Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

PubMed Central

Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

2009-01-01

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

Speech enhancement using the modified phase-opponency model.

PubMed

Deshmukh, Om D; Espy-Wilson, Carol Y; Carney, Laurel H

2007-06-01

In this paper we present a model called the Modified Phase-Opponency (MPO) model for single-channel speech enhancement when the speech is corrupted by additive noise. The MPO model is based on the auditory PO model, proposed for detection of tones in noise. The PO model includes a physiologically realistic mechanism for processing the information in neural discharge times and exploits the frequency-dependent phase properties of the tuned filters in the auditory periphery by using a cross-auditory-nerve-fiber coincidence detection for extracting temporal cues. The MPO model alters the components of the PO model such that the basic functionality of the PO model is maintained but the properties of the model can be analyzed and modified independently. The MPO-based speech enhancement scheme does not need to estimate the noise characteristics nor does it assume that the noise satisfies any statistical model. The MPO technique leads to the lowest value of the LPC-based objective measures and the highest value of the perceptual evaluation of speech quality measure compared to other methods when the speech signals are corrupted by fluctuating noise. Combining the MPO speech enhancement technique with our aperiodicity, periodicity, and pitch detector further improves its performance.

Strategies to enhance the bioavailability of curcumin: a potential antitumor drug

NASA Astrophysics Data System (ADS)

Kumar, Abhishek; Chittigori, Joshna; Li, Lian; Samuelson, Lynne; Sandman, Daniel; Kumar, Jayant

2012-02-01

Curcumin is a polyphenol which has elicited considerable interest for its antioxidant and anti tumor properties. Although curcumin may be used as potential therapeutic drug, it is very sparingly soluble in water which makes it less bioavailable under physiological conditions. We report two approaches to make curcumin more bioavailable. The first approach involves fabricating colloidal dispersions of curcumin in the range of tens of nanometers. The second approach involves functionalization of curcumin with polyethylene glycol (PEG) to render it water dispersible or soluble. Since curcumin is a fluorescent molecule as well as a potential drug, its interactions with cells have been investigated using one and two photon confocal fluorescence imaging. We have also observed strong interaction between curcumin and metal ions, which may have physiological implications.

Role of cholesterol and lipid organization in disease

NASA Astrophysics Data System (ADS)

Maxfield, Frederick R.; Tabas, Ira

2005-12-01

Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.

Selective spatial enhancement: Attentional spotlight size impacts spatial but not temporal perception.

PubMed

Goodhew, Stephanie C; Shen, Elizabeth; Edwards, Mark

2016-08-01

An important but often neglected aspect of attention is how changes in the attentional spotlight size impact perception. The zoom-lens model predicts that a small ("focal") attentional spotlight enhances all aspects of perception relative to a larger ("diffuse" spotlight). However, based on the physiological properties of the two major classes of visual cells (magnocellular and parvocellular neurons) we predicted trade-offs in spatial and temporal acuity as a function of spotlight size. Contrary to both of these accounts, however, across two experiments we found that attentional spotlight size affected spatial acuity, such that spatial acuity was enhanced for a focal relative to a diffuse spotlight, whereas the same modulations in spotlight size had no impact on temporal acuity. This likely reflects the function of attention: to induce the high spatial resolution of the fovea in periphery, where spatial resolution is poor but temporal resolution is good. It is adaptive, therefore, for the attentional spotlight to enhance spatial acuity, whereas enhancing temporal acuity does not confer the same benefit.

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

PubMed

Lalley, Peter M; Mifflin, Steve W

2017-05-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N -methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO 2 /pH chemosensitivity. Copyright © 2017 the American Physiological Society.

Comprehensive characterizations of nanoparticle biodistribution following systemic injection in mice

NASA Astrophysics Data System (ADS)

Liao, Wei-Yin; Li, Hui-Jing; Chang, Ming-Yao; Tang, Alan C. L.; Hoffman, Allan S.; Hsieh, Patrick C. H.

2013-10-01

Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological conditions improved large NP (200-500 nm) distribution in brain tissue. These results reveal the importance of selecting analytic tools and physiological environment when characterizing NP biodistribution for future nanoscale toxicology, therapeutics and diagnostics.Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological conditions improved large NP (200-500 nm) distribution in brain tissue. These results reveal the importance of selecting analytic tools and physiological environment when characterizing NP biodistribution for future nanoscale toxicology, therapeutics and diagnostics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr03954d

Reactive oxygen species-mediated breast cell carcinogenesis enhanced by multiple carcinogens and intervened by dietary ergosterol and mimosine.

PubMed

Pluchino, Lenora Ann; Liu, Amethyst Kar-Yin; Wang, Hwa-Chain Robert

2015-03-01

Most breast cancers occur sporadically due to long-term exposure to low-dose carcinogens in the diet and the environment. Specifically, smoke, polluted air, and high-temperature cooked meats comprise multiple carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), benzo[α]pyrene (B[α]P), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). We sought to determine if these carcinogens act together to induce breast cell carcinogenesis, and if so, whether noncytotoxic dietary agents could intervene. We demonstrated that coexposure to physiologically achievable doses of NNK, B[α]P, and PhIP (NBP) holistically enhanced initiation and progression of breast cell carcinogenesis. Reactive oxygen species (ROS) and activation of the ERK pathway were transiently induced by NBP in each exposure, and cross talk between reinforced ROS elevation and ERK activation played an essential role in increased DNA oxidation and damage. After cumulative exposures to NBP, this cross talk contributed to enhanced initiation of cellular carcinogenesis and led to enhanced acquisition of cancer-associated properties. Using NBP-induced transient changes, such as ROS elevation and ERK pathway activation, and cancer-associated properties as targeted endpoints, we revealed, for the first time, that two less-studied dietary compounds, ergosterol and mimosine, at physiologically achievable noncytotoxic levels, were highly effective in intervention of NBP-induced cellular carcinogenesis. Combined ergosterol and mimosine were more effective than individual agents in blocking NBP-induced transient endpoints, including ROS-mediated DNA oxidation, which accounted for their preventive ability to suppress progression of NBP-induced cellular carcinogenesis. Thus, dietary components, such as mushrooms containing ergosterol and legumes containing mimosine, should be considered for affordable prevention of sporadic breast cancer associated with long-term exposure to environmental and dietary carcinogens. Copyright © 2014 Elsevier Inc. All rights reserved.

Student perceptions and learning outcomes of computer-assisted versus traditional instruction in physiology.

PubMed

Richardson, D

1997-12-01

This study compared student perceptions and learning outcomes of computer-assisted instruction against those of traditional didactic lectures. Components of Quantitative Circulatory Physiology (Biological Simulators) and Mechanical Properties of Active Muscle (Trinity Software) were used to teach regulation of tissue blood flow and muscle mechanics, respectively, in the course Medical Physiology. These topics were each taught, in part, by 1) standard didactic lectures, 2) computer-assisted lectures, and 3) computer laboratory assignment. Subjective evaluation was derived from a questionnaire assessing student opinions of the effectiveness of each method. Objective evaluation consisted of comparing scores on examination questions generated from each method. On a 1-10 scale, effectiveness ratings were higher (P < 0.0001) for the didactic lectures (7.7) compared with either computer-assisted lecture (3.8) or computer laboratory (4.2) methods. A follow-up discussion with representatives from the class indicated that students did not perceive computer instruction as being time effective. However, examination scores from computer laboratory questions (94.3%) were significantly higher compared with ones from either computer-assisted (89.9%; P < 0.025) or didactic (86.6%; P < 0.001) lectures. Thus computer laboratory instruction enhanced learning outcomes in medical physiology despite student perceptions to the contrary.

Space Physiology within an Exercise Physiology Curriculum

ERIC Educational Resources Information Center

Carter, Jason R.; West, John B.

2013-01-01

Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.

PubMed

Hasselmo, Michael E

2005-01-01

The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm. Copyright 2005 Wiley-Liss, Inc.

A Methodology for Measuring the Physiological Strain of Enhanced Soldiers: The 1998 Soldier Combat System Enhancement Study

DTIC Science & Technology

1998-11-01

a BSc in Physiology (1988), BPhEd in Kinesiology (1989) and MPhEd (1992) in physiological and epidemiological aspects of hypothermia. He moved to...Hong Kong in 1979 in Biology and Biochemistry and obtained his M. Phil in environmental biology in 1981. Supported by a Croucher Foundation

TiO2 nanoparticles for enhancing the refractive index of hydrogels for ophthalmological applications

NASA Astrophysics Data System (ADS)

Hampp, Norbert; Dams, Christian; Badur, Thorben; Reinhardt, Hendrik

2017-02-01

Intraocular lenses (IOL) are currently the only treatment for cataract dependent vision impairment and blindness [1]. A polymer suitable for IOL manufacture needs to meet a plurality of properties, biocompatibility, excellent transmission in the visible range, a high flexibility for micro invasive surgery, a high refractive index as well as a good ABBE-number, just to mention the most important ones [2]. We present the use of in situ generated TiO2-nanoparticles to enhance the refractive index of poly-HEMA hydrogels - with are suitable polymers for IOL manufacture[3] - from 1.44 to 1.527 at 589.3 nm combined with an excellent ABBE-number of 54. The nanoparticles were prepared using titaniumdiisopropoxide- bis(acetylacetonate) as a precursor. First the titanium salt was diffused into the poly-HEMA matrix and then it was transformed into TiO2 in boiling water. The resulting pHEMA [TiO2] hydrogel was dried for 10 days under ambient conditions. By lathing these polymers were machined into lens precursors, the so-called Saturn-rings. After reswelling in physiological saline solutions flexible polymer lenses with high surface quality, shape memory and superior optical properties were obtained. The crystal structure of the formed TiO2 nanoparticles was identified as anatase via Xray. No release of titanium ions or TiO2 nanoparticles was observe under physiological conditions. Such hybrid materials of TiO2 nanoparticles and poly-HEMA like hydrogels are promising materials for IOL.

[On the biological properties of fragrance compounds and essential oils].

PubMed

Buchbauer, Gerhard

2004-11-01

In the present review the physiological and/or pharmacological properties of essential oils and of single fragrance compounds are discussed. Essential oils are known and have been used since ancient times as natural medicines. As natural products essential oils are dependent on climate and their composition varies according to conditions of soil, to solar irradiation, to harvest time, to production methods, to storage conditions and similar facts which are discussed in chapter 2 of this review. The next chapters deal with the therapeutic use of essential oils in treating diseases, disorders or ailments of the nervous system, against cancer and as penetration enhancers. For space-saving reasons, however, the manifold antimicrobial and antifungal properties of these natural products have been left out. In the last chapter, the pros and cons in the use of essential oils in therapy are also discussed.

Fluid-acoustic interactions and their impact on pathological voiced speech

NASA Astrophysics Data System (ADS)

Erath, Byron D.; Zanartu, Matias; Peterson, Sean D.; Plesniak, Michael W.

2011-11-01

Voiced speech is produced by vibration of the vocal fold structures. Vocal fold dynamics arise from aerodynamic pressure loadings, tissue properties, and acoustic modulation of the driving pressures. Recent speech science advancements have produced a physiologically-realistic fluid flow solver (BLEAP) capable of prescribing asymmetric intraglottal flow attachment that can be easily assimilated into reduced order models of speech. The BLEAP flow solver is extended to incorporate acoustic loading and sound propagation in the vocal tract by implementing a wave reflection analog approach for sound propagation based on the governing BLEAP equations. This enhanced physiological description of the physics of voiced speech is implemented into a two-mass model of speech. The impact of fluid-acoustic interactions on vocal fold dynamics is elucidated for both normal and pathological speech through linear and nonlinear analysis techniques. Supported by NSF Grant CBET-1036280.

Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

PubMed

Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun

2015-11-01

Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

Structural and Kinetic Characterization of the Intrinsically Disordered Protein SeV NTAIL through Enhanced Sampling Simulations.

PubMed

Bernetti, Mattia; Masetti, Matteo; Pietrucci, Fabio; Blackledge, Martin; Jensen, Malene Ringkjobing; Recanatini, Maurizio; Mollica, Luca; Cavalli, Andrea

2017-10-19

Intrinsically disordered proteins (IDPs) are emerging as an important class of the proteome. Being able to interact with different molecular targets, they participate in many physiological and pathological activities. However, due to their intrinsically heterogeneous nature, determining the equilibrium properties of IDPs is still a challenge for biophysics. Herein, we applied state-of-the-art enhanced sampling methods to Sev N TAIL , a test case of IDPs, and constructed a bin-based kinetic model to unveil the underlying kinetics. To validate our simulation strategy, we compared the predicted NMR properties against available experimental data. Our simulations reveal a rough free-energy surface comprising multiple local minima, which are separated by low energy barriers. Moreover, we identified interconversion rates between the main kinetic states, which lie in the sub-μs time scales, as suggested in previous works for Sev N TAIL . Therefore, the emerging picture is in agreement with the atomic-level properties possessed by the free IDP in solution. By providing both a thermodynamic and kinetic characterization of this IDP test case, our study demonstrates how computational methods can be effective tools for studying this challenging class of proteins.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

PubMed Central

Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

2016-01-01

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

Physiologic TLR9-CpG-DNA interaction is essential for the homeostasis of the intestinal immune system.

PubMed

Hofmann, Claudia; Dunger, Nadja; Doser, Kristina; Lippert, Elisabeth; Siller, Sebastian; Edinger, Matthias; Falk, Werner; Obermeier, Florian

2014-01-01

Cytosine-guanosine dinucleotide (CpG) motifs are immunostimulatory components of bacterial DNA and activators of innate immunity through Toll-like receptor 9 (TLR9). Administration of CpG oligodeoxynucleotides before the onset of experimental colitis prevents intestinal inflammation by enforcement of regulatory mechanisms. It was investigated whether physiologic CpG/TLR9 interactions are critical for the homeostasis of the intestinal immune system. Mesenteric lymph node cell and lamina propria mononuclear cell (LPMC) populations from BALB/c wild-type (wt) or TLR9 mice were assessed by flow cytometry and proteome profiling. Cytokine secretion was determined and nuclear extracts were analyzed for nuclear factor kappa B (NF-κB) and cAMP response-element binding protein activity. To assess the colitogenic potential of intestinal T cells, CD4-enriched cells from LPMC of wt or TLR9 donor mice were injected intraperitoneally in recipient CB-17 SCID mice. TLR9 deficiency was accompanied by slight changes in cellular composition and phosphorylation of signaling proteins of mesenteric lymph node cell and LPMC. LPMC from TLR9 mice displayed an increased proinflammatory phenotype compared with wt LPMC. NF-κB activity in cells from TLR9 mice was enhanced, whereas cAMP response-element binding activity was reduced compared with wt. Transfer of lamina propria CD4-enriched T cells from TLR9 mice induced severe colitis, whereas wt lamina propria CD4-enriched T cells displayed an attenuated phenotype. Lack of physiologic CpG/TLR9 interaction impairs the function of the intestinal immune system indicated by enhanced proinflammatory properties. Thus, physiologic CpG/TLR interaction is essential for homeostasis of the intestinal immune system as it is required for the induction of counterregulating anti-inflammatory mechanisms.

Ecosystem services and plant physiological status during endophyte-assisted phytoremediation of metal contaminated soil.

PubMed

Burges, Aritz; Epelde, Lur; Blanco, Fernando; Becerril, José M; Garbisu, Carlos

2017-04-15

Mining sites shelter a characteristic biodiversity with large potential for the phytoremediation of metal contaminated soils. Endophytic plant growth-promoting bacteria were isolated from two metal-(hyper)accumulator plant species growing in a metal contaminated mine soil. After characterizing their plant growth-promoting traits, consortia of putative endophytes were used to carry out an endophyte-assisted phytoextraction experiment using Noccaea caerulescens and Rumex acetosa (singly and in combination) under controlled conditions. We evaluated the influence of endophyte-inoculated plants on soil physicochemical and microbial properties, as well as plant physiological parameters and metal concentrations. Data interpretation through the grouping of soil properties within a set of ecosystem services was also carried out. When grown together, we observed a 41 and 16% increase in the growth of N. caerulescens and R. acetosa plants, respectively, as well as higher values of Zn phytoextraction and soil microbial biomass and functional diversity. Inoculation of the consortia of putative endophytes did not lead to higher values of plant metal uptake, but it improved the plants' physiological status, by increasing the content of chlorophylls and carotenoids by up to 28 and 36%, respectively, indicating a reduction in the stress level of plants. Endophyte-inoculation also stimulated soil microbial communities: higher values of acid phosphatase activity (related to the phosphate solubilising traits of the endophytes), bacterial and fungal abundance, and structural diversity. The positive effects of plant growth and endophyte inoculation on soil properties were reflected in an enhancement of some ecosystem services (biodiversity, nutrient cycling, water flow regulation, water purification and contamination control). Copyright © 2016 Elsevier B.V. All rights reserved.

CO2 microbubble contrast enhancement in x-ray angiography.

PubMed

Kariya, S; Komemushi, A; Nakatani, M; Yoshida, R; Sawada, S; Tanigawa, N

2013-04-01

To demonstrate that carbon dioxide (CO2) microbubble contrast enhancement depicts blood vessels when used for x-ray examinations. Microbubbles were generated by cavitation of physiological saline to which CO2 gas had been added using an ejector-type microbubble generator. The input pressure values for CO2 gas and physiological saline that produced a large quantity of CO2 microbubbles were obtained in a phantom. In an animal study, angiography was performed in three swine using three types of contrast: CO2 microbubbles, conventional CO2 gas, and iodinated contrast medium. For CO2 microbubble contrast enhancement, physiological saline, and CO2 gas were supplied at the input pressures calculated in the phantom experiment. Regions of interest were set in the abdominal aorta, external iliac arteries, and background. The difference in digital values between each artery and the background was calculated. The input pressures obtained in the phantom experiment were 0.16 MPa for physiological saline and 0.5 MPa for CO2 gas, with physiological saline input volume being 8.1 ml/s. Three interventional radiologists all evaluated the depictions of all arteries as "present" in the CO2 microbubble contrast enhancement, conventional CO2 contrast enhancement, and iodinated contrast enhancement performed in three swine. Digital values for all vessels with microbubble CO2 contrast enhancement were higher than background values. In x-ray angiography, blood vessels can be depicted by CO2 microbubble contrast enhancement, in which a large quantity of CO2 microbubbles is generated within blood vessels. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Intracellular Physiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators

DTIC Science & Technology

1992-01-10

Physiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators . I-f 12. PERSONAL AUTHOR(S) F...interplay between intrinsic electrophysiological properties, amino-acid-mediated synaptic transmission, and neuromodulation . We have continued to study the

A triarylmethyl spin label for long-range distance measurement at physiological temperatures using T1 relaxation enhancement

NASA Astrophysics Data System (ADS)

Yang, Zhongyu; Bridges, Michael D.; López, Carlos J.; Rogozhnikova, Olga Yu.; Trukhin, Dmitry V.; Brooks, Evan K.; Tormyshev, Victor; Halpern, Howard J.; Hubbell, Wayne L.

2016-08-01

Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy has become an important tool for measuring distances in proteins on the order of a few nm. For this purpose pairs of spin labels, most commonly nitroxides, are site-selectively introduced into the protein. Recent efforts to develop new spin labels are focused on tailoring the intrinsic properties of the label to either extend the upper limit of measurable distances at physiological temperature, or to provide a unique spectral lineshape so that selective pairwise distances can be measured in a protein or complex containing multiple spin label species. Triarylmethyl (TAM) radicals are the foundation for a new class of spin labels that promise to provide both capabilities. Here we report a new methanethiosulfonate derivative of a TAM radical that reacts rapidly and selectively with an engineered cysteine residue to generate a TAM containing side chain (TAM1) in high yield. With a TAM1 residue and Cu2+ bound to an engineered Cu2+ binding site, enhanced T1 relaxation of TAM should enable measurement of interspin distances up to 50 Å at physiological temperature. To achieve favorable TAM1-labeled protein concentrations without aggregation, proteins are tethered to a solid support either site-selectively using an unnatural amino acid or via native lysine residues. The methodology is general and readily extendable to complex systems, including membrane proteins.

Impact of phytoplankton community structure and function on marine particulate optical properties

NASA Astrophysics Data System (ADS)

McFarland, Malcolm Neil

Phytoplankton are an ecologically important and diverse group of organisms whose distribution, abundance, and population dynamics vary significantly over small spatial (cm) and temporal (minutes) scales in the coastal ocean. Our inability to observe phytoplankton community structure and function at these small scales has severely limited our understanding of the fundamental ecological and evolutionary mechanisms that drive phytoplankton growth, mortality, adaptation and speciation. The goal of this dissertation was to enhance our understanding of phytoplankton ecology by improving in situ observational techniques based on the optical properties of cells, colonies, populations, and communities. Field and laboratory studies were used to determine the effects of phytoplankton species composition, morphology, and physiology on the inherent optical properties of communities and to explore the adaptive significance of bio-optically important cellular characteristics. Initial field studies found a strong association between species composition and the relative magnitude and shape of particulate absorption, scattering, and attenuation coefficient spectra. Subsequent field studies using scanning flow cytometry to directly measure optically important phytoplankton and non-algal particle characteristics demonstrated that the size and pigment content of large (>20 microm) phytoplankton cells and colonies vary significantly with the slope of particulate attenuation and absorption spectra, and with the ratio of particulate scattering to absorption. These relationships enabled visualization of phytoplankton community composition and mortality over small spatial and temporal scales derived from high resolution optical measurements acquired with an autonomous profiling system. Laboratory studies with diverse uni-algal cultures showed that morphological and physiological characteristics of cells and colonies can account for ˜30% of the optical variation observed in natural communities and that complex morphologies and low intracellular pigment concentrations minimize pigment self-shading that could otherwise limit bio-optical fitness. These results demonstrate that optical properties reveal detailed information about the distribution, abundance, morphology, and physiology of phytoplankton that can help explain their ecological dynamics over small spatial scales and the bio-optical function of diverse forms in the ocean.

Investigation of pajama properties on skin under mild cold conditions: the interaction between skin and clothing.

PubMed

Yao, Lei; Gohel, Mayur D I; Li, Yi; Chung, Waiyee J

2011-07-01

Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response. © 2011 The International Society of Dermatology.

"Physiology in the News": Using Press Releases to Enhance Lay Communication and Introduce Current Physiology Research to Undergraduates

ERIC Educational Resources Information Center

Kelly, Kevin L.; Poteracki, James M.; Steury, Michael D.; Wehrwein, Erica A.

2015-01-01

Michigan State University's senior-level undergraduate physiology capstone laboratory uses a simple exercise termed "Physiology in the News," to help students explore the current research within the field of physiology while also learning to communicate science in lay terms. "Physiology in the News" is an activity that charges…

Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum.

PubMed

Oh, Myoung Jin; Cho, Young Hoon; Cha, So Yoon; Lee, Eun Ok; Kim, Jin Wook; Kim, Sun Ki; Park, Chang Seo

2017-01-01

Ceramides in the human stratum corneum (SC) are a mixture of diverse N -acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N -acylated FAs and compare them with C18-ceramide N -stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer.

The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments.

PubMed

West, Daniel W D; Lee-Barthel, Ann; McIntyre, Todd; Shamim, Baubak; Lee, Cassandra A; Baar, Keith

2015-10-15

Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post-exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue-engineered ligaments is enhanced by serum obtained post-exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ∼7-fold greater than resting serum (P < 0.001), whereas IGF-1 was not elevated at this time point (P = 0.21 vs. rest). Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post-exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 ± 33 vs. 215 ± 40 μg per construct P = 0.001) and ligament mechanical properties - maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF-1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post-exercise serum activated mTORC1 and ERK1/2. In conclusion, the post-exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Drug-induced modification of the system properties associated with spontaneous human electroencephalographic activity

NASA Astrophysics Data System (ADS)

Liley, David T.; Cadusch, Peter J.; Gray, Marcus; Nathan, Pradeep J.

2003-11-01

The benzodiazepine (BZ) class of minor tranquilizers are important modulators of the γ-amino butyric acid (GABAA)/BZ receptor complex that are well known to affect the spectral properties of spontaneous electroencephalographic activity. While it is experimentally well established that the BZs reduce total alpha band (8 13 Hz) power and increase total beta band (13 30 Hz) power, it is unclear what the physiological basis for this effect is. Based on a detailed theory of cortical electrorhythmogenesis it is conjectured that such an effect is explicable in terms of the modulation of GABAergic neurotransmission within locally connected populations of excitatory and inhibitory cortical neurons. Motivated by this theory, fixed order autoregressive moving average (ARMA) models were fitted to spontaneous eyes-closed electroencephalograms recorded from subjects before and approximately 2 h after the oral administration of a single 1 mg dose of the BZ alprazolam. Subsequent pole-zero analysis revealed that BZs significantly transform the dominant system pole such that its frequency and damping increase. Comparisons of ARMA derived power spectra with fast Fourier transform derived spectra indicate an enhanced ability to identify benzodiazepine induced electroencephalographic changes. This experimental result is in accord with the theoretical predictions implying that alprazolam enhances inhibition acting on inhibitory neurons more than inhibition acting on excitatory neurons. Further such a result is consistent with reported cortical neuronal distributions of the various GABAA receptor pharmacological subtypes. Therefore physiologically specified fixed order ARMA modeling is expected to become an important tool for the systematic investigation and modeling of a wide range of cortically acting compounds.

Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability.

PubMed

Manju, S; Sreenivasan, K

2011-07-01

Polymer-drug conjugates have gained much attention largely to circumvent lower drug solubility and to enhance drug stability. Curcumin is widely known for its medicinal properties including its anticancer efficacy. One of the serious drawbacks of curcumin is its poor water solubility which leads to reduced bioavailability. With a view to address these issues, we synthesized hyaluronic acid-curcumin (HA-Cur) conjugate. The drug conjugate was characterized using FT-IR, NMR, Dynamic light scattering and TEM techniques. The conjugates, interestingly found to assembles as micelles in aqueous phase. The formation of micelles seems to improve the stability of the drug in physiological pH. We also assessed cytotoxicity of the conjugate using L929 fibroblast cells and quantified by MTT assay. Copyright © 2011 Elsevier Inc. All rights reserved.

PBPK models for the prediction of in vivo performance of oral dosage forms.

PubMed

Kostewicz, Edmund S; Aarons, Leon; Bergstrand, Martin; Bolger, Michael B; Galetin, Aleksandra; Hatley, Oliver; Jamei, Masoud; Lloyd, Richard; Pepin, Xavier; Rostami-Hodjegan, Amin; Sjögren, Erik; Tannergren, Christer; Turner, David B; Wagner, Christian; Weitschies, Werner; Dressman, Jennifer

2014-06-16

Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the formulation and interplay with the underlying physiological properties of the GI tract. The ability to accurately predict oral drug absorption during drug product development is becoming more relevant given the current challenges facing the pharmaceutical industry. Physiologically-based pharmacokinetic (PBPK) modeling provides an approach that enables the plasma concentration-time profiles to be predicted from preclinical in vitro and in vivo data and can thus provide a valuable resource to support decisions at various stages of the drug development process. Whilst there have been quite a few successes with PBPK models identifying key issues in the development of new drugs in vivo, there are still many aspects that need to be addressed in order to maximize the utility of the PBPK models to predict drug absorption, including improving our understanding of conditions in the lower small intestine and colon, taking the influence of disease on GI physiology into account and further exploring the reasons behind population variability. Importantly, there is also a need to create more appropriate in vitro models for testing dosage form performance and to streamline data input from these into the PBPK models. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the current status of PBPK models available. The current challenges in PBPK set-ups for oral drug absorption including the composition of GI luminal contents, transit and hydrodynamics, permeability and intestinal wall metabolism are discussed in detail. Further, the challenges regarding the appropriate integration of results from in vitro models, such as consideration of appropriate integration/estimation of solubility and the complexity of the in vitro release and precipitation data, are also highlighted as important steps to advancing the application of PBPK models in drug development. It is expected that the "innovative" integration of in vitro data from more appropriate in vitro models and the enhancement of the GI physiology component of PBPK models, arising from the OrBiTo project, will lead to a significant enhancement in the ability of PBPK models to successfully predict oral drug absorption and advance their role in preclinical and clinical development, as well as for regulatory applications. Copyright © 2013 Elsevier B.V. All rights reserved.

[PHYSIOLOGY AND PHARMACOLOGICAL PROPERTIES OF NANOMATERIALS].

PubMed

Chekman, I S

2015-01-01

Literature data and results of our department studies on theoretical and practical basics of nanoscience were summarized in the article. Much attention is paid to research in the field of physical, chemical, biological, medical, physiological, pharmacological, and toxicological properties of nanomaterials with the aim of their wider implementation into practice lately. The discovery of new quantum/wave properties of nanoparticles is of particular importance. The author of the article advances an idea: wave properties of nanomaterials play greater role with a decrease in particle size. The preponderance of wave properties compared with corpuscular ones in nanostructures determines a great change in their physical. chemical properties and an increase in physical, mechanical biological, physiological, pharmacological, and toxicologica activity. The idea advanced in the article hasn't been verified by theoretical or experimental studies for now. Joined efforts of scientists of different scientific fields are needed. A confirmation of hypothesis by specific findings will be of great importance for physiology, medicine, pharmacology and promote an implementation of new efficacious preparations into clinical practice. New fundamental discoveries could be made only by multidisciplinary approach.

Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program.

PubMed

Morrison-Nozik, Alexander; Anand, Priti; Zhu, Han; Duan, Qiming; Sabeh, Mohamad; Prosdocimo, Domenick A; Lemieux, Madeleine E; Nordsborg, Nikolai; Russell, Aaron P; MacRae, Calum A; Gerber, Anthony N; Jain, Mukesh K; Haldar, Saptarsi M

2015-12-08

Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.

Review of optical breast imaging and spectroscopy

NASA Astrophysics Data System (ADS)

Grosenick, Dirk; Rinneberg, Herbert; Cubeddu, Rinaldo; Taroni, Paola

2016-09-01

Diffuse optical imaging and spectroscopy of the female breast is an area of active research. We review the present status of this field and discuss the broad range of methodologies and applications. Starting with a brief overview on breast physiology, the remodeling of vasculature and extracellular matrix caused by solid tumors is highlighted that is relevant for contrast in optical imaging. Then, the various instrumental techniques and the related methods of data analysis and image generation are described and compared including multimodality instrumentation, fluorescence mammography, broadband spectroscopy, and diffuse correlation spectroscopy. We review the clinical results on functional properties of malignant and benign breast lesions compared to host tissue and discuss the various methods to improve contrast between healthy and diseased tissue, such as enhanced spectroscopic information, dynamic variations of functional properties, pharmacokinetics of extrinsic contrast agents, including the enhanced permeability and retention effect. We discuss research on monitoring neoadjuvant chemotherapy and on breast cancer risk assessment as potential clinical applications of optical breast imaging and spectroscopy. Moreover, we consider new experimental approaches, such as photoacoustic imaging and long-wavelength tissue spectroscopy.

Interfacing with the brain using organic electronics (Presentation Recording)

NASA Astrophysics Data System (ADS)

Malliaras, George G.

2015-10-01

Implantable electrodes are being used for diagnostic purposes, for brain-machine interfaces, and for delivering electrical stimulation to alleviate the symptoms of diseases such as Parkinson's. The field of organic electronics made available devices with a unique combination of attractive properties, including mixed ionic/electronic conduction, mechanical flexibility, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic electrodes, transistors and other devices for recording and stimulation of brain activity and discuss how they can improve our understanding of brain physiology and pathology, and how they can be used to deliver new therapies.

Enhancing photothermal cancer therapy by clustering gold nanoparticles into spherical polymeric nanoconstructs

NASA Astrophysics Data System (ADS)

Iodice, Carmen; Cervadoro, Antonio; Palange, AnnaLisa; Key, Jaehong; Aryal, Santosh; Ramirez, Maricela R.; Mattu, Clara; Ciardelli, Gianluca; O'Neill, Brian E.; Decuzzi, Paolo

2016-01-01

Gold nanoparticles (AuNPs) have been proposed as agents for enhancing photothermal therapy in cancer and cardiovascular diseases. Different geometrical configurations have been used, ranging from spheres to rods and more complex star shapes, to modulate optical and ablating properties. In this work, multiple, ultra-small 6 nm AuNPs are encapsulated into larger spherical polymeric nanoconstructs (SPNs), made out of a poly(lactic acid-co-glycol acid) (PLGA) core stabilized by a superficial lipid-PEG monolayer. The optical and photothermal properties of the resulting nanoconstructs (Au-SPNs) are modulated by varying the initial loading input of AuNPs, ranging between 25 and 150 μgAu. Au-SPNs exhibit a hydrodynamic diameter varying from ~100 to 180 nm, growing with the gold content, and manifest up to 2-fold increase in thermal energy production per unit mass of gold for an initial input of 100 μgAu. Au-SPNs are stable under physiological conditions up to 7 days and have direct cytotoxic effect on tumor cells. The superior photothermal performance of Au-SPNs is assessed in vitro on monolayers of breast cancer cells (SUM-159) and tumor spheroids of glioblastoma multiforme cells (U87-MG). The encapsulation of small AuNPs into larger spherical nanoconstructs enhances photothermal ablation and could favor tumor accumulation.

Attributes of God: Conceptual Foundations of a Foundational Belief.

PubMed

Shtulman, Andrew; Lindeman, Marjaana

2016-04-01

Anthropomorphism, or the attribution of human properties to nonhuman entities, is often posited as an explanation for the origin and nature of God concepts, but it remains unclear which human properties we tend to attribute to God and under what conditions. In three studies, participants decided whether two types of human properties-psychological (mind-dependent) properties and physiological (body-dependent) properties-could or could not be attributed to God. In Study 1 (n = 1,525), participants made significantly more psychological attributions than physiological attributions, and the frequency of those attributions was correlated both with participants' religiosity and with their attribution of abstract, theological properties. In Study 2 (n = 99) and Study 3 (n = 138), participants not only showed the same preference for psychological properties but were also significantly faster, more consistent, and more confident when attributing psychological properties to God than when attributing physiological properties. And when denying properties to God, they showed the reverse pattern-that is, they were slower, less consistent, and less confident when denying psychological properties than when denying physiological properties. These patterns were observed both in a predominantly Christian population (Study 2) and a predominantly Hindu population (Study 3). Overall, we argue that God is conceptualized not as a person in general but as an agent in particular, attributed a mind by default but attributed a body only upon further consideration. Copyright © 2015 Cognitive Science Society, Inc.

Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons.

PubMed

Franzen, Delwen L; Gleiss, Sarah A; Berger, Christina; Kümpfbeck, Franziska S; Ammer, Julian J; Felmy, Felix

2015-01-15

Passive and active membrane properties determine the voltage responses of neurons. Within the auditory brain stem, refinements in these intrinsic properties during late postnatal development usually generate short integration times and precise action-potential generation. This developmentally acquired temporal precision is crucial for auditory signal processing. How the interactions of these intrinsic properties develop in concert to enable auditory neurons to transfer information with high temporal precision has not yet been elucidated in detail. Here, we show how the developmental interaction of intrinsic membrane parameters generates high firing precision. We performed in vitro recordings from neurons of postnatal days 9-28 in the ventral nucleus of the lateral lemniscus of Mongolian gerbils, an auditory brain stem structure that converts excitatory to inhibitory information with high temporal precision. During this developmental period, the input resistance and capacitance decrease, and action potentials acquire faster kinetics and enhanced precision. Depending on the stimulation time course, the input resistance and capacitance contribute differentially to action-potential thresholds. The decrease in input resistance, however, is sufficient to explain the enhanced action-potential precision. Alterations in passive membrane properties also interact with a developmental change in potassium currents to generate the emergence of the mature firing pattern, characteristic of coincidence-detector neurons. Cholinergic receptor-mediated depolarizations further modulate this intrinsic excitability profile by eliciting changes in the threshold and firing pattern, irrespective of the developmental stage. Thus our findings reveal how intrinsic membrane properties interact developmentally to promote temporally precise information processing. Copyright © 2015 the American Physiological Society.

Self-Assembling Nanoclay Diffusion Gels for Bioactive Osteogenic Microenvironments.

PubMed

Shi, Pujiang; Kim, Yang-Hee; Mousa, Mohamed; Sanchez, Roxanna Ramnarine; Oreffo, Richard O C; Dawson, Jonathan I

2018-06-17

Laponite nanoparticles have attracted attention in the tissue engineering field for their protein interactions, gel-forming properties, and, more recently, osteogenic bioactivity. Despite growing interest in the osteogenic properties of Laponite, the application of Laponite colloidal gels to host the osteogenic differentiation of responsive stem cell populations remains unexplored. Here, the potential to harness the gel-forming properties of Laponite to generate injectable bioactive microenvironments for osteogenesis is demonstrated. A diffusion/dialysis gelation method allows the rapid formation of stable transparent gels from injectable, thixotropic Laponite suspensions in physiological fluids. Upon contact with buffered saline or blood serum, nanoporous gel networks exhibiting, respectively, fivefold and tenfold increases in gel stiffness are formed due to the reorganization of nanoparticle interactions. Laponite diffusion gels are explored as osteogenic microenvironments for skeletal stem cell containing populations. Laponite films support cell adhesion, proliferation, and differentiation of human bone marrow stromal cells in 2D. Laponite gel encapsulation significantly enhances osteogenic protein expression compared with 3D pellet culture controls. In both 2D and 3D conditions, cell associated mineralization is strongly enhanced. This study demonstrates that Laponite diffusion gels offer considerable potential as biologically active and clinically relevant bone tissue engineering scaffolds. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The symbiosis with the arbuscular mycorrhizal fungus Rhizophagus irregularis drives root water transport in flooded tomato plants.

PubMed

Calvo-Polanco, Monica; Molina, Sonia; Zamarreño, Angel María; García-Mina, Jose María; Aroca, Ricardo

2014-05-01

It is known that the presence of arbuscular mycorrhizal fungi within the plant roots enhances the tolerance of the host plant to different environmental stresses, although the positive effect of the fungi in plants under waterlogged conditions has not been well studied. Tolerance of plants to flooding can be achieved through different molecular, physiological and anatomical adaptations, which will affect their water uptake capacity and therefore their root hydraulic properties. Here, we investigated the root hydraulic properties under non-flooded and flooded conditions in non-mycorrhizal tomato plants and plants inoculated with the arbuscular mycorrhizal fungus Rhizophagus irregularis. Only flooded mycorrhizal plants increased their root hydraulic conductivity, and this effect was correlated with a higher expression of the plant aquaporin SlPIP1;7 and the fungal aquaporin GintAQP1. There was also a higher abundance of the PIP2 protein phoshorylated at Ser280 in mycorrhizal flooded plants. The role of plant hormones (ethylene, ABA and IAA) in root hydraulic properties was also taken into consideration, and it was concluded that, in mycorrhizal flooded plants, ethylene has a secondary role regulating root hydraulic conductivity whereas IAA may be the key hormone that allows the enhancement of root hydraulic conductivity in mycorrhizal plants under low oxygen conditions.

A chemical genetic screen uncovers a small molecule enhancer of the N-acylethanolamine degrading enzyme, fatty acid amide hydrolase, in Arabidopsis

DOE PAGES

Khan, Bibi Rafeiza; Faure, Lionel; Chapman, Kent D.; ...

2017-01-23

N-Acylethanolamines (NAEs) are a group of fatty acid amides that play signaling roles in diverse physiological processes in eukaryotes. We used fatty acid amide hydrolase (FAAH) degrades NAE into ethanolamine and free fatty acid to terminate its signaling function. In animals, chemical inhibitors of FAAH for therapeutic treatment of pain and as tools to probe deeper into biochemical properties of FAAH. In a chemical genetic screen for small molecules that dampened the inhibitory effect of N-lauroylethanolamine (NAE 12:0) on Arabidopsis thaliana seedling growth, we identified 6-(2-methoxyphenyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3 H,6 H)-dione (or MDPD). MDPD alleviated the growth inhibitory effects of NAE 12:0, inmore » part by enhancing the enzymatic activity of Arabidopsis FAAH (AtFAAH). In vitro, biochemical assays showed that MDPD enhanced the apparent Vmax of AtFAAH but did not alter the affinity of AtFAAH for its NAE substrates. Furthermore, structural analogs of MDPD did not affect AtFAAH activity or dampen the inhibitory effect of NAE 12:0 on seedling growth indicating that MDPD is a specific synthetic chemical activator of AtFAAH. Our study demonstrates the feasibility of using an unbiased chemical genetic approach to identify new pharmacological tools for manipulating FAAH- and NAE-mediated physiological processes in plants.« less

Laser Nitriding of the Newly Developed Ti-20Nb-13Zr at.% Biomaterial Alloy to Enhance Its Mechanical and Corrosion Properties in Simulated Body Fluid

NASA Astrophysics Data System (ADS)

Hussein, M. A.; Kumar, A. Madhan; Yilbas, Bekir S.; Al-Aqeeli, N.

2017-11-01

Despite the widespread application of Ti alloy in the biomedical field, surface treatments are typically applied to improve its resistance to corrosion and wear. A newly developed biomedical Ti-20Nb-13Zr at.% alloy (TNZ) was laser-treated in nitrogen environment to improve its surface characteristics with corrosion protection performance. Surface modification of the alloy by laser was performed through a Nd:YAG laser. The structural and surface morphological alterations in the laser nitrided layer were investigated by XRD and a FE-SEM. The mechanical properties have been evaluated using nanoindentation for laser nitride and as-received samples. The corrosion protection behavior was estimated using electrochemical corrosion analysis in a physiological medium (SBF). The obtained results revealed the production of a dense and compact film of TiN fine grains (micro-/nanosize) with 9.1 µm below the surface. The mechanical assessment results indicated an improvement in the modulus of elasticity, hardness, and resistance of the formed TiN layer to plastic deformation. The electrochemical analysis exhibited that the surface protection performance of the laser nitrided TNZ substrates in the SBF could be considerably enhanced compared to that of the as-received alloy due to the presence of fine grains in the TiN layer resulting from laser nitriding. Furthermore, the untreated and treated Ti-20Nb-13Zr alloy exhibited higher corrosion resistance than the CpTi and Ti6Al4V commercial alloys. The improvements in the surface hardness and corrosion properties of Ti alloy in a simulated body obtained using laser nitriding make this approach a suitable candidate for enhancing the properties of biomaterials.

Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond

PubMed Central

D'hondt, Catheleyne; Iyyathurai, Jegan; Himpens, Bernard; Leybaert, Luc; Bultynck, Geert

2014-01-01

Intercellular communication in primary bovine corneal endothelial cells (BCECs) is mainly driven by the release of extracellular ATP through Cx43 hemichannels. Studying the characteristics of Ca2+-wave propagation in BCECs, an important form of intercellular communication, in response to physiological signaling events has led to the discovery of important insights in the functional properties and regulation of native Cx43 hemichannels. Together with ectopic expression models for Cx43 hemichannels and truncated/mutated Cx43 versions, it became very clear that loop/tail interactions play a key role in controlling the activity of Cx43 hemichannels. Interestingly, the negative regulation of Cx43 hemichannels by enhanced actin/myosin contractility seems to impinge upon loss of these loop/tail interactions essential for opening Cx43 hemichannels. Finally, these molecular insights have spurred the development of novel peptide tools that can selectively inhibit Cx43 hemichannels, but neither Cx43 gap junctions nor hemichannels formed by other Cx isoforms. These tools now set the stage to hunt for novel physiological functions for Cx43 hemichannels in primary cells and tissues and to tackle disease conditions associated with excessive, pathological Cx43-hemichannel openings. PMID:25309448

Caffeine and exercise.

PubMed

Paluska, Scott A

2003-08-01

Caffeine is the most commonly consumed drug in the world, and athletes frequently use it as an ergogenic aid. It improves performance and endurance during prolonged, exhaustive exercise. To a lesser degree it also enhances short-term, high-intensity athletic performance. Caffeine improves concentration, reduces fatigue, and enhances alertness. Habitual intake does not diminish caffeine's ergogenic properties. Several mechanisms have been proposed to explain the physiologic effects of caffeine, but adenosine receptor antagonism most likely accounts for the primary mode of action. It is relatively safe and has no known negative performance effects, nor does it cause significant dehydration or electrolyte imbalance during exercise. Routine caffeine consumption may cause tolerance or dependence, and abrupt discontinuation produces irritability, mood shifts, headache, drowsiness, or fatigue. Major sport governing bodies ban excessive use of caffeine, but current monitoring techniques are inadequate, and ethical dilemmas persist regarding caffeine intake by athletes.

Physiologically Low Oxygen Enhances Biomolecule Production and Stemness of Mesenchymal Stem Cell Spheroids

PubMed Central

Shearier, Emily; Xing, Qi; Qian, Zichen

2016-01-01

Multicellular human mesenchymal stem cell (hMSC) spheroids have been demonstrated to be valuable in a variety of applications, including cartilage regeneration, wound healing, and neoangiogenesis. Physiological relevant low oxygen culture can significantly improve in vitro hMSC expansion by preventing cell differentiation. We hypothesize that hypoxia-cultured hMSC spheroids can better maintain the regenerative properties of hMSCs. In this study, hMSC spheroids were fabricated using hanging drop method and cultured under 2% O2 and 20% O2 for up to 96 h. Spheroid diameter and viability were examined, as well as extracellular matrix (ECM) components and growth factor levels between the two oxygen tensions at different time points. Stemness was measured among the spheroid culture conditions and compared to two-dimensional cell cultures. Spheroid viability and structural integrity were studied using different needle gauges to ensure no damage would occur when implemented in vivo. Spheroid attachment and integration within a tissue substitute were also demonstrated. The results showed that a three-dimensional hMSC spheroid cultured at low oxygen conditions can enhance the production of ECM proteins and growth factors, while maintaining the spheroids' stemness and ability to be injected, attached, and potentially be integrated within a tissue. PMID:26830500

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

Khan, Bibi Rafeiza; Faure, Lionel; Chapman, Kent D.

N-Acylethanolamines (NAEs) are a group of fatty acid amides that play signaling roles in diverse physiological processes in eukaryotes. We used fatty acid amide hydrolase (FAAH) degrades NAE into ethanolamine and free fatty acid to terminate its signaling function. In animals, chemical inhibitors of FAAH for therapeutic treatment of pain and as tools to probe deeper into biochemical properties of FAAH. In a chemical genetic screen for small molecules that dampened the inhibitory effect of N-lauroylethanolamine (NAE 12:0) on Arabidopsis thaliana seedling growth, we identified 6-(2-methoxyphenyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3 H,6 H)-dione (or MDPD). MDPD alleviated the growth inhibitory effects of NAE 12:0, inmore » part by enhancing the enzymatic activity of Arabidopsis FAAH (AtFAAH). In vitro, biochemical assays showed that MDPD enhanced the apparent Vmax of AtFAAH but did not alter the affinity of AtFAAH for its NAE substrates. Furthermore, structural analogs of MDPD did not affect AtFAAH activity or dampen the inhibitory effect of NAE 12:0 on seedling growth indicating that MDPD is a specific synthetic chemical activator of AtFAAH. Our study demonstrates the feasibility of using an unbiased chemical genetic approach to identify new pharmacological tools for manipulating FAAH- and NAE-mediated physiological processes in plants.« less

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization

NASA Astrophysics Data System (ADS)

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-05-01

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting molecules within a crowded microenvironment. The excluded volume effect (arising from crowding) increases the effective concentration of actin, which increases the reaction rate, while the microviscosity does not increase sufficiently to lower the reaction rate. This study reveals finer details about the mechanism of MMC.

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization.

PubMed

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-04-30

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting molecules within a crowded microenvironment. The excluded volume effect (arising from crowding) increases the effective concentration of actin, which increases the reaction rate, while the microviscosity does not increase sufficiently to lower the reaction rate. This study reveals finer details about the mechanism of MMC.

Performance enhancement for audio-visual speaker identification using dynamic facial muscle model.

PubMed

Asadpour, Vahid; Towhidkhah, Farzad; Homayounpour, Mohammad Mehdi

2006-10-01

Science of human identification using physiological characteristics or biometry has been of great concern in security systems. However, robust multimodal identification systems based on audio-visual information has not been thoroughly investigated yet. Therefore, the aim of this work to propose a model-based feature extraction method which employs physiological characteristics of facial muscles producing lip movements. This approach adopts the intrinsic properties of muscles such as viscosity, elasticity, and mass which are extracted from the dynamic lip model. These parameters are exclusively dependent on the neuro-muscular properties of speaker; consequently, imitation of valid speakers could be reduced to a large extent. These parameters are applied to a hidden Markov model (HMM) audio-visual identification system. In this work, a combination of audio and video features has been employed by adopting a multistream pseudo-synchronized HMM training method. Noise robust audio features such as Mel-frequency cepstral coefficients (MFCC), spectral subtraction (SS), and relative spectra perceptual linear prediction (J-RASTA-PLP) have been used to evaluate the performance of the multimodal system once efficient audio feature extraction methods have been utilized. The superior performance of the proposed system is demonstrated on a large multispeaker database of continuously spoken digits, along with a sentence that is phonetically rich. To evaluate the robustness of algorithms, some experiments were performed on genetically identical twins. Furthermore, changes in speaker voice were simulated with drug inhalation tests. In 3 dB signal to noise ratio (SNR), the dynamic muscle model improved the identification rate of the audio-visual system from 91 to 98%. Results on identical twins revealed that there was an apparent improvement on the performance for the dynamic muscle model-based system, in which the identification rate of the audio-visual system was enhanced from 87 to 96%.

Competitive resource allocation to metabolic pathways contributes to overflow metabolisms and emergent properties in cross-feeding microbial consortia.

PubMed

Carlson, Ross P; Beck, Ashley E; Phalak, Poonam; Fields, Matthew W; Gedeon, Tomas; Hanley, Luke; Harcombe, William R; Henson, Michael A; Heys, Jeffrey J

2018-04-17

Resource scarcity is a common stress in nature and has a major impact on microbial physiology. This review highlights microbial acclimations to resource scarcity, focusing on resource investment strategies for chemoheterotrophs from the molecular level to the pathway level. Competitive resource allocation strategies often lead to a phenotype known as overflow metabolism; the resulting overflow byproducts can stabilize cooperative interactions in microbial communities and can lead to cross-feeding consortia. These consortia can exhibit emergent properties such as enhanced resource usage and biomass productivity. The literature distilled here draws parallels between in silico and laboratory studies and ties them together with ecological theories to better understand microbial stress responses and mutualistic consortia functioning. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Effect of the side chain spacer structure on the pH-responsive properties of polycarboxylates.

PubMed

Harada, Atsushi; Teranishi, Ryoma; Yuba, Eiji; Kono, Kenji

The properties of stimuli-responsive polymers change significantly with changes to their environment, such as temperature and pH. This behavior can be utilized for the preparation of stimuli-responsive carriers for efficient cytosolic delivery of active drugs. Among the possible environmental conditions, pH is one of the most useful stimuli because the pH in an endosome is lower than under physiological conditions, depending on endosomal development. This pH difference is an important factor in the design of pH-responsive polymers, which can be used to enhance the transport of endocytosed drugs from the endosomal compartment to the cytoplasm. Such polymers can destabilize the endosomal bilayer under mildly acidic conditions and be nondisruptive at pH 7.4 not only for efficient endosomal escape but also for the suppression of nonspecific interaction with lipids existing under physiological conditions. In this study, we developed polycarboxylates with well-controlled pH-responsive properties bearing various spacer structures with different hydrophobicity. 3-methyl glutarylated polyallylamine and 2-carboxy-cyclohexanoylated polyallylamine were synthesized through the reaction between primary amine of PAA and acid anhydrides. Side chain spacers with higher hydrophobicity induced significant interactions with liposomal membranes at higher pH. pH-destabilizing liposomes could be modulated through the changing the composition of spacer structures with different hydrophobicity. Such formulations may represent an attractive strategy for the improvement of cytosolic delivery of active molecules.

Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum

PubMed Central

Oh, Myoung Jin; Cho, Young Hoon; Cha, So Yoon; Lee, Eun Ok; Kim, Jin Wook; Kim, Sun Ki; Park, Chang Seo

2017-01-01

Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer. PMID:28979153

Development of simulation interfaces for evaluation task with the use of physiological data and virtual reality applied to a vehicle simulator

NASA Astrophysics Data System (ADS)

Miranda, Mateus R.; Costa, Henrik; Oliveira, Luiz; Bernardes, Thiago; Aguiar, Carla; Miosso, Cristiano; Oliveira, Alessandro B. S.; Diniz, Alberto C. G. C.; Domingues, Diana Maria G.

2015-03-01

This paper aims at describing an experimental platform used to evaluate the performance of individuals at training immersive physiological games. The platform proposed is embedded in an immersive environment in a CAVE of Virtual Reality and consists on a base frame with actuators with three degrees of freedom, sensor array interface and physiological sensors. Physiological data of breathing, galvanic skin resistance (GSR) and pressure on the hand of the user and a subjective questionnaire were collected during the experiments. The theoretical background used in a project focused on Software Engineering, Biomedical Engineering in the field of Ergonomics and Creative Technologies in order to presents this case study, related of an evaluation of a vehicular simulator located inside the CAVE. The analysis of the simulator uses physiological data of the drivers obtained in a period of rest and after the experience, with and without movements at the simulator. Also images from the screen are captured through time at the embedded experience and data collected through physiological data visualization (average frequency and RMS graphics). They are empowered by the subjective questionnaire as strong lived experience provided by the technological apparatus. The performed immersion experience inside the CAVE allows to replicate behaviors from physical spaces inside data space enhanced by physiological properties. In this context, the biocybrid condition is expanded beyond art and entertainment, as it is applied to automotive engineering and biomedical engineering. In fact, the kinesthetic sensations amplified by synesthesia replicates the sensation of displacement in the interior of an automobile, as well as the sensations of vibration and vertical movements typical of a vehicle, different speeds, collisions, etc. The contribution of this work is the possibility to tracing a stress analysis protocol for drivers while operating a vehicle getting affective behaviors coming from physiological data, mixed to embedded simulation in Mixed Reality.

Interactive effects of phosphorus deficiency and exogenous auxin on root morphological and physiological traits in white lupin (Lupinus albus L.).

PubMed

Tang, Hongliang; Shen, Jianbo; Zhang, Fusuo; Rengel, Zed

2013-04-01

White lupin (Lupinus albus) exhibits strong root morphological and physiological responses to phosphorus (P) deficiency and auxin treatments, but the interactive effects of P and auxin in regulating root morphological and physiological traits are not fully understood. This study aimed to assess white lupin root traits as influenced by P (0 or 250 μmol L(-1)) and auxin (10(-8) mol L(-1) NAA) in nutrient solution. Both P deficiency and auxin treatments significantly altered root morphological traits, as evidenced by reduced taproot length, increased number and density of first-order lateral roots, and enhanced cluster-root formation. Changes in root physiological traits were also observed, i.e., increased proton, citrate, and acid phosphatase exudation. Exogenous auxin enhanced root responses and sensitivity to P deficiency. A significant interplay exists between P and auxin in the regulation of root morphological and physiological traits. Principal component analysis showed that P availability explained 64.8% and auxin addition 21.3% of the total variation in root trait parameters, indicating that P availability is much more important than auxin in modifying root responses of white lupin. This suggests that white lupin can coordinate root morphological and physiological responses to enhance acquisition of P resources, with an optimal trade-off between root morphological and physiological traits regulated by external stimuli such as P availability and auxin.

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

Nguyen, Thao D.; Grazier, John Mark; Boyce, Brad Lee

Biological tissues are uniquely structured materials with technologically appealing properties. Soft tissues such as skin, are constructed from a composite of strong fibrils and fluid-like matrix components. This was the first coordinated experimental/modeling project at Sandia or in the open literature to consider the mechanics of micromechanically-based anisotropy and viscoelasticity of soft biological tissues. We have exploited and applied Sandia's expertise in experimentation and mechanics modeling to better elucidate the behavior of collagen fibril-reinforced soft tissues. The purpose of this project was to provide a detailed understanding of the deformation of ocular tissues, specifically the highly structured skin-like tissue inmore » the cornea. This discovery improved our knowledge of soft/complex materials testing and modeling. It also provided insight into the way that cornea tissue is bio-engineered such that under physiologically-relevant conditions it has a unique set of properties which enhance functionality. These results also provide insight into how non-physiologic loading conditions, such as corrective surgeries, may push the cornea outside of its natural design window, resulting in unexpected non-linear responses. Furthermore, this project created a clearer understanding of the mechanics of soft tissues that could lead to bio-inspired materials, such as highly supple and impact resistant body armor, and improve our design of human-machine interfaces, such as micro-electrical-mechanical (MEMS) based prosthetics.« less

Vibrational spectroscopy and microscopic imaging: novel approaches for comparing barrier physical properties in native and human skin equivalents.

PubMed

Yu, Guo; Zhang, Guojin; Flach, Carol R; Mendelsohn, Richard

2013-06-01

Vibrational spectroscopy and imaging have been used to compare barrier properties in human skin, porcine skin, and two human skin equivalents, Epiderm 200X with an enhanced barrier and Epiderm 200 with a normal barrier. Three structural characterizations were performed. First, chain packing and conformational order were compared in isolated human stratum corneum (SC), isolated porcine SC, and in the Epiderm 200X surface layers. The infrared (IR) spectrum of isolated human SC revealed a large proportion of orthorhombically packed lipid chains at physiological temperatures along with a thermotropic phase transition to a state with hexagonally packed chains. In contrast, the lipid phase at physiological temperatures in both porcine SC and in Epiderm 200X, although dominated by conformationally ordered chains, lacked significant levels of orthorhombic subcell packing. Second, confocal Raman imaging of cholesterol bands showed extensive formation of cholesterol-enriched pockets within the human skin equivalents (HSEs). Finally, IR imaging tracked lipid barrier dimensions as well as the spatial disposition of ordered lipids in human SC and Epiderm 200X. These approaches provide a useful set of experiments for exploring structural differences between excised human skin and HSEs, which in turn may provide a rationale for the functional differences observed among these preparations.

Engineering mechanical gradients in next generation biomaterials - Lessons learned from medical textile design.

PubMed

Ng, Joanna L; Collins, Ciara E; Knothe Tate, Melissa L

2017-07-01

Nonwoven and textile membranes have been applied both externally and internally to prescribe boundary conditions for medical conditions as diverse as oedema and tissue defects. Incorporation of mechanical gradients in next generation medical membrane design offers great potential to enhance function in a dynamic, physiological context. Yet the gradient properties and resulting mechanical performance of current membranes are not well described. To bridge this knowledge gap, we tested and compared the mechanical properties of bounding membranes used in both external (compression sleeves for oedema, exercise bands) and internal (surgical membranes) physiological contexts. We showed that anisotropic compression garment textiles, isotropic exercise bands and surgical membranes exhibit similar ranges of resistance to tension under physiologic strains. However, their mechanical gradients and resulting stress-strain relationships show differences in work capacity and energy expenditure. Exercise bands' moduli of elasticity and respective thicknesses allow for controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. In contrast, the gradients intrinsic to compression sleeve design exhibit gaps in the middle range (1-5N) of physiological strains and also inconsistencies along the length of the sleeve, resulting in less than optimal performance of these devices. These current shortcomings in compression textile and garment design may be addressed in the future through implementation of novel approaches. For example, patterns, fibre compositions, and fibre anisotropy can be incorporated into biomaterial design to achieve seamless mechanical gradients in structure and resulting dynamic function, which would be particularly useful in physiological contexts. These concepts can be applied further to biomaterial design to deliver pressure gradients during movement of oedematous limbs (compression garments) and facilitate transport of molecules and cells during tissue genesis within tissue defects (surgical membranes). External and internal biomaterial membranes prescribe boundary conditions for treatment of medical disorders, from oedema to tissue defects. Studies are needed to guide the design of next generation biomaterials and devices that incorporate gradient engineering approaches, which offer great potential to enhance function in a dynamic and physiological context. Mechanical gradients intrinsic to currently implemented biomaterials such as medical textiles and surgical interface membranes are poorly understood. Here we characterise quantitatively the mechanics of textile and nonwoven biomaterial membranes for external and internal use. The lack of seamless gradients in compression medical textiles contrasts with the graded mechanical effects achieved by elastomeric exercise bands, which are designed to deliver controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. Engineering textiles with a prescient choice of fibre composition/size, type of knit/weave and inlay fibres, and weave density/anisotropy will enable creation of fabrics that can deliver spatially and temporally controlled mechanical gradients to maintain force balances at tissue boundaries, e.g. to treat oedema or tissue defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

PubMed

Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

2016-10-14

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure-Function Relations in Physiology Education: Where's the Mechanism?

ERIC Educational Resources Information Center

Lira, Matthew E.; Gardner, Stephanie M.

2017-01-01

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such…

Implementation of physiological fluids to provide insight into the characterization, fate, and biological interactions of silver nanoparticles.

PubMed

Breitner, Emily K; Burns, Katherine E; Hussain, Saber M; Comfort, Kristen K

2018-06-22

Silver nanoparticles (AgNPs) are being increasingly utilized in consumer and medical applications. However, there remains conflicting reports on their safety, which are evaluated through a combination of in vitro and in vivo exposure models. These discrepancies may arise, in part, due to the inherent differences between cell-based and animal systems. It is well established that nanotoxicological effects are highly dependent on the unique physicochemical properties and behavior of the particle set, including size, surface chemistry, agglomeration, and ionic dissolution. However, recent studies have identified that these properties vary as a function of exposure environment; providing a rationale for the contradictory results between in vitro and in vivo assessments. Artificial physiological fluids are emerging as a powerful tool as they allow for the characterization of NPs in an environment which they would likely encounter in vivo, in addition to having the experimental advantages of flexibility and consistency. Here, we demonstrated that the utilization of artificial fluids provided a mechanism to assess AgNP behavior and induced bioresponses in environments that they would likely encounter in vivo. AgNPs were introduced within an alveolar-based exposure model, which included alveolar epithelial (A549) cells incubated within artificial alveolar fluid (AF). Additionally, the particles underwent extensive characterization within both AF and lysosomal fluid, which the AgNPs would encounter following cellular internalization. Following incubation in physiological environments AgNP properties were significantly modified versus a traditional media environment, including alterations to both extent of agglomeration and rate of ionic dissolution. Moreover, when A549s were exposed to AgNPs in AF, the cells displayed lower cytotoxicity and stress rates, corresponding to a fluid-dependent drop in silver ion production. This work highlights the need for enhanced in vitro models that more closely mimic in vivo exposure environments in order to capture true NP behaviors and cellular interactions.

Implementation of physiological fluids to provide insight into the characterization, fate, and biological interactions of silver nanoparticles

NASA Astrophysics Data System (ADS)

Breitner, Emily K.; Burns, Katherine E.; Hussain, Saber M.; Comfort, Kristen K.

2018-06-01

Silver nanoparticles (AgNPs) are being increasingly utilized in consumer and medical applications. However, there remains conflicting reports on their safety, which are evaluated through a combination of in vitro and in vivo exposure models. These discrepancies may arise, in part, due to the inherent differences between cell-based and animal systems. It is well established that nanotoxicological effects are highly dependent on the unique physicochemical properties and behavior of the particle set, including size, surface chemistry, agglomeration, and ionic dissolution. However, recent studies have identified that these properties vary as a function of exposure environment; providing a rationale for the contradictory results between in vitro and in vivo assessments. Artificial physiological fluids are emerging as a powerful tool as they allow for the characterization of NPs in an environment which they would likely encounter in vivo, in addition to having the experimental advantages of flexibility and consistency. Here, we demonstrated that the utilization of artificial fluids provided a mechanism to assess AgNP behavior and induced bioresponses in environments that they would likely encounter in vivo. AgNPs were introduced within an alveolar-based exposure model, which included alveolar epithelial (A549) cells incubated within artificial alveolar fluid (AF). Additionally, the particles underwent extensive characterization within both AF and lysosomal fluid, which the AgNPs would encounter following cellular internalization. Following incubation in physiological environments AgNP properties were significantly modified versus a traditional media environment, including alterations to both extent of agglomeration and rate of ionic dissolution. Moreover, when A549s were exposed to AgNPs in AF, the cells displayed lower cytotoxicity and stress rates, corresponding to a fluid-dependent drop in silver ion production. This work highlights the need for enhanced in vitro models that more closely mimic in vivo exposure environments in order to capture true NP behaviors and cellular interactions.

Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma.

PubMed

Pillai, Krishna; Akhter, Javed; Chua, Terence C; Morris, David Lawson

2013-05-01

Bromelain is a mixture of proteolytic enzymes that is capable of hydrolyzing glycosidic linkages in glycoprotein. Glycoprotein's are ubiquitously distributed throughout the body and serve a variety of physiologic functions. Faulty glycosylation of proteins may lead to cancer. Antitumor properties of bromelain have been demonstrated in both, in vitro and in vivo studies, along with scanty anecdotal human studies. Various mechanistic pathways have been proposed to explain the anticancer properties of bromelain. However, proteolysis by bromelain has been suggested as a main pathway by some researchers. MUC1 is a glycoprotein that provides tumor cells with invasive, metastatic, and chemo-resistant properties. To date, there is no study that examines the effect of bromelain on MUC1. However, the viability of MUC1 expressing pancreatic and breast cancer cells are adversely affected by bromelain. Further, the efficacy of cisplatin and 5-FU are enhanced by adjuvant treatment with bromelain, indicating that the barrier function of MUC1 may be affected. Other studies have also indicated that there is a greater accumulation of 5-FU in the cell compartment on treatment with 5-FU and bromelain. Malignant peritoneal mesothelioma (MPM) expresses MUC1 and initial studies have shown that the viability of MPM cells is adversely affected by exposure to bromelain. Further, bromelain in combination with either 5-FU or cisplatin, the efficacy of the chemotherapeutic drug is enhanced. Hence, current evidence indicates that bromelain may have the potential of being developed into an effective anticancer agent for MPM.

Neurophysiology and neural engineering: a review.

PubMed

Prochazka, Arthur

2017-08-01

Neurophysiology is the branch of physiology concerned with understanding the function of neural systems. Neural engineering (also known as neuroengineering) is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, enhance, or otherwise exploit the properties and functions of neural systems. In most cases neural engineering involves the development of an interface between electronic devices and living neural tissue. This review describes the origins of neural engineering, the explosive development of methods and devices commencing in the late 1950s, and the present-day devices that have resulted. The barriers to interfacing electronic devices with living neural tissues are many and varied, and consequently there have been numerous stops and starts along the way. Representative examples are discussed. None of this could have happened without a basic understanding of the relevant neurophysiology. I also consider examples of how neural engineering is repaying the debt to basic neurophysiology with new knowledge and insight. Copyright © 2017 the American Physiological Society.

Genomics of Actinobacteria: Tracing the Evolutionary History of an Ancient Phylum†

PubMed Central

Ventura, Marco; Canchaya, Carlos; Tauch, Andreas; Chandra, Govind; Fitzgerald, Gerald F.; Chater, Keith F.; van Sinderen, Douwe

2007-01-01

Summary: Actinobacteria constitute one of the largest phyla among Bacteria and represent gram-positive bacteria with a high G+C content in their DNA. This bacterial group includes microorganisms exhibiting a wide spectrum of morphologies, from coccoid to fragmenting hyphal forms, as well as possessing highly variable physiological and metabolic properties. Furthermore, Actinobacteria members have adopted different lifestyles, and can be pathogens (e.g., Corynebacterium, Mycobacterium, Nocardia, Tropheryma, and Propionibacterium), soil inhabitants (Streptomyces), plant commensals (Leifsonia), or gastrointestinal commensals (Bifidobacterium). The divergence of Actinobacteria from other bacteria is ancient, making it impossible to identify the phylogenetically closest bacterial group to Actinobacteria. Genome sequence analysis has revolutionized every aspect of bacterial biology by enhancing the understanding of the genetics, physiology, and evolutionary development of bacteria. Various actinobacterial genomes have been sequenced, revealing a wide genomic heterogeneity probably as a reflection of their biodiversity. This review provides an account of the recent explosion of actinobacterial genomics data and an attempt to place this in a biological and evolutionary context. PMID:17804669

Charge transfer in trans-combretastatins

NASA Astrophysics Data System (ADS)

Holzmann, Nicole; Bernasconi, Leonardo; Callaghan, Kathrin M.; Bisby, Roger H.; Parker, Anthony W.

2018-01-01

The non-toxic trans isomer of combretastatin-A4 can be photoisomerised in physiological conditions to cis-CA4, a potential anticancer drug. Absorption at wavelengths with high tissue penetration can be achieved by functionalization with substituents influencing the degree of charge-transfer (CT) of the S1 state, in which the isomerisation occurs. We present a TDDFT study of the excited state properties of a series of substituted combretastatins with various degrees of CT character. Increasing the CT character determines a redshift of absorption and an intensity enhancement, but it disfavours the isomerisation. An appropriate choice of substituents is therefore required to achieve optimal isomerisation conditions.

Enhanced thermogenesis in rats by Panax ginseng, multivitamins and minerals

NASA Astrophysics Data System (ADS)

Kumar, Ratan; Grover, S. K.; Divekar, H. M.; Gupta, A. K.; Shyam, Radhey; Srivastava, K. K.

1996-12-01

Substances which enhance endurance for physical and mental work and increase non-specific resistance to stress during a prolonged stay in physiologically adverse habitats are called ‘adaptogens’. Panax ginseng is well known for its anti-stress and adaptogenic properties. In the present study, adaptogenic activity by the intake of a herbo-vitamin-mineral preparation (HVMP) containing P. ginseng and multivitamin-mineral preparation (MVMP) was evaluated using the cold-hypoxia-restrained (C-H-R) animal model. The aim was to determine whether the cold tolerance and recovery from acute hypothermia mediated by P. ginseng was modified by simultaneous intake of additional vitamins and minerals. Results suggest that the adaptogenic effect of HVMP was more or less the sum total of its two components P. ginseng and MVMP. In HVMP, P. ginseng was found to be effective for developing resistance to cooling and MVMP helped in stimulating faster recovery from acute hypothermia.

Plant ecdysteroids: plant sterols with intriguing distributions, biological effects and relations to plant hormones.

PubMed

Tarkowská, Danuše; Strnad, Miroslav

2016-09-01

The present review summarises current knowledge of phytoecdysteroids' biosynthesis, distribution within plants, biological importance and relations to plant hormones. Plant ecdysteroids (phytoecdysteroids) are natural polyhydroxylated compounds that have a four-ringed skeleton, usually composed of either 27 carbon atoms or 28-29 carbon atoms (biosynthetically derived from cholesterol or other plant sterols, respectively). Their physiological roles in plants have not yet been confirmed and their occurrence is not universal. Nevertheless, they are present at high concentrations in various plant species, including commonly consumed vegetables, and have a broad spectrum of pharmacological and medicinal properties in mammals, including hepatoprotective and hypoglycaemic effects, and anabolic effects on skeletal muscle, without androgenic side-effects. Furthermore, phytoecdysteroids can enhance stress resistance by promoting vitality and enhancing physical performance; thus, they are considered adaptogens. This review summarises current knowledge of phytoecdysteroids' biosynthesis, distribution within plants, biological importance and relations to plant hormones.

Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

PubMed

Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P; Güler, Ali D; Wanat, Matthew J; Roller, Bryan A; La Torre, Anna; Amieux, Paul S; McKnight, G Stanley; Bamford, Nigel S; Palmiter, Richard D

2012-11-01

The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

[Meteoadaptogenic properties of peptide drugs in healthy volunteers].

PubMed

Shabanov, P D; Ganapol'skiĭ, V P; Aleksandrov, P V

2007-01-01

The meteoadaptogenic properties of a series of drugs with peptide (cortexin, noopept, dilept) and nonpeptide (vinpotropil) structure were investigated in a climate thermobarocomplex (Tabay, Japan) on a group of healthy volunteers aged 20-24. All the studied drugs produced a meteoadaptogenic action, the extent of which depended on the environmental test conditions (overcooling, overheating, hypobaric hypoxia). Vinpotropil, optimizing a physiological component of the functional state, can be recommended as a meteoadaptogen for both cold and hot climate as well as for hypobaric hypoxia, where it improved the psychological component of the functional state. Cortexin is qualified as an adaptogen and actoprotector only for hypobaric hypoxia conditions (uplands). Noopept, affecting positively a psychological component of the functional state, can be used for rapid adaptation to both cold and hot climate. In the hot climate, noopept also enhanced the physical work capacity. Dilept mostly elevated the psychological component of the functional state and can be considered as a psychomotor enhancer and adaptogen. Therefore, all the drugs studied (vinpotropil, cortexin, noopept and dilept) can be recommended as the agents producing activation, support and recovery of the physical and psychological efficiency under rapidly changing environment conditions.

Development of Biodegradable Poly(citrate)-Polyhedral Oligomeric Silsesquioxanes Hybrid Elastomers with High Mechanical Properties and Osteogenic Differentiation Activity.

PubMed

Du, Yuzhang; Yu, Meng; Chen, Xiaofeng; Ma, Peter X; Lei, Bo

2016-02-10

Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.

Electrospun microcrimped fibers with nonlinear mechanical properties enhance ligament fibroblast phenotype.

PubMed

Grace Chao, Pen-hsiu; Hsu, Hsiang-Yi; Tseng, Hsiao-Yun

2014-09-01

Fiber structure and order greatly impact the mechanical behavior of fibrous materials. In biological tissues, the nonlinear mechanics of fibrous scaffolds contribute to the functionality of the material. The nonlinear mechanical properties of the wavy structure (crimp) in collagen allow tissue flexibility while preventing over-extension. A number of approaches have tried to recreate this complex mechanical functionality. We generated microcrimped fibers by briefly heating electrospun parallel fibers over the glass transition temperature or by ethanol treatment. The crimp structure is similar to those of collagen fibers found in native aorta, intestines, or ligaments. Using poly-L-lactic acid fibers, we demonstrated that the bulk materials exhibit changed stress-strain behaviors with a significant increase in the toe region in correlation to the degree of crimp, similar to those observed in collagenous tissues. In addition to mimicking the stress-strain behavior of biological tissues, the microcrimped fibers are instructive in cell morphology and promote ligament phenotypic gene expression. This effect can be further enhanced by dynamic tensile loading, a physiological perturbation in vivo. This rapid and economical approach for microcrimped fiber production provides an accessible platform to study structure-function relationships and a novel functional scaffold for tissue engineering and cell mechanobiology studies.

Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro.

PubMed

McCord, Amy M; Jamal, Muhammad; Shankavaram, Uma T; Shankavarum, Uma T; Lang, Frederick F; Camphausen, Kevin; Tofilon, Philip J

2009-04-01

In vitro investigations of tumor stem-like cells (TSC) isolated from human glioblastoma (GB) surgical specimens have been done primarily at an atmospheric oxygen level of 20%. To determine whether an oxygen level more consistent with in situ conditions affects their stem cell-like characteristics, we compared GB TSCs grown under conditions of 20% and 7% oxygen. Growing CD133(+) cells sorted from three GB neurosphere cultures at 7% O(2) reduced their doubling time and increased the self-renewal potential as reflected by clonogenicity. Furthermore, at 7% oxygen, the cultures exhibited an enhanced capacity to differentiate along both the glial and neuronal pathways. As compared with 20%, growth at 7% oxygen resulted in an increase in the expression levels of the neural stem cell markers CD133 and nestin as well as the stem cell markers Oct4 and Sox2. In addition, whereas hypoxia inducible factor 1alpha was not affected in CD133(+) TSCs grown at 7% O(2), hypoxia-inducible factor 2alpha was expressed at higher levels as compared with 20% oxygen. Gene expression profiles generated by microarray analysis revealed that reducing oxygen level to 7% resulted in the up-regulation and down-regulation of a significant number of genes, with more than 140 being commonly affected among the three CD133(+) cultures. Furthermore, Gene Ontology categories up-regulated at 7% oxygen included those associated with stem cells or GB TSCs. Thus, the data presented indicate that growth at the more physiologically relevant oxygen level of 7% enhances the stem cell-like phenotype of CD133(+) GB cells.

Biofilm based attached cultivation technology for microalgal biorefineries-A review.

PubMed

Wang, Junfeng; Liu, Wen; Liu, Tianzhong

2017-11-01

The attached cultivation for microalga has many superiorities over the conventional aqua-suspend methods, which make it a promising pathway to supply feedstock for microalgae based bio-refinery attempts. In this review, the current reports on bioreactor, application, modeling, substratum material and engineering aspects were summarized and the future research and developments should be focused on the following aspects: 1) Build principles and guidelines for rational structure design by studying the relationship of physiological properties with typical structures and light regimes; 2) Set up theory foundation of substratum material selection by studying the physic-chemical properties of algal cells and substratum materials; 3) Further understanding the mass transfer behaviors of both CO 2 and nutrients in biofilm for enhanced growth rate and products accumulation; 4) New equipment and machines for inoculation, harvesting and moisture keeping should be developed and integrated with bioreactor structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyaluronan-Inorganic Nanohybrid Materials for Biomedical Applications.

PubMed

Cai, Zhixiang; Zhang, Hongbin; Wei, Yue; Cong, Fengsong

2017-06-12

Nanomaterials, including gold, silver, and magnetic nanoparticles, carbon, and mesoporous materials, possess unique physiochemical and biological properties, thus offering promising applications in biomedicine, such as in drug delivery, biosensing, molecular imaging, and therapy. Recent advances in nanotechnology have improved the features and properties of nanomaterials. However, these nanomaterials are potentially cytotoxic and demonstrate a lack of cell-specific function. Thus, they have been functionalized with various polymers, especially polysaccharides, to reduce toxicity and improve biocompatibility and stability under physiological conditions. In particular, nanomaterials have been widely functionalized with hyaluronan (HA) to enhance their distribution in specific cells and tissues. This review highlights the most recent advances on HA-functionalized nanomaterials for biotechnological and biomedical applications, as nanocarriers in drug delivery, contrast agents in molecular imaging, and diagnostic agents in cancer therapy. A critical evaluation of barriers affecting the use of HA-functionalized nanomaterials is also discussed, and insights into the outlook of the field are explored.

Platelet-rich plasma: a biomimetic approach to enhancement of surgical wound healing.

PubMed

Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Cabrera, Fernando J; Barbosa, Zonia; Medrano Del Rosal, Guillermo; Weiner, Bradley K; Ellsworth, Warren A; Tasciotti, Ennio

2017-01-01

Platelets are small anucleate cytoplasmic cell bodies released by megakaryocytes in response to various physiologic triggers. Traditionally thought to be solely involved in the mechanisms of hemostasis, platelets have gained much attention due to their involvement wound healing, immunomodulation, and antiseptic properties. As the field of surgery continues to evolve so does the need for therapies to aid in treating the increasingly complex patients seen. With over 14 million obstetric, musculoskeletal, and urological and gastrointestinal surgeries performed annually, the healing of surgical wounds continues to be of upmost importance to the surgeon and patient. Platelet-rich plasma, or platelet concentrate, has emerged as a possible adjuvant therapy to aid in the healing of surgical wounds and injuries. In this review, we will discuss the wound healing properties of platelet-rich plasma and various surgical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Functional Groups on Biodegradation and Pre-osteoblastic Cell Response on the Plasma-Polymerized Magnesium Surface

NASA Astrophysics Data System (ADS)

Ko, Yeong-Mu; Lee, Kang; Kim, Byung-Hoon

2013-01-01

Magnesium (Mg) is light, has biocompatibility, and has mechanical properties close to those of natural bone. However, pure Mg severely corrodes in a physiological environment, which may result in fracture prior to substantial tissue healing. In this study, the Mg surface was modified by depositing a thin polymeric film containing COOH, NH2, and OH groups through plasma polymerization of acrylic acid, allyl amine, and allyl alcohol in order to improve its anticorrosion and bioactive properties. The -COOH group had a significant effect on bonelike apatite formation compared with -NH2 and -OH. It was also concluded that a bonelike-apatite formed COOH/Mg surface was more effective for reducing biodegradation rate than the other surfaces. The results of in vitro cell test revealed significantly enhanced cell proliferation and differentiation on the COOH/Mg and NH2/Mg surfaces compared with other surfaces.

Neuron-astrocyte signaling is preserved in the aging brain.

PubMed

Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

2017-04-01

Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley Periodicals, Inc.

Beyond the Printed Page: Physiology Education without a Textbook?

ERIC Educational Resources Information Center

Stavrianeas, Stasinos; Stewart, Mark; Harmer, Peter

2008-01-01

Pedagogical innovations, ideas, and outcomes designed to enhance student learning in physiology courses are encouraged by our professional organizations and are actively discussed at conferences and in "Advances in Physiological Education." Here, we report our experiment with freely available internet-based material as a substitute for the…

A Hybrid FPGA-Based System for EEG- and EMG-Based Online Movement Prediction.

PubMed

Wöhrle, Hendrik; Tabie, Marc; Kim, Su Kyoung; Kirchner, Frank; Kirchner, Elsa Andrea

2017-07-03

A current trend in the development of assistive devices for rehabilitation, for example exoskeletons or active orthoses, is to utilize physiological data to enhance their functionality and usability, for example by predicting the patient's upcoming movements using electroencephalography (EEG) or electromyography (EMG). However, these modalities have different temporal properties and classification accuracies, which results in specific advantages and disadvantages. To use physiological data analysis in rehabilitation devices, the processing should be performed in real-time, guarantee close to natural movement onset support, provide high mobility, and should be performed by miniaturized systems that can be embedded into the rehabilitation device. We present a novel Field Programmable Gate Array (FPGA) -based system for real-time movement prediction using physiological data. Its parallel processing capabilities allows the combination of movement predictions based on EEG and EMG and additionally a P300 detection, which is likely evoked by instructions of the therapist. The system is evaluated in an offline and an online study with twelve healthy subjects in total. We show that it provides a high computational performance and significantly lower power consumption in comparison to a standard PC. Furthermore, despite the usage of fixed-point computations, the proposed system achieves a classification accuracy similar to systems with double precision floating-point precision.

A Hybrid FPGA-Based System for EEG- and EMG-Based Online Movement Prediction

PubMed Central

Wöhrle, Hendrik; Tabie, Marc; Kim, Su Kyoung; Kirchner, Frank; Kirchner, Elsa Andrea

2017-01-01

A current trend in the development of assistive devices for rehabilitation, for example exoskeletons or active orthoses, is to utilize physiological data to enhance their functionality and usability, for example by predicting the patient’s upcoming movements using electroencephalography (EEG) or electromyography (EMG). However, these modalities have different temporal properties and classification accuracies, which results in specific advantages and disadvantages. To use physiological data analysis in rehabilitation devices, the processing should be performed in real-time, guarantee close to natural movement onset support, provide high mobility, and should be performed by miniaturized systems that can be embedded into the rehabilitation device. We present a novel Field Programmable Gate Array (FPGA) -based system for real-time movement prediction using physiological data. Its parallel processing capabilities allows the combination of movement predictions based on EEG and EMG and additionally a P300 detection, which is likely evoked by instructions of the therapist. The system is evaluated in an offline and an online study with twelve healthy subjects in total. We show that it provides a high computational performance and significantly lower power consumption in comparison to a standard PC. Furthermore, despite the usage of fixed-point computations, the proposed system achieves a classification accuracy similar to systems with double precision floating-point precision. PMID:28671632

A systematic review investigating measurement properties of physiological tests in rugby.

PubMed

Chiwaridzo, Matthew; Oorschot, Sander; Dambi, Jermaine M; Ferguson, Gillian D; Bonney, Emmanuel; Mudawarima, Tapfuma; Tadyanemhandu, Cathrine; Smits-Engelsman, Bouwien C M

2017-01-01

This systematic review was conducted with the first objective aimed at providing an overview of the physiological characteristics commonly evaluated in rugby and the corresponding tests used to measure each construct. Secondly, the measurement properties of all identified tests per physiological construct were evaluated with the ultimate purpose of identifying tests with strongest level of evidence per construct. The review was conducted in two stages. In all stages, electronic databases of EBSCOhost, Medline and Scopus were searched for full-text articles. Stage 1 included studies examining physiological characteristics in rugby. Stage 2 included studies evaluating measurement properties of all tests identified in Stage 1 either in rugby or related sports such as Australian Rules football and Soccer. Two independent reviewers screened relevant articles from titles and abstracts for both stages. Seventy studies met the inclusion criteria for Stage 1. The studies described 63 tests assessing speed (8), agility/change of direction speed (7), upper-body muscular endurance (8), upper-body muscular power (6), upper-body muscular strength (5), anaerobic endurance (4), maximal aerobic power (4), lower-body muscular power (3), prolonged high-intensity intermittent running ability/endurance (5), lower-body muscular strength (5), repeated high-intensity exercise performance (3), repeated-sprint ability (2), repeated-effort ability (1), maximal aerobic speed (1) and abdominal endurance (1). Stage 2 identified 20 studies describing measurement properties of 21 different tests. Only moderate evidence was found for the reliability of the 30-15 Intermittent Fitness. There was limited evidence found for the reliability and/or validity of 5 m, 10 m, 20 m speed tests, 505 test, modified 505 test, L run test, Sergeant Jump test and bench press repetitions-to-fatigue tests. There was no information from high-quality studies on the measurement properties of all the other tests identified in stage 1. A number of physiological characteristics are evaluated in rugby. Each physiological construct has multiple tests for measurement. However, there is paucity of information on measurement properties from high-quality studies for the tests. This raises questions about the usefulness and applicability of these tests in rugby and creates a need for high-quality future studies evaluating measurement properties of these physiological tests. PROSPERO CRD 42015029747.

Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds

PubMed Central

Subramony, Siddarth D.; Su, Amanda; Yeager, Keith; Lu, Helen H.

2014-01-01

Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation. PMID:24267271

Contrasting effects of non-starch polysaccharide and resistant starch-based diets on the disposition and excretion of the food carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), in a rat model.

PubMed

Ferguson, Lynnette R; Zhu, Shuotun; Kestell, Philip

2003-06-01

It has commonly been believed that increasing fibre in the diet should reduce the incidence of cancers, especially those of the colon and rectum. The earliest definitions of dietary fibre restricted the term to plant cell walls in which non-starch polysaccharides are key chemical components. However, new definitions encompass a wider range of materials, including starches resistant to digestion in the colon (resistant starches). Nevertheless, most definitions require that "dietary fibres" show physiological effects considered beneficial against cancer, including enhanced laxation and faecal bulking. On theoretical grounds, such properties might be expected to dilute the concentration of any carcinogen present and move it more rapidly through the colon, thereby reducing bioavailability. We have compared the properties of two dietary fibre preparations that are primarily non-starch polysaccharides with two resistant starch preparations for effects on carcinogen disposition in a rodent model. Although both preparations enhanced laxation and faecal bulking, only the non-starch polysaccharide preparation reduced carcinogen biovailability. Indeed, carcinogen biovailability was significantly enhanced by resistant starch. We suggest that there may be fundamental differences in the manner by which non-starch polysaccharides or resistant starches affect carcinogen disposition, and express concern that the events seen with the resistant starches [RS] are unlikely to be beneficial with respect to protection against cancer by exogenous carcinogens. Furthermore, the data reveal that the observation of enhanced laxation and faecal bulking does not necessarily imply a reduction in carcinogen bioavailability.

Electrophoretic deposition of colloidal particles on Mg with cytocompatibility, antibacterial performance, and corrosion resistance.

PubMed

Sun, Jiadi; Zhu, Ye; Meng, Long; Chen, Peng; Shi, Tiantian; Liu, Xiaoya; Zheng, Yufeng

2016-11-01

Magnesium (Mg) has recently received increasing attention due to its unique biological performance, including cytocompatibility, antibacterial and biodegradable properties. However, rapid corrosion in physiological environment and potential toxicity limits its clinical applications. To improve the corrosion resistance meanwhile not compromise other excellent performance, self-assembled colloidal particles were deposited onto magnesium surfaces in ethanol by a simple and effective electrophoretic deposition (EPD) method. The fabricated functional nanostructured coatings were investigated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analyses, and scanning electron microscopy (SEM). The electrochemical test, pH value, and Mg ion concentration data show that the corrosion resistance of Mg samples is enhanced appreciably after surface treatment. In vitro cellular response and antibacterial capability of the modified Mg substrates are performed. Significantly increased cell adhesion and viability are observed from the coated Mg samples, and the amounts of adherent bacteria on the treated Mg surfaces diminish remarkably compared to the bare Mg. Furthermore, the bare and coated Mg samples were implanted in New Zealand white rabbits for 12 weeks to examine the in vivo long-term corrosion performance and in situ inflammation behavior. The experiment results confirmed that compared with bare Mg substrate the corrosion and foreign-body reactions of the coated Mg samples were suppressed. The above results suggested that our coatings, which effectively enhance the biocompatibility, antimicrobial properties, and corrosion resistance of Mg substrate, provide a simple and practical strategy to expedite clinical acceptance of biodegradableMg and its alloys. Biomedical Mg metals have been considered as promising biodegradable implants because of their intended functions, such as cytocompatibility, antibacterial, and biodegradable properties. However, rapid corrosion in physiological environment limits their clinical applications. Alloying and surface coatings have been used to reduce the degradation rate. But this would compromise other excellent performance of Mg samples, including antibacterial and anti-inflammatory activity. Thus, while the rapid degradation of Mg samples must be solved, good antibacterial property and acceptable cytocompatibility are also necessary. In this study, polymer-based coatings were fabricated on Mg surfaces by electrophoretic deposition of poly(isobornyl acrylate-co-dimethylaminoethyl methacrylate)/tannic acid (P(ISA-co-DMA)/TA) colloidal particles. It suggested that the coating materials effectively improved the biocompatibility, antimicrobial behavior, and corrosion resistance of biomedical Mg. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Diffuse optical tomography and spectroscopy of breast cancer and fetal brain

NASA Astrophysics Data System (ADS)

Choe, Regine

Diffuse optical techniques utilize light in the near infrared spectral range to measure tissue physiology non-invasively. Based on these measurements, either on average or a three-dimensional spatial map of tissue properties such as total hemoglobin concentration, blood oxygen saturation and scattering can be obtained using model-based reconstruction algorithms. In this thesis, diffuse optical techniques were applied for in vivo breast cancer imaging and trans-abdominal fetal brain oxygenation monitoring. For in vivo breast cancer imaging, clinical diffuse optical tomography and related instrumentation was developed and used in several contexts. Bulk physiological properties were quantified for fifty-two healthy subjects in the parallel-plate transmission geometry. Three-dimensional images of breast were reconstructed for subjects with breast tumors and, tumor contrast with respect to normal tissue was found in total hemoglobin concentration and scattering and was quantified for twenty-two breast carcinomas. Tumor contrast and tumor volume changes during neoadjuvant chemotherapy were tracked for one subject and compared to the dynamic contrast-enhanced MRI. Finally, the feasibility for measuring blood flow of breast tumors using optical methods was demonstrated for seven subjects. In a qualitatively different set of experiments, the feasibility for trans-abdominal fetal brain oxygenation monitoring was demonstrated on pregnant ewes with induced fetal hypoxia. Preliminary clinical experiences were discussed to identify future directions. In total, this research has translated diffuse optical tomography techniques into clinical research environment.

Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

PubMed Central

Vu, Dung M.; Mendez, Heather M.; Jakhar, Shailja; Mukundan, Harshini

2017-01-01

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential for their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. The biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review. PMID:28677660

Color variation assay of the anthocyanins from Açai Fruit (Euterpe oleracea): a potential new dye for vitreoretinal surgery.

PubMed

Peris, Cristiane Siqueira; Badaro, Emmerson; Ferreira, Magno Antonio; Lima-Filho, Acácio Alves Souza; Ferreira, Eber Lopes; Maia, Andre; Rodrigues, Eduardo Buchele; Farah, Michel Eid; Maia, Maurício

2013-10-01

The goals of this study were to determine the potential for use of the natural anthocyanins from the açai fruit (Euterpe oleracea) during vitreoretinal surgery and the ideal physicochemical properties of the dye. We evaluated the color variations of the dye at different pHs and osmolarities with or without the use of mordants as a potential new tool for internal limiting membrane peeling. The extracts of anthocyanin from the açai fruit were analyzed by spectrophotometry to determine the degree of color variations associated with various pHs and osmolarities. The experiments were conducted in test tubes filled with tryptophan soya media and Petri dishes prepared with agar media. We observed various shades of green, red, and purple in the extracts of the anthocyanin dye at different pHs and osmolarities. The assay to adjust the anthocyanin solution similar to the physiologic retinal environment (osmolarity, 300 mOsm; pH, 7.00) resulted in a shade of purple that may be useful to stain the intraocular microstructures during vitreoretinal surgery. The physicochemical property of the purple anthocyanin solutions from the açai fruit was observed at physiologic pH and osmolarity. Anthocyanins from the açai fruit may be useful to enhance visualization of the intraocular microstructures during vitreoretinal surgery.

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

PubMed

Zhang, Rui Xue; Li, Jason; Zhang, Tian; Amini, Mohammad A; He, Chunsheng; Lu, Brian; Ahmed, Taksim; Lip, HoYin; Rauth, Andrew M; Wu, Xiao Yu

2018-05-01

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

A tale of two CLCs: biophysical insights toward understanding ClC-5 and ClC-7 function in endosomes and lysosomes

PubMed Central

Zifarelli, Giovanni

2015-01-01

Abstract The CLC protein family comprises both Cl− channels and H+-coupled anion transporters. The understanding of the critical role of CLC proteins in a number of physiological functions has greatly contributed to a revision of the classical paradigm that attributed to Cl− ions only a marginal role in human physiology. The endosomal ClC-5 and the lysosomal ClC-7 are the best characterized human CLC transporters. Their dysfunction causes Dent’s disease and osteopetrosis, respectively. It had been originally proposed that they would provide a Cl− shunt conductance allowing efficient acidification of intracellular compartments. However, this model seems to conflict with the transport properties of these proteins and with recent physiological evidence. Currently, there is no consensus on their specific physiological role. CLC proteins present also a number of peculiar biophysical properties, such as the dimeric architecture, the co-existence of intrinsically different thermodynamic modes of transport based on similar structural principles, and the gating mechanism recently emerging for the transporters, just to name a few. This review focuses on the biophysical properties and physiological roles of ClC-5 and ClC-7. PMID:26036722

The Role of Flipped Learning in Managing the Cognitive Load of a Threshold Concept in Physiology

ERIC Educational Resources Information Center

Akkaraju, Shylaja

2016-01-01

To help students master challenging, threshold concepts in physiology, I used the flipped learning model in a human anatomy and physiology course with very encouraging results in terms of student motivation, preparedness, engagement, and performance. The flipped learning model was enhanced by pre-training and formative assessments that provided…

Evaluating the influence of plant-specific physiological parameterizations on the partitioning of land surface energy fluxes

NASA Astrophysics Data System (ADS)

Sulis, Mauro; Langensiepen, Matthias; Shrestha, Prabhakar; Schickling, Anke; Simmer, Clemens; Kollet, Stefan

2015-04-01

Vegetation has a significant influence on the partitioning of radiative forcing, the spatial and temporal variability of soil water and soil temperature. Therefore plant physiological properties play a key role in mediating and amplifying interactions and feedback mechanisms in the soil-vegetation-atmosphere continuum. Because of the direct impact on latent heat fluxes, these properties may also influence weather generating processes, such as the evolution of the atmospheric boundary layer (ABL). In land surface models, plant physiological properties are usually obtained from literature synthesis by unifying several plant/crop species in predefined vegetation classes. In this work, crop-specific physiological characteristics, retrieved from detailed field measurements, are included in the bio-physical parameterization of the Community Land Model (CLM), which is a component of the Terrestrial Systems Modeling Platform (TerrSysMP). The measured set of parameters for two typical European mid-latitudinal crops (sugar beet and winter wheat) is validated using eddy covariance measurements (sensible heat and latent heat) over multiple years from three measurement sites located in the North Rhine-Westphalia region, Germany. We found clear improvements of CLM simulations, when using the crop-specific physiological characteristics of the plants instead of the generic crop type when compared to the measurements. In particular, the increase of latent heat fluxes in conjunction with decreased sensible heat fluxes as simulated by the two new crop-specific parameter sets leads to an improved quantification of the diurnal energy partitioning. These findings are cross-validated using estimates of gross primary production extracted from net ecosystem exchange measurements. This independent analysis reveals that the better agreement between observed and simulated latent heat using the plant-specific physiological properties largely stems from an improved simulation of the photosynthesis process owing to a better estimation of the Rubisco enzyme kinematics. Finally, to evaluate the effects of the crop-specific parameterizations on the ABL dynamics, we perform a series of semi-idealized land-atmosphere coupled simulations by hypothesizing three cropland configurations. These numerical experiments reveal different heat and moisture budgets of the ABL that clearly impact the evolution of the boundary layer when using the crop-specific physiological properties.

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain.

PubMed

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca(2+) indicator in the MBs, we investigated synaptic transmission and plasticity at the AL-MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca(2+) responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca(2+) responses were mediated through Drosophila NMDA receptors (dNRs). AL-MB synaptic transmission was enhanced more than 2 h after the simultaneous 'associative-stimulation' of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL-MB synapses but not at the AFV-MB synapses. AL-MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL-MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL-MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL-MB LTE might be a relevant cellular model for olfactory memory.

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain

PubMed Central

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca2+ indicator in the MBs, we investigated synaptic transmission and plasticity at the AL–MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca2+ responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca2+ responses were mediated through Drosophila NMDA receptors (dNRs). AL–MB synaptic transmission was enhanced more than 2 h after the simultaneous ‘associative-stimulation’ of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL–MB synapses but not at the AFV–MB synapses. AL–MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL–MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL–MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL–MB LTE might be a relevant cellular model for olfactory memory. PMID:23027817

Topical drug delivery to the eye: dorzolamide.

PubMed

Loftsson, Thorsteinn; Jansook, Phatsawee; Stefánsson, Einar

2012-11-01

Topically applied carbonic anhydrase inhibitors (CAIs) in eye drop solutions are commonly used to treat glaucoma. However, local eye irritation and multiple daily administrations may hamper their clinical usefulness. Aqueous eye drop formulations that improve their topical bioavailability and reduce their eye irritation can improve their clinical efficacy. Earlier studies showed that dorzolamide and closely related CAIs are more effectively delivered into the eye from acidic eye drop solutions than from comparable neutral solutions. Consequently, dorzolamide was marketed as an aqueous pH 5.6 eye drop solution (Trusopt(®) , Merck). Later, it was shown that increasing the pH of the eye drops from pH 5.6 to physiologic pH significantly reduced their local irritation. Earlier attempts to use cyclodextrins (CDs) as ocular penetration enhancers in dorzolamide eye drop solutions failed since; although the CDs were able to enhance the aqueous solubility of dorzolamide, increasing the pH from 5.6 to physiologic pH reduced the ability of the drug to permeate into the eye. Later, it was discovered that formulating the drug as aqueous dorzolamide/γCD eye drop microparticle suspension resulted in significant bioavailability enhancement. The solid dorzolamide/γCD microparticles are mucoadhesive and release dorzolamide into the aqueous tear fluid for extended time period. Consequently, sustained high dorzolamide concentrations in aqueous humour and various eye tissues were observed after single administration of the aqueous dorzolamide/γCD eye drop microsuspension. The microsuspension has a potential of being developed into a once-a-day eye drop product. This article reviews the physicochemical properties of dorzolamide, its permeation characteristics and topical bioavailability. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Use of physiological knowledge to control the invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes.

PubMed

Siefkes, Michael J

2017-01-01

Sea lamprey ( Petromyzon marinus ) control in the Laurentian Great Lakes of North America is an example of using physiological knowledge to successfully control an invasive species and rehabilitate an ecosystem and valuable fishery. The parasitic sea lamprey contributed to the devastating collapse of native fish communities after invading the Great Lakes during the 1800s and early 1900s. Economic tragedy ensued with the loss of the fishery and severe impacts to property values and tourism resulting from sea lamprey-induced ecological changes. To control the sea lamprey and rehabilitate the once vibrant Great Lakes ecosystem and economy, the Great Lakes Fishery Commission (Commission) was formed by treaty between Canada and the United States in 1955. The Commission has developed a sea lamprey control programme based on their physiological vulnerabilities, which includes (i) the application of selective pesticides (lampricides), which successfully kill sedentary sea lamprey larvae in their natal streams; (ii) barriers to spawning migrations and associated traps to prevent infestations of upstream habitats and remove adult sea lamprey before they reproduce; and (iii) the release of sterilized males to reduce the reproductive potential of spawning populations in select streams. Since 1958, the application of the sea lamprey control programme has suppressed sea lamprey populations by ~90% from peak abundance. Great Lakes fish populations have rebounded and the economy is now thriving. In hopes of further enhancing the efficacy and selectivity of the sea lamprey control programme, the Commission is exploring the use of (i) sea lamprey chemosensory cues (pheromones and alarm cues) to manipulate behaviours and physiologies, and (ii) genetics to identify and manipulate genes associated with key physiological functions, for control purposes. Overall, the Commission capitalizes on the unique physiology of the sea lamprey and strives to develop a diverse integrated programme to successfully control a once devastating invasive species.

Use of physiological knowledge to control the invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes

PubMed Central

2017-01-01

Abstract Sea lamprey (Petromyzon marinus) control in the Laurentian Great Lakes of North America is an example of using physiological knowledge to successfully control an invasive species and rehabilitate an ecosystem and valuable fishery. The parasitic sea lamprey contributed to the devastating collapse of native fish communities after invading the Great Lakes during the 1800s and early 1900s. Economic tragedy ensued with the loss of the fishery and severe impacts to property values and tourism resulting from sea lamprey-induced ecological changes. To control the sea lamprey and rehabilitate the once vibrant Great Lakes ecosystem and economy, the Great Lakes Fishery Commission (Commission) was formed by treaty between Canada and the United States in 1955. The Commission has developed a sea lamprey control programme based on their physiological vulnerabilities, which includes (i) the application of selective pesticides (lampricides), which successfully kill sedentary sea lamprey larvae in their natal streams; (ii) barriers to spawning migrations and associated traps to prevent infestations of upstream habitats and remove adult sea lamprey before they reproduce; and (iii) the release of sterilized males to reduce the reproductive potential of spawning populations in select streams. Since 1958, the application of the sea lamprey control programme has suppressed sea lamprey populations by ~90% from peak abundance. Great Lakes fish populations have rebounded and the economy is now thriving. In hopes of further enhancing the efficacy and selectivity of the sea lamprey control programme, the Commission is exploring the use of (i) sea lamprey chemosensory cues (pheromones and alarm cues) to manipulate behaviours and physiologies, and (ii) genetics to identify and manipulate genes associated with key physiological functions, for control purposes. Overall, the Commission capitalizes on the unique physiology of the sea lamprey and strives to develop a diverse integrated programme to successfully control a once devastating invasive species. PMID:28580146

Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery.

PubMed

Chen, Chih-Kuang; Lin, Wei-Jen; Hsia, Yu; Lo, Leu-Wei

2017-03-01

Well-defined poly(ethylene glycol)-b-allyl functional polylactide-b-polylactides (PEG-APLA-PLAs) are synthesized through sequential ring-opening polymerization. PEG-APLA-PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core-shell interface cross-linked micelles (ICMs) by micellization and UV-initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological-mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug-ICM formulations possess slow and sustained drug release profiles under physiological-mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox-loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross-linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

PubMed

Nagano, Nobuo; Tsutsui, Takaaki

2016-06-01

Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.

Melatonin: Nature's most versatile biological signal?

PubMed

Pandi-Perumal, S R; Srinivasan, V; Maestroni, G J M; Cardinali, D P; Poeggeler, B; Hardeland, R

2006-07-01

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.

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

Blue-Enriched White Light Enhances Physiological Arousal But Not Behavioral Performance during Simulated Driving at Early Night

PubMed Central

Rodríguez-Morilla, Beatriz; Madrid, Juan A.; Molina, Enrique; Correa, Angel

2017-01-01

Vigilance usually deteriorates over prolonged driving at non-optimal times of day. Exposure to blue-enriched light has shown to enhance arousal, leading to behavioral benefits in some cognitive tasks. However, the cognitive effects of long-wavelength light have been less studied and its effects on driving performance remained to be addressed. We tested the effects of a blue-enriched white light (BWL) and a long-wavelength orange light (OL) vs. a control condition of dim light on subjective, physiological and behavioral measures at 21:45 h. Neurobehavioral tests included the Karolinska Sleepiness Scale and subjective mood scale, recording of distal-proximal temperature gradient (DPG, as index of physiological arousal), accuracy in simulated driving and reaction time in the auditory psychomotor vigilance task. The results showed that BWL decreased the DPG (reflecting enhanced arousal), while it did not improve reaction time or driving performance. Instead, blue light produced larger driving errors than OL, while performance in OL was stable along time on task. These data suggest that physiological arousal induced by light does not necessarily imply cognitive improvement. Indeed, excessive arousal might deteriorate accuracy in complex tasks requiring precision, such as driving. PMID:28690558

Oxidative stress and mitochondria-mediated cell death mechanisms triggered by the familial Danish dementia ADan amyloid

PubMed Central

Todd, Krysti; Ghiso, Jorge; Rostagno, Agueda

2015-01-01

Familial Danish Dementia (FDD), an early-onset non-amyloid-β (Aβ) cerebral amyloidosis, is neuropathologically characterized by widespread cerebral amyloid angiopathy, parenchymal amyloid and preamyloid deposits, as well as neurofibrillary degeneration indistinguishable to that seen in Alzheimer’s disease (AD). The main amyloid subunit composing FDD lesions, a 34-amino acid de-novo generated peptide ADan, is the direct result of a genetic defect at the 3’-end of the BRI2 gene and the physiologic action of furin-like proteolytic processing at the C-terminal region of the ADan precursor protein. We aimed to study the impact of the FDD mutation, the additional formation of the pyroglutamate (pE) posttranslational modification as well as the relevance of C-terminal truncations –all major components of the heterogeneous FDD deposits–on the structural and neurotoxic properties of the molecule. Our data indicates that whereas the mutation generated a β-sheet-rich hydrophobic ADan subunit of high oligomerization/fibrillization propensity and the pE modification further enhanced these properties, C-terminal truncations had the opposite effect mostly abolishing these features. The potentiation of pro-amyloidogenic properties correlated with the initiation of neuronal cell death mechanisms involving oxidative stress, perturbation of mitochondrial membrane potential, release of mitochondrial cytochrome c, and downstream activation of caspase-mediated apoptotic pathways. The amyloid-induced toxicity was inhibited by targeting specific components of these detrimental cellular pathways, using reactive oxygen scavengers and monoclonal antibodies recognizing the pathological amyloid subunit. Taken together, the data indicate that the FDD mutation and the pE posttranslational modification are both primary elements driving intact ADan into an amyloidogenic/neurotoxic pathway while truncations at the C-terminus eliminate the pro-amyloidogenic characteristics of the molecule, likely reflecting effect of physiologic clearance mechanisms. PMID:26459115

A single bout of resistance exercise can enhance episodic memory performance.

PubMed

Weinberg, Lisa; Hasni, Anita; Shinohara, Minoru; Duarte, Audrey

2014-11-01

Acute aerobic exercise can be beneficial to episodic memory. This benefit may occur because exercise produces a similar physiological response as physical stressors. When administered during consolidation, acute stress, both physical and psychological, consistently enhances episodic memory, particularly memory for emotional materials. Here we investigated whether a single bout of resistance exercise performed during consolidation can produce episodic memory benefits 48 h later. We used a one-leg knee extension/flexion task for the resistance exercise. To assess the physiological response to the exercise, we measured salivary alpha amylase (a biomarker of central norepinephrine), heart rate, and blood pressure. To test emotional episodic memory, we used a remember-know recognition memory paradigm with equal numbers of positive, negative, and neutral IAPS images as stimuli. The group that performed the exercise, the active group, had higher overall recognition accuracy than the group that did not exercise, the passive group. We found a robust effect of valence across groups, with better performance on emotional items as compared to neutral items and no difference between positive and negative items. This effect changed based on the physiological response to the exercise. Within the active group, participants with a high physiological response to the exercise were impaired for neutral items as compared to participants with a low physiological response to the exercise. Our results demonstrate that a single bout of resistance exercise performed during consolidation can enhance episodic memory and that the effect of valence on memory depends on the physiological response to the exercise. Copyright © 2014 Elsevier B.V. All rights reserved.

The Constraints, Construction, and Verification of a Strain-Specific Physiologically Based Pharmacokinetic Rat Model.

PubMed

Musther, Helen; Harwood, Matthew D; Yang, Jiansong; Turner, David B; Rostami-Hodjegan, Amin; Jamei, Masoud

2017-09-01

The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically incorporated within physiologically based pharmacokinetic (PBPK) models, can harness in vitro drug data and enhance understanding of in vivo pharmacokinetics. This study's objective was to develop a user-friendly rat (250 g, male Sprague-Dawley) IVIVE-linked PBPK model. A 13-compartment PBPK model including mechanistic absorption models was developed, with required system data (anatomical, physiological, and relevant IVIVE scaling factors) collated from literature and analyzed. Overall, 178 system parameter values for the model are provided. This study also highlights gaps in available system data required for strain-specific rat PBPK model development. The model's functionality and performance were assessed using previous literature-sourced in vitro properties for diazepam, metoprolol, and midazolam. The results of simulations were compared against observed pharmacokinetic rat data. Predicted and observed concentration profiles in 10 tissues for diazepam after a single intravenous (i.v.) dose making use of either observed i.v. clearance (CL iv ) or in vitro hepatocyte intrinsic clearance (CL int ) for simulations generally led to good predictions in various tissue compartments. Overall, all i.v. plasma concentration profiles were successfully predicted. However, there were challenges in predicting oral plasma concentration profiles for metoprolol and midazolam, and the potential reasons and according solutions are discussed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel.

PubMed

Li, Guo; Yan, Qiang; Xia, Hesheng; Zhao, Yue

2015-06-10

Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a strong hydrogel due to the multiple H-bonding between the two constituents. A temporary shape of the hydrogel can be obtained by deformation of the hydrogel (∼65 wt % water) at room temperature, followed by fixation of the deformation by freezing/thawing the hydrogel under strain, which induces crystallization of PVA. We show that the ultrasound delivered by a commercially available device designed for the patient's pain relief could trigger the shape recovery process as a result of ultrasound-induced local heating in the hydrogel that melts the crystallized PVA cross-linking. This hydrogel is thus interesting for potential applications because it combines many desirable properties, being mechanically strong, biocompatible, and self-healable and displaying the shape memory capability triggered by a physiological stimulus.

Figure-ground segregation in a recurrent network architecture.

PubMed

Roelfsema, Pieter R; Lamme, Victor A F; Spekreijse, Henk; Bosch, Holger

2002-05-15

Here we propose a model of how the visual brain segregates textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped together. Boundary detection and grouping of image regions require different connection schemes, which are accommodated in a single network architecture by implementing them in different layers. As a result, all units carry signals related to boundary detection as well as grouping of image regions, in accordance with cortical physiology. Boundaries yield an early enhancement of network responses, but at a later point, an entire figural region is grouped together, because units that respond to it are labeled with enhanced activity. The model predicts which image regions are preferentially perceived as figure or as background and reproduces the spatio-temporal profile of neuronal activity in the visual cortex during texture segregation in intact animals, as well as in animals with cortical lesions.

Climate resilient crops for improving global food security and safety.

PubMed

Dhankher, Om Parkash; Foyer, Christine H

2018-05-01

Food security and the protection of the environment are urgent issues for global society, particularly with the uncertainties of climate change. Changing climate is predicted to have a wide range of negative impacts on plant physiology metabolism, soil fertility and carbon sequestration, microbial activity and diversity that will limit plant growth and productivity, and ultimately food production. Ensuring global food security and food safety will require an intensive research effort across the food chain, starting with crop production and the nutritional quality of the food products. Much uncertainty remains concerning the resilience of plants, soils, and associated microbes to climate change. Intensive efforts are currently underway to improve crop yields with lower input requirements and enhance the sustainability of yield through improved biotic and abiotic stress tolerance traits. In addition, significant efforts are focused on gaining a better understanding of the root/soil interface and associated microbiomes, as well as enhancing soil properties. © 2018 The Authors Plant, Cell & Environment Published by John Wiley & Sons Ltd.

Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain.

PubMed

Manthey, Daniela; Asimiadou, Stella; Stefovska, Vanya; Kaindl, Angela M; Fassbender, Jessica; Ikonomidou, Chrysanthy; Bittigau, Petra

2005-06-01

Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children can cause cognitive impairment. One mechanism implicated in the development of neurocognitive deficits is a pathologic enhancement of physiologically occurring apoptotic neuronal death in the developing brain. We investigated whether the newer antiepileptic drug levetiracetam (LEV) and the older antiepileptic drug sulthiame (SUL) have neurotoxic properties in the developing rat brain. SUL significantly enhanced neuronal death in the brains of rat pups ages 0 to 7 days at doses of 100 mg/kg and above, whereas LEV did not show this neurotoxic effect. Dosages of both drugs used in the context of this study comply with an effective anticonvulsant dose range applied in rodent seizure models. Thus, LEV is an AED which lacks neurotoxicity in the developing rat brain and should be considered in the treatment of epilepsy in pregnant women, infants, and toddlers once general safety issues have been properly addressed.

Physiological and psychological stress limits for astronautics Observations during the Skylab I-III missions

NASA Technical Reports Server (NTRS)

Burchard, E. C.

1975-01-01

The physiological and psychological factors of manned space flight had a particular significance in the Skylab missions during which astronauts were subjected to a life in a space environment for longer periods of time than on previous space missions. The Skylab missions demonstrated again the great adaptability of human physiology to the environment of man. The results of Skylab have indicated also approaches for enhancing the capability of man to tolerate the physiological and psychological stresses of space flight.

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin.

PubMed

Chen, Wei-Liang; Li, Fang; Tang, Yan; Yang, Shu-di; Li, Ji-Zhao; Yuan, Zhi-Qiang; Liu, Yang; Zhou, Xiao-Feng; Liu, Chun; Zhang, Xue-Nong

2017-01-01

Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents.

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

PubMed Central

Chen, Wei-liang; Li, Fang; Tang, Yan; Yang, Shu-di; Li, Ji-zhao; Yuan, Zhi-qiang; Liu, Yang; Zhou, Xiao-feng; Liu, Chun; Zhang, Xue-nong

2017-01-01

Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents. PMID:28652730

Student-involved demonstration approach to teach the physiology of vestibular apparatus for undergraduate medical students.

PubMed

Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Nayak, Satheesha

2011-01-01

It is quite difficult to teach complex topics like the physiology of vestibular apparatus to undergraduate students. Understanding the orientation and mode of stimulation of receptors in vestibular apparatus is also quite challenging for the students. As faculty we attempt to use innovative methods to teach physiology and enhance student learning. This article describes a simple and innovative method (student-involved demonstration approach, or SID) to teach the physiology of the vestibular apparatus to the undergraduate medical students. The current study describes a protocol where students engage in role-play sessions in the middle of the regular didactic lectures. Effectiveness of the sessions was later evaluated by using a questionnaire and by comparing the pre-SID and post-SID test results of the students. The posttest score of the students was significantly higher than the pretest score, and this indicates the usefulness of SID sessions on enhancing the student learning in the class. Students also found this method very interesting and useful in better understanding the physiology of the vestibular apparatus.

Using Copper to Improve the Well-Being of the Skin

PubMed Central

Borkow, Gadi

2014-01-01

Copper has two key properties that are being exploited in consumer and medical device products in the last decade. On the one hand, copper has potent biocidal properties. On the other hand, copper is involved in numerous physiological and metabolic processes critical for the appropriate functioning of almost all tissues in the human body. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis. This manuscript reviews clinical studies that show that the use of textile consumer and medical device products, embedded with microscopic copper oxide particles, improve the well-being of the skin. These include studies showing a) cure of athlete’s foot infections and improvement in skin elasticity, especially important for individuals suffering from diabetes; b) reduction of facial fine line and wrinkles; and c) enhancement of wound healing; by copper oxide embedded socks, pillowcases and wound dressings, respectively. The manuscript also reviews and discusses the mechanisms by which the presence of copper in these products improves skin well-being. PMID:26361585

Interfacing with the Brain using Organic Electronics

NASA Astrophysics Data System (ADS)

Malliaras, George

One of the most important scientific and technological frontiers of our time lies in the interface between electronics and the human brain. Interfacing the most advanced human engineering endeavor with nature's most refined creation promises to help elucidate aspects of the brain's working mechanism and deliver new tools for diagnosis and treatment of a host of pathologies including epilepsy and Parkinson's disease. Current solutions, however, are limited by the materials that are brought in contact with the tissue and transduce signals across the biotic/abiotic interface. The field of organic electronics has made available materials with a unique combination of attractive properties, including mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic-based devices for recording and stimulation of brain activity, highlighting the connection between materials properties and device performance. I will show that organic electronic materials provide unparalleled opportunities to design devices that improve our understanding of brain physiology and pathology, and can be used to deliver new therapies.

The Anti-Oxidant Ergothioneine Augments the Immunomodulatory Function of TLR Agonists by Direct Action on Macrophages

PubMed Central

Funami, Kenji; Takaki, Hiromi; Matsumoto, Misako; Kasahara, Masanori; Seya, Tsukasa

2017-01-01

L-Ergothioneine (EGT) is a naturally-occurring amino acid which is characterized by its antioxidant property; yet, the physiological role of EGT has yet to be established. We investigated the immune-enhancing properties of EGT, and found that it acts as a potentiator of toll-like receptor (TLR) signaling. When mouse bone marrow-derived macrophages (BMDMs) were pretreated with EGT, TLR signal-mediated cytokine production was augmented in BMDMs. The results were reproducible with TLR2, 3, 4 and 7 agonists. In particular, IL-6 and IL-12p40 were elevated further by pretreatment with EGT in BMDMs, suggesting the induction of M1 polarization. In co-culture assay with OT-II CD4+ T cells and splenic F4/80+ macrophages, EGT significantly induced Th17 skewing in CD4+ T cells. Thus, EGT is an immune modifier as well as a redox controller under TLR stimulation that induces M1 macrophages and a Th17 shift in inflammation. PMID:28114402

Intracellular production of hydrogels and synthetic RNA granules by multivalent enhancers

PubMed Central

Nakamura, Hideki; Lee, Albert A.; Afshar, Ali Sobhi; Watanabe, Shigeki; Rho, Elmer; Razavi, Shiva; Suarez, Allison; Lin, Yu-Chun; Tanigawa, Makoto; Huang, Brian; DeRose, Robert; Bobb, Diana; Hong, William; Gabelli, Sandra B.; Goutsias, John; Inoue, Takanari

2018-01-01

Non-membrane bound, hydrogel-like entities, such as RNA granules, nucleate essential cellular functions through their unique physico-chemical properties. However, these intracellular hydrogels have not been as extensively studied as their extracellular counterparts, primarily due to technical challenges in probing these materials in situ. Here, by taking advantage of a chemically inducible dimerization paradigm, we developed iPOLYMER, a strategy for rapid induction of protein-based hydrogels inside living cells. A series of biochemical and biophysical characterizations, in conjunction with computational modeling, revealed that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that behaves as a size-dependent molecular sieve. We studied several properties of the gel and functionalized it with RNA binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. Therefore, we here demonstrate that iPOLYMER presents a unique and powerful approach to synthetically reconstitute hydrogel-like structures including RNA granules in intact cells. PMID:29115293

Antiobesity Effect of Exopolysaccharides Isolated from Kefir Grains.

PubMed

Lim, Juha; Kale, Madhuvanti; Kim, Dong-Hyeon; Kim, Hong-Seok; Chon, Jung-Whan; Seo, Kun-Ho; Lee, Hyeon Gyu; Yokoyama, Wallace; Kim, Hyunsook

2017-11-22

Physiological properties of water-soluble exopolysaccharides (EPS) and residues after EPS removal (Res) from the probiotic kefir were determined in high-fat (HF) diet-fed C57BL/6J mice. EPS solutions showed rheological properties and lower viscosity compared to those of β-glucan (BG). EPS significantly suppressed the adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. Mice were fed HF diets containing 5% EPS, 5% BG, 8% Res, or 5% microcrystalline cellulose (control) for 4 weeks. Compared with the control, EPS supplementation significantly reduced HF diet-induced body weight gain, adipose tissue weight, and plasma very-low-density lipoprotein cholesterol concentration (P < 0.05). Res and BG significantly reduced body weight gain; however, reduction in adipose tissue weight was not statistically significant, suggesting that the antiobesity effect of EPS occurs due to viscosity and an additional factor. EPS supplementation significantly enhanced abundance of Akkermansia spp. in feces. These data indicate that EPS shows significant antiobesity effects possibly via intestinal microbiota alterations.

Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

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

Kubicek-Sutherland, Jessica Z.; Vu, Dung M.; Mendez, Heather M.

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential formore » their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. Furthermore, the biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review.« less

Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

DOE PAGES

Kubicek-Sutherland, Jessica Z.; Vu, Dung M.; Mendez, Heather M.; ...

2017-07-04

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential formore » their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. Furthermore, the biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review.« less

Nitric Oxide Inhibits Al-Induced Programmed Cell Death in Root Tips of Peanut (Arachis hypogaea L.) by Affecting Physiological Properties of Antioxidants Systems and Cell Wall

PubMed Central

Pan, Chun-Liu; Yao, Shao-Chang; Xiong, Wei-Jiao; Luo, Shu-Zhen; Wang, Ya-Lun; Wang, Ai-Qin; Xiao, Dong; Zhan, Jie; He, Long-Fei

2017-01-01

It has been reported that nitric oxide (NO) is a negative regulator of aluminum (Al)-induced programmed cell death (PCD) in peanut root tips. However, the inhibiting mechanism of NO on Al-induced PCD is unclear. In order to investigate the mechanism by which NO inhibits Al-induced PCD, the effects of co-treatment Al with the exogenous NO donor or the NO-specific scavenger on peanut root tips, the physiological properties of antioxidants systems and cell wall (CW) in root tip cells of NO inhibiting Al-induced PCD were studied with two peanut cultivars. The results showed that Al exposure induced endogenous NO accumulation, and endogenous NO burst increased antioxidant enzyme activity in response to Al stress. The addition of NO donor sodium nitroprusside (SNP) relieved Al-induced root elongation inhibition, cell death and Al adsorption in CW, as well as oxidative damage and ROS accumulation. Furthermore, co-treatment with the exogenous NO donor decreased MDA content, LOX activity and pectin methylesterase (PME) activity, increased xyloglucan endotransglucosylase (XET) activity and relative expression of the xyloglucan endotransglucosylase/hydrolase (XTH-32) gene. Taken together, exogenous NO alleviated Al-induced PCD by inhibiting Al adsorption in CW, enhancing antioxidant defense and reducing peroxidation of membrane lipids, alleviating the inhibition of Al on root elongation by maintaining the extensibility of CW, decreasing PME activity, and increasing XET activity and relative XTH-32 expression of CW. PMID:29311970

Nitric Oxide Inhibits Al-Induced Programmed Cell Death in Root Tips of Peanut (Arachis hypogaea L.) by Affecting Physiological Properties of Antioxidants Systems and Cell Wall.

PubMed

Pan, Chun-Liu; Yao, Shao-Chang; Xiong, Wei-Jiao; Luo, Shu-Zhen; Wang, Ya-Lun; Wang, Ai-Qin; Xiao, Dong; Zhan, Jie; He, Long-Fei

2017-01-01

It has been reported that nitric oxide (NO) is a negative regulator of aluminum (Al)-induced programmed cell death (PCD) in peanut root tips. However, the inhibiting mechanism of NO on Al-induced PCD is unclear. In order to investigate the mechanism by which NO inhibits Al-induced PCD, the effects of co-treatment Al with the exogenous NO donor or the NO-specific scavenger on peanut root tips, the physiological properties of antioxidants systems and cell wall (CW) in root tip cells of NO inhibiting Al-induced PCD were studied with two peanut cultivars. The results showed that Al exposure induced endogenous NO accumulation, and endogenous NO burst increased antioxidant enzyme activity in response to Al stress. The addition of NO donor sodium nitroprusside (SNP) relieved Al-induced root elongation inhibition, cell death and Al adsorption in CW, as well as oxidative damage and ROS accumulation. Furthermore, co-treatment with the exogenous NO donor decreased MDA content, LOX activity and pectin methylesterase (PME) activity, increased xyloglucan endotransglucosylase (XET) activity and relative expression of the xyloglucan endotransglucosylase/hydrolase ( XTH-32 ) gene. Taken together, exogenous NO alleviated Al-induced PCD by inhibiting Al adsorption in CW, enhancing antioxidant defense and reducing peroxidation of membrane lipids, alleviating the inhibition of Al on root elongation by maintaining the extensibility of CW, decreasing PME activity, and increasing XET activity and relative XTH-32 expression of CW.

An approach to the concept of tonic: suggested definitions and historical aspects.

PubMed

Götti, Robert P; Melzer, Jörg; Saller, Reinhard

2014-01-01

In traditional medicine, especially CAM, the concept of (herbal) tonics has a long history in the different medical systems (TEN -- Traditional European Naturopathy; TCM - Traditional Chinese Medicine). Nevertheless, the ideas concerning the function of a tonic differ, e.g., stimulation of body functions, strengthening of organ function, enhancement of adaption, and well-being. Although no exact pharmacodynamic or pharmacokinetic properties of tonics can be given, the following general definition, even in the transcultural comparison between European and Chinese concepts, seems meaningful: A tonic is an agent that has the capability to restore and/or maintain the physiological functioning of an organ system, leading to the subjective feeling of well-being of the patient treated with it. © 2014 S. Karger AG, Freiburg.

[Enhanced resistance to emotional stress through the use of D-phenylalanine].

PubMed

Iumatov, E A; Sarychev, E I; Kozlovskiĭ, I I; Mineeva, M F; Demidov, V M; Morozov, I S; Kozlovskaia, M M

1991-01-01

Stress-protective action was studied of D-phenylalanine, having an ability to decrease destruction of endogenic enkefalins. In the experiments stability of the experimental (receiving D-phenylalanine) and control groups of male rats of August line to emotional stress was compared in conditions of immobilization stress by parameters of animals survival rate, adrenal glands hypertrophy development, involution of thymus, pathologic changes in lungs (abscesses development), ulcero-dystrophic disturbances in stomach, and also the activity and kinetic properties of enzyme tyrosin-hydroxylase in the hypothalamus were determined. It was shown that by several of the mentioned physiological parameters the D-phenylalanine significantly increased the animals stability to the emotional stress and decreased tyrosinhydroxylase activity which participates in activation of katecholaminergic processes.

The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite.

PubMed

Jayabalan, M; Shalumon, K T; Mitha, M K; Ganesan, K; Epple, M

2010-04-01

The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite.

Bridging the Gap between Physiology and Behavior: Evidence from the sSoTS Model of Human Visual Attention

ERIC Educational Resources Information Center

Mavritsaki, Eirini; Heinke, Dietmar; Allen, Harriet; Deco, Gustavo; Humphreys, Glyn W.

2011-01-01

We present the case for a role of biologically plausible neural network modeling in bridging the gap between physiology and behavior. We argue that spiking-level networks can allow "vertical" translation between physiological properties of neural systems and emergent "whole-system" performance--enabling psychological results to be simulated from…

Method and System for Physiologically Modulating Videogames and Simulations which Use Gesture and Body Image Sensing Control Input Devices

NASA Technical Reports Server (NTRS)

Pope, Alan T. (Inventor); Stephens, Chad L. (Inventor); Habowski, Tyler (Inventor)

2017-01-01

Method for physiologically modulating videogames and simulations includes utilizing input from a motion-sensing video game system and input from a physiological signal acquisition device. The inputs from the physiological signal sensors are utilized to change the response of a user's avatar to inputs from the motion-sensing sensors. The motion-sensing system comprises a 3D sensor system having full-body 3D motion capture of a user's body. This arrangement encourages health-enhancing physiological self-regulation skills or therapeutic amplification of healthful physiological characteristics. The system provides increased motivation for users to utilize biofeedback as may be desired for treatment of various conditions.

Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets

NASA Astrophysics Data System (ADS)

Liu, Teng; Wang, Chao; Cui, Wei; Gong, Hua; Liang, Chao; Shi, Xiaoze; Li, Zhiwei; Sun, Baoquan; Liu, Zhuang

2014-09-01

Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03753g

Assessment of Ablative Therapies in Swine: Response of Respiratory Diaphragm to Varying Doses.

PubMed

Singal, Ashish; Mattison, Lars M; Soule, Charles L; Ballard, John R; Rudie, Eric N; Cressman, Erik N K; Iaizzo, Paul A

2018-03-28

Ablation is a common procedure for treating patients with cancer, cardiac arrhythmia, and other conditions, yet it can cause collateral injury to the respiratory diaphragm. Collateral injury can alter the diaphragm's properties and/or lead to respiratory dysfunction. Thus, it is important to understand the diaphragm's physiologic and biomechanical properties in response to ablation therapies, in order to better understand ablative modalities, minimize complications, and maximize the safety and efficacy of ablative procedures. In this study, we analyzed physiologic and biomechanical properties of swine respiratory diaphragm muscle bundles when exposed to 5 ablative modalities. To assess physiologic properties, we performed in vitro tissue bath studies and measured changes in peak force and baseline force. To assess biomechanical properties, we performed uniaxial stress tests, measuring force-displacement responses, stress-strain characteristics, and avulsion forces. After treating the muscle bundles with all 5 ablative modalities, we observed dose-dependent sustained reductions in peak force and transient increases in baseline force-but no consistent dose-dependent biomechanical responses. These data provide novel insights into the effects of various ablative modalities on the respiratory diaphragm, insights that could enable improvements in ablative techniques and therapies.

Novel metabolic and physiological functions of branched chain amino acids: a review.

PubMed

Zhang, Shihai; Zeng, Xiangfang; Ren, Man; Mao, Xiangbing; Qiao, Shiyan

2017-01-01

It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

A novel mechanical antrum model for the prediction of the gastroretentive potential of dosage forms.

PubMed

Neumann, Marco; Schneider, Felix; Koziolek, Mirko; Garbacz, Grzegorz; Weitschies, Werner

2017-09-15

The development of gastroretentive dosage forms can be significantly enhanced by the reliable estimation of gastroretentive properties in vitro. In this context, it is mandatory to consider the propulsive contraction waves that occur in the antral region of the stomach, since they are regarded as the major physiological hurdle to overcome. Therefore, the aim of this study was to develop an in vitro model that allowed the evaluation of the gastroretentive potential of objects with different properties (e.g. size, shape and elasticity). The model enabled a realistic simulation of the human antrum and occurring contraction waves. We could demonstrate that larger objects made of elastic polyurethane foam were more rapidly emptied by the model than smaller objects having the same shape. Compared to this, rigid as well as slippery objects showed decreased gastroretentive properties. In contrast, a self-formed trichobezoar - an indigestible object known to remain in the stomach - showed the highest gastroretentive potential. We suggest that the gastroretentive potential of objects of a certain size increases if they exhibit compressible and elastic properties along with certain dimensions. The data showed that the development of novel gastroretentive dosage forms may be facilitated with the aid of the mechanical antrum model. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent developments on polyphenol–protein interactions: effects on tea and coffee taste, antioxidant properties and the digestive system.

PubMed

Bandyopadhyay, Prasun; Ghosh, Amit K; Ghosh, Chandrasekhar

2012-06-01

Tea and coffee are widely consumed beverages across the world and they are rich sources of various polyphenols. Polyphenols are responsible for the bitterness and astringency of beverages and are also well known to impart antioxidant properties which is beneficial against several oxidative stress related diseases like cancer, cardiovascular diseases, and aging. On the other hand, proteins are also known to display many important roles in several physiological activities. Polyphenols can interact with proteins through hydrophobic or hydrophilic interactions, leading to the formation of soluble or insoluble complexes. According to recent studies, this complex formation can affect the bioavailability and beneficiary properties of both the individual components, in either way. For example, polyphenol-protein complex formation can reduce or enhance the antioxidant activity of polyphenols; similarly it can also affect the digestion ability of several digestive enzymes present in our body. Surprisingly, no review article has been published recently which has focused on the progress in this area, despite numerous articles having appeared in this field. This review summarizes the recent trends and patterns (2005 onwards) in polyphenol-protein interaction studies focusing on the characterization of the complex, the effect of this complex formation on tea and coffee taste, antioxidant properties and the digestive system.

Role of Klotho in Osteoporosis and Renal Osteodystrophy

DTIC Science & Technology

2014-10-01

about the complex physiology of bone development and maintenance including the endocrine regulation of mineral homeostasis that is absolutely...percentage of bone. This should enhance the effects we have already seen in other lines and enable us to delve further into physiology of the phenotype...Klotho and FGFRs [11,12]. To dissect the role of parathyroid gland resident Klotho in physiology and in pathophysiological states such as CKD, we

Segregation of Form, Color, Movement, and Depth: Anatomy, Physiology, and Perception.

ERIC Educational Resources Information Center

Livingstone, Margaret; Hubel, David

1988-01-01

Summarizes the anatomical, physiological, and psychological evidence related to the primate visual system. States that comparison of perceptual abilities with the electrophysiological properties of neurons may help deduce functions of visual areas. (RT)

Synthetic octacalcium phosphate: a possible carrier for mesenchymal stem cells in bone regeneration.

PubMed

Suzuki, Osamu; Anada, Takahisa

2013-01-01

The present paper reviews biomaterial studies of synthetic octacalcium phosphate (OCP) as a scaffold of osteoblastic cells. OCP crystals have been suggested to be one of precursor phases in hydroxyapatite (HA) crystal formation in bone and tooth. The recent intensive biomaterials and tissue engineering studies using synthetic OCP disclosed the potential function of OCP as a bioactive material as well as synthetic HA materials due to its highly osteoconductive and biodegradable properties. In vitro studies showed that OCP crystals exhibit a positive effect on osteoblastic cell differentiation. In vivo studies confirmed that the materials of OCP in a granule forms and OCP-based composite materials with natural polymers, such as gelatin and collagen, enhance bone regeneration if implanted in various model bone defects with critical-sized diameters, defined as a defect which does not heal spontaneously throughout the lifetime of the animals. One of particular characteristics of OCP, found as a mechanism to enhance bone regeneration in vivo, is a process of progressive conversion from OCP to HA at physiological conditions. The OCP-HA conversion is accompanied by progressive physicochemical changes of the material properties, which affects the tissue reaction around the crystals where osteoblastic cells are encountered. Mesenchymal stem cells (MSCs) seeded in an OCP-based material enhanced bone regeneration in the rat critical-sized calvaria defect more than that by the material alone. The overall results reveal that OCP crystals have an effect on osteoblastic cell differentiation including the differentiation of MSCs in vivo. The evidence collected experimentally in the laboratory was presented.

Applications of physiologically based pharmacokinetic modeling for the optimization of anti-infective therapies.

PubMed

Moss, Darren Michael; Marzolini, Catia; Rajoli, Rajith K R; Siccardi, Marco

2015-01-01

The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicted by integrating in vitro drug properties and mathematical descriptions of human anatomy in physiologically based pharmacokinetic models. This method reduces the need for animal and human studies and is used increasingly in drug development and simulation of clinical scenario such as, for instance, drug-drug interactions, dose optimization, novel formulations and pharmacokinetics in special populations. We have assessed the relevance of physiologically based pharmacokinetic modeling in the anti-infective research field, giving an overview of mechanisms involved in model design and have suggested strategies for future applications of physiologically based pharmacokinetic models. Physiologically based pharmacokinetic modeling provides a powerful tool in anti-infective optimization, and there is now no doubt that both industry and regulatory bodies have recognized the importance of this technology. It should be acknowledged, however, that major challenges remain to be addressed and that information detailing disease group physiology and anti-infective pharmacodynamics is required if a personalized medicine approach is to be achieved.

A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning.

PubMed

Wang, Ching-Fu; Yang, Shih-Hung; Lin, Sheng-Huang; Chen, Po-Chuan; Lo, Yu-Chun; Pan, Han-Chi; Lai, Hsin-Yi; Liao, Lun-De; Lin, Hui-Ching; Chen, Hsu-Yan; Huang, Wei-Chen; Huang, Wun-Jhu; Chen, You-Yin

Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption. However, when the association between the biomarkers of the model and stimulation is unclear, it is difficult to develop an optimal control scheme for other DBS applications, i.e., DBS-enhanced instrumental learning. Furthermore, few studies have investigated the effect of closed-loop DBS control for cognition function, such as instrumental skill learning, and have been implemented in simulation environments. In this paper, we proposed a proof-of-principle design for a closed-loop DBS system, cognitive-enhancing DBS (ceDBS), which enhanced skill learning based on in vivo experimental data. The ceDBS acquired local field potential (LFP) signal from the thalamic central lateral (CL) nuclei of animals through a neural signal processing system. A strong coupling of the theta oscillation (4-7 Hz) and the learning period was found in the water reward-related lever-pressing learning task. Therefore, the theta-band power ratio, which was the averaged theta band to averaged total band (1-55 Hz) power ratio, could be used as a physiological marker for enhancement of instrumental skill learning. The on-line extraction of the theta-band power ratio was implemented on a field-programmable gate array (FPGA). An autoregressive with exogenous inputs (ARX)-based predictor was designed to construct a CL-thalamic DBS model and forecast the future physiological marker according to the past physiological marker and applied DBS. The prediction could further assist the design of a closed-loop DBS controller. A DBS controller based on a fuzzy expert system was devised to automatically control DBS according to the predicted physiological marker via a set of rules. The simulated experimental results demonstrate that the ceDBS based on the closed-loop control architecture not only reduced power consumption using the predictive physiological marker, but also achieved a desired level of physiological marker through the DBS controller. Copyright © 2017 Elsevier Inc. All rights reserved.

Creation of hydrophilic nitric oxide releasing polymers via plasma surface modification.

PubMed

Pegalajar-Jurado, A; Joslin, J M; Hawker, M J; Reynolds, M M; Fisher, E R

2014-08-13

Herein, we describe the surface modification of an S-nitrosated polymer derivative via H2O plasma treatment, resulting in polymer coatings that maintained their nitric oxide (NO) releasing capabilities, but exhibited dramatic changes in surface wettability. The poly(lactic-co-glycolic acid)-based hydrophobic polymer was nitrosated to achieve a material capable of releasing the therapeutic agent NO. The NO-loaded films were subjected to low-temperature H2O plasma treatments, where the treatment power (20-50 W) and time (1-5 min) were varied. The plasma treated polymer films were superhydrophilic (water droplet spread completely in <100 ms), yet retained 90% of their initial S-nitrosothiol content. Under thermal conditions, NO release profiles were identical to controls. Under buffer soak conditions, the NO release profile was slightly lowered for the plasma-treated materials; however, they still result in physiologically relevant NO fluxes. XPS, SEM-EDS, and ATR-IR characterization suggests the plasma treatment resulted in polymer rearrangement and implantation of hydroxyl and carbonyl functional groups. Plasma treated samples maintained both hydrophilic surface properties and NO release profiles after storage at -18 °C for at least 10 days, demonstrating the surface modification and NO release capabilities are stable over time. The ability to tune polymer surface properties while maintaining bulk properties and NO release properties, and the stability of those properties under refrigerated conditions, represents a unique approach toward creating enhanced therapeutic biopolymers.

Antibacterial property of Ag nanoparticle-impregnated N-doped titania films under visible light

PubMed Central

Wong, Ming-Show; Chen, Chun-Wei; Hsieh, Chia-Chun; Hung, Shih-Che; Sun, Der-Shan; Chang, Hsin-Hou

2015-01-01

Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacterial properties. Silver (Ag) is an antibacterial material that disrupts bacterial physiology. Our previous study reported that the high antibacterial property of silver nanoparticles on the surfaces of visible light-responsive nitrogen-doped TiO2 photocatalysts [TiO2(N)] could be further enhanced by visible light illumination. However, the major limitation of this Ag-TiO2 composite material is its durability; the antibacterial property decreased markedly after repeated use. To overcome this limitation, we developed TiO2(N)/Ag/TiO2(N) sandwich films in which the silver is embedded between two TiO2(N) layers. Various characteristics, including silver and nitrogen amounts, were examined in the composite materials. Various analyses, including electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and ultraviolet–visible absorption spectrum and methylene blue degradation rate analyses, were performed. The antibacterial properties of the composite materials were investigated. Here we revealed that the antibacterial durability of these thin films is substantially improved in both the dark and visible light, by which bacteria, such as Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, and Acinetobacter baumannii, could be efficiently eliminated. This study demonstrated a feasible approach to improve the visible-light responsiveness and durability of antibacterial materials that contain silver nanoparticles impregnated in TiO2(N) films. PMID:26156001

Antibacterial property of Ag nanoparticle-impregnated N-doped titania films under visible light

NASA Astrophysics Data System (ADS)

Wong, Ming-Show; Chen, Chun-Wei; Hsieh, Chia-Chun; Hung, Shih-Che; Sun, Der-Shan; Chang, Hsin-Hou

2015-07-01

Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacterial properties. Silver (Ag) is an antibacterial material that disrupts bacterial physiology. Our previous study reported that the high antibacterial property of silver nanoparticles on the surfaces of visible light-responsive nitrogen-doped TiO2 photocatalysts [TiO2(N)] could be further enhanced by visible light illumination. However, the major limitation of this Ag-TiO2 composite material is its durability; the antibacterial property decreased markedly after repeated use. To overcome this limitation, we developed TiO2(N)/Ag/TiO2(N) sandwich films in which the silver is embedded between two TiO2(N) layers. Various characteristics, including silver and nitrogen amounts, were examined in the composite materials. Various analyses, including electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and ultraviolet-visible absorption spectrum and methylene blue degradation rate analyses, were performed. The antibacterial properties of the composite materials were investigated. Here we revealed that the antibacterial durability of these thin films is substantially improved in both the dark and visible light, by which bacteria, such as Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, and Acinetobacter baumannii, could be efficiently eliminated. This study demonstrated a feasible approach to improve the visible-light responsiveness and durability of antibacterial materials that contain silver nanoparticles impregnated in TiO2(N) films.

Enhanced bioactive scaffolds for bone tissue regeneration

NASA Astrophysics Data System (ADS)

Karnik, Sonali

Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37]. The focus of this dissertation was to design and develop novel implant materials for coating titanium to improve its biological properties. These natural and/or semi-synthetic materials improved cellular adhesion, biological response to the scaffolds and prevented growth of bacteria when they were enhanced with growth factor and anti-infective loaded nanotubes. The implant materials showed promise when tested in vitro for cell proliferation, differentiation and bacterial growth inhibition.

In Vivo Assessment of Cold Tolerance through Chlorophyll-a Fluorescence in Transgenic Zoysiagrass Expressing Mutant Phytochrome A

PubMed Central

Gururani, Mayank Anand; Venkatesh, Jelli; Ganesan, Markkandan; Strasser, Reto Jörg; Han, Yunjeong; Kim, Jeong-Il; Lee, Hyo-Yeon; Song, Pill-Soon

2015-01-01

Chlorophyll-a fluorescence analysis provides relevant information about the physiology of plants growing under abiotic stress. In this study, we evaluated the influence of cold stress on the photosynthetic machinery of transgenic turfgrass, Zoysia japonica, expressing oat phytochrome A (PhyA) or a hyperactive mutant phytochrome A (S599A) with post-translational phosphorylation blocked. Biochemical analysis of zoysiagrass subjected to cold stress revealed reduced levels of hydrogen peroxide, increased proline accumulation, and enhanced specific activities of antioxidant enzymes compared to those of control plants. Detailed analyses of the chlorophyll-a fluorescence data through the so-called OJIP test exhibited a marked difference in the physiological status among transgenic and control plants. Overall, these findings suggest an enhanced level of cold tolerance in S599A zoysiagrass cultivars as reflected in the biochemical and physiological analyses. Further, we propose that chlorophyll-a fluorescence analysis using OJIP test is an efficient tool in determining the physiological status of plants under cold stress conditions. PMID:26010864

Evolution of brain-computer interfaces: going beyond classic motor physiology

PubMed Central

Leuthardt, Eric C.; Schalk, Gerwin; Roland, Jarod; Rouse, Adam; Moran, Daniel W.

2010-01-01

The notion that a computer can decode brain signals to infer the intentions of a human and then enact those intentions directly through a machine is becoming a realistic technical possibility. These types of devices are known as brain-computer interfaces (BCIs). The evolution of these neuroprosthetic technologies could have significant implications for patients with motor disabilities by enhancing their ability to interact and communicate with their environment. The cortical physiology most investigated and used for device control has been brain signals from the primary motor cortex. To date, this classic motor physiology has been an effective substrate for demonstrating the potential efficacy of BCI-based control. However, emerging research now stands to further enhance our understanding of the cortical physiology underpinning human intent and provide further signals for more complex brain-derived control. In this review, the authors report the current status of BCIs and detail the emerging research trends that stand to augment clinical applications in the future. PMID:19569892

Calcium sensitivity of residual force enhancement in rabbit skinned fibers.

PubMed

Joumaa, V; Herzog, W

2014-08-15

Isometric force after active stretch of muscles is higher than the purely isometric force at the corresponding length. This property is termed residual force enhancement. Active force in skeletal muscle depends on calcium attachment characteristics to the regulatory proteins. Passive force has been shown to influence calcium attachment characteristics, specifically the sarcomere length dependence of calcium sensitivity. Since one of the mechanisms proposed to explain residual force enhancement is the increase in passive force that results from engagement of titin upon activation and stretch, our aim was to test if calcium sensitivity of residual force enhancement was different from that of its corresponding purely isometric contraction and if such a difference was related to the molecular spring titin. Force-pCa curves were established in rabbit psoas skinned fibers for reference and residual force-enhanced states at a sarcomere length of 3.0 μm 1) in a titin-intact condition, 2) after treatment with trypsin to partially eliminate titin, and 3) after treatment with trypsin and osmotic compression with dextran T-500 to decrease the lattice spacing in the absence of titin. The force-pCa curves of residual force enhancement were shifted to the left compared with their corresponding controls in titin-intact fibers, indicating increased calcium sensitivity. No difference in calcium sensitivity was observed between reference and residual force-enhanced contractions in trypsin-treated and osmotically compressed trypsin-treated fibers. Furthermore, calcium sensitivity after osmotic compression was lower than that observed for residual force enhancement in titin-intact skinned fibers. These results suggest that titin-based passive force regulates the increase in calcium sensitivity of residual force enhancement by a mechanism other than reduction of the myofilament lattice spacing. Copyright © 2014 the American Physiological Society.

Growth, physiological, antioxidants, and immune response of African catfish, Clarias gariepinus (B.), to dietary clove basil, Ocimum gratissimum, leaf extract and its susceptibility to Listeria monocytogenes infection.

PubMed

Abdel-Tawwab, Mohsen; Adeshina, Ibrahim; Jenyo-Oni, Adetola; Ajani, Emmanuel K; Emikpe, Benjami O

2018-04-26

Clove basil, Ocimum gratissimum, is a native plant to Africa and grows virtually in tropical and subtropical regions. It has good aroma and its leaves have become used as a spicy and in traditional medicine. The use of plant leaves in fish diets may deteriorate their growth because it may content anti-nutritional factors. Thus, it is better to use plants leaves extract. In the current study, clove basil leaves extract (CBLE) was administrated to African catfish, Clarias gariepinus (B.) to evaluate its effect on growth performance, physiological, antioxidants, and innate immunity variables. Fish (10.7 ± 0.5 g) were fed on diets enriched with 0.0, 5, 10, or 15 g CBLE/kg diet for 12 weeks. After the feeding trial, fish were further exposed to pathogenic bacteria (Listeria monocytogenes) for 14 days. Fish performance and feed intake were significantly enhanced with increasing CBLE levels and its optimum level is found to be 12 g/kg diet. It is noticed that the dietary CBLE in African catfish diets increased significantly the intestinal villi length, villi width, and absorption area in a dose-dependent manner and fish weight was highly correlated with villi length, villi width, and absorption area (R 2 = 0.91, 0.91, and 0.92, respectively). On the other side, Dietary CBLE has significant modulatory effect on hemato- and physiological variables of African catfish in a dose-dependent manner. In this regard, blood glucose and cholesterol levels decreased significantly; mean while total protein, albumin, and globulin increased significantly in fish fed high CBLE levels (10-15 g/kg diet). Furthermore, activities of aspartate aminotransferase and alanine aminotransferase, alkaline phosphatase, urea, and creatinine levels were significantly elevated with increasing dietary CBLE levels and their maximum values were detected in fish fed 15 g CBLE/kg diet. Antioxidants and immunity variables were significantly enhanced by CBLE supplementation. Additionally, fish mortality after bacterial challenge was highest in fish fed the control diet (85%) than those fed CBLE-enriched diets. The lowest fish mortality was observed in fish fed 15 g CBLE/kg diet (13.5%). This study evoked that CBLE administration enhanced the performance, feed utilization, antioxidant, and innate immunity properties of African catfish with optimum level of 12 g/kg diet. Also, its supplementation enhanced fish challenge against L. monocytogenes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Establishment, characterization and immortalization of a fibroblast cell line from the Chinese red belly toad Bombina maxima skin.

PubMed

Xiang, Yang; Gao, Qian; Su, Weiting; Zeng, Lin; Wang, Jinhuan; Hu, Yi; Nie, Wenhui; Ma, Xutong; Zhang, Yong; Lee, Wenhui; Zhang, Yun

2012-01-01

The skin of the amphibian Bombina maxima is rich in biologically active proteins and peptides, most of which have mammalian analogues. The physiological functions of most of the mammalian analogues are still unknown. Thus, Bombina maxima skin may be a promising model to reveal the physiological role of these proteins and peptides because of their large capacity for secretion. To investigate the physiological role of these proteins and peptides in vitro, a fibroblast cell line was successfully established from Bombina maxima tadpole skin. The cell line grew to form a monolayer with cells of a uniform shape and abundant rough endoplasmic reticulum, which are typical characteristics of fibroblasts. Further identification at a molecular level revealed that they strongly expressed the fibroblast marker protein vimentin. The chromosome number of these cells is 2n = 28, and most of them were diploid. Growth property analysis showed that they grew well for 14 passages. However, cells showed decreased proliferative ability after passage 15. Thus, we tried to immortalize the cells through the overexpression of SV40 T antigen. After selecting by G418, cells stably expressed SV40 large T antigen and showed enhanced proliferative ability and increased telomerase activity. Signal transduction analysis revealed functional p42 mitogen-activated protein (MAP) kinase in immortalized Bombina maxima dermal fibroblasts. Primary fibroblast cells and the immortalized fibroblast cells from Bombina maxima cultured in the present study can be used to investigate the physiological role of Bombina maxima skin-secreted proteins and peptides. In addition, the methods for primary cell culturing and cell immortalization will be useful for culturing and immortalizing cells from other types of amphibians.

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

β2-adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+-K+-ATPase Vmax in trained men.

PubMed

Hostrup, M; Kalsen, A; Ortenblad, N; Juel, C; Mørch, K; Rzeppa, S; Karlsson, S; Backer, V; Bangsbo, J

2014-12-15

The aim of the present study was to examine the effect of β2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca(2+) release and uptake, and Na(+)-K(+)-ATPase activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 males, EXP2, n = 20 males), where β2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction (MVC) of m. quadriceps was measured, followed by exercise to fatigue at 120% of maximal oxygen uptake (V̇O2, max ). A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m. quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45 s sprints. Non-fatigued MVCs were 6 ± 3 and 6 ± 2% higher (P < 0.05) with terbutaline than placebo in EXP1 and EXP2, respectively. Furthermore, peak twitch force was 11 ± 7% higher (P < 0.01) with terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to the same levels with terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half-relaxation time was prolonged (P < 0.05) with terbutaline. Rates of SR Ca(2+) release and uptake at 400 nm [Ca(2+)] were 15 ± 5 and 14 ± 5% (P < 0.05) higher, respectively, with terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na(+)-K(+)-ATPase activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in maximum rate of activity (Vmax) at time of fatigue. In conclusion, increased contractile force induced by β2-adrenergic stimulation is associated with enhanced rate of Ca(2+) release in humans. While β2-adrenergic stimulation elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps, these effects are blunted when muscles fatigue. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Bridging different perspectives of the physiological and mathematical disciplines.

PubMed

Batzel, Jerry Joseph; Hinghofer-Szalkay, Helmut; Kappel, Franz; Schneditz, Daniel; Kenner, Thomas; Goswami, Nandu

2012-12-01

The goal of this report is to discuss educational approaches for bridging the different perspectives of the physiological and mathematical disciplines. These approaches can enhance the learning experience for physiology, medical, and mathematics students and simultaneously act to stimulate mathematical/physiological/clinical interdisciplinary research. While physiology education incorporates mathematics, via equations and formulas, it does not typically provide a foundation for interdisciplinary research linking mathematics and physiology. Here, we provide insights and ideas derived from interdisciplinary seminars involving mathematicians and physiologists that have been conducted over the last decade. The approaches described here can be used as templates for giving physiology and medical students insights into how sophisticated tools from mathematics can be applied and how the disciplines of mathematics and physiology can be integrated in research, thereby fostering a foundation for interdisciplinary collaboration. These templates are equally applicable to linking mathematical methods with other life and health sciences in the educational process.

Neo-Darwinism, the Modern Synthesis and selfish genes: are they of use in physiology?

PubMed Central

Noble, Denis

2011-01-01

This article argues that the gene-centric interpretations of evolution, and more particularly the selfish gene expression of those interpretations, form barriers to the integration of physiological science with evolutionary theory. A gene-centred approach analyses the relationships between genotypes and phenotypes in terms of differences (change the genotype and observe changes in phenotype). We now know that, most frequently, this does not correctly reveal the relationships because of extensive buffering by robust networks of interactions. By contrast, understanding biological function through physiological analysis requires an integrative approach in which the activity of the proteins and RNAs formed from each DNA template is analysed in networks of interactions. These networks also include components that are not specified by nuclear DNA. Inheritance is not through DNA sequences alone. The selfish gene idea is not useful in the physiological sciences, since selfishness cannot be defined as an intrinsic property of nucleotide sequences independently of gene frequency, i.e. the ‘success’ in the gene pool that is supposed to be attributable to the ‘selfish’ property. It is not a physiologically testable hypothesis. PMID:21135048

Neo-Darwinism, the modern synthesis and selfish genes: are they of use in physiology?

PubMed

Noble, Denis

2011-03-01

This article argues that the gene-centric interpretations of evolution, and more particularly the selfish gene expression of those interpretations, form barriers to the integration of physiological science with evolutionary theory. A gene-centred approach analyses the relationships between genotypes and phenotypes in terms of differences (change the genotype and observe changes in phenotype). We now know that, most frequently, this does not correctly reveal the relationships because of extensive buffering by robust networks of interactions. By contrast, understanding biological function through physiological analysis requires an integrative approach in which the activity of the proteins and RNAs formed from each DNA template is analysed in networks of interactions. These networks also include components that are not specified by nuclear DNA. Inheritance is not through DNA sequences alone. The selfish gene idea is not useful in the physiological sciences, since selfishness cannot be defined as an intrinsic property of nucleotide sequences independently of gene frequency, i.e. the 'success' in the gene pool that is supposed to be attributable to the 'selfish' property. It is not a physiologically testable hypothesis.

Long-range correlations and fractal dynamics in C. elegans: Changes with aging and stress

NASA Astrophysics Data System (ADS)

Alves, Luiz G. A.; Winter, Peter B.; Ferreira, Leonardo N.; Brielmann, Renée M.; Morimoto, Richard I.; Amaral, Luís A. N.

2017-08-01

Reduced motor control is one of the most frequent features associated with aging and disease. Nonlinear and fractal analyses have proved to be useful in investigating human physiological alterations with age and disease. Similar findings have not been established for any of the model organisms typically studied by biologists, though. If the physiology of a simpler model organism displays the same characteristics, this fact would open a new research window on the control mechanisms that organisms use to regulate physiological processes during aging and stress. Here, we use a recently introduced animal-tracking technology to simultaneously follow tens of Caenorhabdits elegans for several hours and use tools from fractal physiology to quantitatively evaluate the effects of aging and temperature stress on nematode motility. Similar to human physiological signals, scaling analysis reveals long-range correlations in numerous motility variables, fractal properties in behavioral shifts, and fluctuation dynamics over a wide range of timescales. These properties change as a result of a superposition of age and stress-related adaptive mechanisms that regulate motility.

Therapeutic applications of hydrogels in oral drug delivery

PubMed Central

Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

2015-01-01

Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

PubMed

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Puzzle Assembly Strategy for Fabrication of Large Engineered Cartilage Tissue Constructs

PubMed Central

Nover, Adam B.; Jones, Brian K.; Yu, William T.; Donovan, Daniel S.; Podolnick, Jeremy D.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

2016-01-01

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID:26895780

Design and Application of Multifunctional DNA Nanocarriers for Therapeutic Delivery

PubMed Central

Charoenphol, Phapanin; Bermudez, Harry

2013-01-01

The unique programmability of nucleic acids offers versatility and flexibility in the creation of self-assembled DNA nanostructures. To date, many three-dimensional DNA architectures have been precisely formed of varying sizes and shapes. Their biocompatibility, biodegradability, and high intrinsic stability in physiological environments emphasize their emerging use as carriers for drug and gene delivery. Furthermore, DNA nanocarriers have been shown to enter cells efficiently and without the aid of transfection reagents. A key strength of DNA nanocarriers over other delivery systems is their modularity and their ability to control the spatial distribution of cargoes and ligands. Optimizing DNA nanocarrier properties to dictate their localization, uptake, and intracellular trafficking is also possible. In this review, we present design considerations for DNA nanocarriers and examples of their use in the context of therapeutic delivery applications. The assembly of DNA nanocarriers and approaches for loading and releasing cargo are described. The stability and safety of DNA nanocarriers is also discussed, with particular attention to the in vivo physiological environment. Mechanisms of cellular uptake and intracellular trafficking are examined, and we conclude with strategies to enhance the delivery efficiency of DNA nanocarriers. PMID:23896566

Extensive Evolution of Cereal Ribosome-Inactivating Proteins Translates into Unique Structural Features, Activation Mechanisms, and Physiological Roles

PubMed Central

De Zaeytijd, Jeroen; Van Damme, Els J. M.

2017-01-01

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic enzymes that can depurinate rRNAs thereby inhibiting protein translation. Although these proteins have also been detected in bacteria, fungi, and even some insects, they are especially prevalent in the plant kingdom. This review focuses on the RIPs from cereals. Studies on the taxonomical distribution and evolution of plant RIPs suggest that cereal RIPs have evolved at an enhanced rate giving rise to a large and heterogeneous RIP gene family. Furthermore, several cereal RIP genes are characterized by a unique domain architecture and the lack of a signal peptide. This advanced evolution of cereal RIPs translates into distinct structures, activation mechanisms, and physiological roles. Several cereal RIPs are characterized by activation mechanisms that include the proteolytic removal of internal peptides from the N-glycosidase domain, a feature not documented for non-cereal RIPs. Besides their role in defense against pathogenic fungi or herbivorous insects, cereal RIPs are also involved in endogenous functions such as adaptation to abiotic stress, storage, induction of senescence, and reprogramming of the translational machinery. The unique properties of cereal RIPs are discussed in this review paper. PMID:28353660

Extracellular Control of Limb Regeneration

NASA Astrophysics Data System (ADS)

Calve, S.; Simon, H.-G.

Adult newts possess the ability to completely regenerate organs and appendages. Immediately after limb loss, the extracellular matrix (ECM) undergoes dramatic changes that may provide mechanical and biochemical cues to guide the formation of the blastema, which is comprised of uncommitted stem-like cells that proliferate to replace the lost structure. Skeletal muscle is a known reservoir for blastema cells but the mechanism by which it contributes progenitor cells is still unclear. To create physiologically relevant culture conditions for the testing of primary newt muscle cells in vitro, the spatio-temporal distribution of ECM components and the mechanical properties of newt muscle were analyzed. Tenascin-C and hyaluronic acid (HA) were found to be dramatically upregulated in the amputated limb and were co-expressed around regenerating skeletal muscle. The transverse stiffness of muscle measured in situ was used as a guide to generate silicone-based substrates of physiological stiffness. Culturing newt muscle cells under different conditions revealed that the cells are sensitive to both matrix coating and substrate stiffness: Myoblasts on HA-coated soft substrates display a rounded morphology and become more elongated as the stiffness of the substrate increases. Coating of soft substrates with matrigel or fibronectin enhanced cell spreading and eventual cell fusion.

Towards novel compact laser sources for non-invasive diagnostics and treatment

NASA Astrophysics Data System (ADS)

Rafailov, Edik U.; Litvinova, Karina S.; Sokolovski, Sergei G.

2015-08-01

An important field of application of lasers is biomedical optics. Here, they offer great utility for diagnosis, therapy and surgery. For the development of novel methods of laser-based biomedical diagnostics careful study of light propagation in biological tissues is necessary to enhance our understanding of the optical measurements undertaken, increase research and development capacity and the diagnostic reliability of optical technologies. Ultimately, fulfilling these requirements will increase uptake in clinical applications of laser based diagnostics and therapeutics. To address these challenges informative biomarkers relevant to the biological and physiological function or disease state of the organism must be selected. These indicators are the results of the analysis of tissues and cells, such as blood. For non-invasive diagnostics peripheral blood, cells and tissue can potentially provide comprehensive information on the condition of the human organism. A detailed study of the light scattering and absorption characteristics can quickly detect physiological and morphological changes in the cells due to thermal, chemical, antibiotic treatments, etc [1-5]. The selection of a laser source to study the structure of biological particles also benefits from the fact that gross pathological changes are not induced and diagnostics make effective use of the monochromatic directional coherence properties of laser radiation.

[Pre- and post-conditioning phenomena: the protective physiological mechanisms in the aspect of pathogenesis and the theory of treatment of ENT pathology].

PubMed

Zhuravskiĭ, S G; Galagudza, M M; Ivanov, S A

2013-01-01

The objective of the present work was to expose the universal general biological significance of the protective pre- and postconditioning phenomena and to provide an insight into the possibility of application of therapeutic modalities based on these effects in current otorhinolaryngological practice. Pre- and postconditioning phenomena (Pre-C and Post-C respectively) began to be studied as protective physiological mechanisms since the 1980s, first in cardiology and thereafter in other fields of experimental medicine. At the same time, their protective properties had been known and intuitively used much earlier among the established human cultural and social stereotypes, psychophysical training techniques, and methods of traditional and empirical medicine. The widespread application of these phenomena gives evidence of their universal biological nature as factors involved in the interactions between the organism and pathogens (including co-morbidity), the process leading to the enhancement of non-specific resistance, mechanisms underlying realization of pharmacodynamic effects of a number of pharmaceutical products,etc. The understanding of the protective potential of PreC and PostC dictates the necessity to revise and further elaborate the present-day strategy of prophylaxis and treatment of the most serious chronic ENT diseases.

Intragroup Emotions: Physiological Linkage and Social Presence.

PubMed

Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

2016-01-01

We investigated how technologically mediating two different components of emotion-communicative expression and physiological state-to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

Heat and Moisture transport of socks

NASA Astrophysics Data System (ADS)

Komárková, P.; Glombíková, V.; Havelka, A.

2017-10-01

Investigating the liquid moisture transport and thermal properties is essential for understanding physiological comfort of clothes. This study reports on an experimental investigation of moisture management transport and thermal transport on the physiological comfort of commercially available socks. There are subjective evaluation and objective measurements. Subjective evaluation of the physiological comfort of socks is based on individual sensory perception of probands during and after physical exertion. Objective measurements were performed according to standardized methods using Moisture Management tester for measuring the humidity parameters and C-term TCi analyzer for thermal conductivity and thermal effusivity. The obtained values of liquid moisture transport and thermal properties were related to the material composition and structure of the tested socks. In summary, these results show that objective measurement corresponds with probands feelings.

Morphology, physiology, genetics, enigmas, and status of an extremely rare tree: Mutant tanoak

Treesearch

Philip M. McDonald; Jianwei Zhang; Randy S. Senock; Jessica W. Wright

2013-01-01

Important physical characteristics, morphological attributes, physiological functions, and genetic properties of mutant tanoak, Notholithocarpus densiflorus f. attenuato-dentatus (Fagaceae), and normal tanoak, Notholithocarpus densiflorus (Hook. & Arn.) Manos, Cannon & S. H. Oh, were studied on the Challenge...

Effects of plyometric and isometric training on muscle and tendon stiffness in vivo.

PubMed

Kubo, Keitaro; Ishigaki, Tomonobu; Ikebukuro, Toshihiro

2017-08-01

The purpose of this study was to compare the effects of plyometric and isometric training on tendon properties during ramp and ballistic contractions and muscle stiffness under passive and active conditions. Eleven subjects completed 12 weeks (3 days/week) of a unilateral training program for the plantar flexors. They performed plyometric training on one side (PLY) and isometric training on the other side (ISO). Active muscle stiffness in the medial gastrocnemius muscle was calculated according to changes in estimated muscle force and fascicle length during fast stretching after submaximal isometric contractions. Passive muscle stiffness was also calculated from estimated passive muscle force and fascicle length during slow passive stretching. Stiffness and hysteresis of tendon structures were measured using ultrasonography during ramp and ballistic contractions. Passive muscle stiffness and tendon hysteresis did not change for PLY or ISO Active muscle stiffness significantly increased for PLY, but not for ISO Tendon stiffness during ramp and ballistic contractions increased significantly for ISO, but not for PLY In addition, tendon elongation values at force production levels beyond 100 N during ballistic contractions increased for PLY These results suggest that plyometric training (but not isometric training) enhances the extensibility of tendon structures during ballistic contractions and active muscle stiffness during fast stretching, and these changes may be related to improved performances during stretch-shortening cycle exercises. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

A Neural Network Guide to Teaching. Fastback 431.

ERIC Educational Resources Information Center

Baker, Justine C.; Martin, Francis G.

This booklet proposes a model for learning that provides insight into the underlying physiology of the brain and suggests teaching strategies of repetition, variety and pattern, and incubation consistent with that physiology. It discusses how these three strategies can be used to enhance learning in the cognitive, psychomotor, and affective…

Practical Application of Fundamental Concepts in Exercise Physiology

ERIC Educational Resources Information Center

Ramsbottom R.; Kinch, R. F. T.; Morris, M. G.; Dennis, A. M.

2007-01-01

The collection of primary data in laboratory classes enhances undergraduate practical and critical thinking skills. The present article describes the use of a lecture program, running in parallel with a series of linked practical classes, that emphasizes classical or standard concepts in exercise physiology. The academic and practical program ran…

Impact of serotonin 2C receptor null mutation on physiology and behavior associated with nigrostriatal dopamine pathway function.

PubMed

Abdallah, Luna; Bonasera, Stephen J; Hopf, F Woodward; O'Dell, Laura; Giorgetti, Marco; Jongsma, Minke; Carra, Scott; Pierucci, Massimo; Di Giovanni, Giuseppe; Esposito, Ennio; Parsons, Loren H; Bonci, Antonello; Tecott, Laurence H

2009-06-24

The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT(2C)R) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT(2C)Rs produces marked alterations in the activity and functional output of this pathway. 5-HT(2C)R mutant mice displayed increased activity of substantia nigra pars compacta (SNc) dopaminergic neurons, elevated baseline extracellular dopamine concentrations in the dorsal striatum (DSt), alterations in grooming behavior, and enhanced sensitivity to the stereotypic behavioral effects of d-amphetamine and GBR 12909. These psychostimulant responses occurred in the absence of phenotypic differences in drug-induced extracellular dopamine concentration, suggesting a phenotypic alteration in behavioral responses to released dopamine. This was further suggested by enhanced behavioral responses of mutant mice to the D(1) receptor agonist SKF 81297. Differences in DSt D(1) or D(2) receptor expression were not found, nor were differences in medium spiny neuron firing patterns or intrinsic membrane properties following dopamine stimulation. We conclude that 5-HT(2C)Rs regulate nigrostriatal dopaminergic activity and function both at SNc dopaminergic neurons and at a locus downstream of the DSt.

Functionalization of biodegradable magnesium alloy implants with alkylphosphonate self-assembled films.

PubMed

Grubač, Z; Metikoš-Huković, M; Babić, R; Rončević, I Škugor; Petravić, M; Peter, R

2013-05-01

Mg and Mg-alloys are promising materials for biodegradable implants. In order to slowdown the Mg-alloy (AZ91D) degradation and enhance its biocompatibility, the alloy surface was modified with alkylphosphonate self-assembling films. The binding configuration and the structural organization of alkylphosphonate monolayers on the Mg-alloy surface were investigated using contact angle measurements, FTIR, and XPS. Combination of FTIR and XPS data indicated the presence of several different bonding modes (mono-, di-, and tri dentate) of phosphonate head groups with the alloy surface. The existence of well organized and ordered self-assembled alkylphosphonate monolayers with good barrier protecting properties in a physiological solution is a key step in the development of biocompatible Mg-alloy implants. Copyright © 2013 Elsevier B.V. All rights reserved.

Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical properties of cells

NASA Astrophysics Data System (ADS)

Gardel, M. L.; Nakamura, F.; Hartwig, J. H.; Crocker, J. C.; Stossel, T. P.; Weitz, D. A.

2006-02-01

We show that actin filaments, shortened to physiological lengths by gelsolin and cross-linked with recombinant human filamins (FLNs), exhibit dynamic elastic properties similar to those reported for live cells. To achieve elasticity values of comparable magnitude to those of cells, the in vitro network must be subjected to external prestress, which directly controls network elasticity. A molecular requirement for the strain-related behavior at physiological conditionsis a flexible hinge found in FLNa and some FLNb molecules. Basic physical properties of the in vitro filamin-F-actin network replicate the essential mechanical properties of living cells. This physical behavior could accommodate passive deformation and internal organelle trafficking at low strains yet resist externally or internally generated high shear forces. cytoskeleton | cell mechanics | nonlinear rheology

Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

PubMed Central

Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

2010-01-01

Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue in the sac of our models could have an effect on the compliance of the model neck. Conclusions Ideal AAA models with physiological properties were manufactured. The behaviour of these models due to pressurisation was predicted using FEA, validating this technique for the future design of realistic, physiological AAA models. Addition of ILT analogues in the aneurysm sac was shown to affect neck behaviour. This could have implications for endovascular AAA repair due to the importance of the neck for stent-graft fixation. PMID:20524746

Fundamentals of quantitative dynamic contrast-enhanced MR imaging.

PubMed

Paldino, Michael J; Barboriak, Daniel P

2009-05-01

Quantitative analysis of dynamic contrast-enhanced MR imaging (DCE-MR imaging) has the power to provide information regarding physiologic characteristics of the microvasculature and is, therefore, of great potential value to the practice of oncology. In particular, these techniques could have a significant impact on the development of novel anticancer therapies as a promising biomarker of drug activity. Standardization of DCE-MR imaging acquisition and analysis to provide more reproducible measures of tumor vessel physiology is of crucial importance to realize this potential. The purpose of this article is to review the pathophysiologic basis and technical aspects of DCE-MR imaging techniques.

Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom.

PubMed

Fontana, Andréia Cristina Karklin; de Oliveira Beleboni, Renê; Wojewodzic, Marcin Wlodzimierz; Ferreira Dos Santos, Wagner; Coutinho-Netto, Joaquim; Grutle, Nina Julie; Watts, Spencer D; Danbolt, Niels Christian; Amara, Susan G

2007-11-01

Previous studies have shown that a compound purified from the spider Parawixia bistriata venom stimulates the activity of glial glutamate transporters and can protect retinal tissue from ischemic damage. To understand the mechanism by which this compound enhances transport, we examined its effects on the functional properties of glutamate transporters after solubilization and reconstitution in liposomes and in transfected COS-7 cells. Here, we demonstrate in both systems that Parawixin1 promotes a direct and selective enhancement of glutamate influx by the EAAT2 transporter subtype through a mechanism that does not alter the apparent affinities for the cosubstrates glutamate or sodium. In liposomes, we observed maximal enhancement by Parawixin1 when extracellular sodium and intracellular potassium concentrations are within physiological ranges. Moreover, the compound does not enhance the reverse transport of glutamate under ionic conditions that favor efflux, when extracellular potassium is elevated and the sodium gradient is reduced, nor does it alter the exchange of glutamate in the absence of internal potassium. These observations suggest that Parawixin1 facilitates the reorientation of the potassium-bound transporter, the rate-limiting step in the transport cycle, a conclusion further supported by experiments showing that Parawixin1 does not stimulate uptake by an EAAT2 transport mutant (E405D) defective in the potassium-dependent reorientation step. Thus, Parawixin1 enhances transport through a novel mechanism targeting a step in the transport cycle distinct from substrate influx or efflux and provides a basis for the design of new drugs that act allosterically on transporters to increase glutamate clearance.

Enhancing team-sport athlete performance: is altitude training relevant?

PubMed

Billaut, François; Gore, Christopher J; Aughey, Robert J

2012-09-01

Field-based team sport matches are composed of short, high-intensity efforts, interspersed with intervals of rest or submaximal exercise, repeated over a period of 60-120 minutes. Matches may also be played at moderate altitude where the lower oxygen partial pressure exerts a detrimental effect on performance. To enhance run-based performance, team-sport athletes use varied training strategies focusing on different aspects of team-sport physiology, including aerobic, sprint, repeated-sprint and resistance training. Interestingly, 'altitude' training (i.e. living and/or training in O(2)-reduced environments) has only been empirically employed by athletes and coaches to improve the basic characteristics of speed and endurance necessary to excel in team sports. Hypoxia, as an additional stimulus to training, is typically used by endurance athletes to enhance performance at sea level and to prepare for competition at altitude. Several approaches have evolved in the last few decades, which are known to enhance aerobic power and, thus, endurance performance. Altitude training can also promote an increased anaerobic fitness, and may enhance sprint capacity. Therefore, altitude training may confer potentially-beneficial adaptations to team-sport athletes, which have been overlooked in contemporary sport physiology research. Here, we review the current knowledge on the established benefits of altitude training on physiological systems relevant to team-sport performance, and conclude that current evidence supports implementation of altitude training modalities to enhance match physical performances at both sea level and altitude. We hope that this will guide the practice of many athletes and stimulate future research to better refine training programmes.

Intragroup Emotions: Physiological Linkage and Social Presence

PubMed Central

Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

2016-01-01

We investigated how technologically mediating two different components of emotion—communicative expression and physiological state—to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

Modulation of Emotional Appraisal by False Physiological Feedback during fMRI

PubMed Central

Gray, Marcus A.; Harrison, Neil A.; Wiens, Stefan; Critchley, Hugo D.

2007-01-01

Background James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. Methodology/Principal Findings We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. Conclusions/Significance Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order “cognitive” representations of bodily arousal state. PMID:17579718

Saponins from Tribulus terrestris L. protect human keratinocytes from UVB-induced damage.

PubMed

Sisto, Margherita; Lisi, Sabrina; D'Amore, Massimo; De Lucro, Raffaella; Carati, Davide; Castellana, Donatello; La Pesa, Velia; Zuccarello, Vincenzo; Lofrumento, Dario D

2012-12-05

Chronic exposure to solar UVB radiation damages skin, increasing the risk to develop cancer. Hence the identification of compounds with a photoprotective efficacy is essential. This study examined the role of saponins derived from Tribulus terrestris L. (TT) on the modulation of apoptosis in normal human keratinocytes (NHEK) exposed to physiological doses of UVB and to evaluate their antitumoral properties. In NHEK, TT saponins attenuate UVB-induced programmed cell death through inhibition of intrinsic apoptotic pathway. In squamous cell carcinomas (SCC) TT saponins do not make the malignant keratinocytes more resistant to UVB and determine an enhanced apoptotic response. The photoprotective effect of TT saponins is tightly correlated to the enhancement of NER genes expression and the block of UVB-mediated NF-κB activation. Collectively, our study shows experimental evidence that TT has a preventive efficacy against UVB-induced carcinogenesis and the molecular knowledge on the mechanisms through which TT saponins regulate cell death suggests great potential for TT to be developed into a new medicine for cancer patients. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.

Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, themore » released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.« less

Enhanced butyric acid tolerance and bioproduction by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor.

PubMed

Jiang, Ling; Wang, Jufang; Liang, Shizhong; Cai, Jin; Xu, Zhinan; Cen, Peilin; Yang, Shangtian; Li, Shuang

2011-01-01

Repeated fed-batch fermentation of glucose by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor (FBB) was successfully employed to produce butyric acid at a high final concentration as well as to adapt a butyric-acid-tolerant strain. At the end of the eighth fed-batch fermentation, the butyric acid concentration reached 86.9 ± 2.17 g/L, which to our knowledge is the highest butyric acid concentration ever produced in the traditional fermentation process. To understand the mechanism and factors contributing to the improved butyric acid production and enhanced acid tolerance, adapted strains were harvested from the FBB and characterized for their physiological properties, including specific growth rate, acid-forming enzymes, intracellular pH, membrane-bound ATPase and cell morphology. Compared with the original culture used to seed the bioreactor, the adapted culture showed significantly reduced inhibition effects of butyric acid on specific growth rate, cellular activities of butyric-acid-forming enzyme phosphotransbutyrylase (PTB) and ATPase, together with elevated intracellular pH, and elongated rod morphology. © 2010 Wiley Periodicals, Inc.

Manipulating neural activity in physiologically classified neurons: triumphs and challenges

PubMed Central

Gore, Felicity; Schwartz, Edmund C.; Salzman, C. Daniel

2015-01-01

Understanding brain function requires knowing both how neural activity encodes information and how this activity generates appropriate responses. Electrophysiological, imaging and immediate early gene immunostaining studies have been instrumental in identifying and characterizing neurons that respond to different sensory stimuli, events and motor actions. Here we highlight approaches that have manipulated the activity of physiologically classified neurons to determine their role in the generation of behavioural responses. Previous experiments have often exploited the functional architecture observed in many cortical areas, where clusters of neurons share response properties. However, many brain structures do not exhibit such functional architecture. Instead, neurons with different response properties are anatomically intermingled. Emerging genetic approaches have enabled the identification and manipulation of neurons that respond to specific stimuli despite the lack of discernable anatomical organization. These approaches have advanced understanding of the circuits mediating sensory perception, learning and memory, and the generation of behavioural responses by providing causal evidence linking neural response properties to appropriate behavioural output. However, significant challenges remain for understanding cognitive processes that are probably mediated by neurons with more complex physiological response properties. Currently available strategies may prove inadequate for determining how activity in these neurons is causally related to cognitive behaviour. PMID:26240431

Cactus stem (Opuntia ficus-indica Mill): anatomy, physiology and chemical composition with emphasis on its biofunctional properties.

PubMed

Ventura-Aguilar, Rosa Isela; Bosquez-Molina, Elsa; Bautista-Baños, Silvia; Rivera-Cabrera, Fernando

2017-12-01

Cactus stem (Opuntia ficus-indica Mill) is native to Mesoamerica and marketed in different forms such as fresh, frozen or pre-cooked. Worldwide, this vegetable is recognized for its pharmaceutical actions, including its antioxidant, diuretic, anticarcinogenic, anti-inflammatory, anti-diabetic, and anti-hypercholesterolemic properties, as well as their antiviral and antispermatogenic effects. However, not all of these properties have been associated with its chemical composition; therefore, this review aims to present and integrate information available on the physiology and anatomy of cactus stem and its chemical composition, focusing on some of the many factors that determine its biofunctionality. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

[In life determination of the physiological status of decapod crustaceans (Crustacea: Decapoda) by hematological characteristics].

PubMed

Aleksandrova, E N; Kovacheva, N P

2010-01-01

The application of hematological analysis techniques to detecting the physiological status of the economically valued decapods during their culturing, and in monitoring of the condition of their natural populations, is restrained by the incomplete knowledge of these invertebrates circulatory system and its properties. Scarce data on the use of hematological indicators for determining the physiological status of decapods may be found sporadically in published sources; there is shortage of basic standards needed for interpretation of the analytical results. In this regard the paper considers some data on the major properties of hemolymph and its cellular elements; on methods of their examination; and on the results of application of hematological characteristics to assessing the physiological condition of various species of decapods. The hematological indicators suitable for the analysis of live decapods include: time of coagulation and buffer characteristic of hemolymph; concentration of total proteins, copper, calcium, glucose and lactates in it; total number of hemocytes with the consideration of granulocytes share.

A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction.

PubMed

Sharma, Neeraj; LaRusch, Jessica; Sosnay, Patrick R; Gottschalk, Laura B; Lopez, Andrea P; Pellicore, Matthew J; Evans, Taylor; Davis, Emily; Atalar, Melis; Na, Chan-Hyun; Rosson, Gedge D; Belchis, Deborah; Milewski, Michal; Pandey, Akhilesh; Cutting, Garry R

2016-12-01

The development of cystic fibrosis transmembrane conductance regulator (CFTR) targeted therapy for cystic fibrosis has generated interest in maximizing membrane residence of mutant forms of CFTR by manipulating interactions with scaffold proteins, such as sodium/hydrogen exchange regulatory factor-1 (NHERF1). In this study, we explored whether COOH-terminal sequences in CFTR beyond the PDZ-binding motif influence its interaction with NHERF1. NHERF1 displayed minimal self-association in blot overlays (NHERF1, K d = 1,382 ± 61.1 nM) at concentrations well above physiological levels, estimated at 240 nM from RNA-sequencing and 260 nM by liquid chromatography tandem mass spectrometry in sweat gland, a key site of CFTR function in vivo. However, NHERF1 oligomerized at considerably lower concentrations (10 nM) in the presence of the last 111 amino acids of CFTR (20 nM) in blot overlays and cross-linking assays and in coimmunoprecipitations using differently tagged versions of NHERF1. Deletion and alanine mutagenesis revealed that a six-amino acid sequence 1417 EENKVR 1422 and the terminal 1478 TRL 1480 (PDZ-binding motif) in the COOH-terminus were essential for the enhanced oligomerization of NHERF1. Full-length CFTR stably expressed in Madin-Darby canine kidney epithelial cells fostered NHERF1 oligomerization that was substantially reduced (∼5-fold) on alanine substitution of EEN, KVR, or EENKVR residues or deletion of the TRL motif. Confocal fluorescent microscopy revealed that the EENKVR and TRL sequences contribute to preferential localization of CFTR to the apical membrane. Together, these results indicate that COOH-terminal sequences mediate enhanced NHERF1 interaction and facilitate the localization of CFTR, a property that could be manipulated to stabilize mutant forms of CFTR at the apical surface to maximize the effect of CFTR-targeted therapeutics. Copyright © 2016 the American Physiological Society.

Post-fertilization physiology and growth performance of loblolly pine clones

Treesearch

N.T. King; J.R. Seiler; T.R. Fox; KurtH Johnsen

2008-01-01

The physiological processes leading to enhanced growth of loblolly pine (Pinus taeda L.) following fertilization are not clearly understood. Part of the debate revolves around the temporal response of net photosynthetic rate (An) to fertilization and whether the An response is always positive. We measured light-saturated photosynthetic rate (Asat), dark respiration...

Short-term effects of fertilization on loblolly pine (Pinus taeda L.) physiology

Treesearch

C.M. Gough; J.R. Seiler; Chris A. Maier

2004-01-01

Fertilization commonly increases biomass production in loblolly pine (Pinus taeda L.). However, the sequence of short-term physiological adjustments allowing for the establishment of leaf area and enhanced growth is not well understood. The effects of fertilization on photosynthetic parameters, root respiration, and growth for over 200 d following...

Adventures in Exercise Physiology: Enhancing Problem Solving and Assessment

ERIC Educational Resources Information Center

FitzPatrick, Kathleen A.

2004-01-01

I altered the format of an exercise physiology course from traditional lecture to emphasizing daily reading quizzes and group problem-solving activities. I used the SALGains evaluation to compare the two approaches and saw significant improvements in the evaluation ratings of students who were taught using the new format. Narrative responses…

Physiological response to water immersion: a method for sport recovery?

PubMed

Wilcock, Ian M; Cronin, John B; Hing, Wayne A

2006-01-01

Recovery from exercise can be an important factor in performance during repeated bouts of exercise. In a tournament situation, where athletes may compete numerous times over a few days, enhancing recovery may provide a competitive advantage. One method that is gaining popularity as a means to enhance post-game or post-training recovery is immersion in water. Much of the literature on the ability of water immersion as a means to improve athletic recovery appears to be based on anecdotal information, with limited research on actual performance change. Water immersion may cause physiological changes within the body that could improve recovery from exercise. These physiological changes include intracellular-intravascular fluid shifts, reduction of muscle oedema and increased cardiac output (without increasing energy expenditure), which increases blood flow and possible nutrient and waste transportation through the body. Also, there may be a psychological benefit to athletes with a reduced cessation of fatigue during immersion. Water temperature alters the physiological response to immersion and cool to thermoneutral temperatures may provide the best range for recovery. Further performance-orientated research is required to determine whether water immersion is beneficial to athletes.

Composite Materials with Magnetically Aligned Carbon Nanoparticles Having Enhanced Electrical Properties and Methods of Preparation

NASA Technical Reports Server (NTRS)

Peterson, G.P. (Bud) (Inventor); Hong, Haiping (Inventor); Salem, David R. (Inventor)

2016-01-01

Magnetically aligned carbon nanoparticle composites have enhanced electrical properties. The composites comprise carbon nanoparticles, a host material, magnetically sensitive nanoparticles and a surfactant. In addition to enhanced electrical properties, the composites can have enhanced mechanical and thermal properties.

Novel use of a noninvasive hemodynamic monitor in a personalized, active learning simulation.

PubMed

Zoller, Jonathan K; He, Jianghua; Ballew, Angela T; Orr, Walter N; Flynn, Brigid C

2017-06-01

The present study furthered the concept of simulation-based medical education by applying a personalized active learning component. We tested this novel approach utilizing a noninvasive hemodynamic monitor with the capability to measure and display in real time numerous hemodynamic parameters in the exercising participant. Changes in medical knowledge concerning physiology were examined with a pre-and posttest. Simply by observation of one's own hemodynamic variables, the understanding of complex physiological concepts was significantly enhanced. Copyright © 2017 the American Physiological Society.

Enzyme technology for precision functional food ingredient processes.

PubMed

Meyer, Anne S

2010-03-01

A number of naturally occurring dietary substances may exert physiological benefits. The production of enhanced levels or particularly tailored versions of such candidate functional compounds can be targeted by enzymatic catalysis. The recent literature contains examples of enhancing bioavailability of iron via enzyme-catalyzed degradation of phytate in wheat bran, increasing diacyl-glycerol and conjugated linoleic acid levels by lipase action, enhancing the absorption of the citrus flavonoid hesperetin via rhamnosidase treatment, and obtaining solubilized dietary fiber via enzymatic modification of potato starch processing residues. Such targeted enzyme-catalyzed reactions provide new invention opportunities for designing functional foods with significant health benefits. The provision of well-defined naturally structured compounds can, moreover, assist in obtaining the much-needed improved understanding of the physiological benefits of complex natural substances.

A PP2A-mediated feedback mechanism controls Ca2+-dependent NO synthesis under physiological oxygen.

PubMed

Keeley, Thomas P; Siow, Richard C M; Jacob, Ron; Mann, Giovanni E

2017-12-01

Intracellular O 2 is a key regulator of NO signaling, yet most in vitro studies are conducted in atmospheric O 2 levels, hyperoxic with respect to the physiologic milieu. We investigated NO signaling in endothelial cells cultured in physiologic (5%) O 2 and stimulated with histamine or shear stress. Culture of cells in 5% O 2 (>5 d) decreased histamine- but not shear stress-stimulated endothelial (e)NOS activity. Unlike cells adapted to a hypoxic environment (1% O 2 ), those cultured in 5% O 2 still mobilized sufficient Ca 2+ to activate AMPK. Enhanced expression and membrane targeting of PP2A-C was observed in 5% O 2 , resulting in greater interaction with eNOS in response to histamine. Moreover, increased dephosphorylation of eNOS in 5% O 2 was Ca 2+ -sensitive and reversed by okadaic acid or PP2A-C siRNA. The present findings establish that Ca 2+ mobilization stimulates both NO synthesis and PP2A-mediated eNOS dephosphorylation, thus constituting a novel negative feedback mechanism regulating eNOS activity not present in response to shear stress. This, coupled with enhanced NO bioavailability, underpins differences in NO signaling induced by inflammatory and physiologic stimuli that are apparent only in physiologic O 2 levels. Furthermore, an explicit delineation between physiologic normoxia and genuine hypoxia is defined here, with implications for our understanding of pathophysiological hypoxia.-Keeley, T. P., Siow, R. C. M., Jacob, R., Mann, G. E. A PP2A-mediated feedback mechanism controls Ca 2+ -dependent NO synthesis under physiological oxygen. © The Author(s).

Stress inoculation training supported by physiology-driven adaptive virtual reality stimulation.

PubMed

Popović, Sinisa; Horvat, Marko; Kukolja, Davor; Dropuljić, Branimir; Cosić, Kresimir

2009-01-01

Significant proportion of psychological problems related to combat stress in recent large peacekeeping operations underscores importance of effective methods for strengthening the stress resistance of military personnel. Adaptive control of virtual reality (VR) stimulation, based on estimation of the subject's emotional state from physiological signals, may enhance existing stress inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor the progress of stressful stimuli delivery to the physiological characteristics of each individual, which is indicated for improvement in stress resistance. Therefore, following an overview of SIT and its applications in the military setting, generic concept of physiology-driven adaptive VR stimulation is presented in the paper. Toward the end of the paper, closed-loop adaptive control strategy applicable to SIT is outlined.

Physiology-driven adaptive virtual reality stimulation for prevention and treatment of stress related disorders.

PubMed

Cosić, Kresimir; Popović, Sinisa; Kukolja, Davor; Horvat, Marko; Dropuljić, Branimir

2010-02-01

The significant proportion of severe psychological problems related to intensive stress in recent large peacekeeping operations underscores the importance of effective methods for strengthening the prevention and treatment of stress-related disorders. Adaptive control of virtual reality (VR) stimulation presented in this work, based on estimation of the person's emotional state from physiological signals, may enhance existing stress inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor the progress of stressful stimuli delivery to the physiological characteristics of each individual, which is indicated for improvement in stress resistance. Following an overview of physiology-driven adaptive VR stimulation, its major functional subsystems are described in more detail. A specific algorithm of stimuli delivery applicable to SIT is outlined.

Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells

DOE PAGES

Hayashi, Yohei; Caboni, Laura; Das, Debanu; ...

2015-03-30

NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its structural analysis are poorly understood. Here we determined the crystal structure of the human NANOG homeodomain (hNANOG HD) bound to an OCT4 promoter DNA, which revealed amino acid residues involved in DNA recognition that are likely to be functionally important. We generated a series of hNANOG HD alanine substitution mutantsmore » based on the protein–DNA interaction and evolutionary conservation and determined their biological activities. Some mutant proteins were less stable, resulting in loss or decreased affinity for DNA binding. Overexpression of the orthologous mouse NANOG (mNANOG) mutants failed to maintain self-renewal of mouse embryonic stem cells without leukemia inhibitory factor. These results suggest that these residues are critical for NANOG transcriptional activity. Interestingly, one mutant, hNANOG L122A, conversely enhanced protein stability and DNA-binding affinity. The mNANOG L122A, when overexpressed in mouse embryonic stem cells, maintained their expression of self-renewal markers even when retinoic acid was added to forcibly drive differentiation. When overexpressed in epiblast stem cells or human induced pluripotent stem cells, the L122A mutants enhanced reprogramming into ground-state pluripotency. These findings indicate that structural and biophysical information on key transcriptional factors provides insights into the manipulation of stem cell behaviors and a framework for rational protein engineering.« less

Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells

PubMed Central

Hayashi, Yohei; Caboni, Laura; Das, Debanu; Yumoto, Fumiaki; Clayton, Thomas; Deller, Marc C.; Nguyen, Phuong; Farr, Carol L.; Chiu, Hsiu-Ju; Miller, Mitchell D.; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Tomoda, Kiichiro; Conklin, Bruce R.; Wilson, Ian A.; Yamanaka, Shinya; Fletterick, Robert J.

2015-01-01

NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its structural analysis are poorly understood. Here we determined the crystal structure of the human NANOG homeodomain (hNANOG HD) bound to an OCT4 promoter DNA, which revealed amino acid residues involved in DNA recognition that are likely to be functionally important. We generated a series of hNANOG HD alanine substitution mutants based on the protein–DNA interaction and evolutionary conservation and determined their biological activities. Some mutant proteins were less stable, resulting in loss or decreased affinity for DNA binding. Overexpression of the orthologous mouse NANOG (mNANOG) mutants failed to maintain self-renewal of mouse embryonic stem cells without leukemia inhibitory factor. These results suggest that these residues are critical for NANOG transcriptional activity. Interestingly, one mutant, hNANOG L122A, conversely enhanced protein stability and DNA-binding affinity. The mNANOG L122A, when overexpressed in mouse embryonic stem cells, maintained their expression of self-renewal markers even when retinoic acid was added to forcibly drive differentiation. When overexpressed in epiblast stem cells or human induced pluripotent stem cells, the L122A mutants enhanced reprogramming into ground-state pluripotency. These findings demonstrate that structural and biophysical information on key transcriptional factors provides insights into the manipulation of stem cell behaviors and a framework for rational protein engineering. PMID:25825768

Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells

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

Hayashi, Yohei; Caboni, Laura; Das, Debanu

NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its structural analysis are poorly understood. Here we determined the crystal structure of the human NANOG homeodomain (hNANOG HD) bound to an OCT4 promoter DNA, which revealed amino acid residues involved in DNA recognition that are likely to be functionally important. We generated a series of hNANOG HD alanine substitution mutantsmore » based on the protein–DNA interaction and evolutionary conservation and determined their biological activities. Some mutant proteins were less stable, resulting in loss or decreased affinity for DNA binding. Overexpression of the orthologous mouse NANOG (mNANOG) mutants failed to maintain self-renewal of mouse embryonic stem cells without leukemia inhibitory factor. These results suggest that these residues are critical for NANOG transcriptional activity. Interestingly, one mutant, hNANOG L122A, conversely enhanced protein stability and DNA-binding affinity. The mNANOG L122A, when overexpressed in mouse embryonic stem cells, maintained their expression of self-renewal markers even when retinoic acid was added to forcibly drive differentiation. When overexpressed in epiblast stem cells or human induced pluripotent stem cells, the L122A mutants enhanced reprogramming into ground-state pluripotency. These findings indicate that structural and biophysical information on key transcriptional factors provides insights into the manipulation of stem cell behaviors and a framework for rational protein engineering.« less

Drug-Loaded Nanoemulsions/Microbubbles for Combined Tumor Imaging and Therapy

NASA Astrophysics Data System (ADS)

Rapoport, Natalya; Gao, Zhonggao; Kennedy, Ann

2007-05-01

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated intracellular drug delivery was developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. The nanodroplets convert into microbubbles upon heating to physiological temperatures. The phase state of the systems and nanodroplet size may be controlled by the copolymer/perfluorocarbon volume ratio. Three areas observed in phase diagrams correspond to micelles; micelle/microbubble coexistence; and nano/microbubble coexistence. These systems manifest a relatively high drug loading capacity (about 15 % wt/wt). As indicated by biodistribution measurements and ultrasound imaging, the micelles and nanobubbles extravasate selectively into the tumor interstitia. Microbubble cavitate and collapse under the action of tumor-directed ultrasound, resulting in a dramatically enhanced intracellular drug uptake by the tumor cells. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume confirming nanobubble extravasation through the defected tumor microvasculature and suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Tumor contrast increases in time confirming gradual accumulation of echogenic microbubbles in the tumor tissue, presumably via the enhanced penetration and retention (EPR) effect.

Membrane lipid physiology and toxin catabolism underlie ethanol and acetic acid tolerance in Drosophila melanogaster.

PubMed

Montooth, Kristi L; Siebenthall, Kyle T; Clark, Andrew G

2006-10-01

Drosophila melanogaster has evolved the ability to tolerate and utilize high levels of ethanol and acetic acid encountered in its rotting-fruit niche. Investigation of this phenomenon has focused on ethanol catabolism, particularly by the enzyme alcohol dehydrogenase. Here we report that survival under ethanol and acetic acid stress in D. melanogaster from high- and low-latitude populations is an integrated consequence of toxin catabolism and alteration of physical properties of cellular membranes by ethanol. Metabolic detoxification contributed to differences in ethanol tolerance between populations and acclimation temperatures via changes in both alcohol dehydrogenase and acetyl-CoA synthetase mRNA expression and enzyme activity. Independent of changes in ethanol catabolism, rapid thermal shifts that change membrane fluidity had dramatic effects on ethanol tolerance. Cold temperature treatments upregulated phospholipid metabolism genes and enhanced acetic acid tolerance, consistent with the predicted effects of restoring membrane fluidity. Phospholipase D was expressed at high levels in all treatments that conferred enhanced ethanol tolerance, suggesting that this lipid-mediated signaling enzyme may enhance tolerance by sequestering ethanol in membranes as phophatidylethanol. These results reveal new candidate genes underlying toxin tolerance and membrane adaptation to temperature in Drosophila and provide insight into how interactions between these phenotypes may underlie the maintenance of latitudinal clines in ethanol tolerance.

Intrinsic Plasticity Induced by Group II Metabotropic Glutamate Receptors via Enhancement of High Threshold KV Currents in Sound Localizing Neurons

PubMed Central

Hamlet, William R.; Lu, Yong

2016-01-01

Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization. We found that activation of mGluR II by synthetic agonists resulted in a selective increase of the high threshold KV currents. More importantly, synaptically released glutamate (with reuptake blocked) also enhanced the high threshold KV currents. The enhancement was frequency-coding region dependent, being more pronounced in low frequency neurons compared to middle and high frequency neurons. The intracellular mechanism involved the Gβγ signaling pathway associated with phospholipase C and protein kinase C. The modulation strengthened membrane outward rectification, sharpened action potentials, and improved the ability of NL neurons to follow high frequency inputs. These data suggest that mGluR II provides a feedforward modulatory mechanism that may regulate temporal processing under the condition of heightened synaptic inputs. PMID:26964678

Phage Therapy: Eco-Physiological Pharmacology

PubMed Central

Abedon, Stephen T.

2014-01-01

Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies), impact on body-associated microbiota (as ecological communities), and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology. PMID:25031881

The carbohydrate maintenance properties of an experimental sports drink.

PubMed Central

White, J. A.; Ford, M. A.

1984-01-01

The effects of an experimental sports drink (Q) were compared with a commercial sports drink (D) of proven ergogenic efficacy. Seven highly trained subjects performed two hours of cycle ergometry exercise at approximately 65% maximal aerobic power (VO2 max) while receiving levels of Q and D in quantities designed to supply approximately 28% of the total energy requirement of the exercise task. Both Q and D formulations were supplied at 15 minute intervals at 16 degrees C, in volumes required to provide equivalent carbohydrate loads from two products of differing concentrations and compositions. Q was equally as effective as D in terms of the maintenance of plasma glucose concentrations during exercise, while selected physiological indices of work performance favoured Q. However, the time course of plasma glucose concentration changes during and after exercise indicated a trend towards more rapid uptake and assimilation of carbohydrate in the case of Q. The findings suggest that Q may provide a more readily available carbohydrate source during exercise and may enhance work performance through its ergogenic properties. Images p64-a p64-b PMID:6466932

Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

PubMed Central

Diez-Silva, Monica; Park, YongKeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

2012-01-01

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host. PMID:22937223

Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

NASA Astrophysics Data System (ADS)

Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

2012-08-01

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper.

PubMed

Farmakis, Dimitrios; Alvarez, Julian; Gal, Tuvia Ben; Brito, Dulce; Fedele, Francesco; Fonseca, Candida; Gordon, Anthony C; Gotsman, Israel; Grossini, Elena; Guarracino, Fabio; Harjola, Veli-Pekka; Hellman, Yaron; Heunks, Leo; Ivancan, Visnja; Karavidas, Apostolos; Kivikko, Matti; Lomivorotov, Vladimir; Longrois, Dan; Masip, Josep; Metra, Marco; Morelli, Andrea; Nikolaou, Maria; Papp, Zoltán; Parkhomenko, Alexander; Poelzl, Gerhard; Pollesello, Piero; Ravn, Hanne Berg; Rex, Steffen; Riha, Hynek; Ricksten, Sven-Erik; Schwinger, Robert H G; Vrtovec, Bojan; Yilmaz, M Birhan; Zielinska, Marzenna; Parissis, John

2016-11-01

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Inhibitory spectrum of alpha 2-plasmin inhibitor.

PubMed Central

Saito, H; Goldsmith, G H; Moroi, M; Aoki, N

1979-01-01

alpha 2-Plasmin inhibitor (alpha 2PI) has been recently characterized as a fast-reacting inhibitor of plasmin in human plasma and appears to play an important role in the regulation of fibrinolysis in vivo. We have studied the effect of purified alpha 2PI upon various proteases participating in human blood coagulation and kinin generation. At physiological concentration (50 microgram/ml), alpha 2PI inhibited the clot-promoting and prekallikrein-activating activity of Hageman factor fragments, the amidolytic, kininogenase, and clot-promoting activities of plasma kallikrein, and the clot-promoting properties of activated plasma thromboplastin antecedent (PTA, Factor XIa) and thrombin. alpha 2PI had minimal inhibitory effect on surface-bound activated PTA and activated Stuart factor (Factor Xa). alpha 2PI did not inhibit the activity of activated Christmas factor (Factor IXa) or urinary kallikrein. Heparin (1.5-2.0 units/ml) did not enhance the inhibitory function of alpha 2PI. These results suggest that, like other plasma protease inhibitors, alpha 2PI possesses a broad in vitro spectrum of inhibitory properties. PMID:156364

The potential use of nanosilver-decorated titanium dioxide nanofibers for toxin decomposition with antimicrobial and self-cleaning properties

NASA Astrophysics Data System (ADS)

Srisitthiratkul, Chutima; Pongsorrarith, Voraluck; Intasanta, Narupol

2011-08-01

While chemical and biological attacks pose risk to human health, clean air is of scientific, environmental and physiological concerns. In the present contribution, the potential use of nanosilver-decorated titanium dioxide (TiO 2) nanofibers for toxin decomposition with antimicrobial activity and self-cleaning properties was investigated. Titanium dioxide nanofibers were prepared through sol-gel reaction followed by an electrospinning process. Following the Japan Industrial Standard (JIS) protocol, decompositions of nitrogen oxide (NOx) and volatile organic compound (VOC) by the TiO 2 nanofibers suggested that these materials were capable of air treatment. To further enhance their anti-microbial activity, silver nanoparticles were decorated onto the TiO 2 nanofibers' surfaces via photoreduction of silver ion in the presence of the nanofibers suspension. Furthermore, tests of photocatalytic activity of the samples were performed by photodegrading methylene blue in water. The nanofibrous membranes prepared from these nanofibers showed superhydrophilicity under UV. Finally, the possibility of using these hybrid nanofibers in environmental and hygienic nanofiltration was proposed, where the self-cleaning characteristics was expected to be valuable in maintenance processes.

Ion release from magnesium materials in physiological solutions under different oxygen tensions.

PubMed

Feyerabend, Frank; Drücker, Heiko; Laipple, Daniel; Vogt, Carla; Stekker, Michael; Hort, Norbert; Willumeit, Regine

2012-01-01

Although magnesium as degradable biomaterial already showed clinical proof of concepts, the design of new alloys requires predictive in vitro methods, which are still lacking. Incubation under cell culture conditions to obtain "physiological" corrosion may be a solution. The aim of this study was to analyse the influence of different solutions, addition of proteins and of oxygen availability on the corrosion of different magnesium materials (pure Mg, WE43, and E11) with different surface finishing. Oxygen content in solution, pH, osmolality and ion release were determined. Corrosion led to a reduction of oxygen in solution. The influence of oxygen on pH was enhanced by proteins, while osmolality was not influenced. Magnesium ion release was solution-dependent and enhanced in the initial phase by proteins with delayed release of alloying elements. The main corrosion product formed was magnesium carbonate. Therefore, cell culture conditions are proposed as first step toward physiological corrosion.

The interplay of non-specific binding, target-mediated clearance and FcRn interactions on the pharmacokinetics of humanized antibodies

PubMed Central

Datta-Mannan, Amita; Lu, Jirong; Witcher, Derrick R; Leung, Donmienne; Tang, Ying; Wroblewski, Victor J

2015-01-01

The application of protein engineering technologies toward successfully improving antibody pharmacokinetics has been challenging due to the multiplicity of biochemical factors that influence monoclonal antibody (mAb) disposition in vivo. Physiological factors including interactions with the neonatal Fc receptor (FcRn) and specific antigen binding properties of mAbs, along with biophysical properties of the mAbs themselves play a critical role. It has become evident that applying an integrated approach to understand the relative contribution of these factors is critical to rationally guide and apply engineering strategies to optimize mAb pharmacokinetics. The study presented here evaluated the influence of unintended non-specific interactions on the disposition of mAbs whose clearance rates are governed predominantly by either non-specific (FcRn) or target-mediated processes. The pharmacokinetics of 8 mAbs representing a diverse range of these properties was evaluated in cynomolgus monkeys. Results revealed complementarity-determining region (CDR) charge patch engineering to decrease charge-related non-specific binding can have a significant impact on improving the clearance. In contrast, the influence of enhanced in vitro FcRn binding was mixed, and related to both the strength of charge interaction and the general mechanism predominant in governing the clearance of the particular mAb. Overall, improved pharmacokinetics through enhanced FcRn interactions were apparent for a CDR charge-patch normalized mAb which was affected by non-specific clearance. The findings in this report are an important demonstration that mAb pharmacokinetics requires optimization on a case-by-case basis to improve the design of molecules with increased therapeutic application. PMID:26337808

Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries--a review.

PubMed

Eshun, Kojo; He, Qian

2004-01-01

Scientific investigations on Aloe vera have gained more attention over the last several decades due to its reputable medicinal properties. Some publications have appeared in reputable Scientific Journals that have made appreciable contributions to the discovery of the functions and utilizations of Aloe--"nature's gift." Chemical analysis reveals that Aloe vera contains various carbohydrate polymers, notably glucomannans, along with a range of other organic and inorganic components. Although many physiological properties of Aloe vera have been described, it still remains uncertain as to which of the component(s) is responsible for these physiological properties. Further research needs to be done to unravel the myth surrounding the biological activities and the functional properties of A. vera. Appropriate processing techniques should be employed during the stabilization of the gel in order to affect and extend its field of utilization.

A wearable device for emotional recognition using facial expression and physiological response.

PubMed

Jangho Kwon; Da-Hye Kim; Wanjoo Park; Laehyun Kim

2016-08-01

This paper introduces a glasses-typed wearable system to detect user's emotions using facial expression and physiological responses. The system is designed to acquire facial expression through a built-in camera and physiological responses such as photoplethysmogram (PPG) and electrodermal activity (EDA) in unobtrusive way. We used video clips for induced emotions to test the system suitability in the experiment. The results showed a few meaningful properties that associate emotions with facial expressions and physiological responses captured by the developed wearable device. We expect that this wearable system with a built-in camera and physiological sensors may be a good solution to monitor user's emotional state in daily life.

Impact of time-of-day on diffusivity measures of brain tissue derived from diffusion tensor imaging.

PubMed

Thomas, Cibu; Sadeghi, Neda; Nayak, Amrita; Trefler, Aaron; Sarlls, Joelle; Baker, Chris I; Pierpaoli, Carlo

2018-06-01

Diurnal fluctuations in MRI measures of structural and functional properties of the brain have been reported recently. These fluctuations may have a physiological origin, since they have been detected using different MRI modalities, and cannot be explained by factors that are typically known to confound MRI measures. While preliminary evidence suggests that measures of structural properties of the brain based on diffusion tensor imaging (DTI) fluctuate as a function of time-of-day (TOD), the underlying mechanism has not been investigated. Here, we used a longitudinal within-subjects design to investigate the impact of time-of-day on DTI measures. In addition to using the conventional monoexponential tensor model to assess TOD-related fluctuations, we used a dual compartment tensor model that allowed us to directly assess if any change in DTI measures is due to an increase in CSF/free-water volume fraction or due to an increase in water diffusivity within the parenchyma. Our results show that Trace or mean diffusivity, as measured using the conventional monoexponential tensor model tends to increase systematically from morning to afternoon scans at the interface of grey matter/CSF, most prominently in the major fissures and the sulci of the brain. Interestingly, in a recent study of the glymphatic system, these same regions were found to show late enhancement after intrathecal injection of a CSF contrast agent. The increase in Trace also impacts DTI measures of diffusivity such as radial and axial diffusivity, but does not affect fractional anisotropy. The dual compartment analysis revealed that the increase in diffusivity measures from PM to AM was driven by an increase in the volume fraction of CSF-like free-water. Taken together, our findings provide important insight into the likely physiological origins of diurnal fluctuations in MRI measurements of structural properties of the brain. Published by Elsevier Inc.

Oxidative stress and mitochondria-mediated cell death mechanisms triggered by the familial Danish dementia ADan amyloid.

PubMed

Todd, Krysti; Ghiso, Jorge; Rostagno, Agueda

2016-01-01

Familial Danish Dementia (FDD), an early-onset non-amyloid-β (Aβ) cerebral amyloidosis, is neuropathologically characterized by widespread cerebral amyloid angiopathy, parenchymal amyloid and preamyloid deposits, as well as neurofibrillary degeneration indistinguishable to that seen in Alzheimer's disease (AD). The main amyloid subunit composing FDD lesions, a 34-amino acid de-novo generated peptide ADan, is the direct result of a genetic defect at the 3'-end of the BRI2 gene and the physiologic action of furin-like proteolytic processing at the C-terminal region of the ADan precursor protein. We aimed to study the impact of the FDD mutation, the additional formation of the pyroglutamate (pE) posttranslational modification as well as the relevance of C-terminal truncations -all major components of the heterogeneous FDD deposits- on the structural and neurotoxic properties of the molecule. Our data indicates that whereas the mutation generated a β-sheet-rich hydrophobic ADan subunit of high oligomerization/fibrillization propensity and the pE modification further enhanced these properties, C-terminal truncations had the opposite effect mostly abolishing these features. The potentiation of pro-amyloidogenic properties correlated with the initiation of neuronal cell death mechanisms involving oxidative stress, perturbation of mitochondrial membrane potential, release of mitochondrial cytochrome c, and downstream activation of caspase-mediated apoptotic pathways. The amyloid-induced toxicity was inhibited by targeting specific components of these detrimental cellular pathways, using reactive oxygen scavengers and monoclonal antibodies recognizing the pathological amyloid subunit. Taken together, the data indicate that the FDD mutation and the pE posttranslational modification are both primary elements driving intact ADan into an amyloidogenic/neurotoxic pathway while truncations at the C-terminus eliminate the pro-amyloidogenic characteristics of the molecule, likely reflecting effect of physiologic clearance mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of Interactive Live Digital Imaging to Enhance Histology Learning in Introductory Level Anatomy and Physiology Classes

ERIC Educational Resources Information Center

Higazi, Tarig B.

2011-01-01

Histology is one of the main subjects in introductory college-level Human Anatomy and Physiology classes. Institutions are moving toward the replacement of traditional microscope-based histology learning with virtual microscopy learning amid concerns of losing the valuable learning experience of traditional microscopy. This study used live digital…

Study of Physiological Responses to Acute Carbon Monoxide Exposure with a Human Patient Simulator

ERIC Educational Resources Information Center

Cesari, Whitney A.; Caruso, Dominique M.; Zyka, Enela L.; Schroff, Stuart T.; Evans, Charles H., Jr.; Hyatt, Jon-Philippe K.

2006-01-01

Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design,…

Enhancing Learning through Optimal Sequencing of Web-Based and Manikin Simulators to Teach Shock Physiology in the Medical Curriculum

ERIC Educational Resources Information Center

Cendan, Juan C.; Johnson, Teresa R.

2011-01-01

The Association of American Medical Colleges has encouraged educators to investigate proper linkage of simulation experiences with medical curricula. The authors aimed to determine if student knowledge and satisfaction differ between participation in web-based and manikin simulations for learning shock physiology and treatment and to determine if…

Novel properties of the wheat aluminum tolerance organic acid transporter (TaALMT1) revealed by electrophysiological characterization in Xenopus Oocytes: functional and structural implications.

PubMed

Piñeros, Miguel A; Cançado, Geraldo M A; Kochian, Leon V

2008-08-01

Many plant species avoid the phytotoxic effects of aluminum (Al) by exuding dicarboxylic and tricarboxylic acids that chelate and immobilize Al(3+) at the root surface, thus preventing it from entering root cells. Several novel genes that encode membrane transporters from the ALMT and MATE families recently were cloned and implicated in mediating the organic acid transport underlying this Al tolerance response. Given our limited understanding of the functional properties of ALMTs, in this study a detailed characterization of the transport properties of TaALMT1 (formerly named ALMT1) from wheat (Triticum aestivum) expressed in Xenopus laevis oocytes was conducted. The electrophysiological findings are as follows. Although the activity of TaALMT1 is highly dependent on the presence of extracellular Al(3+) (K(m1/2) of approximately 5 microm Al(3+) activity), TaALMT1 is functionally active and can mediate ion transport in the absence of extracellular Al(3+). The lack of change in the reversal potential (E(rev)) upon exposure to Al(3+) suggests that the "enhancement" of TaALMT1 malate transport by Al is not due to alteration in the transporter's selectivity properties but is solely due to increases in its anion permeability. The consistent shift in the direction of the E(rev) as the intracellular malate activity increases indicates that TaALMT1 is selective for the transport of malate over other anions. The estimated permeability ratio between malate and chloride varied between 1 and 30. However, the complex behavior of the E(rev) as the extracellular Cl(-) activity was varied indicates that this estimate can only be used as a general guide to understanding the relative affinity of TaALMT1 for malate, representing only an approximation of those expected under physiologically relevant ionic conditions. TaALMT1 can also mediate a large anion influx (i.e. outward currents). TaALMT1 is permeable not only to malate but also to other physiologically relevant anions such as Cl(-), NO(3)(-), and SO(4)(2-) (to a lesser degree).

Emerson Enhancement Effect: A New Student Experiment.

ERIC Educational Resources Information Center

Orr, Alan R.; Knudtson, Dan L.

1977-01-01

Discusses the potential use, by students in cell biology and plant physiology, of isolated chloroplasts for determining the Emerson enhancement effect. The experiment designed to measure spectrophotometrically the photoreduction of a dye by illuminating chloroplasts with short- and long-wavelength light is presented. (HM)

Ontology of physics for biology: representing physical dependencies as a basis for biological processes.

PubMed

Cook, Daniel L; Neal, Maxwell L; Bookstein, Fred L; Gennari, John H

2013-12-02

In prior work, we presented the Ontology of Physics for Biology (OPB) as a computational ontology for use in the annotation and representations of biophysical knowledge encoded in repositories of physics-based biosimulation models. We introduced OPB:Physical entity and OPB:Physical property classes that extend available spatiotemporal representations of physical entities and processes to explicitly represent the thermodynamics and dynamics of physiological processes. Our utilitarian, long-term aim is to develop computational tools for creating and querying formalized physiological knowledge for use by multiscale "physiome" projects such as the EU's Virtual Physiological Human (VPH) and NIH's Virtual Physiological Rat (VPR). Here we describe the OPB:Physical dependency taxonomy of classes that represent of the laws of classical physics that are the "rules" by which physical properties of physical entities change during occurrences of physical processes. For example, the fluid analog of Ohm's law (as for electric currents) is used to describe how a blood flow rate depends on a blood pressure gradient. Hooke's law (as in elastic deformations of springs) is used to describe how an increase in vascular volume increases blood pressure. We classify such dependencies according to the flow, transformation, and storage of thermodynamic energy that occurs during processes governed by the dependencies. We have developed the OPB and annotation methods to represent the meaning-the biophysical semantics-of the mathematical statements of physiological analysis and the biophysical content of models and datasets. Here we describe and discuss our approach to an ontological representation of physical laws (as dependencies) and properties as encoded for the mathematical analysis of biophysical processes.

An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2015-01-01

Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the oral supplement by athletes to achieve the fine sporting art results due to the buffering activities of carnosine and its related imidazole- containing compounds which contribute to the maintenance of the acid-base balance in the acting muscles. This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts. The therapeutic interventions utilizing the specific oral formulation (Can-C Plus), timing dosing and pharmaco-nutritional boost of imidazolecontaining dipeptides can maintain health, enhance physical exercise performance and prevent aging. The patented therapeutic concept protects the existence of the interesting physiological major activities, better controls and therapeutic treatments for aging/age-related disorders (including age-related loss of muscle mass and muscle function) using carnosine dipeptide for cellular rejuvenation and manipulating telomeres and enzyme telomerase activity that may reduce some of the physiological declines that accompany aging.

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

PubMed Central

Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

2012-01-01

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

Impact of naturally leaking carbon dioxide on soil properties and ecosystems in the Qinghai-Tibet plateau.

PubMed

Zhao, Xiaohong; Deng, Hongzhang; Wang, Wenke; Han, Feng; Li, Chunrong; Zhang, Hui; Dai, Zhenxue

2017-06-07

One of the major concerns for CO 2 capture and storage (CCS) is the potential risk of CO 2 leakage from storage reservoirs on the shallow soil property and vegetation. This study utilizes a naturally occurring CO 2 leaking site in the Qinghai-Tibet Plateau to analog a "leaking CCS site". Our observations from this site indicates that long-term CO 2 invasion in the vadose zone results in variations of soil properties, such as pH fluctuation, slight drop of total organic carbon, reduction of nitrogen and phosphorus, and concentration changes of soluble ions. Simultaneously, XRD patterns of the soil suggest that crystallization of soil is enhanced and mineral contents of calcite and anorthite in soil are increased substantially. Parts of the whole ecosystem such as natural wild plants, soil dwelling animals and microorganisms in shallow soil are affected as well. Under a moderate CO 2 concentration (less than 110000 ppm), wild plant growth and development are improved, while an intensive CO 2 flux over 112000 ppm causes adverse effects on the plant growth, physiological and biochemical system of plants, and crop quality of wheat. Results of this study provide valuable insight for understanding the possible environmental impacts associated with potential CO 2 leakage into shallow sediments at carbon sequestration sites.

Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology.

PubMed

Sizemore, Rachel J; Seeger-Armbruster, Sonja; Hughes, Stephanie M; Parr-Brownlie, Louise C

2016-04-01

Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients. Copyright © 2016 the American Physiological Society.

Phosphatidylserine in atherosclerosis.

PubMed

Darabi, Maryam; Kontush, Anatol

2016-08-01

It is now widely acknowledged that phosphatidylserine is a multifunctional bioactive lipid. In this review, we focus on the function of phosphatidylserine in modulating cholesterol metabolism, influencing inflammatory response and regulating coagulation system, and discuss promising phosphatidylserine-based therapeutic approaches and detection techniques in atherosclerosis. Phosphatidylserine has been suggested to play important roles in physiological processes, such as apoptosis, inflammation, and coagulation. Recent data demonstrate atheroprotective potential of phosphatidylserine, reflecting its capacity to inhibit inflammation, modulate coagulation, and enhance HDL functionality. Furthermore, modern lipidomic approaches have enabled the investigation of phosphatidylserine properties relevant to the lipid-based drug delivery and development of reconstituted HDL. Studies of phosphatidylserine in relation to atherosclerosis represent an area of opportunity. Additional research elucidating mechanisms underlying experimentally observed atheroprotective effects of phosphatidylserine is required to fully explore therapeutic potential of this naturally occurring phospholipid in cardiovascular disease.

Three-dimensional mechanisms of macro-to-micro-scale transport and absorption enhancement by gut villi motions

NASA Astrophysics Data System (ADS)

Wang, Yanxing; Brasseur, James G.

2017-06-01

We evaluate the potential for physiological control of intestinal absorption by the generation of "micromixing layers" (MMLs) induced by coordinated motions of mucosal villi coupled with lumen-scale "macro" eddying motions generated by gut motility. To this end, we apply a three-dimensional (3D) multigrid lattice-Boltzmann model of a lid-driven macroscale cavity flow with microscale fingerlike protuberances at the lower surface. Integrated with a previous 2D study of leaflike villi, we generalize to 3D the 2D mechanisms found there to enhance nutrient absorption by controlled villi motility. In three dimensions, increased lateral spacing within villi within groups that move axially with the macroeddy reduces MML strength and absorptive enhancement relative to two dimensions. However, lateral villi motions create helical 3D particle trajectories that enhance absorption rate to the level of axially moving 2D leaflike villi. The 3D enhancements are associated with interesting fundamental adjustments to 2D micro-macro-motility coordination mechanisms and imply a refined potential for physiological or pharmaceutical control of intestinal absorption.

The role of retinal bipolar cell in early vision: an implication with analogue networks and regularization theory.

PubMed

Yagi, T; Ohshima, S; Funahashi, Y

1997-09-01

A linear analogue network model is proposed to describe the neuronal circuit of the outer retina consisting of cones, horizontal cells, and bipolar cells. The model reflects previous physiological findings on the spatial response properties of these neurons to dim illumination and is expressed by physiological mechanisms, i.e., membrane conductances, gap-junctional conductances, and strengths of chemical synaptic interactions. Using the model, we characterized the spatial filtering properties of the bipolar cell receptive field with the standard regularization theory, in which the early vision problems are attributed to minimization of a cost function. The cost function accompanying the present characterization is derived from the linear analogue network model, and one can gain intuitive insights on how physiological mechanisms contribute to the spatial filtering properties of the bipolar cell receptive field. We also elucidated a quantitative relation between the Laplacian of Gaussian operator and the bipolar cell receptive field. From the computational point of view, the dopaminergic modulation of the gap-junctional conductance between horizontal cells is inferred to be a suitable neural adaptation mechanism for transition between photopic and mesopic vision.

Unravelling chemical priming machinery in plants: the role of reactive oxygen-nitrogen-sulfur species in abiotic stress tolerance enhancement.

PubMed

Antoniou, Chrystalla; Savvides, Andreas; Christou, Anastasis; Fotopoulos, Vasileios

2016-10-01

Abiotic stresses severely limit crop yield and their detrimental effects are aggravated by climate change. Chemical priming is an emerging field in crop stress management. The exogenous application of specific chemical agents before stress events results in tolerance enhancement and reduction of stress impacts on plant physiology and growth. However, the molecular mechanisms underlying the remarkable effects of chemical priming on plant physiology remain to be elucidated. Reactive oxygen, nitrogen and sulfur species (RONSS) are molecules playing a vital role in the stress acclimation of plants. When applied as priming agents, RONSS improve stress tolerance. This review summarizes the recent knowledge on the role of RONSS in cell signalling and gene regulation contributing to abiotic stress tolerance enhancement. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disentangling Fun and Enjoyment in Exergames Using an Expanded Design, Play, Experience Framework: A Narrative Review.

PubMed

Mellecker, Robin; Lyons, Elizabeth J; Baranowski, Tom

2013-06-01

With exergames (as with physical activity in general), more intense and longer-duration game play should accrue more health benefits. Exergames, however, appear to be played for relatively short durations, often at medium or lower intensities. Ostensibly games are played for fun or enjoyment. Enhancing the fun or enjoyment experienced during exergame play should enhance the intensity and duration of physical activity, and thereby the health benefits. Research, reviewed herein, indicates fun and/or enjoyment in games are inherently laden with psychosocial, physiological, and embodiment substrates. Physical activity may also have separate or closely related psychosocial, physiological, and embodiment enjoyment substrates. Research is needed to integrate these levels of experience and to identify the game mechanics that enhance, and even maximize, the fun or enjoyment experienced in exergames, to thereby increase the health benefit.

Young children's reasoning about the effects of emotional and physiological states on academic performance.

PubMed

Amsterlaw, Jennifer; Lagattuta, Kristin Hansen; Meltzoff, Andrew N

2009-01-01

This study assessed young children's understanding of the effects of emotional and physiological states on cognitive performance. Five, 6-, 7-year-olds, and adults (N= 96) predicted and explained how children experiencing a variety of physiological and emotional states would perform on academic tasks. Scenarios included: (a) negative and positive emotions, (b) negative and positive physiological states, and (c) control conditions. All age groups understood the impairing effects of negative emotions and physiological states. Only 7-year-olds, however, showed adult-like reasoning about the potential enhancing effects of positive internal states and routinely cited cognitive mechanisms to explain how internal states affect performance. These results shed light on theory-of-mind development and also have significance for children's everyday school success.

Assessment and comparison of student engagement in a variety of physiology courses.

PubMed

Hopper, Mari K

2016-03-01

Calls for reform in science education have promoted active learning as a means to improve student engagement (SENG). SENG is generally acknowledged to have a positive effect on student learning, satisfaction, and retention. A validated 14-question survey was used to assess SENG in a variety of upper- and lower-level physiology courses, including 100-level Anatomy and Physiology 1, 300-level Animal Physiology, 400-level Advanced Physiology, and 500-level Medical Physiology courses. The results indicated that SENG did not vary consistently by course level, format, or curriculum. The highest levels of SENG were found in the Advanced Physiology course, which included SENG as a primary objective of the course. Physiology student SENG scores were compared with National Survey of Student Engagement (NSSE) scores. The results demonstrated that physiology students enrolled in the Anatomy and Physiology 1 course reported lower levels of SENG than first-year students that completed the NSSE. Students enrolled in the Advanced Physiology course reported higher levels of SENG than fourth-year students that completed the NSSE. Assessment of SENG offers insights as to how engaged students are, identifies where efforts may best be applied to enhance SENG, and provides a baseline measure for future comparisons after targeted course modifications. Copyright © 2016 The American Physiological Society.

Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

PubMed Central

Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

2013-01-01

The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

Synaptic proteins associate with a sub-set of lipid rafts when isolated from nerve endings at physiological temperature.

PubMed

Gil, Carles; Cubí, Roger; Blasi, Juan; Aguilera, José

2006-10-06

Although the high presence of cholesterol in nerve terminals is well documented, specific roles of this lipid in transmitter release have remained elusive. Since cholesterol is a highly enriched component in the membrane microdomains known as lipid rafts, it is probable that these domains are very important in synaptic function. The extraction of lipid rafts using Brij 98 at 37 degrees C avoids the formation of nonspecific membrane aggregates at low temperature, allowing the isolation of more physiologically relevant lipid rafts. In the present work, we examine, by means of buoyancy analysis in sucrose gradients after solubilization of the membranes with Brij 98 or with Lubrol WX, the presence of proteins involved in exocytosis in detergent-resistant membranes (DRM) using rat brain synaptosomes as a neurological model. Significant proportions of the proteins tested in the present work, which are involved in neurotransmitter release, are found in Brij 98 raft fractions, demonstrating that significant pools of synaptic proteins are segregated in specific parts of the membrane at physiological temperature. On the other hand, Lubrol WX is unable to solubilize the major fraction of the proteins tested. Treatment of synaptosomes with methyl-beta-cyclodextrin (mbetaCD) causes alteration in the buoyancy properties of proteins initially present in Brij- as well as in Lubrol-resistant membranes, indicating the cholesterol-dependency of both kinds of microdomains. Finally, we detect the depolarization-induced enhancement of the cholesterol-dependent association of syntaxin 1 with Brij 98-rafts, under the same conditions in which prolonged neurotransmitter release is stimulated.

Finite element models of the human shoulder complex: a review of their clinical implications and modelling techniques.

PubMed

Zheng, Manxu; Zou, Zhenmin; Bartolo, Paulo Jorge Da Silva; Peach, Chris; Ren, Lei

2017-02-01

The human shoulder is a complicated musculoskeletal structure and is a perfect compromise between mobility and stability. The objective of this paper is to provide a thorough review of previous finite element (FE) studies in biomechanics of the human shoulder complex. Those FE studies to investigate shoulder biomechanics have been reviewed according to the physiological and clinical problems addressed: glenohumeral joint stability, rotator cuff tears, joint capsular and labral defects and shoulder arthroplasty. The major findings, limitations, potential clinical applications and modelling techniques of those FE studies are critically discussed. The main challenges faced in order to accurately represent the realistic physiological functions of the shoulder mechanism in FE simulations involve (1) subject-specific representation of the anisotropic nonhomogeneous material properties of the shoulder tissues in both healthy and pathological conditions; (2) definition of boundary and loading conditions based on individualised physiological data; (3) more comprehensive modelling describing the whole shoulder complex including appropriate three-dimensional (3D) representation of all major shoulder hard tissues and soft tissues and their delicate interactions; (4) rigorous in vivo experimental validation of FE simulation results. Fully validated shoulder FE models would greatly enhance our understanding of the aetiology of shoulder disorders, and hence facilitate the development of more efficient clinical diagnoses, non-surgical and surgical treatments, as well as shoulder orthotics and prosthetics. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Technology in the teaching of neuroscience: enhanced student learning.

PubMed

Griffin, John D

2003-12-01

The primary motivation for integrating any form of education technology into a particular course or curriculum should always be to enhance student learning. However, it can be difficult to determine which technologies will be the most appropriate and effective teaching tools. Through the alignment of technology-enhanced learning experiences with a clear set of learning objectives, teaching becomes more efficient and effective and learning is truly enhanced. In this article, I describe how I have made extensive use of technology in two neuroscience courses that differ in structure and content. Course websites function as resource centers and provide a forum for student interaction. PowerPoint presentations enhance formal lectures and provide an organized outline of presented material. Some lectures are also supplemented with interactive CD-ROMs, used in the presentation of difficult physiological concepts. In addition, a computer-based physiological recording system is used in laboratory sessions, improving the hands-on experience of group learning while reinforcing the concepts of the research method. Although technology can provide powerful teaching tools, the enhancement of the learning environment is still dependent on the instructor. It is the skill and enthusiasm of the instructor that determines whether technology will be used effectively.

Neuronal Oscillations with Non-sinusoidal Morphology Produce Spurious Phase-to-Amplitude Coupling and Directionality

PubMed Central

Lozano-Soldevilla, Diego; ter Huurne, Niels; Oostenveld, Robert

2016-01-01

Neuronal oscillations support cognitive processing. Modern views suggest that neuronal oscillations do not only reflect coordinated activity in spatially distributed networks, but also that there is interaction between the oscillations at different frequencies. For example, invasive recordings in animals and humans have found that the amplitude of fast oscillations (>40 Hz) occur non-uniformly within the phase of slower oscillations, forming the so-called cross-frequency coupling (CFC). However, the CFC patterns might be influenced by features in the signal that do not relate to underlying physiological interactions. For example, CFC estimates may be sensitive to spectral correlations due to non-sinusoidal properties of the alpha band wave morphology. To investigate this issue, we performed CFC analysis using experimental and synthetic data. The former consisted in a double-blind magnetoencephalography pharmacological study in which participants received either placebo, 0.5 or 1.5 mg of lorazepam (LZP; GABAergic enhancer) in different experimental sessions. By recording oscillatory brain activity with during rest and working memory (WM), we were able to demonstrate that posterior alpha (8–12 Hz) phase was coupled to beta-low gamma band (20–45 Hz) amplitude envelope during all sessions. Importantly, bicoherence values around the harmonics of the alpha frequency were similar both in magnitude and topographic distribution to the cross-frequency coherence (CFCoh) values observed in the alpha-phase to beta-low gamma coupling. In addition, despite the large CFCoh we found no significant cross-frequency directionality (CFD). Critically, simulations demonstrated that a sizable part of our empirical CFCoh between alpha and beta-low gamma coupling and the lack of CFD could be explained by two-three harmonics aligned in zero phase-lag produced by the physiologically characteristic alpha asymmetry in the amplitude of the peaks relative to the troughs. Furthermore, we showed that periodic signals whose waveform deviate from pure sine waves produce non-zero CFCoh with predictable CFD. Our results reveal the important role of the non-sinusoidal wave morphology on state of the art CFC metrics and we recommend caution with strong physiological interpretations of CFC and suggest basic data quality checks to enhance the mechanistic understanding of CFC. PMID:27597822

Electro-kinetically driven peristaltic transport of viscoelastic physiological fluids through a finite length capillary: Mathematical modeling.

PubMed

Tripathi, Dharmendra; Yadav, Ashu; Bég, O Anwar

2017-01-01

Analytical solutions are developed for the electro-kinetic flow of a viscoelastic biological liquid in a finite length cylindrical capillary geometry under peristaltic waves. The Jefferys' non-Newtonian constitutive model is employed to characterize rheological properties of the fluid. The unsteady conservation equations for mass and momentum with electro-kinetic and Darcian porous medium drag force terms are reduced to a system of steady linearized conservation equations in an axisymmetric coordinate system. The long wavelength, creeping (low Reynolds number) and Debye-Hückel linearization approximations are utilized. The resulting boundary value problem is shown to be controlled by a number of parameters including the electro-osmotic parameter, Helmholtz-Smoluchowski velocity (maximum electro-osmotic velocity), and Jefferys' first parameter (ratio of relaxation and retardation time), wave amplitude. The influence of these parameters and also time on axial velocity, pressure difference, maximum volumetric flow rate and streamline distributions (for elucidating trapping phenomena) is visualized graphically and interpreted in detail. Pressure difference magnitudes are enhanced consistently with both increasing electro-osmotic parameter and Helmholtz-Smoluchowski velocity, whereas they are only elevated with increasing Jefferys' first parameter for positive volumetric flow rates. Maximum time averaged flow rate is enhanced with increasing electro-osmotic parameter, Helmholtz-Smoluchowski velocity and Jefferys' first parameter. Axial flow is accelerated in the core (plug) region of the conduit with greater values of electro-osmotic parameter and Helmholtz-Smoluchowski velocity whereas it is significantly decelerated with increasing Jefferys' first parameter. The simulations find applications in electro-osmotic (EO) transport processes in capillary physiology and also bio-inspired EO pump devices in chemical and aerospace engineering. Copyright © 2016 Elsevier Inc. All rights reserved.

Is crying a self-soothing behavior?

PubMed Central

Gračanin, Asmir; Bylsma, Lauren M.; Vingerhoets, Ad J. J. M.

2014-01-01

This contribution describes the current state-of-the-art of the scientific literature regarding the self-soothing effects of crying. Starting from the general hypothesis that crying is a self-soothing behavior, we consider different mechanisms through which these effects may appear. In the first section, we briefly explain the main functions of human crying. Then we define self-soothing in terms of homeostatic processes of mood regulation and stress reduction and we underline the importance of distinguishing self-soothing effects of crying from social-soothing that it may elicit. We then provide a comprehensive review of the putative mood-enhancing and -relieving effects of crying and their variations stemming from characteristics of crying person, antecedents, manifestations, and social consequences of crying. We also discuss the possible methodological explanations for the seemingly discrepant findings regarding mood improvement and relief that may follow crying. We then provide theoretical and empirical support for our general hypothesis that crying is a self-soothing behavior by presenting and evaluating the possible physiological, cognitive, and behavioral mechanisms that may play a mediating role in the relationship between crying and homeostatic regulation that includes mood improvement and relief. Starting from the idea that social-soothing and self-soothing mechanisms share the same physiological systems, we propose that biological processes act in parallel with learning and reappraisal processes that accompany crying, which results in homeostatic regulation. Given the parallels between self-soothing behaviors in humans and animals, we also propose that crying might self-soothe through a mechanism that shares key properties with rhythmical, stereotypic behaviors. We conclude that, in addition to the importance of socially mediated mechanisms for the mood-enhancing effects of crying, there is converging evidence for the direct, self-soothing effects of crying. PMID:24904511

Odors enhance slow-wave activity in non-rapid eye movement sleep.

PubMed

Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam; Hairston, Ilana S

2016-05-01

Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. Copyright © 2016 the American Physiological Society.

Microfluidic Fabrication of Cell Adhesive Chitosan Microtubes

PubMed Central

Oh, Jonghyun; Kim, Keekyoung; Won, Sung Wook; Cha, Chaenyung; Gaharwar, Akhilesh; Selimović, Šeila; Bae, Hojae; Lee, Kwang Ho; Lee, Dong Hwan; Lee, Sang-Hoon; Khademhosseini, Ali

2013-01-01

Chitosan has been used as a scaffolding material in tissue engineering due to its mechanical properties and biocompatibility. With increased appreciation of the effect of micro- and nanoscale environments on cellular behavior, there is increased emphasis on generating microfabricated chitosan structures. Here we employed a microfluidic coaxial flow-focusing system to generate cell adhesive chitosan microtubes of controlled sizes by modifying the flow rates of a chitosan pre-polymer solution and phosphate buffered saline (PBS). The microtubes were extruded from a glass capillary with a 300 μm inner diameter. After ionic crosslinking with sodium tripolyphosphate (TPP), fabricated microtubes had inner and outer diameter ranges of 70-150 μm and 120-185 μm. Computational simulation validated the controlled size of microtubes and cell attachment. To enhance cell adhesiveness on the microtubes, we mixed gelatin with the chitosan pre-polymer solution and adjusted the pH values of the chitosan pre-polymer solution with gelatin and TPP. During the fabrication of microtubes, fibroblasts suspended in core PBS flow adhered to the inner surface of chitosan-gelatin microtubes. To achieve physiological pH values, we adjusted pH values of chiotsan pre-polymer solution and TPP. In particular, we were able to improve cell viability to 92% with pH values of 5.8 and 7.4 for chitosan and TPP solution respectively. Cell culturing for three days showed that the addition of the gelatin enhanced cell spreading and proliferation inside the chitosan-gelatin microtubes. The microfluidic fabrication method for ionically crosslinked chitosan microtubes at physiological pH can be compatible with a variety of cells and used as a versatile platform for microengineered tissue engineering. PMID:23355068

Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol.

PubMed

Vandegrift, Bertha J; You, Chang; Satta, Rosalba; Brodie, Mark S; Lasek, Amy W

2017-01-01

Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.

Theta frequency background tunes transmission but not summation of spiking responses.

PubMed

Parameshwaran, Dhanya; Bhalla, Upinder S

2013-01-01

Hippocampal neurons are known to fire as a function of frequency and phase of spontaneous network rhythms, associated with the animal's behaviour. This dependence is believed to give rise to precise rate and temporal codes. However, it is not well understood how these periodic membrane potential fluctuations affect the integration of synaptic inputs. Here we used sinusoidal current injection to the soma of CA1 pyramidal neurons in the rat brain slice to simulate background oscillations in the physiologically relevant theta and gamma frequency range. We used a detailed compartmental model to show that somatic current injection gave comparable results to more physiological synaptically driven theta rhythms incorporating excitatory input in the dendrites, and inhibitory input near the soma. We systematically varied the phase of synaptic inputs with respect to this background, and recorded changes in response and summation properties of CA1 neurons using whole-cell patch recordings. The response of the cell was dependent on both the phase of synaptic inputs and frequency of the background input. The probability of the cell spiking for a given synaptic input was up to 40% greater during the depolarized phases between 30-135 degrees of theta frequency current injection. Summation gain on the other hand, was not affected either by the background frequency or the phasic afferent inputs. This flat summation gain, coupled with the enhanced spiking probability during depolarized phases of the theta cycle, resulted in enhanced transmission of summed inputs during the same phase window of 30-135 degrees. Overall, our study suggests that although oscillations provide windows of opportunity to selectively boost transmission and EPSP size, summation of synaptic inputs remains unaffected during membrane oscillations.

Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol

PubMed Central

Vandegrift, Bertha J.; You, Chang; Satta, Rosalba; Brodie, Mark S.

2017-01-01

Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission. PMID:29107956

Biodegradable toughened nanohybrid shape memory polymer for smart biomedical applications.

PubMed

Biswas, Arpan; Singh, Akhand Pratap; Rana, Dipak; Aswal, Vinod K; Maiti, Pralay

2018-05-31

A polyurethane nanohybrid has been prepared through the in situ polymerization of an aliphatic diisocyanate, ester polyol and a chain extender in the presence of two-dimensional platelets. Polymerization within the platelet galleries helps to intercalate, generate diverse nanostructure and improve the nano to macro scale self-assembly, which leads to a significant enhancement in the toughness and thermal stability of the nanohybrid in comparison to pure polyurethane. The extensive interactions, the reason for property enhancement, between nanoplatelets and polymer chains are revealed through spectroscopic measurements and thermal studies. The nanohybrid exhibits significant improvement in the shape memory phenomena (91% recovery) at the physiological temperature, which makes it suitable for many biomedical applications. The structural alteration, studied through temperature dependent small angle neutron scattering and X-ray diffraction, along with unique crystallization behavior have extensively revealed the special shape memory behavior of this nanohybrid and facilitated the understanding of the molecular flipping in the presence of nanoplatelets. Cell line studies and subsequent imaging testify that this nanohybrid is a superior biomaterial that is suitable for use in the biomedical arena. In vivo studies on albino rats exhibit the potential of the shape memory effect of the nanohybrid as a self-tightening suture in keyhole surgery by appropriately closing the lips of the wound through the recovery of the programmed shape at physiological temperature with faster healing of the wound and without the formation of any scar. Further, the improved biodegradable nature along with the rapid self-expanding ability of the nanohybrid at 37 °C make it appropriate for many biomedical applications including a self-expanding stent for occlusion recovery due to its tough and flexible nature.

Photoautotrophic organisms control microbial abundance, diversity, and physiology in different types of biological soil crusts.

PubMed

Maier, Stefanie; Tamm, Alexandra; Wu, Dianming; Caesar, Jennifer; Grube, Martin; Weber, Bettina

2018-04-01

Biological soil crusts (biocrusts) cover about 12% of the Earth's land masses, thereby providing ecosystem services and affecting biogeochemical fluxes on a global scale. They comprise photoautotrophic cyanobacteria, algae, lichens and mosses, which grow together with heterotrophic microorganisms, forming a model system to study facilitative interactions and assembly principles in natural communities. Biocrusts can be classified into cyanobacteria-, lichen-, and bryophyte-dominated types, which reflect stages of ecological succession. In this study, we examined whether these categories include a shift in heterotrophic communities and whether this may be linked to altered physiological properties. We analyzed the microbial community composition by means of qPCR and high-throughput amplicon sequencing and utilized flux measurements to investigate their physiological properties. Our results revealed that once 16S and 18S rRNA gene copy numbers increase, fungi become more predominant and alpha diversity increases with progressing succession. Bacterial communities differed significantly between biocrust types with a shift from more generalized to specialized organisms along succession. CO 2 gas exchange measurements revealed large respiration rates of late successional crusts being significantly higher than those of initial biocrusts, and different successional stages showed distinct NO and HONO emission patterns. Thus, our study suggests that the photoautotrophic organisms facilitate specific microbial communities, which themselves strongly influence the overall physiological properties of biocrusts and hence local to global nutrient cycles.

Psychrometric chart for physiological research

NASA Technical Reports Server (NTRS)

Chambers, A. B.

1971-01-01

Chart facilitates use of graphical techniques for solving problems involving thermodynamic properties of moist air. The properties are presented, and their units of measurement are listed. Chart presenting conditions at standard atmosphere pressure at sea level is most useful.

Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia

NASA Technical Reports Server (NTRS)

Loeppky, J. A.; Roach, R. C.; Selland, M. A.; Scotto, P.; Greene, E. R.; Luft, U. C.

1993-01-01

To determine the effects of hypoxia on physiological responses to simulated zero-gravity cardiopulmonary and fluid balance measurements were made in 6 subjects before and during 5-degree head-down bed rest (HDBR) over 8 d at 10,678 ft and a second time at this altitude as controls (CON). The V-dot(O2)(max) increased by 9 percent after CON, but fell 3 percent after HDBR. This reduction in work capacity during HDBR could be accounted for by inactivity. The heart rate response to a head-up tilt was greatly enhanced following HDBR, while mean blood pressure was lower. No significant negative impact of HDBR was noted on the ability to acclimatize to hypoxia in terms of pulmonary mechanics, gas exchange, circulatory or mental function measurements. No evidence of pulmonary interstitial edema or congestion was noted during HDBR at the lower PIO2 and blood rheology properties were not negatively altered. Symptoms of altitude illness were more prevalent, but not marked, during HDBR and arterial blood gases and oxygenation were not seriously effected by simulated microgravity. Declines in base excess with altitude were similar in both conditions. The study demonstrated a minimal effect of HDBR on the ability to adjust to this level of hypoxia.

Mechanical Characterization of Microengineered Epithelial Cysts by Using Atomic Force Microscopy.

PubMed

Shen, Yusheng; Guan, Dongshi; Serien, Daniela; Takeuchi, Shoji; Tong, Penger; Yobas, Levent; Huang, Pingbo

2017-01-24

Most organs contain interconnected tubular tissues that are one-cell-thick, polarized epithelial monolayers enclosing a fluid-filled lumen. Such tissue organization plays crucial roles in developmental and normal physiology, and the proper functioning of these tissues depends on their regulation by complex biochemical perturbations and equally important, but poorly understood, mechanical perturbations. In this study, by combining micropatterning techniques and atomic force microscopy, we developed a simple in vitro experimental platform for characterizing the mechanical properties of the MDCK II cyst, the simplest model of lumen-enclosing epithelial monolayers. By using this platform, we estimated the elasticity of the cyst monolayer and showed that the presence of a luminal space influences cyst mechanics substantially, which could be attributed to polarization and tissue-level coordination. More interestingly, the results from force-relaxation experiments showed that the cysts also displayed tissue-level poroelastic characteristics that differed slightly from those of single cells. Our study provides the first quantitative findings, to our knowledge, on the tissue-level mechanics of well-polarized epithelial cysts and offers new insights into the interplay between cyst mechanics and cyst physiology. Moreover, our simple platform is a potentially useful tool for enhancing the current understanding of cyst mechanics in health and disease. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Effect of prebiotics of Agave salmiana fed to healthy Wistar rats.

PubMed

Jasso-Padilla, Iliana; Juárez-Flores, Bertha; Alvarez-Fuentes, Gregorio; De la Cruz-Martínez, Alejandro; González-Ramírez, José; Moscosa-Santillán, Mario; González-Chávez, Marco; Oros-Ovalle, Cuauhtemoc; Prell, Florian; Czermak, Peter; Martinez-Gutierrez, Fidel

2017-01-01

Inulin and other fructans are synthesized and stored in mezcal agave (Agave salmiana). Fructans provide several health benefits and have excellent technological properties, but only few data report their physiological effect when added in the diet. Here, we studied the physiological effects of fructans obtained from A. salmiana when added in the diet of Wistar rats. Results showed favorable changes on Wistar rats when the fructans was added to their diet, including the decrease of the pH in the feces and the increase of the number of lactic acid bacteria (CFU g -1 ) (Lactobacillus spp. and Bifidobacterium spp.), even these changes were enhanced with the synbiotic diet (fructans plus B. animalis subsp. lactis). Synbiotic diet, developed changes in the reduction of cholesterol and triglycerides concentrations in serum, with statistical differences (P < 0.05). Histological analysis of colon sections showed that synbiotic diet promoted colon cells growth suggesting that fructans from A. salmiana confer beneficial health effects through gut microbiota modulation. Our data underline the advantage of targeting the gut microbiota by colonic nutrients like specific structure of fructans from A. salmiana, with their beneficial effects. More studies are necessary to define the role of fructans to develop more solid therapeutic solutions in humans. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Physiological characteristics of bacteria isolated from water brines within permafrost

NASA Astrophysics Data System (ADS)

Shcherbakova, V.; Rivkina, E.; Laurinavichuis, K.; Pecheritsina, S.; Gilichinsky, D.

2004-01-01

In the Arctic there are lenses of overcooled water brines (cryopegs) sandwiched within permafrost marine sediments 100 120 thousand years old. We have investigated the physiological properties of the pure cultures of anaerobic Clostridium sp. strain 14D1 and two strains of aerobic bacteria Psychrobacter sp. isolated from these cryopegs. The structural and physiological characteristics of new bacteria from water brines have shown their ability to survive and develop under harsh conditions, such as subzero temperatures and high salinity.

Using Bio-Optics to Reveal Phytoplankton Physiology from a Wirewalker Autonomous Platform

NASA Technical Reports Server (NTRS)

Omand, M. M.; Cetinic, I.; Lucas, A. J.

2017-01-01

Rapid, wave-powered profiling of bio-optical properties from an autonomous Wirewalker platform provides useful insights into phytoplankton physiology, including the patterns of diel growth, phytoplankton mortality, nonphotochemical quenching of chlorophyll a fluorescence, and natural (sun-induced) fluorescence of mixed communities. Methods are proposed to quantify each of these processes. Such autonomous measurements of phytoplankton physiological rates and responses open up new possibilities for studying phytoplankton in situ, over longer periods, and under a broader range of environmental conditions.

Lectures Replaced by Prescribed Reading with Frequent Assessment: Enhanced Student Performance in Animal Physiology

ERIC Educational Resources Information Center

Chevins, Peter F. D.

2005-01-01

This article describes a study of the effects of partial replacement of lectures with a system of prescribed reading, supported by weekly objective testing in a second year animal physiology module. Formative tests with feedback within 24 hours were followed a week later with summative tests on the same material, utilising a proportion of the same…

Collaborative Teaching Strategies Lead to Retention of Skills in Acid-Base Physiology: A 2-Yr Follow-Up Study

ERIC Educational Resources Information Center

Hartmann, Jacob P.; Toksvang, Linea Natalie; Berg, Ronan M. G.

2015-01-01

A basic understanding of acid-base physiology is critical for the correct assessment of arterial blood gases in the clinical setting. In this context, collaborative teaching strategies in the undergraduate classroom setting may be useful, since it has been reported to enhance both transfer and retention of learned material in a time-efficient…

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

PubMed

Santacruz, Lucia; Arciniegas, Antonio Jose Luis; Darrabie, Marcus; Mantilla, Jose G; Baron, Rebecca M; Bowles, Dawn E; Mishra, Rajashree; Jacobs, Danny O

2017-08-01

Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Comparative proteomic analysis reveals the positive effect of exogenous spermidine on photosynthesis and salinity tolerance in cucumber seedlings.

PubMed

Sang, Ting; Shan, Xi; Li, Bin; Shu, Sheng; Sun, Jin; Guo, Shirong

2016-08-01

Our results based on proteomics data and physiological alterations proposed the putative mechanism of exogenous Spd enhanced salinity tolerance in cucumber seedlings. Current studies showed that exogenous spermidine (Spd) could alleviate harmful effects of salinity. It is important to increase our understanding of the beneficial physiological responses of exogenous Spd treatment, and to determine the molecular responses underlying these responses. Here, we combined a physiological analysis with iTRAQ-based comparative proteomics of cucumber (Cucumis sativus L.) leaves, treated with 0.1 mM exogenous Spd, 75 mM NaCl and/or exogenous Spd. A total of 221 differentially expressed proteins were found and involved in 30 metabolic pathways, such as photosynthesis, carbohydrate metabolism, amino acid metabolism, stress response, signal transduction and antioxidant. Based on functional classification of the differentially expressed proteins and the physiological responses, we found cucumber seedlings treated with Spd under salt stress had higher photosynthesis efficiency, upregulated tetrapyrrole synthesis, stronger ROS scavenging ability and more protein biosynthesis activity than NaCl treatment, suggesting that these pathways may promote salt tolerance under high salinity. This study provided insights into how exogenous Spd protects photosynthesis and enhances salt tolerance in cucumber seedlings.

Cholesterol blocks spontaneous insertion of membrane proteins into liposomes of phosphatidylcholine.

PubMed

Nakamura, Shota; Suzuki, Sonomi; Saito, Hiroaki; Nishiyama, Ken-Ichi

2018-04-01

Spontaneous insertion of membrane proteins into liposomes formed from Escherichia coli polar phospholipids is blocked by diacylglycerol (DAG) at a physiological level. We found that cholesterol also blocks this spontaneous insertion, although a much larger amount is necessary for sufficient blockage. Reversely, sphingomyelin enhanced the spontaneous insertion. DAG at a physiological level was found not to block spontaneous insertion into liposomes formed from phosphatidylcholine (PC), while non-physiologically high concentrations of DAG reduced it. On the other hand, cholesterol blocked the spontaneous insertion into PC liposomes at a physiological level, explaining that both PC and cholesterol are absent in E. coli. While sphingomyelin did not enhance spontaneous insertion into PC liposomes, the effect of cholesterol on blockage of spontaneous insertion was dominant over that of sphingomyelin, suggesting that cholesterol functions as a blocker of disordered spontaneous insertion in eukaryotic cells. Lower amount of cholesterol was necessary to block spontaneous insertion into ER-mimic liposomes, explaining that ER membranes contain less amount of cholesterol. These results also explain that cholesterol, but not DAG, is involved in blockage of spontaneous insertion in eukaryotic cells, since DAG plays an important role as a second messenger in signal transduction.

Signal enhancement ratio (SER) quantified from breast DCE-MRI and breast cancer risk

NASA Astrophysics Data System (ADS)

Wu, Shandong; Kurland, Brenda F.; Berg, Wendie A.; Zuley, Margarita L.; Jankowitz, Rachel C.; Sumkin, Jules; Gur, David

2015-03-01

Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue composition and vascularity. Breast DCE-MRI characterizes certain physiologic properties of breast tissue that are potentially related to breast cancer risk. Studies have shown that increased background parenchymal enhancement (BPE), which is the contrast enhancement occurring in normal cancer-unaffected breast tissues in post-contrast sequences, predicts increased breast cancer risk. Signal enhancement ratio (SER) computed from pre-contrast and post-contrast sequences in DCE-MRI measures change in signal intensity due to contrast uptake over time and is a measure of contrast enhancement kinetics. SER quantified in breast tumor has been shown potential as a biomarker for characterizing tumor response to treatments. In this work we investigated the relationship between quantitative measures of SER and breast cancer risk. A pilot retrospective case-control study was performed using a cohort of 102 women, consisting of 51 women who had diagnosed with unilateral breast cancer and 51 matched controls (by age and MRI date) with a unilateral biopsy-proven benign lesion. SER was quantified using fully-automated computerized algorithms and three SER-derived quantitative volume measures were compared between the cancer cases and controls using logistic regression analysis. Our preliminary results showed that SER is associated with breast cancer risk, after adjustment for the Breast Imaging Reporting and Data System (BI-RADS)-based mammographic breast density measures. This pilot study indicated that SER has potential for use as a risk factor for breast cancer risk assessment in women at elevated risk of developing breast cancer.

Attitude of medical students towards Early Clinical Exposure in learning endocrine physiology

PubMed Central

Sathishkumar, Solomon; Thomas, Nihal; Tharion, Elizabeth; Neelakantan, Nithya; Vyas, Rashmi

2007-01-01

Background Different teaching-learning methods have been used in teaching endocrine physiology for the medical students, so as to increase their interest and enhance their learning. This paper describes the pros and cons of the various approaches used to reinforce didactic instruction in endocrine physiology and goes on to describe the value of adding an Early Clinical Exposure program (ECE) to didactic instruction in endocrine physiology, as well as student reactions to it as an alternative approach. Discussion Various methods have been used to reinforce didactic instruction in endocrine physiology such as case-stimulated learning, problem-based learning, patient-centred learning and multiple-format sessions. We devised a teaching-learning intervention in endocrine physiology, which comprised of traditional didactic lectures, supplemented with an ECE program consisting of case based lectures and a hospital visit to see patients. A focus group discussion was conducted with the medical students and, based on the themes that emerged from it, a questionnaire was developed and administered to further enquire into the attitude of all the students towards ECE in learning endocrine physiology. The students in their feedback commented that ECE increased their interest for the subject and motivated them to read more. They also felt that ECE enhanced their understanding of endocrine physiology, enabled them to remember the subject better, contributed to their knowledge of the subject and also helped them to integrate their knowledge. Many students said that ECE increased their sensitivity toward patient problems and needs. They expressed a desire and a need for ECE to be continued in teaching endocrine physiology for future groups of students and also be extended for teaching other systems as well. The majority of the students (96.4%) in their feedback gave an overall rating of the program as good to excellent on a 5 point Likert scale. Summary The ECE program was introduced as an alternative approach to reinforce didactic instruction in endocrine physiology for the first year medical students. The study demonstrated that students clearly enjoyed the experience and perceived that it was valuable. This method could potentially be used for other basic science topics as well. PMID:17784967

Fluorinated graphenes as advanced biosensors - effect of fluorine coverage on electron transfer properties and adsorption of biomolecules

NASA Astrophysics Data System (ADS)

Urbanová, Veronika; Karlický, František; Matěj, Adam; Šembera, Filip; Janoušek, Zbyněk; Perman, Jason A.; Ranc, Václav; Čépe, Klára; Michl, Josef; Otyepka, Michal; Zbořil, Radek

2016-06-01

Graphene derivatives are promising materials for the electrochemical sensing of diverse biomolecules and development of new biosensors owing to their improved electron transfer kinetics compared to pristine graphene. Here, we report complex electrochemical behavior and electrocatalytic performance of variously fluorinated graphene derivatives prepared by reaction of graphene with a nitrogen-fluorine mixture at 2 bars pressure. The fluorine content was simply controlled by varying the reaction time and temperature. The studies revealed that electron transfer kinetics and electrocatalytic activity of CFx strongly depend on the degree of fluorination. The versatility of fluorinated graphene as a biosensor platform was demonstrated by cyclic voltammetry for different biomolecules essential in physiological processes, i.e. NADH, ascorbic acid and dopamine. Importantly, the highest electrochemical performance, even higher than pristine graphene, was obtained for fluorinated graphene with the lowest fluorine content (CF0.084) due to its high conductivity and enhanced adsorption properties combining π-π stacking interaction with graphene regions with hydrogen-bonding interaction with fluorine atoms.Graphene derivatives are promising materials for the electrochemical sensing of diverse biomolecules and development of new biosensors owing to their improved electron transfer kinetics compared to pristine graphene. Here, we report complex electrochemical behavior and electrocatalytic performance of variously fluorinated graphene derivatives prepared by reaction of graphene with a nitrogen-fluorine mixture at 2 bars pressure. The fluorine content was simply controlled by varying the reaction time and temperature. The studies revealed that electron transfer kinetics and electrocatalytic activity of CFx strongly depend on the degree of fluorination. The versatility of fluorinated graphene as a biosensor platform was demonstrated by cyclic voltammetry for different biomolecules essential in physiological processes, i.e. NADH, ascorbic acid and dopamine. Importantly, the highest electrochemical performance, even higher than pristine graphene, was obtained for fluorinated graphene with the lowest fluorine content (CF0.084) due to its high conductivity and enhanced adsorption properties combining π-π stacking interaction with graphene regions with hydrogen-bonding interaction with fluorine atoms. Electronic supplementary information (ESI) available: SEM, HRTEM, and AFM images the sheet in pristine graphene sample, survey XPS spectrum, high resolution C 1s XPS spectrum, and Raman spectrum of pristine graphene precursor used for controlled fluorination, survey and high resolution F 1s XPS spectra of the CF0.084, CF0.158, and CF0.218 samples, EDS chemical mapping of fluorine in CF0.158, contact angle measurement of CF0.084, CF0.158, CF0.218, and HOPG, and additional electrochemical data. See DOI: 10.1039/c6nr00353b

MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS

EPA Science Inventory

There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

LIMITATIONS IN THE USE OF MAGNETIC FIELDS TO EXAMINE GAP JUNCTION COMMUNICATION

EPA Science Inventory

OBJECTIVE: We have previously shown that gap junction communication (GJC) in mouse primary hepatocytes can be enhanced by treatment with physiological levels of melatonin, and that 45-Hz magnetic fields can eliminate this enhancement in a time-dependent manner. The objective of t...

Comparison of quantitative myocardial perfusion imaging CT to fluorescent microsphere-based flow from high-resolution cryo-images

NASA Astrophysics Data System (ADS)

Eck, Brendan L.; Fahmi, Rachid; Levi, Jacob; Fares, Anas; Wu, Hao; Li, Yuemeng; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

2016-03-01

Myocardial perfusion imaging using CT (MPI-CT) has the potential to provide quantitative measures of myocardial blood flow (MBF) which can aid the diagnosis of coronary artery disease. We evaluated the quantitative accuracy of MPI-CT in a porcine model of balloon-induced LAD coronary artery ischemia guided by fractional flow reserve (FFR). We quantified MBF at baseline (FFR=1.0) and under moderate ischemia (FFR=0.7) using MPI-CT and compared to fluorescent microsphere-based MBF from high-resolution cryo-images. Dynamic, contrast-enhanced CT images were obtained using a spectral detector CT (Philips Healthcare). Projection-based mono-energetic images were reconstructed and processed to obtain MBF. Three MBF quantification approaches were evaluated: singular value decomposition (SVD) with fixed Tikhonov regularization (ThSVD), SVD with regularization determined by the L-Curve criterion (LSVD), and Johnson-Wilson parameter estimation (JW). The three approaches over-estimated MBF compared to cryo-images. JW produced the most accurate MBF, with average error 33.3+/-19.2mL/min/100g, whereas LSVD and ThSVD had greater over-estimation, 59.5+/-28.3mL/min/100g and 78.3+/-25.6 mL/min/100g, respectively. Relative blood flow as assessed by a flow ratio of LAD-to-remote myocardium was strongly correlated between JW and cryo-imaging, with R2=0.97, compared to R2=0.88 and 0.78 for LSVD and ThSVD, respectively. We assessed tissue impulse response functions (IRFs) from each approach for sources of error. While JW was constrained to physiologic solutions, both LSVD and ThSVD produced IRFs with non-physiologic properties due to noise. The L-curve provided noise-adaptive regularization but did not eliminate non-physiologic IRF properties or optimize for MBF accuracy. These findings suggest that model-based MPI-CT approaches may be more appropriate for quantitative MBF estimation and that cryo-imaging can support the development of MPI-CT by providing spatial distributions of MBF.

Electrophysiological characteristics of embryonic stem cell-derived cardiomyocytes are cell line-dependent.

PubMed

Hannes, Tobias; Wolff, Marie; Doss, Michael Xavier; Pfannkuche, Kurt; Haustein, Moritz; Müller-Ehmsen, Jochen; Sachinidis, Agapios; Hescheler, Jürgen; Khalil, Markus; Halbach, Marcel

2015-01-01

Modelling of cardiac development, physiology and pharmacology by differentiation of embryonic stem cells (ESCs) requires comparability of cardiac differentiation between different ESC lines. To investigate whether the outcome of cardiac differentiation is consistent between different ESC lines, we compared electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs) of different murine ESC lines. Two wild-type (D3 and R1) and two transgenic ESC lines (D3/aPIG44 and CGR8/AMPIGX-7) were differentiated under identical culture conditions. The transgenic cell lines expressed enhanced green fluorescent protein (eGFP) and puromycin-N-acetyltransferase under control of the cardiac specific α-myosin heavy chain (αMHC) promoter. Action potentials (APs) were recorded using sharp electrodes and multielectrode arrays in beating clusters of ESC-CMs. Spontaneous AP frequency and AP duration (APD) as well as maximal upstroke velocity differed markedly between unpurified CMs of the four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term recordings showed a high degree of variability within and between recordings in CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the αMHC+ population by puromycin treatment posed only minor changes to APD in D3/aPIG44, but significantly shortened APD in CGR8/AMPIGX-7. Electrophysiological properties of ESC-CMs are strongly cell line-dependent and can be influenced by purification of cardiomyocytes by antibiotic selection. Thus, conclusions on cardiac development, physiology and pharmacology derived from single stem cell lines have to be interpreted carefully. © 2015 S. Karger AG, Basel.

Tree diversity affects chlorophyll a fluorescence and other leaf traits of tree species in a boreal forest.

PubMed

Pollastrini, Martina; Nogales, Ana Garcia; Benavides, Raquel; Bonal, Damien; Finer, Leena; Fotelli, Mariangela; Gessler, Arthur; Grossiord, Charlotte; Radoglou, Kalliopi; Strasser, Reto J; Bussotti, Filippo

2017-02-01

An assemblage of tree species with different crown properties creates heterogeneous environments at the canopy level. Changes of functional leaf traits are expected, especially those related to light interception and photosynthesis. Chlorophyll a fluorescence (ChlF) properties in dark-adapted leaves, specific leaf area, leaf nitrogen content (N) and carbon isotope composition (δ13C) were measured on Picea abies (L.) H.Karst., Pinus sylvestris L. and Betula pendula Roth. in monospecific and mixed boreal forests in Europe, in order to test whether they were affected by stand species richness and composition. Photosynthetic efficiency, assessed by induced emission of leaf ChlF, was positively influenced in B. pendula by species richness, whereas P. abies showed higher photosynthetic efficiency in monospecific stands. Pinus sylvestris had different responses when it coexisted with P. abies or B. pendula. The presence of B. pendula, but not of P. abies, in the forest had a positive effect on the efficiency of photosynthetic electron transport and N in P. sylvestris needles, and the photosynthetic responses were positively correlated with an increase of leaf δ13C. These effects on P. sylvestris may be related to high light availability at the canopy level due to the less dense canopy of B. pendula. The different light requirements of coexisting species was the most important factor affecting the distribution of foliage in the canopy, driving the physiological responses of the mixed species. Future research directions claim to enhance the informative potential of the methods to analyse the responses of pure and mixed forests to environmental factors, including a broader set of plant species' functional traits and physiological responses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

PubMed

Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

2016-12-01

Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adenosine receptors regulate gap junction coupling of the human cerebral microvascular endothelial cells hCMEC/D3 by Ca2+ influx through cyclic nucleotide-gated channels.

PubMed

Bader, Almke; Bintig, Willem; Begandt, Daniela; Klett, Anne; Siller, Ina G; Gregor, Carola; Schaarschmidt, Frank; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Hell, Stefan W; Ngezahayo, Anaclet

2017-04-15

Gap junction channels are essential for the formation and regulation of physiological units in tissues by allowing the lateral cell-to-cell diffusion of ions, metabolites and second messengers. Stimulation of the adenosine receptor subtype A 2B increases the gap junction coupling in the human blood-brain barrier endothelial cell line hCMEC/D3. Although the increased gap junction coupling is cAMP-dependent, neither the protein kinase A nor the exchange protein directly activated by cAMP were involved in this increase. We found that cAMP activates cyclic nucleotide-gated (CNG) channels and thereby induces a Ca 2+ influx, which leads to the increase in gap junction coupling. The report identifies CNG channels as a possible physiological link between adenosine receptors and the regulation of gap junction channels in endothelial cells of the blood-brain barrier. The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood-brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT-PCR. Scrape loading/dye transfer was used to evaluate the impact of the A 2A and A 2B adenosine receptor subtype agonist 2-phenylaminoadenosine (2-PAA) on the gap junction coupling. We found that 2-PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration-dependent manner. This enhancement was accompanied by an increase in gap junction plaques formed by Cx43. Inhibition of protein kinase A did not affect the 2-PAA-related enhancement of gap junction coupling. In contrast, the cyclic nucleotide-gated (CNG) channel inhibitor l-cis-diltiazem, as well as the chelation of intracellular Ca 2+ with BAPTA, or the absence of external Ca 2+ , suppressed the 2-PAA-related enhancement of gap junction coupling. Moreover, we observed a 2-PAA-dependent activation of CNG channels by a combination of electrophysiology and pharmacology. In conclusion, the stimulation of adenosine receptors in hCMEC/D3 cells induces a Ca 2+ influx by opening CNG channels in a cAMP-dependent manner. Ca 2+ in turn induces the formation of new gap junction plaques and a consecutive sustained enhancement of gap junction coupling. The report identifies CNG channels as a physiological link that integrates gap junction coupling into the adenosine receptor-dependent signalling of endothelial cells of the blood-brain barrier. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Physiological Plasticity to Water Flow Habitat in the Damselfish, Acanthochromis polyacanthus: Linking Phenotype to Performance

PubMed Central

Binning, Sandra A.; Ros, Albert F. H.; Nusbaumer, David; Roche, Dominique G.

2015-01-01

The relationships among animal form, function and performance are complex, and vary across environments. Therefore, it can be difficult to identify morphological and/or physiological traits responsible for enhancing performance in a given habitat. In fishes, differences in swimming performance across water flow gradients are related to morphological variation among and within species. However, physiological traits related to performance have been less well studied. We experimentally reared juvenile damselfish, Acanthochromis polyacanthus, under different water flow regimes to test 1) whether aspects of swimming physiology and morphology show plastic responses to water flow, 2) whether trait divergence correlates with swimming performance and 3) whether flow environment relates to performance differences observed in wild fish. We found that maximum metabolic rate, aerobic scope and blood haematocrit were higher in wave-reared fish compared to fish reared in low water flow. However, pectoral fin shape, which tends to correlate with sustained swimming performance, did not differ between rearing treatments or collection sites. Maximum metabolic rate was the best overall predictor of individual swimming performance; fin shape and fish total length were 3.3 and 3.7 times less likely than maximum metabolic rate to explain differences in critical swimming speed. Performance differences induced in fish reared in different flow environments were less pronounced than in wild fish but similar in direction. Our results suggest that exposure to water motion induces plastic physiological changes which enhance swimming performance in A. polyacanthus. Thus, functional relationships between fish morphology and performance across flow habitats should also consider differences in physiology. PMID:25807560

Changes in the physiological properties and kinetics of citric acid accumulation via carbon ion irradiation mutagenesis of Aspergillus niger *

PubMed Central

Hu, Wei; Chen, Ji-hong; Wang, Shu-yang; Liu, Jing; Song, Yuan; Wu, Qing-feng; Li, Wen-jian

2016-01-01

The objective of this work was to produce citric acid from corn starch using a newly isolated mutant of Aspergillus niger, and to analyze the relationship between changes in the physiological properties of A. niger induced by carbon ion irradiation and citric acid accumulation. Our results showed that the physiological characteristics of conidia in A. niger were closely related to citric acid accumulation and that lower growth rate and viability of conidia may be beneficial to citric acid accumulation. Using corn starch as a raw material, a high-yielding citric acid mutant, named HW2, was obtained. In a 10-L bioreactor, HW2 can accumulate 118.9 g/L citric acid with a residual total sugar concentration of only 14.4 g/L. This represented an 18% increase in citric acid accumulation and a 12.5% decrease in sugar utilization compared with the original strain.

Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.

PubMed

Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula

2017-08-02

Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social interactions, contributing to their isolation. Here, a mouse model of FXS was used to investigate the auditory brainstem where basic sound information is first processed. Loss of the Fragile X mental retardation protein leads to excessive excitatory compared with inhibitory inputs in neurons extracting information about sound levels. Functionally, this elevated excitation results in increased firing rates, and abnormal coding of frequency and binaural sound localization cues. Imbalanced early-stage sound level processing could partially explain the auditory processing deficits in FXS. Copyright © 2017 the authors 0270-6474/17/377403-17$15.00/0.

Study of electromechanical and mechanical properties of bacteria using force microscopy

NASA Astrophysics Data System (ADS)

Reukov, Vladimir; Thompson, Gary; Nikiforov, Maxim; Guo, Senli; Ovchinnikov, Oleg; Jesse, Stephen; Kalinin, Sergei; Vertegel, Alexey

2010-03-01

The application of scanning probe microscopy (SPM) to biological systems has evolved over the past decade into a multimodal and spectroscopic instrument that provides multiple information channels at each spatial pixel acquired. Recently, functional recognition imaging based on differing electromechanical properties between Gram negative and Gram positive bacteria was achieved using artificial neural network analysis of band excitation piezoresponse force microscopy (BEPFM) data. The immediate goal of this project was to study mechanical and electromechanical properties of bacterial systems physiologically-relevant solutions using Band-width Excitation Piezoresponce Force Microscopy (BE PFM) in combination with Force Mapping. Electromechanical imaging in physiological environments will improve the versatility of functional recognition imaging and open the way for application of the rapid BEPFM line mode method to other living cell systems.

Ontology of physics for biology: representing physical dependencies as a basis for biological processes

PubMed Central

2013-01-01

Background In prior work, we presented the Ontology of Physics for Biology (OPB) as a computational ontology for use in the annotation and representations of biophysical knowledge encoded in repositories of physics-based biosimulation models. We introduced OPB:Physical entity and OPB:Physical property classes that extend available spatiotemporal representations of physical entities and processes to explicitly represent the thermodynamics and dynamics of physiological processes. Our utilitarian, long-term aim is to develop computational tools for creating and querying formalized physiological knowledge for use by multiscale “physiome” projects such as the EU’s Virtual Physiological Human (VPH) and NIH’s Virtual Physiological Rat (VPR). Results Here we describe the OPB:Physical dependency taxonomy of classes that represent of the laws of classical physics that are the “rules” by which physical properties of physical entities change during occurrences of physical processes. For example, the fluid analog of Ohm’s law (as for electric currents) is used to describe how a blood flow rate depends on a blood pressure gradient. Hooke’s law (as in elastic deformations of springs) is used to describe how an increase in vascular volume increases blood pressure. We classify such dependencies according to the flow, transformation, and storage of thermodynamic energy that occurs during processes governed by the dependencies. Conclusions We have developed the OPB and annotation methods to represent the meaning—the biophysical semantics—of the mathematical statements of physiological analysis and the biophysical content of models and datasets. Here we describe and discuss our approach to an ontological representation of physical laws (as dependencies) and properties as encoded for the mathematical analysis of biophysical processes. PMID:24295137

Design of a framework for modeling, integration and simulation of physiological models.

PubMed

Erson, E Zeynep; Cavuşoğlu, M Cenk

2012-09-01

Multiscale modeling and integration of physiological models carry challenges due to the complex nature of physiological processes. High coupling within and among scales present a significant challenge in constructing and integrating multiscale physiological models. In order to deal with such challenges in a systematic way, there is a significant need for an information technology framework together with related analytical and computational tools that will facilitate integration of models and simulations of complex biological systems. Physiological Model Simulation, Integration and Modeling Framework (Phy-SIM) is an information technology framework providing the tools to facilitate development, integration and simulation of integrated models of human physiology. Phy-SIM brings software level solutions to the challenges raised by the complex nature of physiological systems. The aim of Phy-SIM, and this paper is to lay some foundation with the new approaches such as information flow and modular representation of the physiological models. The ultimate goal is to enhance the development of both the models and the integration approaches of multiscale physiological processes and thus this paper focuses on the design approaches that would achieve such a goal. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

NASA Astrophysics Data System (ADS)

Zhang, Xinjie; Lü, Shaoyu; Gao, Chunmei; Chen, Chen; Zhang, Xuan; Liu, Mingzhu

2013-06-01

The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00835e

Reactive oxygen species enhance insulin sensitivity

PubMed Central

Loh, Kim; Deng, Haiyang; Fukushima, Atsushi; Cai, Xiaochu; Boivin, Benoit; Galic, Sandra; Bruce, Clinton; Shields, Benjamin J.; Skiba, Beata; Ooms, Lisa M.; Stepto, Nigel; Wu, Ben; Mitchell, Christina A.; Tonks, Nicholas K.; Watt, Matthew J.; Febbraio, Mark A.; Crack, Peter J.; Andrikopoulos, Sofianos; Tiganis, Tony

2010-01-01

SUMMARY Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high fat diet-induced insulin resistance. The increased insulin sensitivity in Gpx1−/− mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the anti-oxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo. PMID:19808019

Hybrid Enhanced Epidermal SpaceSuit Design Approaches

NASA Astrophysics Data System (ADS)

Jessup, Joseph M.

A Space suit that does not rely on gas pressurization is a multi-faceted problem that requires major stability controls to be incorporated during design and construction. The concept of Hybrid Epidermal Enhancement space suit integrates evolved human anthropomorphic and physiological adaptations into its functionality, using commercially available bio-medical technologies to address shortcomings of conventional gas pressure suits, and the impracticalities of MCP suits. The prototype HEE Space Suit explored integumentary homeostasis, thermal control and mobility using advanced bio-medical materials technology and construction concepts. The goal was a space suit that functions as an enhanced, multi-functional bio-mimic of the human epidermal layer that works in attunement with the wearer rather than as a separate system. In addressing human physiological requirements for design and construction of the HEE suit, testing regimes were devised and integrated into the prototype which was then subject to a series of detailed tests using both anatomical reproduction methods and human subject.

Disentangling Fun and Enjoyment in Exergames Using an Expanded Design, Play, Experience Framework: A Narrative Review

PubMed Central

Mellecker, Robin; Baranowski, Tom

2013-01-01

Abstract With exergames (as with physical activity in general), more intense and longer-duration game play should accrue more health benefits. Exergames, however, appear to be played for relatively short durations, often at medium or lower intensities. Ostensibly games are played for fun or enjoyment. Enhancing the fun or enjoyment experienced during exergame play should enhance the intensity and duration of physical activity, and thereby the health benefits. Research, reviewed herein, indicates fun and/or enjoyment in games are inherently laden with psychosocial, physiological, and embodiment substrates. Physical activity may also have separate or closely related psychosocial, physiological, and embodiment enjoyment substrates. Research is needed to integrate these levels of experience and to identify the game mechanics that enhance, and even maximize, the fun or enjoyment experienced in exergames, to thereby increase the health benefit. PMID:24761322

FKBP5/FKBP51 enhances autophagy to synergize with antidepressant action

PubMed Central

Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Rein, Theo

2015-01-01

Levels of autophagy markers rise upon treatment of cells with antidepressants. However, it was not known whether this phenomenon might be linked to other antidepressant pathways or to any physiological effect. In this punctum, we summarize and discuss our recent findings that provide evidence for a role of the cochaperone FKBP5/FKBP51 (FK506 binding protein 5) in autophagy as a prerequisite for antidepressant action in cells, mice, and humans. FKBP5 associates with BECN1, changes its phosphorylation and protein levels and enhances markers of autophagy and autophagic flux. The effects of antidepressants on autophagy as well as their physiological effects in mice and human depend on FKBP5. PMID:25714272

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.

PubMed

Berry, Elliot M; Mechoulam, Raphael

2002-08-01

The physiological control of appetite and satiety, in which numerous neurotransmitters and neuropeptides play a role, is extremely complex. Here we describe the involvement of endocannabinoids in these processes. These endogenous neuromodulators enhance appetite in animals. The same effect is observed in animals and in humans with the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol, which is an approved appetite-enhancing drug. The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced by the endocannabinoids. If administered to mice pups, this antagonist blocks suckling. In obese humans, it causes weight reduction. Very little is known about the physiological and biochemical mechanisms involved in the effects of Delta(9)-tetrahydrocannabinol and the cannabinoids in feeding and appetite.

Effects of Wounding on Cytokinin Activity in Cucumber Cotyledons

PubMed Central

Crane, Karen E.; Ross, Cleon W.

1986-01-01

Three known physiological responses to exogenous cytokinins were measured in wounded and nonwounded cotyledons from cucumber (Cucumis sativus L. cv Marketer) seedlings grown in darkness. Enhanced cell division, chlorophyll formation, and cotyledon expansion were detected in wounded cotyledons. The data suggest that wounding enhances endogenous cytokinin activity. PMID:16665151

Effects of wounding on cytokinin activity in cucumber cotyledons.

PubMed

Crane, K E; Ross, C W

1986-12-01

Three known physiological responses to exogenous cytokinins were measured in wounded and nonwounded cotyledons from cucumber (Cucumis sativus L. cv Marketer) seedlings grown in darkness. Enhanced cell division, chlorophyll formation, and cotyledon expansion were detected in wounded cotyledons. The data suggest that wounding enhances endogenous cytokinin activity.

Development of an Arm Phantom for Testing Non-Invasive Blood Pressure Monitors

NASA Astrophysics Data System (ADS)

Anderson-Jackson, LaTecia D.

Approximately one in every three adults age 20 older are diagnosed with high blood pressure or hypertension. It is estimated that hypertension affects 78 million people in the United States, is equally prevalent in both men and woman (Crabtree, Stuart-Shor, & McAllister, 2013). In the United States, around 78% of people suffering from hypertension are aware of their condition, with only 68% using hypertensive medications to control their blood pressure (Writing Group et al., 2010). Clinically, blood pressure measurements may lack accuracy, which can be attributed to various factors, including device limitations, cuff mis-sizing and misplacement, white-coat effect, masked hypertension, and lifestyle factors. The development of an arm phantom to simulate physiologic properties of a human arm and arterial BP waveforms may allow us to better assess the accuracy of non-invasive blood pressure (NIBP) monitors. The objective of this study are to: (1) Develop an arm phantom to replicate physiological properties of the human arm, and (2) Incorporate the arm phantom into a mock circulatory flow loop to simulate different physiological blood pressure readings on the bench. A tissue mimicking material, styrene-ethylene-butylene-styrene (SEBS), a co-block polymer was used to develop the arm phantom for in-vitro testing. To determine the optimal mechanical properties for the arm phantom, individual arm components were isolated and tested. A protocol was developed to evaluate various components for optimal arm phantom development. Mechanical testing was conducted on 10%, 15%, and 20% SEBS gel samples for modulus of elasticity measurements in order to simulate physiological properties of the human arm. As a result of the SEBS polymer being a new material for this application, this investigation will contribute to resolving the limitations that occurred during experimentation. In this study, we demonstrated that although SEBS polymer may be an ideal material to use for simulating tissue, further research on the material properties should be conducted.

Cardiac damage in athlete's heart: When the "supernormal" heart fails!

PubMed

Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-06-26

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

Affect labeling enhances exposure effectiveness for public speaking anxiety.

PubMed

Niles, Andrea N; Craske, Michelle G; Lieberman, Matthew D; Hur, Christopher

2015-05-01

Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cardiac damage in athlete’s heart: When the “supernormal” heart fails!

PubMed Central

Carbone, Andreina; D’Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-01-01

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete’s blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete’s heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded. PMID:28706583

The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015).

PubMed

Miklya, I

2016-11-01

Deprenyl/Selegiline (DEP), created by Joseph Knoll in the 1960s, registered in more than 60 countries to treat Parkinson's disease, Alzheimer's disease, major depressive disorder; and used as an anti-aging drug, achieved its place in research and therapy as the first selective inhibitor of B-type monoamine oxidase (MAO-B). The demonstration that the DEP analog (-)-1-phenyl-2-propylaminopentane devoid of MAO inhibitory property, enhanced like DEP the activity of the catecholaminergic brain engine revealed that this effect is unrelated to the selective inhibition of MAO-B. β-Phenylethylamine (PEA), the important trace-amine in the mammalian brain, is known to be a releaser of catecholamines. Amphetamine and methamphetamine, the best known synthetic PEA derivatives are also releasers of catecholamines like their parent compound. DEP is a unique synthetic PEA derivative devoid of the catecholamine releasing property. As the releasing effect conceals the catecholaminergic activity enhancer (CAE) effect, it remained undiscovered until DEP uncovered that PEA is a natural CAE substance; and only releases catecholamines in high concentration. Discovering that tryptamine is a natural enhancer of catecholaminergic and serotonergic neurons catalyzed the development of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane (BPAP); the most potent and selective enhancer substance, and it exerts its enhancer effect in 0.0001 mg kg -1 . DEP and BPAP initiated an analysis of the enhancer regulation in the mammalian brain. Studies regarding the nature of the enhancer regulation revealed that this regulation is enhanced after weaning and sex hormones return it to the pre-weaning level. Thus, sex hormones elicit the transition of the developmental phase of life into the post-developmental, downhill (aging) period. The aging-related, slow decline in the enhancer regulation of the catecholaminergic brain engine, the main activator of the cortex, is the prime factor of brain aging. The enhancer regulation's decay in the most rapidly aging dopaminergic system is, for example, mainly responsible for the decline in learning ability and sexual activity over time. According to the Knoll concept, based on two longevity studies performed on male rats, to keep the catecholaminergic brain engine, from the beginning of the downhill period of life, via the administration of a small daily dose of a CAE substance (presently DEP is the only available drug) on a higher activity level, thus to fight against the physiological aging-related slow decay of the catecholaminergic system, is a suitable anti-aging therapy. As our present knowledge regarding the enhancer regulation in the mammalian brain is like seeing a peak of an iceberg, the future of this new line of brain research looks promising from both theoretical and practical aspects.

Endospore surface properties of commonly used Bacillus anthracis surrogates vary in aqueous solution

EPA Science Inventory

The hydrophobic character and electrophoretic mobility of microorganisms are vital aspects of understanding their interactions with the environment. These properties are fundamental in fate-and-transport, physiological, and virulence studies, and thus integral in surrogate select...

Questionable Benefit of Visual and Peer Mediated Learning on Overall Learning Outcomes of a First-Year Physiology Course

ERIC Educational Resources Information Center

Ernst, Hardy; McGahan, William T.; Harrison, John

2015-01-01

This paper reports on attempts to incorporate creative visual literacy, by way of student owned technology, and sharing of student-generated multimedia amongst peers to enhance learning in a first year human physiology course. In 2013, students were set the task of producing an animated video, which outlined the pathogenesis of a chosen disease.…

Enhancing Learning Objectives by Use of Simple Virtual Microscopic Slides in Cellular Physiology and Histology: Impact and Attitudes

ERIC Educational Resources Information Center

Anyanwu, Godson Emeka; Agu, Augustine Uchechukwu; Anyaehie, Ugochukwu Bond

2012-01-01

The impact and perception of students on the use of a simple, low technology-driven version of a virtual microscope in teaching and assessments in cellular physiology and histology were studied. Its impact on the time and resources of the faculty were also assessed. Simple virtual slides and conventional microscopes were used to conduct the same…

Using Neurological Feedback to Enhance Resilience and Recuperation

DTIC Science & Technology

2011-04-01

well-being, stress management and experience, and physiological markers of stress, anxiety and depression. During the upcoming symposium the...health and well-being, stress management and experience, and physiological markers of stress, anxiety and depression. During the upcoming symposium the...120 seconds are necessary to calculate reliable HRV information. This implies that feedback based on this method is always delayed and can not be used

Conformational ensemble of human α-synuclein physiological form predicted by molecular simulations.

PubMed

Rossetti, G; Musiani, F; Abad, E; Dibenedetto, D; Mouhib, H; Fernandez, C O; Carloni, P

2016-02-17

We perform here enhanced sampling simulations of N-terminally acetylated human α-synuclein, an intrinsically disordered protein involved in Parkinson's disease. The calculations, consistent with experiments, suggest that the post-translational modification leads to the formation of a transient amphipathic α-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions.

Co-Adaptive Aiding and Automation Enhance Operator Performance

DTIC Science & Technology

2013-03-01

activation system. There is a close relation between physiologically activated adaptive aiding and brain- computer interfaces ( BCI ). BCI here refers...classification of EEG signals (Farwell & Donchin, 1988). Physiologically activated adaptive aiding is, in a sense, a special case of BCI wherein the...as passive BCI , e.g. Zander, Kothe, Jatzev, & 3 Distribution A: Approved for public release; distribution unlimited. 88 ABW Cleared 05/13/2013

Do 'mind over muscle' strategies work? Examining the effects of attentional association and dissociation on exertional, affective and physiological responses to exercise.

PubMed

Lind, Erik; Welch, Amy S; Ekkekakis, Panteleimon

2009-01-01

Despite the well established physical and psychological benefits derived from leading a physically active life, rates of sedentary behaviour remain high. Dropout and non-compliance are major contributors to the problem of physical inactivity. Perceptions of exertion, affective responses (e.g. displeasure or discomfort), and physiological stress could make the exercise experience aversive, particularly for beginners. Shifting one's attentional focus towards environmental stimuli (dissociation) instead of one's body (association) has been theorized to enhance psychological responses and attenuate physiological stress. Research evidence on the effectiveness of attentional focus strategies, however, has been perplexing, covering the entire gamut of possible outcomes (association and dissociation having been shown to be both effective and ineffective). This article examines the effects of manipulations of attentional focus on exertional and affective responses, as well as on exercise economy and tolerance. The possible roles of the characteristics of the exercise stimulus (intensity, duration) and the exercise participants, methodological issues, and limitations of experimental designs are discussed. In particular, the critical role of exercise intensity is emphasized. Dissociative strategies may be more effective in reducing perceptions of exertion and enhancing affective responses at low to moderate exercise intensities, but their effectiveness may be diminished at higher and near-maximal levels, at which physiological cues dominate. Conversely, associative strategies could enable the exerciser to regulate intensity to avoid injury or overexertion. Thus, depending on intensity, both strategies have a place in the 'toolbox' of the public health or exercise practitioner as methods of enhancing the exercise experience and promoting long-term compliance.

Do Glucose and Caffeine Nasal Sprays Influence Exercise or Cognitive Performance?

PubMed

De Pauw, Kevin; Roelands, Bart; Van Cutsem, Jeroen; Decroix, Lieselot; Valente, Angelica; Taehee, Kim; Lettan, Robert B; Carrillo, Andres E; Meeusen, Romain

2017-10-01

Nasal spray (NAS) containing caffeine (CAF) or glucose (GLUC) activates sensory(motor) cortices. To investigate the influence of CAF or GLUC NAS on exercise and cognitive performance. Eleven male subjects (age 22 ± 2 y) performed a maximal cycle test and 2 familiarization and 3 experimental trials. Each trial included a 30-s Wingate test and a 30-min time-trial (TT) performance test interspersed by 15 min of rest. Before and after each exercise test a Stroop task was conducted. Placebo NAS with or without CAF or GLUC was provided before each exercise session and at each completed 25% of the TT. Exercise-performance, physiological, and cognitive measures were obtained. Magnitude-based inferences determined the likelihood that NAS solutions would be beneficial, trivial, or negative to exercise-performance measures based on the smallest worthwhile effect. Physiological and cognitive measures were analyzed using (non)parametric tests (P < .05). GLUC NAS substantially increased the average power output during the TT (very likely beneficial: 98%). No further worthwhile exercise-performance enhancements were found for both substances. In addition, no significant differences in physiological and cognitive measures were observed. In line with mouth rinsing, GLUC was shown to substantially enhance endurance performance, probably due to the activation of the olfactory pathway and/or extra-oral sweet-taste receptors. GLUC NAS enhances endurance performance, which indicates a novel administration route. The higher activity in sensory brain cortices probably elicited the ergogenic effect. However, no further physiological and cognitive changes occurred, indicating that higher doses of substrates might be required.

Water consumption and water-saving characteristics of a ground cover rice production system

NASA Astrophysics Data System (ADS)

Jin, Xinxin; Zuo, Qiang; Ma, Wenwen; Li, Sen; Shi, Jianchu; Tao, Yueyue; Zhang, Yanan; Liu, Yang; Liu, Xiaofei; Lin, Shan; Ben-Gal, Alon

2016-09-01

The ground cover rice production system (GCRPS) offers a potentially water-saving alternative to the traditional paddy rice production system (TPRPS) by furrow irrigating mulched soil beds and maintaining soils under predominately unsaturated conditions. The guiding hypothesis of this study was that a GCRPS would decrease both physiological and non-physiological water consumption of rice compared to a TPRPS while either maintaining or enhancing production. This was tested in a two-year field experiment with three treatments (TPRPS, GCRPSsat keeping root zone average soil water content near saturated, and GCRPS80% keeping root zone average soil water content as 80-100% of field water capacity) and a greenhouse experiment with four treatments (TPRPS, GCRPSsat, GCRPSfwc keeping root zone average soil water content close to field water capacity, and GCRPS80%). The water-saving characteristics of GCRPS were analyzed as a function of the measured soil water conditions, plant parameters regarding growth and production, and water input and consumption. In the field experiment, significant reduction in both physiological and non-physiological water consumption under GCRPS lead to savings in irrigation water of ∼61-84% and reduction in total input water of ∼35-47%. Compared to TPRPS, deep drainage was reduced ∼72-88%, evaporation was lessened ∼83-89% and transpiration was limited ∼6-10% under GCRPS. In addition to saving water, plant growth and grain yield were enhanced under GCRPS due to increased soil temperature in the root zone. Therefore, water use efficiencies (WUEs), based on transpiration, irrigation and total input water, were respectively improved as much as 27%, 609% and 110% under GCRPS. Increased yield attributed to up to ∼19%, decreased deep drainage accounted for ∼75%, decreased evaporation accounted for ∼14% and reduced transpiration for ∼5% of the enhancement in WUE of input water under GCRPS, while increased runoff and water storage had negative influence on WUE (-7.5 and -3.7%, respectively) for GCRPS compared to TPRPS. The greenhouse experiment validated the results obtained in the field by simplifying the non-physiological water consumption processes, and thus confirming the relative importance of physiological processes and increased WUE under GCRPS.

Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis.

PubMed

Wong, Raymond C S; Cloherty, Shaun L; Ibbotson, Michael R; O'Brien, Brendan J

2012-10-01

Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.

A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

PubMed

Salinas, Evelia Y; Hu, Jerry C; Athanasiou, Kyriacos

2018-04-26

The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile loading are used to tissue-engineer AC. Our goal is to provide a practical guide to their use and optimization of loading parameters. For each loading condition, we will also present and discuss benefits and limitations of bioreactor configurations that have been used. The intent is for this review to serve as a reference for including mechanical stimulation strategies as part of AC construct culture regimens.

Endophyte-Mediated Modulation of Defense-Related Genes and Systemic Resistance in Withania somnifera (L.) Dunal under Alternaria alternata Stress.

PubMed

Mishra, Aradhana; Singh, Satyendra Pratap; Mahfooz, Sahil; Singh, Surendra Pratap; Bhattacharya, Arpita; Mishra, Nishtha; Nautiyal, C S

2018-04-15

Endophytes have been explored and found to perform an important role in plant health. However, their effects on the host physiological function and disease management remain elusive. The present study aimed to assess the potential effects of endophytes, singly as well as in combination, in Withania somnifera (L.) Dunal, on various physiological parameters and systemic defense mechanisms against Alternaria alternata Seeds primed with the endophytic bacteria Bacillus amyloliquefaciens and Pseudomonas fluorescens individually and in combination demonstrated an enhanced vigor index and germination rate. Interestingly, plants treated with the two-microbe combination showed the lowest plant mortality rate (28%) under A. alternata stress. Physiological profiling of treated plants showed improved photosynthesis, respiration, transpiration, and stomatal conductance under pathogenic stress. Additionally, these endophytes not only augmented defense enzymes and antioxidant activity in treated plants but also enhanced the expression of salicylic acid- and jasmonic acid-responsive genes in the stressed plants. Reductions in reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with enhanced callose deposition in host plant leaves corroborated well with the above findings. Altogether, the study provides novel insights into the underlying mechanisms behind the tripartite interaction of endophyte- A. alternata - W. somnifera and underscores their ability to boost plant health under pathogen stress. IMPORTANCE W. somnifera is well known for producing several medicinally important secondary metabolites. These secondary metabolites are required by various pharmaceutical sectors to produce life-saving drugs. However, the cultivation of W. somnifera faces severe challenge from leaf spot disease caused by A. alternata To keep pace with the rising demand for this plant and considering its capacity for cultivation under field conditions, the present study was undertaken to develop approaches to enhance production of W. somnifera through intervention using endophytes. Application of bacterial endophytes not only suppresses the pathogenicity of A. alternata but also mitigates excessive ROS/RNS generation via enhanced physiological processes and antioxidant machinery. Expression profiling of plant defense-related genes further validates the efficacy of bacterial endophytes against leaf spot disease. Copyright © 2018 American Society for Microbiology.

[Statistical analysis of articles in "Chinese journal of applied physiology" from 1999 to 2008].

PubMed

Du, Fei; Fang, Tao; Ge, Xue-ming; Jin, Peng; Zhang, Xiao-hong; Sun, Jin-li

2010-05-01

To evaluate the academic level and influence of "Chinese Journal of Applied Physiology" through statistical analysis for the fund sponsored articles published in the recent ten years. The articles of "Chinese Journal of Applied Physiology" from 1999 to 2008 were investigated. The number and the percentage of the fund sponsored articles, the fund organization and the author region were quantitatively analyzed by using the literature metrology method. The number of the fund sponsored articles increased unceasingly. The ratio of the fund from local government significantly enhanced in the latter five years. Most of the articles were from institutes located at Beijing, Zhejiang and Tianjin. "Chinese Journal of Applied Physiology" has a fine academic level and social influence.

Stretch-induced, steady-state force enhancement in single skeletal muscle fibers exceeds the isometric force at optimum fiber length.

PubMed

Rassier, Dilson E; Herzog, Walter; Wakeling, Jennifer; Syme, Douglas A

2003-09-01

Stretch-induced force enhancement has been observed in a variety of muscle preparations and on structural levels ranging from single fibers to in vivo human muscles. It is a well-accepted property of skeletal muscle. However, the mechanism causing force enhancement has not been elucidated, although the sarcomere-length non-uniformity theory has received wide support. The purpose of this paper was to re-investigate stretch-induced force enhancement in frog single fibers by testing specific hypotheses arising from the sarcomere-length non-uniformity theory. Single fibers dissected from frog tibialis anterior (TA) and lumbricals (n=12 and 22, respectively) were mounted in an experimental chamber with physiological Ringer's solution (pH=7.5) between a force transducer and a servomotor length controller. The tetantic force-length relationship was determined. Isometric reference forces were determined at optimum length (corresponding to the maximal, active, isometric force), and at the initial and final lengths of the stretch experiments. Stretch experiments were performed on the descending limb of the force-length relationship after maximal tetanic force was reached. Stretches of 2.5-10% (TA) and 5-15% lumbricals of fiber length were performed at 0.1-1.5 fiber lengths/s. The stretch-induced, steady-state, active isometric force was always equal or greater than the purely isometric force at the muscle length from which the stretch was initiated. Moreover, for stretches of 5% fiber length or greater, and initiated near the optimum length of the fiber, the stretch-enhanced active force always exceeded the maximal active isometric force at optimum length. Finally, we observed a stretch-induced enhancement of passive force. We conclude from these results that the sarcomere length non-uniformity theory alone cannot explain the observed force enhancement, and that part of the force enhancement is associated with a passive force that is substantially greater after active compared to passive muscle stretch.

Improvement of water and light availability after thinning at a xeric site: which matters more? A dual isotope approach.

PubMed

Giuggiola, Arnaud; Ogée, Jérôme; Rigling, Andreas; Gessler, Arthur; Bugmann, Harald; Treydte, Kerstin

2016-04-01

Thinning fosters individual tree growth by increasing the availability of water, light and nutrients. At sites where water rather than light is limiting, thinning also enhances soil evaporation and might not be beneficial. Detailed knowledge of the short- to long-term physiological response underlying the growth responses to thinning is crucial for the management of forests already suffering from recurrent drought-induced dieback. We applied a dual isotope approach together with mechanistic isotope models to study the physiological processes underlying long-term growth enhancement of heavily thinned Pinus sylvestris in a xeric forest in Switzerland. This approach allowed us to identify and disentangle thinning-induced changes in stomatal conductance and assimilation rate. At our xeric study site, the increase in stomatal conductance far outweighed the increase in assimilation, implying that growth release in heavily thinned trees is primarily driven by enhanced water availability rather than increased light availability. We conclude that in forests with relatively isohydric species (drought avoiders) that are growing close to their physiological limits, thinning is recommended to maintain a less negative water balance and thus foster tree growth, and ultimately the survival of forest trees under drought. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

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.

In-situ polymerisation of fully bioresorbable polycaprolactone/phosphate glass fibre composites: In vitro degradation and mechanical properties.

PubMed

Chen, Menghao; Parsons, Andrew J; Felfel, Reda M; Rudd, Christopher D; Irvine, Derek J; Ahmed, Ifty

2016-06-01

Fully bioresorbable composites have been investigated in order to replace metal implant plates used for hard tissue repair. Retention of the composite mechanical properties within a physiological environment has been shown to be significantly affected due to loss of the integrity of the fibre/matrix interface. This study investigated phosphate based glass fibre (PGF) reinforced polycaprolactone (PCL) composites with 20%, 35% and 50% fibre volume fractions (Vf) manufactured via an in-situ polymerisation (ISP) process and a conventional laminate stacking (LS) followed by compression moulding. Reinforcing efficiency between the LS and ISP manufacturing process was compared, and the ISP composites revealed significant improvements in mechanical properties when compared to LS composites. The degradation profiles and mechanical properties were monitored in phosphate buffered saline (PBS) at 37°C for 28 days. ISP composites revealed significantly less media uptake and mass loss (p<0.001) throughout the degradation period. The initial flexural properties of ISP composites were substantially higher (p<0.0001) than those of the LS composites, which showed that the ISP manufacturing process provided a significantly enhanced reinforcement effect than the LS process. During the degradation study, statistically higher flexural property retention profiles were also seen for the ISP composites compared to LS composites. SEM micrographs of fracture surfaces for the LS composites revealed dry fibre bundles and poor fibre dispersion with polymer rich zones, which indicated poor interfacial bonding, distribution and adhesion. In contrast, evenly distributed fibres without dry fibre bundles or polymer rich zones, were clearly observed for the ISP composite samples, which showed that a superior fibre/matrix interface was achieved with highly improved adhesion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kokumi Substances, Enhancers of Basic Tastes, Induce Responses in Calcium-Sensing Receptor Expressing Taste Cells

PubMed Central

Maruyama, Yutaka; Yasuda, Reiko; Kuroda, Motonaka; Eto, Yuzuru

2012-01-01

Recently, we reported that calcium-sensing receptor (CaSR) is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca2+. CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami. PMID:22511946

Dendrimeric Systems and Their Applications in Ocular Drug Delivery

PubMed Central

Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2013-01-01

Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

Enhancement of Survival and Electricity Production in an Engineered Bacterium by Light-Driven Proton Pumping▿ †

PubMed Central

Johnson, Ethan T.; Baron, Daniel B.; Naranjo, Belén; Bond, Daniel R.; Schmidt-Dannert, Claudia; Gralnick, Jeffrey A.

2010-01-01

Microorganisms can use complex photosystems or light-dependent proton pumps to generate membrane potential and/or reduce electron carriers to support growth. The discovery that proteorhodopsin is a light-dependent proton pump that can be expressed readily in recombinant bacteria enables development of new strategies to probe microbial physiology and to engineer microbes with new light-driven properties. Here, we describe functional expression of proteorhodopsin and light-induced changes in membrane potential in the bacterium Shewanella oneidensis strain MR-1. We report that there were significant increases in electrical current generation during illumination of electrochemical chambers containing S. oneidensis expressing proteorhodopsin. We present evidence that an engineered strain is able to consume lactate at an increased rate when it is illuminated, which is consistent with the hypothesis that proteorhodopsin activity enhances lactate uptake by increasing the proton motive force. Our results demonstrate that there is coupling of a light-driven process to electricity generation in a nonphotosynthetic engineered bacterium. Expression of proteorhodopsin also preserved the viability of the bacterium under nutrient-limited conditions, providing evidence that fulfillment of basic energy needs of organisms may explain the widespread distribution of proteorhodopsin in marine environments. PMID:20453141

Enhancement of survival and electricity production in an engineered bacterium by light-driven proton pumping.

PubMed

Johnson, Ethan T; Baron, Daniel B; Naranjo, Belén; Bond, Daniel R; Schmidt-Dannert, Claudia; Gralnick, Jeffrey A

2010-07-01

Microorganisms can use complex photosystems or light-dependent proton pumps to generate membrane potential and/or reduce electron carriers to support growth. The discovery that proteorhodopsin is a light-dependent proton pump that can be expressed readily in recombinant bacteria enables development of new strategies to probe microbial physiology and to engineer microbes with new light-driven properties. Here, we describe functional expression of proteorhodopsin and light-induced changes in membrane potential in the bacterium Shewanella oneidensis strain MR-1. We report that there were significant increases in electrical current generation during illumination of electrochemical chambers containing S. oneidensis expressing proteorhodopsin. We present evidence that an engineered strain is able to consume lactate at an increased rate when it is illuminated, which is consistent with the hypothesis that proteorhodopsin activity enhances lactate uptake by increasing the proton motive force. Our results demonstrate that there is coupling of a light-driven process to electricity generation in a nonphotosynthetic engineered bacterium. Expression of proteorhodopsin also preserved the viability of the bacterium under nutrient-limited conditions, providing evidence that fulfillment of basic energy needs of organisms may explain the widespread distribution of proteorhodopsin in marine environments.

Estradiol selectively enhances auditory function in avian forebrain neurons

PubMed Central

Caras, Melissa L.; O’Brien, Matthew; Brenowitz, Eliot A.; Rubel, Edwin W

2012-01-01

Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or non-breeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate-level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate-level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner. PMID:23223283

Flow of Red Blood Cells in Stenosed Microvessels.

PubMed

Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

2016-06-20

A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis.

Flow of Red Blood Cells in Stenosed Microvessels

NASA Astrophysics Data System (ADS)

Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

2016-06-01

A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis.

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.

Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity.

PubMed

Song, Yuguang; Liu, Yangping; Hemann, Craig; Villamena, Frederick A; Zweier, Jay L

2013-02-15

In this work, we have developed a new class of dendritic TAM radicals (TG, TdG, and dTdG) through a convergent method based on the TAM core CT-03 or its deuterated analogue dCT-03 and trifurcated Newkome-type monomer. Among these radicals, dTdG exhibits the best EPR properties with sharpest EPR singlet and highest O(2) sensitivity due to deuteration of both the ester linker groups and the TAM core CT-03. Like the previous dendritic TAM radicals, these new compounds also show extremely high stability toward various reactive species owing to the dendritic encapsulation. The highly charged nature of these molecules resulting from nine carboxylate groups prevents concentration-dependent EPR line broadening at physiological pH. Furthermore, we demonstrate that these TAM radicals can be easily derivatized (e.g., PEGylation) at the nine carboxylate groups and the resulting PEGylated analogue dTdG-PEG completely inhibits the albumin binding, thereby enhancing suitability for in vivo applications. These new dendritic TAM radicals show great potential for in vivo EPR oximetric applications and provide insights on approaches to develop improved and targeted EPR oximetric probes for biomedical applications.

Effects of polyamines on the DNA-reactive properties of dimeric mithramycin complexed with cobalt(II): implications for anticancer therapy.

PubMed

Hou, Ming-Hon; Lu, Wen-Je; Huang, Chun-Yu; Fan, Ruey-Jane; Yuann, Jeu-Ming P

2009-06-09

Few studies have examined the effects of polyamines on the action of DNA-binding anticancer drugs. Here, a Co(II)-mediated dimeric mithramycin (Mith) complex, (Mith)(2)-Co(II), was shown to be resistant to polyamine competition toward the divalent metal ion when compared to the Fe(II)-mediated drug complexes. Surface plasmon resonance experiments demonstrated that polyamines interfered with the binding capacity and association rates of (Mith)(2)-Co(II) binding to DNA duplexes, while the dissociation rates were not affected. Although (Mith)(2)-Co(II) exhibited the highest oxidative activity under physiological conditions (pH 7.3 and 37 degrees C), polyamines (spermine in particular) inhibited the DNA cleavage activity of the (Mith)(2)-Co(II) in a concentration-dependent manner. Depletion of intracellular polyamines by methylglyoxal bis(guanylhydrazone) (MGBG) enhanced the sensitivity of A549 lung cancer cells to (Mith)(2)-Co(II), most likely due to the decreased intracellular effect of polyamines on the action of (Mith)(2)-Co(II). Our study suggests a novel method for enhancing the anticancer activity of DNA-binding metalloantibiotics through polyamine depletion.

DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

PubMed

Moon, Sue Jin; Jeong, Byong Chang; Kim, Hwa Jin; Lim, Joung Eun; Kwon, Ghee Young; Kim, Jeong Hoon

2018-03-01

Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription is limited. Here we report DBC1 as a key regulator of AR-V7 transcriptional activity and stability in CRPC cells. DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. DBC1 is required for recruitment of AR-V7 to its target enhancers and for long-range chromatin looping between the CDH2 enhancer and promoter. Mechanistically, DBC1 enhances DNA-binding activity of AR-V7 by direct interaction and inhibits CHIP E3 ligase-mediated ubiquitination and degradation of AR-V7 by competing with CHIP for AR-V7 binding, thereby stabilizing and activating AR-V7. Importantly, DBC1 depletion suppresses the tumorigenic and metastatic properties of CRPC cells. Our results firmly establish DBC1 as a critical AR-V7 coactivator that plays a key role in the regulation of DNA binding and stability of AR-V7 and has an important physiological role in CRPC progression.

Slow Wave Sleep Enhancement with Gaboxadol Reduces Daytime Sleepiness During Sleep Restriction

PubMed Central

Walsh, James K.; Snyder, Ellen; Hall, Janine; Randazzo, Angela C.; Griffin, Kara; Groeger, John; Eisenstein, Rhody; Feren, Stephen D.; Dickey, Pam; Schweitzer, Paula K.

2008-01-01

Study Objectives: To evaluate the impact of enhanced slow wave sleep (SWS) on behavioral, psychological, and physiological changes resulting from sleep restriction. Design: A double-blind, parallel group, placebo-controlled design was used to compare gaboxadol (GBX) 15 mg, a SWS-enhancing drug, to placebo during 4 nights of sleep restriction (5 h/night). Behavioral, psychological, and physiological measures of the impact of sleep restriction were assessed in both groups at baseline, during sleep restriction and following recovery sleep. Setting: Sleep research laboratory. Participants: Forty-one healthy adults; 9 males and 12 females (mean age: 32.0 ± 9.9 y) in the placebo group and 10 males and 10 females (mean age: 31.9 ± 10.2 y) in the GBX group. Interventions: Both experimental groups underwent 4 nights of sleep restriction. Each group received either GBX 15 mg or placebo on all sleep restriction nights, and both groups received placebo on baseline and recovery nights. Measurements and Results: Polysomnography documented a SWS-enhancing effect of GBX with no group difference in total sleep time during sleep restriction. The placebo group displayed the predicted deficits due to sleep restriction on the multiple sleep latency test (MSLT) and on introspective measures of sleepiness and fatigue. Compared to placebo, the GBX group showed significantly less physiological sleepiness on the MSLT and lower levels of introspective sleepiness and fatigue during sleep restriction. There were no differences between groups on the psychomotor vigilance task (PVT) and a cognitive test battery, but these measures were minimally affected by sleep restriction in this study. The correlation between change from baseline in MSLT on Day 6 and change from baseline in SWS on Night 6 was significant in the GBX group and in both groups combined. Conclusions: The results of this study are consistent with the hypothesis that enhanced SWS, in this study produced by GBX, reduces physiological sleep tendency and introspective sleepiness and fatigue which typically result from sleep restriction. Citation: Walsh JK; Snyder E; Hall J; Randazzo AC; Griffin K; Groeger J; Eisenstein R; Feren SD; Dickey P; Schweitzer PK. Slow Wave Sleep Enhancement with Gaboxadol Reduces Daytime Sleepiness During Sleep Restriction. SLEEP 2008;31(5):659–672. PMID:18517036

Phase-Locked Loop for Precisely Timed Acoustic Stimulation during Sleep

PubMed Central

Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady; Bellesi, Michele; Tononi, Giulio; Paller, Ken A.; Zee, Phyllis C.

2016-01-01

Background A Brain-Computer Interface could potentially enhance the various benefits of sleep. New Method We describe a strategy for enhancing slow-wave sleep (SWS) by stimulating the sleeping brain with periodic acoustic stimuli that produce resonance in the form of enhanced slow-wave activity in the electroencephalogram (EEG). The system delivers each acoustic stimulus at a particular phase of an electrophysiological rhythm using a Phase-Locked Loop (PLL). Results The PLL is computationally economical and well suited to follow and predict the temporal behavior of the EEG during slow-wave sleep. Comparison with Existing Methods Acoustic stimulation methods may be able to enhance SWS without the risks inherent in electrical stimulation or pharmacological methods. The PLL method differs from other acoustic stimulation methods that are based on detecting a single slow wave rather than modeling slow-wave activity over an extended period of time. Conclusions By providing real-time estimates of the phase of ongoing EEG oscillations, the PLL can rapidly adjust to physiological changes, thus opening up new possibilities to study brain dynamics during sleep. Future application of these methods hold promise for enhancing sleep quality and associated daytime behavior and improving physiologic function. PMID:26617321

Exercise and nutritional interventions for improving aging muscle health.

PubMed

Forbes, Scott C; Little, Jonathan P; Candow, Darren G

2012-08-01

Skeletal muscle mass declines with age (i.e., sarcopenia) resulting in muscle weakness and functional limitations. Sarcopenia has been associated with physiological changes in muscle morphology, protein and hormonal kinetics, insulin resistance, inflammation, and oxidative stress. The purpose of this review is to highlight how exercise and nutritional intervention strategies may benefit aging muscle. It is well known that resistance exercise training increases muscle strength and size and evidence also suggests that resistance training can increase mitochondrial content and decrease oxidative stress in older adults. Recent findings suggest that fast-velocity resistance exercise may be an effective intervention for older adults to enhance muscle power and functional capacity. Aerobic exercise training may also benefit aging skeletal muscle by enhancing mitochondrial bioenergetics, improving insulin sensitivity, and/or decreasing oxidative stress. In addition to exercise, creatine monohydrate, milk-based proteins, and essential fatty acids all have biological effects which could enhance some of the physiological adaptations from exercise training in older adults. Additional research is needed to determine whether skeletal muscle adaptations to increased activity in older adults are further enhanced with effective nutritional interventions and whether this is due to enhanced muscle protein synthesis, improved mitochondrial function, and/or a reduced inflammatory response.

Regulatory properties of 6-phosphofructokinase and control of glycolysis in boar spermatozoa.

PubMed

Kamp, G; Schmidt, H; Stypa, H; Feiden, S; Mahling, C; Wegener, G

2007-01-01

Glycolysis is crucial for sperm functions (motility and fertilization), but how this pathway is regulated in spermatozoa is not clear. This prompted to study the location and the regulatory properties of 6-phosphofructokinase (PFK, EC 2.7.1.11), the most important element for control of glycolytic flux. Unlike some other glycolytic enzymes, PFK showed no tight binding to sperm structures. It could readily be extracted from ejaculated boar spermatozoa by sonication and was then chromatographically purified. At physiological pH, the enzyme was allosterically inhibited by near-physiological concentrations of its co-substrate ATP, which induced co-operativity, i.e. reduced the affinity for the substrate fructose 6-phosphate. Inhibition by ATP was reinforced by citrate and H+. Above pH 8, PFK lost all its regulatory properties and showed maximum activity. However, in the physiological pH range, PFK activity was very sensitive to small changes in effectors. At near-physiological substrate concentrations, PFK activity requires activators (de-inhibitors) of which the combination of AMP and fructose 2,6-bisphosphate (F2,6P2) was most efficient as a result of synergistic effects. The kinetics of PFK suggest AMP, F2,6P2, H+, and citrate as allosteric effectors controlling PFK activity in boar spermatozoa. Using immunogold labeling, PFK was localized in the mid-piece and principal piece of the flagellum as well as in the acrosomal area at the top of the head and in the cytoplasmic droplets released from the mid-piece after ejaculation.

Evaluating dynamic contrast-enhanced and photoacoustic CT to assess intra-tumor heterogeneity in xenograft mouse models

NASA Astrophysics Data System (ADS)

Stantz, Keith M.; Liu, Bo; Cao, Minsong; Reinecke, Dan; Dzemidzic, Mario; Liang, Yun; Kruger, Robert

2006-03-01

Purpose: To evaluate photoacoustic CT spectroscopy (PCT-S) and dynamic contrast-enhanced CT (DCE-CT) ability to measure parameters - oxygen saturation and vascular physiology - associated with the intra-tumor oxygenation status. Material and Methods: Breast (VEGF165 enhance MCF-7) and ovarian (SKOV3x) cancer cells were implanted into the fat pads and flanks of immune deficient mice and allowed to grow to a diameter of 8-15 mm. CT was used to determine physiological parameters by acquiring a sequence of scans over a 10 minute period after an i.v. injection of a radio-opaque contrast agent (Isovue). These time-dependent contrast-enhanced curves were fit to a two-compartmental model determining tumor perfusion, fractional plasma volume, permeability-surface area produce, and fractional interstitial volume on a voxel-by-voxel basis. After which, the tumors were imaged using photoacoustic CT (Optosonics, Inc., Indianapolis, IN 46202). The near infrared spectra (700-910 nm) within the vasculature was fit to linear combination of measured oxy- and deoxy-hemoglobin blood samples to obtain oxygen saturation levels (SaO II). Results: The PCT-S scanner was first calibrated using different samples of oxygenated blood, from which a statistical error ranging from 2.5-6.5% was measured and a plot of the hemoglobin dissociation curve was consistent with empirical formula. In vivo determination of tumor vasculature SaO II levels were measurably tracked, and spatially correlated to the periphery of the tumor. Tumor depend variations in SaO II - 0.32 (ovarian) and 0.60 (breast) - and in vascular physiology - perfusion, 1.03 and 0.063 mL/min/mL, and fractional plasma volume, 0.20 and 0.07 - were observed. Conclusion: Combined, PCT-S and CED-CT has the potential to measure intra-tumor levels of tumor oxygen saturation and vascular physiology, key parameters associated with hypoxia.

Singularity now: using the ventricular assist device as a model for future human-robotic physiology.

PubMed

Martin, Archer K

2016-04-01

In our 21 st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today's world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named "IshBot") can best be studied in ventricular assist devices - VAD.

Singularity now: using the ventricular assist device as a model for future human-robotic physiology

PubMed Central

Martin, Archer K.

2016-01-01

In our 21st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today’s world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named “IshBot”) can best be studied in ventricular assist devices – VAD. PMID:28913480

Heating of foods in space-vehicle environments. [by conductive heat transfer

NASA Technical Reports Server (NTRS)

Bannerot, R. B.; Cox, J. E.; Chen, C. K.; Heidelbaugh, N. D.

1973-01-01

In extended space missions, foods will be heated to enhance the psychological as well as the physiological well-being of the crew. In the low-gravity space environment natural convection is essentially absent so that the heat transfer within the food is by conduction alone. To prevent boiling in reduced pressure environments the maximum temperature of the heating system is severely limited. The Skylab food-heating system utilizes a tray with receptables for the food containers. The walls of the receptacles are lined with thermally controlled, electrical-resistance, blanket-type heating elements. A finite difference model is employed to perform parametric studies on the food-heating system. The effects on heating time of the (1) thermophysical properties of the food, (2) heater power level, (3) initial food temperatures, (4) container geometry, and (5) heater control temperature are presented graphically. The optimal heater power level and container geometry are determined.

Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.

PubMed

Brady, Graham F; Galbán, Stefanie; Liu, Xuwen; Basrur, Venkatesha; Gitlin, Jonathan D; Elenitoba-Johnson, Kojo S J; Wilson, Thomas E; Duckett, Colin S

2010-04-01

In order to balance the cellular requirements for copper with its toxic properties, an elegant set of mechanisms has evolved to regulate and buffer intracellular copper. The X-linked inhibitor of apoptosis (XIAP) protein was recently identified as a copper-binding protein and regulator of copper homeostasis, although the mechanism by which XIAP binds copper in the cytosol is unclear. Here we describe the identification of the copper chaperone for superoxide dismutase (CCS) as a mediator of copper delivery to XIAP in cells. We also find that CCS is a target of the E3 ubiquitin ligase activity of XIAP, although interestingly, ubiquitination of CCS by XIAP was found to lead to enhancement of its chaperone activity toward its physiologic target, superoxide dismutase 1, rather than proteasomal degradation. Collectively, our results reveal novel links among apoptosis, copper metabolism, and redox regulation through the XIAP-CCS complex.

Nanostructured porous Si-based nanoparticles for targeted drug delivery

PubMed Central

Shahbazi, Mohammad-Ali; Herranz, Barbara; Santos, Hélder A.

2012-01-01

One of the backbones in nanomedicine is to deliver drugs specifically to unhealthy cells. Drug nanocarriers can cross physiological barriers and access different tissues, which after proper surface biofunctionalization can enhance cell specificity for cancer therapy. Recent developments have highlighted the potential of mesoporous silica (PSiO2) and silicon (PSi) nanoparticles for targeted drug delivery. In this review, we outline and discuss the most recent advances on the applications and developments of cancer therapies by means of PSiO2 and PSi nanomaterials. Bio-engineering and fine tuning of anti-cancer drug vehicles, high flexibility and potential for sophisticated release mechanisms make these nanostructures promising candidates for “smart” cancer therapies. As a result of their physicochemical properties they can be controllably loaded with large amounts of drugs and coupled to homing molecules to facilitate active targeting. The main emphasis of this review will be on the in vitro and in vivo studies. PMID:23507894

Laser irradiation of Mg-Al-Zn alloy: Reduced electrochemical kinetics and enhanced performance in simulated body fluid.

PubMed

Florian, David C; Melia, Michael A; Steuer, Fritz W; Briglia, Bruce F; Purzycki, Michael K; Scully, John R; Fitz-Gerald, James M

2017-05-11

As a lightweight metal with mechanical properties similar to natural bone, Mg and its alloys are great prospects for biodegradable, load bearing implants. However, rapid degradation and H 2 gas production in physiological media has prevented widespread use of Mg alloys. Surface heterogeneities in the form of intermetallic particles dominate the corrosion response. This research shows that surface homogenization significantly improved the biological corrosion response observed during immersion in simulated body fluid (SBF). The laser processed Mg alloy exhibited a 50% reduction in mass loss and H 2 evolution after 24 h of immersion in SBF when compared to the wrought, cast alloy. The laser processed samples exhibited increased wettability as evident from wetting angle studies, further suggesting improved biocompatibility. Electrochemical analysis by potentiodynamic polarization measurements showed that the anodic and cathodic kinetics were reduced following laser processing and are attributed to the surface chemical homogeneity.

Elicitation: a tool for enriching the bioactive composition of foods.

PubMed

Baenas, Nieves; García-Viguera, Cristina; Moreno, Diego A

2014-09-01

Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin), abiotic (chemical or physical origin) elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods.

Essential oils nanoformulations for stored-product pest control - characterization and biological properties.

PubMed

Werdin González, Jorge Omar; Gutiérrez, María Mercedes; Ferrero, Adriana Alicia; Fernández Band, Beatriz

2014-04-01

The lethal and sublethal activity of poly(ethylene glycol) (PEG) nanoparticles containing essential oils (EO), also the physicochemical characterization, were determined against Tribolium castaneum and Rhizopertha dominica. The 10% ratio EO-PEG nanoparticles showed an average diameter<235 nm (PDI<0.280) and a loading efficacy>75%; after 6 month of storage their size did not change significantly and the amount of the EOs decreased 25%, approximately. Furthermore, during this period, no chemical derivates were observed. The EOs nanoparticles produced a notable increase of the residual contact toxicity apparently due to the slow and persistent release of the active terpenes. In addition, the nanoformulation enhanced the EO contact toxicity and altered the nutritional physiology of both stored product pest. The results indicated that these novel systems could be used in integrated pest management program for T. castaneum and R. dominica control. Copyright © 2013 Elsevier Ltd. All rights reserved.

15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH

PubMed Central

2016-01-01

15N nuclear spins of imidazole-15N2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole-15N2 in methanol:aqueous buffer (∼1:1). Proton binding to a 15N site of imidazole occurs at physiological pH (pKa ∼ 7.0), and the binding event changes the 15N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms. PMID:27379344

15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH.

PubMed

Shchepin, Roman V; Barskiy, Danila A; Coffey, Aaron M; Theis, Thomas; Shi, Fan; Warren, Warren S; Goodson, Boyd M; Chekmenev, Eduard Y

2016-06-24

15 N nuclear spins of imidazole- 15 N 2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15 N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole- 15 N 2 in methanol:aqueous buffer (∼1:1). Proton binding to a 15 N site of imidazole occurs at physiological pH (p K a ∼ 7.0), and the binding event changes the 15 N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15 N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms.

Efficient color correction method for smartphone camera-based health monitoring application.

PubMed

Duc Dang; Chae Ho Cho; Daeik Kim; Oh Seok Kwon; Jo Woon Chong

2017-07-01

Smartphone health monitoring applications are recently highlighted due to the rapid development of hardware and software performance of smartphones. However, color characteristics of images captured by different smartphone models are dissimilar each other and this difference may give non-identical health monitoring results when the smartphone health monitoring applications monitor physiological information using their embedded smartphone cameras. In this paper, we investigate the differences in color properties of the captured images from different smartphone models and apply a color correction method to adjust dissimilar color values obtained from different smartphone cameras. Experimental results show that the color corrected images using the correction method provide much smaller color intensity errors compared to the images without correction. These results can be applied to enhance the consistency of smartphone camera-based health monitoring applications by reducing color intensity errors among the images obtained from different smartphones.

Role of naturally occurring osmolytes in protein folding and stability.

PubMed

Kumar, Raj

2009-11-01

Osmolytes are typically accumulated in the intracellular environment at relatively high concentrations when cells/tissues are subjected to stress conditions. Osmolytes are common in a variety of organisms, including microorganisms, plants, and animals. They enhance thermodynamic stability of proteins by providing natively folded conformations without perturbing other cellular processes. By burying the backbone into the core of folded proteins, osmolytes can provide significant stability to proteins. Two properties of osmolytes are particularly important: (i) their ability to impart increased thermodynamic stability to folded proteins; and (ii) their compatibility in the intracellular environment at high concentrations. Under physiological conditions, the cellular compositions of osmolytes may vary significantly. This may lead to different protein folding pathways utilized in cells depending upon the intracellular environment. Proper understanding of the role of osmolytes in cell regulation should allow predicting the action of osmolytes on macromolecular interactions in stressed and crowded environments typical of cellular conditions.

Complexation induced fluorescence and acid-base properties of dapoxyl dye with γ-cyclodextrin: a drug-binding application using displacement assays.

PubMed

Pal, Kaushik; Mallick, Suman; Koner, Apurba L

2015-06-28

Host-guest complexation of dapoxyl sodium sulphonate (DSS), an intramolecular charge transfer dye with water-soluble and non-toxic macrocycle γ-cyclodextrin (γ-CD), has been investigated in a wide pH range. Steady-state absorption, fluorescence and time-resolved fluorescence measurements confirm the positioning of DSS into the hydrophobic cavity of γ-CD. A large fluorescence enhancement ca. 30 times, due to 1 : 2 complex formation and host-assisted guest-protonation have been utilised for developing a method for the utilisation of CD based drug-delivery applications. A simple fluorescence-displacement based approach is implemented at physiological pH for the assessment of binding strength of pharmaceutically useful small drug molecules (ibuprofen, paracetamol, methyl salicylate, salicylic acid, aspirin, and piroxicam) and six important antibiotic drugs (resazurin, thiamphenicol, chloramphenicol, ampicillin, kanamycin, and sorbic acid) with γ-CD.

Coupling of metals and biominerals: characterizing the interface between ferromagnetic shape-memory alloys and hydroxyapatite.

PubMed

Allenstein, Uta; Selle, Susanne; Tadsen, Meike; Patzig, Christian; Höche, Thomas; Zink, Mareike; Mayr, Stefan G

2015-07-22

Durable, mechanically robust osseointegration of metal implants poses one of the largest challenges in contemporary orthopedics. The application of biomimetic hydroxyapatite (HAp) coatings as mediators for enhanced mechanical coupling to natural bone constitutes a promising approach. Motivated by recent advances in the field of smart metals that might open the venue for alternate therapeutic concepts, we explore their mechanical coupling to sputter-deposited HAp layers in a combined experimental-theoretical study. While experimental delamination tests and comprehensive structural characterization, including high-resolution transmission electron microscopy, are utilized to establish structure-property relationships, density functional theory based total energy calculations unravel the underlying physics and chemistry of bonding and confirm the experimental findings. Experiments and modeling indicate that sputter-deposited HAp coatings are strongly adherent to the exemplary ferromagnetic shape-memory alloys, Ni-Mn-Ga and Fe-Pd, with delamination stresses and interface bonding strength exceeding the physiological scales by orders of magnitude.

Detection of hydrogen peroxide with chemiluminescent micelles

PubMed Central

Lee, Dongwon; Erigala, Venkata R; Dasari, Madhuri; Yu, Junhua; Dickson, Robert M; Murthy, Niren

2008-01-01

The overproduction of hydrogen peroxide is implicated in the progress of numerous life-threatening diseases and there is a great need for the development of contrast agents that can detect hydrogen peroxide in vivo. In this communication, we present a new contrast agent for hydrogen peroxide, termed peroxalate micelles, which detect hydrogen peroxide through chemiluminescence, and have the physical/chemical properties needed for in vivo imaging applications. The peroxalate micelles are composed of amphiphilic peroxalate based copolymers and the fluorescent dye rubrene, they have a ‘stealth’ polyethylene glycol (PEG) corona to evade macrophage phagocytosis, and a diameter of 33 nm to enhance extravasation into permeable tissues. The peroxalate micelles can detect nanomolar concentrations of hydrogen peroxide (>50 nM) and thus have the sensitivity needed to detect physiological concentrations of hydrogen peroxide. We anticipate numerous applications of the peroxalate micelles for in vivo imaging of hydrogen peroxide, given their high sensitivity, small size, and biocompatible PEG corona. PMID:19337415

Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics

PubMed Central

Bakalova, Rumiana; Zhelev, Zhivko; Kokuryo, Daisuke; Spasov, Lubomir; Aoki, Ichio; Saga, Tsuneo

2011-01-01

Background: One of the most attractive properties of quantum dots is their potential to extend the opportunities for fluorescent and multimodal imaging in vivo. The aim of the present study was to clarify whether the composition and structure of organic coating of nanoparticles are crucial for their application in vivo. Methods: We compared quantum dots coated with non-crosslinked amino-functionalized polyamidoamine (PAMAM) dendrimers, quantum dots encapsulated in crosslinked carboxyl-functionalized PAMAM dendrimers, and silica-shelled amino-functionalized quantum dots. A multimodal fluorescent and paramagnetic quantum dot probe was also developed and analyzed. The probes were applied intravenously in anesthetized animals for visualization of brain vasculature using two-photon excited fluorescent microscopy and visualization of tumors using fluorescent IVIS® imaging (Caliper Life Sciences, Hopkinton, MA) and magnetic resonance imaging. Results: Quantum dots coated with non-crosslinked dendrimers were cytotoxic. They induced side effects in vivo, including vasodilatation with a decrease in mean arterial blood pressure and heart rate. The quantum dots penetrated the vessels, which caused the quality of fluorescent imaging to deteriorate. Quantum dots encapsulated in crosslinked dendrimers had low cytotoxicity and were biocompatible. In concentrations <0.3 nmol quantum dots/kg bodyweight, these nanoparticles did not affect blood pressure and heart rate, and did not induce vasodilatation or vasoconstriction. PEGylation (PEG [polyethylene glycol]) was an indispensable step in development of a quantum dot probe for in vivo imaging, based on silica-shelled quantum dots. The non-PEGylated silica-shelled quantum dots possessed low colloidal stability in high-salt physiological fluids, accompanied by rapid aggregation in vivo. The conjugation of silica-shelled quantum dots with PEG1100 increased their stability and half-life in the circulation without significant enhancement of their size. In concentrations <2.5 nmol/kg bodyweight, these quantum dots did not affect the main physiological variables. It was possible to visualize capillaries, which makes this quantum dot probe appropriate for investigation of mediators of vasoconstriction, vasodilatation, and brain circulation in intact animals in vivo. The multimodal silica-shelled quantum dots allowed visualization of tumor tissue in an early stage of its development, using magnetic resonance imaging. Conclusion: The present study shows that the type and structure of organic/bioorganic shells of quantum dots determine their biocompatibility and are crucial for their application in imaging in vivo, due to the effects of the shell on the following properties: colloidal stability, solubility in physiological fluids, influence of the basic physiological parameters, and cytotoxicity. PMID:21980235

Translational physiology: from molecules to public health.

PubMed

Seals, Douglas R

2013-07-15

The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.

Translational physiology: from molecules to public health

PubMed Central

Seals, Douglas R

2013-01-01

The term ‘translational research’ was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by ‘reverse translation’ in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise. PMID:23732641

Physiological responses induced by pleasant stimuli.

PubMed

Watanuki, Shigeki; Kim, Yeon-Kyu

2005-01-01

The specific physiological responses induced by pleasant stimuli were investigated in this study. Various physiological responses of the brain (encephaloelectrogram; EEG), autonomic nervous system (ANS), immune system and endocrine system were monitored when pleasant stimuli such as odors, emotional pictures and rakugo, a typical Japanese comical story-telling, were presented to subjects. The results revealed that (i) EEG activities of the left frontal brain region were enhanced by a pleasant odor; (ii) emotional pictures related to primitive element such as nudes and erotic couples elevated vasomotor sympathetic nervous activity; and (iii) an increase in secretory immunoglobulin A (s-IgA) and a decrease in salivary cortisol (s-cortisol) were induced by rakugo-derived linguistic pleasant emotion. Pleasant emotion is complicated state. However, by considering the evolutionary history of human being, it is possible to assess and evaluate pleasant emotion from certain physiological responses by appropriately summating various physiological parameters.

Hooke's law: applications of a recurring principle.

PubMed

Giuliodori, Mauricio J; Lujan, Heidi L; Briggs, Whitney S; Palani, Gurunanthan; DiCarlo, Stephen E

2009-12-01

Students generally approach topics in physiology as a series of unrelated phenomena that share few underlying principles. However, if students recognized that the same underlying principles can be used to explain many physiological phenomena, they may gain a more unified understanding of physiological systems. To address this concern, we developed a simple, inexpensive, and easy to build model to demonstrate the underlying principles regarding Starling's Law of the Heart as well as lung and arterial elastic recoil. A model was chosen because models significantly enhance student understanding. Working with models also encourages research-oriented learning and helps our students understand complex ideas. Students are drawn into discussion by the power of learning that is associated with manipulating and thinking about objects. Recognizing that the same underlying principles can be used to explain many physiological phenomena may help students gain a more complete understanding of physiological systems.

Physiology education in North American dental schools: the basic science survey series.

PubMed

Gautam, Medha; Shaw, David H; Pate, Ted D; Lambert, H Wayne

2014-06-01

As part of the Basic Science Survey Series for Dentistry, members of the American Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics Section surveyed directors of physiology courses in North American dental schools. The survey was designed to assess, among other things, faculty affiliation and experience of course directors, teaching methods, general course content and emphasis, extent of interdisciplinary (shared) instruction, and impact of recent curricular changes. Responses were received from forty-four of sixty-seven (65.7 percent) U.S. and Canadian dental schools. The findings suggest the following: substantial variation exists in instructional hours, faculty affiliation, class size, and interdisciplinary nature of physiology courses; physiology course content emphasis is similar between schools; student contact hours in physiology, which have remained relatively stable in the past fifteen years, are starting to be reduced; recent curricular changes have often been directed towards enhancing the integrative and clinically relevant aspects of physiology instruction; and a trend toward innovative content delivery, such as use of computer-assisted instruction, is evident. Data from this study may be useful to physiology course directors, curriculum committees, and other dental educators with an interest in integrative and interprofessional education.

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

PubMed

Castellani, John W; Young, Andrew J

2016-04-01

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

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

PubMed

Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

A review of the integrate-and-fire neuron model: II. Inhomogeneous synaptic input and network properties.

PubMed

Burkitt, A N

2006-08-01

The integrate-and-fire neuron model describes the state of a neuron in terms of its membrane potential, which is determined by the synaptic inputs and the injected current that the neuron receives. When the membrane potential reaches a threshold, an action potential (spike) is generated. This review considers the model in which the synaptic input varies periodically and is described by an inhomogeneous Poisson process, with both current and conductance synapses. The focus is on the mathematical methods that allow the output spike distribution to be analyzed, including first passage time methods and the Fokker-Planck equation. Recent interest in the response of neurons to periodic input has in part arisen from the study of stochastic resonance, which is the noise-induced enhancement of the signal-to-noise ratio. Networks of integrate-and-fire neurons behave in a wide variety of ways and have been used to model a variety of neural, physiological, and psychological phenomena. The properties of the integrate-and-fire neuron model with synaptic input described as a temporally homogeneous Poisson process are reviewed in an accompanying paper (Burkitt in Biol Cybern, 2006).

Development and characterization of a rapid polymerizing collagen for soft tissue augmentation.

PubMed

Devore, Dale; Zhu, Jiaxun; Brooks, Robert; McCrate, Rebecca Rone; Grant, David A; Grant, Sheila A

2016-03-01

A liquid collagen has been developed that fibrilizes upon injection. Rapid polymerizing collagen (RPC) is a type I porcine collagen that undergoes fibrillization upon interaction with ionic solutions, such as physiological solutions. The ability to inject liquid collagen would be beneficial for many soft tissue augmentation applications. In this study, RPC was synthesized and characterized as a possible dermal filler. Transmission electron microscopy, ion induced RPC fibrillogenesis tests, collagenase resistance assay, and injection force studies were performed to assess RPC's physicochemical properties. An in vivo study was performed which consisted of a 1-, 3-, and 6-month study where RPC was injected into the ears of miniature swine. The results demonstrated that the liquid RPC requires low injection force (<7 N); fibrillogenesis and banding of collagen occurs when RPC is injected into ionic solutions, and RPC has enhanced resistance to collagenase breakdown. The in vivo study demonstrated long-term biocompatibility with low irritation scores. In conclusion RPC possesses many of the desirable properties of a soft tissue augmentation material. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 758-767, 2016. © 2015 The authors journal of biomedical materials research part a published by wiley periodicals, inc.

Development and characterization of a rapid polymerizing collagen for soft tissue augmentation

PubMed Central

Devore, Dale; Zhu, Jiaxun; Brooks, Robert; McCrate, Rebecca Rone; Grant, David A.

2015-01-01

Abstract A liquid collagen has been developed that fibrilizes upon injection. Rapid polymerizing collagen (RPC) is a type I porcine collagen that undergoes fibrillization upon interaction with ionic solutions, such as physiological solutions. The ability to inject liquid collagen would be beneficial for many soft tissue augmentation applications. In this study, RPC was synthesized and characterized as a possible dermal filler. Transmission electron microscopy, ion induced RPC fibrillogenesis tests, collagenase resistance assay, and injection force studies were performed to assess RPC's physicochemical properties. An in vivo study was performed which consisted of a 1‐, 3‐, and 6‐month study where RPC was injected into the ears of miniature swine. The results demonstrated that the liquid RPC requires low injection force (<7 N); fibrillogenesis and banding of collagen occurs when RPC is injected into ionic solutions, and RPC has enhanced resistance to collagenase breakdown. The in vivo study demonstrated long‐term biocompatibility with low irritation scores. In conclusion RPC possesses many of the desirable properties of a soft tissue augmentation material. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 758–767, 2016. PMID:26488368

Coumarinocoumarin-Based Two-Photon Fluorescent Cysteine Biosensor for Targeting Lysosome.

PubMed

Chen, Chunyang; Zhou, Liuqing; Liu, Wei; Liu, Weisheng

2018-05-15

Coumarinocoumarin, one of the coumarin derivatives, is easy to synthesize and has rich modification sites. The large conjugate plane of coumarinocoumarin gives it a more excellent optical property than conventional coumarin, for example, the two-photon fluorescence property. So, the coumarinocoumarin-based probe (CCy) has been designed and synthesized, which is the first lysosomal targeting fluorescent biosensor for cysteine. This probe was prepared by a three-step procedure as a latent fluorescence probe to achieve high sensitivity and fluorescence turn-on response toward cysteine (Cys) over homocysteine (Hcy), glutathione (GSH), and other various natural amino acids under physiological conditions. Upon addition of Cys to the solution of CCy, remarkable enhancement on 520 nm of fluorescence spectra can be monitored. This probe was then successfully used for fluorescence imaging of Cys in mice organ tissues and HeLa cells, and quantitative determination has been achieved within a certain range, which proved the permeability of CCy. The concentration of Cys in animal serum was measured and the viability exceeded 80%, indicating that CCy can be a biocompatible and rapid probe for Cys in vivo. Simultaneously, its ability to detect Cys in lysosome has been validated by its lysosomal targeting.

ATP regulation of the ligand-binding properties in temperate and cold-adapted haemoglobins. X-ray structure and ligand-binding kinetics in the sub-Antarctic fish Eleginops maclovinus.

PubMed

Coppola, Daniela; Abbruzzetti, Stefania; Nicoletti, Francesco; Merlino, Antonello; Gambacurta, Alessandra; Giordano, Daniela; Howes, Barry D; De Sanctis, Giampiero; Vitagliano, Luigi; Bruno, Stefano; di Prisco, Guido; Mazzarella, Lelio; Smulevich, Giulietta; Coletta, Massimo; Viappiani, Cristiano; Vergara, Alessandro; Verde, Cinzia

2012-10-30

The major haemoglobin of the sub-Antarctic fish Eleginops maclovinus was structurally and functionally characterised with the aim to compare molecular environmental adaptations in the O(2)-transport system of sub-Antarctic fishes of the suborder Notothenioidei with those of their high-latitude relatives. Ligand-binding kinetics of the major haemoglobin of E. maclovinus indicated strong stabilisation of the liganded quaternary T state, enhanced in the presence of the physiological allosteric effector ATP, compared to that of high-Antarctic Trematomus bernacchii. The activation enthalpy for O(2) dissociation was dramatically lower than that in T. bernacchii haemoglobin, suggesting remarkable differences in temperature sensitivity and structural changes associated with O(2) release and exit from the protein. The haemoglobin functional properties, together with the X-ray structure of the CO form at 1.49 Å resolution, the first of a temperate notothenioid, strongly support the hypothesis that in E. maclovinus, whose life-style varies according to changes in habitat, the mechanisms that regulate O(2) affinity and the ATP-induced Root effect differ from those of high-Antarctic Notothenioids.

Structure-odor relationships of linalool, linalyl acetate and their corresponding oxygenated derivatives

NASA Astrophysics Data System (ADS)

Elsharif, Shaimaa; Banerjee, Ashutosh; Buettner, Andrea

2015-10-01

Linalool 1 is an odorant that is commonly perceived as having a pleasant odor, but is also known to elicit physiological effects such as inducing calmness and enhancing sleep. However, no comprehensive studies are at hand to show which structural features are responsible for these prominent effects. Therefore, a total of six oxygenated derivatives were synthesized from both 1 and linalyl acetate 2, and were tested for their odor qualities and relative odor thresholds (OTs) in air. Linalool was found to be the most potent odorant among the investigated compounds, with an average OT of 3.2 ng/L, while the 8-hydroxylinalool derivative was the least odorous compound with an OT of 160 ng/L; 8-carboxylinalool was found to be odorless. The odorant 8-oxolinalyl acetate, which has very similar odor properties to linalool, was the most potent odorant besides linalool, exhibiting an OT of 5.9 ng/L. By comparison, 8-carboxylinalyl acetate had a similar OT (6.1 ng/L) as its corresponding 8-oxo derivative but exhibited divergent odor properties (fatty, greasy, musty). Overall, oxygenation on carbon 8 had a substantial effect on the aroma profiles of structural derivatives of linalool and linalyl acetate.

Rheological, mechanical and degradable properties of injectable chitosan/silk fibroin/hydroxyapatite/glycerophosphate hydrogels.

PubMed

Wu, Jingjing; Liu, Jiaoyan; Shi, Yanmei; Wan, Ying

2016-12-01

Silk fibroin (SF) and hydroxyapatite (HA) were incorporated into chitosan/glycerophosphate (GP) system to prepare new types of hydrogels. The formulated chitosan/SF/GP and chitosan/SF/HA/GP solutions were found to be injectable at room temperature, and able to form into hydrogels at near-physiological temperature and pH. Rheological measurements showed that elastic modulus of certain chitosan/SF/GP and chitosan/SF/HA/GP gels could reach around 1.8 and 15kPa, respectively, and was much higher than their respective viscous modulus. Compressive measurements revealed that some chitosan/SF/GP and chitosan/SF/HA/GP gels had 8 and 20-fold modulus and strength higher than the chitosan/GP gel, respectively, confirming that compressive properties of these gels were greatly improved. Results obtained from in vivo degradation demonstrated that degradation endurance of the optimized chitosan/SF/GP and chitosan/SF/HA/GP gels was significantly enhanced as compared to the chitosan/GP gel, and the degradation rate of the gels could be regulated by the SF component alone or by the combination of SF and HA components. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physiologic and biochemical aspects of skeletal muscle denervation and reinnervation

NASA Technical Reports Server (NTRS)

Max, S. R.; Mayer, R. F.

1984-01-01

Some of the physiologic and biochemical changes that occur in mammalian skeletal muscle following denervation and reinnervation are considered and some comparisons are made with changes observed following altered motor function. The nature of the trophic influence by which nerves control muscle properties are discussed, including the effects of choline acetyltransferase and acetylcholinesterase and the role of the acetylcholine receptor.

A Genomic View of Lactobacilli and Pediococci Demonstrates that Phylogeny Matches Ecology and Physiology

PubMed Central

Zheng, Jinshui; Ruan, Lifang; Sun, Ming

2015-01-01

Lactobacilli are used widely in food, feed, and health applications. The taxonomy of the genus Lactobacillus, however, is confounded by the apparent lack of physiological markers for phylogenetic groups of lactobacilli and the unclear relationships between the diverse phylogenetic groups. This study used the core and pan-genomes of 174 type strains of Lactobacillus and Pediococcus to establish phylogenetic relationships and to identify metabolic properties differentiating phylogenetic groups. The core genome phylogenetic tree separated homofermentative lactobacilli and pediococci from heterofermentative lactobacilli. Aldolase and phosphofructokinase were generally present in homofermentative but not in heterofermentative lactobacilli; a two-domain alcohol dehydrogenase and mannitol dehydrogenase were present in most heterofermentative lactobacilli but absent in most homofermentative organisms. Other genes were predominantly present in homofermentative lactobacilli (pyruvate formate lyase) or heterofermentative lactobacilli (lactaldehyde dehydrogenase and glycerol dehydratase). Cluster analysis of the phylogenomic tree and the average nucleotide identity grouped the genus Lactobacillus sensu lato into 24 phylogenetic groups, including pediococci, with stable intra- and intergroup relationships. Individual groups may be differentiated by characteristic metabolic properties. The link between phylogeny and physiology that is proposed in this study facilitates future studies on the ecology, physiology, and industrial applications of lactobacilli. PMID:26253671

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

PubMed Central

Wood, JodiAnne T.; Williams, John S.; Pandarinathan, Lakshmipathi; Janero, David R.; Lammi-Keefe, Carol J.; Makriyannis, Alexandros

2010-01-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications. PMID:20071693

Bryophyte physiological responses to, and recovery from, long-term nitrogen deposition and phosphorus fertilisation in acidic grassland.

PubMed

Arróniz-Crespo, María; Leake, Jonathan R; Horton, Peter; Phoenix, Gareth K

2008-01-01

Atmospheric nitrogen deposition can cause major declines in bryophyte abundance yet the physiological basis for such declines is not fully understood. Bryophyte physiological responses may also be sensitive bioindicators of both the impacts of, and recovery from, N deposition. Here, responses of tissue nutrients (nitrogen (N), phosphorus (P) and potassium (K): NPK), N and P metabolism enzymes (nitrate reductase and phosphomonoesterase), photosynthetic pigments, chlorophyll fluorescence, sclerophylly and percentage cover of two common bryophytes (Pseudoscleropodium purum and Rhytidiadelphus squarrosus) to long-term (11 yr) enhanced N deposition (+3.5 and +14 g N m(-2) yr(-1)) are reported in factorial combination with P addition. Recovery of responses 22 months after treatment cessation were also assessed. Enhanced N deposition caused up to 90% loss of bryophyte cover but no recovery was observed. Phosphomonoesterase activity and tissue N:P ratios increased up to threefold in response to N loading and showed clear recovery, particularly in P. purum. Smaller responses and recovery were also seen in all chlorophyll fluorescence measurements and altered photosynthetic pigment composition. The P limitation of growth appears to be a key mechanism driving bryophyte loss along with damage to photosystem II. Physiological measurements are more sensitive than measurements of abundance as bioindicators of N deposition impact and of recovery in particular.

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma.

PubMed

Wood, Jodianne T; Williams, John S; Pandarinathan, Lakshmipathi; Janero, David R; Lammi-Keefe, Carol J; Makriyannis, Alexandros

2010-06-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications.

The complex genetics of human insulin-like growth factor 2 are not reflected in public databases.

PubMed

Rotwein, Peter

2018-03-23

Recent advances in genetics present unique opportunities for enhancing knowledge about human physiology and disease susceptibility. Understanding this information at the individual gene level is challenging and requires extracting, collating, and interpreting data from a variety of public gene repositories. Here, I illustrate this challenge by analyzing the gene for human insulin-like growth factor 2 ( IGF2 ) through the lens of several databases. IGF2, a 67-amino acid secreted peptide, is essential for normal prenatal growth and is involved in other physiological and pathophysiological processes in humans. Surprisingly, none of the genetic databases accurately described or completely delineated human IGF2 gene structure or transcript expression, even though all relevant information could be found in the published literature. Although IGF2 shares multiple features with the mouse Igf2 gene, it has several unique properties, including transcription from five promoters. Both genes undergo parental imprinting, with IGF2 / Igf2 being expressed primarily from the paternal chromosome and the adjacent H19 gene from the maternal chromosome. Unlike mouse Igf2 , whose expression declines after birth, human IGF2 remains active throughout life. This characteristic has been attributed to a unique human gene promoter that escapes imprinting, but as shown here, it involves several different promoters with distinct tissue-specific expression patterns. Because new testable hypotheses could lead to critical insights into IGF2 actions in human physiology and disease, it is incumbent that our fundamental understanding is accurate. Similar challenges affecting knowledge of other human genes should promote attempts to critically evaluate, interpret, and correct human genetic data in publicly available databases. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications

PubMed Central

Carta, Gianfranca; Murru, Elisabetta; Banni, Sebastiano; Manca, Claudia

2017-01-01

Palmitic acid (PA) has been for long time negatively depicted for its putative detrimental health effects, shadowing its multiple crucial physiological activities. PA is the most common saturated fatty acid accounting for 20–30% of total fatty acids in the human body and can be provided in the diet or synthesized endogenously via de novo lipogenesis (DNL). PA tissue content seems to be controlled around a well-defined concentration, and changes in its intake do not influence significantly its tissue concentration because the exogenous source is counterbalanced by PA endogenous biosynthesis. Particular physiopathological conditions and nutritional factors may strongly induce DNL, resulting in increased tissue content of PA and disrupted homeostatic control of its tissue concentration. The tight homeostatic control of PA tissue concentration is likely related to its fundamental physiological role to guarantee membrane physical properties but also to consent protein palmitoylation, palmitoylethanolamide (PEA) biosynthesis, and in the lung an efficient surfactant activity. In order to maintain membrane phospholipids (PL) balance may be crucial an optimal intake of PA in a certain ratio with unsaturated fatty acids, especially PUFAs of both n-6 and n-3 families. However, in presence of other factors such as positive energy balance, excessive intake of carbohydrates (in particular mono and disaccharides), and a sedentary lifestyle, the mechanisms to maintain a steady state of PA concentration may be disrupted leading to an over accumulation of tissue PA resulting in dyslipidemia, hyperglycemia, increased ectopic fat accumulation and increased inflammatory tone via toll-like receptor 4. It is therefore likely that the controversial data on the association of dietary PA with detrimental health effects, may be related to an excessive imbalance of dietary PA/PUFA ratio which, in certain physiopathological conditions, and in presence of an enhanced DNL, may further accelerate these deleterious effects. PMID:29167646

In vivo physiological recording from the lateral line of juvenile zebrafish.

PubMed

Olt, Jennifer; Allen, Claire E; Marcotti, Walter

2016-10-01

Zebrafish provide a unique opportunity to investigate in vivo sensory transduction in mature hair cells. We have developed a method for studying the biophysical properties of mature hair cells from the lateral line of juvenile zebrafish. The method involves application of the anaesthetic benzocaine and intubation to maintain ventilation and oxygenation through the gills. The same approach could be used for in vivo functional studies in other sensory and non-sensory systems from juvenile and adult zebrafish. Hair cells are sensory receptors responsible for transducing auditory and vestibular information into electrical signals, which are then transmitted with remarkable precision to afferent neurons. The zebrafish lateral line is emerging as an excellent in vivo model for genetic and physiological analysis of hair cells and neurons. However, research has been limited to larval stages because zebrafish become protected from the time of independent feeding under European law (from 5.2 days post-fertilization (dpf) at 28.5°C). In larval zebrafish, the functional properties of most of hair cells, as well as those of other excitable cells, are still immature. We have developed an experimental protocol to record electrophysiological properties from hair cells of the lateral line in juvenile zebrafish. We found that the anaesthetic benzocaine at 50 mg l(-1) was an effective and safe anaesthetic to use on juvenile zebrafish. Concentrations up to 300 mg l(-1) did not affect the electrical properties or synaptic vesicle release of juvenile hair cells, unlike the commonly used anaesthetic MS-222, which reduces the size of basolateral membrane K(+) currents. Additionally, we implemented a method to maintain gill movement, and as such respiration and blood oxygenation, via the intubation of > 21 dpf zebrafish. The combination of benzocaine and intubation provides an experimental platform to investigate the physiology of mature hair cells from live zebrafish. More generally, this method would allow functional studies involving live imaging and electrophysiology from juvenile and adult zebrafish. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Commercial opportunities in bioseparations and physiological testing aboard Space Station Freedom

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1992-01-01

The Center for Cell Research (CCR) is a NASA Center for the Commercial Development of Space which has as its main goal encouraging industry-driven biomedical/biotechnology space projects. Space Station Freedom (SSF) will provide long duration, crew-tended microgravity environments which will enhance the opportunities for commercial biomedical/biotechnology projects in bioseparations and physiological testing. The CCR bioseparations program, known as USCEPS (for United States Commercial Electrophoresis Program in Space), is developing access for American industry to continuous-flow electrophoresis aboard SSF. In space, considerable scale-up of continuous free-flow electrophoresis is possible for cells, sub cellular particles, proteins, growth factors, and other biological products. The lack of sedemination and buoyancy-driven convection flow enhances purity of separations and the amount of material processed/time. Through the CCR's physiological testing program, commercial organizations will have access aboard SSF to physiological systems experiments (PSE's); the Penn State Biomodule; and telemicroscopy. Physiological systems experiments involve the use of live animals for pharmaceutical product testing and discovery research. The Penn State Biomodule is a computer-controlled mini lab useful for projects involving live cells or tissues and macro molecular assembly studies, including protein crystallization. Telemicroscopy will enable staff on Earth to manipulate and monitor microscopic specimens on SSF for product development and discovery research or for medical diagnosis of astronaut health problems. Space-based product processing, testing, development, and discovery research using USCEPS and CCR's physiological testing program offer new routes to improved health on Earth. Direct crew involvement-in biomedical/biotechnology projects aboard SSF will enable better experimental outcomes. The current data base shows that there is reason for considerable optimism regarding what the CCDS program and the biomedical/biotechnology industry can expect to gain from a permanent manned presence in space.

Comfort and microbial barrier properties of garments worn next to the skin

NASA Astrophysics Data System (ADS)

Kopitar, D.; Rogina-Car, B.; Skenderi, Z.

2017-10-01

Compared with viscose fibre, modal fibre is characterized by some advantageous properties such as higher dry and wet tenacities, higher wet modulus, lower water retention capacity and lower level of swelling. Impact of different knitted fabric structure made of cotton and 97 % CMD/3 % EL fibres on thermo-physiological comfort and microbial barrier properties were investigated. All knitted fabrics have very good physiological properties. The microbial barrier permeability of knitted fabric after extreme contamination with bacterial spores in dry state showed that double jersey offered more effective microbial barrier than the single jersey knitted fabrics respectively the greater thickness of double jersey knitted fabric provide more difficult barrier to bacterial spores to pass. In wet state all knitted fabrics have more effective microbial barrier which could be explained by cellulose fibres swelling. In wet state 97 % CMD/3 % EL single jersey knitted fabric have more effective microbial barrier then cotton double and single jersey knitted fabrics.

Nano-Fiber Reinforced Enhancements in Composite Polymer Matrices

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2009-01-01

Nano-fibers are used to reinforce polymer matrices to enhance the matrix dependent properties that are subsequently used in conventional structural composites. A quasi isotropic configuration is used in arranging like nano-fibers through the thickness to ascertain equiaxial enhanced matrix behavior. The nano-fiber volume ratios are used to obtain the enhanced matrix strength properties for 0.01,0.03, and 0.05 nano-fiber volume rates. These enhanced nano-fiber matrices are used with conventional fiber volume ratios of 0.3 and 0.5 to obtain the composite properties. Results show that nano-fiber enhanced matrices of higher than 0.3 nano-fiber volume ratio are degrading the composite properties.

Impact of naturally leaking carbon dioxide on soil properties and ecosystems in the Qinghai-Tibet plateau

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

Zhao, Xiaohong; Deng, Hongzhang; Wang, Wenke

One of the major concerns for CO 2 capture and storage (CCS) is the potential risk of CO 2 leakage from storage reservoirs on the shallow soil property and vegetation. This study utilizes a naturally occurring CO 2 leaking site in the Qinghai-Tibet Plateau to analog a “leaking CCS site”. Our observations from this site indicates that long-term CO 2 invasion in the vadose zone results in variations of soil properties, such as pH fluctuation, slight drop of total organic carbon, reduction of nitrogen and phosphorus, and concentration changes of soluble ions. Simultaneously, XRD patterns of the soil suggest thatmore » crystallization of soil is enhanced and mineral contents of calcite and anorthite in soil are increased substantially. Parts of the whole ecosystem such as natural wild plants, soil dwelling animals and microorganisms in shallow soil are affected as well. Under a moderate CO 2 concentration (less than 110000 ppm), wild plant growth and development are improved, while an intensive CO2 flux over 112000 ppm causes adverse effects on the plant growth, physiological and biochemical system of plants, and crop quality of wheat. Results of this study provide valuable insight for understanding the possible environmental impacts associated with potential CO 2 leakage into shallow sediments at carbon sequestration sites.« less

How animals move: comparative lessons on animal locomotion.

PubMed

Schaeffer, Paul J; Lindstedt, Stan L

2013-01-01

Comparative physiology often provides unique insights in animal structure and function. It is specifically through this lens that we discuss the fundamental properties of skeletal muscle and animal locomotion, incorporating variation in body size and evolved difference among species. For example, muscle frequencies in vivo are highly constrained by body size, which apparently tunes muscle use to maximize recovery of elastic recoil potential energy. Secondary to this constraint, there is an expected linking of skeletal muscle structural and functional properties. Muscle is relatively simple structurally, but by changing proportions of the few muscle components, a diverse range of functional outputs is possible. Thus, there is a consistent and predictable relation between muscle function and myocyte composition that illuminates animal locomotion. When animals move, the mechanical properties of muscle diverge from the static textbook force-velocity relations described by A. V. Hill, as recovery of elastic potential energy together with force and power enhancement with activation during stretch combine to modulate performance. These relations are best understood through the tool of work loops. Also, when animals move, locomotion is often conveniently categorized energetically. Burst locomotion is typified by high-power outputs and short durations while sustained, cyclic, locomotion engages a smaller fraction of the muscle tissue, yielding lower force and power. However, closer examination reveals that rather than a dichotomy, energetics of locomotion is a continuum. There is a remarkably predictable relationship between duration of activity and peak sustainable performance.

Impact of naturally leaking carbon dioxide on soil properties and ecosystems in the Qinghai-Tibet plateau

DOE PAGES

Zhao, Xiaohong; Deng, Hongzhang; Wang, Wenke; ...

2017-06-07

One of the major concerns for CO 2 capture and storage (CCS) is the potential risk of CO 2 leakage from storage reservoirs on the shallow soil property and vegetation. This study utilizes a naturally occurring CO 2 leaking site in the Qinghai-Tibet Plateau to analog a “leaking CCS site”. Our observations from this site indicates that long-term CO 2 invasion in the vadose zone results in variations of soil properties, such as pH fluctuation, slight drop of total organic carbon, reduction of nitrogen and phosphorus, and concentration changes of soluble ions. Simultaneously, XRD patterns of the soil suggest thatmore » crystallization of soil is enhanced and mineral contents of calcite and anorthite in soil are increased substantially. Parts of the whole ecosystem such as natural wild plants, soil dwelling animals and microorganisms in shallow soil are affected as well. Under a moderate CO 2 concentration (less than 110000 ppm), wild plant growth and development are improved, while an intensive CO2 flux over 112000 ppm causes adverse effects on the plant growth, physiological and biochemical system of plants, and crop quality of wheat. Results of this study provide valuable insight for understanding the possible environmental impacts associated with potential CO 2 leakage into shallow sediments at carbon sequestration sites.« less

Synthesis of curcumin-functionalized gold nanoparticles and cytotoxicity studies in human prostate cancer cell line

NASA Astrophysics Data System (ADS)

Nambiar, Shruti; Osei, Ernest; Fleck, Andre; Darko, Johnson; Mutsaers, Anthony J.; Wettig, Shawn

2018-03-01

Gold nanoparticles synthesized using plant extracts with medicinal properties have gained traction in recent years, especially for their use in various biomedical applications. Colloidal stability of these nanoparticles in different environments is critical to retain the expected therapeutic/diagnostic efficacy and toxicological outcome. Any change in the colloidal stability leads to dramatic changes in the physico-chemical properties of the nanoparticles such as size and surface charge, which in turn may alter the biological activity of the particles. Such changes are imminent in physiologically-relevant environment wherein interactions with different biomolecules, such as serum proteins, may modify the overall properties of the nanoparticles. In this regard, we synthesized 15 nm sized gold nanoparticles using curcumin, a plant extract from turmeric root, to evaluate cytotoxicity, uptake, and localization in human prostate cancer cells using cell-culture medium supplemented with or without fetal bovine serum (FBS). The results indicate a dramatic difference in the cytotoxicity and uptake between cells treated with curcumin-functionalized gold nanoparticles (cur-AuNPs) in cell-culture medium with and without serum. The addition of FBS to the medium not only increased the stability of the nanoparticles but also enhanced the biocompatibility (i.e. minimal cytotoxicity for a wide range of cur-AuNP concentrations). We conclude that the presence of serum proteins significantly impact the therapeutic potential of cur-AuNPs.

Effect of unsaturations on the physical properties of a model membrane with the highly polyunsaturated docosahexaenoic fatty acid

NASA Astrophysics Data System (ADS)

Saiz, Leonor; Klein, Michael L.

2001-03-01

Polyunsaturated fatty acids are an essential component of biomembranes. The docosahexaenoic fatty acid (DHA), in particular, is found in high concentrations in retinal and neuronal tissue and in the olfactory bulb. Furthermore, it is well known the ability of DHA rich membranes to modulate membrane protein function, in some situations, by modifying the membrane physical properties. A particularly well studied situation is the DHA effect onthe activity of the visual receptor (protein) rhodopsin. Here, we study at a microscopic level this type of complex systems under physiological conditions. In this way, we can probe the molecular origin of the peculiarities that the system confers to membranes. To this purpose, the structure of a fully hydrated mixed (saturated/polyunsaturated) chain lipid bilayer in the biologically relevant liquid crystalline phase has been examined by performing molecular dynamics simulations. The model membrane, a 1-stearoyl- 2-docosahexaenoic- sn-glycero- 3-phosphatidylcholine (18:0/22:6 PC) lipid bilayer, was investigated at room temperature and ambient pressure and the results obtained in the nanosecond time scale were in good agreement with the available experimental data. Among the effects of the multiple unsaturations on the physical properties of these membranes, we focus on the enhanced permeability to water and small organic solvents, the decreased area compressibility modulus, and the domain formation and chain segregation.

Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer

PubMed Central

Feng, Y; Zhu, M; Dangelmajer, S; Lee, Y M; Wijesekera, O; Castellanos, C X; Denduluri, A; Chaichana, K L; Li, Q; Zhang, H; Levchenko, A; Guerrero-Cazares, H; Quiñones-Hinojosa, A

2014-01-01

Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM. PMID:25501828

Friction Stir Processing of Stainless Steel for Ascertaining Its Superlative Performance in Bioimplant Applications.

PubMed

Perumal, G; Ayyagari, A; Chakrabarti, A; Kannan, D; Pati, S; Grewal, H S; Mukherjee, S; Singh, S; Arora, H S

2017-10-25

Substrate-cell interactions for a bioimplant are driven by substrate's surface characteristics. In addition, the performance of an implant and resistance to degradation are primarily governed by its surface properties. A bioimplant typically degrades by wear and corrosion in the physiological environment, resulting in metallosis. Surface engineering strategies for limiting degradation of implants and enhancing their performance may reduce or eliminate the need for implant removal surgeries and the associated cost. In the current study, we tailored the surface properties of stainless steel using submerged friction stir processing (FSP), a severe plastic deformation technique. FSP resulted in significant microstructural refinement from 22 μm grain size for the as-received alloy to 0.8 μm grain size for the processed sample with increase in hardness by nearly 1.5 times. The wear and corrosion behavior of the processed alloy was evaluated in simulated body fluid. The processed sample demonstrated remarkable improvement in both wear and corrosion resistance, which is explained by surface strengthening and formation of a highly stable passive layer. The methylthiazol tetrazolium assay demonstrated that the processed sample is better in supporting cell attachment, proliferation with minimal toxicity, and hemolysis. The athrombogenic characteristic of the as-received and processed samples was evaluated by fibrinogen adsorption and platelet adhesion via the enzyme-linked immunosorbent assay and lactate dehydrogenase assay, respectively. The processed sample showed less platelet and fibrinogen adhesion compared with the as-received alloy, signifying its high thromboresistance. The current study suggests friction stir processing to be a versatile toolbox for enhancing the performance and reliability of currently used bioimplant materials.

Impact of a protective vest and spacer garment on exercise-heat strain.

PubMed

Cheuvront, Samuel N; Goodman, Daniel A; Kenefick, Robert W; Montain, Scott J; Sawka, Michael N

2008-03-01

Protective vests worn by global security personnel, and weighted vests worn by athletes, may increase physiological strain due to added load, increased clothing insulation and vapor resistance. The impact of protective vest clothing properties on physiological strain, and the potential of a spacer garment to reduce physiological strain, was examined. Eleven men performed 3 trials of intermittent treadmill walking over 4 h in a hot, dry environment (35 degrees C, 30% rh). Volunteers wore the US Army battledress uniform (trial B), B + protective vest (trial P), and B + P + spacer garment (trial S). Biophysical clothing properties were determined and found similar to many law enforcement, industry, and sports ensembles. Physiological measurements included core (T (c)), mean skin (T (sk)) and chest (T (chest)) temperatures, heart rate (HR), and sweating rate (SR). The independent impact of clothing was determined by equating metabolic rate in all trials. In trial P, HR was +7 b/min higher after 1 h of exercise and +19 b/min by the fourth hour compared to B (P < 0.05). T (c) (+0.30 degrees C), T (sk) (+1.0 degrees C) and Physiological Strain Index were all higher in P than B (P < 0.05). S did not abate these effects except to reduce T (sk) (P > S) via a lower T (chest) (-0.40 degrees C) (P < 0.05). SR was higher (P < 0.05) in P and S versus B, but the magnitude of differences was small. A protective vest increases physiological strain independent of added load, while a spacer garment does not alter this outcome.

Pulsatile perfusion bioreactor for cardiac tissue engineering.

PubMed

Brown, Melissa A; Iyer, Rohin K; Radisic, Milica

2008-01-01

Cardiovascular disease is the number one cause of mortality in North America. Cardiac tissue engineering aims to engineer a contractile patch of physiological thickness to use in surgical repair of diseased heart tissue. We previously reported that perfusion of engineered cardiac constructs resulted in improved tissue assembly. Because heart tissues respond to mechanical stimuli in vitro and experience rhythmic mechanical forces during contraction in vivo, we hypothesized that provision of pulsatile interstitial medium flow to an engineered cardiac patch would result in enhanced tissue assembly by way of mechanical conditioning and improved mass transport. Thus, we constructed a novel perfusion bioreactor capable of providing pulsatile fluid flow at physiologically relevant shear stresses and flow rates. Pulsatile perfusion (PP) was achieved by incorporation of a normally closed solenoid pinch valve into the perfusion loop and was carried out at a frequency of 1 Hz and a flow rate of 1.50 mL/min (PP) or 0.32 mL/min (PP-LF). Nonpulsatile flow at 1.50 mL/min (NP) or 0.32 mL/min (NP-LF) served as controls. Static controls were cultivated in well plates. The main experimental groups were seeded with cells enriched for cardiomyocytes by one preplating step (64% cardiac Troponin I+, 34% prolyl-4-hydroxylase+), whereas pure cardiac fibroblasts and cells enriched for cardiomyocytes by two preplating steps (81% cardiac Troponin I+, 16% prolyl-4-hydroxylase+) served as controls. Cultivation under pulsatile flow had beneficial effects on contractile properties. Specifically, the excitation threshold was significantly lower in the PP condition (pulsatile perfusion at 1.50 mL/min) than in the Static control, and the contraction amplitude was the highest; whereas high maximum capture rate was observed for the PP-LF conditions (pulsatile perfusion at 0.32 mL/min). The enhanced hypertrophy index observed for the PP-LF group was consistent with the highest cellular length and diameter in this group. Within the same cultivation groups (Static, NP-LF, PP-LF, PP, and NP) there were no significant differences in the diameter between fibroblasts and cardiomyocytes, although cardiomyocytes were significantly more elongated than fibroblasts under PP-LF conditions. Cultivation of control cell populations resulted in noncontractile constructs when cardiac fibroblasts were used (as expected) and no overall improvement in functional properties when two steps of preplating were used to enrich for cardiomyocytes in comparison with only one step of preplating.

ATP-mediated intrinsic peroxidase-like activity of Fe3O4-based nanozyme: One step detection of blood glucose at physiological pH.

PubMed

Vallabani, N V Srikanth; Karakoti, Ajay S; Singh, Sanjay

2017-05-01

Fe 3 O 4 nanoparticles (Fe 3 O 4 NPs), demonstrating peroxidase-like activity has garnered attention in the detection of several biomolecules, therefore, emerged as an excellent nano-biosensing agent. The intrinsic peroxidase-like activity of Fe 3 O 4 NPs at acidic pH is the fundamental action driving the oxidation of substrates like TMB, resulting in a colorimetric product formation used in the detection of biomolecules. Hence, the detection sensitivity essentially depends on the ability of oxidation by Fe 3 O 4 NPs in presence of H 2 O 2 . However, the limited sensitivity and pH condition constraint have been identified as the major drawbacks in the detection of biomolecules at physiological pH. Herein, we report overwhelming of the fundamental limitation of acidic pH and tuning the peroxidase-like activity of Fe 3 O 4 NPs at physiological pH by using ATP. In presence of ATP, Fe 3 O 4 NPs exhibited enhanced peroxidase-like activity over a wide range of pH and temperatures. Mechanistically, it was found that the ability of ATP to participate in single electron transfer reaction, through complexation with Fe 3 O 4 NPs, results in the generation of hydroxyl radicals which are responsible for enhanced peroxidase activity at physiological pH. We utilized this ATP-mediated enhanced peroxidase-like activity of Fe 3 O 4 NPs for single step detection of glucose with a colorimetric detection limit of 50μM. Further, we extended this single step detection method to monitor glucose level in human blood serum and detected in a time span of <5min at pH 7.4. Copyright © 2017 Elsevier B.V. All rights reserved.

The natural product chitosan enhances the anti-tumor activity of natural killer cells by activating dendritic cells.

PubMed

Li, Xinxin; Dong, Wenjuan; Nalin, Ansel P; Wang, Yufeng; Pan, Pan; Xu, Bo; Zhang, Yibo; Tun, Steven; Zhang, Jianying; Wang, Li-Shu; He, Xiaoming; Caligiuri, Michael A; Yu, Jianhua

2018-01-01

Natural products comprise an important class of biologically active molecules. Many of these compounds derived from natural sources exhibit specific physiologic or biochemical effects. An example of a natural product is chitosan, which is enriched in the shells of certain seafood that are frequently consumed worldwide. Like other natural products, chitosan has the potential for applications in clinical medicine and perhaps in cancer therapy. Toward this end, the immunomodulatory or anti-cancer properties of chitosan have yet to be reported. In this study, we discovered that chitosan enhanced the anti-tumor activity of natural killer (NK) cells by activating dendritic cells (DCs). In the presence of DCs, chitosan augmented IFN-γ production by human NK cells. Mechanistically, chitosan activated DCs to express pro-inflammatory cytokines such as interleukin (IL)-12 and IL-15, which in turn activated the STAT4 and NF-κB signaling pathways, respectively, in NK cells. Moreover, chitosan promoted NK cell survival, and also enhanced NK cell cytotoxicity against leukemia cells. Finally, a related in vivo study demonstrated that chitosan activated NK cells against B16F10 tumor cells in an immunocompetent syngeneic murine melanoma model. This effect was accompanied by in vivo upregulation of IL-12 and IL-15 in DCs, as well as increased IFN-γ production and cytolytic degranulation in NK cells. Collectively, our results demonstrate that chitosan activates DCs leading to enhanced capacity for immune surveillance by NK cells. We believe that our study has future clinical applications for chitosan in the prevention or treatment of cancer and infectious diseases.

Estimation of the viscous properties of skin and subcutaneous tissue in uniaxial stress relaxation tests.

PubMed

Wu, John Z; Cutlip, Robert G; Welcome, Daniel; Dong, Ren G

2006-01-01

Knowledge of viscoelastic properties of soft tissues is essential for the finite element modelling of the stress/strain distributions in finger-pad during vibratory loading, which is important in exploring the mechanism of hand-arm vibration syndrome. In conventional procedures, skin and subcutaneous tissue have to be separated for testing the viscoelastic properties. In this study, a novel method has been proposed to simultaneously determine the viscoelastic properties of skin and subcutaneous tissue in uniaxial stress relaxation tests. A mathematical approach has been derived to obtain the creep and relaxation characteristics of skin and subcutaneous tissue using uniaxial stress relaxation data of skin/subcutaneous composite specimens. The micro-structures of collagen fiber networks in the soft tissue, which underline the tissue mechanical characteristics, will be intact in the proposed method. Therefore, the viscoelastic properties of soft tissues obtained using the proposed method would be more physiologically relevant than those obtained using the conventional method. The proposed approach has been utilized to measure the viscoelastic properties of soft tissues of pig. The relaxation curves of pig skin and subcutaneous tissue obtained in the current study agree well with those in literature. Using the proposed approach, reliable material properties of soft tissues can be obtained in a cost- and time-efficient manner, which simultaneously improves the physiological relevance.

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach.

PubMed

Tresoldi, Claudia; Bianchi, Elena; Pellegata, Alessandro Filippo; Dubini, Gabriele; Mantero, Sara

2017-08-01

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.

When galectins recognize glycans: from biochemistry to physiology and back again.

PubMed

Di Lella, Santiago; Sundblad, Victoria; Cerliani, Juan P; Guardia, Carlos M; Estrin, Dario A; Vasta, Gerardo R; Rabinovich, Gabriel A

2011-09-20

In the past decade, increasing efforts have been devoted to the study of galectins, a family of evolutionarily conserved glycan-binding proteins with multifunctional properties. Galectins function, either intracellularly or extracellularly, as key biological mediators capable of monitoring changes occurring on the cell surface during fundamental biological processes such as cellular communication, inflammation, development, and differentiation. Their highly conserved structures, exquisite carbohydrate specificity, and ability to modulate a broad spectrum of biological processes have captivated a wide range of scientists from a wide spectrum of disciplines, including biochemistry, biophysics, cell biology, and physiology. However, in spite of enormous efforts to dissect the functions and properties of these glycan-binding proteins, limited information about how structural and biochemical aspects of these proteins can influence biological functions is available. In this review, we aim to integrate structural, biochemical, and functional aspects of this bewildering and ancient family of glycan-binding proteins and discuss their implications in physiologic and pathologic settings. © 2011 American Chemical Society

Hippocampal mechanisms for the context-dependent retrieval of episodes

PubMed Central

Hasselmo, Michael E.; Eichenbaum, Howard B.

2008-01-01

Behaviors ranging from delivering newspapers to waiting tables depend on remembering previous episodes to avoid incorrect repetition. Physiologically, this requires mechanisms for long-term storage and selective retrieval of episodes based on time of occurrence, despite variable intervals and similarity of events in a familiar environment. Here, this process has been modeled based on physiological properties of the hippocampal formation, including mechanisms for sustained activity in entorhinal cortex and theta rhythm oscillations in hippocampal subregions. The model simulates the context-sensitive firing properties of hippocampal neurons including trial specific firing during spatial alternation and trial by trial changes in theta phase precession on a linear track. This activity is used to guide behavior, and lesions of the hippocampal network impair memory-guided behavior. The model links data at the cellular level to behavior at the systems level, describing a physiologically plausible mechanism for the brain to recall a given episode which occurred at a specific place and time. PMID:16263240

The Use of Cognitive Strategies To Enhance Motor Skill Acquisition and Retention in the Elderly.

ERIC Educational Resources Information Center

Anshel, Mark H.

It has been hypothesized that the use of techniques to enhance motor skill acquisition and retention in the elderly may retard the onset of retirement, result in the continuation of a productive professional career, allow continued participation in recreational activities, and possibly slow the decline in physiological functions that normally…

Self-Testing Promotes Superior Retention of Anatomy and Physiology Information

ERIC Educational Resources Information Center

Dobson, John L.; Linderholm, Tracy

2015-01-01

The testing effect shows that learning is enhanced by the act of recalling information after exposure. Although the testing effect is among the most robust findings in cognitive science, much of its empirical support is from laboratory studies and it has been applied as a strategy for enhancing learning in the classroom in a limited fashion. The…

Corrosion behaviour of electropolished AISI 316L austenitic biomaterial in physiological solution

NASA Astrophysics Data System (ADS)

Zatkalíková, V.; Markovičová, L.; Škorvanová, M.

2017-11-01

Due to suitable mechanical properties, satisfactory corrosion resistance and relatively low cost, austenitic stainless steels are important biomaterials for manufacture of implants and various medical instruments and devices. Their corrosion properties and biocompatibility are significantly affected by protective passive surface film quality, which depends on used mechanical and chemical surface treatment. This article deals with corrosion resistance of AISI 316L stainless steel, which is the most widely used Cr-Ni-Mo austenitic biomaterial. Corrosion behaviour of five various surfaces (original, electropolished, three surfaces with combined treatment finished by electropolishing) is evaluated on the bases of cyclic potentiodynamic polarization tests performed in physiological solution at the temperature of 37± 0.5 °C.

Correlating yeast cell stress physiology to changes in the cell surface morphology: atomic force microscopic studies.

PubMed

Canetta, Elisabetta; Walker, Graeme M; Adya, Ashok K

2006-07-06

Atomic Force Microscopy (AFM) has emerged as a powerful biophysical tool in biotechnology and medicine to investigate the morphological, physical, and mechanical properties of yeasts and other biological systems. However, properties such as, yeasts' response to environmental stresses, metabolic activities of pathogenic yeasts, cell-cell/cell-substrate adhesion, and cell-flocculation have rarely been investigated so far by using biophysical tools. Our recent results obtained by AFM on one strain each of Saccharomyces cerevisiae and Schizosaccharomyces pombe show a clear correlation between the physiology of environmentally stressed yeasts and the changes in their surface morphology. The future directions of the AFM related techniques in relation to yeasts are also discussed.

SH2 Domains Recognize Contextual Peptide Sequence Information to Determine Selectivity*

PubMed Central

Liu, Bernard A.; Jablonowski, Karl; Shah, Eshana E.; Engelmann, Brett W.; Jones, Richard B.; Nash, Piers D.

2010-01-01

Selective ligand recognition by modular protein interaction domains is a primary determinant of specificity in signaling pathways. Src homology 2 (SH2) domains fulfill this capacity immediately downstream of tyrosine kinases, acting to recruit their host polypeptides to ligand proteins harboring phosphorylated tyrosine residues. The degree to which SH2 domains are selective and the mechanisms underlying selectivity are fundamental to understanding phosphotyrosine signaling networks. An examination of interactions between 50 SH2 domains and a set of 192 phosphotyrosine peptides corresponding to physiological motifs within FGF, insulin, and IGF-1 receptor pathways indicates that individual SH2 domains have distinct recognition properties and exhibit a remarkable degree of selectivity beyond that predicted by previously described binding motifs. The underlying basis for such selectivity is the ability of SH2 domains to recognize both permissive amino acid residues that enhance binding and non-permissive amino acid residues that oppose binding in the vicinity of the essential phosphotyrosine. Neighboring positions affect one another so local sequence context matters to SH2 domains. This complex linguistics allows SH2 domains to distinguish subtle differences in peptide ligands. This newly appreciated contextual dependence substantially increases the accessible information content embedded in the peptide ligands that can be effectively integrated to determine binding. This concept may serve more broadly as a paradigm for subtle recognition of physiological ligands by protein interaction domains. PMID:20627867

A six-membered-ring incorporated Si-rhodamine for imaging of copper(ii) in lysosomes.

PubMed

Wang, Baogang; Cui, Xiaoyan; Zhang, Zhiqiang; Chai, Xiaoyun; Ding, Hao; Wu, Qiuye; Guo, Zhongwu; Wang, Ting

2016-07-12

The regulation of copper homeostasis in lysosomes of living cells is closely related to various physiological and pathological processes. Thus, it is of urgent need to develop a fluorescent probe for selectively and sensitively monitoring the location and concentration of lysosomal Cu(2+). Herein, a six-membered ring, thiosemicarbazide, was incorporated into a Si-rhodamine (SiR) scaffold for the first time, affording a SiR-based fluorescent probe SiRB-Cu. Through the effective Cu(2+)-triggered ring-opening process, the probe exhibits fast NIR chromogenic and fluorogenic responses to Cu(2+) within 2 min as the result of formation of a highly fluorescent product SiR-NCS. Compared with a five-membered ring, the expanded ring retains great tolerance to H(+), ensuring the superior sensitivity with a detection limit as low as 7.7 nM and 200-fold enhancement of relative fluorescence in the presence of 1.0 equiv. of Cu(2+) in pH = 5.0 solution, the physiological pH of lysosome. Moreover, the thiosemicarbazide moiety acts not only as the chelating and reactive site, but also as an efficient lysosome-targeting group, leading to the proactive accumulation of the probe into lysosomes. Taking advantage of these distinct properties, SiRB-Cu provides a functional probe suitable for imaging exogenous and endogenous lysosomal Cu(2+) with high imaging contrast and fidelity.

An Expanding Range of Functions for the Copper Chaperone/Antioxidant Protein Atox1

PubMed Central

Hatori, Yuta

2013-01-01

Abstract Significance: Antioxidant protein 1 (Atox1 in human cells) is a copper chaperone for the copper export pathway with an essential role in cellular copper distribution. In vitro, Atox1 binds and transfers copper to the copper-transporting ATPases, stimulating their catalytic activity. Inactivation of Atox1 in cells inhibits maturation of secreted cuproenzymes as well as copper export from cells. Recent Advances: Accumulating data suggest that cellular functions of Atox1 are not limited to its copper-trafficking role and may include storage of labile copper, modulation of transcription, and antioxidant defense. The conserved metal binding site of Atox1, CxGC, differs from the metal-binding sites of copper-transporting ATPases and has a physiologically relevant redox potential that equilibrates with the GSH:GSSG pair. Critical Issues: Tight relationship appears to exist between intracellular copper levels and glutathione (GSH) homeostasis. The biochemical properties of Atox1 place it at the intersection of cellular networks that regulate copper distribution and cellular redox balance. Mechanisms through which Atox1 facilitates copper export and contributes to oxidative defense are not fully understood. Future Directions: The current picture of cellular redox homeostasis and copper physiology will be enhanced by further mechanistic studies of functional interactions between the GSH:GSSG pair and copper-trafficking machinery. Antioxid. Redox Signal. 19, 945–957. PMID:23249252

Hyaluronan supplementation as a mechanical regulator of cartilage tissue development under joint-kinematic-mimicking loading.

PubMed

Wu, Yabin; Stoddart, Martin J; Wuertz-Kozak, Karin; Grad, Sibylle; Alini, Mauro; Ferguson, Stephen J

2017-08-01

Articular cartilage plays an essential role in joint lubrication and impact absorption. Through this, the mechanical signals are coupled to the tissue's physiological response. Healthy synovial fluid has been shown to reduce and homogenize the shear stress acting on the cartilage surfaces due to its unique shear-thinning viscosity. As cartilage tissues are sensitive to mechanical changes in articulation, it was hypothesized that replacing the traditional culture medium with a healthy non-Newtonian lubricant could enhance tissue development in a cartilage engineering model, where joint-kinematic-mimicking mechanical loading is applied. Different amounts of hyaluronic acid were added to the culture medium to replicate the viscosities of synovial fluid at different health states. Hyaluronic acid supplementation, especially at a physiologically healthy concentration (2.0 mg ml -1 ), promoted a better preservation of chondrocyte phenotype. The ratio of collagen II to collagen I mRNA was 4.5 times that of the control group, implying better tissue development (however, with no significant difference of measured collagen II content), with a good retention of collagen II and proteoglycan in the mechanically active region. Simulating synovial fluid properties by hyaluronic acid supplementation created a favourable mechanical environment for mechanically loaded constructs. These findings may help in understanding the influence of joint articulation on tissue homeostasis, and moreover, improve methods for functional cartilage tissue engineering. © 2017 The Author(s).

Biomedical imaging and therapy with physically and physiologically tailored magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Khandhar, Amit Praful

Magnetic particle imaging (MPI) and magnetic fluid hyperthermia (MFH) are emerging imaging and therapy approaches that have the potential to improve diagnostic safety and disease management of heart disease and cancer - the number 1 and 2 leading causes of deaths in the United States. MPI promises real-time, tomographic and quantitative imaging of superparamagnetic iron oxide nanoparticle (SPION) tracers distributed in vivo, and is targeted to offer a safer angiography alternative for its first clinical application. MFH uses ac-fields to dissipate heat from SPIONs that can be delivered locally to promote hyperthermia therapy (~42°C) in cancer cells. Both technologies use safe radiofrequency magnetic fields to exploit the fundamental magnetic relaxation properties of superparamagnetic iron oxide nanoparticles (SPIONs), which must be tailored for optimal imaging in the case of MPI, and maximum hyperthermia potency in the case of MFH. Furthermore, the magnetic core and shell of SPIONs are both central to the optimization process; the shell, in particular, bridges the translational gap between the optimized core and its safe and effective use in the physiological environment. Unfortunately, existing SPIONs that were originally designed as MRI contrast agents lack the basic physical properties that enable the clinical translation of MPI and MFH. In this work, the core and shell of monodisperse SPIONs were optimized in concert to accomplish two equally important objectives: (1) biocompatibility, and (2) MPI and MFH efficacy of SPIONs in physiological environments. Critically, it was found that the physical and physiological responses of SPIONs are coupled, and impacting one can have consequences on the other. It was shown that the poly(ethylene glycol) (PEG)-based shell when properly optimized reduced protein adsorption to SPION surface and phagocytic uptake in macrophages - both prerequisites for designing long-circulating SPIONs. In MPI, tailoring the surface coating reduced protein adsorption and improved colloidal stability, which were critical in retaining the magnetization relaxation properties of the SPIONs. The improvements in surface coatings enabled the use of larger SPION cores (> 20 nm core diameter), which were used to demonstrate benchmark-imaging performance in some of the world's first MPI scanners at Philips Medical Imaging and University of California, Berkeley. In MFH, it was shown for the first time that optimization of heat loss from SPIONs (W/g) is possible by tailoring the core size and size distribution for the given ac-field conditions. Biodistribution and blood circulation studies in mice showed that SPIONs accumulated primarily in the liver and spleen with minimal renal involvement, and demonstrated gradual clearance. Circulation time was evaluated using the MPI signal detected over time in blood, which offered insight on the relevant circulation time for angiography applications. In comparison with carboxy-dextran coated ResovistRTM SPIONs, the PEG-coated SPIONs developed in this work circulated substantially longer; furthermore, reducing the hydrodynamic diameter showed a 4.5x improvement in blood half-life. The work presented in this thesis demonstrates that the combined effort in optimizing the core and shell properties of SPIONs enhances biocompatibility and efficacy, with the in vivo studies providing critical feedback on the success (or failure) of the optimization process. Future work will entail designing functionalized SPIONs for targeting specific disease sites, which will further enable the molecular level diagnosis and therapy of diseases.

Conservation physiology in practice: how physiological knowledge has improved our ability to sustainably manage Pacific salmon during up-river migration.

PubMed

Cooke, Steven J; Hinch, Scott G; Donaldson, Michael R; Clark, Timothy D; Eliason, Erika J; Crossin, Glenn T; Raby, Graham D; Jeffries, Ken M; Lapointe, Mike; Miller, Kristi; Patterson, David A; Farrell, Anthony P

2012-06-19

Despite growing interest in conservation physiology, practical examples of how physiology has helped to understand or to solve conservation problems remain scarce. Over the past decade, an interdisciplinary research team has used a conservation physiology approach to address topical conservation concerns for Pacific salmon. Here, we review how novel applications of tools such as physiological telemetry, functional genomics and laboratory experiments on cardiorespiratory physiology have shed light on the effect of fisheries capture and release, disease and individual condition, and stock-specific consequences of warming river temperatures, respectively, and discuss how these findings have or have not benefited Pacific salmon management. Overall, physiological tools have provided remarkable insights into the effects of fisheries capture and have helped to enhance techniques for facilitating recovery from fisheries capture. Stock-specific cardiorespiratory thresholds for thermal tolerances have been identified for sockeye salmon and can be used by managers to better predict migration success, representing a rare example that links a physiological scope to fitness in the wild population. Functional genomics approaches have identified physiological signatures predictive of individual migration mortality. Although fisheries managers are primarily concerned with population-level processes, understanding the causes of en route mortality provides a mechanistic explanation and can be used to refine management models. We discuss the challenges that we have overcome, as well as those that we continue to face, in making conservation physiology relevant to managers of Pacific salmon.

Conservation physiology in practice: how physiological knowledge has improved our ability to sustainably manage Pacific salmon during up-river migration

PubMed Central

Cooke, Steven J.; Hinch, Scott G.; Donaldson, Michael R.; Clark, Timothy D.; Eliason, Erika J.; Crossin, Glenn T.; Raby, Graham D.; Jeffries, Ken M.; Lapointe, Mike; Miller, Kristi; Patterson, David A.; Farrell, Anthony P.

2012-01-01

Despite growing interest in conservation physiology, practical examples of how physiology has helped to understand or to solve conservation problems remain scarce. Over the past decade, an interdisciplinary research team has used a conservation physiology approach to address topical conservation concerns for Pacific salmon. Here, we review how novel applications of tools such as physiological telemetry, functional genomics and laboratory experiments on cardiorespiratory physiology have shed light on the effect of fisheries capture and release, disease and individual condition, and stock-specific consequences of warming river temperatures, respectively, and discuss how these findings have or have not benefited Pacific salmon management. Overall, physiological tools have provided remarkable insights into the effects of fisheries capture and have helped to enhance techniques for facilitating recovery from fisheries capture. Stock-specific cardiorespiratory thresholds for thermal tolerances have been identified for sockeye salmon and can be used by managers to better predict migration success, representing a rare example that links a physiological scope to fitness in the wild population. Functional genomics approaches have identified physiological signatures predictive of individual migration mortality. Although fisheries managers are primarily concerned with population-level processes, understanding the causes of en route mortality provides a mechanistic explanation and can be used to refine management models. We discuss the challenges that we have overcome, as well as those that we continue to face, in making conservation physiology relevant to managers of Pacific salmon. PMID:22566681

Effect of spatial coherence of light on the photoregulation processes in cells

NASA Astrophysics Data System (ADS)

Budagovsky, A. V.; Solovykh, N. V.; Yankovskaya, M. B.; Maslova, M. V.; Budagovskaya, O. N.; Budagovsky, I. A.

2016-07-01

The effect of the statistical properties of light on the value of the photoinduced reaction of the biological objects, which differ in the morphological and physiological characteristics, the optical properties, and the size of cells, was studied. The fruit of apple trees, the pollen of cherries, the microcuttings of blackberries in vitro, and the spores and the mycelium of fungi were irradiated by quasimonochromatic light fluxes with identical energy parameters but different values of coherence length and radius of correlation. In all cases, the greatest stimulation effect occurred when the cells completely fit in the volume of the coherence of the field, while both temporal and spatial coherence have a significant and mathematically certain impact on the physiological activity of cells. It was concluded that not only the spectral, but also the statistical (coherent) properties of the acting light play an important role in the photoregulation process.

The Up- and Down-Regulation of Amusement:Experiential, Behavioral, and Autonomic Consequences

PubMed Central

Giuliani, Nicole R.; McRae, Kateri; Gross, James J.

2014-01-01

A growing body of research has examined the regulation of negative emotions. However, little is known about the physiological processes underlying the regulation of positive emotions, such as when amusement is enhanced during periods of stress, or attenuated in the pursuit of social goals. The aim of this study was to examine the psychophysiological consequences of the cognitive up- and down-regulation of amusement. To address this goal, participants viewed brief, amusing film clips while measurements of experience, behavior, and peripheral physiology were collected. Using an event-related design, participants viewed each film under the instructions either to a) watch, b) use cognitive reappraisal to increase amusement, or c) use cognitive reappraisal to decrease amusement. Findings indicated that emotion experience, emotion-expressive behavior, and autonomic physiology (including heart rate, respiration, and sympathetic nervous system activation) were enhanced and diminished in accordance with regulation instructions. This finding is a critical extension of the growing literature on the voluntary regulation of emotion, and has the potential to help us better understand how people use humor in the service of coping and social goals. PMID:18837622

Functional poly(ε-caprolactone)/chitosan dressings with nitric oxide-releasing property improve wound healing.

PubMed

Zhou, Xin; Wang, He; Zhang, Jimin; Li, Xuemei; Wu, Yifan; Wei, Yongzhen; Ji, Shenglu; Kong, Deling; Zhao, Qiang

2017-05-01

Wound healing dressings are increasingly needed clinically due to the large number of skin damage annually. Nitric oxide (NO) plays a key role in promoting wound healing, thus biomaterials with NO-releasing property receive increasing attention as ideal wound dressing. In present study, we prepared a novel functional wound dressing by combining electrospun poly(ε-caprolactone) (PCL) nonwoven mat with chitosan-based NO-releasing biomaterials (CS-NO). As-prepared PCL/CS-NO dressing released NO sustainably under the physiological conditions, which was controlled by the catalysis of β-galactosidase. In vivo wound healing characteristics were further evaluated on full-thickness cutaneous wounds in mice. Results showed that PCL/CS-NO wound dressings remarkably accelerated wound healing process through enhancing re-epithelialization and granulation formation and effectively improved the organization of regenerated tissues including epidermal-dermal junction, which could be ascribed to the pro-angiogenesis, immunomodulation, and enhanced collagen synthesis provided by the sustained release of NO. Therefore, PCL/CS-NO may be a promising candidate for wound dressings, especially for the chronic wound caused by the ischemia. Serious skin damage caused by trauma, surgery, burn or chronic disease has become one of the most serious clinical problems. Therefore, there is an increasing demand for ideal wound dressing that can improve wound healing. Due to the vital role of nitric oxide (NO), we developed a novel functional wound dressing by combining electrospun polycaprolactone (PCL) mat with NO-releasing biomaterial (CS-NO). The sustained release of NO from PCL/CS-NO demonstrated positive effects on wound healing, including pro-angiogenesis, immunomodulation, and enhanced collagen synthesis. Hence, wound healing process was remarkably accelerated and the organization of regenerated tissues was effectively improved as well. Taken together, PCL/CS-NO dressing may be a promising candidate for wound treatment, especially for the chronic wound caused by the ischemia. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Acclimatization to high-variance habitats does not enhance physiological tolerance of two key Caribbean corals to future temperature and pH.

PubMed

Camp, Emma F; Smith, David J; Evenhuis, Chris; Enochs, Ian; Manzello, Derek; Woodcock, Stephen; Suggett, David J

2016-05-25

Corals are acclimatized to populate dynamic habitats that neighbour coral reefs. Habitats such as seagrass beds exhibit broad diel changes in temperature and pH that routinely expose corals to conditions predicted for reefs over the next 50-100 years. However, whether such acclimatization effectively enhances physiological tolerance to, and hence provides refuge against, future climate scenarios remains unknown. Also, whether corals living in low-variance habitats can tolerate present-day high-variance conditions remains untested. We experimentally examined how pH and temperature predicted for the year 2100 affects the growth and physiology of two dominant Caribbean corals (Acropora palmata and Porites astreoides) native to habitats with intrinsically low (outer-reef terrace, LV) and/or high (neighbouring seagrass, HV) environmental variance. Under present-day temperature and pH, growth and metabolic rates (calcification, respiration and photosynthesis) were unchanged for HV versus LV populations. Superimposing future climate scenarios onto the HV and LV conditions did not result in any enhanced tolerance to colonies native to HV. Calcification rates were always lower for elevated temperature and/or reduced pH. Together, these results suggest that seagrass habitats may not serve as refugia against climate change if the magnitude of future temperature and pH changes is equivalent to neighbouring reef habitats. © 2016 The Author(s).

Synergistic interactions between temporal coupling of complex light and magnetic pulses upon melanoma cell proliferation and planarian regeneration.

PubMed

Murugan, Nirosha J; Karbowski, Lukasz M; Persinger, Michael A

2017-01-01

Synergisms between a physiologically patterned magnetic field that is known to enhance planarian growth and suppress proliferation of malignant cells in culture and three light emitting diode (LED) generated visible wavelengths (blue, green, red) upon planarian regeneration and melanoma cell numbers were discerned. Five days of hourly exposures to either a physiologically patterned (2.5-5.0 μT) magnetic field, one of three wavelengths (3 kLux) or both treatments simultaneously indicated that red light (680 nm), blue light (470 nm) or the magnetic field significantly facilitated regeneration of planarian compared to sham field exposed planarian. Presentation of both light and magnetic field conditions enhanced the effect. Whereas the blue and red light diminished the growth of malignant (melanoma) cells, the effect was not as large as that produced by the magnetic field. Only the paired presentation of the blue light and magnetic field enhanced the suppression. On the other hand, the changes following green light (540 nm) exposure did not differ from the control condition and green light presented with the magnetic field eliminated its effects for both the planarian and melanoma cells. These results indicate specific colors affect positive adaptation that is similar to weak, physiologically patterned frequency modulated (8-24 Hz) magnetic fields and that the two forms of energy can synergistically summate or cancel.

Acclimatization to high-variance habitats does not enhance physiological tolerance of two key Caribbean corals to future temperature and pH

PubMed Central

Smith, David J.; Evenhuis, Chris; Enochs, Ian; Manzello, Derek; Woodcock, Stephen; Suggett, David J.

2016-01-01

Corals are acclimatized to populate dynamic habitats that neighbour coral reefs. Habitats such as seagrass beds exhibit broad diel changes in temperature and pH that routinely expose corals to conditions predicted for reefs over the next 50–100 years. However, whether such acclimatization effectively enhances physiological tolerance to, and hence provides refuge against, future climate scenarios remains unknown. Also, whether corals living in low-variance habitats can tolerate present-day high-variance conditions remains untested. We experimentally examined how pH and temperature predicted for the year 2100 affects the growth and physiology of two dominant Caribbean corals (Acropora palmata and Porites astreoides) native to habitats with intrinsically low (outer-reef terrace, LV) and/or high (neighbouring seagrass, HV) environmental variance. Under present-day temperature and pH, growth and metabolic rates (calcification, respiration and photosynthesis) were unchanged for HV versus LV populations. Superimposing future climate scenarios onto the HV and LV conditions did not result in any enhanced tolerance to colonies native to HV. Calcification rates were always lower for elevated temperature and/or reduced pH. Together, these results suggest that seagrass habitats may not serve as refugia against climate change if the magnitude of future temperature and pH changes is equivalent to neighbouring reef habitats. PMID:27194698

Intracellular Physiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators.

DTIC Science & Technology

1992-08-24

Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators 12. PERSONAL AUTHOR(S) F. Edward Dudek 13a...intrinsic electrical properties, synaptic and non-synaptic transmission, and neuromodulation . We have studied the role of excitatory and inhibitory amino... Neuromodulation : Smithson. K.G.. MacVicar. B.A. and Hatton. G.I. (1983) The Biochemical Control of Neuronal Excitability. Oxford Polyethylene glycol

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy.

PubMed

Zhu, Hai; Zhou, Binwei; Chan, Leung; Du, Yanxin; Chen, Tianfeng

2017-01-01

Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

In silico evaluation of gadofosveset pharmacokinetics in different population groups using the Simcyp® simulator platform.

PubMed

Spanakis, Marios; Marias, Kostas

2014-12-01

Gadofosveset is a Gd-based contrast agent used for magnetic resonance imaging (MRI). Gadolinium kinetic distribution models are implemented in T1-weighted dynamic contrast-enhanced perfusion MRI for characterization of lesion sites in the body. Physiology changes in a disease state potentially can influence the pharmacokinetics of drugs and to this respect modify the distribution properties of contrast agents. This work focuses on the in silico modelling of pharmacokinetic properties of gadofosveset in different population groups through the application of physiologically-based pharmacokinetic models (PBPK) embedded in Simcyp® population pharmacokinetics platform. Physicochemical and pharmacokinetic properties of gadofosveset were introduced into Simcyp® simulator platform and a min-PBPK model was applied. In silico clinical trials were generated simulating the administration of the recommended dose for the contrast agent (i.v., 30 mg/kg) in population cohorts of healthy volunteers, obese, renal and liver impairment, and in a generated virtual oncology population. Results were evaluated regarding basic pharmacokinetic parameters of Cmax, AUC and systemic CL and differences were assessed through ANOVA and estimation of ratio of geometric mean between healthy volunteers and the other population groups. Simcyp® predicted a mean Cmax = 551.60 mg/l, a mean AUC = 4079.12 mg/L*h and a mean systemic CL = 0.56 L/h for the virtual population of healthy volunteers. Obese population showed a modulation in Cmax and CL, attributed to increased administered dose. In renal and liver impairment cohorts a significant modulation in Cmax, AUC and CL of gadofosveset is predicted. Oncology population exhibited statistical significant differences regarding AUC when compared with healthy volunteers. This work employed Simcyp® population pharmacokinetics platform in order to compute gadofosveset's pharmacokinetic profiles through PBPK models and in silico clinical trials and evaluate possible differences between population groups. The approach showed promising results that could provide new insights regarding administration of contrast agents in special population cohorts. In silico pharmacokinetics could further be used for evaluating of possible toxicity, interpretation of MRI PK image maps and development of novel contrast agents.

Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis?

PubMed

Kolios, Leila; Hoerster, Ann Kristin; Sehmisch, Stephan; Malcherek, Marie Christin; Rack, Thomas; Tezval, Mohammed; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Stuermer, Klaus Michael; Stuermer, Ewa Klara

2010-01-01

Osteoporosis is accompanied by predominantly metaphyseal fractures with a delayed and qualitatively reduced healing process. This study addressed the question of whether fracture healing in the context of osteoporosis prophylaxis is improved with estrogen (E) or alendronate (ALN). Thirty-six ovariectomized and 12 sham-operated 12-week-old rats received soy-free (osteoporotic C, sham), E-, or ALN- supplemented diets. After 10 weeks, a metaphyseal tibia osteotomy and standardized T-plate fixation were performed. After a 5-week healing process, the fracture callus was evaluated qualitatively by biomechanical bending test and quantitatively in microradiographic sections. The time course of callus formation was examined using fluorochrome-labeled histological sections. Administration of E improved the biomechanical properties of callus (stiffness [N/mm]: sham: 110.2 + or - 76.07, C: 41.28 + or - 33.70, E: 85.72 + or - 47.24, ALN: 72.07 + or - 34.68). The resistance to microfracturing seen in E-treated animals was significantly enhanced and even superior to sham (yield load [N] sham: 27.44 + or - 9.72, C: 21.04 + or - 12.47, E: 42.85 + or - 13.74(Delta), ALN: 25.28 + or - 6.4(.)) (* P < 0.05 vs. sham group, (Delta) P < 0.05 vs. C group, (*) P < 0.05 vs. E group). Trabecular bone in particular was improved, indicating the presence of physiological endosteal bridging (Tr.Dn [%] sham: 10.53 + or - 18.9, C: 1.01 + or - 0.14, E: 24.13 + or - 34.09(Delta), ALN: 3.99 + or - 8.3(.)). ALN did not help bone healing, as shown by mechanical tests. Compared to the C group, statistically, ALN did not show worse properties. The induction of callus formation under ALN treatment was slightly delayed (Tt.Cl [mm(2)] sham: 3.68 + or - 0.66, C: 3.44 + or - 0.42, E: 3.69 + or - 0.58, ALN: 3.06 + or - 0.56). Osteoporotic metaphyseal fracture healing was qualitatively and quantitatively improved by E prophylaxis. The process of fracture healing occurred nearly physiologically (shamlike). Notably, ALN hardly improved metaphyseal callus properties when assessed as osteoporosis prophylaxis, but to a lesser extent than E.

The Meaning-Enhancing Properties of Psychedelics and Their Mediator Role in Psychedelic Therapy, Spirituality, and Creativity.

PubMed

Hartogsohn, Ido

2018-01-01

Past research has demonstrated to the ability of psychedelics to enhance suggestibility, and pointed to their ability to amplify perception of meaning. This paper examines the existing evidence for the meaning-enhancing properties of psychedelics, and argues that the tendency of these agents to enhance the perception of significance offers valuable clues to explaining their reported ability to stimulate a variety of therapeutic processes, enhance creativity, and instigate mystical-type experiences. Building upon previous research, which suggested the potential role of psychedelic meaning-enhancement in enhancing placebo response, the paper explores the mechanisms by which the meaning-amplifying properties of psychedelics might also play a role in enhancing creativity, as well as in effecting mystical-type experiences. The wider social and public-health implications of this hypothesis are discussed, and suggestions are made as to the various ways in which scientific understanding of the meaning-enhancing properties of psychedelics might be advanced and utilized.

Engineering Lubrication in Articular Cartilage

PubMed Central

McNary, Sean M.; Athanasiou, Kyriacos A.

2012-01-01

Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional tissue engineering of articular cartilage that begins to explore and incorporate methods of lubrication. PMID:21955119

Nanostructured PEG-based hydrogels with tunable physical properties for gene delivery to human mesenchymal stem cells.

PubMed

Li, Yan; Yang, Chuan; Khan, Majad; Liu, Shaoqiong; Hedrick, James L; Yang, Yi-Yan; Ee, Pui-Lai R

2012-09-01

Effective delivery of DNA to direct cell behavior in a well defined three dimensional scaffold offers a superior approach in tissue engineering. In this study, we synthesized biodegradable nanostructured hydrogels with tunable physical properties for cell and gene delivery. The hydrogels were formed via Michael addition chemistry by reacting a four-arm acrylate-terminated PEG with a four-arm thiol-functionalized PEG. Nanosized micelles self-assembled from the amphiphilic PEG-b-polycarbonate diblock copolymer, having reactive end-groups, were chemically incorporated into the hydrogel networks at various contents. The use of Michael addition chemistry allows for in situ hydrogel formation under the physiological conditions. Mechanical property analysis of the hydrogels revealed a correlation between the content of micelles and the storage modulus of the hydrogels. Internal morphology of hydrogels was observed using a field emission scanning electron microscope, which showed that the number and/or size of the pores in the hydrogel increased with increasing micelle content due to reduced crosslinking degree. There exists an optimal micelle content for cell proliferation and gene transfection. MTT assays demonstrated the highest cell viability in the hydrogel with 20% micelles. The gene expression level in hMSCs in the hydrogel with 20% micelles was also significantly higher than that in the hydrogel without micelles. The enhanced cell viability and gene expression in the hydrogel with the optimized micelle content are likely attributed to the physical properties that provide a better environment for cell-matrix interactions. Therefore, incorporating micelles into the hydrogel is a good strategy to control cellular behavior in 3-D through changes in physical properties of the microenvironment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

PubMed

Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

2015-01-01

The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

The Impact of Collective Molecular Dynamics on Physiological and Biological Functionalities of Artificial and Biological Membranes

NASA Astrophysics Data System (ADS)

Rheinstadter, Maikel

2008-03-01

We use neutron, X-ray and light scattering techniques to determine dynamical and structural properties of artificial and biological membranes. The combination of various techniques enlarges the window to length scales from the nearest-neighbor distances of lipid molecules to more than 10-6m, covering time scales from about 0.1 ps to 1 s. The main research objective is to quantify collective molecular fluctuations in these systems and to establish relationships to physiological and biological functions of the bilayers, such as transmembrane transport. The motivation for this project is twofold: 1) By understanding fundamental properties of bilayers at the microscopic and mesoscopic level, we aim to tailor membranes with specific properties such as permeability and elasticity. 2) By relating dynamical fluctuations to physiological and biological functions, we can gain a deeper understanding of the bilayers on a molecular scale that may help optimizing the transmembrane transport of certain drugs. We show how bilayer permeability, elasticity and inter protein excitations can be determined from the experiments. M.C. Rheinstädter et al., Phys. Rev. Lett. 93, 108107 (2004); Phys. Rev. Lett. 97, 048103 (2006); Phys. Rev. E 75, 011907 (2007);J. Vac. Soc. Technol. A 24, 1191 (2006).

An analysis of the relationships between subthreshold electrical properties and excitability in skeletal muscle

PubMed Central

L.-H. Huang, Christopher; Fraser, James A.

2011-01-01

Skeletal muscle activation requires action potential (AP) initiation followed by its sarcolemmal propagation and tubular excitation to trigger Ca2+ release and contraction. Recent studies demonstrate that ion channels underlying the resting membrane conductance (GM) of fast-twitch mammalian muscle fibers are highly regulated during muscle activity. Thus, onset of activity reduces GM, whereas prolonged activity can markedly elevate GM. Although these observations implicate GM regulation in control of muscle excitability, classical theoretical studies in un-myelinated axons predict little influence of GM on membrane excitability. However, surface membrane morphologies differ markedly between un-myelinated axons and muscle fibers, predominantly because of the tubular (t)-system of muscle fibers. This study develops a linear circuit model of mammalian muscle fiber and uses this to assess the role of subthreshold electrical properties, including GM changes during muscle activity, for AP initiation, AP propagation, and t-system excitation. Experimental observations of frequency-dependent length constant and membrane-phase properties in fast-twitch rat fibers could only be replicated by models that included t-system luminal resistances. Having quantified these resistances, the resulting models showed enhanced conduction velocity of passive current flow also implicating elevated AP propagation velocity. Furthermore, the resistances filter passive currents such that higher frequency current components would determine sarcolemma AP conduction velocity, whereas lower frequency components excite t-system APs. Because GM modulation affects only the low-frequency membrane impedance, the GM changes in active muscle would predominantly affect neuromuscular transmission and low-frequency t-system excitation while exerting little influence on the high-frequency process of sarcolemmal AP propagation. This physiological role of GM regulation was increased by high Cl− permeability, as in muscle endplate regions, and by increased extracellular [K+], as observed in working muscle. Thus, reduced GM at the onset of exercise would enhance t-system excitation and neuromuscular transmission, whereas elevated GM after sustained activity would inhibit these processes and thereby accentuate muscle fatigue. PMID:21670208

Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy.

PubMed

Moc, Courtney; Taylor, Amy E; Chesini, Gino P; Zambrano, Cristina M; Barlow, Melissa S; Zhang, Xiaoxue; Gustafsson, Åsa B; Purcell, Nicole H

2015-02-01

To examine the role of physiological Akt signalling in pathological hypertrophy through analysis of PHLPP1 (PH domain leucine-rich repeat protein phosphatase) knock-out (KO) mice. To investigate the in vivo requirement for 'physiological' control of Akt activation in cardiac growth, we examined the effect of deleting the Akt phosphatase, PHLPP, on the induction of cardiac hypertrophy. Basal Akt phosphorylation increased nearly two-fold in the cardiomyocytes from PHLPP1 KO mice and physiological hypertrophy induced by swimming exercise was accentuated as assessed by increased heart size and myocyte cell area. In contrast, the development of pathophysiological hypertrophy induced by pressure overload and assessed by increases in heart size, myocyte cell area, and hypertrophic gene expression was attenuated. This attenuation coincided with decreased fibrosis and cell death in the KO mice. Cast moulding revealed increased capillary density basally in the KO hearts, which was further elevated relative to wild-type mouse hearts in response to pressure overload. In vitro studies with isolated myocytes in co-culture also demonstrated that PHLPP1 deletion in cardiomyocytes can enhance endothelial tube formation. Expression of the pro-angiogenic factor VEGF was also elevated basally and accentuated in response to transverse aortic constriction in hearts from KO mice. Our data suggest that enhancing Akt activity by inhibiting its PHLPP1-mediated dephosphorylation promotes processes associated with physiological hypertrophy that may be beneficial in attenuating the development of pathological hypertrophy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Physiological relaxation induced by horticultural activity: transplanting work using flowering plants.

PubMed

Lee, Min-sun; Park, Bum-jin; Lee, Juyoung; Park, Kun-tae; Ku, Ja-hyeong; Lee, Jun-woo; Oh, Kyung-ok; Miyazaki, Yoshifumi

2013-10-10

Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects. The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants' physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group. This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities.

Physiological relaxation induced by horticultural activity: transplanting work using flowering plants

PubMed Central

2013-01-01

Background Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects. Results The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants’ physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group. Conclusions This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities. PMID:24112302

Physiological integration enhanced the tolerance of Cynodon dactylon to flooding.

PubMed

Li, Z J; Fan, D Y; Chen, F Q; Yuan, Q Y; Chow, W S; Xie, Z Q

2015-03-01

Many flooding-tolerant species are clonal plants; however, the effects of physiological integration on plant responses to flooding have received limited attention. We hypothesise that flooding can trigger changes in metabolism of carbohydrates and ROS (reactive oxygen species) in clonal plants, and that physiological integration can ameliorate the adverse effects of stress, subsequently restoring the growth of flooded ramets. In the present study, we conducted a factorial experiment combining flooding to apical ramets and stolon severing (preventing physiological integration) between apical and basal ramets of Cynodon dactylon, which is a stoloniferous perennial grass with considerable flooding tolerance. Flooding-induced responses including decreased root biomass, accumulation of soluble sugar and starch, as well as increased activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in apical ramets. Physiological integration relieved growth inhibition, carbohydrate accumulation and induction of antioxidant enzyme activity in stressed ramets, as expected, without any observable cost in unstressed ramets. We speculate that relief of flooding stress in clonal plants may rely on oxidising power and electron acceptors transferred between ramets through physiological integration. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase

PubMed Central

Bang, Sookhee; Kim, Seyun; Dailey, Megan J.; Chen, Yong; Moran, Timothy H.; Snyder, Solomon H.; Kim, Sangwon F.

2012-01-01

The AMP-activated kinase (AMPK) senses the energy status of cells and regulates fuel availability, whereas hypothalamic AMPK regulates food intake. We report that inositol polyphosphate multikinase (IPMK) regulates glucose signaling to AMPK in a pathway whereby glucose activates phosphorylation of IPMK at tyrosine 174 enabling the enzyme to bind to AMPK and regulate its activation. Thus, refeeding fasted mice rapidly and markedly stimulates transcriptional enhancement of IPMK expression while down-regulating AMPK. Also, AMPK is up-regulated in mice with genetic depletion of hypothalamic IPMK. IPMK physiologically binds AMPK, with binding enhanced by glucose treatment. Regulation by glucose of phospho-AMPK in hypothalamic cell lines is prevented by blocking AMPK-IPMK binding. These findings imply that IPMK inhibitors will be beneficial in treating obesity and diabetes. PMID:22203993

Physiological and morphological characterization of local interneurons in the Drosophila antennal lobe.

PubMed

Seki, Yoichi; Rybak, Jürgen; Wicher, Dieter; Sachse, Silke; Hansson, Bill S

2010-08-01

The Drosophila antennal lobe (AL) has become an excellent model for studying early olfactory processing mechanisms. Local interneurons (LNs) connect a large number of glomeruli and are ideally positioned to increase computational capabilities of odor information processing in the AL. Although the neural circuit of the Drosophila AL has been intensively studied at both the input and the output level, the internal circuit is not yet well understood. An unambiguous characterization of LNs is essential to remedy this lack of knowledge. We used whole cell patch-clamp recordings and characterized four classes of LNs in detail using electrophysiological and morphological properties at the single neuron level. Each class of LN displayed unique characteristics in intrinsic electrophysiological properties, showing differences in firing patterns, degree of spike adaptation, and amplitude of spike afterhyperpolarization. Notably, one class of LNs had characteristic burst firing properties, whereas the others were tonically active. Morphologically, neurons from three classes innervated almost all glomeruli, while LNs from one class innervated a specific subpopulation of glomeruli. Three-dimensional reconstruction analyses revealed general characteristics of LN morphology and further differences in dendritic density and distribution within specific glomeruli between the different classes of LNs. Additionally, we found that LNs labeled by a specific enhancer trap line (GAL4-Krasavietz), which had previously been reported as cholinergic LNs, were mostly GABAergic. The current study provides a systematic characterization of olfactory LNs in Drosophila and demonstrates that a variety of inhibitory LNs, characterized by class-specific electrophysiological and morphological properties, construct the neural circuit of the AL.

Electrical Advantages of Dendritic Spines

PubMed Central

Gulledge, Allan T.; Carnevale, Nicholas T.; Stuart, Greg J.

2012-01-01

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations. PMID:22532875

Comparison of in vivo vs. ex situ obtained material properties of sheep common carotid artery.

PubMed

Smoljkić, Marija; Verbrugghe, Peter; Larsson, Matilda; Widman, Erik; Fehervary, Heleen; D'hooge, Jan; Vander Sloten, Jos; Famaey, Nele

2018-05-01

Patient-specific biomechanical modelling can improve preoperative surgical planning. This requires patient-specific geometry as well as patient-specific material properties as input. The latter are, however, still quite challenging to estimate in vivo. This study focuses on the estimation of the mechanical properties of the arterial wall. Firstly, in vivo pressure, diameter and thickness of the arterial wall were acquired for sheep common carotid arteries. Next, the animals were sacrificed and the tissue was stored for mechanical testing. Planar biaxial tests were performed to obtain experimental stress-stretch curves. Finally, parameters for the hyperelastic Mooney-Rivlin and Gasser-Ogden-Holzapfel (GOH) material model were estimated based on the in vivo obtained pressure-diameter data as well as on the ex situ experimental stress-stretch curves. Both material models were able to capture the in vivo behaviour of the tissue. However, in the ex situ case only the GOH model provided satisfactory results. When comparing different fitting approaches, in vivo vs. ex situ, each of them showed its own advantages and disadvantages. The in vivo approach estimates the properties of the tissue in its physiological state while the ex situ approach allows to apply different loadings to properly capture the anisotropy of the tissue. Both of them could be further enhanced by improving the estimation of the stress-free state, i.e. by adding residual circumferential stresses in vivo and by accounting for the flattening effect of the tested samples ex vivo. • Competing interests: none declared • Word count: 4716. Copyright © 2018. Published by Elsevier Ltd.

[Project HRANAFINA--Croatian anatomical and physiological terminology].

PubMed

Vodanović, Marin

2012-01-01

HRANAFINA--Croatian Anatomical and Physiological Terminology is a project of the University of Zagreb School of Dental Medicine funded by the Croatian Science Foundation. It is performed in cooperation with other Croatian universities with medical schools. This project has a two-pronged aim: firstly, building of Croatian anatomical and physiological terminology and secondly, Croatian anatomical and physiological terminology usage popularization between health professionals, medical students, scientists and translators. Internationally recognized experts from Croatian universities with medical faculties and linguistics experts are involved in the project. All project activities are coordinated in agreement with the National Coordinator for Development of Croatian Professional Terminology. The project enhances Croatian professional terminology and Croatian language in general, increases competitiveness of Croatian scientists on international level and facilitates the involvement of Croatian scientists, health care providers and medical students in European projects.

Enhancement of photoassimilate utilization by manipulation of starch regulatory enzymes

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

Okita, Thomas W.

ADPglucose pyrophosphorylase (AGPase) and the plastidial starch phosphorylase1 (Pho1) are two regulatory enzymes whose catalytic activities are essential for starch granule synthesis. Conversion of the pre-starch granule to the mature form is dependent on AGPase, which produces ADPglucose, the substrate used by starch synthases. The catalytic activity of AGPase is controlled by small effector molecules and a prime goal of this project was to decipher the role of the two subunit types that comprise the heterotetrameric enzyme structure. Extensive genetic and biochemical studies showed that catalysis was contributed mainly by the small subunit although the large subunit was required formore » maximum activity. Both subunits were needed for allosteric regulatory properties. We had also demonstrated that the AGPase catalyzed reaction limits the amount of starch accumulation in developing rice seeds and that carbon flux into rice seed starch can be increased by expression of a cytoplasmic-localized, up-regulated bacterial AGPase enzyme form. Results of subsequent physiological and metabolite studies showed that the AGPase reaction is no longer limiting in the AGPase transgenic rice lines and that one or more downstream processes prevent further increases in starch biosynthesis. Further studies showed that over-production of ADPglucose dramatically alters the gene program during rice seed development. Although the expression of nearly all of the genes are down-regulated, levels of a starch binding domain containing protein (SBDCP) are elevated. This SBDCP was found to bind to and inhibit the catalytic activity of starch synthase III and, thereby preventing maximum starch synthesis from occurring. Surprisingly, repression of SBDCP elevated expression of starch synthase III resulting in increasing rice grain weight. A second phase of this project examined the structure-function of Pho1, the enzyme required during the initial phase of pre-starch granule formation and its maturation to a starch granule. Although Pho1 catalyzes a reversible reaction, our DoE supported studies clearly demonstrated that the kinetic properties of this enzyme strongly favor synthesis of starch and that these catalytic properties are independent of the L80 peptide, a structural domain that is absent in phosphorylases from other organisms. Interesting expression of a Pho1 lacking the L80 peptide enhanced plant growth and seed yields, suggesting that Pho1 has a second function in controlling growth. Overall, results from these biochemical and physiological studies have increased our fundamental understanding on how these important starch regulatory enzymes operate at the molecular level and in planta, which will collectively aid in efforts to increase the utilization of higher plants as a renewable source of energy.« less

Repetitive Supra-Physiological Shear Stress Impairs Red Blood Cell Deformability and Induces Hemolysis.

PubMed

Horobin, Jarod T; Sabapathy, Surendran; Simmonds, Michael J

2017-11-01

The supra-physiological shear stress that blood is exposed to while traversing mechanical circulatory assist devices affects the physical properties of red blood cells (RBCs), impairs RBC deformability, and may induce hemolysis. Previous studies exploring RBC damage following exposure to supra-physiological shear stress have employed durations exceeding clinical instrumentation, thus we explored changes in RBC deformability following exposure to shear stress below the reported "hemolytic threshold" using shear exposure durations per minute (i.e., duty-cycles) reflective of that employed by circulatory assist devices. Blood collected from 20 male donors, aged 18-38 years, was suspended in a viscous medium and exposed to an intermittent shear stress protocol of 1 s at 100 Pa, every 60 s for 60 duty-cycles. During the remaining 59 s/min, the cells were left at stasis until the subsequent duty-cycle commenced. At discrete time points (15/30/45/60 duty-cycles), an ektacytometer measured RBC deformability immediately after shear exposure at 100 Pa. Plasma-free hemoglobin, a measurement of hemolysis, was quantified via spectrophotometry. Supra-physiological shear stress impaired RBC properties, as indicated by: (1) decreased maximal elongation of RBCs at infinite shear stress following 15 duty-cycles (P <0.05); (2) increased real-time RBC deformability during application of the supra-physiological shear stress protocol (100 Pa) following exposure to 1 duty-cycle (F (1.891, 32.15) = 12.21, P = 0.0001); and (3) increased plasma-free hemoglobin following 60 duty-cycles (P < 0.01). The present study indicates that exposure of RBCs to short-term, repeated supra-physiological shear stress, impairs RBC deformability, with the extent of impairment exacerbated with each duty-cycle, and ultimately precipitates hemolysis. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Carbohydrate terminology and classification.

PubMed

Cummings, J H; Stephen, A M

2007-12-01

Dietary carbohydrates are a group of chemically defined substances with a range of physical and physiological properties and health benefits. As with other macronutrients, the primary classification of dietary carbohydrate is based on chemistry, that is character of individual monomers, degree of polymerization (DP) and type of linkage (alpha or beta), as agreed at the Food and Agriculture Organization/World Health Organization Expert Consultation in 1997. This divides carbohydrates into three main groups, sugars (DP 1-2), oligosaccharides (short-chain carbohydrates) (DP 3-9) and polysaccharides (DP> or =10). Within this classification, a number of terms are used such as mono- and disaccharides, polyols, oligosaccharides, starch, modified starch, non-starch polysaccharides, total carbohydrate, sugars, etc. While effects of carbohydrates are ultimately related to their primary chemistry, they are modified by their physical properties. These include water solubility, hydration, gel formation, crystalline state, association with other molecules such as protein, lipid and divalent cations and aggregation into complex structures in cell walls and other specialized plant tissues. A classification based on chemistry is essential for a system of measurement, predication of properties and estimation of intakes, but does not allow a simple translation into nutritional effects since each class of carbohydrate has overlapping physiological properties and effects on health. This dichotomy has led to the use of a number of terms to describe carbohydrate in foods, for example intrinsic and extrinsic sugars, prebiotic, resistant starch, dietary fibre, available and unavailable carbohydrate, complex carbohydrate, glycaemic and whole grain. This paper reviews these terms and suggests that some are more useful than others. A clearer understanding of what is meant by any particular word used to describe carbohydrate is essential to progress in translating the growing knowledge of the physiological properties of carbohydrate into public health messages.

Enhancing the Benefits of Written Emotional Disclosure through Response Training

PubMed Central

Konig, Andrea; Eonta, Alison; Dyal, Stephanie R.; Vrana, Scott R.

2014-01-01

Writing about a personal stressful event has been found to have psychological and physical health benefits, especially when physiological response increases during writing. Response training was developed to amplify appropriate physiological reactivity in imagery exposure. The present study examined whether response training enhances the benefits of written emotional disclosure. Participants were assigned to either a written emotional disclosure condition (n = 113) or a neutral writing condition (n = 133). Participants in each condition wrote for 20 minutes on three occasions and received response training (n = 79), stimulus training (n = 84) or no training (n = 83). Heart rate and skin conductance were recorded throughout a 10-minute baseline, 20-minute writing, and a 10-minute recovery period. Self-reported emotion was assessed in each session. One month after completing the sessions, participants completed follow-up assessments of psychological and physical health outcomes. Emotional disclosure elicited greater physiological reactivity and self-reported emotion than neutral writing. Response training amplified physiological reactivity to emotional disclosure. Greater heart rate during emotional disclosure was associated with the greatest reductions in event-related distress, depression, and physical illness symptoms at follow-up, especially among response trained participants. Results support an exposure explanation of emotional disclosure effects and are the first to demonstrate that response training facilitates emotional processing and may be a beneficial adjunct to written emotional disclosure. PMID:24680230

Enhancing the benefits of written emotional disclosure through response training.

PubMed

Konig, Andrea; Eonta, Alison; Dyal, Stephanie R; Vrana, Scott R

2014-05-01

Writing about a personal stressful event has been found to have psychological and physical health benefits, especially when physiological response increases during writing. Response training was developed to amplify appropriate physiological reactivity in imagery exposure. The present study examined whether response training enhances the benefits of written emotional disclosure. Participants were assigned to either a written emotional disclosure condition (n=113) or a neutral writing condition (n=133). Participants in each condition wrote for 20 minutes on 3 occasions and received response training (n=79), stimulus training (n=84) or no training (n=83). Heart rate and skin conductance were recorded throughout a 10-minute baseline, 20-minute writing, and a 10-minute recovery period. Self-reported emotion was assessed in each session. One month after completing the sessions, participants completed follow-up assessments of psychological and physical health outcomes. Emotional disclosure elicited greater physiological reactivity and self-reported emotion than neutral writing. Response training amplified physiological reactivity to emotional disclosure. Greater heart rate during emotional disclosure was associated with the greatest reductions in event-related distress, depression, and physical illness symptoms at follow-up, especially among response trained participants. Results support an exposure explanation of emotional disclosure effects and are the first to demonstrate that response training facilitates emotional processing and may be a beneficial adjunct to written emotional disclosure. Copyright © 2014. Published by Elsevier Ltd.

Hydrogel tissue construct-based high-content compound screening.

PubMed

Lam, Vy; Wakatsuki, Tetsuro

2011-01-01

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)-based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds--rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)--for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

PubMed

Lee, Irene; Berdis, Anthony J

2016-01-01

Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. Copyright © 2015 Elsevier B.V. All rights reserved.

A mathematics for medicine: The Network Effect

PubMed Central

West, Bruce J.

2014-01-01

The theory of medicine and its complement systems biology are intended to explain the workings of the large number of mutually interdependent complex physiologic networks in the human body and to apply that understanding to maintaining the functions for which nature designed them. Therefore, when what had originally been made as a simplifying assumption or a working hypothesis becomes foundational to understanding the operation of physiologic networks it is in the best interests of science to replace or at least update that assumption. The replacement process requires, among other things, an evaluation of how the new hypothesis affects modern day understanding of medical science. This paper identifies linear dynamics and Normal statistics as being such arcane assumptions and explores some implications of their retirement. Specifically we explore replacing Normal with fractal statistics and examine how the latter are related to non-linear dynamics and chaos theory. The observed ubiquity of inverse power laws in physiology entails the need for a new calculus, one that describes the dynamics of fractional phenomena and captures the fractal properties of the statistics of physiological time series. We identify these properties as a necessary consequence of the complexity resulting from the network dynamics and refer to them collectively as The Network Effect. PMID:25538622

Beyond Fractals and 1/f Noise: Multifractal Analysis of Complex Physiological Time Series

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch.; Amaral, Luis A. N.; Ashkenazy, Yosef; Stanley, H. Eugene; Goldberger, Ary L.; Hausdorff, Jeffrey M.; Yoneyama, Mitsuru; Arai, Kuniharu

2001-03-01

We investigate time series with 1/f-like spectra generated by two physiologic control systems --- the human heartbeat and human gait. We show that physiological fluctuations exhibit unexpected ``hidden'' structures often described by scaling laws. In particular, our studies indicate that when analyzed on different time scales the heartbeat fluctuations exhibit cascades of branching patterns with self-similar (fractal) properties, characterized by long-range power-law anticorrelations. We find that these scaling features change during sleep and wake phases, and with pathological perturbations. Further, by means of a new wavelet-based technique, we find evidence of multifractality in the healthy human heartbeat even under resting conditions, and show that the multifractal character and nonlinear properties of the healthy heart are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure. In contrast to the heartbeat, we find that the interstride interval time series of healthy human gait, a voluntary process under neural regulation, is described by a single fractal dimension (such as classical 1/f noise) indicating monofractal behavior. Thus our approach can help distinguish physiological and physical signals with comparable frequency spectra and two-point correlations, and guide modeling of their control mechanisms.

Canopy and physiological controls of GPP during drought and heat wave

NASA Astrophysics Data System (ADS)

Zhang, Yao; Xiao, Xiangming; Zhou, Sha; Ciais, Philippe; McCarthy, Heather; Luo, Yiqi

2016-04-01

Vegetation indices (VIs) derived from satellite reflectance measurements are often used as proxies of canopy activity to evaluate the impacts of drought and heat wave on gross primary production (GPP) through production efficiency models. However, GPP is also regulated by physiological processes that cannot be directly detected using reflectance measurements. This study analyzes the co-limitation of canopy and plant physiology (represented by VIs and climate anomalies, respectively) on GPP during the 2003 European summer drought and heat wave for 15 Euroflux sites. During the entire drought period, spatial pattern of GPP anomalies can be quantified by relative changes in VIs. We also find that GPP sensitivity to relative canopy changes is higher for nonforest ecosystems (1.81 ± 0.32%GPP/%enhanced vegetation index), while GPP sensitivity to physiological changes is higher for forest ecosystems (-0.18 ± 0.05 g C m-2 d-1/hPa). A conceptual model is further built to better illustrate the canopy and physiological controls on GPP during drought periods.

THE PASSIVE PROPERTIES OF MUSCLE FIBERS ARE VELOCITY DEPENDENT

PubMed Central

Rehorn, Michael R.; Schroer, Alison K.; Blemker, Silvia S.

2014-01-01

The passive properties of skeletal muscle play an important role in muscle function. While the passive quasi-static elastic properties of muscle fibers have been well characterized, the dynamic visco-elastic passive behavior of fibers has garnered less attention. In particular, it is unclear how the visco-elastic properties are influenced by lengthening velocity, in particular for the range of physiologically relevant velocities. The goals of this work were to: (i) measure the effects of lengthening velocity on the peak stresses within single muscle fibers to determine how passive behavior changes over a range of physiologically relevant lengthening rates (0.1–10 Lo/s), and (ii) develop a mathematical model of fiber viscoelasticity based on these measurements. We found that passive properties depend on strain rate, in particular at the low loading rates (0.1–3 Lo/s), and that the measured behavior can be predicted across a range of loading rates and time histories with a quasi-linear viscoelastic model. In the future, these results can be used to determine the impact of viscoelastic behavior on intramuscular stresses and forces during a variety of dynamic movements. PMID:24360198

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity

PubMed Central

Julik, Emily; Reyes-del Valle, Jorge

2017-01-01

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine. PMID:28934110

Quantum chemistry calculation of resveratrol and related stilbenes

NASA Astrophysics Data System (ADS)

Del Nero, J.; de Melo, C. P.

2003-01-01

We report a semiempirical investigation of the first excited states and of the spectroscopic properties of resveratrol, a phytoalexin with well-known antioxidative properties, and of structurally related stilbenes. The analysis of the calculated bond length and charge rearrangements resulting from the photoexcitation and of the corresponding theoretical spectra gives us some insight of how chemical modifications of these molecules could affect the possible physiological properties of resveratrol.

A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect.

PubMed

Qureshi, Ahmed; Naughton, Declan P; Petroczi, Andrea

2014-03-01

Tribulus terrestris (TT) is a dicotyledonous herbal plant of the Zygophyllaceae family. In ancient medicine, extracts of the aerial parts and fruits have been used for its diuretic, tonic, and aphrodisiac properties. Today, TT is widely used by athletes and bodybuilders based on the belief, fueled by claims in marketing information, that it can enhance testosterone concentrations. To assess TT's effect on testosterone levels in human and animals, an electronic literature search out using seven databases and the patent database up to August 2013 was carried out. Randomized control trials, which included healthy human subjects ingesting TT as sole or combined supplement, along with animal studies with TT as a sole treatment across a number of species were included. Eleven studies met the inclusion criteria, including one patent application. The results showed that trials varied in duration, dosage and supplementation with TT as sole or combined treatment, rendering meta-analysis impossible. A limited number of animal studies displayed a significant increase in serum testosterone levels after TT administration, but this effect was only noted in humans when TT was part of a combined supplement administration. Literature available for the effectiveness of TT on enhancing testosterone concentrations is limited. Evidence to date suggests that TT is ineffective for increasing testosterone levels in humans, thus marketing claims are unsubstantiated. The nitric oxide release effect of TT may offer a plausible explanation for the observed physiological responses to TT supplementation, independent of the testosterone level.

Enhancing Human Cognition with Cocoa Flavonoids

PubMed Central

Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele

2017-01-01

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects. PMID:28560212

Plant growth-promoting activities of Streptomyces spp. in sorghum and rice.

PubMed

Gopalakrishnan, Subramaniam; Srinivas, Vadlamudi; Sree Vidya, Meesala; Rathore, Abhishek

2013-01-01

Five strains of Streptomyces (CAI-24, CAI-121, CAI-127, KAI-32 and KAI-90) were earlier reported by us as biological control agents against Fusarium wilt of chickpea caused by Fusarium oxysporum f. sp. ciceri (FOC). In the present study, the Streptomyces were characterized for enzymatic activities, physiological traits and further evaluated in greenhouse and field for their plant growth promotion (PGP) of sorghum and rice. All the Streptomyces produced lipase, β-1-3-glucanase and chitinase (except CAI-121 and CAI-127), grew in NaCl concentrations of up to 6%, at pH values between 5 and 13 and temperatures between 20 and 40°C and were highly sensitive to Thiram, Benlate, Captan, Benomyl and Radonil at field application level. When the Streptomyces were evaluated in the greenhouse on sorghum all the isolates significantly enhanced all the agronomic traits over the control. In the field, on rice, the Streptomyces significantly enhanced stover yield (up to 25%; except CAI-24), grain yield (up to 10%), total dry matter (up to 18%; except CAI-24) and root length, volume and dry weight (up to 15%, 36% and 55%, respectively, except CAI-24) over the control. In the rhizosphere soil, the Streptomyces significantly enhanced microbial biomass carbon (except CAI-24), nitrogen, dehydrogenase (except CAI-24), total N, available P and organic carbon (up to 41%, 52%, 75%, 122%, 53% and 13%, respectively) over the control. This study demonstrates that the selected Streptomyces which were antagonistic to FOC also have PGP properties.

Enhancing Human Cognition with Cocoa Flavonoids.

PubMed

Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele

2017-01-01

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.

Gene doping: a review of performance-enhancing genetics.

PubMed

Gaffney, Gary R; Parisotto, Robin

2007-08-01

Unethical athletes and their mentors have long arrogated scientific and medical advances to enhance athletic performance, thus gaining a dishonest competitive advantage. Building on advances in genetics, a new threat arises from athletes using gene therapy techniques in the same manner that some abused performance-enhancing drugs were used. Gene doping, as this is known, may produce spectacular physiologic alterations to dramatically enhance athletic abilities or physical appearance. Furthermore, gene doping may present pernicious problems for the regulatory agencies and investigatory laboratories that are entrusted to keep sporting events fair and ethical. Performance-enhanced genetics will likewise present unique challenges to physicians in many spheres of their practice.

An Investigation into the Psychometric Properties of the Test Anxiety Measure for College Students

ERIC Educational Resources Information Center

Lowe, Patricia A.

2018-01-01

The psychometric properties of a new, multidimensional measure of test anxiety, the Test Anxiety Measure for College Students (TAM-C), were examined in a sample of 720 undergraduate students. Results of confirmatory factor analyses provided support for a six-factor (Cognitive Interference, Physiological Hyperarousal, Social Concerns,…

Heavy metal accumulation and signal transduction in herbaceous and woody plants: Paving the way for enhancing phytoremediation efficiency.

PubMed

Luo, Zhi-Bin; He, Jiali; Polle, Andrea; Rennenberg, Heinz

2016-11-01

Heavy metal (HM)-accumulating herbaceous and woody plants are employed for phytoremediation. To develop improved strategies for enhancing phytoremediation efficiency, knowledge of the microstructural, physiological and molecular responses underlying HM-accumulation is required. Here we review the progress in understanding the structural, physiological and molecular mechanisms underlying HM uptake, transport, sequestration and detoxification, as well as the regulation of these processes by signal transduction in response to HM exposure. The significance of genetic engineering for enhancing phytoremediation efficiency is also discussed. In herbaceous plants, HMs are taken up by roots and transported into the root cells via transmembrane carriers for nutritional ions. The HMs absorbed by root cells can be further translocated to the xylem vessels and unloaded into the xylem sap, thereby reaching the aerial parts of plants. HMs can be sequestered in the cell walls, vacuoles and the Golgi apparatuses. Plant roots initially perceive HM stress and trigger the signal transduction, thereby mediating changes at the molecular, physiological, and microstructural level. Signaling molecules such as phytohormones, reactive oxygen species (ROS) and nitric oxide (NO), modulate plant responses to HMs via differentially expressed genes, activation of the antioxidative system and coordinated cross talk among different signaling molecules. A number of genes participated in HM uptake, transport, sequestration and detoxification have been functionally characterized and transformed to target plants for enhancing phytoremediation efficiency. Fast growing woody plants hold an advantage over herbaceous plants for phytoremediation in terms of accumulation of high HM-amounts in their large biomass. Presumably, woody plants accumulate HMs using similar mechanisms as herbaceous counterparts, but the processes of HM accumulation and signal transduction can be more complex in woody plants. Copyright © 2016 Elsevier Inc. All rights reserved.

Hericium erinaceus: an edible mushroom with medicinal values.

PubMed

Khan, Md Asaduzzaman; Tania, Mousumi; Liu, Rui; Rahman, Mohammad Mijanur

2013-05-24

Mushrooms are considered as nutritionally functional foods and source of physiologically beneficial medicines. Hericium erinaceus, also known as Lion's Mane Mushroom or Hedgehog Mushroom, is an edible fungus, which has a long history of usage in traditional Chinese medicine. This mushroom is rich in some physiologically important components, especially β-glucan polysaccharides, which are responsible for anti-cancer, immuno-modulating, hypolipidemic, antioxidant and neuro-protective activities of this mushroom. H. erinaceus has also been reported to have anti-microbial, anti-hypertensive, anti-diabetic, wound healing properties among other therapeutic potentials. This review article has overviewed the recent advances in the research and study on H. erinaceus and discussed the potential health beneficial activities of this mushroom, with the recognition of bioactive compounds responsible for these medicinal properties.

Entrapment of Ciliates at the Water-Air Interface

PubMed Central

Ferracci, Jonathan; Ueno, Hironori; Numayama-Tsuruta, Keiko; Imai, Yohsuke; Yamaguchi, Takami; Ishikawa, Takuji

2013-01-01

The importance of water-air interfaces (WAI) on microorganism activities has been recognized by many researchers. In this paper, we report a novel phenomenon: the entrapment of ciliates Tetrahymena at the WAI. We first characterized the behavior of cells at the interface and showed that the cells' swimming velocity was considerably reduced at the WAI. To verify the possible causes of the entrapment, we investigated the effects of positive chemotaxis for oxygen, negative geotaxis and surface properties. Even though the taxes were still effective, the entrapment phenomenon was not dependent on the physiological conditions, but was instead affected by the physical properties at the interface. This knowledge is useful for a better understanding of the physiology of microorganisms at interfaces in nature and in industry. PMID:24130692

Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside-induced attenuation of high blood pressure in SHR.

PubMed

Hossain, Ekhtear; Sarkar, Oli; Li, Yuan; Anand-Srivastava, Madhu B

2018-03-01

We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins which was attributed to the decreased levels of nitric oxide (NO), because elevation of the intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the enhanced expression of Giα proteins. Since the enhanced expression of Giα proteins is implicated in the pathogenesis of hypertension, the present study was undertaken to investigate if treatment of SHR with SNP could also attenuate the development of high blood pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2 weeks into SHR attenuated the high blood pressure by about 80 mmHg without affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels of superoxide anion (O 2 - ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO - ), and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the overexpression of different subunits of NADPH oxidase; Nox-1, Nox-2, Nox-4, P 22phox , and P 47phox , and Giα proteins in VSMC from SHR were also attenuated by SNP treatment. On the other hand, SNP treatment augmented the decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These results suggest that SNP treatment attenuates the development of high BP in SHR through the elevation of intracellular levels of cGMP and inhibition of the enhanced levels of Giα proteins and nitroxidative stress. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators.

PubMed

Wei, Ruihan; Parsons, Sean P; Huizinga, Jan D

2017-03-01

What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ICC network as a two-dimensional network of weakly coupled oscillators with a frequency gradient and showed changes over time in video and graphical formats. Model parameters were obtained from slow-wave-driven contraction patterns in the mouse intestine and pacemaker slow-wave activities from the cat intestine. Marked changes in propagating oscillation patterns (including changes from propagation to non-propagating) were observed by changing network parameters (coupling strength between oscillators, the frequency gradient and frequency noise), which affected synchronization, propagation velocity and occurrence of dislocations (termination of an oscillation). Complete uncoupling of a circumferential ring of oscillators caused the proximal and distal section to desynchronize, but complete synchronization was maintained with only a single oscillator connecting the sections with high enough coupling. The network of oscillators could withstand loss; even with 40% of oscillators lost randomly within the network, significant synchronization and anterograde propagation remained. A local increase in pacemaker frequency diminished anterograde propagation; the effects were strongly dependent on location, frequency gradient and coupling strength. In summary, the model puts forth the hypothesis that fundamental changes in oscillation patterns (ICC slow-wave activity or circular muscle contractions) can occur through physiological modulation of network properties. Strong evidence is provided to accept the ICC network as a system of coupled oscillators. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Tendon biomechanics and mechanobiology - a mini-review of basic concepts and recent advancements

PubMed Central

Wang, James H-C.; Guo, Qianping; Li, Bin

2011-01-01

Due to their unique hierarchical structure and composition, tendons possess characteristic biomechanical properties, including high mechanical strength and viscoelasticity, which enable them to carry and transmit mechanical loads (muscular forces) effectively. Tendons are also mechano-responsive by adaptively changing their structure and function in response to altered mechanical loading conditions. In general, mechanical loading at physiological levels is beneficial to tendons, but excessive loading or disuse of tendons is detrimental. This mechano-adaptability is due to the cells present in tendons. Tendon fibroblasts (tenocytes) are the dominant tendon cells responsible for tendon homeostasis and repair. Tendon stem cells (TSCs), which were recently discovered, also play a vital role in tendon maintenance and repair by virtue of their ability to self-renew and differentiate into tenocytes. TSCs may also be responsible for chronic tendon injury, or tendinopathy, by undergoing aberrant differentiation into non-tenocytes in response to excessive mechanical loading. Thus, it is necessary to devise optimal rehabilitation protocols in order to enhance tendon healing while reducing scar tissue formation and tendon adhesions. Moreover, along with scaffolds that can mimic tendon matrix environments and platelet-rich plasma (PRP), which serves as a source of growth factors, TSCs may be the optimal cell type for enhancing repair of injured tendons. PMID:21925835

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

PubMed

Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

2017-02-28

Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation of Bioactive Polysaccharide Nanoparticles with Enhanced Radical Scavenging Activity and Antimicrobial Activity.

PubMed

Qin, Yang; Xiong, Liu; Li, Man; Liu, Jing; Wu, Hao; Qiu, Hongwei; Mu, Hongyan; Xu, Xingfeng; Sun, Qingjie

2018-05-02

Because of their biocompatibility and biodegradability in vivo, natural polysaccharides are effective nanocarriers for delivery of active ingredients or drugs. Moreover, bioactive polysaccharides, such as tea, Ganoderma lucidum, and Momordica charantia polysaccharides (TP, GLP, and MCP), have antibacterial, antioxidant, antitumor, and antiviral properties. In this study, tea, Ganoderma lucidum, and Momordica charantia polysaccharide nanoparticles (TP-NPs, GLP-NPs, and MCP-NPs) were prepared via the nanoprecipitation approach. When the ethanol to water ratio was 10:1, the diameter of the spherical polysaccharide nanoparticles was the smallest, and the mean particle size of the TP-NPs, GLP-NPs, and MCP-NPs was 99 ± 15, 95 ± 7, and 141 ± 9 nm, respectively. When exposed to heat, increased ionic strength and pH levels, the nanoparticles exhibited superior stability and higher activity than the corresponding polysaccharides. In physiological conditions (pH 7.4), the nanoparticles underwent different protein adsorption capacities in the following order: MCP-NPs> TP-NPs> GLP-NPs. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical, and superoxide anion radical scavenging rates of the nanoparticles were increased by 9-25% as compared to the corresponding polysaccharides. Compared to the bioactive polysaccharides, the nanoparticles enhanced antimicrobial efficacy markedly and exhibited long-acting antibacterial activity.

Characterization of a novel strain phylogenetically related to Kocuria rhizophila and its chemical modification to improve performance of microbial fuel cells.

PubMed

Luo, Jianmei; Li, Ming; Zhou, Minghua; Hu, Youshuang

2015-07-15

It is certainly an important research area to discovery new exoelectrogens for microbial fuel cells (MFCs), and how to effectively manipulate its cell property to improve power performance is still a great challenge. In this study, a new electrochemically active bacterium phylogenetically related to Kocuria rhizophila was first isolated and found electrogenic in MFCs, which was identified through the combination methods of molecular biology, physiological, biochemical and morphological characteristics. The MFCs inoculated with this strain generated power from a wide variety of substrates, reached a maximum power density of 75mW/m(2) in the substrate of 1g/L glucose. And the electron transfer mechanism was confirmed to be dominantly direct biofilm mechanism. Chemical treatment with five reagents was verified to be a feasible strategy to improve the power density of MFCs, increasing approximately 1.75 fold at most after treated with lysozyme. This enhancement was contributed to the significant enhancement on cell permeability, cell membrane fluidity and Coenzyme Q10 (the electron carrier). Thus this work offered a novel Gram-positive electrogenic bacterium and proved chemical treatment was a feasible strategy to improve electron transfer for application in MFCs. Copyright © 2015 Elsevier B.V. All rights reserved.

Apolipoprotein C-III in triglyceride-rich lipoprotein metabolism.

PubMed

Ramms, Bastian; Gordts, Philip L S M

2018-06-01

Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements. Clinical and preclinical studies established that apoC-III raises plasma triglyceride levels predominantly by inhibiting hepatic TRL clearance. Mechanistic insights into missense variants indicate accelerated renal clearance of apoC-III variants resulting in enhanced TRL catabolism. In contrast, an APOC3 gain-of-function variant enhances de novo lipogenesis and hepatic TRL production. Multiple studies confirmed the correlation between increased apoC-III levels and cardiovascular disease. This has opened up new therapeutic avenues allowing targeting of specific apoC-III properties in triglyceride metabolism. Novel in vivo models and APOC3 missense variants revealed unique mechanisms by which apoC-III inhibits TRL catabolism. Clinical trials with Volanesorsen, an APOC3 antisense oligonucleotide, report very promising lipid-lowering outcomes. However, future studies will need to address if acute apoC-III lowering will have the same clinical benefits as a life-long reduction.

Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy.

PubMed

Jeong, Juseong; Park, Choon-Ho; Kim, Inbo; Kim, Young-Ho; Yoon, Jae-Min; Kim, Kwang-Soo; Kim, Jong-Bae

2017-01-21

Korean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle. We examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model. Interestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice. Our results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.

Carbohydrates for Soccer: A Focus on Skilled Actions and Half-Time Practices

PubMed Central

Hills, Samuel P.; Russell, Mark

2017-01-01

Carbohydrate consumption is synonymous with soccer performance due to the established effects on endogenous energy store preservation, and physical capacity maintenance. For performance-enhancement purposes, exogenous energy consumption (in the form of drinks, bars, gels and snacks) is recommended on match-day; specifically, before and during match-play. Akin to the demands of soccer, limited opportunities exist to consume carbohydrates outside of scheduled breaks in competition, such as at half-time. The link between cognitive function and blood glucose availability suggests that carbohydrates may influence decision-making and technical proficiency (e.g., soccer skills). However, relatively few reviews have focused on technical, as opposed to physical, performance while also addressing the practicalities associated with carbohydrate consumption when limited in-play feeding opportunities exist. Transient physiological responses associated with reductions in activity prevalent in scheduled intra-match breaks (e.g., half-time) likely have important consequences for practitioners aiming to optimize match-day performance. Accordingly, this review evaluated novel developments in soccer literature regarding (1) the ergogenic properties of carbohydrates for skill performance; and (2) novel considerations concerning exogenous energy provision during half-time. Recommendations are made to modify half-time practices in an aim to enhance subsequent performance. Viable future research opportunities exist regarding a deeper insight into carbohydrate provision on match-day. PMID:29295583

Surface functionalization of 3D glass-ceramic porous scaffolds for enhanced mineralization in vitro

NASA Astrophysics Data System (ADS)

Ferraris, Sara; Vitale-Brovarone, Chiara; Bretcanu, Oana; Cassinelli, Clara; Vernè, Enrica

2013-04-01

Bone reconstruction after tissue loosening due to traumatic, pathological or surgical causes is in increasing demand. 3D scaffolds are a widely studied solution for supporting new bone growth. Bioactive glass-ceramic porous materials can offer a three-dimensional structure that is able to chemically bond to bone. The ability to surface modify these devices by grafting biologically active molecules represents a challenge, with the aim of stimulating physiological bone regeneration with both inorganic and organic signals. In this research work glass ceramic scaffolds with very high mechanical properties and moderate bioactivity have been functionalized with the enzyme alkaline phosphatase (ALP). The material surface was activated in order to expose hydroxyl groups. The activated surface was further grafted with ALP both via silanization and also via direct grafting to the surface active hydroxyl groups. Enzymatic activity of grafted samples were measured by means of UV-vis spectroscopy before and after ultrasonic washing in TRIS-HCl buffer solution. In vitro inorganic bioactivity was investigated by soaking the scaffolds after the different steps of functionalization in a simulated body fluid (SBF). SEM observations allowed the monitoring of the scaffold morphology and surface chemical composition after soaking in SBF. The presence of ALP enhanced the in vitro inorganic bioactivity of the tested material.

Vitronectin as a Micromanager of Cell Response in Material-Driven Fibronectin Nanonetworks.

PubMed

Cantini, Marco; Gomide, Karina; Moulisova, Vladimira; González-García, Cristina; Salmerón-Sánchez, Manuel

2017-09-01

Surface functionalization strategies of synthetic materials for regenerative medicine applications comprise the development of microenvironments that recapitulate the physical and biochemical cues of physiological extracellular matrices. In this context, material-driven fibronectin (FN) nanonetworks obtained from the adsorption of the protein on poly(ethyl acrylate) provide a robust system to control cell behavior, particularly to enhance differentiation. This study aims at augmenting the complexity of these fibrillar matrices by introducing vitronectin, a lower-molecular-weight multifunctional glycoprotein and main adhesive component of serum. A cooperative effect during co-adsorption of the proteins is observed, as the addition of vitronectin leads to increased fibronectin adsorption, improved fibril formation, and enhanced vitronectin exposure. The mobility of the protein at the material interface increases, and this, in turn, facilitates the reorganization of the adsorbed FN by cells. Furthermore, the interplay between interface mobility and engagement of vitronectin receptors controls the level of cell fusion and the degree of cell differentiation. Ultimately, this work reveals that substrate-induced protein interfaces resulting from the cooperative adsorption of fibronectin and vitronectin fine-tune cell behavior, as vitronectin micromanages the local properties of the microenvironment and consequently short-term cell response to the protein interface and higher order cellular functions such as differentiation.

Tendon biomechanics and mechanobiology--a minireview of basic concepts and recent advancements.

PubMed

Wang, James H-C; Guo, Qianping; Li, Bin

2012-01-01

Due to their unique hierarchical structure and composition, tendons possess characteristic biomechanical properties, including high mechanical strength and viscoelasticity, which enable them to carry and transmit mechanical loads (muscular forces) effectively. Tendons are also mechanoresponsive by adaptively changing their structure and function in response to altered mechanical loading conditions. In general, mechanical loading at physiological levels is beneficial to tendons, but excessive loading or disuse of tendons is detrimental. This mechanoadaptability is due to the cells present in tendons. Tendon fibroblasts (tenocytes) are the dominant tendon cells responsible for tendon homeostasis and repair. Tendon stem cells (TSCs), which were recently discovered, also play a vital role in tendon maintenance and repair by virtue of their ability to self-renew and differentiate into tenocytes. TSCs may also be responsible for chronic tendon injury, or tendinopathy, by undergoing aberrant differentiation into nontenocytes in response to excessive mechanical loading. Thus, it is necessary to devise optimal rehabilitation protocols to enhance tendon healing while reducing scar tissue formation and tendon adhesions. Moreover, along with scaffolds that can mimic tendon matrix environments and platelet-rich plasma, which serves as a source of growth factors, TSCs may be the optimal cell type for enhancing repair of injured tendons. Copyright © 2012 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Characterizing uncertainty and variability in physiologically based pharmacokinetic models: state of the science and needs for research and implementation.

PubMed

Barton, Hugh A; Chiu, Weihsueh A; Setzer, R Woodrow; Andersen, Melvin E; Bailer, A John; Bois, Frédéric Y; Dewoskin, Robert S; Hays, Sean; Johanson, Gunnar; Jones, Nancy; Loizou, George; Macphail, Robert C; Portier, Christopher J; Spendiff, Martin; Tan, Yu-Mei

2007-10-01

Physiologically based pharmacokinetic (PBPK) models are used in mode-of-action based risk and safety assessments to estimate internal dosimetry in animals and humans. When used in risk assessment, these models can provide a basis for extrapolating between species, doses, and exposure routes or for justifying nondefault values for uncertainty factors. Characterization of uncertainty and variability is increasingly recognized as important for risk assessment; this represents a continuing challenge for both PBPK modelers and users. Current practices show significant progress in specifying deterministic biological models and nondeterministic (often statistical) models, estimating parameters using diverse data sets from multiple sources, using them to make predictions, and characterizing uncertainty and variability of model parameters and predictions. The International Workshop on Uncertainty and Variability in PBPK Models, held 31 Oct-2 Nov 2006, identified the state-of-the-science, needed changes in practice and implementation, and research priorities. For the short term, these include (1) multidisciplinary teams to integrate deterministic and nondeterministic/statistical models; (2) broader use of sensitivity analyses, including for structural and global (rather than local) parameter changes; and (3) enhanced transparency and reproducibility through improved documentation of model structure(s), parameter values, sensitivity and other analyses, and supporting, discrepant, or excluded data. Longer-term needs include (1) theoretical and practical methodological improvements for nondeterministic/statistical modeling; (2) better methods for evaluating alternative model structures; (3) peer-reviewed databases of parameters and covariates, and their distributions; (4) expanded coverage of PBPK models across chemicals with different properties; and (5) training and reference materials, such as cases studies, bibliographies/glossaries, model repositories, and enhanced software. The multidisciplinary dialogue initiated by this Workshop will foster the collaboration, research, data collection, and training necessary to make characterizing uncertainty and variability a standard practice in PBPK modeling and risk assessment.

Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

PubMed

Nelson, Sarah J

2011-07-01

MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti-proliferative properties as opposed to having a direct effect on tumor cell viability. Copyright © 2011 John Wiley & Sons, Ltd.

Genome-wide profiling of 24 hr diel rhythmicity in the water flea, Daphnia pulex: network analysis reveals rhythmic gene expression and enhances functional gene annotation.

PubMed

Rund, Samuel S C; Yoo, Boyoung; Alam, Camille; Green, Taryn; Stephens, Melissa T; Zeng, Erliang; George, Gary F; Sheppard, Aaron D; Duffield, Giles E; Milenković, Tijana; Pfrender, Michael E

2016-08-18

Marine and freshwater zooplankton exhibit daily rhythmic patterns of behavior and physiology which may be regulated directly by the light:dark (LD) cycle and/or a molecular circadian clock. One of the best-studied zooplankton taxa, the freshwater crustacean Daphnia, has a 24 h diel vertical migration (DVM) behavior whereby the organism travels up and down through the water column daily. DVM plays a critical role in resource tracking and the behavioral avoidance of predators and damaging ultraviolet radiation. However, there is little information at the transcriptional level linking the expression patterns of genes to the rhythmic physiology/behavior of Daphnia. Here we analyzed genome-wide temporal transcriptional patterns from Daphnia pulex collected over a 44 h time period under a 12:12 LD cycle (diel) conditions using a cosine-fitting algorithm. We used a comprehensive network modeling and analysis approach to identify novel co-regulated rhythmic genes that have similar network topological properties and functional annotations as rhythmic genes identified by the cosine-fitting analyses. Furthermore, we used the network approach to predict with high accuracy novel gene-function associations, thus enhancing current functional annotations available for genes in this ecologically relevant model species. Our results reveal that genes in many functional groupings exhibit 24 h rhythms in their expression patterns under diel conditions. We highlight the rhythmic expression of immunity, oxidative detoxification, and sensory process genes. We discuss differences in the chronobiology of D. pulex from other well-characterized terrestrial arthropods. This research adds to a growing body of literature suggesting the genetic mechanisms governing rhythmicity in crustaceans may be divergent from other arthropod lineages including insects. Lastly, these results highlight the power of using a network analysis approach to identify differential gene expression and provide novel functional annotation.

Enzyme Kinetics in Microgravity

NASA Astrophysics Data System (ADS)

Liu, C. C.; Licata, V. J.

2010-04-01

The kinetics of some enzymes have been found to be enhanced by the microgravity environment. This is a relatively small effect, but is sufficient to have physiological effects and to impact pharmaceutical therapy in microgravity.

N-fertilization has different effects on the growth, carbon and nitrogen physiology, and wood properties of slow- and fast-growing Populus species

PubMed Central

Luo, Zhi-Bin

2012-01-01

To investigate how N-fertilization affects the growth, carbon and nitrogen (N) physiology, and wood properties of poplars with contrasting growth characteristics, slow-growing (Populus popularis, Pp) and fast-growing (P. alba×P. glandulosa, Pg) poplar saplings were exposed to different N levels. Above-ground biomass, leaf area, photosynthetic rates (A), instantaneous photosynthetic nitrogen use efficiency (PNUE i), chlorophyll and foliar sugar concentrations were higher in Pg than in Pp. Foliar nitrate reductase (NR) activities and root glutamate synthase (GOGAT) activities were higher in Pg than in Pp as were the N amount and NUE of new shoots. Lignin contents and calorific values of Pg wood were less than that of Pp wood. N-fertilization reduced root biomass of Pg more than of Pp, but increased leaf biomass, leaf area, A, and PNUEi of Pg more than of Pp. Among 13 genes involved in the transport of ammonium or nitrate or in N assimilation, transcripts showed more pronounced changes to N-fertilization in Pg than in Pp. Increases in NR activities and N contents due to N-fertilization were larger in Pg than in Pp. In both species, N-fertilization resulted in lower calorific values as well as shorter and wider vessel elements/fibres. These results suggest that growth, carbon and N physiology, and wood properties are more sensitive to increasing N availability in fast-growing poplars than in slow-growing ones, which is probably due to prioritized resource allocation to the leaves and accelerated N physiological processes in fast-growing poplars under higher N levels. PMID:23028021

N-fertilization has different effects on the growth, carbon and nitrogen physiology, and wood properties of slow- and fast-growing Populus species.

PubMed

Li, Hong; Li, Mengchun; Luo, Jie; Cao, Xu; Qu, Long; Gai, Ying; Jiang, Xiangning; Liu, Tongxian; Bai, Hua; Janz, Dennis; Polle, Andrea; Peng, Changhui; Luo, Zhi-Bin

2012-10-01

To investigate how N-fertilization affects the growth, carbon and nitrogen (N) physiology, and wood properties of poplars with contrasting growth characteristics, slow-growing (Populus popularis, Pp) and fast-growing (P. alba×P. glandulosa, Pg) poplar saplings were exposed to different N levels. Above-ground biomass, leaf area, photosynthetic rates (A), instantaneous photosynthetic nitrogen use efficiency (PNUE (i)), chlorophyll and foliar sugar concentrations were higher in Pg than in Pp. Foliar nitrate reductase (NR) activities and root glutamate synthase (GOGAT) activities were higher in Pg than in Pp as were the N amount and NUE of new shoots. Lignin contents and calorific values of Pg wood were less than that of Pp wood. N-fertilization reduced root biomass of Pg more than of Pp, but increased leaf biomass, leaf area, A, and PNUE(i) of Pg more than of Pp. Among 13 genes involved in the transport of ammonium or nitrate or in N assimilation, transcripts showed more pronounced changes to N-fertilization in Pg than in Pp. Increases in NR activities and N contents due to N-fertilization were larger in Pg than in Pp. In both species, N-fertilization resulted in lower calorific values as well as shorter and wider vessel elements/fibres. These results suggest that growth, carbon and N physiology, and wood properties are more sensitive to increasing N availability in fast-growing poplars than in slow-growing ones, which is probably due to prioritized resource allocation to the leaves and accelerated N physiological processes in fast-growing poplars under higher N levels.

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of glucagon-like peptide-2: Implications and applications for production and health of ruminants.

PubMed

Connor, E E; Evock-Clover, C M; Walker, M P; Elsasser, T H; Kahl, S

2015-02-01

Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide derived from proteolytic cleavage of proglucagon by prohormone convertase 1/3 in enteroendocrine L cells. Studies conducted in humans, in rodent models, and in vitro indicate that GLP-2 is secreted in response to the presence of molecules in the intestinal lumen, including fatty acids, carbohydrates, amino acids, and bile acids, which are detected by luminal chemosensors. The physiological actions of GLP-2 are mediated by its G protein-coupled receptor expressed primarily in the intestinal tract on enteric neurons, enteroendocrine cells, and myofibroblasts. The biological activity of GLP-2 is further regulated by dipeptidyl peptidase IV, which rapidly cleaves the N-terminus of GLP-2 that is responsible for GLP-2 receptor activation. Within the gut, GLP-2 increases nutrient absorption, crypt cell proliferation, and mesenteric blood flow and decreases gut permeability and motility, epithelial cell apoptosis, and inflammation. Outside the gut, GLP-2 reduces bone resorption, can suppress appetite, and is cytoprotective in the lung. Thus, GLP-2 has been studied intensively as a therapeutic to improve intestinal function of humans during parenteral nutrition and following small bowel resection and, more recently, as a treatment for osteoporosis and obesity-related disorders and to reduce cellular damage associated with inflammation of the gut and lungs. Recent studies demonstrate that many biological actions and properties of GLP-2 in ruminants are similar to those in nonruminants, including the potential to reduce intestinal nitro-oxidative stress in calves caused by parasitic diseases such as coccidiosis. Because of its beneficial impacts on nutrient absorption, gut healing, and normal gut development, GLP-2 therapy offers significant opportunities to improve calf health and production efficiency. However, GLP-2 therapies require an extended time course to achieve desired physiological responses, as well as daily administration because of the hormone's short half-life. Thus, practical means of administration and alternative strategies to enhance basal GLP-2 secretion (e.g., through specific feed additives), which are more likely to achieve consumer acceptance, are needed. Opportunities to address these challenges are discussed.

Nanoscale Packing Differences in Sphingomyelin and Phosphatidylcholine Revealed by BODIPY Fluorescence in Monolayers: Physiological Implications

PubMed Central

2015-01-01

Phosphatidycholines (PC) with two saturated acyl chains (e.g., dipalmitoyl) mimic natural sphingomyelin (SM) by promoting raft formation in model membranes. However, sphingoid-based lipids, such as SM, rather than saturated-chain PCs have been implicated as key components of lipid rafts in biomembranes. These observations raise questions about the physical packing properties of the phase states that can be formed by these two major plasma membrane lipids with identical phosphocholine headgroups. To investigate, we developed a monolayer platform capable of monitoring changes in surface fluorescence by acquiring multiple spectra during measurement of a lipid force–area isotherm. We relied on the concentration-dependent emission changes of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-labeled PC to detect nanoscale alterations in lipid packing and phase state induced by monolayer lateral compression. The BODIPY-PC probe contained an indacene ring with four symmetrically located methyl (Me) substituents to enhance localization to the lipid hydrocarbon region. Surface fluorescence spectra indicated changes in miscibility even when force–area isotherms showed no deviation from ideal mixing behavior in the surface pressure versus cross-sectional molecular area response. We detected slightly better mixing of Me4-BODIPY-8-PC with the fluid-like, liquid expanded phase of 1-palmitoyl-2-oleoyl-PC compared to N-oleoyl-SM. Remarkably, in the gel-like, liquid condensed phase, Me4-BODIPY-8-PC mixed better with N-palmitoyl-SM than dipalmitoyl-PC, suggesting naturally abundant SMs with saturated acyl chains form gel-like lipid phase(s) with enhanced ability to accommodate deeply embedded components compared to dipalmitoyl-PC gel phase. The findings reveal a fundamental difference in the lateral packing properties of SM and PC that occurs even when their acyl chains match. PMID:24564829

Properties of Ca2+ release induced by clofibric acid from the sarcoplasmic reticulum of mouse skeletal muscle fibres

PubMed Central

Ikemoto, Takaaki; Endo, Makoto

2001-01-01

To characterize the effect of clofibric acid (Clof) on the Ca2+ release mechanism in the sarcoplasmic reticulum (SR) of skeletal muscle, we analysed the properties of Clof-induced Ca2+ release under various conditions using chemically skinned skeletal muscle fibres of the mouse.Clof (>0.5 mM) released Ca2+ from the SR under Ca2+-free conditions buffered with 10 mM EGTA (pCa >8).Co-application of ryanodine and Clof at pCa >8 but not ryanodine alone reduced the Ca2+ uptake capacity of the SR. Thus, Ca2+ release induced by Clof at pCa >8 must be a result of the activation of the ryanodine receptor (RyR).At pCa >8, (i) Clof-induced Ca2+ release was inhibited by adenosine monophosphate (AMP), (ii) the inhibitory effect of Mg2+ on the Clof-induced Ca2+ release was saturated at about 1 mM, and (iii) Clof-induced Ca2+ release was not inhibited by procaine (10 mM). These results indicate that Clof may activate the RyR-Ca2+ release channels in a manner different from Ca2+-induced Ca2+ release (CICR).In addition to this unique mode of opening, Clof also enhanced the CICR mode of opening of RyR-Ca2+ release channels.Apart from CICR, a high concentration of Ca2+ might also enhance the unique mode of opening by Clof.These results suggest that some features of Ca2+ release activated by Clof are similar to those of physiological Ca2+ release (PCR) in living muscle cells and raise the possibility that Clof may be useful in elucidating the mechanism of PCR in skeletal muscle. PMID:11606311

Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic β-cell line.

PubMed

Mooranian, Armin; Negrulj, Rebecca; Arfuso, Frank; Al-Salami, Hani

2016-11-01

We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic β-cells. Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-α concentrations. CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels. The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment.

Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk-benefit.

PubMed

Heuberger, Jules A A C; Cohen Tervaert, Joost M; Schepers, Femke M L; Vliegenthart, Adriaan D B; Rotmans, Joris I; Daniels, Johannes M A; Burggraaf, Jacobus; Cohen, Adam F

2013-06-01

Imagine a medicine that is expected to have very limited effects based upon knowledge of its pharmacology and (patho)physiology and that is studied in the wrong population, with low-quality studies that use a surrogate end-point that relates to the clinical end-point in a partial manner at most. Such a medicine would surely not be recommended. The use of recombinant human erythropoietin (rHuEPO) to enhance performance in cycling is very common. A qualitative systematic review of the available literature was performed to examine the evidence for the ergogenic properties of this drug, which is normally used to treat anaemia in chronic renal failure patients. The results of this literature search show that there is no scientific basis from which to conclude that rHuEPO has performance-enhancing properties in elite cyclists. The reported studies have many shortcomings regarding translation of the results to professional cycling endurance performance. Additionally, the possibly harmful side-effects have not been adequately researched for this population but appear to be worrying, at least. The use of rHuEPO in cycling is rife but scientifically unsupported by evidence, and its use in sports is medical malpractice. What its use would have been, if the involved team physicians had been trained in clinical pharmacology and had investigated this properly, remains a matter of speculation. A single well-controlled trial in athletes in real-life circumstances would give a better indication of the real advantages and risk factors of rHuEPO use, but it would be an oversimplification to suggest that this would eradicate its use. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Exploring plant growth-promotion actinomycetes from vermicompost and rhizosphere soil for yield enhancement in chickpea

PubMed Central

Sreevidya, M.; Gopalakrishnan, S.; Kudapa, H.; Varshney, R.K.

2016-01-01

The main objective of the present study was to isolate and characterize actinomycetes for their plant growth-promotion in chickpea. A total of 89 actinomycetes were screened for their antagonism against fungal pathogens of chickpea by dual culture and metabolite production assays. Four most promising actinomycetes were evaluated for their physiological and plant growth-promotion properties under in vitro and in vivo conditions. All the isolates exhibited good growth at temperatures from 20 °C to 40 °C, pH range of 7–11 and NaCl concentrations up to 8%. These were also found highly tolerant to Bavistin, slightly tolerant to Thiram and Captan (except VAI-7 and VAI-40) but susceptible to Benlate and Ridomil at field application levels and were found to produce siderophore, cellulase, lipase, protease, chitinase (except VAI-40), hydrocyanic acid (except VAI-7 and VAI-40), indole acetic acid and β-1,3-glucanase. When the four actinomycetes were evaluated for their plant growth-promotion properties under field conditions on chickpea, all exhibited increase in nodule number, shoot weight and yield. The actinomycetes treated plots enhanced total N, available P and organic C over the un-inoculated control. The scanning electron microscope studies exhibited extensive colonization by actinomycetes on the root surface of chickpea. The expression profiles for indole acetic acid, siderophore and β-1,3-glucanase genes exhibited up-regulation for all three traits and in all four isolates. The actinomycetes were identified as Streptomyces but different species in the 16S rDNA analysis. It was concluded that the selected actinomycetes have good plant growth-promotion and biocontrol potentials on chickpea. PMID:26887230

Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.

PubMed

Cieniewski-Bernard, Caroline; Montel, Valerie; Berthoin, Serge; Bastide, Bruno

2012-01-01

O-N-acetylglucosaminylation is a reversible post-translational modification which presents a dynamic and highly regulated interplay with phosphorylation. New insights suggest that O-GlcNAcylation might be involved in striated muscle physiology, in particular in contractile properties such as the calcium activation parameters. By the inhibition of O-GlcNAcase, we investigated the effect of the increase of soleus O-GlcNAcylation level on the contractile properties by establishing T/pCa relationships. We increased the O-GlcNAcylation level on soleus biopsies performing an organ culture of soleus treated or not with PUGNAc or Thiamet-G, two O-GlcNAcase inhibitors. The enhancement of O-GlcNAcylation pattern was associated with an increase of calcium affinity on slow soleus skinned fibers. Analysis of the glycoproteins pattern showed that this effect is solely due to O-GlcNAcylation of proteins extracted from skinned biopsies. We also characterized the O-GlcNAcylated contractile proteins using a proteomic approach, and identified among others troponin T and I as being O-GlcNAc modified. We quantified the variation of O-GlcNAc level on all these identified proteins, and showed that several regulatory contractile proteins, predominantly fast isoforms, presented a drastic increase in their O-GlcNAc level. Since the only slow isoform of contractile protein presenting an increase of O-GlcNAc level was MLC2, the effect of enhanced O-GlcNAcylation pattern on calcium activation parameters could involve the O-GlcNAcylation of sMLC2, without excluding that an unidentified O-GlcNAc proteins, such as TnC, could be potentially involved in this mechanism. All these data strongly linked O-GlcNAcylation to the modulation of contractile activity of skeletal muscle.

Fabrication and characterization of highly porous barium titanate based scaffold coated by Gel/HA nanocomposite with high piezoelectric coefficient for bone tissue engineering applications.

PubMed

Ehterami, Arian; Kazemi, Mansure; Nazari, Bahareh; Saraeian, Payam; Azami, Mahmoud

2018-03-01

It is well established that the piezoelectric effect plays an important physiological role in bone growth, remodeling and fracture healing. Barium titanate, as a well-known piezoelectric ceramic, is especially an attractive material as a scaffold for bone tissue engineering applications. In this regard, we tried to fabricate a highly porous barium titanate based scaffolds by foam replication method and polarize them by applying an external electric field. In order to enhance the mechanical and biological properties, polarized/non-polarized scaffolds were coated with gelatin and nanostructured HA and characterized for their morphologies, porosities, piezoelectric and mechanical properties. The results showed that the compressive strength and piezoelectric coefficient of porous scaffolds increased with the increase of sintering temperature. After being coated with Gel/HA nanocomposite, the interconnected porous structure and pore size of the scaffolds almost remain unchanged while the Gel/nHA-coated scaffolds exhibited enhanced compressive strength and elastic modulus compared with the uncoated samples. Also, the effect of polarizing and coating of optimal scaffolds on adhesion, viability, and proliferation of the MG63 osteoblast-like cell line was evaluated by scanning electron microscope (SEM) and MTT assay. The cell culture experiments revealed that developed scaffolds had good biocompatibility and cells were able to adhere, proliferate and migrate into pores of the scaffolds. Furthermore, cell density was significantly higher in the coated scaffolds at all tested time-points. These results indicated that highly porous barium titanate scaffolds coated with Gel/HA nanocomposite has great potential in tissue engineering applications for bone tissue repair and regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila

PubMed Central

Achal, Madhulika; Trujillo, Adriana S.; Melkani, Girish C.; Farman, Gerrie P.; Ocorr, Karen; Viswanathan, Meera C.; Kaushik, Gaurav; Newhard, Christopher S.; Glasheen, Bernadette M.; Melkani, Anju; Suggs, Jennifer A.; Moore, Jeffrey R.; Swank, Douglas M.; Bodmer, Rolf; Cammarato, Anthony; Bernstein, Sanford I.

2016-01-01

An “invariant proline” separates the myosin S1 head from its S2 tail and is proposed to be critical for orienting S1 during its interaction with actin, a process that leads to muscle contraction. Mutation of the invariant proline to leucine (P838L) caused dominant restrictive cardiomyopathy in a pediatric patient (Karam et al., Congenit. Heart Dis. 3:138–43, 2008). Here, we use Drosophila melanogaster to model this mutation and dissect its effects on the biochemical and biophysical properties of myosin, as well as on the structure and physiology of skeletal and cardiac muscles. P838L mutant myosin isolated from indirect flight muscles of transgenic Drosophila showed elevated ATPase and actin sliding velocity in vitro. Furthermore, the mutant heads exhibited increased rotational flexibility, and there was an increase in the average angle between the two heads. Indirect flight muscle myofibril assembly was minimally affected in mutant homozygotes, and isolated fibers displayed normal mechanical properties. However, myofibrils degraded during aging, correlating with reduced flight abilities. In contrast, hearts from homozygotes and heterozygotes showed normal morphology, myofibrillar arrays, and contractile parameters. When P838L was placed in trans to Mhc5, an allele known to cause cardiac restriction in flies, it did not yield the constricted phenotype. Overall, our studies suggest that increased rotational flexibility of myosin S1 enhances myosin ATPase and actin sliding. Moreover, instability of P838L myofibrils leads to decreased function during aging of Drosophila skeletal muscle, but not cardiac muscle, despite the strong evolutionary conservation of the P838 residue. PMID:27107639

[Influence of physiologic 17 beta-estradiol concentrations on gene E6 expression in HVP type 18 in vitro].

PubMed

Dziubińska-Parol, Izabella; Gasowska, Urszula; Rzymowska, Jolanta; Kwaśniewska, Anna

2003-09-01

Many recent studies indicate that long term use of contraceptives is a strong risk factor in the development of cervical cancer. Steroid hormones, in persistent papilloma virus infection act on various levels, one of them is enhancing transforming activity of the virus. The aim of the study was to estimate if physiological concentrations of 17 beta-estradiol could influence expression of viral transforming genes. HeLa cell lines were incubated with three different physiological concentrations and and on the third day of incubation the level of E6 gene expression was determined. Results show no differences in expression between the control culter, and cultures incubated with physiological concentrations. It indicates that normal levels of 17 beta-estradiol don't play role in transforming process but it also shows need to analyse higher levels of hormones by quantitative analyses in prospective studies.

Computer support for physiological cell modelling using an ontology on cell physiology.

PubMed

Takao, Shimayoshi; Kazuhiro, Komurasaki; Akira, Amano; Takeshi, Iwashita; Masanori, Kanazawa; Tetsuya, Matsuda

2006-01-01

The development of electrophysiological whole cell models to support the understanding of biological mechanisms is increasing rapidly. Due to the complexity of biological systems, comprehensive cell models, which are composed of many imported sub-models of functional elements, can get quite complicated as well, making computer modification difficult. Here, we propose a computer support to enhance structural changes of cell models, employing the markup languages CellML and our original PMSML (physiological model structure markup language), in addition to a new ontology for cell physiological modelling. In particular, a method to make references from CellML files to the ontology and a method to assist manipulation of model structures using markup languages together with the ontology are reported. Using these methods three software utilities, including a graphical model editor, are implemented. Experimental results proved that these methods are effective for the modification of electrophysiological models.

Planning a sports training program using Adaptive Particle Swarm Optimization with emphasis on physiological constraints.

PubMed

Kumyaito, Nattapon; Yupapin, Preecha; Tamee, Kreangsak

2018-01-08

An effective training plan is an important factor in sports training to enhance athletic performance. A poorly considered training plan may result in injury to the athlete, and overtraining. Good training plans normally require expert input, which may have a cost too great for many athletes, particularly amateur athletes. The objectives of this research were to create a practical cycling training plan that substantially improves athletic performance while satisfying essential physiological constraints. Adaptive Particle Swarm Optimization using ɛ-constraint methods were used to formulate such a plan and simulate the likely performance outcomes. The physiological constraints considered in this study were monotony, chronic training load ramp rate and daily training impulse. A comparison of results from our simulations against a training plan from British Cycling, which we used as our standard, showed that our training plan outperformed the benchmark in terms of both athletic performance and satisfying all physiological constraints.

Physiological stability and renal clearance of ultrasmall zwitterionic gold nanoparticles: Ligand length matters

NASA Astrophysics Data System (ADS)

Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, Rodrigo D.; Yu, Mengxiao; Zheng, Jie

2017-05-01

Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.

Orderly recruitment of motor units under optical control in vivo.

PubMed

Llewellyn, Michael E; Thompson, Kimberly R; Deisseroth, Karl; Delp, Scott L

2010-10-01

A drawback of electrical stimulation for muscle control is that large, fatigable motor units are preferentially recruited before smaller motor units by the lowest-intensity electrical cuff stimulation. This phenomenon limits therapeutic applications because it is precisely the opposite of the normal physiological (orderly) recruitment pattern; therefore, a mechanism to achieve orderly recruitment has been a long-sought goal in physiology, medicine and engineering. Here we demonstrate a technology for reliable orderly recruitment in vivo. We find that under optical control with microbial opsins, recruitment of motor units proceeds in the physiological recruitment sequence, as indicated by multiple independent measures of motor unit recruitment including conduction latency, contraction and relaxation times, stimulation threshold and fatigue. As a result, we observed enhanced performance and reduced fatigue in vivo. These findings point to an unanticipated new modality of neural control with broad implications for nervous system and neuromuscular physiology, disease research and therapeutic innovation.

[Diastolic dysfunction in the elderly subjects. Disease or a physiological manifestation of ageing?].

PubMed

Meluzín, J; Podroužková, H; Gregorová, Z; Panovský, R

2013-05-01

The purpose of this summary paper is to discuss the current knowledge of the impact of age on diastolic function of the left ventricle. Data from the literature: Reports published till this time have convincingly demonstrated a significant relationship of age to diastolic function of the left ventricle. Ageing is a physiological process accompanied by structural changes in both myocardium and arterial bed resulting in worsening of parameters characterizing the left ventricular diastolic function. This "physiological" diastolic dysfunction in the elderly subjects can be explained by the deterioration of passive left ventricular filling properties and by worsening of left ventricular relaxation. The detailed analysis of published reports shows problems in distiguishing this "physiological" diastolic dysfunction resulting from physiological tissue ageing from "pathological" diastolic dysfunction reflecting a disease of cardiovascular system. To interprete correctly values of parameters quantifying diastolic function of the left ventricle, one should take into account the age of subjects under the examination. Further studies are necessary to distinguish exactly "physiological" deterioration of diastolic function associated with ageing from really "pathological" diastolic dysfunction in the elderly subjects.

Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

NASA Astrophysics Data System (ADS)

Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

2016-04-01

Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

EEG-based alpha neurofeedback training for mood enhancement.

PubMed

Phneah, Swee Wu; Nisar, Humaira

2017-06-01

The aim of this paper is to develop a preliminary neurofeedback system to improve the mood of the subjects using audio signals by enhancing their alpha brainwaves. Assessment of the effect of music on the human subjects is performed using three methods; subjective assessment of mood with the help of a questionnaire, the effect on brain by analysing EEG signals, and the effect on body by physiological assessment. In this study, two experiments have been designed. The first experiment was to determine the short-term effect of music on soothing human subjects, whereas the second experiment was to determine its long-term effect. Two types of music were used in the first experiment, the favourite music selected by the participants and a relaxing music with alpha wave binaural beats. The research findings showed that the relaxing music has a better soothing effect on the participants psychologically and physiologically. However, the one-way analysis of variance (ANOVA) results showed that the short-term soothing effect of both favourite music and relaxing music was not significant in changing the mean alpha absolute power and mean physiological measures (blood pressure and heart rate) at the significance level of 0.05. The second experiment was somewhat similar to an alpha neurofeedback training whereby the participants trained their brains to produce more alpha brainwaves by listening to the relaxing music with alpha wave binaural beats for a duration of 30 min daily. The results showed that the relaxing music has a long-term psychological and physiological effect on soothing the participants, as can be observed from the increase in alpha power and decrease in physiological measures after each session of training. The training was found to be effective in increasing the alpha power significantly [F(2,12) = 11.5458 and p = 0.0016], but no significant reduction in physiological measures was observed at the significance level of 0.05.

Graphene Sheet-Induced Global Maturation of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.

PubMed

Wang, Jiaxian; Cui, Chang; Nan, Haiyan; Yu, Yuanfang; Xiao, Yini; Poon, Ellen; Yang, Gang; Wang, Xijie; Wang, Chenchen; Li, Lingsong; Boheler, Kenneth Richard; Ma, Xu; Cheng, Xin; Ni, Zhenhua; Chen, Minglong

2017-08-09

Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, or physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate, which is a biocompatible and superconductive material. The hiPSCs lines were successfully maintained on the graphene sheets and were able to differentiate into functional cardiomyocytes. This strategy markedly increased the myofibril ultrastructural organization, elevated the conduction velocity, and enhanced both the Ca 2+ handling and electrophysiological properties in the absence of electrical stimulation. On the graphene substrate, the expression of connexin 43 increased along with the conduction velocity. Interestingly, the bone morphogenetic proteins signaling was also significantly activated during early cardiogenesis, confirmed by RNA sequencing analysis. Here, we reasoned that graphene substrate as a conductive biomimetic surface could facilitate the intrinsic electrical propagation, mimicking the microenvironment of the native heart, to further promote the global maturation of hiPSC-CMs. Our findings highlight the capability of electrically active substrates to influence cardiomyocyte development. We believe that application of graphene sheets will be useful for simple, fast, and scalable maturation of regenerated cardiomyocytes.

Discerning apical and basolateral properties of HT-29/B6 and IPEC-J2 cell layers by impedance spectroscopy, mathematical modeling and machine learning.

PubMed

Schmid, Thomas; Bogdan, Martin; Günzel, Dorothee

2013-01-01

Quantifying changes in partial resistances of epithelial barriers in vitro is a challenging and time-consuming task in physiology and pathophysiology. Here, we demonstrate that electrical properties of epithelial barriers can be estimated reliably by combining impedance spectroscopy measurements, mathematical modeling and machine learning algorithms. Conventional impedance spectroscopy is often used to estimate epithelial capacitance as well as epithelial and subepithelial resistance. Based on this, the more refined two-path impedance spectroscopy makes it possible to further distinguish transcellular and paracellular resistances. In a next step, transcellular properties may be further divided into their apical and basolateral components. The accuracy of these derived values, however, strongly depends on the accuracy of the initial estimates. To obtain adequate accuracy in estimating subepithelial and epithelial resistance, artificial neural networks were trained to estimate these parameters from model impedance spectra. Spectra that reflect behavior of either HT-29/B6 or IPEC-J2 cells as well as the data scatter intrinsic to the used experimental setup were created computationally. To prove the proposed approach, reliability of the estimations was assessed with both modeled and measured impedance spectra. Transcellular and paracellular resistances obtained by such neural network-enhanced two-path impedance spectroscopy are shown to be sufficiently reliable to derive the underlying apical and basolateral resistances and capacitances. As an exemplary perturbation of pathophysiological importance, the effect of forskolin on the apical resistance of HT-29/B6 cells was quantified.

Heterogeneous binary interactions of taste primaries: perceptual outcomes, physiology, and future directions.

PubMed

Wilkie, Lynn M; Capaldi Phillips, Elizabeth D

2014-11-01

Complex taste experiences arise from the combinations of five taste primaries. Here we review the literature on binary interactions of heterogeneous taste primaries, focusing on perceptual results of administering mixtures of aqueous solutions to human participants. Some interactions proved relatively consistent across tastants and experimental methods: sour acids enhanced saltiness, salts and sweeteners suppressed bitterness, sweeteners suppressed sourness, and sour acids enhanced bitterness. However, for the majority of interactions there were differential effects based on the tastants and their concentrations. Drawing conclusions about interactions with umami is currently not possible due to the low number of primary source studies investigating it and the confounding sodium ions in monosodium glutamate (MSG). Speculative physiological explanations are provided that fit the current data and suggestions for future research studies are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemotaxis towards autoinducer 2 mediates autoaggregation in Escherichia coli

PubMed Central

Laganenka, Leanid; Colin, Remy; Sourjik, Victor

2016-01-01

Bacteria communicate by producing and sensing extracellular signal molecules called autoinducers. Such intercellular signalling, known as quorum sensing, allows bacteria to coordinate and synchronize behavioural responses at high cell densities. Autoinducer 2 (AI-2) is the only known quorum-sensing molecule produced by Escherichia coli but its physiological role remains elusive, although it is known to regulate biofilm formation and virulence in other bacterial species. Here we show that chemotaxis towards self-produced AI-2 can mediate collective behaviour—autoaggregation—of E. coli. Autoaggregation requires motility and is strongly enhanced by chemotaxis to AI-2 at physiological cell densities. These effects are observed regardless whether cell–cell interactions under particular growth conditions are mediated by the major E. coli adhesin (antigen 43) or by curli fibres. Furthermore, AI-2-dependent autoaggregation enhances bacterial stress resistance and promotes biofilm formation. PMID:27687245

Tissue physiological metabolic adaptability in young and old leaves of reed (Phragmites communis) in Songnen grassland.

PubMed

Guo, Rui; Bai, Zhenzi; Zhou, Ji; Zhong, XiuLi; Gu, FengXue; Liu, Qi; Li, HaoRu

2018-07-01

Common reed (Phragmites communis) is widely distributed as the dominant plant species in the Songnen Plain of China. The aim of this study was to investigate different physiological adaptive mechanisms to salinity tolerance between young and old leaves. The profiles of 68 metabolites were measured and studied in reed leaves by gas chromatography-mass spectrometer. The nitrogen, carbon, and pigment contents showed stronger growth inhibition for older leaves with salinity stress. In young leaves, high K + contents not only promoted cell growth, but also prevented influx of superfluous Na + ions in cells; the Ca 2+ accumulation in old leaves implied that Ca 2+ triggered the SOS-Na + exclusion system and reduced Na + toxicity. Thus, the mechanism of enhanced tolerance differed between young and old leaves. The metabolite results indicated that the young and old leaves had different mechanisms of osmotic regulation; sugars/polyols and amino acids played important roles in developing salinity tolerance in young leaves but high contents of fatty acids were important for old leaves. These results implied dramatically enhanced sugars and amino acid synthesis but inhibited energy metabolism in young leaves. In contrast, fatty acid synthesis was enhanced in old leaves. The results extended our understanding of the differences in physiological metabolism in adaptive to the salt-alkalization of soil in Songnen grassland between young and old leaves of reeds. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Examining the effects of rational emotive behavior therapy on performance outcomes in elite paralympic athletes.

PubMed

Wood, A G; Barker, J B; Turner, M J; Sheffield, D

2018-01-01

Traditionally a psychotherapeutic intervention, rational emotive behavior therapy (REBT) is receiving increasing attention within the extant literature as an intervention to enhance the athletic performance and psychological well-being of competitive athletes. Whilst the benefits of REBT on psychological health are established, less is understood about the effects on athletic performance. This study aimed to examine the immediate and maintained effects of REBT on physiological, psychological, and performance outcomes with elite Paralympic athletes. Using a single-case research design, eight athletes recruited from the same Paralympic sport (M=40.12, SD=12.99) received five, one-to-one REBT sessions. Measures of irrational beliefs were collected weekly, whereas the remaining psychological and physiological measures were collected at a pre-, post-, and at a 9-month follow-up time point. Visual and statistical analyzes of the data indicates reductions in irrational beliefs were coupled with reductions in systolic blood pressure indicative of an adaptive physiological response, improved athletic performance during competition simulations, and reductions in avoidance goals. Furthermore, social validation data indicated greater self-awareness, emotional control, and enhanced focus during competition as a result of the REBT intervention. This study contributes to growing literature supporting the efficacy of REBT as an intervention that not only facilitates psychological health but also enhances athletic performance. Results are discussed with reference to theory, limitations, and future recommendations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

DTIC Science & Technology

2003-02-01

that intermittent androgen ablation therapy can be enhanced by finasteride , an inhibitor of T to DHT conversion, To test our hypothesis in animal...models, it is necessary to deliver exogenous T at physiologic levels and finasteride over a long period of time, We have worked out conditions to deliver T and finasteride in nude mice, which will allow us to test our hypothesis.

Enhancing Centrifugal Separation With Electrophoresis

NASA Technical Reports Server (NTRS)

Herrmann, F. T.

1986-01-01

Separation of biological cells by coil-planet centrifuge enhanced by electrophoresis. By itself, coil-planet centrifuge offers relatively gentle method of separating cells under low centrifugal force in physiological medium that keeps cells alive. With addition of voltage gradient to separation column of centrifuge, separation still gentle but faster and more complete. Since separation apparatus contains no rotary seal, probability of leakage, contamination, corrosion, and short circuits reduced.

Water deficit mechanisms in perennial shrubs Cerasus humilis leaves revealed by physiological and proteomic analyses.

PubMed

Yin, Zepeng; Ren, Jing; Zhou, Lijuan; Sun, Lina; Wang, Jiewan; Liu, Yulong; Song, Xingshun

2016-01-01

Drought (Water deficit, WD) poses a serious threat to extensively economic losses of trees throughout the world. Chinese dwarf cherry ( Cerasus humilis ) is a good perennial plant for studying the physiological and sophisticated molecular network under WD. The aim of this study is to identify the effect of WD on C. humilis through physiological and global proteomics analysis and improve understanding of the WD resistance of plants. Currently, physiological parameters were applied to investigate C. humilis response to WD. Moreover, we used two-dimensional gel electrophoresis (2DE) to identify differentially expressed proteins in C. humilis leaves subjected to WD (24 d). Furthermore, we also examined the correlation between protein and transcript levels. Several physiological parameters, including relative water content and Pn were reduced by WD. In addition, the malondialdehyde (MDA), relative electrolyte leakage (REL), total soluble sugar, and proline were increased in WD-treated C. humilis . Comparative proteomic analysis revealed 46 protein spots (representing 43 unique proteins) differentially expressed in C. humilis leaves under WD. These proteins were mainly involved in photosynthesis, ROS scavenging, carbohydrate metabolism, transcription, protein synthesis, protein processing, and nitrogen and amino acid metabolisms, respectively. WD promoted the CO 2 assimilation by increase light reaction and Calvin cycle, leading to the reprogramming of carbon metabolism. Moreover, the accumulation of osmolytes (i.e., proline and total soluble sugar) and enhancement of ascorbate-glutathione cycle and glutathione peroxidase/glutathione s-transferase pathway in leaves could minimize oxidative damage of membrane and other molecules under WD. Importantly, the regulation role of carbohydrate metabolisms (e. g. glycolysis, pentose phosphate pathways, and TCA) was enhanced. These findings provide key candidate proteins for genetic improvement of perennial plants metabolism under WD.

[Preliminary studies on physicochemical properties of Angelica sinensis polysaccharide-iron complex].

PubMed

Wang, Kai-ping; Zhang, Yu; Dai, Li-quan

2006-05-01

To study some physicochemical properties of Angelica sinensis polysaccharide-iron complex (APC). Based on the qualitatively identified reactions of iron (III), the qualitatively identified reactions of APC were found out by comparing hydroxide. The content of iron (III) in APC was determined with iodometry. The stability of APC under physiological pH conditions was judged by titrating APC with sodium hydroxide. The deoxidization of APC was tested with colorimetric analysis. APC showed the qualitatively identified reactions of iron (III). The content of iron (III) in APC ranged from 10% to 40%, and the water-solubility of APC was related to the content of iron (III). The complex was stable at physiological pH from 3 to 12, without precipitation and dissociation. At 37 degrees C, Fe (III) in the complex was completely reduced to Fe (III) by ascorbic acid in about 6 hours. APC can be qualitatively identified by using the qualitatively identified reactions of iron (III). When its iron (III) content is within 20%-25%, APC has a better ability to dissolve in water. And the complex is stable under physiological pH conditions.

The physiological rationale of heat and moisture exchangers in post-laryngectomy pulmonary rehabilitation: a review.

PubMed

Zuur, J K; Muller, S H; de Jongh, F H C; van Zandwijk, N; Hilgers, F J M

2006-01-01

Total laryngectomy results in a permanent disconnection of the upper and lower airways and inevitably leads to chronic pulmonary complaints like frequent involuntary coughing, increased sputum production and repeated daily forced expectoration to clean the airway. Heat and moisture exchangers (HMEs), applied in an attempt to compensate for the lost functions of the upper respiratory tract, have been found to diminish these symptoms and improve the quality of life significantly. An HME has three physical properties that might be responsible for these improvements. First, its heat and moisture exchanging capacity improves intra-airway preservation of heat and water. Since the condensation and evaporation of moisture are accompanied by the release and uptake of thermal energy, these parameters are inseparable. Secondly, the HME's resistance may reduce dynamic airway compression, thereby improving ventilation. Thirdly, to some extent, an HME might filter out particles, thereby cleaning inspiratory breathing air. This article summarizes our present knowledge of changes in respiratory physiology after total laryngectomy and the influence of the HME by reviewing the physiological impact of these three physical properties separately for in vitro and in vivo data.

Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles

PubMed Central

Iraci, Nunzio; Leonardi, Tommaso; Gessler, Florian; Vega, Beatriz; Pluchino, Stefano

2016-01-01

Extracellular vesicles (EVs) are a heterogeneous population of secreted membrane vesicles, with distinct biogenesis routes, biophysical properties and different functions both in physiological conditions and in disease. The release of EVs is a widespread biological process, which is conserved across species. In recent years, numerous studies have demonstrated that several bioactive molecules are trafficked with(in) EVs, such as microRNAs, mRNAs, proteins and lipids. The understanding of their final impact on the biology of specific target cells remains matter of intense debate in the field. Also, EVs have attracted great interest as potential novel cell-free therapeutics. Here we describe the proposed physiological and pathological functions of EVs, with a particular focus on their molecular content. Also, we discuss the advances in the knowledge of the mechanisms regulating the secretion of EV-associated molecules and the specific pathways activated upon interaction with the target cell, highlighting the role of EVs in the context of the immune system and as mediators of the intercellular signalling in the brain. PMID:26861302

Mapping Thermal Habitat of Ectotherms Based on Behavioral Thermoregulation in a Controlled Thermal Environment

NASA Astrophysics Data System (ADS)

Fei, T.; Skidmore, A.; Liu, Y.

2012-07-01

Thermal environment is especially important to ectotherm because a lot of physiological functions rely on the body temperature such as thermoregulation. The so-called behavioural thermoregulation function made use of the heterogeneity of the thermal properties within an individual's habitat to sustain the animal's physiological processes. This function links the spatial utilization and distribution of individual ectotherm with the thermal properties of habitat (thermal habitat). In this study we modelled the relationship between the two by a spatial explicit model that simulates the movements of a lizard in a controlled environment. The model incorporates a lizard's transient body temperatures with a cellular automaton algorithm as a way to link the physiology knowledge of the animal with the spatial utilization of its microhabitat. On a larger spatial scale, 'thermal roughness' of the habitat was defined and used to predict the habitat occupancy of the target species. The results showed the habitat occupancy can be modelled by the cellular automaton based algorithm at a smaller scale, and can be modelled by the thermal roughness index at a larger scale.

A general multiple-compartment model for the transport of trace elements through animals

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

Assimakopoulos, P.A.; Ioannides, K.G.; Pakou, A.A.

1991-08-01

Multiple-compartment models employed in the analysis of trace element transport in animals are often based on linear differential equations which relate the rate of change of contaminant (or contaminant concentration) in each compartment to the amount of contaminant (or contaminant concentration) in every other compartment in the system. This has the serious disadvantage of mixing intrinsic physiological properties with the geometry of the animal. The basic equations on which the model presented here is developed are derived from the actual physical process under way and are capable of separating intrinsic physiological properties from geometry. It is thus expected that ratemore » coefficients determined through this model will be applicable to a wider category of physiologically similar animals. A specific application of the model for the study of contamination of sheep--or indeed for any ruminant--is presented, and the temporal evolution of contaminant concentration in the various compartments of the animal is calculated. The application of this model to a system of compartments with changing geometry is also presented.« less

Effect of pitcher age on trapping efficiency and natural prey capture in carnivorous Nepenthes rafflesiana plants.

PubMed

Bauer, Ulrike; Willmes, Christoph; Federle, Walter

2009-06-01

Nepenthes pitchers are sophisticated traps that employ a variety of mechanisms to attract, capture and retain prey. The underlying morphological structures and physiological processes are subject to change over the lifetime of a pitcher. Here an investigation was carried out on how pitcher properties and capture efficiency change over the first 2 weeks after pitcher opening. Prey capture, trapping efficiency, extrafloral nectar secretion, pitcher odour, as well as pH and viscoelasticity of the digestive fluid in N. rafflesiana pitchers were monitored in the natural habitat from pitcher opening up to an age of 2 weeks. Pitchers not only increased their attractiveness over this period by becoming more fragrant and secreting more nectar, but also gained mechanical trapping efficiency via an enhanced wettability of the upper pitcher rim (peristome). Consistently, natural prey capture was initially low and increased 3-6 d after opening. It was, however, highly variable within and among pitchers. At the same time, the pH and viscoelasticity of the digestive fluid decreased, suggesting that the latter is not essential for effective prey capture. Prey capture and attraction by Nepenthes are dynamic processes strongly influenced by the changing properties of the pitcher. The results confirm insect aquaplaning on the peristome as the main capture mechanism in N. rafflesiana.

Silk Fibroin as Edible Coating for Perishable Food Preservation

NASA Astrophysics Data System (ADS)

Marelli, B.; Brenckle, M. A.; Kaplan, D. L.; Omenetto, F. G.

2016-05-01

The regeneration of structural biopolymers into micelles or nanoparticles suspended in water has enabled the design of new materials with unique and compelling properties that can serve at the interface between the biotic and the abiotic worlds. In this study, we leveraged silk fibroin quintessential properties (i.e. polymorphism, conformability and hydrophobicity) to design a water-based protein suspension that self-assembles on the surface of food upon dip coating. The water-based post-processing control of the protein polymorphism enables the modulation of the diffusion of gases through the silk fibroin thin membranes (e.g. O2 and CO2 diffusion, water vapour permeability), which is a key parameter to manage food freshness. In particular, an increased beta-sheet content corresponds to a reduction in oxygen diffusion through silk fibroin thin films. By using the dip coating of strawberries and bananas as proof of principle, we have shown that the formation of micrometre-thin silk fibroin membranes around the fruits helps the management of postharvest physiology of the fruits. Thus, silk fibroin coatings enhance fruits’ shelf life at room conditions by reducing cell respiration rate and water evaporation. The water-based processing and edible nature of silk fibroin makes this approach a promising alternative for food preservation with a naturally derived material.