Background: People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the…

Acceleration of Object Permanence with Severely and Profoundly Retarded Children.

ERIC Educational Resources Information Center

Kahn, James V.

Examined was the effectiveness of training four severely and profoundly retarded children (3-6 years old) to improve their level of functioning on a measure of object permanence and to demonstrate generalization to other areas of sensorimotor intelligence. Ss were given a pretest and posttest on the I. Uzgiris and J. Hunt instrument which consists…

The Influence of Phonological Mechanisms in Written Spelling of Profoundly Deaf Children

ERIC Educational Resources Information Center

Colombo, Lucia; Arfe, Barbara; Bronte, Tiziana

2012-01-01

In the present study, the effect of phonological and working memory mechanisms involved in spelling Italian single words was explored in two groups of children matched for grade level: a group of normally hearing children and a group of pre-verbally deaf children, with severe-to-profound hearing loss. Three-syllable and four-syllable familiar…

Enhancing Literacy Skills of Students with Congenital and Profound Hearing Impairment in Nigeria Using Babudoh's Comprehension Therapy

ERIC Educational Resources Information Center

Babudoh, Gladys B.

2014-01-01

This study reports the effect of a treatment tool called "Babudoh's comprehension therapy" in enhancing the comprehension and writing skills of 10 junior secondary school students with congenital and profound hearing impairment in Plateau State, Nigeria. The study adopted the single group pretest-posttest quasi-experimental research…

Distinct Modes of Macrophage Recognition for Apoptotic and Necrotic Cells Are Not Specified Exclusively by Phosphatidylserine Exposure

PubMed Central

Cocco, Regina E.; Ucker, David S.

2001-01-01

The distinction between physiological (apoptotic) and pathological (necrotic) cell deaths reflects mechanistic differences in cellular disintegration and is of functional significance with respect to the outcomes that are triggered by the cell corpses. Mechanistically, apoptotic cells die via an active and ordered pathway; necrotic deaths, conversely, are chaotic and passive. Macrophages and other phagocytic cells recognize and engulf these dead cells. This clearance is believed to reveal an innate immunity, associated with inflammation in cases of pathological but not physiological cell deaths. Using objective and quantitative measures to assess these processes, we find that macrophages bind and engulf native apoptotic and necrotic cells to similar extents and with similar kinetics. However, recognition of these two classes of dying cells occurs via distinct and noncompeting mechanisms. Phosphatidylserine, which is externalized on both apoptotic and necrotic cells, is not a specific ligand for the recognition of either one. The distinct modes of recognition for these different corpses are linked to opposing responses from engulfing macrophages. Necrotic cells, when recognized, enhance proinflammatory responses of activated macrophages, although they are not sufficient to trigger macrophage activation. In marked contrast, apoptotic cells profoundly inhibit phlogistic macrophage responses; this represents a cell-associated, dominant-acting anti-inflammatory signaling activity acquired posttranslationally during the process of physiological cell death. PMID:11294896

Be different--the diversity of peroxisomes in the animal kingdom.

PubMed

Islinger, M; Cardoso, M J R; Schrader, M

2010-08-01

Peroxisomes represent so-called "multipurpose organelles" as they contribute to various anabolic as well as catabolic pathways. Thus, with respect to the physiological specialization of an individual organ or animal species, peroxisomes exhibit a functional diversity, which is documented by significant variations in their proteome. These differences are usually regarded as an adaptational response to the nutritional and environmental life conditions of a specific organism. Thus, human peroxisomes can be regarded as an in part physiologically unique organellar entity fulfilling metabolic functions that differ from our animal model systems. In line with this, a profound understanding on how peroxisomes acquired functional heterogeneity in terms of an evolutionary and mechanistic background is required. This review summarizes our current knowledge on the heterogeneity of peroxisomal physiology, providing insights into the genetic and cell biological mechanisms, which lead to the differential localization or expression of peroxisomal proteins and further gives an overview on peroxisomal biochemical pathways, which are specialized in different animal species and organs. Moreover, it addresses the impact of proteome studies on our understanding of differential peroxisome function describing the utility of mass spectrometry and computer-assisted algorithms to identify peroxisomal target sequences for the detection of new organ- or species-specific peroxisomal proteins. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Biological Hydropersulfides and Related Polysulfides: A New Concept and Perspective in Redox Biology.

PubMed

Fukuto, Jon M; Ignarro, Louis J; Nagy, Peter; Wink, David A; Kevil, Christopher G; Feelisch, Martin; Cortese-Krott, Miriam M; Bianco, Christopher L; Kumagai, Yoshito; Hobbs, Adrian J; Lin, Joseph; Ida, Tomoaki; Akaike, Takaaki

2018-05-12

The chemical biology of thiols (RSH, e.g., cysteine and cysteine containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS n H, RSS n R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS n H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nutritional and environmental effects on reproduction in small ruminants.

PubMed

Martin, G B; Rodger, J; Blache, D

2004-01-01

Animals live in environments that are both complex and continually changing, so they have to respond to short- and long-term variations in a wide range of factors, such as photoperiod, nutrition and sociosexual signals. Before they were domesticated, animals developed reproductive strategies that coped with these changes and often took advantage of them. The physiological processes that implement these strategies have been modified to some extent during several millennia of controlled breeding, but most persist. Thus, many genotypes still exhibit profound responses to external inputs, such as the induction of ovulation by sociosexual signals and the doubling of litter size by a change in nutrition. The complexity in these responses is now becoming clearer. For example, with sociosexual signals, we now need to consider the stimulatory effects of males on females, of females on males and of females on females. Similarly, the impact of nutrition has been extended beyond the control of puberty and the production of gametes to include phenomena such as 'fetal programming', with its potentially profound effects on the life-long performance of the animals. Fortunately, our capacity to research these phenomena has been greatly enhanced by technical improvements in hormone assays, molecular and cellular biology, and real-time ultrasound. This has brought us a better understanding of several of the environmental influences on reproduction, including: the cellular processes within ovarian follicles that mediate the effect of nutrition on ovulation rate; the neuroendocrine pathways through which nutritional inputs affect the brain centres that control appetite and reproduction; and the intracerebral pathways through which sociosexual signals (olfactory and non-olfactory) stimulate the reproductive axis. Importantly, we are now beginning to realise that, as well as considering interactions between environmental inputs and genotype, we need to take into account interactions between the environmental factors themselves, just as the animals do. We still have a long way to go for a complete understanding, but we are nevertheless in a position where we can begin to use this information to develop new management systems for our animals to improve their productivity.

Mammal-like muscles power swimming in a cold-water shark.

PubMed

Bernal, Diego; Donley, Jeanine M; Shadwick, Robert E; Syme, Douglas A

2005-10-27

Effects of temperature on muscle contraction and powering movement are profound, outwardly obvious, and of great consequence to survival. To cope with the effects of environmental temperature fluctuations, endothermic birds and mammals maintain a relatively warm and constant body temperature, whereas most fishes and other vertebrates are ectothermic and conform to their thermal niche, compromising performance at colder temperatures. However, within the fishes the tunas and lamnid sharks deviate from the ectothermic strategy, maintaining elevated core body temperatures that presumably confer physiological advantages for their roles as fast and continuously swimming pelagic predators. Here we show that the salmon shark, a lamnid inhabiting cold, north Pacific waters, has become so specialized for endothermy that its red, aerobic, locomotor muscles, which power continuous swimming, seem mammal-like, functioning only within a markedly elevated temperature range (20-30 degrees C). These muscles are ineffectual if exposed to the cool water temperatures, and when warmed even 10 degrees C above ambient they still produce only 25-50% of the power produced at 26 degrees C. In contrast, the white muscles, powering burst swimming, do not show such a marked thermal dependence and work well across a wide range of temperatures.

Levels of maternal care in dogs affect adult offspring temperament

NASA Astrophysics Data System (ADS)

Foyer, Pernilla; Wilsson, Erik; Jensen, Per

2016-01-01

Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs.

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

PubMed Central

Skene, Debra J.; Arendt, Josephine; Cade, Janet E.; Grant, Peter J.; Hardie, Laura J.

2016-01-01

Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important. PMID:27763782

Relabelling Behaviour. The Effects of Psycho-Education on the Perceived Severity and Causes of Challenging Behaviour in People with Profound Intellectual and Multiple Disabilities

ERIC Educational Resources Information Center

Poppes, P.; van der Putten, A.; Post, W.; Frans, N.; ten Brug, A.; van Es, A.; Vlaskamp, C.

2016-01-01

Background: Prevalence rates of challenging behaviour are high in children and adults with profound intellectual and multiple disabilities (PIMD). Moreover, many of these behaviours are observed daily. Direct support staff report that most challenging behaviour identified has little impact on the person with PIMD and attribute challenging…

Absence of Intervention Training Programs: Effects Upon the Severely and Profoundly Retarded, Part I: Selected Cases of Emotional and Behavioral Disturbances.

ERIC Educational Resources Information Center

Balthazar, Earl E.; And Others

Fifteen institutionalized profoundly retarded Ss, median age 7 years, who received no intervention training program, were assessed on the Balthazar Scales of Adaptive Behavior (BSAB), Sections I and II to determine whether social coping behavior would improve spontaneous maturation during a 6-month period. The Ss were recommended by nursing…

Effects of Inservice Teacher Training on Correct Implementation of Assessment and Instructional Procedures for Teachers of Students with Profound Multiple Disabilities

ERIC Educational Resources Information Center

Horrocks, Erin L.; Morgan, Robert L.

2011-01-01

A multicomponent training package (live training, video modeling, role playing, and feedback) was used to train teachers to conduct assessment and to instruct students with profound multiple disabilities. Phase 1 of the study involved training seven teachers to conduct assessment in three areas: (a) preference assessment (i.e., identification of…

The Effect of Frequency Transposition on Speech Perception in Adolescents and Young Adults with Profound Hearing Loss

ERIC Educational Resources Information Center

Gou, J.; Smith, J.; Valero, J.; Rubio, I.

2011-01-01

This paper reports on a clinical trial evaluating outcomes of a frequency-lowering technique for adolescents and young adults with severe to profound hearing impairment. Outcomes were defined by changes in aided thresholds, speech perception, and acceptance. The participants comprised seven young people aged between 13 and 25 years. They were…

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology.

PubMed

Nilsen, Kari-Anne; Ihle, Kate E; Frederick, Katy; Fondrk, M Kim; Smedal, Bente; Hartfelder, Klaus; Amdam, Gro V

2011-05-01

Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee's ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain.

Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

PubMed Central

Birge, R B; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, R A; Huang, X; Hutchins, J T; Freimark, B; Empig, C; Mercer, J; Schroit, A J; Schett, G; Herrmann, M

2016-01-01

Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics. PMID:26915293

Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer.

PubMed

Birge, R B; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, R A; Huang, X; Hutchins, J T; Freimark, B; Empig, C; Mercer, J; Schroit, A J; Schett, G; Herrmann, M

2016-06-01

Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics.

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology

PubMed Central

Nilsen, Kari-Anne; Ihle, Kate E.; Frederick, Katy; Fondrk, M. Kim; Smedal, Bente; Hartfelder, Klaus; Amdam, Gro V.

2011-01-01

SUMMARY Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee's ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain. PMID:21490257

High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment

PubMed Central

Taylor, Andrew T.

2011-01-01

High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler. PMID:23908794

How tree roots respond to drought

PubMed Central

Brunner, Ivano; Herzog, Claude; Dawes, Melissa A.; Arend, Matthias; Sperisen, Christoph

2015-01-01

The ongoing climate change is characterized by increased temperatures and altered precipitation patterns. In addition, there has been an increase in both the frequency and intensity of extreme climatic events such as drought. Episodes of drought induce a series of interconnected effects, all of which have the potential to alter the carbon balance of forest ecosystems profoundly at different scales of plant organization and ecosystem functioning. During recent years, considerable progress has been made in the understanding of how aboveground parts of trees respond to drought and how these responses affect carbon assimilation. In contrast, processes of belowground parts are relatively underrepresented in research on climate change. In this review, we describe current knowledge about responses of tree roots to drought. Tree roots are capable of responding to drought through a variety of strategies that enable them to avoid and tolerate stress. Responses include root biomass adjustments, anatomical alterations, and physiological acclimations. The molecular mechanisms underlying these responses are characterized to some extent, and involve stress signaling and the induction of numerous genes, leading to the activation of tolerance pathways. In addition, mycorrhizas seem to play important protective roles. The current knowledge compiled in this review supports the view that tree roots are well equipped to withstand drought situations and maintain morphological and physiological functions as long as possible. Further, the reviewed literature demonstrates the important role of tree roots in the functioning of forest ecosystems and highlights the need for more research in this emerging field. PMID:26284083

Stem cell-biomaterial interactions for regenerative medicine.

PubMed

Martino, Sabata; D'Angelo, Francesco; Armentano, Ilaria; Kenny, Josè Maria; Orlacchio, Aldo

2012-01-01

The synergism of stem cell biology and biomaterial technology promises to have a profound impact on stem-cell-based clinical applications for tissue regeneration. Biomaterials development is rapidly advancing to display properties that, in a precise and physiological fashion, could drive stem-cell fate both in vitro and in vivo. Thus, the design of novel materials is trying to recapitulate the molecular events involved in the production, clearance and interaction of molecules within tissue in pathologic conditions and regeneration of tissue/organs. In this review we will report on the challenges behind translating stem cell biology and biomaterial innovations into novel clinical therapeutic applications for tissue and organ replacements (graphical abstract). Copyright © 2011 Elsevier Inc. All rights reserved.

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract

PubMed Central

Mimee, Andrea

2015-01-01

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. PMID:25695291

The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects.

PubMed

Claessens, M; Calame, W; Siemensma, A D; van Baak, M A; Saris, W H M

2009-01-01

To study the effect of four protein hydrolysates from vegetable (pea, gluten, rice and soy) and two protein hydrolysates from animal origin (whey and egg) on glucagon and insulin responses. Eight healthy normal-weight male subjects participated in this study. The study employed a repeated-measures design with Latin square randomization and single-blind trials. Protein hydrolysates used in this study (pea, rice, soy, gluten, whey and egg protein hydrolysate) consisted of 0.2 g hydrolysate per kg body weight (bw) and 0.2 g maltodextrin per kg bw and were compared to maltodextrin alone. Postprandial plasma glucose, glucagon, insulin and amino acids were determined over 2 h. All protein hydrolysates induced an enhanced insulin secretion compared to maltodextrin alone and a correspondingly low plasma glucose response. A significant difference was observed in area under the curve (AUC) for plasma glucagon between protein hydrolysates and the maltodextrin control drink (P<0.05). Gluten protein hydrolysate induced the lowest glucagon response. High amino-acid-induced glucagon response does not necessarily go together with low insulin response. Protein hydrolysate source affects AUC for glucagon more profoundly than for insulin, although the protein load used in this study seemed to be at lower level for significant physiological effects.

Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells.

PubMed

Ortega, J Alberto; Sirois, Carissa L; Memi, Fani; Glidden, Nicole; Zecevic, Nada

2017-07-01

The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation. Small changes in O2 levels profoundly affected RGC survival, proliferation, and differentiation. Physiological hypoxia (3% O2) promoted neurogenesis, whereas anoxia (<1% O2) and severe hypoxia (1% O2) arrested the differentiation of human RGCs, mainly by altering the generation of glutamatergic neurons. The in vitro activation of Wnt-β-catenin signaling rescued the proliferation and neuronal differentiation of RGCs subjected to anoxia. Pathologic hypoxia (≤1% O2) also exerted negative effects on gliogenesis, by decreasing the number of O4+ preoligodendrocytes and increasing the number of reactive astrocytes derived from cortical RGCs. O2-dependent alterations in glutamatergic neurogenesis and oligodendrogenesis can lead to significant changes in cortical circuitry formation. A better understanding of the cellular effects caused by changes in O2 levels during human cortical development is essential to elucidating the etiology of numerous neurodevelopmental disorders. Published by Oxford University Press 2016.

Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

PubMed

Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

2018-04-20

Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P < 0.05). Four of seven animals exhibited apneas of ≥20 sec requiring immediate termination of perineural blockade. Breathing rates decreased from the baseline value of 53 ± 12 to 24 ± 20 breaths/min during blockade despite an increased PaCO 2 (P < 0.001). Following blockade, breathing patterns returned to baseline values despite marked hypocapnia (PaCO 2 33 ± 3 torr; P = 0.03). Respiratory depression and apneas were independent of sleep states. This study provides the much needed physiologic evidence that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Rather, change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Perception of persons with severe or profound deafness about the communication process during health care.

PubMed

Cardoso, Adriane Helena Alves; Rodrigues, Karla Gomes; Bachion, Maria Márcia

2006-01-01

This study describes a qualitative approach with the objective of characterizing the perceptions of people with severe or profound deafness about the communication process in the context of health care services. Study participants were 11 people with severe and/or profound deafness, who were interviewed using Brazilian sign language (LIBRAS). The interactions were videotaped and then transcribed. Care was taken to maintain the grammatical construction which was characteristic in the expression of each person. Three categories emerged from thematic analysis: Understanding, Need for Mediation, Feelings. Deaf persons do not achieve effective communication in health care, during which they experience negative feelings. Hence, the presence of a professional interpreter is needed.

Growth efficiency in transgenic tilapia (Oreochromis sp.) carrying a single copy of an homologous cDNA growth hormone.

PubMed

Martínez, R; Juncal, J; Zaldívar, C; Arenal, A; Guillén, I; Morera, V; Carrillo, O; Estrada, M; Morales, A; Estrada, M P

2000-01-07

Growth hormone (GH) has been shown to have a profound impact on fish physiology and metabolism. However, detailed studies in transgenic fish have not been conducted. We have characterized the food conversion efficiency, protein profile, and biochemical correlates of growth rate in transgenic tilapia expressing the tilapia GH cDNA under the control of human cytomegalovirus regulatory sequences. Transgenic tilapia exhibited about 3.6-fold less food consumption than nontransgenic controls (P < 0.001). The food conversion efficiency was significantly (P < 0.05) higher (290%) in transgenic tilapia (2.3 +/- 0.4) than in the control group (0.8 +/- 0.2). Efficiency of growth, synthesis retention, anabolic stimulation, and average protein synthesis were higher in transgenic than in nontransgenic tilapia. Distinctive metabolic differences were found in transgenic juvenile tilapia. We had found differences in hepatic glucose, and in agreement with previous results we observed differences in the level of enzymatic activities in target organs. We conclude that GH-transgenic juvenile tilapia show altered physiological and metabolic conditions and are biologically more efficient. Copyright 2000 Academic Press.

Development of the infant intestinal microbiome: A bird's eye view of a complex process.

PubMed

Meropol, Sharon B; Edwards, Amy

2015-12-01

Infants undergo profound shifts in colonizing intestinal microorganisms during their first year, especially during and after birth and during weaning. Microbiota are passed to infants through the placenta, during the vaginal birth process, and from early diet and other environmental exposures. These microbiota play an active role in the development of healthy infant metabolic and immunologic systems; profound shifts in microbiotal populations can be persistent, are associated with immediate alterations in gene expression, metabolic, immunologic, and neurologic function, and with downstream metabolic and immunologic consequences such as obesity, allergies, asthma, autoimmune diseases, and potentially neurologic conditions. Many modern exposures, including Cesarean section, formula feeding, and antibiotics, have been associated with microbiome shifts, and also with downstream diseases; while many published studies considered exposures individually, a more comprehensive understanding of their interaction and impact will consider the entirety of the infant's environment. It is not possible, nor desirable, to return to a world without toilets, sewers, tap water, delivery room antisepsis, Cesarean sections, antibiotics, immunizations, and refrigerators; our other alternative is to better understand these complex changes in infant developmental and molecular physiology. Protecting and repairing the developmental processes of the healthy infant microbiome is the modern medical frontier. © 2015 Wiley Periodicals, Inc.

An acoustic analysis of laughter produced by congenitally deaf and normally hearing college students1

PubMed Central

Makagon, Maja M.; Funayama, E. Sumie; Owren, Michael J.

2008-01-01

Relatively few empirical data are available concerning the role of auditory experience in nonverbal human vocal behavior, such as laughter production. This study compared the acoustic properties of laughter in 19 congenitally, bilaterally, and profoundly deaf college students and in 23 normally hearing control participants. Analyses focused on degree of voicing, mouth position, air-flow direction, temporal features, relative amplitude, fundamental frequency, and formant frequencies. Results showed that laughter produced by the deaf participants was fundamentally similar to that produced by the normally hearing individuals, which in turn was consistent with previously reported findings. Finding comparable acoustic properties in the sounds produced by deaf and hearing vocalizers confirms the presumption that laughter is importantly grounded in human biology, and that auditory experience with this vocalization is not necessary for it to emerge in species-typical form. Some differences were found between the laughter of deaf and hearing groups; the most important being that the deaf participants produced lower-amplitude and longer-duration laughs. These discrepancies are likely due to a combination of the physiological and social factors that routinely affect profoundly deaf individuals, including low overall rates of vocal fold use and pressure from the hearing world to suppress spontaneous vocalizations. PMID:18646991

Obesity, Asthma, and Exercise in Child and Adolescent Health

PubMed Central

Lu, Kim D.; Manoukian, Krikor; Radom-Aizik, Shlomit; Cooper, Dan M.; Galant, Stanley P.

2018-01-01

Obesity increases the risk of asthma throughout life but the underlying mechanisms linking these all too common threats to child health are poorly understood. Acute bouts of exercise, aerobic fitness, and levels of physical activity clearly play a role in the pathogenesis and/or management of both childhood obesity and asthma. Moreover, both obesity and physical inactivity are associated with asthma symptomatology and response to therapy (a particularly challenging feature of obesity-related asthma). In this article, we review current understandings of the link between physical activity, aerobic fitness and the asthma-obesity link in children and adolescents (e.g., the impact of chronic low-grade inflammation, lung mechanics, and direct effects of metabolic health on the lung). Gaps in our knowledge regarding the physiological mechanisms linking asthma, obesity and exercise are often compounded by imprecise estimations of adiposity and challenges of assessing aerobic fitness in children. Addressing these gaps could lead to practical interventions and clinical approaches that could mitigate the profound health care crisis of the increasing comorbidity of asthma, physical inactivity, and obesity in children. PMID:26618409

Scaling the metabolic balance of the oceans.

PubMed

López-Urrutia, Angel; San Martin, Elena; Harris, Roger P; Irigoien, Xabier

2006-06-06

Oceanic communities are sources or sinks of CO2, depending on the balance between primary production and community respiration. The prediction of how global climate change will modify this metabolic balance of the oceans is limited by the lack of a comprehensive underlying theory. Here, we show that the balance between production and respiration is profoundly affected by environmental temperature. We extend the general metabolic theory of ecology to the production and respiration of oceanic communities and show that ecosystem rates can be reliably scaled from theoretical knowledge of organism physiology and measurement of population abundance. Our theory predicts that the differential temperature-dependence of respiration and photosynthesis at the organism level determines the response of the metabolic balance of the epipelagic ocean to changes in ambient temperature, a prediction that we support with empirical data over the global ocean. Furthermore, our model predicts that there will be a negative feedback of ocean communities to climate warming because they will capture less CO2 with a future increase in ocean temperature. This feedback of marine biota will further aggravate the anthropogenic effects on global warming.

Real-time sweat analysis via alternating current conductivity of artificial and human sweat

NASA Astrophysics Data System (ADS)

Liu, Gengchen; Alomari, Mahmoud; Sahin, Bunyamin; Snelgrove, Samuel E.; Edwards, Jeffrey; Mellinger, Axel; Kaya, Tolga

2015-03-01

Dehydration is one of the most profound physiological challenges that significantly affects athletes and soldiers if not detected early. Recently, a few groups have focused on dehydration detection using sweat as the main biomarker. Although there are some proposed devices, the electrical and chemical characteristics of sweat have yet to be incorporated into the validations. In this work, we have developed a simple test setup to analyze artificial sweat that is comprised the main components of human sweat. We provide theoretical and experimental details on the electrical and chemical behavior of the artificial sweat for various concentration values within a temperature range of 5 °C to 50 °C. We have also developed an efficient sweat collecting and detection system based on 3D printing. Human studies were conducted and this particular protocol has shown that dehydration starts to take effect as early as 40 min into the physical activity if there is no fluid intake during the exercise. We believe that our device will lead to developing viable real-time sweat analysis systems.

Docosahexaenoic Acid and Cognition throughout the Lifespan

PubMed Central

Weiser, Michael J.; Butt, Christopher M.; Mohajeri, M. Hasan

2016-01-01

Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action. PMID:26901223

Theoretical and practical considerations in the application of whole body plethysmography to sleep research.

PubMed

Stephenson, Richard; Gucciardi, Enza J

2002-07-01

The sleep-wake state has a profound influence on many, perhaps most, aspects of normal physiology and is strongly implicated in the mediation (or remediation) of impaired health and performance. Many sleep disorders stem from abnormal respiratory anatomy or sleep-induced changes in respiratory control, underscoring the need for research into the effects of the sleep-wake state on respiratory control processes. Whole body plethysmography is being increasingly used to study respiration in freely behaving animals, and is especially well suited to studies of sleeping animals and human subjects. The method is simple in principle, but care is required in its application to ensure reliable results, and there are circumstances in which it is an inappropriate technique. This review describes the main advantages, pitfalls, and limitations inherent in the use of whole body plethysmography for non-invasive measurement of lung ventilation and metabolic rate in sleeping animals. Sources of potential error, and ways of avoiding such errors, are discussed, with reference to studies involving animal models of sleep-related breathing disorders.

Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression.

PubMed

Gamé, Xavier; Allard, Julien; Escourrou, Ghislaine; Gourdy, Pierre; Tack, Ivan; Rischmann, Pascal; Arnal, Jean-François; Malavaud, Bernard

2008-03-01

Estrogens are known to modulate lower urinary tract (LUT) trophicity and neuronal nitric oxide synthase (nNOS) expression in several organs. The aim of this study was to explore the effects of endogenous and supraestrus levels of 17beta-estradiol (E2) on LUT and urethral nNOS expression and function. LUT function and histology and urethral nNOS expression were studied in adult female mice subjected either to sham surgery, surgical castration, or castration plus chronic E2 supplementation (80 microg.kg(-1).day(-1), i.e., pregnancy level). The micturition pattern was profoundly altered by long-term supraestrus levels of E2 with decreased frequency paralleled by increased residual volumes higher than those of ovariectomized mice. Urethral resistance was increased twofold in E2-treated mice, with no structural changes in urethra, supporting a pure tonic mechanism. Acute nNOS inhibition by 7-nitroindazole decreased frequency and increased residual volumes in ovariectomized mice but had no additive effect on the micturition pattern of long-term supraestrus mice, showing that long-term supraestrus E2 levels and acute inhibition of nNOS activity had similar functional effects. Finally, E2 decreased urethral nNOS expression in ovariectomized mice. Long-term supraestrus levels of E2 increased urethral tone through inhibition of nNOS expression, whereas physiological levels of E2 had no effect.

Does social environment influence learning ability in a family-living lizard?

PubMed

Riley, Julia L; Noble, Daniel W A; Byrne, Richard W; Whiting, Martin J

2017-05-01

Early developmental environment can have profound effects on individual physiology, behaviour, and learning. In birds and mammals, social isolation during development is known to negatively affect learning ability; yet in other taxa, like reptiles, the effect of social isolation during development on learning ability is unknown. We investigated how social environment affects learning ability in the family-living tree skink (Egernia striolata). We hypothesized that early social environment shapes cognitive development in skinks and predicted that skinks raised in social isolation would have reduced learning ability compared to skinks raised socially. Offspring were separated at birth into two rearing treatments: (1) raised alone or (2) in a pair. After 1 year, we quantified spatial learning ability of skinks in these rearing treatments (N = 14 solitary, 14 social). We found no effect of rearing treatment on learning ability. The number of skinks to successfully learn the task, the number of trials taken to learn the task, the latency to perform the task, and the number of errors in each trial did not differ between isolated and socially reared skinks. Our results were unexpected, yet the facultative nature of this species' social system may result in a reduced effect of social isolation on behaviour when compared to species with obligate sociality. Overall, our findings do not provide evidence that social environment affects development of spatial learning ability in this family-living lizard.

Home alone: a systematic review and meta-analysis on the effects of individual housing on body weight, food intake and visceral fat mass in rodents.

PubMed

Schipper, L; Harvey, L; van der Beek, E M; van Dijk, G

2018-05-01

Rats and mice are widely used to study environmental effects on psychological and metabolic health. Study designs differ widely and are often characterized by varying (social) housing conditions. In itself, housing has a profound influence on physiology and behaviour of rodents, affecting energy balance and sustainable metabolic health. However, evidence for potential long-term consequences of individual versus social housing on body weight and metabolic phenotype is inconsistent. We conducted a systematic literature review and meta-analyses assessing effects of individual versus social housing of rats and mice, living under well-accepted laboratory conditions, on measures of metabolic health, including body weight, food intake and visceral adipose tissue mass. Seventy-one studies were included in this review; 59 were included in the meta-analysis. Whilst housing did not affect body weight, both food intake and visceral adipose tissue mass were significantly higher in individually compared with socially housed animals. A combination of emotional stress and lack of social thermoregulation likely contributed to these effects. Increased awareness of consequences and improved specifications of housing conditions are necessary to accurately evaluate efficacy of drugs, diets or other interventions on metabolic and other health outcomes because housing conditions are rarely considered as possible moderators of reported outcomes. © 2018 World Obesity Federation.

Anatomy and computational modeling of networks underlying cognitive-emotional interaction.

PubMed

John, Yohan J; Bullock, Daniel; Zikopoulos, Basilis; Barbas, Helen

2013-01-01

The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top-down signals from prefrontal cortex realize "cognitive control" in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior.

Expanding application of the Wiggers diagram to teach cardiovascular physiology.

PubMed

Mitchell, Jamie R; Wang, Jiun-Jr

2014-06-01

Dr. Carl Wiggers' careful observations have provided a meaningful resource for students to learn how the heart works. Throughout the many years from his initial reports, the Wiggers diagram has been used, in various degrees of complexity, as a fundamental tool for cardiovascular instruction. Often, the various electrical and mechanical plots are the novice learner's first exposure to simulated data. As the various temporal relationships throughout a heartbeat could simply be memorized, the challenge for the cardiovascular instructor is to engage the learner so the underlying mechanisms governing the changing electrical and mechanical events are truly understood. Based on experience, we suggest some additions to the Wiggers diagram that are not commonly used to enhance cardiovascular pedagogy. For example, these additions could be, but are not limited to, introducing the concept of energy waves and their role in influencing pressure and flow in health and disease. Also, integrating concepts of exercise physiology, and the differences in cardiac function and hemodynamics between an elite athlete and normal subject, can have a profound impact on student engagement. In describing the relationship between electrical and mechanical events, the instructor may find the introduction of premature ventricular contractions as a useful tool to further understanding of this important principle. It is our hope that these examples can aid cardiovascular instructors to engage their learners and promote fundamental understanding at the expense of simple memorization. Copyright © 2014 The American Physiological Society.

Immune System Dysfunction in the Elderly.

PubMed

Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

2017-01-01

Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

Hepatic stellate cells in liver development, regeneration, and cancer

PubMed Central

Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.

2013-01-01

Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans

PubMed Central

Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; Kala, G.; Rodgers, A. S.; Rogers, A.; Inniss, A. M.; Rice, B. L.; Ericson, K.; Coburn, S.; Bourbeau, Y.; Hudson, E.; Mathew, G.; DeKerlegand, D. E.; Sams, C. F.; Heer, M. A.; Paloski, W. H.; Smith, S. M.

2009-01-01

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum α- and γ-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma β-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest. PMID:19074571

The Hands with Eyes and Nose in the Palm: As Effective Communication Alternatives for Profoundly Deaf People in Zimbabwe

ERIC Educational Resources Information Center

Mutswanga, Phillipa

2017-01-01

Drawing from the experiences and testimonies of people with profound deafness, the study qualitatively explored the use of the hands with eyes and nose in the palm as communication alternatives in the field of deafness. The study was prompted by the 27 year old lady, Leah Katz-Hernandez who is deaf who got engaged in March 2015 as the 2016…

Effectiveness of a nurse-led preadmission intervention for parents of children with profound multiple disabilities undergoing hip-joint surgery: A quasi-experimental pilot study.

PubMed

Seliner, Brigitte; Latal, Beatrice; Spirig, Rebecca

2017-07-01

The aim of this study was to assess the effectiveness of a family-centered care (FCC) intervention provided by an advanced practice nurse (APN) for parents of children with profound disabilities undergoing surgery. In a quasi-experimental design, we used the MPOC-20 to assess satisfaction with FCC and interviews to identify potential mechanisms for improving satisfaction. There was a positive effect on the MPOC-20 domain "general information," albeit with a small effect size (Cohen's d = 0.35). The interviewed parents expected additional support. Emphasis should be placed on providing comprehensive care coordination by an experienced APN. Shared care management is crucial in improving FCC. © 2017 Wiley Periodicals, Inc.

Cancer: Mitochondrial Origins.

PubMed

Stefano, George B; Kream, Richard M

2015-12-01

The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial matrix. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionary fashioned chemiosmotic production of ATP as a high-efficiency biological process. The mechanistic bases of carcinogenesis have demonstrated profound alteration of normative mitochondrial function, notably dysregulated respiratory processes. Accordingly, the classic Warburg effect functionally links aerobic glycolysis, aberrant production and release of lactate, and metabolic down-regulation of mitochondrial oxidative processes with the carcinogenetic phenotype. We surmise, however, that aerobic fermentation by cancer cells may also represent a developmental re-emergence of an evolutionarily conserved early phenotype, which was "sidelined" with the emergence of mitochondrial oxidative phosphorylation as a primary mechanism for ATP production in normal cells. Regardless of state-dependent physiological status in mixed populations of cancer cells, it has been established that mitochondria are functionally linked to the initiation of cancer and its progression. Biochemical, molecular, and physiological differences in cancer cell mitochondria, notably mtDNA heteroplasmy and allele-specific expression of selected nuclear genes, may represent major focal points for novel targeting and elimination of cancer cells in metastatic disease afflicting human populations. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial targeted therapies has not been forthcoming.

Passive warming reduces stress and shifts reproductive effort in the Antarctic moss, Polytrichastrum alpinum

PubMed Central

Shortlidge, Erin E.; Eppley, Sarah M.; Kohler, Hans; Rosenstiel, Todd N.; Zúñiga, Gustavo E.; Casanova-Katny, Angélica

2017-01-01

Background and Aims The Western Antarctic Peninsula is one of the most rapidly warming regions on Earth, and many biotic communities inhabiting this dynamic region are responding to these well-documented climatic shifts. Yet some of the most prevalent organisms of terrestrial Antarctica, the mosses, and their responses to warming have been relatively overlooked and understudied. In this research, the impacts of 6 years of passive warming were investigated using open top chambers (OTCs), on moss communities of Fildes Peninsula, King George Island, Antarctica. Methods The effects of experimental passive warming on the morphology, sexual reproductive effort and stress physiology of a common dioicous Antarctic moss, Polytrichastrum alpinum, were tested, gaining the first species-specific mechanistic insight into moss responses to warming in the Antarctic. Additionally community analyses were conducted examining the impact of warming on overall moss percentage cover and sporophyte production in intact Antarctic moss communities. Key Results Our results show a generally greater percentage moss cover under warming conditions as well as increased gametangia production in P. alpinum. Distinct morphological and physiological shifts in P. alpinum were found under passive warming compared with those without warming: warmed mosses reduced investment in cellular stress defences, but invested more towards primary productivity and gametangia development. Conclusions Taken together, results from this study of mosses under passive warming imply that in ice-free moss-dominated regions, continued climate warming will probably have profound impacts on moss biology and colonization along the Western Antarctic Peninsula. Such findings highlight the fundamental role that mosses will play in influencing the terrestrialization of a warming Antarctica. PMID:27794516

Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation

PubMed Central

Gong, Yuanying; Ma, Yufang; Sinyuk, Maksim; Loganathan, Sudan; Thompson, Reid C.; Sarkaria, Jann N.; Chen, Wenbiao; Lathia, Justin D.; Mobley, Bret C.; Clark, Stephen W.; Wang, Jialiang

2016-01-01

Background Metabolic complications such as obesity, hyperglycemia, and type 2 diabetes are associated with poor outcomes in patients with glioblastoma. To control peritumoral edema, use of chronic high-dose steroids in glioblastoma patients is common, which can result in de novo diabetic symptoms. These metabolic complications may affect tumors via profound mechanisms, including activation of insulin receptor (InsR) and the related insulin-like growth factor 1 receptor (IGF1R) in malignant cells. Methods In the present study, we assessed expression of InsR in glioblastoma surgical specimens and glioblastoma response to insulin at physiologically relevant concentrations. We further determined whether genetic or pharmacological targeting of InsR affected oncogenic functions of glioblastoma in vitro and in vivo. Results We showed that InsR was commonly expressed in glioblastoma surgical specimens and xenograft tumor lines, with mitogenic isoform-A predominating. Insulin at physiologically relevant concentrations promoted glioblastoma cell growth and survival, potentially via Akt activation. Depletion of InsR impaired cellular functions and repressed orthotopic tumor growth. The absence of InsR compromised downstream Akt activity, but yet stimulated IGF1R expression. Targeting both InsR and IGF1R with dual kinase inhibitors resulted in effective blockade of downstream signaling, loss of cell viability, and repression of xenograft tumor growth. Conclusions Taken together, our work suggests that glioblastoma is sensitive to the mitogenic functions of insulin, thus significant insulin exposure imposes risks to glioblastoma patients. Additionally, dual inhibition of InsR and IGF1R exhibits promise for treating glioblastoma. PMID:26136493

Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

PubMed

Ferner, Robin E; Aronson, Jeffrey K

2016-01-01

We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

Transcription Factor-Mediated Control of Anthocyanin Biosynthesis in Vegetative Tissues1[OPEN

PubMed Central

Outchkourov, Nikolay S.; Schrama, Xandra; Blilou, Ikram; Jongedijk, Esmer; Simon, Carmen Diez; Bosch, Dirk; Hall, Robert D.

2018-01-01

Plants accumulate secondary metabolites to adapt to environmental conditions. These compounds, here exemplified by the purple-colored anthocyanins, are accumulated upon high temperatures, UV-light, drought, and nutrient deficiencies, and may contribute to tolerance to these stresses. Producing compounds is often part of a more broad response of the plant to changes in the environment. Here we investigate how a transcription-factor-mediated program for controlling anthocyanin biosynthesis also has effects on formation of specialized cell structures and changes in the plant root architecture. A systems biology approach was developed in tomato (Solanum lycopersicum) for coordinated induction of biosynthesis of anthocyanins, in a tissue- and development-independent manner. A transcription factor couple from Antirrhinum that is known to control anthocyanin biosynthesis was introduced in tomato under control of a dexamethasone-inducible promoter. By application of dexamethasone, anthocyanin formation was induced within 24 h in vegetative tissues and in undifferentiated cells. Profiles of metabolites and gene expression were analyzed in several tomato tissues. Changes in concentration of anthocyanins and other phenolic compounds were observed in all tested tissues, accompanied by induction of the biosynthetic pathways leading from Glc to anthocyanins. A number of pathways that are not known to be involved in anthocyanin biosynthesis were observed to be regulated. Anthocyanin-producing plants displayed profound physiological and architectural changes, depending on the tissue, including root branching, root epithelial cell morphology, seed germination, and leaf conductance. The inducible anthocyanin-production system reveals a range of phenomena that accompanies anthocyanin biosynthesis in tomato, including adaptions of the plants architecture and physiology. PMID:29192027

Multiple trauma in children: critical care overview.

PubMed

Wetzel, Randall C; Burns, R Cartland

2002-11-01

Multiple trauma is more than the sum of the injuries. Management not only of the physiologic injury but also of the pathophysiologic responses, along with integration of the child's emotional and developmental needs and the child's family, forms the basis of trauma care. Multiple trauma in children also elicits profound psychological responses from the healthcare providers involved with these children. This overview will address the pathophysiology of multiple trauma in children and the general principles of trauma management by an integrated trauma team. Trauma is a systemic disease. Multiple trauma stimulates the release of multiple inflammatory mediators. A lethal triad of hypothermia, acidosis, and coagulopathy is the direct result of trauma and secondary injury from the systemic response to trauma. Controlling and responding to the secondary pathophysiologic sequelae of trauma is the cornerstone of trauma management in the multiply injured, critically ill child. Damage control surgery is a new, rational approach to the child with multiple trauma. The selection of children for damage control surgery depends on the severity of injury. Major abdominal vascular injuries and multiple visceral injuries are best considered for this approach. The effective management of childhood multiple trauma requires a combined team approach, consideration of the child and family, an organized trauma system, and an effective quality assurance and improvement mechanism.

Theoretical studies on the control of oxidative phosphorylation in muscle mitochondria: application to mitochondrial deficiencies.

PubMed

Korzeniewski, B; Mazat, J P

1996-10-01

1. The dynamic model of oxidative phosphorylation developed previously for rat liver mitochondria incubated with succinate was adapted for muscle mitochondria respiring on pyruvate. We introduced the following changes considering: (1) a higher external ATP/ADP ratio and an ATP/ADP carrier less displaced from equilibrium; (2) a substrate dehydrogenation more sensitive to the NADH/NAD+ ratio; and (3) the respiratory chain, ATP synthase and phosphate carrier being more displaced from equilibrium. The experimental flux control coefficients already determined in state 3 for respiratory rate and ATP synthesis were used to adjust some parameters. This new oxidative phosphorylation model enabled us to simulate the whole titration curves obtained experimentally in state 3. These curves, which mimic the effect of mitochondrial complex deficiencies on oxidative phosphorylation, show a threshold effect, which is reproduced by the model. 2. the model was also used to simulate other physiological conditions such as (i) state 3.5, conditions in-between state 4 and state 3; and (ii) hypoxic conditions. In both cases a profound change in the pattern of the control coefficients was shown. 3. This model was thus found useful in investigating a variety of new conditions, the most interesting of which can then be experimentally studied.

Socioecological predictors of immune defences in wild spotted hyenas

PubMed Central

Flies, Andrew S.; Mansfield, Linda S.; Flies, Emily J.; Grant, Chris K.; Holekamp, Kay E.

2016-01-01

Summary Social rank can profoundly affect many aspects of mammalian reproduction and stress physiology, but little is known about how immune function is affected by rank and other socio-ecological factors in free-living animals.In this study we examine the effects of sex, social rank, and reproductive status on immune function in long-lived carnivores that are routinely exposed to a plethora of pathogens, yet rarely show signs of disease.Here we show that two types of immune defenses, complement-mediated bacterial killing capacity (BKC) and total IgM, are positively correlated with social rank in wild hyenas, but that a third type, total IgG, does not vary with rank.Female spotted hyenas, which are socially dominant to males in this species, have higher BKC, and higher IgG and IgM concentrations, than do males.Immune defenses are lower in lactating than pregnant females, suggesting the immune defenses may be energetically costly.Serum cortisol and testosterone concentrations are not reliable predictors of basic immune defenses in wild female spotted hyenas.These results suggest that immune defenses are costly and multiple socioecological variables are important determinants of basic immune defenses among wild hyenas. Effects of these variables should be accounted for when attempting to understand disease ecology and immune function. PMID:27833242

Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts.

PubMed

Mellinghoff, Ingo K; Tran, Chris; Sawyers, Charles L

2002-09-15

Experiments with human prostate cancer cell lines have shown that forced overexpression of the ErbB2-receptor tyrosine kinase (RTK) promotes androgen-independent growth and increases androgen receptor-transcriptional activity in a ligand-independent fashion. To investigate the relationship between ErbB-RTK signaling and androgen in genetically unmanipulated human prostate cancer, we performed biochemical and biological studies with the dual ErbB1/ErbB2 RTK inhibitor PKI-166 using human prostate cancer xenograft models with isogenic sublines reflecting the transition from androgen-dependent to androgen-independent growth. In the presence of low androgen concentrations, PKI-166 showed profound growth-inhibitory effects on tumor growth, which could be partially reversed by androgen add-back. At physiological androgen concentrations, androgen withdrawal greatly enhanced the ability of PKI-166 to retard tumor growth. The level of extracellular signal-regulated kinase activation correlated with the response to PKI-166 treatment, whereas the expression levels of ErbB1 and ErbB2 did not. These results suggest that ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent prostate cancer and provide a rationale for clinical evaluation of inhibitors targeted to this pathway.

Microbiota-targeted therapies on the intensive care unit.

PubMed

Haak, Bastiaan W; Levi, Marcel; Wiersinga, W Joost

2017-04-01

The composition and diversity of the microbiota of the human gut, skin, and several other sites is severely deranged in critically ill patients on the ICU, and it is likely that these disruptions can negatively affect outcome. We here review new and ongoing studies that investigate the use of microbiota-targeted therapeutics in the ICU, and provide recommendations for future research. Practically every intervention in the ICU as well as the physiological effects of critical illness itself can have a profound impact on the gut microbiota. Therapeutic modulation of the microbiota, aimed at restoring the balance between 'pathogenic' and 'health-promoting' microbes is therefore of significant interest. Probiotics have shown to be effective in the treatment of ventilator-associated pneumonia, and the first fecal microbiota transplantations have recently been safely and successfully performed in the ICU. However, all-encompassing data in this vulnerable patient group remain sparse, and only a handful of novel studies that study microbiota-targeted therapies in the ICU are currently ongoing. Enormous strides have been made in characterizing the gut microbiome of critically ill patients in the ICU, and an increasing amount of preclinical data reveals the huge potential of microbiota-targeted therapies. Further understanding of the causes and consequences of dysbiosis on ICU-related outcomes are warranted to push the field forward.

Nonenzymatic glycation of guanosine 5'-triphosphate by glyceraldehyde: an in vitro study of AGE formation.

PubMed

Li, Yuyuan; Dutta, Udayan; Cohenford, Menashi A; Dain, Joel A

2007-12-01

Guanosine 5'-triphosphate (GTP) plays a significant role in the bioenergetics, metabolism, and signaling of cells; consequently, any modifications to the structure of the molecule can have profound effects on a cell's survival and function. Previous studies in our laboratory demonstrated that like proteins, purines, and pyrimidines can nonenzymatically react with sugars to generate advanced glycation endproducts (AGEs) and that these AGEs can form in vitro under physiological conditions. The objective of this investigation was twofold. First, it was to evaluate the susceptibility of ATP, GTP, CTP, and TTP to nonenzymatic modification by D-glucose and DL-glyceraldehyde, and second to assess the effect of various factors such as temperature, pH and incubation time, and sugar concentration on the rate and extent of nucleotide triphosphate AGE formation. Of the four nucleotide triphosphates that were studied, only GTP was significantly reactive forming a heterogeneous group of compounds with DL-glyceraldehyde. D-Glucose exhibited no significant reactivity with any of the nucleotide triphosphates, a finding that was supported by UV and fluorescence spectroscopy. Capillary electrophoresis, high-performance liquid chromatography and mass spectrometry allowed for a thorough analysis of the glycated GTP products and demonstrated that the modification of GTP by dl-glyceraldehyde occurred via the classical Amadori pathway.

How to optimise antimicrobial prescriptions in the Intensive Care Unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics.

PubMed

Roberts, Jason A; Joynt, Gavin M; Choi, Gordon Y S; Gomersall, Charles D; Lipman, Jeffrey

2012-03-01

Optimising antimicrobial dosing for critically ill patients is highly challenging and when it is not achieved can lead to worse patient outcomes. To this end, use of dosing regimens recommended in package inserts from drug manufacturers is frequently insufficient to guide dosing in these patients appropriately. Whilst the effect of critical illness pathophysiology on the pharmacokinetic (PK) behaviour of antimicrobials can be profound, the variability of these changes between patients is still being quantified. The PK effects of hypoproteinaemia, organ dysfunction and the presence of augmented renal clearance may lead to plasma antimicrobial concentrations that are difficult to predict at the bedside, which may result in excess toxicity or suboptimal bacterial killing. This paper outlines the factors that affect pharmacokinetics in critically ill patients and how knowledge of these factors can increase the likelihood of achieving optimal antimicrobial plasma concentrations. In selected settings, we advocate individualised dosing of renally cleared antimicrobials using physiological data such as measured creatinine clearance and published non-renal clearance data. Where such data do not exist, therapeutic drug monitoring may be a useful alternative and has been associated with significant clinical benefits, although it is not currently widely available. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Supporting end of life decision making: Case studies of relational closeness in supported decision making for people with severe or profound intellectual disability.

PubMed

Watson, Joanne; Wilson, Erin; Hagiliassis, Nick

2017-11-01

The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) promotes the use of supported decision making in lieu of substitute decision making. To date, there has been a lack of focus on supported decision making for people with severe or profound intellectual disability, including for end of life decisions. Five people with severe or profound intellectual disability's experiences of supported decision making were examined. This article is particularly focused on one participant's experiences at the end of his life. All five case studies identified that supporters were most effective in providing decision-making support for participants when they were relationally close to the person and had knowledge of the person's life story, particularly in relation to events that demonstrated preference. Findings from this study provide new understandings of supported decision making for people with severe or profound intellectual disability and have particular relevance for supporting decision making at the end of life. © 2017 John Wiley & Sons Ltd.

Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids

PubMed Central

Kuramoto, Kenta; Wang, Nan; Fan, Yuying; Zhang, Weiran; Schoenen, Frank J.; Frankowski, Kevin J.; Marugan, Juan; Zhou, Yifa; Huang, Sui; He, Congcong

2016-01-01

ABSTRACT Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases. The pathogenic mechanisms of cannabinoid tolerance are not fully understood, and little is known about its prevention. Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids. To target BECN2 therapeutically, we established a competitive recruitment model of BECN2 and identified novel synthetic, natural or physiological stimuli of autophagy that sequester BECN2 from its binding with GPRASP1, a receptor protein for CNR1 degradation. Co-administration of these autophagy inducers effectively restores the level and signaling of brain CNR1 and protects mice from developing tolerance to repeated cannabinoid usage. Overall, our findings demonstrate the functional link among autophagy, receptor signaling and animal behavior regulated by psychoactive drugs, and develop a new strategy to prevent tolerance and improve medical efficacy of cannabinoids by modulating the BECN2 interactome and autophagy activity. PMID:27305347

Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle

PubMed Central

Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

2012-01-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca2+ handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca2+] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca2+ handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca2+ handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness. PMID:22687611

Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.

PubMed

Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

2012-08-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.

Glucocorticoids, stress, and fertility.

PubMed

Whirledge, S; Cidlowski, J A

2010-06-01

Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]); 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.

Feasting in fresh water: impacts of food concentration on freshwater tolerance and the evolution of food × salinity response during the expansion from saline into fresh water habitats

PubMed Central

Lee, Carol Eunmi; Moss, Wynne E; Olson, Nora; Chau, Kevin Fongching; Chang, Yu-Mei; Johnson, Kelsey E

2013-01-01

Saline to freshwater invasions have become increasingly common in recent years. A key hypothesis is that rates of freshwater invasions have been amplified in recent years by increased food concentration, yet this hypothesis has remained unexplored. We examined whether elevated food concentration could enhance freshwater tolerance, and whether this effect evolves following saline to freshwater invasions. We examined physiological response to salinity and food concentration in a 2 × 2 factorial design, using ancestral brackish and freshwater invading populations of the copepod Eurytemora affinis. We found that high food concentration significantly increases low-salinity tolerance. This effect was reduced in the freshwater population, indicating evolution following the freshwater invasion. Thus, ample food could enable freshwater invasions, allowing subsequent evolution of low-salinity tolerance even under food-poor conditions. We also compared effects of food concentration on freshwater survival between two brackish populations from the native range. Impacts of food concentration on freshwater survival differed between the brackish populations, suggesting variation in functional properties affecting their propensity to invade freshwater habitats. The key implication is that high food concentration could profoundly extend range expansions of brackishwater species into freshwater habitats, potentially allowing for condition-specific competition between saline invaders and resident freshwater species. PMID:23789033

Progesterone promotes maternal–fetal tolerance by reducing human maternal T‐cell polyfunctionality and inducing a specific cytokine profile

PubMed Central

Eldershaw, Suzy A.; Inman, Charlotte F.; Coomarasamy, Aravinthan; Moss, Paul A. H.; Kilby, Mark D.

2015-01-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4+ and CD8+ T cells, with reductions not only in potentially deleterious IFN‐γ and TNF‐α production but also in IL‐10 and IL‐5. Conversely, production of IL‐4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL‐4. This was accompanied by reduced T‐cell proliferation. Using fetal and viral antigen‐specific CD8+ T‐cell clones, we confirmed that this as a direct, nonantigen‐specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4+ and CD8+ T cells responded to progesterone in a dose‐dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal–fetal interface. This characterization of how progesterone modulates T‐cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. PMID:26249148

Pulpal status of human primary teeth with physiological root resorption.

PubMed

Monteiro, Joana; Day, Peter; Duggal, Monty; Morgan, Claire; Rodd, Helen

2009-01-01

The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption. The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid-coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one-third, one-third to two-thirds, and more than two-thirds of their root length. Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data). This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption.

Ghrelin

PubMed Central

Wu, James T.; Kral, John G.

2004-01-01

Objective: Ghrelin is a novel gastric hormone recognized in 1999 as a mediator of growth hormone release. Since growth hormone is anabolic, an important function of ghrelin may be to coordinate energy needs with the growth process. Newly discovered biologic roles of ghrelin imply that it may have other important physiological functions as well. This is a review of recent clinically relevant, yet less well-known, physiologic actions of ghrelin. Summary Background Data: Ghrelin has profound orexigenic, adipogenic, and somatotrophic properties, increasing food intake and body weight. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue receptor in the pituitary gland, thus fulfilling criteria of a brain-gut peptide. The brain-gut axis is the effector of anabolism by regulating growth, feeding, and metabolism via vagal afferents mediating ghrelin signaling. However, the wide tissue distribution of ghrelin suggests that it may have other functions as well. Methods: Systematic literature review of all PubMed citations between 1999 and August 2003 focusing on clinically relevant biochemical and physiological characteristics of ghrelin. Results: Ghrelin is an important component of an integrated regulatory system of growth and metabolism acting via the vagus nerve, and is implicated in a variety of altered energy states such as obesity, eating disorders, neoplasia, and cachexia. It also enhances immune responses and potentially down-regulates anti-inflammatory molecules. Ghrelin's role as a brain-gut peptide emphasizes the significance of afferent vagal fibers as a major pathway to the brain, serving the purpose of maintaining physiologic homeostasis. Conclusions: The discovery of ghrelin has increased our understanding of feeding regulation, nutritional homeostasis, and metabolic processes. Further characterization of ghrelin's functions will likely generate new pharmacological approaches to diagnose and treat different disease entities including those related to the over-nutrition of obesity and the catabolic response to surgical trauma. PMID:15024307

Conditions for Effectiveness.

ERIC Educational Resources Information Center

Wright, Jeannette T.

1988-01-01

The most effective college presidents are those whose leadership styles are dominant, decisive, and when appropriate, autocratic. The president has to believe profoundly in the intrinsic value of the college. (Author/MSE)

Hypothalamic Ventricular Ependymal Thyroid Hormone Deiodinases Are an Important Element of Circannual Timing in the Siberian Hamster (Phodopus sungorus)

PubMed Central

Bolborea, Matei; Wilson, Dana; Mercer, Julian G.; Ebling, Francis J. P.; Morgan, Peter J.; Barrett, Perry

2013-01-01

Exposure to short days (SD) induces profound changes in the physiology and behaviour of Siberian hamsters, including gonadal regression and up to 30% loss in body weight. In a continuous SD environment after approximately 20 weeks, Siberian hamsters spontaneously revert to a long day (LD) phenotype, a phenomenon referred to as the photorefractory response. Previously we have identified a number of genes that are regulated by short photoperiod in the neuropil and ventricular ependymal (VE) cells of the hypothalamus, although their importance and contribution to photoperiod induced physiology is unclear. In this refractory model we hypothesised that the return to LD physiology involves reversal of SD expression levels of key hypothalamic genes to their LD values and thereby implicate genes required for LD physiology. Male Siberian hamsters were kept in either LD or SD for up to 39 weeks during which time SD hamster body weight decreased before increasing, after more than 20 weeks, back to LD values. Brain tissue was collected between 14 and 39 weeks for in situ hybridization to determine hypothalamic gene expression. In VE cells lining the third ventricle, expression of nestin, vimentin, Crbp1 and Gpr50 were down-regulated at 18 weeks in SD photoperiod, but expression was not restored to the LD level in photorefractory hamsters. Dio2, Mct8 and Tsh-r expression were altered by SD photoperiod and were fully restored, or even exceeded values found in LD hamsters in the refractory state. In hypothalamic nuclei, expression of Srif and Mc3r mRNAs was altered at 18 weeks in SD, but were similar to LD expression values in photorefractory hamsters. We conclude that in refractory hamsters not all VE cell functions are required to establish LD physiology. However, thyroid hormone signalling from ependymal cells and reversal of neuronal gene expression appear to be essential for the SD refractory response. PMID:23637944

An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease.

PubMed

Suratt, Benjamin T; Ubags, Niki D J; Rastogi, Deepa; Tantisira, Kelan G; Marsland, Benjamin J; Petrache, Irina; Allen, Janice B; Bates, Jason H T; Holguin, Fernando; McCormack, Meredith C; Michelakis, Evangelos D; Black, Stephen M; Jain, Manu; Mora, Ana L; Natarajan, Viswanathan; Miller, Yury I; Fessler, Michael B; Birukov, Konstantin G; Summer, Ross S; Shore, Stephanie A; Dixon, Anne E

2017-06-01

The world is in the midst of an unprecedented epidemic of obesity. This epidemic has changed the presentation and etiology of common diseases. For example, steatohepatitis, directly attributable to obesity, is now the most common cause of cirrhosis in the United States. Type 2 diabetes is increasingly being diagnosed in children. Pulmonary researchers and clinicians are just beginning to appreciate the impact of obesity and altered metabolism on common pulmonary diseases. Obesity has recently been identified as a major risk factor for the development of asthma and for acute respiratory distress syndrome. Obesity is associated with profound changes in pulmonary physiology, the development of pulmonary hypertension, sleep-disordered breathing, and altered susceptibility to pulmonary infection. In short, obesity is leading to dramatic changes in lung health and disease. Simultaneously, the rapidly developing field of metabolism, including mitochondrial function, is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Altered metabolism can lead to profound changes in both innate and adaptive immunity, as well as the function of structural cells. To address this emerging field, a 3-day meeting on obesity, metabolism, and lung disease was convened in October 2015 to discuss recent findings, foster research initiatives, and ultimately guide clinical care. The major findings arising from this meeting are reported in this document.

Environmental salinity modulates the effects of elevated CO2 levels on juvenile hard-shell clams, Mercenaria mercenaria.

PubMed

Dickinson, Gary H; Matoo, Omera B; Tourek, Robert T; Sokolova, Inna M; Beniash, Elia

2013-07-15

Ocean acidification due to increasing atmospheric CO2 concentrations results in a decrease in seawater pH and shifts in the carbonate chemistry that can negatively affect marine organisms. Marine bivalves such as the hard-shell clam, Mercenaria mercenaria, serve as ecosystem engineers in estuaries and coastal zones of the western Atlantic and, as for many marine calcifiers, are sensitive to the impacts of ocean acidification. In estuaries, the effects of ocean acidification can be exacerbated by low buffering capacity of brackish waters, acidic inputs from freshwaters and land, and/or the negative effects of salinity on the physiology of organisms. We determined the interactive effects of 21 weeks of exposure to different levels of CO2 (~395, 800 and 1500 μatm corresponding to pH of 8.2, 8.1 and 7.7, respectively) and salinity (32 versus 16) on biomineralization, shell properties and energy metabolism of juvenile hard-shell clams. Low salinity had profound effects on survival, energy metabolism and biomineralization of hard-shell clams and modulated their responses to elevated PCO2. Negative effects of low salinity in juvenile clams were mostly due to the strongly elevated basal energy demand, indicating energy deficiency, that led to reduced growth, elevated mortality and impaired shell maintenance (evidenced by the extensive damage to the periostracum). The effects of elevated PCO2 on physiology and biomineralization of hard-shell clams were more complex. Elevated PCO2 (~800-1500 μatm) had no significant effects on standard metabolic rates (indicative of the basal energy demand), but affected growth and shell mechanical properties in juvenile clams. Moderate hypercapnia (~800 μatm PCO2) increased shell and tissue growth and reduced mortality of juvenile clams in high salinity exposures; however, these effects were abolished under the low salinity conditions or at high PCO2 (~1500 μatm). Mechanical properties of the shell (measured as microhardness and fracture toughness of the shells) were negatively affected by elevated CO2 alone or in combination with low salinity, which may have important implications for protection against predators or environmental stressors. Our data indicate that environmental salinity can strongly modulate responses to ocean acidification in hard-shell clams and thus should be taken into account when predicting the effects of ocean acidification on estuarine bivalves.

Changes in optical properties during heating of ex vivo liver tissues

NASA Astrophysics Data System (ADS)

Nagarajan, Vivek Krishna; Gogineni, Venkateshwara R.; White, Sarah B.; Yu, Bing

2017-02-01

Thermal ablation is the use of heat to induce cell death through coagulative necrosis. Ideally, complete ablation of tumor cells with no damage to surrounding critical structures such as blood vessels, nerves or even organs is desired. Ablation monitoring techniques are often employed to ensure optimal tumor ablation. In thermal tissue ablation, tissue damage is known to be dependent on the temperature and time of exposure. Aptly, current methods for monitoring ablation rely profoundly on local tissue temperature and duration of heating to predict the degree of tissue damage. However, such methods do not take into account the microstructural and physiological changes in tissues as a result of thermocoagulation. Light propagation within biological tissues is known to be dependent on the tissue microstructure and physiology. During tissue denaturation, changes in tissue structure alter light propagations in tissue which could be used to directly assess the extent of thermal tissue damage. We report the use of a spectroscopic system for monitoring the tissue optical properties during heating of ex vivo liver tissues. We observed that during tissue denaturation, continuous changes in wavelength-averaged μa(λ) and μ's(λ) followed a sigmoidal trend and are correlated with damage predicted by Arrhenius model.

Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress

PubMed Central

Wollny, Damian; Clark, Rod J.; Roopra, Avtar; Colman, Ricki J.; MacDougald, Ormond A.; Shedd, Timothy A.; Nelson, David W.; Yen, Mei-I; Yen, Chi-Liang Eric; Alexander, Caroline M.

2014-01-01

Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology. PMID:25101993

Experience with pericyazine in profoundly and severely retarded children.

PubMed

Tischler, B; Patriasz, K; Beresford, J; Bunting, R

1972-01-22

The effectiveness of pericyazine in severe behavioural disorders was evaluated in 15 profoundly and severely retarded children. Pericyazine provided significant improvement in such parameters as co-operation, temper, purposeless activities, hyperactivity, communication and mood. It proved to be statistically superior to the minor tranquillizers in improving co-operation and helpfulness, temper, mood, the understanding of commands and table manners, and in reducing self-abusiveness and abusiveness to staff. The safety of this agent was confirmed and photosensitivity was not found to be associated with its use.

Anatomy and computational modeling of networks underlying cognitive-emotional interaction

PubMed Central

John, Yohan J.; Bullock, Daniel; Zikopoulos, Basilis; Barbas, Helen

2013-01-01

The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top–down signals from prefrontal cortex realize “cognitive control” in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior. PMID:23565082

Neurobiology of addictive behaviors and its relationship to methadone maintenance.

PubMed

Stimmel, B; Kreek, M J

2000-01-01

Scientific information about the neurobiology of addictive behaviors provides an increasingly important rationale to support opioid agonist pharmacotherapy, primarily methadone maintenance treatment, for long-term heroin addiction. In late 1963 and 1964, the first research was performed at The Rockefeller Institute for Medical Research by Dole, Nyswander, and Kreek in an attempt to develop a new pharmacotherapy for opiate addiction. The hypothesis underlying that research was that heroin addiction was a disease. However, the evidence for heroin addiction being a disease was based primarily on clinical anecdotes and the natural history of opiate addiction. Until then chronic addiction was managed primarily using abstinence-based, medication-free behavioral approaches. Such approaches were uniformly successful in only a small percent of long-term heroin addicts. Subsequent research, both clinical research as well as laboratory-based research, using a variety of appropriate animal models as well as in vitro techniques, has shown that drugs of abuse in general, and specifically the short-acting opiates, such as heroin, may profoundly alter molecular and neurochemical indices, and thus physiologic functions. Also, research has shown that after chronic exposure to a short-acting opiate,these alterations may be persistent, or even permanent, and may contribute directly to the perpetuation of self-administration of opiates, and even the return to opiate use after achieving a drug-free and medication-free state. There is ample evidence now that disruption of several components of the endogenous opioid system, ranging from changes in gene expression to changes in behavior, may occur during cycles of short-acting opiate abuse. Also, there are very convincing studies that suggest that stress responsivity is profoundly altered by chronic abuse of short-acting opiates including: documentation of atypical hypo-responsivity to stressors during cycles of heroin addiction; evidence of sustained hyper-responsivity to stressors in the medication-free, illicit-opiate-free state; and in contrast, normalization of stress responsivity, as reflected by the hypothalamic-pituitary-adrenal axis function in long-term, methadone-maintained patients. Thus, both laboratory and clinical research studies provide firm documentation that the disruption of physiologic, as well as behavioral, functions occurs during chronic administration of short-acting opiates. Also, there is research evidence of an epidemiologic, and more recently of a molecular genetics type, that a genetic vulnerability to develop addictions in general, and opiate addiction specifically, may exist, and that early environmental factors may alter physiology to enhance vulnerability to develop opiate addiction when self-exposed.

Anesthesia For In Utero Repair of Myelomeningocele

PubMed Central

Ferschl, Marla; Ball, Robert; Lee, Hanmin; Rollins, Mark D.

2013-01-01

Recently published results suggest that prenatal repair of fetal myelomeningocele is a potentially preferable alternative when compared to postnatal repair. In this article, the pathology of myelomeningocele, unique physiologic considerations, perioperative anesthetic management, and ethical considerations of open fetal surgery for prenatal myelomeningocele repair are discussed. Open fetal surgeries have many unique anesthetic issues such as inducing profound uterine relaxation, vigilance for maternal or fetal blood loss, fetal monitoring, and possible fetal resuscitation. Postoperative management, including the requirement for postoperative tocolysis and maternal analgesia are also reviewed. The success of intrauterine myelomeningocele repair relies on a well-coordinated multidisciplinary approach. Fetal surgery is an important topic for anesthesiologists to understand, as the number of fetal procedures is likely to increase as new fetal treatment centers are opened across the United States. PMID:23508219

Pregnancy in a woman with proportionate (primordial) dwarfism: a case report and literature review.

PubMed

Vance, C E; Desmond, M; Robinson, A; Johns, J; Zacharin, M; Savarirayan, R; König, K; Warrillow, S; Walker, S P

2012-09-01

Primordial dwarfism is a rare form of severe proportionate dwarfism which poses significant challenges in pregnancy. A 27-year-old with primordial dwarfism (height 97 cm, weight 22 kg) and coexisting morbidities of familial hypercholesterolaemia and hypertension presented to our unit. Early pregnancy was complicated by difficult blood pressure control, sinus tachycardia, biochemical hyperthyroidism and insulin-requiring gestational diabetes. Delivery was indicated at 24 weeks with uncontrollable hypertension, progressive renal impairment and intrauterine growth restriction. A caesarean section was performed under general anaesthesia, resulting in the delivery of a 486 g male infant. This case highlights the difficulties of managing pregnancy in a woman with primordial dwarfism. Her limited capacity to respond to the physiological demands of pregnancy created a life-threatening situation, culminating in profound preterm birth.

Glucocorticoid receptor signaling in health and disease

PubMed Central

Kadmiel, Mahita; Cidlowski, John A.

2013-01-01

Glucocorticoids are steroid hormones regulated in a circadian and stres-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the last few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor, a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we will provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body. PMID:23953592

Modeling human risk: Cell & molecular biology in context

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

NONE

It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small butmore » highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.« less

Earthing (Grounding) the Human Body Reduces Blood Viscosity—a Major Factor in Cardiovascular Disease

PubMed Central

Chevalier, Gaétan; Sinatra, Stephen T.; Delany, Richard M.

2013-01-01

Abstract Objectives Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects Ten (10) healthy adult subjects were recruited by word-of-mouth. Results Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events. PMID:22757749

Earthing (grounding) the human body reduces blood viscosity-a major factor in cardiovascular disease.

PubMed

Chevalier, Gaétan; Sinatra, Stephen T; Oschman, James L; Delany, Richard M

2013-02-01

Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. SUBJECTS were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Ten (10) healthy adult subjects were recruited by word-of-mouth. Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events.

Responses of Haloarchaea to Simulated Microgravity

NASA Astrophysics Data System (ADS)

Dornmayr-Pfaffenhuemer, Marion; Legat, Andrea; Schwimbersky, Karin; Fendrihan, Sergiu; Stan-Lotter, Helga

2011-04-01

Various effects of microgravity on prokaryotes have been recognized in recent years, with the focus on studies of pathogenic bacteria. No archaea have been investigated yet with respect to their responses to microgravity. For exposure experiments on spacecrafts or on the International Space Station, halophilic archaea (haloarchaea) are usually embedded in halite, where they accumulate in fluid inclusions. In a liquid environment, these cells will experience microgravity in space, which might influence their viability and survival. Two haloarchaeal strains, Haloferax mediterranei and Halococcus dombrowskii, were grown in simulated microgravity (SMG) with the rotary cell culture system (RCCS, Synthecon). Initially, salt precipitation and detachment of the porous aeration membranes in the RCCS were observed, but they were avoided in the remainder of the experiment by using disposable instead of reusable vessels. Several effects were detected, which were ascribed to growth in SMG: Hfx. mediterranei's resistance to the antibiotics bacitracin, erythromycin, and rifampicin increased markedly; differences in pigmentation and whole cell protein composition (proteome) of both strains were noted; cell aggregation of Hcc. dombrowskii was notably reduced. The results suggest profound effects of SMG on haloarchaeal physiology and cellular processes, some of which were easily observable and measurable. This is the first report of archaeal responses to SMG. The molecular mechanisms of the effects induced by SMG on prokaryotes are largely unknown; haloarchaea could be used as nonpathogenic model systems for their elucidation and in addition could provide information about survival during lithopanspermia (interplanetary transport of microbes inside meteorites).

Mild Lipid Stress Induces Profound Loss of MC4R Protein Abundance and Function

PubMed Central

Cragle, Faith K.

2014-01-01

Food intake is controlled at the central level by the melanocortin pathway in which the agonist α-MSH binds to melanocortin 4 receptor (MC4R), a Gs-coupled G protein-coupled receptor expressed by neurons in the paraventricular nuclei of the hypothalamus, which signals to reduce appetite. Consumption of a high-fat diet induces hypothalamic accumulation of palmitate, endoplasmic reticulum (ER) stress, apoptosis, and unresponsiveness to prolonged treatment with MC4R agonists. Here we have modeled effects of lipid stress on MC4R by using mHypoE-42 immortalized hypothalamic neurons expressing endogenous MC4R and Neuro2A cells expressing a tagged MC4R reporter, HA-MC4R-GFP. In the hypothalamic neurons, exposure to elevated palmitate in the physiological range induced splicing of X-box binding protein 1, but it did not activate C/EBP-homologous protein or induce increased levels of cleaved caspase-3, indicating mild ER stress. Such mild ER stress coexisted with a minimal loss of MC4R mRNA and yet a profound loss of cAMP signaling in response to incubation with the agonist. These findings were mirrored in the Neuro2A cells expressing HA-MC4R-GFP, in which protein abundance of the tagged receptor was decreased, whereas the activity per receptor number was maintained. The loss of cAMP signaling in response to α-MSH by elevated palmitate was corrected by treatment with a chemical chaperone, 4-phenylbutyrate in both mHypoE-42 hypothalamic neurons and in Neuro2A cells in which protein abundance of HA-MC4R-GFP was increased. The data indicate that posttranscriptional decrease of MC4R protein contribute to lower the response to α-MSH in hypothalamic neurons exposed to even a mild level of lipid stress and that a chemical chaperone corrects such a defect. PMID:24506538

Artificial light at night affects body mass but not oxidative status in free-living nestling songbirds: an experimental study.

PubMed

Raap, Thomas; Casasole, Giulia; Costantini, David; AbdElgawad, Hamada; Asard, Han; Pinxten, Rianne; Eens, Marcel

2016-10-19

Artificial light at night (ALAN), termed light pollution, is an increasingly important anthropogenic environmental pressure on wildlife. Exposure to unnatural lighting environments may have profound effects on animal physiology, particularly during early life. Here, we experimentally investigated for the first time the impact of ALAN on body mass and oxidative status during development, using nestlings of a free-living songbird, the great tit (Parus major), an important model species. Body mass and blood oxidative status were determined at baseline (=13 days after hatching) and again after a two night exposure to ALAN. Because it is very difficult to generalise the oxidative status from one or two measures we relied on a multi-biomarker approach. We determined multiple metrics of both antioxidant defences and oxidative damage: molecular antioxidants GSH, GSSG; antioxidant enzymes GPX, SOD, CAT; total non-enzymatic antioxidant capacity and damage markers protein carbonyls and TBARS. Light exposed nestlings showed no increase in body mass, in contrast to unexposed individuals. None of the metrics of oxidative status were affected. Nonetheless, our study provides experimental field evidence that ALAN may negatively affect free-living nestlings' development and hence may have adverse consequences lasting throughout adulthood.

Artificial light at night affects body mass but not oxidative status in free-living nestling songbirds: an experimental study

PubMed Central

Raap, Thomas; Casasole, Giulia; Costantini, David; AbdElgawad, Hamada; Asard, Han; Pinxten, Rianne; Eens, Marcel

2016-01-01

Artificial light at night (ALAN), termed light pollution, is an increasingly important anthropogenic environmental pressure on wildlife. Exposure to unnatural lighting environments may have profound effects on animal physiology, particularly during early life. Here, we experimentally investigated for the first time the impact of ALAN on body mass and oxidative status during development, using nestlings of a free-living songbird, the great tit (Parus major), an important model species. Body mass and blood oxidative status were determined at baseline (=13 days after hatching) and again after a two night exposure to ALAN. Because it is very difficult to generalise the oxidative status from one or two measures we relied on a multi-biomarker approach. We determined multiple metrics of both antioxidant defences and oxidative damage: molecular antioxidants GSH, GSSG; antioxidant enzymes GPX, SOD, CAT; total non-enzymatic antioxidant capacity and damage markers protein carbonyls and TBARS. Light exposed nestlings showed no increase in body mass, in contrast to unexposed individuals. None of the metrics of oxidative status were affected. Nonetheless, our study provides experimental field evidence that ALAN may negatively affect free-living nestlings’ development and hence may have adverse consequences lasting throughout adulthood. PMID:27759087

Osteoinductive implants: the mise-en-scène for drug-bearing biomimetic coatings.

PubMed

Liu, Y; de Groot, K; Hunziker, E B

2004-03-01

In orthopaedic and dental implantology, novel tools and techniques are being sought to improve the regeneration of bone tissue. Numerous attempts have been made to enhance the osteoconductivity of titanium prostheses, including modifications in their surface properties and coating with layers of calcium phosphate. The technique whereby such layers are produced has recently undergone a revolutionary change, which has had profound consequences for their potential to serve as drug-carrier systems. Hitherto, calcium phosphate layers were deposited upon the surfaces of metal implants under highly unphysiological physical conditions, which precluded the incorporation of proteinaceous osteoinductive drugs. These agents could only be adsorbed, superficially, upon preformed layers. Such superficially adsorbed molecules are released too rapidly within a biological milieu to be effective in their osteoinductive capacity. Now, it is possible to deposit calcium phosphate layers under physiological conditions of temperature and pH by the so-called biomimetic process, during which bioactive agents can be coprecipitated. Since these molecules are integrated into the inorganic latticework, they are released gradually in vivo as the layer undergoes degradation. This feature enhances the capacity of these coatings to act as a carrier system for osteogenic agents.

Food as exposure: Nutritional epigenetics and the new metabolism

PubMed Central

Landecker, Hannah

2011-01-01

Nutritional epigenetics seeks to explain the effects of nutrition on gene expression. For social science, it is an area of life science whose analysis reveals a concentrated form of a wider shift in the understanding of food and metabolism. Rather than the chemical conversion of food to energy and body matter of classic metabolism, food is now also a conditioning environment that shapes the activity of the genome and the physiology of the body. It is thought that food in prenatal and early postnatal life impacts adult-onset diseases such as diabetes and heart disease; exposure to food is seen as a point of potential intervention in long-term health of individuals and populations. This article analyzes how food has become environment in nutritional epigenetics, with a focus on the experimental formalization of food. The experimental image of human life generated in rodent models, it is argued, generates concepts of food as a form of molecular exposure. This scientific discourse has profound implications for how food is perceived, manufactured and regulated, as well as for social theories and analyses of the social body that have a long history of imbrication with scientific models of metabolism. PMID:23227106

Significant differences in genotoxicity induced by retrovirus integration in human T cells and induced pluripotent stem cells.

PubMed

Zheng, Weiyan; Wang, Yingjia; Chang, Tammy; Huang, He; Yee, Jiing-Kuan

2013-04-25

Retrovirus is frequently used in the genetic modification of mammalian cells and the establishment of induced pluripotent stem cells (iPSCs) via cell reprogramming. Vector-induced genotoxicity could induce profound effect on the physiology and function of these stem cells and their differentiated progeny. We analyzed retrovirus-induced genotoxicity in somatic cell Jurkat and two iPSC lines. In Jurkat cells, retrovirus frequently activated host gene expression and gene activation was not dependent on the distance between the integration site and the transcription start site of the host gene. In contrast, retrovirus frequently down-regulated host gene expression in iPSCs, possibly due to the action of chromatin silencing that spreads from the provirus to the nearby host gene promoter. Our data raises the issue that some of the phenotypic variability observed among iPSC clones derived from the same parental cell line may be caused by retrovirus-induced gene expression changes rather than by the reprogramming process itself. It also underscores the importance of characterizing retrovirus integration and carrying out risk assessment of iPSCs before they can be applied in basic research and clinics. Copyright © 2013 Elsevier B.V. All rights reserved.

Stress responsiveness and anxiety-like behavior: The early social environment differentially shapes stability over time in a small rodent.

PubMed

Sangenstedt, Susanne; Jaljuli, Iman; Sachser, Norbert; Kaiser, Sylvia

2017-04-01

The early social environment can profoundly affect behavioral and physiological phenotypes. We investigated how male wild cavy offspring, whose mothers had either lived in a stable (SE) or an unstable social environment (UE) during pregnancy and lactation, differed in their anxiety-like behavior and stress responsiveness. At two different time points in life, we tested the offspring's anxiety-like behavior in a dark-light test and their endocrine reaction to challenge in a cortisol reactivity test. Furthermore, we analyzed whether individual traits remained stable over time. There was no effect of the early social environment on anxiety-like behavior and stress responsiveness. However, at an individual level, anxiety-like behavior was stable over time in UE- but not in SE-sons. Stress responsiveness, in turn, was rather inconsistent in UE-sons and temporally stable in SE-sons. Conclusively, we showed for the first time that the early social environment differentially shapes the stability of behavioral and endocrine traits. At first glance, these results may be surprising, but they can be explained by the different functions anxiety-like behavior and stress responsiveness have. Copyright © 2017 Elsevier Inc. All rights reserved.

Caloric restriction: Impact upon pituitary function and reproduction

PubMed Central

Martin, Bronwen; Golden, Erin; Carlson, Olga D.; Egan, Josephine M.; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

Reduced energy intake, or caloric restriction (CR), is known to extend life span and to retard age-related health decline in a number of different species, including worms, flies, fish, mice and rats. CR has been shown to reduce oxidative stress, improve insulin sensitivity, and alter neuroendocrine responses and central nervous system (CNS) function in animals. CR has particularly profound and complex actions upon reproductive health. At the reductionist level the most crucial physiological function of any organism is its capacity to reproduce. For a successful species to thrive, the balance between available energy (food) and the energy expenditure required for reproduction must be tightly linked. An ability to coordinate energy balance and fecundity involves complex interactions of hormones from both the periphery and the CNS and primarily centers upon the master endocrine gland, the anterior pituitary. In this review article we review the effects of CR on pituitary gonadotrope function and on the male and female reproductive axes. A better understanding of how dietary energy intake affects reproductive axis function and endocrine pulsatility could provide novel strategies for the prevention and management of reproductive dysfunction and its associated comorbidities. PMID:18329344

A Physicist’s Quest in Biology: Max Delbrück and “Complementarity”

PubMed Central

Strauss, Bernard S.

2017-01-01

Max Delbrück was trained as a physicist but made his major contribution in biology and ultimately shared a Nobel Prize in Physiology or Medicine. He was the acknowledged leader of the founders of molecular biology, yet he failed to achieve his key scientific goals. His ultimate scientific aim was to find evidence for physical laws unique to biology: so-called “complementarity.” He never did. The specific problem he initially wanted to solve was the nature of biological replication but the discovery of the mechanism of replication was made by others, in large part because of his disdain for the details of biochemistry. His later career was spent investigating the effect of light on the fungus Phycomyces, a topic that turned out to be of limited general interest. He was known both for his informality but also for his legendary displays of devastating criticism. His life and that of some of his closest colleagues was acted out against a background of a world in conflict. This essay describes the man and his career and searches for an explanation of his profound influence. PMID:28592501

Development of the Digestive System-Experimental Challenges and Approaches of Infant Lipid Digestion.

PubMed

Abrahamse, Evan; Minekus, Mans; van Aken, George A; van de Heijning, Bert; Knol, Jan; Bartke, Nana; Oozeer, Raish; van der Beek, Eline M; Ludwig, Thomas

2012-12-01

At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the nervous and digestive systems, depends fundamentally on these. Epidemiological data suggest that human milk provides unique health benefits during early infancy that extend to long-lasting benefits. Preclinical findings show that qualitative changes in dietary lipids, i.e., lipid structure and FA composition, during early life may contribute to the reported long-term effects. Little is known in this respect about the development of digestive function and the digestion and absorption of lipids by the newborn. This review gives a detailed overview of the distinct functionalities that dietary lipids from human milk and infant formula provide and the profound differences in the physiology and biochemistry of lipid digestion between infants and adults. Fundamental mechanisms of infant lipid digestion can, however, almost exclusively be elucidated in vitro. Experimental approaches and their challenges are reviewed in depth.

A Physicist's Quest in Biology: Max Delbrück and "Complementarity".

PubMed

Strauss, Bernard S

2017-06-01

Max Delbrück was trained as a physicist but made his major contribution in biology and ultimately shared a Nobel Prize in Physiology or Medicine. He was the acknowledged leader of the founders of molecular biology, yet he failed to achieve his key scientific goals. His ultimate scientific aim was to find evidence for physical laws unique to biology: so-called "complementarity." He never did. The specific problem he initially wanted to solve was the nature of biological replication but the discovery of the mechanism of replication was made by others, in large part because of his disdain for the details of biochemistry. His later career was spent investigating the effect of light on the fungus Phycomyces , a topic that turned out to be of limited general interest. He was known both for his informality but also for his legendary displays of devastating criticism. His life and that of some of his closest colleagues was acted out against a background of a world in conflict. This essay describes the man and his career and searches for an explanation of his profound influence. Copyright © 2017 by the Genetics Society of America.

Utilizing Trigger Films to Enhance Communication Skills of Home Care Clinicians.

PubMed

Brennan-Cook, Jill; Molloy, Margory A

2016-01-01

The purpose of this article is to describe an innovative method to help home care clinicians better communicate with older adults experiencing normal physiologic changes that impact their ability to communicate effectively. Developmental changes such as hearing, speech, vision, and cognition profoundly impede an older adult's ability to communicate with others, potentially undermining the quality of care delivered. The use of trigger films as an educational intervention can assist home care clinicians to improve communication with their patients. Trigger films are 2- to 4-minute video clips that end abruptly, encouraging learners to analyze clinical situations in a safe environment, such as a staff conference room. Trigger films are easy to make with the use of a smart phone and two staff members portraying the role of home care clinician and patient. Allowing discussion after viewing the trigger film places clinicians in an active learning role, thus fostering the sharing of ideas and best practice. Addressing age-related barriers to communication with this modality serves to improve patient interaction and healthcare outcomes. The use of trigger films is another tool that empowers the clinician to provide improved care for patients with communication deficits.

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

PubMed

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

PubMed Central

Kourtesi, Christina; Ball, Anthony R; Huang, Ying-Ying; Jachak, Sanjay M; Vera, D Mariano A; Khondkar, Proma; Gibbons, Simon; Hamblin, Michael R; Tegos, George P

2013-01-01

Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches. PMID:23569468

Inhibition of Ca2+ channels and adrenal catecholamine release by G protein coupled receptors.

PubMed

Currie, Kevin P M

2010-11-01

Catecholamines and other transmitters released from adrenal chromaffin cells play central roles in the "fight-or-flight" response and exert profound effects on cardiovascular, endocrine, immune, and nervous system function. As such, precise regulation of chromaffin cell exocytosis is key to maintaining normal physiological function and appropriate responsiveness to acute stress. Chromaffin cells express a number of different G protein coupled receptors (GPCRs) that sense the local environment and orchestrate this precise control of transmitter release. The primary trigger for catecholamine release is Ca2+ entry through voltage-gated Ca2+ channels, so it makes sense that these channels are subject to complex regulation by GPCRs. In particular G protein βγ heterodimers (Gbc) bind to and inhibit Ca2+ channels. Here I review the mechanisms by which GPCRs inhibit Ca2+ channels in chromaffin cells and how this might be altered by cellular context. This is related to the potent autocrine inhibition of Ca2+ entry and transmitter release seen in chromaffin cells. Recent data that implicate an additional inhibitory target of Gβγ on the exocytotic machinery and how this might fine tune neuroendocrine secretion are also discussed.

Profound vision loss impairs psychological well-being in young and middle-aged individuals.

PubMed

Garcia, Giancarlo A; Khoshnevis, Matin; Gale, Jesse; Frousiakis, Starleen E; Hwang, Tiffany J; Poincenot, Lissa; Karanjia, Rustum; Baron, David; Sadun, Alfredo A

2017-01-01

The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. A questionnaire was issued to individuals aged 13-65 years with profound vision loss resulting from Leber's hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from -10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = -5) and career goals (median IR = -6) were observed; both ratings were worse ( P <0.001) for depressed versus nondepressed subjects. Older age at diagnosis corresponded to higher depression prevalence and increased incidence of negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids ( P =0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by age and use of electronic vision aids. Ophthalmologists, in addition to managing vision loss, may serve an important role in the emotional adaptation of these patients.

Diuretic effects of medetomidine compared with xylazine in healthy dogs.

PubMed

Talukder, Md Hasanuzzaman; Hikasa, Yoshiaki

2009-07-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 microg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine's effect is less dose-dependent than xylazine's effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation.

Pathophysiological and neurobehavioral injuries in mice experimentally envenomed with Androctonus liouvillei (Pallary, 1928) scorpion venom.

PubMed

El Hidan, Moulay Abdelmonaim; Touloun, Oulaid; El Hiba, Omar; Boumezzough, Ali

2016-01-01

The genus Androctonus is represented by 7 scorpion species in Morocco. All studies conducted on the characterization of Androctonus species venom are limited to Androctonus mauritanicus. However, there is other species which arouses also interest of scientists due to their high toxicity. Thus, we chose to assess the toxic effect of Androctonus liouvillei venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. In addition, we aimed to characterize the neurobehavioral impairments, in Swiss mice, 3h, 6h and 12h following envenomation. The LD50 of A. liouvillei scorpion venom was found to be 0.29mg/kg by subcutaneous injection route. Venom administration induced glomerular destruction and disorganization in the Bowman's spac. Examination of lungs showed a remarkable focal rupture of the alveolar structure and intra-alveolar hemorrhage. Concurrently, there was a significant enhancement in the serum enzymes levels of AST, ALT, CPK and LDH, and a high level of glucose and creatinine. Proteinuria was also observed. Regarding the behavioral effects we noted a hypoactivity and anxiogenic-like effect, manifested by an increased time spent in the open arms in groups tested 30min and 12h after the injection. Concomitantly with an increased immobility time in the tail suspension test. The present finding show an obvious profound neuromodulatory effect of A. liouvillei venom manifested by an impaired neurobehavioral and physiological patterns in mice that may in part explain the toxic effect of the venom in human as one of the potent death agents. Copyright © 2015 Elsevier GmbH. All rights reserved.

Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer.

PubMed

Anbalagan, Muralidharan; Rowan, Brian G

2015-12-15

Estrogen receptor α (ERα) is a member of the nuclear receptor superfamily of transcription factors that regulates cell proliferation, differentiation and homeostasis in various tissues. Sustained exposure to estrogen/estradiol (E2) increases the risk of breast, endometrial and ovarian cancers. ERα function is also regulated by phosphorylation through various kinase signaling pathways that will impact various ERα functions including chromatin interaction, coregulator recruitment and gene expression, as well impact breast tumor growth/morphology and breast cancer patient response to endocrine therapy. However, many of the previously characterized ERα phosphorylation sites do not fully explain the impact of receptor phosphorylation on ERα function. This review discusses work from our laboratory toward understanding a role of ERα site-specific phosphorylation in ERα function and breast cancer. The key findings discussed in this review are: (1) the effect of site specific ERα phosphorylation on temporal recruitment of ERα and unique coactivator complexes to specific genes; (2) the impact of stable disruption of ERα S118 and S167 phosphorylation in breast cancer cells on eliciting unique gene expression profiles that culminate in significant effects on breast cancer growth/morphology/migration/invasion; (3) the Src kinase signaling pathway that impacts ERα phosphorylation to alter ERα function; and (4) circadian disruption by light exposure at night leading to elevated ERK1/2 and Src kinase and phosphorylation of ERα, concomitant with tamoxifen resistance in breast tumor models. Results from these studies demonstrate that even changes to single ERα phosphorylation sites can have a profound impact on ERα function in breast cancer. Future work will extend beyond single site phosphorylation analysis toward identification of specific patterns/profiles of ERα phosphorylation under different physiological/pharmacological conditions to understand how common phosphorylation profiles in breast cancer program specific physiological endpoints such as growth, apoptosis, migration/invasion, and endocrine therapy response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The psychological and physiological effects of acute occupational stress in new anesthesiology residents: a pilot trial.

PubMed

Eisenach, John H; Sprung, Juraj; Clark, Matthew M; Shanafelt, Tait D; Johnson, Bruce D; Kruse, Timothy N; Chantigian, Daniel P; Carter, Jason R; Long, Timothy R

2014-10-01

Occupational stress in resident physicians has profound implications for wellness, professionalism, and patient care. This observational pilot trial measured psychological and physiological stress biomarkers before, during, and after the start of anesthesia residency. Eighteen physician interns scheduled to begin anesthesia residency were recruited for evaluation at three time points: baseline (collected remotely before residency in June 2013); first-month visit 1 (July); and follow-up visit 2 (residency months 3 to 5, September-November). Validated scales were used to measure stress, anxiety, resilience, and wellness at all three time points. During visits 1 and 2, the authors measured resting heart-rate variability, responses to laboratory mental stress (hemodynamic, catecholamine, cortisol, and interleukin-6), and chronic stress indices (C-reactive protein, 24-h ambulatory heart rate and blood pressure, 24-h urinary cortisol and catecholamines, overnight heart-rate variability). Thirteen interns agreed to participate (72% enrollment). There were seven men and six women, aged 27 to 33 yr. The mean ± SD of all study variables are reported. The novelty of this report is the prospective design in a defined cohort of residents newly exposed to the similar occupational stress of the operating environment. Because of the paucity of literature specific to the measures and stress conditions in this investigation, no data were available to generate a priori definition of primary outcomes and a data analytic plan. These findings will allow power analysis for future design of trials examining occupational stress and stress-reducing interventions. Given the importance of physician burnout in our country, the impact of chronic stress on resident wellness requires further study.

Hysteresis of heart rate and heat exchange of fasting and postprandial savannah monitor lizards (Varanus exanthematicus).

PubMed

Zaar, Morten; Larsen, Einer; Wang, Tobias

2004-04-01

Reptiles are ectothermic, but regulate body temperatures (T(b)) by behavioural and physiological means. Body temperature has profound effects on virtually all physiological functions. It is well known that heating occurs faster than cooling, which seems to correlate with changes in cutaneous perfusion. Increased cutaneous perfusion, and hence elevated cardiac output, during heating is reflected in an increased heart rate (f(H)), and f(H), at a given T(b), is normally higher during heating compared to cooling ('hysteresis of heart rate'). Digestion is associated with an increased metabolic rate. This is associated with an elevated f(H) and many species of reptiles also exhibited a behavioural selection of higher T(b) during digestion. Here, we examine whether digestion affects the rate of heating and cooling as well as the hysteresis of heart rate in savannah monitor lizards (Varanus exanthematicus). Fasting lizards were studied after 5 days of food deprivation while digesting lizards were studied approximately 24 h after ingesting dead mice that equalled 10% of their body mass. Heart rate was measured while T(b) increased from 28 to 38 degrees C under a heat lamp and while T(b) decreased during a subsequent cooling phase. The lizards exhibited hysteresis of heart rate, and heating occurred faster than cooling. Feeding led to an increased f(H) (approximately 20 min(-1) irrespective of T(b)), but did not affect the rate of temperature change during heating or cooling. Therefore, it is likely that the increased blood flows during digestion are distributed exclusively to visceral organs and that the thermal conductance remains unaffected by the elevated metabolic rate during digestion.

Physiological roles of taurine in heart and muscle

PubMed Central

2010-01-01

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals. PMID:20804594

Physiological roles of taurine in heart and muscle.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ramila, K C; Azuma, Junichi

2010-08-24

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals.

Passive warming reduces stress and shifts reproductive effort in the Antarctic moss, Polytrichastrum alpinum.

PubMed

Shortlidge, Erin E; Eppley, Sarah M; Kohler, Hans; Rosenstiel, Todd N; Zúñiga, Gustavo E; Casanova-Katny, Angélica

2017-01-01

The Western Antarctic Peninsula is one of the most rapidly warming regions on Earth, and many biotic communities inhabiting this dynamic region are responding to these well-documented climatic shifts. Yet some of the most prevalent organisms of terrestrial Antarctica, the mosses, and their responses to warming have been relatively overlooked and understudied. In this research, the impacts of 6 years of passive warming were investigated using open top chambers (OTCs), on moss communities of Fildes Peninsula, King George Island, Antarctica. The effects of experimental passive warming on the morphology, sexual reproductive effort and stress physiology of a common dioicous Antarctic moss, Polytrichastrum alpinum ,: were tested, gaining the first species-specific mechanistic insight into moss responses to warming in the Antarctic. Additionally community analyses were conducted examining the impact of warming on overall moss percentage cover and sporophyte production in intact Antarctic moss communities. Our results show a generally greater percentage moss cover under warming conditions as well as increased gametangia production in P. alpinum Distinct morphological and physiological shifts in P. alpinum were found under passive warming compared with those without warming: warmed mosses reduced investment in cellular stress defences, but invested more towards primary productivity and gametangia development. Taken together, results from this study of mosses under passive warming imply that in ice-free moss-dominated regions, continued climate warming will probably have profound impacts on moss biology and colonization along the Western Antarctic Peninsula. Such findings highlight the fundamental role that mosses will play in influencing the terrestrialization of a warming Antarctica. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Designing PolyHEMA Substrates that Mimic the Viscoelastic Response of Soft Tissue

PubMed Central

Holt, Brian; Tripathi, Anubhav; Morgan, Jeffrey R.

2011-01-01

Matching the mechanical properties of a biomaterial to soft tissue is often overlooked despite the fact that it’s well known that cells respond to and are capable of changing their mechanical environment. In this paper, we used NaCl and alginate beads as porogens to make a series of micro- and macro-porous pHEMA substrates [poly(2-hydroxyethly methacrylate)] and quantified their mechanical behavior under low-magnitude shear loads over physiologically relevant frequencies. Using a stress-controlled rheometer, we performed isothermal (37°C) frequency response experiments between 0.628 and 75.4 rad/s [0.01–12Hz] at 0.1% strain. Both micro- and macro-porous pHEMA substrates were predominately elastic in nature with a narrow range of G′ and G″ values that mimicked the response of human skin. The magnitude of the G′ and G″ values of the macro-porous substrates were designed to closely match human skin. To determine how cell growth might alter their mechanical properties, pHEMA substrates were functionalized and human skin fibroblasts grown on them for fourteen days. As a result of cell growth, the magnitude of G′ and G″ increased at low frequencies while also altering the degree of high frequency dependence, indicating that cellular interactions with the micro-pore infrastructure has a profound effect on the viscoelastic behavior of the substrates. These data could be fit to a mathematical model describing a soft solid. A quantitative understanding of the mechanical behavior of biomaterials in regimes that are physiologically relevant and how these mechanics may change after implantation may aid in the design of new materials. PMID:21496821

Chemicals on plant surfaces as a heretofore unrecognized, but ecologically informative, class for investigations into plant defence.

PubMed

LoPresti, Eric F

2016-11-01

Plants produce and utilize a great diversity of chemicals for a variety of physiological and ecological purposes. Many of these chemicals defend plants against herbivores, pathogens and competitors. The location of these chemicals varies within the plant, some are located entirely within plant tissues, others exist in the air- (or water-) space around plants, and still others are secreted onto plant surfaces as exudates. I argue herein that the location of a given defensive chemical has profound implications for its ecological function; specifically, I focus on the characteristics of chemical defences secreted onto plant surfaces. Drawing from a broad literature encompassing ecology, evolution, taxonomy and physiology, I found that these external chemical defences (ECDs) are common and widespread in plants and algae; hundreds of examples have been detailed, yet they are not delineated as a separate class from internal chemical defences (ICDs). I propose a novel typology for ECDs and, using existing literature, explore the ecological consequences of the hypothesized unique characteristics of ECDs. The axis of total or proportional investment in ECDs versus ICDs should be considered as one axis of investment by a plant, in the same way as quantitative versus qualitative chemical defences or induced versus constitutive defences is considered. The ease of manipulating ECDs in many plant systems presents a powerful tool to help test plant defence theory (e.g. optimal defence). The framework outlined here integrates various disciplines of botany and ecology and suggests a need for further examinations of exudates in a variety of contexts, as well as recognition of the effects of within-plant localization of defences. © 2015 Cambridge Philosophical Society.

Climate warming is predicted to reduce omega-3, long-chain, polyunsaturated fatty acid production in phytoplankton.

PubMed

Hixson, Stefanie M; Arts, Michael T

2016-08-01

Phytoplankton are the main source of energy and omega-3 (n-3) long-chain essential fatty acids (EFA) in aquatic ecosystems. Their growth and biochemical composition are affected by surrounding environmental conditions, including temperature, which continues to increase as a result of climate warming. Increasing water temperatures may negatively impact the production of EFA by phytoplankton through the process of homeoviscous adaptation. To investigate this, we conducted an exploratory data synthesis with 952 fatty acid (FA) profiles from six major groups of marine and freshwater phytoplankton. Temperature was strongly correlated with a decrease in the proportion of n-3 long-chain polyunsaturated FA (LC-PUFA) and an increase in omega-6 FA and saturated FA. Based on linear regression models, we predict that global n-3 LC-PUFA production will be reduced by 8.2% for eicosapentaenoic acid (EPA) and 27.8% for docosahexaenoic acid (DHA) with an increase in water temperature of 2.5 °C. Using a previously published estimate of the global production of EPA by diatoms, which contribute to most of the world's supply of EPA, we predict a loss of 14.2 Mt of EPA annually as a result of ocean warming. The n-3 LC-PUFA are vitally important for an array of key physiological functions in aquatic and terrestrial organisms, and these FA are mainly produced by phytoplankton. Therefore, reduced production of these EFA, as a consequence of climate warming, is predicted to negatively affect species that depend on these compounds for optimum physiological function. Such profound changes in the biochemical composition of phytoplankton cell membranes can lead to cascading effects throughout the world's ecosystems. © 2016 John Wiley & Sons Ltd.

Environmental enrichment strengthens corticocortical interactions and reduces amyloid-β oligomers in aged mice

PubMed Central

Mainardi, Marco; Di Garbo, Angelo; Caleo, Matteo; Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto

2013-01-01

Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes. PMID:24478697

The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent.

PubMed

Bosch, Oliver J; Nair, Hemanth P; Ahern, Todd H; Neumann, Inga D; Young, Larry J

2009-05-01

Social relationships significantly influence physiology and behavior, including the hypothalamo-pituitary-adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-coping behaviors indicative of depressive-like behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-coping behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.

Environmental enrichment strengthens corticocortical interactions and reduces amyloid-β oligomers in aged mice.

PubMed

Mainardi, Marco; Di Garbo, Angelo; Caleo, Matteo; Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto

2014-01-01

Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.

Hearing rehabilitation with a binaural cochlear implant in a patient with Erdheim-Chester disease.

PubMed

Querat, Charlotte; Thai-Van, Hung; Durand, Denis Vital; Cotton, François; Gallego, Stéphane; Truy, Eric

2015-09-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis. This paper reports an exceptional case of bilateral neural involvement, responsible for profound hearing loss. Bilateral cochlear implantation was performed. We present a 57-year-old man affected by ECD with profound bilateral hearing loss. The patient underwent cochlear implantation with a binaural Digisonic(®) cochlear implant, 7 years after the initial diagnosis. Speech intelligibility rose to a plateau after about 6 months of cochlear implant use. The average outcome of speech intelligibility over time was 55% for dissyllabic words without lip reading, and 70% for sentences. Perception score decreased before the patient died from ECD. A description of the ECD and its otological manifestations is presented. This paper reports the effective hearing rehabilitation of profound bilateral hearing loss by the means of a binaural Digisonic(®) cochlear implant.

Study I: effects of 0.06% and 0.10% blood alcohol concentration on human postural control.

PubMed

Modig, F; Patel, M; Magnusson, M; Fransson, P A

2012-03-01

Alcohol intoxication causes many accidental falls presented at emergency departments, with the injury severity often related to level of blood alcohol concentration (BAC). One way to evaluate the decline in postural control and the fall risk is to assess standing stability when challenged. The study objective was to comprehensively investigate alcohol-related impairments on postural control and adaptive motor learning at specific BAC levels. Effects of alcohol intoxication at 0.06% and 0.10% BAC were examined with posturography when unperturbed or perturbed by calf vibration. Twenty-five participants (mean age 25.1 years) were investigated standing with either eyes open or closed. Our results revealed several significant findings: (1) stability declined much faster from alcohol intoxication between 0.06% and 0.10% BAC (60-140%) compared with between 0.0% and 0.06% BAC (30%); (2) sustained exposure to repeated balance perturbations augmented the alcohol-related destabilization; (3) there were stronger effects of alcohol intoxication on stability in lateral direction than in anteroposterior direction; and (4) there was a gradual degradation of postural control particularly in lateral direction when the balance perturbations were repeated at 0.06% and 0.10% BAC, indicating adaptation deficits when intoxicated. To summarize, alcohol has profound deteriorating effects on human postural control, which are dose dependent, time dependent and direction specific. The maximal effects of alcohol intoxication on physiological performance might not be evident initially, but may be revealed first when under sustained sensory-motor challenges. Copyright © 2011 Elsevier B.V. All rights reserved.

Long-term empirical evidence of ocean warming leading to tropicalization of fish communities, increased herbivory, and loss of kelp

PubMed Central

Vergés, Adriana; Doropoulos, Christopher; Malcolm, Hamish A.; Skye, Mathew; Garcia-Pizá, Marina; Marzinelli, Ezequiel M.; Campbell, Alexandra H.; Ballesteros, Enric; Hoey, Andrew S.; Vila-Concejo, Ana; Steinberg, Peter D.

2016-01-01

Some of the most profound effects of climate change on ecological communities are due to alterations in species interactions rather than direct physiological effects of changing environmental conditions. Empirical evidence of historical changes in species interactions within climate-impacted communities is, however, rare and difficult to obtain. Here, we demonstrate the recent disappearance of key habitat-forming kelp forests from a warming tropical–temperate transition zone in eastern Australia. Using a 10-y video dataset encompassing a 0.6 °C warming period, we show how herbivory increased as kelp gradually declined and then disappeared. Concurrently, fish communities from sites where kelp was originally abundant but subsequently disappeared became increasingly dominated by tropical herbivores. Feeding assays identified two key tropical/subtropical herbivores that consumed transplanted kelp within hours at these sites. There was also a distinct increase in the abundance of fishes that consume epilithic algae, and much higher bite rates by this group at sites without kelp, suggesting a key role for these fishes in maintaining reefs in kelp-free states by removing kelp recruits. Changes in kelp abundance showed no direct relationship to seawater temperatures over the decade and were also unrelated to other measured abiotic factors (nutrients and storms). Our results show that warming-mediated increases in fish herbivory pose a significant threat to kelp-dominated ecosystems in Australia and, potentially, globally. PMID:27849585

The Role of Dafachronic Acid Signaling in Development and Longevity in Caenorhabditis elegans: Digging Deeper Using Cutting-Edge Analytical Chemistry.

PubMed

Aguilaniu, Hugo; Fabrizio, Paola; Witting, Michael

2016-01-01

Steroid hormones regulate physiological processes in species ranging from plants to humans. A wide range of steroid hormones exist, and their contributions to processes, such as growth, reproduction, development, and aging, is almost always complex. Understanding the biosynthetic pathways that generate steroid hormones and the signaling pathways that mediate their effects is thus of fundamental importance. In this work, we review recent advances in (i) the biological role of steroid hormones in the roundworm Caenorhabditis elegans and (ii) the development of novel methods to facilitate the detection and identification of these molecules. Our current understanding of steroid signaling in this simple organism serves to illustrate the challenges we face moving forward. First, it seems clear that we have not yet identified all of the enzymes responsible for steroid biosynthesis and/or degradation. Second, perturbation of steroid signaling affects a wide range of phenotypes, and subtly different steroid molecules can have distinct effects. Finally, steroid hormone levels are critically important, and minute variations in quantity can profoundly impact a phenotype. Thus, it is imperative that we develop innovative analytical tools and combine them with cutting-edge approaches including comprehensive and highly selective liquid chromatography coupled to mass spectrometry based on new methods such as supercritical fluid chromatography coupled to mass spectrometry (SFC-MS) if we are to obtain a better understanding of the biological functions of steroid signaling.

Long-term empirical evidence of ocean warming leading to tropicalization of fish communities, increased herbivory, and loss of kelp.

PubMed

Vergés, Adriana; Doropoulos, Christopher; Malcolm, Hamish A; Skye, Mathew; Garcia-Pizá, Marina; Marzinelli, Ezequiel M; Campbell, Alexandra H; Ballesteros, Enric; Hoey, Andrew S; Vila-Concejo, Ana; Bozec, Yves-Marie; Steinberg, Peter D

2016-11-29

Some of the most profound effects of climate change on ecological communities are due to alterations in species interactions rather than direct physiological effects of changing environmental conditions. Empirical evidence of historical changes in species interactions within climate-impacted communities is, however, rare and difficult to obtain. Here, we demonstrate the recent disappearance of key habitat-forming kelp forests from a warming tropical-temperate transition zone in eastern Australia. Using a 10-y video dataset encompassing a 0.6 °C warming period, we show how herbivory increased as kelp gradually declined and then disappeared. Concurrently, fish communities from sites where kelp was originally abundant but subsequently disappeared became increasingly dominated by tropical herbivores. Feeding assays identified two key tropical/subtropical herbivores that consumed transplanted kelp within hours at these sites. There was also a distinct increase in the abundance of fishes that consume epilithic algae, and much higher bite rates by this group at sites without kelp, suggesting a key role for these fishes in maintaining reefs in kelp-free states by removing kelp recruits. Changes in kelp abundance showed no direct relationship to seawater temperatures over the decade and were also unrelated to other measured abiotic factors (nutrients and storms). Our results show that warming-mediated increases in fish herbivory pose a significant threat to kelp-dominated ecosystems in Australia and, potentially, globally.

Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model

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

Altman, J.

1987-10-01

In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brainmore » regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. 109 references.« less

Biological responses of Habrobracon to spaceflight.

PubMed

von Borstel, R C; Smith, R H; Whiting, A R; Grosch, D S

1970-01-01

Since the interaction of the parasitic wasp Habrobracon with the space environment could not be prejudged, we decided to test approximately 30 different parameters of a genetic, mutational, biochemical, behavioral, and physiological character in the one spaceflight we had at our disposal. These parameters were examined at six different exposures of gamma-radiation (including 0 dose) in flight, resulting in about 180 different endpoints in all. The most profound effects of spaceflight in conjunction with radiation were decreased hatchability and enhanced fecundity of eggs exposed to spaceflight at different stages of oogenesis. The interpretation we favor is that these two endpoints are reflections of chromosomal non-disjunction in the former case and inhibition of cell division in the latter. Our most comprehensive study of mutagenesis was on sperm, where dominant lethality, recessive lethality, translocations, and visible mutations were assayed; the only effect found was a threefold enhancement of the recessive lethal mutation frequency in the non-irradiated sperm in the orbited Habrobracon males. Behavioral and biochemical differences were found. Mating activity of orbited males was severely disrupted and xanthine dehydrogenase activity was sharply decreased in the irradiated flight animals, an unexpected observation. Postflight experiments were like the ground-based control experiments in all aspects but one. Under conditions of vibration similar to those encountered during the launch and re-entry, the mutation frequency in the sperm increased by a factor of three over that of the non-vibrated control.

The cost of metamorphosis in flatfishes

NASA Astrophysics Data System (ADS)

Geffen, A. J.; van der Veer, H. W.; Nash, R. D. M.

2007-07-01

Flatfish development includes a unique physical metamorphosis with morphological and physiological changes associated with eye migration, a 90° rotation in posture and asymmetrical pigmentation. Flatfish larvae also undergo settlement, a behavioural and ecological change associated with a transition from a pelagic to a benthic existence. These processes are often assumed to be critical in determining recruitment in flatfish, through their impact on feeding, growth and survival. The timing of metamorphosis in relation to settlement varies between different flatfish species and this suggests that growth and development are not closely coupled. Existing information on feeding, growth and survival during metamorphosis and settlement is reviewed. Growth during metamorphosis is reduced in some but not all species. Despite the profound internal and external changes, there are no indications that the process of metamorphosis results in an increased mortality or that it might affect recruitment in flatfishes.

Lysosomal Adaptation: How the Lysosome Responds to External Cues

PubMed Central

Settembre, Carmine; Ballabio, Andrea

2014-01-01

Recent evidence indicates that the importance of the lysosome in cell metabolism and organism physiology goes far beyond the simple disposal of cellular garbage. This dynamic organelle is situated at the crossroad of the most important cellular pathways and is involved in sensing, signaling, and transcriptional mechanisms that respond to environmental cues, such as nutrients. Two main mediators of these lysosomal adaptation mechanisms are the mTORC1 kinase complex and the transcription factor EB (TFEB). These two factors are linked in a lysosome-to-nucleus signaling pathway that provides the lysosome with the ability to adapt to extracellular cues and control its own biogenesis. Modulation of lysosomal function by acting on TFEB has a profound impact on cellular clearance and energy metabolism and is a promising therapeutic target for a large variety of disease conditions. PMID:24799353

Ethical issues regarding human cloning: a nursing perspective.

PubMed

Dinç, Leyla

2003-05-01

Advances in cloning technology and successful cloning experiments in animals raised concerns about the possibility of human cloning in recent years. Despite many objections, this is not only a possibility but also a reality. Human cloning is a scientific revolution. However, it also introduces the potential for physical and psychosocial harm to human beings. From this point of view, it raises profound ethical, social and health related concerns. Human cloning would have an impact on the practice of nursing because it could result in the creation of new physiological and psychosocial conditions that would require nursing care. The nursing profession must therefore evaluate the ethics of human cloning, in particular the potential role of nurses. This article reviews the ethical considerations of reproductive human cloning, discusses the main reasons for concern, and reflects a nursing perspective regarding this issue.

Research on Automatic Ticketing Interface Design of Tianjin South Station under the Background of Aging

NASA Astrophysics Data System (ADS)

Zhenghui, Zhao

2018-04-01

Based on the context of increasingly serious aging problem in China, the psychological characteristics of elders in using public self-service facilities and the development status and the future trend of public self-service ticketing service. The approach is analysing physiological and psychological characteristics, education level of the elderly and studying its characteristics of consumer psychology and regional cultural characteristics profoundly before conducting comprehensive analysis and research in combination with the interface features of public self-service ticketing machine. The interface design will be more personalized, intelligent, regional and international. Strategies of caring for the elderly in the regional public self-service facility interface design innovation develops the concept of taking care of the elderly in the entire region as an indispensable people-benefiting optimization system in the modern social services.

STUDIES ON THE SYNDROME OF FAT EMBOLIZATION.

PubMed

SPROULE, B J; BRADY, J L; GILBERT, J A

1964-05-30

Three patients, all of whom were well-muscled young adult males who had suffered fractures of long bones, were studied by means of measurement of ventilatory function and arterial blood gases. They had degrees of mental change varying from mild confusion to stupor. Anemia, hypocalcemia, skin petechiae and radiologic pulmonary infiltrates were demonstrated in all three.In the absence of any clinical cyanosis, profound arterial O(2) desaturation was demonstrated in all. Physiologic studies indicated that the desaturation was the result of a diffusion defect early in the course of the syndrome and later from venous admixture. The lungs were stiff and the work of breathing was increased. The anemia appeared to be hemolytic in type.It is suggested that anemia, hypocalcemia and arterial O(2) desaturation may contribute significantly to the cerebral symptomatology associated with the syndrome of fat embolization.

The "fourth dimension" of gene transcription.

PubMed

O'Malley, Bert W

2009-05-01

The three dimensions of space provide our relationship to position on the earth, but the fourth dimension of time has an equally profound influence on our lives. Everything from light and sound to weather and biology operate on the principle of measurable temporal periodicity. Consequently, a wide variety of time clocks affect all aspects of our existence. The annual (and biannual) cycles of activity, metabolism, and mating, the monthly physiological clocks of women and men, and the 24-h diurnal rhythms of humans are prime examples. Should it be surprising to us that the fourth dimension also impinges upon gene expression and that the genome itself is regulated by the fastest running of all biological clocks? Recent evidence substantiates the existence of such a ubiquitin-dependent transcriptional clock that is based upon the activation and destruction of transcriptional coactivators.

The “Fourth Dimension” of Gene Transcription

PubMed Central

O'Malley, Bert W.

2009-01-01

The three dimensions of space provide our relationship to position on the earth, but the fourth dimension of time has an equally profound influence on our lives. Everything from light and sound to weather and biology operate on the principle of measurable temporal periodicity. Consequently, a wide variety of time clocks affect all aspects of our existence. The annual (and biannual) cycles of activity, metabolism, and mating, the monthly physiological clocks of women and men, and the 24-h diurnal rhythms of humans are prime examples. Should it be surprising to us that the fourth dimension also impinges upon gene expression and that the genome itself is regulated by the fastest running of all biological clocks? Recent evidence substantiates the existence of such a ubiquitin-dependent transcriptional clock that is based upon the activation and destruction of transcriptional coactivators. PMID:19221049

Pregnancy in a woman with proportionate (primordial) dwarfism: a case report and literature review

PubMed Central

Vance, C E; Desmond, M; Robinson, A; Johns, J; Zacharin, M; Savarirayan, R; König, K; Warrillow, S; Walker, S P

2012-01-01

Primordial dwarfism is a rare form of severe proportionate dwarfism which poses significant challenges in pregnancy. A 27-year-old with primordial dwarfism (height 97 cm, weight 22 kg) and coexisting morbidities of familial hypercholesterolaemia and hypertension presented to our unit. Early pregnancy was complicated by difficult blood pressure control, sinus tachycardia, biochemical hyperthyroidism and insulin-requiring gestational diabetes. Delivery was indicated at 24 weeks with uncontrollable hypertension, progressive renal impairment and intrauterine growth restriction. A caesarean section was performed under general anaesthesia, resulting in the delivery of a 486 g male infant. This case highlights the difficulties of managing pregnancy in a woman with primordial dwarfism. Her limited capacity to respond to the physiological demands of pregnancy created a life-threatening situation, culminating in profound preterm birth. PMID:27582869

Environmental science. Rethinking the marine carbon cycle: factoring in the multifarious lifestyles of microbes.

PubMed

Worden, Alexandra Z; Follows, Michael J; Giovannoni, Stephen J; Wilken, Susanne; Zimmerman, Amy E; Keeling, Patrick J

2015-02-13

The profound influence of marine plankton on the global carbon cycle has been recognized for decades, particularly for photosynthetic microbes that form the base of ocean food chains. However, a comprehensive model of the carbon cycle is challenged by unicellular eukaryotes (protists) having evolved complex behavioral strategies and organismal interactions that extend far beyond photosynthetic lifestyles. As is also true for multicellular eukaryotes, these strategies and their associated physiological changes are difficult to deduce from genome sequences or gene repertoires—a problem compounded by numerous unknown function proteins. Here, we explore protistan trophic modes in marine food webs and broader biogeochemical influences. We also evaluate approaches that could resolve their activities, link them to biotic and abiotic factors, and integrate them into an ecosystems biology framework. Copyright © 2015, American Association for the Advancement of Science.

Viewpoint: exploring the human interior: the roles of cadaver dissection and radiologic imaging in teaching anatomy.

PubMed

Gunderman, Richard B; Wilson, Philip K

2005-08-01

For a variety of reasons, new radiological imaging techniques are supplanting traditional cadaver dissection in the teaching of human anatomy. The authors briefly review the historical forces behind this transition, and then explore the advantages and drawbacks of each approach. Cadaver dissection offers an active, hands-on exploration of human structure, provides deep insights into the meaning of human embodiment and mortality, and represents a profound rite of passage into the medical profession. Radiological imaging permits in vivo visualization, offers physiologic as well as anatomic insights, and represents the context in which contemporary practicing physicians most frequently encounter their patients' otherwise hidden internal anatomy. Despite its important strengths, radiology cannot simply substitute for cadaver dissection, and the best models for teaching gross anatomy will incorporate both cadaver dissection and radiological imaging.

Bringing Hearing to the Deaf

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

Shipsey, Ian

In his talk, Shipsey will discuss the cochlear implant, the first device to successfully allow the profoundly deaf to regain some sense of hearing. A cochlear implant is a small electronic apparatus. Unlike a normal hearing aid, which amplifies sound, a cochlear implant is surgically implanted behind the ear where it converts sound waves into electrical impulses. These implants have instigated a popular but controversial revolution in the treatment of deafness, and they serve as a model for research in neuroscience and biomedical engineering. Shipsey will discuss the physiology of natural hearing from the perspective of a physicist. He willmore » also touch on the function of cochlear implants in the context of historical treatments, electrical engineering, psychophysics, clinical evaluation of efficacy and personal experience. Finally, Shipsey will address the social implications of cochlear implantation and the future outlook for auditory prostheses.« less

Effect of electronic media on children.

PubMed

Ray, Munni; Jat, Kana Ram

2010-07-01

Radio, television (TV), movies, video games, cell phones, and computer networks have assumed central roles in our children's daily lives. The media has demonstrated potentially profound effects, both positive and negative, on children's cognitive, social, and behavioral development. Considering the increasing exposure of children to newer forms of media, we decided to review the current literature on the effects of media on child health both in the Western countries and India. It is widely accepted that media has profound influence on child health, including violence, obesity, tobacco and alcohol use, and risky sexual behaviors. Simultaneously, media may have some positive effects on child health. We need to find ways to optimize the role of media in our society, taking advantage of their positive attributes and minimizing their negative ones. We need to understand better how to reverse the negative impact of media and make it more positive.

What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia.

PubMed

Alba-Ferrara, L M; de Erausquin, Gabriel A

2013-01-01

Schizophrenia is a common, severe, and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI). Indices commonly derived from DTI include (1) mean diffusivity, independent of direction, (2) fractional anisotropy (FA) or relative anisotropy (RA), (3) axial diffusivity, and (4) radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes (OLG), and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased FA in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

The concomitant apoptosis and EMT underlie the fundamental functions of TGF-β.

PubMed

Song, Jianguo; Shi, Weiwei

2018-01-01

TGF-β's multipotent cellular effects and their relations are critical for TGF-β's pathophysiological functions. However, these effects may appear to be paradoxical in understanding TGF-β's functions. Apoptosis and epithelial-mesenchymal transition (EMT) are two fundamental events that are deeply linked to various physiological and disease-related processes. These two major cellular fates are subtly regulated and can be potently stimulated by TGF-β, which profoundly contribute to the biological roles of TGF-β. Moreover, these two events are also indirectly and directly correlated with TGF-β-mediated growth inhibition and are relevant to the current understanding of the roles of TGF-β in tumorigenesis and cancer progression. Although TGF-β-induced apoptosis and EMT can be singly independent cellular events, they can also be mutually exclusive but interrelated concomitant events in various cases. Thus, the modulation of apoptosis and EMT is essential for the seemingly paradoxical functions of TGF-β. However, the concomitant effect of TGF-β on apoptosis and EMT, the balance and regulated alterations of them are still been ignored or underestimated. This review focuses on the TGF-β-induced concomitant apoptosis and EMT. We aim to provide an insight in understanding their significance, balance, and modulation in TGF-β-mediated biological functions. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Structural analysis of thermostabilizing mutations of cocaine esterase

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

Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan

Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstablemore » at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.« less

Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglia neurons

PubMed Central

Schink, Martin; Leipolcf, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H.

2016-01-01

Dorsal root ganglia (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 µM) or low-intensity blue-light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8−/−), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and at higher concentrations progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure. PMID:26383867

Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

PubMed

Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

2016-01-01

Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

Interictal cardiorespiratory variability in temporal lobe and absence epilepsy in childhood.

PubMed

Varon, Carolina; Montalto, Alessandro; Jansen, Katrien; Lagae, Lieven; Marinazzo, Daniele; Faes, Luca; Van Huffel, Sabine

2015-04-01

It is well known that epilepsy has a profound effect on the autonomic nervous system, especially on the autonomic control of heart rate and respiration. This effect has been widely studied during seizure activity, but less attention has been given to interictal (i.e. seizure-free) activity. The studies that have been done on this topic, showed that heart rate and respiration can be affected individually, even without the occurrence of seizures. In this work, the interactions between these two individual physiological variables are analysed during interictal activity in temporal lobe and absence epilepsy in childhood. These interactions are assessed by decomposing the predictive information about heart rate variability, into different components like the transfer entropy, cross-entropy, self- entropy and the conditional self entropy. Each one of these components quantifies different types of shared information. However, when using the cross-entropy and the conditional self entropy, it is possible to split the information carried by the heart rate, into two main components, one related to respiration and one related to different mechanisms, like sympathetic activation. This can be done after assuming a directional link going from respiration to heart rate. After analysing all the entropy components, it is shown that in subjects with absence epilepsy the information shared by respiration and heart rate is significantly lower than for normal subjects. And a more remarkable finding indicates that this type of epilepsy seems to have a long term effect on the cardiac and respiratory control mechanisms of the autonomic nervous system.

Interactions between β-amyloid and central cholinergic neurons: implications for Alzheimer's disease

PubMed Central

Kar, Satyabrata; Slowikowski, Stephen P.M.; Westaway, David; Mount, Howard T.J.

2004-01-01

Alzheimer's disease is an age-related neurodegenerative disorder that is characterized by a progressive loss of memory and deterioration of higher cognitive functions. The brain of an individual with Alzheimer's disease exhibits extracellular plaques of aggregated β-amyloid protein (Aβ), intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein and a profound loss of basal forebrain cholinergic neurons that innervate the hippocampus and the neocortex. Aβ accumulation may trigger or contribute to the process of neurodegeneration. However, the mechanisms whereby Aβ induces basal forebrain cholinergic cell loss and cognitive impairment remain obscure. Physiologically relevant concentrations of Aβ-related peptides have acute, negative effects on multiple aspects of acetylcholine (ACh) synthesis and release, without inducing toxicity. These data suggest a neuromodulatory influence of the peptides on central cholinergic functions. Long-term exposure to micromolar Aβ induces cholinergic cell toxicity, possibly via hyperphosphorylation of tau protein. Conversely, activation of selected cholinergic receptors has been shown to alter the processing of the amyloid precursor protein as well as phosphorylation of tau protein. A direct interaction between Aβ and nicotinic ACh receptors has also been demonstrated. This review addresses the role of Aβ-related peptides in regulating the function and survival of central cholinergic neurons and the relevance of these effects to cholinergic deficits in Alzheimer's disease. Understanding the functional interrelations between Aβ peptides, cholinergic neurons and tau phosphorylation will unravel the biologic events that precede neurodegeneration and may lead to the development of more effective pharmacotherapies for Alzheimer's disease. PMID:15644984

Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile.

PubMed

Lissauer, David; Eldershaw, Suzy A; Inman, Charlotte F; Coomarasamy, Aravinthan; Moss, Paul A H; Kilby, Mark D

2015-10-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4(+) and CD8(+) T cells, with reductions not only in potentially deleterious IFN-γ and TNF-α production but also in IL-10 and IL-5. Conversely, production of IL-4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL-4. This was accompanied by reduced T-cell proliferation. Using fetal and viral antigen-specific CD8(+) T-cell clones, we confirmed that this as a direct, nonantigen-specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4(+) and CD8(+) T cells responded to progesterone in a dose-dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal-fetal interface. This characterization of how progesterone modulates T-cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Longitudinal studies of time-dependent changes in both bladder and erectile function after streptozotocin-induced diabetes in Fischer 344 male rats.

PubMed

Melman, Arnold; Zotova, Elena; Kim, Mimi; Arezzo, Joseph; Davies, Kelvin; DiSanto, Michael; Tar, Moses

2009-11-01

To provide sensitive physiological endpoints for the onset and long-term progression of deficits induced by diabetes mellitus (DM) in bladder and erectile function in male rats, and to evaluate parallel changes in urogenital and nerve function induced by hyperglycaemia over a protracted period as a model for chronic deficits in patients with diabetes. The study comprised in 877 male, 3-month-old, Fischer 344 rats; 666 were injected intraperitoneally with 35 mg/kg streptozotocin (STZ) and divided into insulin-treated and untreated diabetic groups. The rats were studied over 8 months and measurements made of both erectile and bladder function, as well as nerve conduction studies over the duration of the study. There was an early (first month) abnormality of both erectile and bladder function that persisted through the 8 months of the study. The erectile dysfunction was manifest as reduced intracavernous pressure/blood pressure ratio, and the bladder dysfunction as a persistent increase in detrusor overactivity with no detrusor decompensation. Insulin treatment prevented or modified the abnormality in each organ. Hyperglycaemia caused a progressive decrease in caudal nerve conduction velocity. The mean digital sensory and tibial motor nerve conduction velocity did not deteriorate over time. Correlation measurements of nerve and organ function were not consistent. The results of this extensive long-term study show early and profound effects of hyperglycaemia on the smooth muscle of the penis and bladder, that were persistent and stable in surviving rats over the 8 months. The physiological changes did not correlate well with neurological measurements of those organs. Significantly, diverse smooth-muscle cellular and subcellular events antedated the measured neurological manifestations of the hyperglycaemia by several months. Although autonomic diabetic neuropathy is a primary life-threatening complication of long-term diabetes in humans, this rat model of STZ-induced diabetes showed that the rapid onset of physiological manifestations was based on many molecular changes in the smooth muscle cells in this model of type 1 DM.

Multiple Oxygen Tension Environments Reveal Diverse Patterns of Transcriptional Regulation in Primary Astrocytes

PubMed Central

Zhou, Yu; Wang, Liyun; Park, Sung-Soo; Martin, Bronwen; Wang, Rui; Becker, Kevin G.; Wood, William H.; Zhang, Yongqing; Peers, Chris; Maudsley, Stuart

2011-01-01

The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity. PMID:21738745

Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles.

PubMed

Carlander, Ulrika; Li, Dingsheng; Jolliet, Olivier; Emond, Claude; Johanson, Gunnar

2016-01-01

To assess the potential toxicity of nanoparticles (NPs), information concerning their uptake and disposition (biokinetics) is essential. Experience with industrial chemicals and pharmaceutical drugs reveals that biokinetics can be described and predicted accurately by physiologically-based pharmacokinetic (PBPK) modeling. The nano PBPK models developed to date all concern a single type of NP. Our aim here was to extend a recent model for pegylated polyacrylamide NP in order to develop a more general PBPK model for nondegradable NPs injected intravenously into rats. The same model and physiological parameters were applied to pegylated polyacrylamide, uncoated polyacrylamide, gold, and titanium dioxide NPs, whereas NP-specific parameters were chosen on the basis of the best fit to the experimental time-courses of NP accumulation in various tissues. Our model describes the biokinetic behavior of all four types of NPs adequately, despite extensive differences in this behavior as well as in their physicochemical properties. In addition, this simulation demonstrated that the dose exerts a profound impact on the biokinetics, since saturation of the phagocytic cells at higher doses becomes a major limiting step. The fitted model parameters that were most dependent on NP type included the blood:tissue coefficients of permeability and the rate constant for phagocytic uptake. Since only four types of NPs with several differences in characteristics (dose, size, charge, shape, and surface properties) were used, the relationship between these characteristics and the NP-dependent model parameters could not be elucidated and more experimental data are required in this context. In this connection, intravenous biodistribution studies with associated PBPK analyses would provide the most insight.

Effect of skin wettedness on sweat gland response

NASA Technical Reports Server (NTRS)

Nadel, E. R.; Stolwijk, J. A. J.

1973-01-01

Investigation of the effect of skin wettedness upon sweating rate. Several techniques were used to gain a better understanding of the quantitative nature of this effect. The results include the finding that the evaporative power of the environment has a profound effect on the relationship between body temperature and sweating rate.

Systemic Inflammatory Response Syndrome After Administration of Unmodified T Lymphocytes

PubMed Central

Papadopoulou, Anastasia; Krance, Robert A; Allen, Carl E; Lee, Daniel; Rooney, Cliona M; Brenner, Malcolm K; Leen, Ann M; Heslop, Helen E

2014-01-01

Systemic inflammatory response syndrome (SIRS) is a rare systemic inflammatory response associated with fever, tachycardia, profound hypotension, and respiratory distress, which has been reported in cancer patients receiving T cells genetically modified with chimeric antigen receptors to retarget their specificity to tumor-associated antigens. The syndrome usually occurs following significant in vivo expansion of the infused cells and has been associated with tumor destruction/lysis. Analysis of patient plasma has shown elevated cytokine levels, and resolution of symptoms has been reported after administration of steroids and/or antibodies (such as anti–tumor necrosis factor and anti-interleukin (IL)-6 receptor antibodies) that interfere with cytokine responses.To date, SIRS has not been reported in subjects receiving genetically unmodified T cells with native receptors directed against tumor antigens, in which greater physiological control of T-cell activation and expansion may occur. Here, however, we report a patient with bulky refractory Epstein-Barr virus (EBV)–associated lymphoma, who developed this syndrome 2 weeks after receiving T cells directed against EBV antigens through their native receptors. She was treated with steroids and etanercept, with rapid resolution of symptoms. SIRS may therefore occur even when T cells recognize antigens physiologically through their “wild-type” native receptors and should be acknowledged as a potential complication of this therapy. PMID:24651135

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

PubMed Central

Seldin, Marcus M.; Byerly, Mardi S.; Petersen, Pia S.; Swanson, Roy; Balkema-Buschmann, Anne; Groschup, Martin H.; Wong, G. William

2014-01-01

Mammalian hibernation elicits profound changes in whole-body physiology. The liver-derived hibernation protein (HP) complex, consisting of HP-20, HP-25 and HP-27, was shown to oscillate circannually, and this oscillation in the central nervous system (CNS) was suggested to play a role in hibernation. The HP complex has been found in hibernating chipmunks but not in related non-hibernating tree squirrels, leading to the suggestion that hibernation-specific genes may underlie the origin of hibernation. Here, we show that non-hibernating mammals express and regulate the conserved homologous HP complex in a seasonal manner, independent of hibernation. Comparative analyses of cow and chipmunk HPs revealed extensive biochemical and structural conservations. These include liver-specific expression, assembly of distinct heteromeric complexes that circulate in the blood and cerebrospinal fluid, and the striking seasonal oscillation of the HP levels in the blood and CNS. Central administration of recombinant HPs affected food intake in mice, without altering body temperature, physical activity levels or energy expenditure. Our results demonstrate that HP complex is not unique to the hibernators and suggest that the HP-regulated liver–brain circuit may couple seasonal changes in the environment to alterations in physiology. PMID:25079892

RABBIT POX

PubMed Central

Greene, Harry S. N.

1935-01-01

The epidemiological significance of age, race, sex, genetic constitution and physiological status were studied by means of a differential analysis of the mortality data derived from a devastating epidemic of rabbit pox and, with the exception of sex, were found to be factors of the utmost importance in the determination of susceptibility. Young animals were more susceptible than adults and although the most susceptible age varied with the epidemic phase, it corresponded in general with the period of weaning. The influence of physiological status was further indicated by the increased susceptibility incident to lactation. Racial variations in susceptibility were obscured by age factors in young animals, but were of profound importance in the adult population and formed the most significant feature of the analysis. A high degree of conformity was found in the susceptibility of racially related breeds, and this similarity in behavior increased with the proximity of relationship. Moreover, a study of the hybrids obtained from the crossing of pure breeds showed that two separable groups of hereditary factors were concerned in the determination of breed susceptibility, one group consisting of essential racial characters, the other of constitutional factors incorporated in the stock by chance association, and that the final expression of susceptibility or resistance was the result of their combined interaction. PMID:19870417

Nature, nomenclature and taxonomy of obligate methanol utilizing strains.

PubMed

Cercel, M

1999-01-01

In a screening program, a number of different bacterial strains with the ability to utilize methanol as a sole carbon and energy source were isolated and described. They are well known methanol utilizing genera Pseudomonas, Klebsiella, Micrococcus, Methylomonas or, on the contrary, the new, unknown genera and species of methylotrophic bacteria. In the last category, Acinetobacter and Alcaligenes are the new reported genera of organisms able to use methanol as a sole carbon and energy source. The present paper reports the very complex physiological and biochemical modifications when very versatile bacteria such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus are cultured on methanol and when the obligate methylotrophic state is compared with the facultative methylotrophic state of the same bacterial strain. Based on experiments and comparisons with literature data, it seems that Methylomonas methanica is the obligate methylotrophic state of Pseudomonas aeruginosa and that Acinetobacter calcoaceticus is the facultative methylotrophic state of Methylococcus capsulatus, an obligate methylotroph. The relationship of the obligate to the facultative and of the facultative to the obligate methylotrophy were established. These new methylotrophic genera and species, the profound physiological and biochemical modifications as well as the new data concerning nature, nomenclature and taxonomy of methanol utilizing bateria were reported for the first time in 1983.

Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans.

PubMed

Hoye, Bethany J; Fouchier, Ron A M; Klaassen, Marcel

2012-02-07

Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host-pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (-25.3±0.4) than their non-infected counterparts (-26.3±0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness.

LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.

PubMed

Gut, Philipp; Reischauer, Sven; Stainier, Didier Y R; Arnaout, Rima

2017-07-01

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date. Copyright © 2017 the American Physiological Society.

Enteric infections, diarrhea, and their impact on function and development

PubMed Central

Petri, William A.; Miller, Mark; Binder, Henry J.; Levine, Myron M.; Dillingham, Rebecca; Guerrant, Richard L.

2008-01-01

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding. PMID:18382740

Developmental dysgraphia with profound hearing impairment: intervention by auditory methods enabled by cochlear implant.

PubMed

Fukushima, Kunihiro; Kawasaki, Akihiro; Nagayasu, Rie; Kunisue, Kazuya; Maeda, Yukihide; Kariya, Shin; Kataoka, Yuko; Nishizaki, Kazunori

2008-06-01

Learning disability combined with hearing impairment (LDHI) is a poor prognostic factor for the language development of hearing impaired children after educational intervention. A typical example of a child with LDHI and effective interventions provided by cochlear implants are presented in this report. A case of congenital cytomegaloviral infection that showed dysgraphia as well as profound deafness was reported and an underlying visual processing problem diagnosed in the present case caused the patient's dysgraphia. The dysgraphia could be circumvented by the use of auditory memory fairly established by a cochlear implant.

Honoring Leslie A. Geddes - farewell ...

PubMed

Valentinuzzi, Max E

2010-01-05

Honor thy father and thy mother, say the Holy Scriptures1, for they at least gave thee this biological life, but honor thy teachers, too, for they gave thee knowledge and example.Leslie Alexander Geddes took off on a long, long trip, Sunday October 25, 2009, leaving his body for medical and research use. The departing station was West Lafayette, Indiana, where he set foot in 1974, at Purdue University, stamping there a unique deep imprint, similar and probably more profound than the one left at Baylor College of Medicine (BCM), Houston, Texas, in the period 1955-1974. Memories came back as a flood the minute after a message broke the news to me: When I first met him visiting the Department of Physiology at BCM back in 1962, my first Classical Physiology with Modern Instrumentation Summer Course ... The versatile Physiograph was the main equipment, an electronic-mechanical three or four channel recorder that could pick up a variety of physiological variables. Les and his collaborators had introduced also the impedance pneumograph, which was a simplified version of previous developments made by others. It became a ubiquitous unit that trod many roads in the hands of eager and curious students. Ventricular fibrillation and especially its counterpart, defibrillation, stand out as subjects occupying his concern along the years. Many were the students recruited to such effort and long is the list of papers on the subject. Physiological signals attracted considerable part of his activities because one of his perennial mottos was measurement is essential in physiology. He has written thirteen books and over eight hundred scientific papers, receiving also several prizes and distinctions. Not only his interests stayed within the academic environment but an industrial hue was manifested in over 20 USA patents, all applied to medical use. History of science and technology was another area in which, often with Hebbel Hoff, he uncovered astounding and delightful information. It is beyond my capability to review everything Les did, least of all what he did during the long span at Purdue.

Water, temperature, and defoliation effects on perennial grassland respiration

USDA-ARS?s Scientific Manuscript database

Changes in respiration can have a profound effect on ecosystem C balance. This talk will present results from eddy covariance studies describing environment and management effects on ecosystem C flux from cool- and warm-season perennial grasslands. In addition, stable C isotope studies that partitio...

In vivo evidence that N-oleoylglycine acts independently of its conversion to oleamide.

PubMed

Chaturvedi, Shalini; Driscoll, William J; Elliot, Brenda M; Faraday, Martha M; Grunberg, Neil E; Mueller, Gregory P

2006-12-01

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly developed enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide.

Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout.

PubMed

Chhana, Ashika; Callon, Karen E; Pool, Bregina; Naot, Dorit; Watson, Maureen; Gamble, Greg D; McQueen, Fiona M; Cornish, Jillian; Dalbeth, Nicola

2011-09-01

Bone erosion is a common manifestation of chronic tophaceous gout. To investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function. The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteoblast-like cell lines, and primary rat and primary human osteoblasts cultured with MSU crystals. Quantitative real-time PCR and von Kossa stained mineralised bone formation assays were used to assess the effects of MSU crystals on osteoblast differentiation using MC3T3-E1 cells. The numbers of osteoblasts and bone lining cells were quantified in bone samples from patients with gout. MSU crystals rapidly reduced viability in all cell types in a dose-dependent manner. The inhibitory effect on cell viability was independent of crystal phagocytosis and was not influenced by differing crystal length or addition of serum. Long-term culture of MC3T3-E1 cells with MSU crystals showed a reduction in mineralisation and decreased mRNA expression of genes related to osteoblast differentiation such as Runx2, Sp7 (osterix), Ibsp (bone sialoprotein), and Bglap (osteocalcin). Fewer osteoblast and lining cells were present on bone directly adjacent to gouty tophus than bone unaffected by tophus in patients with gout. MSU crystals have profound inhibitory effects on osteoblast viability and differentiation. These data suggest that bone erosion in gout occurs at the tophus-bone interface through alteration of physiological bone turnover, with both excessive osteoclast formation, and reduced osteoblast differentiation from mesenchymal stem cells.

Developmental origins of inflammatory and immune diseases

PubMed Central

Chen, Ting; Liu, Han-xiao; Yan, Hui-yi; Wu, Dong-mei; Ping, Jie

2016-01-01

Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the ‘developmental programming’ and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic–pituitary–adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention. PMID:27226490

Predicting the effects of ocean acidification on predator-prey interactions: a conceptual framework based on coastal molluscs.

PubMed

Kroeker, Kristy J; Sanford, Eric; Jellison, Brittany M; Gaylord, Brian

2014-06-01

The influence of environmental change on species interactions will affect population dynamics and community structure in the future, but our current understanding of the outcomes of species interactions in a high-CO2 world is limited. Here, we draw upon emerging experimental research examining the effects of ocean acidification on coastal molluscs to provide hypotheses of the potential impacts of high-CO2 on predator-prey interactions. Coastal molluscs, such as oysters, mussels, and snails, allocate energy among defenses, growth, and reproduction. Ocean acidification increases the energetic costs of physiological processes such as acid-base regulation and calcification. Impacted molluscs can display complex and divergent patterns of energy allocation to defenses and growth that may influence predator-prey interactions; these include changes in shell properties, body size, tissue mass, immune function, or reproductive output. Ocean acidification has also been shown to induce complex changes in chemoreception, behavior, and inducible defenses, including altered cue detection and predator avoidance behaviors. Each of these responses may ultimately alter the susceptibility of coastal molluscs to predation through effects on predator handling time, satiation, and search time. While many of these effects may manifest as increases in per capita predation rates on coastal molluscs, the ultimate outcome of predator-prey interactions will also depend on how ocean acidification affects the specified predators, which also exhibit complex responses to ocean acidification. Changes in predator-prey interactions could have profound and unexplored consequences for the population dynamics of coastal molluscs in a high-CO2 ocean. © 2014 Marine Biological Laboratory.

In Vivo Evidence that N-Oleoylglycine Acts Independently of Its Conversion to Oleamide

PubMed Central

Chaturvedi, Shalini; Driscoll, William J.; Elliot, Brenda M.; Faraday, Martha M.; Grunberg, Neil E.; Mueller, Gregory P.

2006-01-01

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly development enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80 mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide, and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide. PMID:17085322

The pressor response to water drinking in humans : a sympathetic reflex?

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Black, B. K.; Ali, Y.; Farley, M.; Costa, F.; Diedrich, A.; Robertson, R. M.; Biaggioni, I.; Robertson, D.

2000-01-01

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Profound Effects of Population Density on Fitness-Related Traits in an Invasive Freshwater Snail

PubMed Central

Zachar, Nicholas; Neiman, Maurine

2013-01-01

Population density can profoundly influence fitness-related traits and population dynamics, and density dependence plays a key role in many prominent ecological and evolutionary hypotheses. Here, we evaluated how individual-level changes in population density affect growth rate and embryo production early in reproductive maturity in two different asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that is an important model system for ecotoxicology and the evolution of sexual reproduction as well as a potentially destructive worldwide invader. We showed that population density had a major influence on individual growth rate and early-maturity embryo production, effects that were often apparent even when comparing treatments that differed in population density by only one individual. While individual growth rate generally decreased as population density increased, we detected a hump-shaped relationship between embryo production and density, with females from intermediate-density treatments producing the most embryos and females from low- and high-density treatments producing the fewest embryos. The two lineages responded similarly to the treatments, indicating that these effects of population density might apply more broadly across P. antipodarum. These results indicate that there are profound and complex relationships between population density, growth rate, and early-maturity embryo production in at least two lineages of this important model system, with potential implications for the study of invasive populations, research on the maintenance of sex, and approaches used in ecotoxicology. PMID:24278240

Profound effects of population density on fitness-related traits in an invasive freshwater snail.

PubMed

Zachar, Nicholas; Neiman, Maurine

2013-01-01

Population density can profoundly influence fitness-related traits and population dynamics, and density dependence plays a key role in many prominent ecological and evolutionary hypotheses. Here, we evaluated how individual-level changes in population density affect growth rate and embryo production early in reproductive maturity in two different asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that is an important model system for ecotoxicology and the evolution of sexual reproduction as well as a potentially destructive worldwide invader. We showed that population density had a major influence on individual growth rate and early-maturity embryo production, effects that were often apparent even when comparing treatments that differed in population density by only one individual. While individual growth rate generally decreased as population density increased, we detected a hump-shaped relationship between embryo production and density, with females from intermediate-density treatments producing the most embryos and females from low- and high-density treatments producing the fewest embryos. The two lineages responded similarly to the treatments, indicating that these effects of population density might apply more broadly across P. antipodarum. These results indicate that there are profound and complex relationships between population density, growth rate, and early-maturity embryo production in at least two lineages of this important model system, with potential implications for the study of invasive populations, research on the maintenance of sex, and approaches used in ecotoxicology.

Book Discounts and Cost-Plus Pricing

ERIC Educational Resources Information Center

Andresen, David C.

1974-01-01

The adoption of cost-plus pricing by a major book jobber may have profound effects on the discounts that libraries receive. The article explains the pricing system and presents a set of graphs for libraries to use to determine its effects. (Author)

Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

PubMed

Driessen, Mieke M P; Hui, Wei; Bijnens, Bart H; Dragulescu, Andreea; Mertens, Luc; Meijboom, Folkert J; Friedberg, Mark K

2016-06-01

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Pulse-drought atop press-drought: unexpected plant responses and implications for dryland ecosystems.

PubMed

Hoover, David L; Duniway, Michael C; Belnap, Jayne

2015-12-01

In drylands, climate change is predicted to cause chronic reductions in water availability (press-droughts) through reduced precipitation and increased temperatures as well as increase the frequency and intensity of short-term extreme droughts (pulse-droughts). These changes in precipitation patterns may have profound ecosystem effects, depending on the sensitivities of the dominant plant functional types (PFTs). Here we present the responses of four Colorado Plateau PFTs to an experimentally imposed, 4-year, press-drought during which a natural pulse-drought occurred. Our objectives were to (1) identify the drought sensitivities of the PFTs, (2) assess the additive effects of the press- and pulse-drought, and (3) examine the interactive effects of soils and drought. Our results revealed that the C3 grasses were the most sensitive PFT to drought, the C3 shrubs were the most resistant, and the C4 grasses and shrubs had intermediate drought sensitivities. Although we expected the C3 grasses would have the greatest response to drought, the higher resistance of C3 shrubs relative to the C4 shrubs was contrary to our predictions based on the higher water use efficiency of C4 photosynthesis. Also, the additive effects of press- and pulse-droughts caused high morality in C3 grasses, which has large ecological and economic ramifications for this region. Furthermore, despite predictions based on the inverse texture hypothesis, we observed no interactive effects of soils with the drought treatment on cover or mortality. These results suggest that plant responses to droughts in drylands may differ from expectations and have large ecological effects if press- and pulse-droughts push species beyond physiological and mortality thresholds.

Pulse-drought atop press-drought: unexpected plant responses and implications for dryland ecosystems

USGS Publications Warehouse

Hoover, David L.; Duniway, Michael C.; Belnap, Jayne

2015-01-01

In drylands, climate change is predicted to cause chronic reductions in water availability (press-droughts) through reduced precipitation and increased temperatures as well as increase the frequency and intensity of short-term extreme droughts (pulse-droughts). These changes in precipitation patterns may have profound ecosystem effects, depending on the sensitivities of the dominant plant functional types (PFTs). Here we present the responses of four Colorado Plateau PFTs to an experimentally imposed, 4-year, press-drought during which a natural pulse-drought occurred. Our objectives were to (1) identify the drought sensitivities of the PFTs, (2) assess the additive effects of the press- and pulse-drought, and (3) examine the interactive effects of soils and drought. Our results revealed that the C3 grasses were the most sensitive PFT to drought, the C3shrubs were the most resistant, and the C4 grasses and shrubs had intermediate drought sensitivities. Although we expected the C3 grasses would have the greatest response to drought, the higher resistance of C3 shrubs relative to the C4 shrubs was contrary to our predictions based on the higher water use efficiency of C4 photosynthesis. Also, the additive effects of press- and pulse-droughts caused high morality in C3 grasses, which has large ecological and economic ramifications for this region. Furthermore, despite predictions based on the inverse texture hypothesis, we observed no interactive effects of soils with the drought treatment on cover or mortality. These results suggest that plant responses to droughts in drylands may differ from expectations and have large ecological effects if press- and pulse-droughts push species beyond physiological and mortality thresholds.

Implications of nutritional stress as nestling or fledgling on subsequent attractiveness and fecundity in zebra finches (Taeniopygia guttata).

PubMed

Honarmand, Mariam; Krause, E Tobias; Naguib, Marc

2017-01-01

The conditions an organism experiences during early development can have profound and long lasting effects on its subsequent behavior, attractiveness, and life history decisions. Most previous studies have exposed individuals to different conditions throughout development until nutritional independence. Yet under natural conditions, individuals may experience limitations for much shorter periods due to transient environmental fluctuations. Here, we used zebra finches ( Taeniopygia guttata ) in captivity to determine if conditions experienced during distinctly different early developmental phases contribute differently to male and female attractiveness and subsequent reproduction. We conducted a breeding experiment in which offspring were exposed to food regimes with (a) low quality food provided only during the nestling period, (b) low quality food provided only during the fledgling period, or (c) high quality food throughout early development. We show that despite short-term effects on biometry and physiology, there were no effects on either male or female attractiveness, as tested in two-way mate choice free-flight aviary experiments. In a subsequent breeding experiment, the offspring from the initial experiment were allowed to breed themselves. The next generation offspring from mothers raised under lower quality nutrition as either nestling or fledging were lighter at hatching compared to offspring from mothers raised under higher quality nutrition whereas paternal early nutrition had no such effects. The lack of early developmental limitations on attractiveness suggests that attractiveness traits were not affected or that birds compensated for any such effects. Furthermore, maternal trans-generational effects of dietary restrictions emphasize the importance of role of limited periods of early developmental stress in the expression of environmentally determined fitness components.

Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies.

PubMed

Wise, P M; Dubal, D B; Wilson, M E; Rau, S W; Böttner, M; Rosewell, K L

2001-11-01

We have shown that 17beta-estradiol exerts profound protective effects against stroke-like ischemic injury in female rats. These effects are evident using physiological levels of estradiol replacement in ovariectomized rats and require hormone treatment prior to the time of injury. The protective actions of estradiol appear to be most prominent in the cerebral cortex, where cell death is not apparent until at least 4 h after the initiation of ischemic injury and where cell death is thought to be apoptotic in nature. Middle-aged rats remain equally responsive to the protective actions of estradiol. The maintenance of responsiveness of the cerebral cortex to the neuroprotective actions of estradiol was unexpected since responsiveness of the hypothalamus to estradiol decreases dramatically by the time animals are middle-aged. We believe that the protective actions of estradiol require the estrogen receptor-alpha, since estradiol does not protect in estrogen receptor-alpha knockout mice. We have also implemented a method of culturing cerebral cortical explants to assess the protective effects of estradiol in vitro. This model exhibits remarkable parallelisms with our in vivo model of brain injury. We have found that 17beta-estradiol decreases the extent of cell death and that this protective effect requires hormone pretreatment. Finally, 17alpha-estradiol, which does not interact effectively with the estrogen receptor, does not protect; and addition of ICI 182,780, an estrogen receptor antagonist, blocks the protective actions of estradiol. We have begun to explore the molecular and cellular mechanisms of estradiol-mediated protection. In summary, our findings demonstrate that estradiol exerts powerful protective effects both in vivo and in vitro and suggest that these actions are mediated by estrogen receptors.

Diuretic effects of medetomidine compared with xylazine in healthy dogs

PubMed Central

Talukder, Md. Hasanuzzaman; Hikasa, Yoshiaki

2009-01-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 μg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine’s effect is less dose-dependent than xylazine’s effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation. PMID:19794896

Sugammadex compared with neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a systematic review and economic evaluation†

PubMed Central

Paton, F.; Paulden, M.; Chambers, D.; Heirs, M.; Duffy, S.; Hunter, J. M.; Sculpher, M.; Woolacott, N.

2010-01-01

Summary The cost-effectiveness of sugammadex for the routine reversal of muscle relaxation produced by rocuronium or vecuronium in UK practice is uncertain. We performed a systematic review of randomized controlled trials of sugammadex compared with neostigmine/glycopyrrolate and an economic assessment of sugammadex for the reversal of moderate or profound neuromuscular block (NMB) produced by rocuronium or vecuronium. The economic assessment aimed to establish the reduction in recovery time and the ‘value of time saved’ which would be necessary for sugammadex to be potentially cost-effective compared with existing practice. Three trials indicated that sugammadex 2 mg kg−1 (4 mg kg−1) produces more rapid recovery from moderate (profound) NMB than neostigmine/glycopyrrolate. The economic assessment indicated that if the reductions in recovery time associated with sugammadex in the trials are replicated in routine practice, sugammadex would be cost-effective if those reductions are achieved in the operating theatre (assumed value of staff time, £4.44 per minute), but not if they are achieved in the recovery room (assumed value of staff time, £0.33 per minute). However, there is considerable uncertainty in these results. Sugammadex has the potential to be cost-effective compared with neostigmine/glycopyrrolate for the reversal of rocuronium-induced moderate or profound NMB, provided that the time savings observed in trials can be achieved and put to productive use in clinical practice. Further research is required to evaluate the effects of sugammadex on patient safety, predictability of recovery from NMB, patient outcomes, and efficient use of resources. PMID:20935005

Protection throughout the life span: the psychoneuroimmunologic impact of Indo-Tibetan meditative and yogic practices.

PubMed

Olivo, Erin L

2009-08-01

The Indo-Tibetan tradition claims that proficiency in the suggested longevity practices of meditation, diet, and physical exercise (yoga), will result in profound anti-aging, stress-mediating and health enhancing effects. Western biomedical research has begun to demonstrate that the psychobiological states induced and cultivated by cognitive behavioral practices which are emblematic of those contained within the Indo-Tibetan tradition (hypnosis, meditation, visualization, systematic relaxation), indeed do have a profound impact on the body's protective and regulatory systems. Although continued study is necessary, much of the early research illuminating the mechanisms responsible for the life-span extending and health-enhancing effects of these cognitive behavioral practices points to the importance of their anti-inflammatory, anti-stress, and antioxidant effects as well as their impact in enhancing the production of endogenous substances that possess general longevity-enhancing, regenerative properties.

Observations on Working Psychoanalytically with a Profoundly Amnesic Patient

PubMed Central

Moore, Paul A.; Salas, Christian E.; Dockree, Suvi; Turnbull, Oliver H.

2017-01-01

Individuals with profound amnesia are markedly impaired in explicitly recalling new episodic events, but appear to preserve the capacity to use information from other sources. Amongst these preserved capacities is the ability to form new memories of an emotional nature – a skill at the heart of developing and sustaining interpersonal relationships. The psychoanalytic study of individuals with profound amnesia might contribute to the understanding the importance of each memory system, including effects on key analytic processes such as transference and countertransference. However, psychoanalytic work in the presence of profound amnesia might also require important technical modifications. In the first report of its kind, we describe observations from a long term psychoanalytic process (72 sessions) with an individual (JL) who has profound amnesia after an anoxic episode. The nature of therapy was shaped by JL’s impairment in connecting elements that belong to distant (and even relatively close) moments in the therapeutic process. However, we were also able to document areas of preservation, in what appears to be a functioning therapeutic alliance. As regards transference, the relationship between JL and his analyst can be viewed as the evolution of a narcissistic transference, and case material is provided that maps this into three phases: (i) rejecting; (ii) starting to take in; and (iii) full use of the analytic space – where each phase exhibits differing degrees of permeability between JL and the analyst. This investigation appears to have important theoretical implications for psychoanalytic practice, and for psychotherapy in general – and not only with regard to brain injured populations. We especially note that it raises questions concerning the mechanism of therapeutic action in psychoanalysis and psychotherapy, and the apparent unimportance of episodic memory for many elements of therapeutic change. PMID:28890703

Effects of Corrosion and Fatigue on the Load-Carrying Capacity of Structural and Reinforcing Steel

DOT National Transportation Integrated Search

1994-03-01

Pitting and crevice corrosion have profound effects on the fatigue life of structural and reinforcing steels used in bridge construction. Stress concentration factors were measured on actual corroded plates with strain gage instrumentation. Using cor...

Distribution of Auditory Response Behaviors in Normal Infants and Profoundly Multihandicapped Children.

ERIC Educational Resources Information Center

Flexer, Carol; Gans, Donald P.

1986-01-01

A study compared the responsiveness to sound by normal infants and profoundly multihandicapped children. Results revealed that the profoundly multihandicapped subjects displayed relatively more reflexive than attentive type behaviors and exhibited fewer behaviors per response. (Author/CB)

Cognitive development: no stages please--we're British.

PubMed

Goswami, U

2001-02-01

British cognitive developmental psychology is characterized by its interest in philosophical questions, its preference for linking basic research to applied issues in education and cognitive disorders, and its willingness to learn both methodologically and theoretically from work in animal psychology and in physiology more generally. It has also been influenced profoundly by Jean Piaget's cognitive stage theory although in general British work has focused on demonstrating early strengths, rather than early deficits, in infant and child cognition. Following an overview of British work that encompasses past and present interests, issues and challenges for the future are highlighted. While the perspectives of the founding members of the British Psychological Society (BPS), as outlined by Edgell (1947), are still apparent in British research in cognitive developmental psychology today, it is argued that future cognitive work must become even more interdisciplinary and that the symbiotic relationship between research in adult cognition and in cognitive development needs greater recognition.

Cognitive development: No stages please - we're British.

PubMed

Goswami, Usha

2001-02-01

British cognitive developmental psychology is characterized by its interest in philosophical questions, its preference for linking basic research to applied issues in education and cognitive disorders, and its willingness to learn both methodologically and theoretically from work in animal psychology and in physiology more generally. It has also been influenced profoundly by Jean Piaget's cognitive stage theory although in general British work has focused on demonstrating early strengths, rather than early deficits, in infant and child cognition. Following an overview of British work that encompasses past and present interests, issues and challenges for the future are highlighted. While the perspectives of the founding members of the British Psychological Society (BPS), as outlined by Edgell (1947), are still apparent in British research in cognitive developmental psychology today, it is argued that future cognitive work must become even more interdisciplinary and that the symbiotic relationship between research in adult cognition and in cognitive development needs greater recognition.

Some comments on the Freudian unconscious.

PubMed

Modell, Arnold H

2013-08-01

Freud's insight that mental processes are fundamentally unconscious is now an unquestioned assumption of neuroscience and cognitive psychology. Psychoanalysts are now faced with the question, What differentiated the psychoanalytic unconscious from that of other disciplines? Behind this question lies a more profound issue, the mind-body or mind-brain problem. It appears to be an insoluble paradox. Freud's concept of repression as a defense "mechanism" illustrates this paradox. To describe repression as a "mechanism" is to claim that it is analogous to a physiological process. Yet we know that repression is highly individualistic and subject to cultural values. In examining the Freudian concept of the primary process, the Noble prize-winning psychologist Daniel Kahneman has shown that the primary process is not wish fulfilling, as Freud claimed, but adaptive. The waking primary process is in the service of the reality principle. The growth of contemporary neuroscience has created challenging problems for psychoanalysis that did not exist in Freud's lifetime.

Microbiome, autoimmunity, allergy, and helminth infection: The importance of the pregnancy period.

PubMed

Chen, Xian; Liu, Su; Tan, Qiao; Shoenfeld, Yehuda; Zeng, Yong

2017-08-01

Pregnancy is a special physical period in reproductive age women, which has a beneficial influence on the course of certain autoimmune diseases. It has been recently suggested that the microbiome undergoes profound changes during pregnancy that are associated with host physiological and immunological adaptations. The maternal microbiome remodeling during pregnancy is an active response of the mother, possibly to alter immune system status and to facilitate metabolic and immunological adaptations, which are needed for a successful pregnancy. In this review, we attempt to discuss (i) the role of maternal microbiome in pregnancy outcomes known to adversely influence neonatal and infant health, including preterm birth, cardiometabolic complications of pregnancy, and gestational weight gain; (ii) the association of microbiome with autoimmunity, allergy diseases, and asthma during pregnancy; and (iii) the impact of helminth infection during pregnancy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Metamorphosis in Teleosts

PubMed Central

McMenamin, Sarah K.; Parichy, David M.

2017-01-01

Teleosts are the largest and most diverse group of vertebrates, and many species undergo morphological, physiological, and behavioral transitions, “metamorphoses,” as they progress between morphologically divergent life stages. The larval metamorphosis that generally occurs as teleosts mature from larva to juvenile involves the loss of embryo-specific features, the development of new adult features, major remodeling of different organ systems, and changes in physical proportions and overall phenotype. Yet, in contrast to anuran amphibians, for example, teleost metamorphosis can entail morphological change that is either sudden and profound, or relatively gradual and subtle. Here, we review the definition of metamorphosis in teleosts, the diversity of teleost metamorphic strategies and the transitions they involve, and what is known of their underlying endocrine and genetic bases. We suggest that teleost metamorphosis offers an outstanding opportunity for integrating our understanding of endocrine mechanisms, cellular processes of morphogenesis and differentiation, and the evolution of diverse morphologies and life histories. PMID:23347518

Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification

PubMed Central

Palacios-Prado, Nicolás; Huetteroth, Wolf; Pereda, Alberto E.

2014-01-01

Unapposed hemichannels (HCs) formed by hexamers of gap junction proteins are now known to be involved in various cellular processes under both physiological and pathological conditions. On the other hand, less is known regarding how differences in the molecular composition of HCs impact electrical synaptic transmission between neurons when they form intercellular heterotypic gap junctions (GJs). Here we review data indicating that molecular differences between apposed HCs at electrical synapses are generally associated with rectification of electrical transmission. Furthermore, this association has been observed at both innexin and connexin (Cx) based electrical synapses. We discuss the possible molecular mechanisms underlying electrical rectification, as well as the potential contribution of intracellular soluble factors to this phenomenon. We conclude that asymmetries in molecular composition and sensitivity to cellular factors of each contributing hemichannel can profoundly influence the transmission of electrical signals, endowing electrical synapses with more complex functional properties. PMID:25360082

Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

PubMed Central

Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

2013-01-01

This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

Aneuploidy-induced cellular stresses limit autophagic degradation

PubMed Central

Santaguida, Stefano; Vasile, Eliza; White, Eileen; Amon, Angelika

2015-01-01

An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Aneuploid cells experience a number of stresses that are caused by aneuploidy-induced proteomic changes. How the aneuploidy-associated stresses affect cells and whether cells respond to them are only beginning to be understood. Here we show that autophagosomal cargo such as protein aggregates accumulate within lysosomes in aneuploid cells. This causes a lysosomal stress response. Aneuploid cells activate the transcription factor TFEB, a master regulator of autophagic and lysosomal gene expression, thereby increasing the expression of genes needed for autophagy-mediated protein degradation. Accumulation of autophagic cargo within the lysosome and activation of TFEB-responsive genes are also observed in cells in which proteasome function is inhibited, suggesting that proteotoxic stress causes TFEB activation. Our results reveal a TFEB-mediated lysosomal stress response as a universal feature of the aneuploid state. PMID:26404941

MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection

PubMed Central

Kubinak, Jason L.; Stephens, W. Zac; Soto, Ray; Petersen, Charisse; Chiaro, Tyson; Gogokhia, Lasha; Bell, Rickesha; Ajami, Nadim J.; Petrosino, Joseph F.; Morrison, Linda; Potts, Wayne K.; Jensen, Peter E.; O'Connell, Ryan M.; Round, June L.

2015-01-01

The presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can have a profound impact on host physiology. Here we use an MHC congenic mouse model to test the hypothesis that genetic variation at MHC genes among individuals mediates susceptibility to disease by controlling microbiota composition. We find that MHC genotype significantly influences antibody responses against commensals in the gut, and that these responses are correlated with the establishment of unique microbial communities. Transplantation experiments in germfree mice indicate that MHC-mediated differences in microbiota composition are sufficient to explain susceptibility to enteric infection. Our findings indicate that MHC polymorphisms contribute to defining an individual's unique microbial fingerprint that influences health. PMID:26494419

Voltage gating of mechanosensitive PIEZO channels.

PubMed

Moroni, Mirko; Servin-Vences, M Rocio; Fleischer, Raluca; Sánchez-Carranza, Oscar; Lewin, Gary R

2018-03-15

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

Charophytes: Evolutionary Giants and Emerging Model Organisms

PubMed Central

Domozych, David S.; Popper, Zoë A.; Sørensen, Iben

2016-01-01

Charophytes are the group of green algae whose ancestral lineage gave rise to land plants in what resulted in a profoundly transformative event in the natural history of the planet. Extant charophytes exhibit many features that are similar to those found in land plants and their relatively simple phenotypes make them efficacious organisms for the study of many fundamental biological phenomena. Several taxa including Micrasterias, Penium, Chara, and Coleochaete are valuable model organisms for the study of cell biology, development, physiology and ecology of plants. New and rapidly expanding molecular studies are increasing the use of charophytes that in turn, will dramatically enhance our understanding of the evolution of plants and the adaptations that allowed for survival on land. The Frontiers in Plant Science series on “Charophytes” provides an assortment of new research reports and reviews on charophytes and their emerging significance as model plants. PMID:27777578

State-of-the-Art Methods for Skeletal Muscle Glycogen Analysis in Athletes-The Need for Novel Non-Invasive Techniques.

PubMed

Greene, Jacob; Louis, Julien; Korostynska, Olga; Mason, Alex

2017-02-23

Muscle glycogen levels have a profound impact on an athlete's sporting performance, thus measurement is vital. Carbohydrate manipulation is a fundamental component in an athlete's lifestyle and is a critical part of elite performance, since it can provide necessary training adaptations. This paper provides a critical review of the current invasive and non-invasive methods for measuring skeletal muscle glycogen levels. These include the gold standard muscle biopsy, histochemical analysis, magnetic resonance spectroscopy, and musculoskeletal high frequency ultrasound, as well as pursuing future application of electromagnetic sensors in the pursuit of portable non-invasive quantification of muscle glycogen. This paper will be of interest to researchers who wish to understand the current and most appropriate techniques in measuring skeletal muscle glycogen. This will have applications both in the lab and in the field by improving the accuracy of research protocols and following the physiological adaptations to exercise.

Apoptosis-induced lymphopenia in sepsis and other severe injuries.

PubMed

Girardot, Thibaut; Rimmelé, Thomas; Venet, Fabienne; Monneret, Guillaume

2017-02-01

Sepsis and other acute injuries such as severe trauma, extensive burns, or major surgeries, are usually followed by a period of marked immunosuppression. In particular, while lymphocytes play a pivotal role in immune response, their functions and numbers are profoundly altered after severe injuries. Apoptosis plays a central role in this process by affecting immune response at various levels. Indeed, apoptosis-induced lymphopenia duration and depth have been associated with higher risk of infection and mortality in various clinical settings. Therapies modulating apoptosis represent an interesting approach to restore immune competence after acute injury, although their use in clinical practice still presents several limitations. After briefly describing the apoptosis process in physiology and during severe injuries, we will explore the immunological consequences of injury-induced lymphocyte apoptosis, and describe associations with clinically relevant outcomes in patients. Therapeutic perspectives targeting apoptosis will also be discussed.

Sex differences in the developing brain as a source of inherent risk.

PubMed

McCarthy, Margaret M

2016-12-01

Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics. Markedly distinct signaling pathways direct differentiation in specific brain regions, resulting in mosaicism of relative maleness, femaleness, and sameness through-out the brain, while canalization both exaggerates and constrains sex differences. Non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains. This higher baseline of inflammation is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation.

Moving in a moving medium: new perspectives on flight

PubMed Central

Shepard, Emily L. C.; Portugal, Steven J.

2016-01-01

One of the defining features of the aerial environment is its variability; air is almost never still. This has profound consequences for flying animals, affecting their flight stability, speed selection, energy expenditure and choice of flight path. All these factors have important implications for the ecology of flying animals, and the ecosystems they interact with, as well as providing bio-inspiration for the development of unmanned aerial vehicles. In this introduction, we touch on the factors that drive the variability in airflows, the scales of variability and the degree to which given airflows may be predictable. We then summarize how papers in this volume advance our understanding of the sensory, biomechanical, physiological and behavioural responses of animals to air flows. Overall, this provides insight into how flying animals can be so successful in this most fickle of environments. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’. PMID:27528772

The Plant Polyester Cutin: Biosynthesis, Structure, and Biological Roles.

PubMed

Fich, Eric A; Segerson, Nicholas A; Rose, Jocelyn K C

2016-04-29

Cutin, a polyester composed mostly of oxygenated fatty acids, serves as the framework of the plant cuticle. The same types of cutin monomers occur across most plant lineages, although some evolutionary trends are evident. Additionally, cutins from some species have monomer profiles that are characteristic of the related polymer suberin. Compositional differences likely have profound structural consequences, but little is known about cutin's molecular organization and architectural heterogeneity. Its biological importance is suggested by the wide variety of associated mutants and gene-silencing lines that show a disruption of cuticular integrity, giving rise to numerous physiological and developmental abnormalities. Mapping and characterization of these mutants, along with suppression of gene paralogs through RNA interference, have revealed much of the biosynthetic pathway and several regulatory factors; however, the mechanisms of cutin polymerization and its interactions with other cuticle and cell wall components are only now beginning to be resolved.

TUTORIAL: Development of a cortical visual neuroprosthesis for the blind: the relevance of neuroplasticity

NASA Astrophysics Data System (ADS)

Fernández, E.; Pelayo, F.; Romero, S.; Bongard, M.; Marin, C.; Alfaro, A.; Merabet, L.

2005-12-01

Clinical applications such as artificial vision require extraordinary, diverse, lengthy and intimate collaborations among basic scientists, engineers and clinicians. In this review, we present the state of research on a visual neuroprosthesis designed to interface with the occipital visual cortex as a means through which a limited, but useful, visual sense could be restored in profoundly blind individuals. We review the most important physiological principles regarding this neuroprosthetic approach and emphasize the role of neural plasticity in order to achieve desired behavioral outcomes. While full restoration of fine detailed vision with current technology is unlikely in the immediate near future, the discrimination of shapes and the localization of objects should be possible allowing blind subjects to navigate in a unfamiliar environment and perhaps even to read enlarged text. Continued research and development in neuroprosthesis technology will likely result in a substantial improvement in the quality of life of blind and visually impaired individuals.

Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials.

PubMed

Franz, Sandra; Rammelt, Stefan; Scharnweber, Dieter; Simon, Jan C

2011-10-01

A key for long-term survival and function of biomaterials is that they do not elicit a detrimental immune response. As biomaterials can have profound impacts on the host immune response the concept emerged to design biomaterials that are able to trigger desired immunological outcomes and thus support the healing process. However, engineering such biomaterials requires an in-depth understanding of the host inflammatory and wound healing response to implanted materials. One focus of this review is to outline the up-to-date knowledge on immune responses to biomaterials. Understanding the complex interactions of host response and material implants reveals the need for and also the potential of "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies of triggering appropriate immune responses by functional biomaterials and highlight recent approaches of biomaterials that mimic the physiological extracellular matrix and modify cellular immune responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

On viewer motivation, unit of analysis, and the VIMAP. Comment on "Move me, astonish me ... delight my eyes and brain: The Vienna Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates" by Matthew Pelowski et al.

NASA Astrophysics Data System (ADS)

Tinio, Pablo P. L.

2017-07-01

The Vienna Integrated Model of Art Perception (VIMAP; [5]) is the most comprehensive model of the art experience today. The model incorporates bottom-up and top-down cognitive processes and accounts for different outcomes of the art experience, such as aesthetic evaluations, emotions, and physiological and neurological responses to art. In their presentation of the model, Pelowski et al. also present hypotheses that are amenable to empirical testing. These features make the VIMAP an ambitious model that attempts to explain how meaningful, complex, and profound aspects of the art experience come about, which is a significant extension of previous models of the art experience (e.g., [1-3,10]), and which gives the VIMAP good explanatory power.

Genetically Encoded Biosensors in Plants: Pathways to Discovery.

PubMed

Walia, Ankit; Waadt, Rainer; Jones, Alexander M

2018-04-29

Genetically encoded biosensors that directly interact with a molecule of interest were first introduced more than 20 years ago with fusion proteins that served as fluorescent indicators for calcium ions. Since then, the technology has matured into a diverse array of biosensors that have been deployed to improve our spatiotemporal understanding of molecules whose dynamics have profound influence on plant physiology and development. In this review, we address several types of biosensors with a focus on genetically encoded calcium indicators, which are now the most diverse and advanced group of biosensors. We then consider the discoveries in plant biology made by using biosensors for calcium, pH, reactive oxygen species, redox conditions, primary metabolites, phytohormones, and nutrients. These discoveries were dependent on the engineering, characterization, and optimization required to develop a successful biosensor; they were also dependent on the methodological developments required to express, detect, and analyze the readout of such biosensors.

Cost Effectiveness of Childhood Cochlear Implantation and Deaf Education in Nicaragua: A Disability Adjusted Life Year Model.

PubMed

Saunders, James E; Barrs, David M; Gong, Wenfeng; Wilson, Blake S; Mojica, Karen; Tucci, Debara L

2015-09-01

Cochlear implantation (CI) is a common intervention for severe-to-profound hearing loss in high-income countries, but is not commonly available to children in low resource environments. Owing in part to the device costs, CI has been assumed to be less economical than deaf education for low resource countries. The purpose of this study is to compare the cost effectiveness of the two interventions for children with severe-to-profound sensorineural hearing loss (SNHL) in a model using disability adjusted life years (DALYs). Cost estimates were derived from published data, expert opinion, and known costs of services in Nicaragua. Individual costs and lifetime DALY estimates with a 3% discounting rate were applied to both two interventions. Sensitivity analysis was implemented to evaluate the effect on the discounted cost of five key components: implant cost, audiology salary, speech therapy salary, number of children implanted per year, and device failure probability. The costs per DALY averted are $5,898 and $5,529 for CI and deaf education, respectively. Using standards set by the WHO, both interventions are cost effective. Sensitivity analysis shows that when all costs set to maximum estimates, CI is still cost effective. Using a conservative DALY analysis, both CI and deaf education are cost-effective treatment alternatives for severe-to-profound SNHL. CI intervention costs are not only influenced by the initial surgery and device costs but also by rehabilitation costs and the lifetime maintenance, device replacement, and battery costs. The major CI cost differences in this low resource setting were increased initial training and infrastructure costs, but lower medical personnel and surgery costs.

Charge Inversion in semi-permeable membranes

NASA Astrophysics Data System (ADS)

Das, Siddhartha; Sinha, Shayandev; Jing, Haoyuan

Role of semi-permeable membranes like lipid bilayer is ubiquitous in a myriad of physiological and pathological phenomena. Typically, lipid membranes are impermeable to ions and solutes; however, protein channels embedded in the membrane allow the passage of selective, small ions across the membrane enabling the membrane to adopt a semi-permeable nature. This semi-permeability, in turn, leads to electrostatic potential jump across the membrane, leading to effects such as regulation of intracellular calcium, extracellular-vesicle-membrane interactions, etc. In this study, we theoretically demonstrate that this semi-permeable nature may trigger the most remarkable charge inversion (CI) phenomenon in the cytosol-side of the negatively-charged lipid bilayer membrane that are selectively permeable to only positive ions of a given salt. This CI is manifested as the changing of the sign of the electrostatic potential from negative to positive from the membrane-cytosol interface to deep within the cytosol. We study the impact of the parameters such as the concentration of this salt with selectively permeable ions as well as the concentration of an external salt in the development of this CI phenomenon. We anticipate such CI will profoundly influence the interaction of membrane and intra-cellular moieties (e.g., exosome or multi-cellular vesicles) having implications for a host of biophysical processes.

Turn up the heat: thermal tolerances of lizards at La Selva, Costa Rica.

PubMed

Brusch, George A; Taylor, Emily N; Whitfield, Steven M

2016-02-01

Global temperature increases over the next century are predicted to contribute to the extinction of a number of taxa, including up to 40% of all lizard species. Lizards adapted to living in lowland tropical areas are especially vulnerable because of their dependence on specific microhabitats, low vagility, and a reduced capacity to physiologically adjust to environmental change. To assess the potential effects of climate change on lizards in the lowland tropics, we measured the critical thermal maximum (CTmax) of ten species from La Selva, Costa Rica. We also examined how well body size, microhabitat type, and species predicted the CTmax. We used current temperature data along with projected temperature increases for 2080 to predict which species may be at the greatest risk at La Selva. Of the ten species sampled, four are at serious risk of lowland extirpation and three others might also be at risk under the highest predicted temperature-increase models. Forest floor lizards at La Selva have already experienced significant population declines over the past 40 years, and we found that each of the forest floor species we studied is at serious risk of local extirpation. We also found that microhabitat type is the strongest predictor of CTmax, demonstrating the profound impact habitat specialization has on the thermal limits of tropical lizards.

Phylogenetic appearance of Neuropeptide S precursor proteins in tetrapods

PubMed Central

Reinscheid, Rainer K.

2007-01-01

Sleep and emotional behavior are two hallmarks of vertebrate animal behavior, implying that specialized neuronal circuits and dedicated neurochemical messengers may have been developed during evolution to regulate such complex behaviors. Neuropeptide S (NPS) is a newly identified peptide transmitter that activates a typical G protein-coupled receptor. Central administration of NPS produces profound arousal, enhances wakefulness and suppresses all stages of sleep. In addition, NPS can alleviate behavioral responses to stress by producing anxiolytic-like effects. A bioinformatic analysis of current genome databases revealed that the NPS peptide precursor gene is present in all vertebrates with the exception of fish. A high level of sequence conservation, especially of aminoterminal structures was detected, indicating stringent requirements for agonist-induced receptor activation. Duplication of the NPS precursor gene was only found in one out of two marsupial species with sufficient genome coverage (Monodelphis domestica; opossum), indicating that the duplicated opossum NPS sequence might have arisen as an isolated event. Pharmacological analysis of both Monodelphis NPS peptides revealed that only the closely related NPS peptide retained agonistic activity at NPS receptors. The duplicated precursor might be either a pseudogene or could have evolved different receptor selectivity. Together, these data show that NPS is a relatively recent gene in vertebrate evolution whose appearance might coincide with its specialized physiological functions in terrestrial vertebrates. PMID:17293003

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

PubMed Central

Kechele, Daniel O.; Blue, R. Eric; Zwarycz, Bailey; Espenschied, Scott T.; Mah, Amanda T.; Siegel, Marni B.; Perou, Charles M.; Ding, Shengli; Magness, Scott T.; Lund, P. Kay

2017-01-01

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation. PMID:28094771

Microbe-surface interactions in biofouling and biocorrosion processes.

PubMed

Beech, Iwona B; Sunner, Jan A; Hiraoka, Kenzo

2005-09-01

The presence of microorganisms on material surfaces can have a profound effect on materials performance. Surface-associated microbial growth, i.e. a biofilm, is known to instigate biofouling. The presence of biofilms may promote interfacial physico-chemical reactions that are not favored under abiotic conditions. In the case of metallic materials, undesirable changes in material properties due to a biofilm (or a biofouling layer) are referred to as biocorrosion or microbially influenced corrosion (MIC). Biofouling and biocorrosion occur in aquatic and terrestrial habitats varying in nutrient content, temperature, pressure and pH. Interfacial chemistry in such systems reflects a wide variety of physiological activities carried out by diverse microbial populations thriving within biofilms. Biocorrosion can be viewed as a consequence of coupled biological and abiotic electron-transfer reactions, i.e. redox reactions of metals, enabled by microbial ecology. Microbially produced extracellular polymeric substances (EPS), which comprise different macromolecules, mediate initial cell adhesion to the material surface and constitute a biofilm matrix. Despite their unquestionable importance in biofilm development, the extent to which EPS contribute to biocorrosion is not well-understood. This review offers a current perspective on material/microbe interactions pertinent to biocorrosion and biofouling, with EPS as a focal point, while emphasizing the role atomic force spectroscopy and mass spectrometry techniques can play in elucidating such interactions.

The Immune System’s Role in Sepsis Progression, Resolution and Long-Term Outcome

PubMed Central

Delano, Matthew J.; Ward, Peter A.

2016-01-01

SUMMARY Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. Since so many sepsis survivors succumb later to persistent, recurrent, nosocomial and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality. PMID:27782333

The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation

PubMed Central

Labialle, Stéphane; Marty, Virginie; Bortolin-Cavaillé, Marie-Line; Hoareau-Osman, Magali; Pradère, Jean-Philippe; Valet, Philippe; Martin, Pascal GP; Cavaillé, Jérôme

2014-01-01

In mammals, birth entails complex metabolic adjustments essential for neonatal survival. Using a mouse knockout model, we identify crucial biological roles for the miR-379/miR-410 cluster within the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 locus, also named C14MC in humans, is the largest known placental mammal-specific miRNA cluster, whose 39 miRNA genes are expressed only from the maternal allele. We found that heterozygote pups with a maternal—but not paternal—deletion of the miRNA cluster display partially penetrant neonatal lethality with defects in the maintenance of energy homeostasis. This maladaptive metabolic response is caused, at least in part, by profound changes in the activation of the neonatal hepatic gene expression program, pointing to as yet unidentified regulatory pathways that govern this crucial metabolic transition in the newborn's liver. Not only does our study highlight the physiological importance of miRNA genes that recently evolved in placental mammal lineages but it also unveils additional layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on metabolic control at birth and have likely contributed to mammal evolution. PMID:25124681

Physical trade-offs shape the evolution of buoyancy control in sharks.

PubMed

Gleiss, Adrian C; Potvin, Jean; Goldbogen, Jeremy A

2017-11-15

Buoyancy control is a fundamental aspect of aquatic life that has major implications for locomotor performance and ecological niche. Unlike terrestrial animals, the densities of aquatic animals are similar to the supporting fluid, thus even small changes in body density may have profound effects on locomotion. Here, we analysed the body composition (lipid versus lean tissue) of 32 shark species to study the evolution of buoyancy. Our comparative phylogenetic analyses indicate that although lean tissue displays minor positive allometry, liver volume exhibits pronounced positive allometry, suggesting that larger sharks evolved bulkier body compositions by adding lipid tissue to lean tissue rather than substituting lean for lipid tissue, particularly in the liver. We revealed a continuum of buoyancy control strategies that ranged from more buoyant sharks with larger livers in deeper ecosystems to relatively denser sharks with small livers in epipelagic habitats. Across this eco-morphological spectrum, our hydrodynamic modelling suggests that neutral buoyancy yields lower drag and more efficient steady swimming, whereas negative buoyancy may be more efficient during accelerated movements. The evolution of buoyancy control in sharks suggests that ecological and physiological factors mediate the selective pressures acting on these traits along two major gradients, body size and habitat depth. © 2017 The Author(s).

Being cool: how body temperature influences ageing and longevity.

PubMed

Keil, Gerald; Cummings, Elizabeth; de Magalhães, João Pedro

2015-08-01

Temperature is a basic and essential property of any physical system, including living systems. Even modest variations in temperature can have profound effects on organisms, and it has long been thought that as metabolism increases at higher temperatures so should rates of ageing. Here, we review the literature on how temperature affects longevity, ageing and life history traits. From poikilotherms to homeotherms, there is a clear trend for lower temperature being associated with longer lifespans both in wild populations and in laboratory conditions. Many life-extending manipulations in rodents, such as caloric restriction, also decrease core body temperature. Nonetheless, an inverse relationship between temperature and lifespan can be obscured or reversed, especially when the range of body temperatures is small as in homeotherms. An example is observed in humans: women appear to have a slightly higher body temperature and yet live longer than men. The mechanisms involved in the relationship between temperature and longevity also appear to be less direct than once thought with neuroendocrine processes possibly mediating complex physiological responses to temperature changes. Lastly, we discuss species differences in longevity in mammals and how this relates to body temperature and argue that the low temperature of the long-lived naked mole-rat possibly contributes to its exceptional longevity.

Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice

PubMed Central

Grenz, Almut; Bauerle, Jessica D.; Dalton, Julee H.; Ridyard, Douglas; Badulak, Alexander; Tak, Eunyoung; McNamee, Eóin N.; Clambey, Eric; Moldovan, Radu; Reyes, German; Klawitter, Jost; Ambler, Kelly; Magee, Kristann; Christians, Uwe; Brodsky, Kelley S.; Ravid, Katya; Choi, Doo-Sup; Wen, Jiaming; Lukashev, Dmitriy; Blackburn, Michael R.; Osswald, Hartmut; Coe, Imogen R.; Nürnberg, Bernd; Haase, Volker H.; Xia, Yang; Sitkovsky, Michail; Eltzschig, Holger K.

2012-01-01

A complex biologic network regulates kidney perfusion under physiologic conditions. This system is profoundly perturbed following renal ischemia, a leading cause of acute kidney injury (AKI) — a life-threatening condition that frequently complicates the care of hospitalized patients. Therapeutic approaches to prevent and treat AKI are extremely limited. Better understanding of the molecular pathways promoting postischemic reflow could provide new candidate targets for AKI therapeutics. Due to its role in adapting tissues to hypoxia, we hypothesized that extracellular adenosine has a regulatory function in the postischemic control of renal perfusion. Consistent with the notion that equilibrative nucleoside transporters (ENTs) terminate adenosine signaling, we observed that pharmacologic ENT inhibition in mice elevated renal adenosine levels and dampened AKI. Deletion of the ENTs resulted in selective protection in Ent1–/– mice. Comprehensive examination of adenosine receptor–knockout mice exposed to AKI demonstrated that renal protection by ENT inhibitors involves the A2B adenosine receptor. Indeed, crosstalk between renal Ent1 and Adora2b expressed on vascular endothelia effectively prevented a postischemic no-reflow phenomenon. These studies identify ENT1 and adenosine receptors as key to the process of reestablishing renal perfusion following ischemic AKI. If translatable from mice to humans, these data have important therapeutic implications. PMID:22269324

Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

PubMed

Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

2009-07-01

The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the Eye.

PubMed

Crooke, Almudena; Guzman-Aranguez, Ana; Carracedo, Gonzalo; de Lara, Maria J Perez; Pintor, Jesus

Diadenosine tetraphosphate abbreviated Ap 4 A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap 4 A are mostly carried out by P2Y 2 receptors, but the participation of P2X2 and P2Y 6 in processes such as the regulation of intraocular pressure (IOP), together with the P2Y 2 , is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of Ap 4 A to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where Ap 4 A actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.

Biofilms Formed by Gram-Negative Bacteria Undergo Increased Lipid A Palmitoylation, Enhancing In Vivo Survival

PubMed Central

Chalabaev, Sabina; Chauhan, Ashwini; Novikov, Alexey; Iyer, Pavithra; Szczesny, Magdalena; Beloin, Christophe; Caroff, Martine

2014-01-01

ABSTRACT Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. PMID:25139899

Sulfide toxicity: Mechanical ventilation and hypotension determine survival rate and brain necrosis

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

Baldelli, R.J.; Green, F.H.Y.; Auer, R.N.

1993-09-01

Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause [open quotes]knockdown[close quotes] (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, the authors sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilatedmore » rats given high-dose sulfide (a dose that was lethal in [ge]50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to [le]35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. The authors conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect. 32 refs., 5 figs.« less

Effects of dim or bright-light exposure during the daytime on human gastrointestinal activity.

PubMed

Sone, Yoshiaki; Hyun, Ki-Ja; Nishimura, Shinya; Lee, Young-Ah; Tokura, Hiromi

2003-01-01

On the basis of our previous findings that bright-light exposure during the daytime has profound influence on physiological parameters such as melatonin secretion and tympanic temperature in humans, we proposed the hypothesis that bright vs. dim light-exposure during the daytime has a different influence on the activity of the digestive system via the endocrine and/or autonomic nervous system. To examine this hypothesis, we conducted a series of counterbalanced experiments in which subjects stayed the daytime (7:00 to 15:00h) under either a dim (80 lux) or bright (5,000 lux) light condition. We measured gastrointestinal activity using a breath hydrogen (indicative of carbohydrate malabsorption) and an electrogastrography (EGG, indicative of gastric myoelectric activity) test. The results showed the postprandial breath hydrogen excretion during the following nighttime period after daytime exposure to the dim-light condition was significantly higher than under the bright-light condition (p < 0.05). In addition, the spectrum total power of the EGG recorded after taking the evening meal was significantly lower for the dim than bright-light condition (p < 0.05). These results support our hypothesis and indicate that dim-light exposure during the daytime suppresses the digestion of the evening meal, resulting in malabsorption of dietary carbohydrates in it.

Nutritional Aspects of Essential Trace Elements in Oral Health and Disease: An Extensive Review

PubMed Central

Hussain, Mohsina

2016-01-01

Human body requires certain essential elements in small quantities and their absence or excess may result in severe malfunctioning of the body and even death in extreme cases because these essential trace elements directly influence the metabolic and physiologic processes of the organism. Rapid urbanization and economic development have resulted in drastic changes in diets with developing preference towards refined diet and nutritionally deprived junk food. Poor nutrition can lead to reduced immunity, augmented vulnerability to various oral and systemic diseases, impaired physical and mental growth, and reduced efficiency. Diet and nutrition affect oral health in a variety of ways with influence on craniofacial development and growth and maintenance of dental and oral soft tissues. Oral potentially malignant disorders (OPMD) are treated with antioxidants containing essential trace elements like selenium but even increased dietary intake of trace elements like copper could lead to oral submucous fibrosis. The deficiency or excess of other trace elements like iodine, iron, zinc, and so forth has a profound effect on the body and such conditions are often diagnosed through their early oral manifestations. This review appraises the biological functions of significant trace elements and their role in preservation of oral health and progression of various oral diseases. PMID:27433374

Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota

PubMed Central

Neuendorf, Elizabeth; Gajer, Pawel; Bowlin, Anne K.; Marques, Patricia X.; Ma, Bing; Yang, Hongqiu; Fu, Li; Humphrys, Michael S.; Forney, Larry J.; Myers, Garry S.A.; Bavoil, Patrik M.; Rank, Roger G.; Ravel, Jacques

2015-01-01

In humans, the vaginal microbiota is thought to be the first line of defense again pathogens including Chlamydia trachomatis. The guinea pig has been extensively used as a model to study chlamydial infection because it shares anatomical and physiological similarities with humans, such as a squamous vaginal epithelium as well as some of the long-term outcomes caused by chlamydial infection. In this study, we aimed to evaluate the guinea pig-C. caviae model of genital infection as a surrogate for studying the role of the vaginal microbiota in the early steps of C. trachomatis infection in humans. We used culture-independent molecular methods to characterize the relative and absolute abundance of bacterial phylotypes in the guinea pig vaginal microbiota in animals non-infected, mock-infected or infected by C. caviae. We showed that the guinea pig and human vaginal microbiotas are of different bacterial composition and abundance. Chlamydia caviae infection had a profound effect on the absolute abundance of bacterial phylotypes but not on the composition of the guinea pig vaginal microbiota. Our findings compromise the validity of the guinea pig-C. caviae model to study the role of the vaginal microbiota during the early steps of sexually transmitted infection. PMID:25761873

Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota.

PubMed

Neuendorf, Elizabeth; Gajer, Pawel; Bowlin, Anne K; Marques, Patricia X; Ma, Bing; Yang, Hongqiu; Fu, Li; Humphrys, Michael S; Forney, Larry J; Myers, Garry S A; Bavoil, Patrik M; Rank, Roger G; Ravel, Jacques

2015-06-01

In humans, the vaginal microbiota is thought to be the first line of defense again pathogens including Chlamydia trachomatis. The guinea pig has been extensively used as a model to study chlamydial infection because it shares anatomical and physiological similarities with humans, such as a squamous vaginal epithelium as well as some of the long-term outcomes caused by chlamydial infection. In this study, we aimed to evaluate the guinea pig-C. caviae model of genital infection as a surrogate for studying the role of the vaginal microbiota in the early steps of C. trachomatis infection in humans. We used culture-independent molecular methods to characterize the relative and absolute abundance of bacterial phylotypes in the guinea pig vaginal microbiota in animals non-infected, mock-infected or infected by C. caviae. We showed that the guinea pig and human vaginal microbiotas are of different bacterial composition and abundance. Chlamydia caviae infection had a profound effect on the absolute abundance of bacterial phylotypes but not on the composition of the guinea pig vaginal microbiota. Our findings compromise the validity of the guinea pig-C. caviae model to study the role of the vaginal microbiota during the early steps of sexually transmitted infection. © FEMS 2015.

De Novo Deep Transcriptome Analysis of Medicinal Plants for Gene Discovery in Biosynthesis of Plant Natural Products.

PubMed

Han, R; Rai, A; Nakamura, M; Suzuki, H; Takahashi, H; Yamazaki, M; Saito, K

2016-01-01

Study on transcriptome, the entire pool of transcripts in an organism or single cells at certain physiological or pathological stage, is indispensable in unraveling the connection and regulation between DNA and protein. Before the advent of deep sequencing, microarray was the main approach to handle transcripts. Despite obvious shortcomings, including limited dynamic range and difficulties to compare the results from distinct experiments, microarray was widely applied. During the past decade, next-generation sequencing (NGS) has revolutionized our understanding of genomics in a fast, high-throughput, cost-effective, and tractable manner. By adopting NGS, efficiency and fruitful outcomes concerning the efforts to elucidate genes responsible for producing active compounds in medicinal plants were profoundly enhanced. The whole process involves steps, from the plant material sampling, to cDNA library preparation, to deep sequencing, and then bioinformatics takes over to assemble enormous-yet fragmentary-data from which to comb and extract information. The unprecedentedly rapid development of such technologies provides so many choices to facilitate the task, which can cause confusion when choosing the suitable methodology for specific purposes. Here, we review the general approaches for deep transcriptome analysis and then focus on their application in discovering biosynthetic pathways of medicinal plants that produce important secondary metabolites. © 2016 Elsevier Inc. All rights reserved.

Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism

PubMed Central

Pfattheicher, Stefan; Schindler, Simon

2016-01-01

The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O’Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O’Malley. Overall, small-to-medium sized correlations were found, indicating that far from all conservatives see profoundness in bullshit statements. PMID:27128318

Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

PubMed

Pfattheicher, Stefan; Schindler, Simon

2016-01-01

The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O'Malley. Overall, small-to-medium sized correlations were found, indicating that far from all conservatives see profoundness in bullshit statements.

Like cognitive function, decision making across the life span shows profound age-related changes.

PubMed

Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

2013-10-15

It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

The educational settings of profoundly deaf children with cochlear implants compared with age-matched peers with hearing aids: implications for management.

PubMed

Archbold, Sue M; Nikolopoulos, Thomas P; Lutman, Mark E; O'Donoghue, Gerard M

2002-04-01

The educational settings of 42 implanted profoundly deaf children 3 years after implantation were compared with the respective settings of 635 age-matched severely deaf and 511 profoundly deaf children with hearing aids. All implanted children received their implants before beginning school. The results revealed that 3 years after implantation. 38% (16 children) of the implanted profoundly deaf children attended mainstream schools, whereas 57% (24 children) were in a unit, or special class, in a mainstream school, and 5% (two children) were in schools for the deaf. With regard to the age-matched profoundly deaf children with hearing aids, 12% (63 children) attended mainstream schools, whereas 55% (281 children) were in a unit of a mainstream school, and 33% (167 children) were in schools for the deaf. In the group of age-matched severely deaf children, 38% (239 children) attended mainstream schools, whereas 51% (326 children) were in a unit of a mainstream school, and 11% (70 children) were in schools for the deaf. Statistical analysis revealed a highly significant difference between the educational placement of implanted children and hearing-aided profoundly deaf children (p<0.00001), whereas there was no statistically significant difference between implanted children and hearing-aided severely deaf children. In conclusion, implanted profoundly deaf children who have received their implants before beginning school have the same profile of educational placement as aided severely deaf children rather than aided profoundly deaf children of the same age in the UK. This is likely to have significant implications for the future management of profoundly deaf children and to influence future planning of educational support services.

Impact of imidacloprid on new queens of imported fire ants, Solenopsis invicta (Hymenoptera: Formicidae)

USDA-ARS?s Scientific Manuscript database

Neonicotinoid insecticides are commonly used in managing pest ants, including the imported fire ant, Solenopsis invicta Buren. There is increasing evidence that neonicotinoid insecticides at sublethal concentrations have profound effects on social insects. However, the sublethal effect of neonicot...

The Reflexive Modernization of Australian Universities

ERIC Educational Resources Information Center

Pick, David

2004-01-01

The profound changes occurring in Australian higher education are viewed here in the context of the social, cultural, political and economic effects of globalization. Particular attention is paid to providing a theoretical foundation for understanding these effects using the reflexive modernization perspective. Highlighted are some of the…

Magnesium, stress and neuropsychiatric disorders.

PubMed

Galland, L

Magnesium has a profound effect on neural excitability; the most characteristic signs and symptoms of Mg deficiency are produced by neural and neuromuscular hyperexcitability. These create a constellation of clinical findings termed tetany syndrome (TS). TS symptoms include muscle spasms, cramps and hyperarousal, hyperventilation and asthenia. Physical signs (Chvostek's, Trousseau's or von Bonsdorff's) and abnormalities of the electromyogram or electroencephalogram can usually be elicited. Signs and symptoms of TS are frequently encountered in clinical practice, especially among patients with functional or stress-related disorders. The role of Mg deficit in TS is suggested by relatively low levels of serum or erythrocyte Mg and by the clinical response to oral Mg salts, which has been demonstrated in controlled studies. Among the more serious neurologic sequelae of TS are migraine attacks, transient ischemic attacks, sensorineural hearing loss and convulsions. Mg deficiency may predispose to hyperventilation and may sensitize the cerebral vasculature to the effects of hypocarbia. Mg deficiency increases susceptibility to the physiologic damage produced by stress, and Mg administration has a protective effect; studies on noise stress and noise-induced hearing loss are taken as an example. In addition, the adrenergic effects of psychological stress induce a shift of Mg from the intracellular to the extracellular space, increasing urinary excretion and eventually depleting body stores. Drugs used in neurology and psychiatry may affect Mg levels in blood and may diminish signs of tetany, making assessment of Mg status more difficult. Pharmacologic use of Mg can decrease neurologic deficit in experimental head trauma, possibly by blockade of N-methyl-D-aspartate receptors. In conjunction with high doses of pyridoxine, Mg salts benefit 40% of patients with autism, possibly by an effect on dopamine metabolism.

Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy.

PubMed

Jurkić, Lela Munjas; Cepanec, Ivica; Pavelić, Sandra Kraljević; Pavelić, Krešimir

2013-01-08

Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

Will Global Change Effect Primary Productivity in Coastal Ecosystems?

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.; Peterson, David L. (Technical Monitor)

1997-01-01

Algae are the base of coastal food webs because they provide the source of organic carbon for the remaining members of the community. Thus, the rate that they produce organic carbon to a large extent controls the productivity of the entire ecosystem. Factors that control algal productivity range from the physical (e.g., temperature, light), chemical (e.g., nutrient levels) to the biological (e.g., grazing). Currently, levels of atmospheric carbon dioxide surficial fluxes of ultraviolet radiation are rising. Both of these environmental variables can have a profound effect on algal productivity. Atmospheric carbon dioxide may increase surficial levels of dissolved inorganic carbon. Our laboratory and field studies of algal mats and phytoplankton cultures under ambient and elevated levels of pCO2 show that elevated levels of inorganic carbon can cause an increase in photosynthetic rates. In some cases, this increase will cause an increase in phytoplankton numbers. There may be an increase in the excretion of fixed carbon, which in turn may enhance bacterial productivity. Alternatively, in analogy with studies on the effect of elevated pCO2 on plants, the phytoplankton could change their carbon to nitrogen ratios, which will effect the feeding of the planktonic grazers. The seasonal depletion of stratospheric ozone has resulted in elevated fluxes of UVB radiation superimposed on the normal seasonal variation. Present surface UV fluxes have a significant impact on phytoplankton physiology, including the inhibition of the light and dark reactions of photosynthesis, inhibition of nitrogenase activity, inhibition of heterocyst formation, reduction in motility, increased synthesis of the UV-screening pigment scytonemin, and mutation. After reviewing these issues, recent work in our lab on measuring the effect of UV radiation on phytoplankton in the San Francisco Bay Estuary will be presented.

Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

PubMed

Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

2013-01-01

Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

Effects of Pre-Experience of Social Exclusion on Hypothalamus-Pituitary-Adrenal Axis and Catecholaminergic Responsiveness to Public Speaking Stress

PubMed Central

Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

2013-01-01

Backround Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Methods Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Results Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. Conclusions We replicated our previous study result of a supressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective. PMID:23573255

Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism

PubMed Central

Graves, Steven M.; Clark, Mary J.; Traynor, John R.; Hu, Xiu-Ti; Napier, T. Celeste

2014-01-01

Methamphetamine profoundly increases brain monoamines and is a widely abused psychostimulant. The effects of methamphetamine self-administration on neuron function are not known for the nucleus accumbens, a brain region involved in addictive behaviors, including drug-seeking. One therapeutic target showing preclinical promise at attenuating psychostimulant-seeking is 5-HT2C receptors; however, the effects of 5-HT2C receptor ligands on neuronal physiology are unclear. 5-HT2C receptor agonism decreases psychostimulant-mediated behaviors, and the putative 5-HT2C receptor inverse agonist, SB 206553, attenuates methamphetamine-seeking in rats. To ascertain the effects of methamphetamine, and 5-HT2C receptor inverse agonism and agonism, on neuronal function in the nucleus accumbens, we evaluated methamphetamine, SB 206553, and the 5-HT2C receptor agonist and Ro 60-0175, on neuronal excitability within the accumbens shell subregion using whole-cell current-clamp recordings in forebrain slices ex vivo. We reveal that methamphetamine self-administration decreased generation of evoked action potentials. In contrast, SB 206553 and Ro 60-0175 increased evoked spiking, effects that were prevented by the 5-HT2C receptor antagonist, SB 242084. We also assessed signaling mechanisms engaged by 5-HT2C receptors, and determined that accumbal 5-HT2C receptors stimulated Gq, but not Gi/o. These findings demonstrate that methamphetamine-induced decreases in excitability of neurons within the nucleus accumbens shell were abrogated by both 5-HT2C inverse agonism and agonism, and this effect likely involved activation of Gq–mediated signaling pathways. PMID:25229719

Aging and estradiol effects on gene expression in the medial preoptic area, bed nucleus of the stria terminalis, and posterodorsal medial amygdala of male rats

PubMed Central

Nutsch, Victoria L.; Bell, Margaret R.; Will, Ryan G.; Yin, Weiling; Wolfe, Andrew; Gillette, Ross; Dominguez, Juan M.; Gore, Andrea C.

2017-01-01

Studies on the role of hormones in male reproductive aging have traditionally focused on testosterone, but estradiol also plays important roles in the control of masculine physiology and behavior. Our goal was to examine the effects of E2 on the expression of genes selected for E2-sensitivity, involvement in behavioral neuroendocrine functions, and impairments with aging. Mature adult (MAT, 5 mo.) and aged (AG, 18 mo.) Sprague-Dawley male rats were castrated, implanted with either vehicle or estradiol (E2) subcutaneous capsules, and euthanized one month later. Bilateral punches were taken from the bed nucleus of the stria terminalis (BnST), posterodorsal medial amygdala (MePD) and the preoptic area (POA). RNA was extracted, and expression of 48 genes analyzed by qPCR using Taqman low-density arrays. Results showed that effects of age and E2 were age- and region-specific. In the POA, 5 genes were increased with E2 compared to vehicle, and there were no age effects. By contrast the BnST showed primarily age-related changes, with 6 genes decreasing with age. The MePD had 5 genes that were higher in aged than mature males, and 17 genes with significant interactions between age and E2. Gene families identified in the MePD included nuclear hormone receptors, neurotransmitters and neuropeptides and their receptors. Ten serum hormones were assayed in these same males, with results revealing both age- and E2-effects, in several cases quite profound. These results support the idea that the male brain continues to be highly sensitive to estradiol even with aging, but the nature of the response can be substantially different in mature and aging animals. PMID:28007657

A role for the mitochondrial pyruvate carrier as a repressor of the Warburg Effect and colon cancer cell growth

PubMed Central

Schell, John C.; Olson, Kristofor A.; Jiang, Lei; Hawkins, Amy J.; Van Vranken, Jonathan G.; Xie, Jianxin; Egnatchik, Robert A.; Earl, Espen G.; Deberardinis, Ralph J.; Rutter, Jared

2014-01-01

Summary Cancer cells are typically subject to profound metabolic alterations, including the Warburg effect wherein cancer cells oxidize a decreased fraction of the pyruvate generated from glycolysis. We show herein that the mitochondrial pyruvate carrier (MPC), composed of the products of the MPC1 and MPC2 genes, modulates fractional pyruvate oxidation. MPC1 is deleted or underexpressed in multiple cancers and correlates with poor prognosis. Cancer cells re-expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. MPC re-expression exerted profound effects in anchorage-independent growth conditions, however, including impaired colony formation in soft agar, spheroid formation, and xenograft growth. We also observed a decrease in markers of stemness and traced the growth effects of MPC expression to the stem cell compartment. We propose that reduced MPC activity is an important aspect of cancer metabolism, perhaps through altering the maintenance and fate of stem cells. PMID:25458841

Developmental dysplasia of the hip: a history of innovation.

PubMed

Tarpada, Sandip P; Girdler, Steven J; Morris, Matthew T

2018-05-01

Developmental dysplasia of the hip (DDH) is a relatively common malady that has profound consequences in the infant if left untreated. Effective and early treatment of DDH has been praised as one of the most successful ventures of modern pediatric orthopedics. Yet, before the modern management of DDH came into existence, there were extensive technological developments in the field of harnesses, casts, and traction methods. This paper aims to identify the centuries-old history of advancement in DDH treatment and the many important people involved. Their devices, thoughts, and ideas continue to have a profound impact on the current practice of orthopedic surgery.

Phytoplankton response to a plume front in the northern South China Sea

NASA Astrophysics Data System (ADS)

Li, Qian P.; Zhou, Weiwen; Chen, Yinchao; Wu, Zhengchao

2018-04-01

Due to a strong river discharge during April-June 2016, a persistent salinity front, with freshwater flushing seaward on the surface but seawater moving landward at the bottom, was formed in the coastal waters west of the Pearl River estuary (PRE) over the northern South China Sea (NSCS) shelf. Hydrographic measurements revealed that the salinity front was influenced by both the river plume and coastal upwelling. On shipboard nutrient-enrichment experiments with size-fractionation chlorophyll a measurements were taken on both sides of the front as well as in the frontal zone to diagnose the spatial variations of phytoplankton physiology across the frontal system. We also assessed the size-fractionated responses of phytoplankton to the treatment of plume water at the frontal zone and the sea side of the front. The biological impact of vertical mixing or upwelling was further examined by the response of surface phytoplankton to the addition of local bottom water. Our results suggested that there was a large variation in phytoplankton physiology on the sea side of the front, driven by dynamic nutrient fluxes, although P limitation was prevailing on the shore side of the front and at the frontal zone. The spreading of plume water at the frontal zone would directly improve the growth of microphytoplankton, while nano- and picophytoplankton growths could have become saturated at high percentages of plume water. Also, the mixing of bottom water would stimulate the growth of surface phytoplankton on both sides of the front by altering the surface N/P ratio to make it closer to the Redfield stoichiometry. In summary, phytoplankton growth and physiology could be profoundly influenced by the physical dynamics in the frontal system during the spring-summer of 2016.

Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and cell division under physiological conditions.

PubMed

Swee, Lee Kim; Tan, Zhen Wei; Sanecka, Anna; Yoshida, Nagisa; Patel, Harshil; Grotenbreg, Gijsbert; Frickel, Eva-Maria; Ploegh, Hidde L

2016-11-01

T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity-hence reactivity to self-and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2 b haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 L d -restricted epitope, derived from the Rop7 protein of Toxoplasma gondii We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels. First, we demonstrate the common occurrence of secondary rearrangements in endogenously rearranged loci. Furthermore, we characterized and compared the response of Rop7-specific CD8 T-cell clones upon Toxoplasma gondii infection as well as effector function and TCR signalling upon antigenic stimulation in vitro Antigen-independent TCR cross-linking in vitro uncovered profound intrinsic differences in the effector functions between T-cell clones. Finally, by assessing the degree of self-reactivity and comparing the transcriptomes of naive Rop7 CD8 T cells, we show that lower self-reactivity correlates with lower effector capacity, whereas higher self-reactivity is associated with enhanced effector function as well as cell cycle entry under physiological conditions. Altogether, our data show that potential effector functions and basal proliferation of CD8 T cells are set by self-reactivity thresholds. © 2016 The Authors.

Searching for the molecular benchmark of physiological intestinal anastomotic healing in rats: an experimental study.

PubMed

Seifert, Gabriel J; Seifert, Michael; Kulemann, Birte; Holzner, Philipp A; Glatz, Torben; Timme, Sylvia; Sick, Olivia; Höppner, Jens; Hopt, Ulrich T; Marjanovic, Goran

2014-01-01

This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. In eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The healthy intestinal tissue resected for this operation was used as a control. On days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and perianastomotic segments were examined with an Affymetrix microarray chip to assess changes in gene regulation. Microarray findings were validated using real-time PCR for selected genes. In addition to screening global gene expression, we identified genes intensely regulated during healing and also subjected our data sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto Encyclopedia for Genes and Genomes (KEGG). Compared to the control group, we observed that the number of differentially regulated genes peaked on day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to 1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13 showed not only identical transcription patterns but also analogous regulation intensity. When setting the cutoff of upregulation at 10-fold to identify genes likely to be relevant, the total gene count was significantly lower with 55, 45 and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories were significantly overrepresented during anastomotic healing. Furthermore, 23 overrepresented KEGG pathways were identified. This study is the first of its kind that focuses explicitly on gene transcription during intestinal anastomotic healing under standardized conditions. Our work sets a foundation for further studies toward a more profound understanding of the physiology of anastomotic healing.

Different responses of circulating ghrelin, obestatin levels to fasting, re-feeding and different food compositions, and their local expressions in rats.

PubMed

Guo, Zhi-Fu; Ren, An-Jing; Zheng, Xing; Qin, Yong-Wen; Cheng, Fang; Zhang, Jing; Wu, Hong; Yuan, Wen-Jun; Zou, Lin

2008-07-01

Obestatin, a sibling of ghrelin derived from preproghrelin, opposes several physiological actions of ghrelin. Our previous study has demonstrated that both plasma ghrelin and obestatin levels were decreased significantly 2h after food intake in human. To further expand current knowledge, we investigated the temporal profiles of their levels in ad libitum fed rats, 48h fasted rats and 48h fasted rats refed 2h with a standard chow, crude fiber, 50% glucose or water, and their expressions in stomach, liver and pancreatic islets immunohistochemically. Plasma ghrelin and obestatin levels were measured by EIA. Plasma leptin, insulin and glucose levels were also evaluated. Both plasma ghrelin and obestatin levels increased significantly in fasted rats compared with ad libitum fed rats. The ingestion of standard chow produced a profound and sustained suppression of ghrelin levels, whereas plasma obestatin levels decreased significantly but recovered quickly. Intake of crude fiber or 50% glucose, however, produced a more profound and sustained suppression of obestatin levels, though they had relatively less impact on ghrelin levels. Plasma glucose was the only independent predictor of ghrelin levels, obestatin levels, and ghrelin to obestatin ratios. Obestatin immunoreactivity was detected in the fundus of stomach, liver and pancreatic islets, with roughly similar patterns of distribution to ghrelin. These data show quantitative and qualitative differences in circulating ghrelin and obestatin responses to the short-term feeding status and nutrient composition, and may support a role for obestatin in regulating metabolism and energy homeostasis.

DOE Scientists Contribute to 2007 Nobel Peace Prize Research about Climate

Science.gov Websites

and resources were devoted to modeling the interactive effects of consequences, that is to say effects are more immediate and profound than previously anticipated, and old questions (are humans the Lawrence Livermore National Laboratory, DOE Technical Report, May 2005 Climate Effects of Global Land Cover

Examining the Effect of Feedback in Beginning L2 Composition

ERIC Educational Resources Information Center

Gascoigne, Carolyn

2004-01-01

Although L2 teachers tend to operate under the assumption that feedback on student compositions has a profound and positive effect on student revisions, few investigations have examined the results of teacher feedback. The present study, therefore, replicated a 1997 study by Ferris on the type and effect of feedback on advanced…

Individuals with Profound Disabilities: Instructional and Assistive Strategies. Third Edition.

ERIC Educational Resources Information Center

Sternberg, Les, Ed.

This collection of 14 essays focuses on the education of individuals with profound disabilities. The essays include: (1) "Individuals with Profound Disabilities: Definitions, Characteristics, and Conceptual Framework" (Les Sternberg); (2) "Creating Environments That Support and Enhance the Lives of All Individuals" (Lucille Zeph); (3) "Biomedical…

Preparing Students for Practice in a Managed Care Environment

ERIC Educational Resources Information Center

Claiborne, Nancy; Fortune, Anne

2005-01-01

Managed care has profound effects on health and mental health service delivery in the United States. This article describes the knowledge that students need for effective social work practice within a managed care environment and evaluates a course to deliver the content. (Contains 3 tables.)

PLATE: Powerful Learning and Teaching Environments

ERIC Educational Resources Information Center

Housand, Angela

2009-01-01

The environment has a profound effect on the ability of students to regulate their behavior or disposition and effectively engage in the learning processes. Active engagement is important because it increases performance. Certain types of environmental structures actually increase students' ability to be agents of their own learning. These…

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

Landreh, Michael; Stukenborg, Jan-Bernd; Willander, Hanna

Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrilsmore » formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.« less

Effects of intermittent fasting on glucose and lipid metabolism.

PubMed

Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

2017-08-01

Two intermittent fasting variants, intermittent energy restriction (IER) and time-restricted feeding (TRF), have received considerable interest as strategies for weight-management and/or improving metabolic health. With these strategies, the pattern of energy restriction and/or timing of food intake are altered so that individuals undergo frequently repeated periods of fasting. This review provides a commentary on the rodent and human literature, specifically focusing on the effects of IER and TRF on glucose and lipid metabolism. For IER, there is a growing evidence demonstrating its benefits on glucose and lipid homeostasis in the short-to-medium term; however, more long-term safety studies are required. Whilst the metabolic benefits of TRF appear quite profound in rodents, findings from the few human studies have been mixed. There is some suggestion that the metabolic changes elicited by these approaches can occur in the absence of energy restriction, and in the context of IER, may be distinct from those observed following similar weight-loss achieved via modest continuous energy restriction. Mechanistically, the frequently repeated prolonged fasting intervals may favour preferential reduction of ectopic fat, beneficially modulate aspects of adipose tissue physiology/morphology, and may also impinge on circadian clock regulation. However, mechanistic evidence is largely limited to findings from rodent studies, thus necessitating focused human studies, which also incorporate more dynamic assessments of glucose and lipid metabolism. Ultimately, much remains to be learned about intermittent fasting (in its various forms); however, the findings to date serve to highlight promising avenues for future research.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

PubMed

Carhart-Harris, Robin L; Erritzoe, David; Williams, Tim; Stone, James M; Reed, Laurence J; Colasanti, Alessandro; Tyacke, Robin J; Leech, Robert; Malizia, Andrea L; Murphy, Kevin; Hobden, Peter; Evans, John; Feilding, Amanda; Wise, Richard G; Nutt, David J

2012-02-07

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

Native arbuscular mycorrhizal symbiosis alters foliar bacterial community composition.

PubMed

Poosakkannu, Anbu; Nissinen, Riitta; Kytöviita, Minna-Maarit

2017-11-01

The effects of arbuscular mycorrhizal (AM) fungi on plant-associated microbes are poorly known. We tested the hypothesis that colonization by an AM fungus affects microbial species richness and microbial community composition of host plant tissues. We grew the grass, Deschampsia flexuosa in a greenhouse with or without the native AM fungus, Claroideoglomus etunicatum. We divided clonally produced tillers into two parts: one inoculated with AM fungus spores and one without AM fungus inoculation (non-mycorrhizal, NM). We characterized bacterial (16S rRNA gene) and fungal communities (internal transcribed spacer region) in surface-sterilized leaf and root plant compartments. AM fungus inoculation did not affect microbial species richness or diversity indices in leaves or roots, but the AM fungus inoculation significantly affected bacterial community composition in leaves. A total of three OTUs in leaves belonging to the phylum Firmicutes positively responded to the presence of the AM fungus in roots. Another six OTUs belonging to the Proteobacteria (Alpha, Beta, and Gamma) and Bacteroidetes were significantly more abundant in NM plants when compared to AM fungus-inoculated plants. Further, there was a significant correlation between plant dry weight and leaf microbial community compositional shift. Also, there was a significant correlation between leaf bacterial community compositional shift and foliar nitrogen content changes due to AM fungus inoculation. The results suggest that AM fungus colonization in roots has a profound effect on plant physiology that is reflected in leaf bacterial community composition.

Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis.

PubMed

Funk, Janet L; Frye, Jennifer B; Oyarzo, Janice N; Kuscuoglu, Nesrin; Wilson, Jonathan; McCaffrey, Gwen; Stafford, Gregory; Chen, Guanjie; Lantz, R Clark; Jolad, Shivanand D; Sólyom, Aniko M; Kiela, Pawel R; Timmermann, Barbara N

2006-11-01

Scientific evidence is lacking for the antiarthritic efficacy of turmeric dietary supplements that are being promoted for arthritis treatment. Therefore, we undertook studies to determine the antiarthritic efficacy and mechanism of action of a well-characterized turmeric extract using an animal model of rheumatoid arthritis (RA). The composition of commercial turmeric dietary supplements was determined by high-performance liquid chromatography. A curcuminoid-containing turmeric extract similar in composition to these supplements was isolated and administered intraperitoneally to female Lewis rats prior to or after the onset of streptococcal cell wall-induced arthritis. Efficacy in preventing joint swelling and destruction was determined clinically, histologically, and by measurement of bone mineral density. Mechanism of action was elucidated by analysis of turmeric's effect on articular transcription factor activation, microarray analysis of articular gene expression, and verification of the physiologic effects of alterations in gene expression. A turmeric fraction depleted of essential oils profoundly inhibited joint inflammation and periarticular joint destruction in a dose-dependent manner. In vivo treatment prevented local activation of NF-kappaB and the subsequent expression of NF-kappaB-regulated genes mediating joint inflammation and destruction, including chemokines, cyclooxygenase 2, and RANKL. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E(2), and periarticular osteoclast formation were inhibited by turmeric extract treatment. These translational studies demonstrate in vivo efficacy and identify a mechanism of action for a well-characterized turmeric extract that supports further clinical evaluation of turmeric dietary supplements in the treatment of RA.

Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines, erythrocytes, and platelets

NASA Technical Reports Server (NTRS)

Gridley, Daila S.; Nelson, Gregory A.; Peters, Luanne L.; Kostenuik, Paul J.; Bateman, Ted A.; Morony, Sean; Stodieck, Louis S.; Lacey, David L.; Simske, Steven J.; Pecaut, Michael J.

2003-01-01

This portion of the study quantified the effects of a 12-day space shuttle mission (Space Transport System-108/UF-1) on body and lymphoid organ masses, activation marker expression, cytokine secretion, and erythrocyte and thrombocyte characteristics in C57BL/6 mice. Animals in flight (Flt group) had 10-12% lower body mass compared with ground controls housed either in animal enclosure modules or under standard vivarium conditions (P < 0.001) and the smallest thymus and spleen masses. Percentages of CD25(+) lymphocytes, CD3(+)/CD25(+) T cells, and NK1.1(+)/CD25(+) natural killer cells from Flt mice were higher compared with both controls (P < 0.05). In contrast, CD71 expression was depressed in the Flt and animal enclosure module control mice compared with vivarium control animals (P < 0.001). Secretion of interferon-gamma, IL-2, and IL-4, but not tumor necrosis factor-alpha and IL-5, by splenocytes from Flt mice was decreased relative to either one or both ground controls (P < 0.05). Flt mice also had high red blood cell and thrombocyte counts compared with both sets of controls; low red blood cell volume and distribution width, percentage of reticulocytes, and platelet volume were also noted (P < 0.05) and were consistent with dehydration. These data indicate that relatively short exposure to the spaceflight environment can induce profound changes that may become significant during long-term space missions.

Managing aluminum phosphide poisonings

PubMed Central

Gurjar, Mohan; Baronia, Arvind K; Azim, Afzal; Sharma, Kalpana

2011-01-01

Aluminum phosphide (AlP) is a cheap, effective and commonly used pesticide. However, unfortunately, it is now one of the most common causes of poisoning among agricultural pesticides. It liberates lethal phosphine gas when it comes in contact either with atmospheric moisture or with hydrochloric acid in the stomach. The mechanism of toxicity includes cellular hypoxia due to the effect on mitochondria, inhibition of cytochrome C oxidase and formation of highly reactive hydroxyl radicals. The signs and symptoms are nonspecific and instantaneous. The toxicity of AlP particularly affects the cardiac and vascular tissues, which manifest as profound and refractory hypotension, congestive heart failure and electrocardiographic abnormalities. The diagnosis of AlP usually depends on clinical suspicion or history, but can be made easily by the simple silver nitrate test on gastric content or on breath. Due to no known specific antidote, management remains primarily supportive care. Early arrival, resuscitation, diagnosis, decrease the exposure of poison (by gastric lavage with KMnO4, coconut oil), intensive monitoring and supportive therapy may result in good outcome. Prompt and adequate cardiovascular support is important and core in the management to attain adequate tissue perfusion, oxygenation and physiologic metabolic milieu compatible with life until the tissue poison levels are reduced and spontaneous circulation is restored. In most of the studies, poor prognostic factors were presence of acidosis and shock. The overall outcome improved in the last decade due to better and advanced intensive care management. PMID:21887030

Plasma lactate concentrations in free-ranging moose (Alces alces) immobilized with etorphine.

PubMed

Haga, Henning A; Wenger, Sandra; Hvarnes, Silje; Os, Oystein; Rolandsen, Christer M; Solberg, Erling J

2009-11-01

To investigate plasma lactate concentrations of etorphine-immobilized moose in relation to environmental, temporal and physiological parameters. Prospective clinical study. Fourteen female and five male moose (Alces alces), estimated age range 1-7 years. The moose were darted from a helicopter with 7.5 mg etorphine per animal using projectile syringes and a dart gun. Once immobilized, the moose were approached, a venous blood sample was obtained and vital signs including pulse oximetry were recorded. Diprenorphine was administered to reverse the effects of etorphine. Timing of events, ambient temperature and snow depth were recorded. Blood samples were cooled and centrifuged before plasma was harvested and frozen. The plasma was thawed later and lactate analysed. Data were analysed using descriptive statistics and regression analysis. All animals recovered uneventfully and were alive 12 weeks after immobilization. Mean +/- SD plasma lactate was found to be 9.2 +/- 2.1 mmol L(-1). Plasma lactate concentrations were related positively to snow depth and negatively to time from induction of immobilization to blood sampling. The model that best described the variability in plasma lactate concentrations used induction time (time from firing the dart to the moose being immobilized). The second best model included induction time and snow depth. Plasma lactate concentrations in these etorphine-immobilized moose were in the range reported for other immobilized wild ruminants. Decreasing induction time, which may be related to a more profound etorphine effect, and increasing snow depth possibly may increase plasma lactate concentrations in etorphine-immobilized moose.

Combination of photodynamic and ultrasonic therapy for treatment of infected wounds in animal model

NASA Astrophysics Data System (ADS)

Menyaev, Yulian A.; Zharov, Vladimir P.

2006-02-01

One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40+/-20 μm wavelength of light emitting diodes (LED) array - 660+/-10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.