The pathophysiology of heart failure.

PubMed

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

Inflammatory Mechanisms Linking Periodontal Diseases to Cardiovascular Diseases

PubMed Central

Schenkein, Harvey A.; Loos, Bruno G.

2015-01-01

Aims In this paper, inflammatory mechanisms that link periodontal diseases to cardiovascular diseases (CVD) are reviewed. Materials and Methods and Results This paper is a literature review. Studies in the literature implicate a number of possible mechanisms that could be responsible for increased inflammatory responses in atheromatous lesions due to periodontal infections. These include increased systemic levels of inflammatory mediators stimulated by bacteria and their products at sites distant from the oral cavity, elevated thrombotic and hemostatic markers that promote a prothrombotic state and inflammation, cross-reactive systemic antibodies that promote inflammation and interact with the atheroma, promotion of dyslipidemia with consequent increases in proinflammatory lipid classes and subclasses, and common genetic susceptibility factors present in both disease leading to increased inflammatory responses. Conclusions Such mechanisms may be thought to act in concert to increase systemic inflammation in periodontal disease and to promote or exacerbate atherogenesis. However, proof that the increase in systemic inflammation attributable to periodontitis impacts inflammatory responses during atheroma development, thrombotic events, or myocardial infarction or stroke is lacking. PMID:23627334

How does tissue regeneration influence the mechanical behavior of additively manufactured porous biomaterials?

PubMed

Hedayati, R; Janbaz, S; Sadighi, M; Mohammadi-Aghdam, M; Zadpoor, A A

2017-01-01

Although the initial mechanical properties of additively manufactured porous biomaterials are intensively studied during the last few years, almost no information is available regarding the evolution of the mechanical properties of implant-bone complex as the tissue regeneration progresses. In this paper, we studied the effects of tissue regeneration on the static and fatigue behavior of selective laser melted porous titanium structures with three different porosities (i.e. 77, 81, and 85%). The porous structures were filled with four different polymeric materials with mechanical properties in the range of those observed for de novo bone (0.7GPa

Quantifying the net economic benefits of mechanical wildfire hazard treatments on timberlands of the western United States

Treesearch

Jeffrey P. Prestemon; Karen L. Abt; James R. Barbour

2012-01-01

Mechanical treatment of vegetation is done on public and private lands for many possible reasons, including enhancing wildlife habitat, increasing timber growth of residual stands, and improving resistance to damaging pests. Few studies, however, have focused on the circumstances under which mechanical wildfire hazard reduction treatments can yield positive net...

The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

PubMed

Andrade, Jason; Khairy, Paul; Dobrev, Dobromir; Nattel, Stanley

2014-04-25

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

Spinal Cord Injury-Induced Osteoporosis: Pathogenesis and Emerging Therapies

PubMed Central

Battaglino, Ricardo A.; Lazzari, Antonio A.; Garshick, Eric; Morse, Leslie R.

2012-01-01

Spinal cord injury causes rapid, severe osteoporosis with increased fracture risk. Mechanical unloading after paralysis results in increased osteocyte expression of sclerostin, suppressed bone formation, and indirect stimulation of bone resorption. At this time there are no clinical guidelines to prevent bone loss after SCI and fractures are common. More research is required to define the pathophysiology and epidemiology of SCI-induced osteoporosis. This review summarizes emerging therapeutics including anti-sclerostin antibodies, mechanical loading of the lower extremity with electrical stimulation, and mechanical stimulation via vibration therapy. PMID:22983921

Environmental pollution and lung effects in children.

PubMed

Searing, Daniel A; Rabinovitch, Nathan

2011-06-01

Studies over the last 2 years have added important new information on the relationship between air pollution and asthma incidence and severity. Outdoor air pollution has been associated with asthma exacerbations, including emergency department visits and hospitalizations, as well as with the onset of asthma. Possible mechanisms mediating both incidence and severity effects include the induction of oxidative stress, and/or allergic sensitization, as well as increased susceptibility to viral infections. Some of these mechanisms may be occurring in utero including epigenetic changes that may increase risk for development of asthma. Factors related to increased susceptibility for air pollution-related asthma severity include age, season and genetic polymorphisms related to antioxidant enzymes. Ambient pollution levels may be associated with both asthma incidence and severity. Susceptibility to air pollution may be higher in children with genetic polymorphisms related to the 'oxidant stress pathways'. Potential interventions for susceptible children at risk for asthma development and/or severity include decreased exposure on high air pollution days, especially in the summer months, and antioxidant supplementation. On the population level, changes in school and home zoning to increase distance from busy roadways may help reduce both asthma incidence and severity.

Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies

PubMed Central

Meng, Ian D; Dodick, David; Ossipov, Michael H; Porreca, Frank

2017-01-01

Introduction Medication overuse headache (MOH) is a clinical concern in the management of migraine headache. MOH arises from the frequent use of medications used for the treatment of a primary headache. Medications that can cause MOH include opioid analgesics as well as formulations designed for the treatment of migraine, such as triptans, ergot alkaloids, or drug combinations that include caffeine and barbiturates. Literature review Gathering evidence indicates that migraine patients are more susceptible to development of MOH, and that prolonged use of these medications increases the prognosis for development of chronic migraine, leading to the suggestion that similar underlying mechanisms may drive both migraine headache and MOH. In this review, we examine the link between several mechanisms that have been linked to migraine headache and a potential role in MOH. For example, cortical spreading depression (CSD), associated with migraine development, is increased in frequency with prolonged use of topiramate or paracetamol. Conclusions Increased CGRP levels in the blood have been linked to migraine and elevated CGRP can be casued by prolonged sumatriptan exposure. Possible mechanisms that may be common to both migraine and MOH include increased endogenous facilitation of pain and/or diminished diminished endogenous pain inhibition. Neuroanatomical pathways mediating these effects are examined. PMID:21444643

Analysis of small crack behavior for airframe applications

NASA Technical Reports Server (NTRS)

Mcclung, R. C.; Chan, K. S.; Hudak, S. J., Jr.; Davidson, D. L.

1994-01-01

The small fatigue crack problem is critically reviewed from the perspective of airframe applications. Different types of small cracks-microstructural, mechanical, and chemical-are carefully defined and relevant mechanisms identified. Appropriate analysis techniques, including both rigorous scientific and practical engineering treatments, are briefly described. Important materials data issues are addressed, including increased scatter in small crack data and recommended small crack test methods. Key problems requiring further study are highlighted.

Cisplatin: mode of cytotoxic action and molecular basis of resistance.

PubMed

Siddik, Zahid H

2003-10-20

Cisplatin is one of the most potent antitumor agents known, displaying clinical activity against a wide variety of solid tumors. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of cisplatin-based chemotherapy. The mechanisms responsible for cisplatin resistance are several, and contribute to the multifactorial nature of the problem. Resistance mechanisms that limit the extent of DNA damage include reduced drug uptake, increased drug inactivation, and increased DNA adduct repair. Origins of these pharmacologic-based mechanisms, however, are at the molecular level. Mechanisms that inhibit propagation of the DNA damage signal to the apoptotic machinery include loss of damage recognition, overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3-K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and interference in caspase activation. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance.

Adenosine and preeclampsia.

PubMed

Salsoso, Rocío; Farías, Marcelo; Gutiérrez, Jaime; Pardo, Fabián; Chiarello, Delia I; Toledo, Fernando; Leiva, Andrea; Mate, Alfonso; Vázquez, Carmen M; Sobrevia, Luis

2017-06-01

Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters, or cell signalling mechanisms. This review summarizes the evidence available on the potential involvement of the adenosine in the clinical, pathophysiology, and therapeutic features of preeclampsia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thigmomorphogenesis: field and laboratory studies of Abies fraseri in response to wind or mechanical perturbation

NASA Technical Reports Server (NTRS)

Telewski, F. W.; Jaffe, M. J.

1986-01-01

Field- and greenhouse-grown Abies fraseri (Pursh) Poir. (Fraser fir) were analyzed for wind- or mechanically-induced flexure changes. These changes included inhibition of stem and needle elongation, reinforcement of branch bases around the stem, and increased radial growth in the direction of the mechanical perturbation (MP). Mature trees exposed to high wind conditions were severely flag-formed. These modified tree crowns had a lower drag than crowns of non-flag formed trees in wind-tunnel tests. In both field-grown and greenhouse-grown A. fraseri, MP induced a decrease in flexibility and increased elasticity of the stems. The increased radial growth of the stems overrode the increase in elasticity, resulting in the overall decrease in flexibility. The increase in radial growth caused by wind or mechanical flexure was due to greater cell divisions of the vascular cambium, resulting in increased numbers of tracheids. The decrease in stem elongation in these trees was due, at least in part, to a decrease in tracheid length. The potential biological and mechanical significance of these induced growth changes in trees are addressed. The data support the thigmomorphogenetic theory, which states that plants respond to wind and other mechanical perturbations in a way that is favorable to the plant for continued survival in windy environments.

Thigmomorphogenesis: field and laboratory studies of Abies fraseri in response to wind or mechanical perturbation.

PubMed

Telewski, F W; Jaffe, M J

1986-01-01

Field- and greenhouse-grown Abies fraseri (Pursh) Poir. (Fraser fir) were analyzed for wind- or mechanically-induced flexure changes. These changes included inhibition of stem and needle elongation, reinforcement of branch bases around the stem, and increased radial growth in the direction of the mechanical perturbation (MP). Mature trees exposed to high wind conditions were severely flag-formed. These modified tree crowns had a lower drag than crowns of non-flag formed trees in wind-tunnel tests. In both field-grown and greenhouse-grown A. fraseri, MP induced a decrease in flexibility and increased elasticity of the stems. The increased radial growth of the stems overrode the increase in elasticity, resulting in the overall decrease in flexibility. The increase in radial growth caused by wind or mechanical flexure was due to greater cell divisions of the vascular cambium, resulting in increased numbers of tracheids. The decrease in stem elongation in these trees was due, at least in part, to a decrease in tracheid length. The potential biological and mechanical significance of these induced growth changes in trees are addressed. The data support the thigmomorphogenetic theory, which states that plants respond to wind and other mechanical perturbations in a way that is favorable to the plant for continued survival in windy environments.

Regulation of platelet granule exocytosis by S-nitrosylation

PubMed Central

Morrell, Craig N.; Matsushita, Kenji; Chiles, Kelly; Scharpf, Robert B.; Yamakuchi, Munekazu; Mason, Rebecca J. A.; Bergmeier, Wolfgang; Mankowski, Joseph L.; Baldwin, William M.; Faraday, Nauder; Lowenstein, Charles J.

2005-01-01

Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and α-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis. PMID:15738422

Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease

PubMed Central

Dai, Dao-Fu; Chen, Tony; Johnson, Simon C.; Szeto, Hazel

2012-01-01

Abstract Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several “anti-aging” strategies that treat CVDs and improve healthy cardiac aging. PMID:22229339

Deconstructing Pancreas Developmental Biology

PubMed Central

Benitez, Cecil M.; Goodyer, William R.

2012-01-01

The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development. PMID:22587935

Biological mechanisms discriminating growth rate and adult body weight phenotypes in two Chinese indigenous chicken breeds.

PubMed

Dou, Tengfei; Zhao, Sumei; Rong, Hua; Gu, Dahai; Li, Qihua; Huang, Ying; Xu, Zhiqiang; Chu, Xiaohui; Tao, Linli; Liu, Lixian; Ge, Changrong; Te Pas, Marinus F W; Jia, Junjing

2017-06-20

Intensive selection has resulted in increased growth rates and muscularity in broiler chickens, in addition to adverse effects, including delayed organ development, sudden death syndrome, and altered metabolic rates. The biological mechanisms underlying selection responses remain largely unknown. Non-artificially-selected indigenous Chinese chicken breeds display a wide variety of phenotypes, including differential growth rate, body weight, and muscularity. The Wuding chicken breed is a fast growing large chicken breed, and the Daweishan mini chicken breed is a slow growing small chicken breed. Together they form an ideal model system to study the biological mechanisms underlying broiler chicken selection responses in a natural system. The objective of this study was to study the biological mechanisms underlying differential phenotypes between the two breeds in muscle and liver tissues, and relate these to the growth rate and body development phenotypes of the two breeds. The muscle tissue in the Wuding breed showed higher expression of muscle development genes than muscle tissue in the Daweishan chicken breed. This expression was accompanied by higher expression of acute inflammatory response genes in Wuding chicken than in Daweishan chicken. The muscle tissue of the Daweishan mini chicken breed showed higher expression of genes involved in several metabolic mechanisms including endoplasmic reticulum, protein and lipid metabolism, energy metabolism, as well as specific immune traits than in the Wuding chicken. The liver tissue showed fewer differences between the two breeds. Genes displaying higher expression in the Wuding breed than in the Daweishan breed were not associated with a specific gene network or biological mechanism. Genes highly expressed in the Daweishan mini chicken breed compared to the Wuding breed were enriched for protein metabolism, ABC receptors, signal transduction, and IL6-related mechanisms. We conclude that faster growth rates and larger body size are related to increased expression of genes involved in muscle development and immune response in muscle, while slower growth rates and smaller body size are related to increased general cellular metabolism. The liver of the Daweishan breed displayed increased expression of metabolic genes.

Soil Penetration by Earthworms and Plant Roots—Mechanical Energetics of Bioturbation of Compacted Soils

PubMed Central

2015-01-01

We quantify mechanical processes common to soil penetration by earthworms and growing plant roots, including the energetic requirements for soil plastic displacement. The basic mechanical model considers cavity expansion into a plastic wet soil involving wedging by root tips or earthworms via cone-like penetration followed by cavity expansion due to pressurized earthworm hydroskeleton or root radial growth. The mechanical stresses and resulting soil strains determine the mechanical energy required for bioturbation under different soil hydro-mechanical conditions for a realistic range of root/earthworm geometries. Modeling results suggest that higher soil water content and reduced clay content reduce the strain energy required for soil penetration. The critical earthworm or root pressure increases with increased diameter of root or earthworm, however, results are insensitive to the cone apex (shape of the tip). The invested mechanical energy per unit length increase with increasing earthworm and plant root diameters, whereas mechanical energy per unit of displaced soil volume decreases with larger diameters. The study provides a quantitative framework for estimating energy requirements for soil penetration work done by earthworms and plant roots, and delineates intrinsic and external mechanical limits for bioturbation processes. Estimated energy requirements for earthworm biopore networks are linked to consumption of soil organic matter and suggest that earthworm populations are likely to consume a significant fraction of ecosystem net primary production to sustain their subterranean activities. PMID:26087130

Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

PubMed Central

Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

2016-01-01

Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma.

PubMed

Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

2016-01-01

Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.

Effects of prebiotics on mineral absorption: mechanisms of action

USDA-ARS?s Scientific Manuscript database

There is extensive evidence in experimental animals that prebiotics, such as inulin-type fructans, can increase the absorption of a variety of minerals, including calcium, magnesium, iron, and zinc, and that they may act through several possible mechanisms. The purpose of this review is to discuss t...

Distinct mechanisms of the ORANGE protein in controlling carotenoid flux in melon fruit

USDA-ARS?s Scientific Manuscript database

Beta-carotene adds nutritious value and determines the color of many fruits including melon. In melon mesocarp, beta-carotene accumulation is governed by the Orange gene (CmOr) ‘golden’ SNP through a yet to be discovered mechanism. In Arabidopsis, OR increases carotenoid levels by posttranscriptiona...

Modeling Near-Crack-Tip Plasticity from Nano- to Micro-Scales

NASA Technical Reports Server (NTRS)

Glaessgen, Edward H.; Saether, Erik; Hochhalter, Jake D.; Yamakov, Vesselin I.

2010-01-01

Several efforts that are aimed at understanding the plastic deformation mechanisms related to crack propagation at the nano-, meso- and micro-length scales including atomistic simulation, discrete dislocation plasticity, strain gradient plasticity and crystal plasticity are discussed. The paper focuses on discussion of newly developed methodologies and their application to understanding damage processes in aluminum and its alloys. Examination of plastic mechanisms as a function of increasing length scale illustrates increasingly complex phenomena governing plasticity

Epigenetics in Paediatric Gastroenterology, Hepatology, and Nutrition: Present Trends and Future Perspectives.

PubMed

Zilbauer, Matthias; Zellos, Aglaia; Heuschkel, Robert; Gasparetto, Marco; Kraiczy, Judith; Postberg, Jan; Greco, Luigi; Auricchio, Renata; Galatola, Martina; Embleton, Nicholas; Wirth, Stefan; Jenke, Andreas

2016-04-01

Epigenetics can be defined as stable, potentially heritable changes in the cellular phenotype caused by mechanisms other than alterations to the underlying DNA sequence. As such, any observed phenotypic changes including organ development, aging, and the occurrence of disease could be driven by epigenetic mechanisms in the presence of stable cellular DNA sequences. Indeed, with the exception of rare mutations, the human genome-sequence has remained remarkably stable over the past centuries. In contrast, substantial changes to our environment as part of our modern life style have not only led to a significant reduction of certain infectious diseases but also seen the exponential increase in complex traits including obesity and multifactorial diseases such as autoimmune disorders. It is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment, and a large body of existing evidence supports the importance of environmental factors such as diet and nutrition, infections, and exposure to toxins on human health. This seems to be particularly the case during vulnerable periods of human development such as pregnancy and early life. Importantly, as the first point of contact for many of such environmental factors including nutrition, the digestive system is being increasingly linked to a number of "modern" pathologies. In this review article, we aim to give a brief introduction to the basic molecular principals of epigenetics and provide a concise summary of the existing evidence for the role of epigenetic mechanisms in gastrointestinal health and disease, hepatology, and nutrition.

Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

PubMed

Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

2016-06-01

Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

Mechanisms of northeastern Brazil rainfall anomalies due to Southern Tropical Atlantic variability

NASA Astrophysics Data System (ADS)

Neelin, J.; Su, H.

2004-05-01

Observational studies have shown that the rainfall anomalies in eastern equatorial South America, including Nordeste Brazil, have a positive correlation with tropical southern Atlantic sea surface temperature (SST) anomalies. Such relationships are reproduced in model simulations with the quasi-equilibrium tropical circulation model (QTCM), which includes a simple land model. A suite of model ensemble experiments is analysed using observed SST over the tropical oceans, the tropical Atlantic and the tropical southern Atlantic (30S-0), respectively (with climatological SST in the remainder of the oceans). Warm tropical south Atlantic SST anomalies yield positive precipitation anomalies over the Nordeste and the southern edge of the Atlantic marine intertropical convergence zone (ITCZ). Mechanisms associated with moisture variations are responsible for the land precipitation changes. Increases in moisture over the Atlantic cause positive anomalies in moisture advection, spreading increased moisture downwind. Where the basic state is far from the convective stability threshold, moisture changes have little effect, but the margins of the climatological convection zone are affected. The increased moisture supply due to advection is enhanced by increases in low-level convergence required by moist static energy balances. The moisture convergence term is several times larger, but experiments altering the moisture advection confirm that the feedback is initiated by wind acting on moisture gradient. This mechanism has several features in common with the recently published "upped-ante" mechanism for El Nino impacts on this region. In that case, the moisture gradient is initiated by warm free tropospheric temperature anomalies increasing the typical value of low-level moisture required to sustain convection in the convection zones. Both mechanisms suggest the usefulness of coordinating ocean and land in situ observations of boundary layer moisture.

Respiratory Mechanics and Plasma Levels of Tumor Necrosis Factor Alpha and Interleukin 6 Are Affected by Gas Humidification during Mechanical Ventilation in Dogs

PubMed Central

Hernández-Jiménez, Claudia; García-Torrentera, Rogelio; Olmos-Zúñiga, J. Raúl; Jasso-Victoria, Rogelio; Gaxiola-Gaxiola, Miguel O.; Baltazares-Lipp, Matilde; Gutiérrez-González, Luis H.

2014-01-01

The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation. PMID:25036811

Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

PubMed

Hernández-Jiménez, Claudia; García-Torrentera, Rogelio; Olmos-Zúñiga, J Raúl; Jasso-Victoria, Rogelio; Gaxiola-Gaxiola, Miguel O; Baltazares-Lipp, Matilde; Gutiérrez-González, Luis H

2014-01-01

The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

Eucalyptus tolerance mechanisms to lanthanum and cerium: subcellular distribution, antioxidant system and thiol pools.

PubMed

Shen, Yichang; Zhang, Shirong; Li, Sen; Xu, Xiaoxun; Jia, Yongxia; Gong, Guoshu

2014-12-01

Guanglin 9 (Eucalyptus grandis × Eucalyptus urophlla) and Eucalyptus grandis 5 are two eucalyptus species which have been found to grow normally in soils contaminated with lanthanum and cerium, but the tolerance mechanisms are not clear yet. In this study, a pot experiment was conducted to investigate the tolerance mechanisms of the eucalyptus to lanthanum and cerium. Cell walls stored 45.40-63.44% of the metals under lanthanum or cerium stress. Peroxidase and catalase activities enhanced with increasing soil La or Ce concentrations up to 200 mg kg(-1), while there were no obvious changes in glutathione and ascorbate concentrations. Non-protein thiols concentrations increased with increasing treatment levels up to 200 mg kg(-1), and then decreased. Phytochelatins concentrations continued to increase under La or Ce stress. Therefore, the two eucalyptus species are La and Ce tolerant plants, and the tolerance mechanisms include cell wall deposition, antioxidant system response, and thiol compound synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vivo quantification of spatially-varying mechanical properties in developing tissues

PubMed Central

Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Kealhofer, David A.; Lucio, Adam A.; Hockenbery, Zachary M.; Campàs, Otger

2017-01-01

It is generally believed that the mechanical properties of the cellular microenvironment and their spatiotemporal variations play a central role in sculpting embryonic tissues, maintaining organ architecture and controlling cell behavior, including cell differentiation. However, no direct in vivo and in situ measurement of mechanical properties within developing 3D tissues and organs has been performed yet. Here we introduce a technique that employs biocompatible ferrofluid microdroplets as local mechanical actuators and allows quantitative spatiotemporal measurements of mechanical properties in vivo. Using this technique, we show that vertebrate body elongation entails spatially-varying tissue mechanics along the anteroposterior axis. Specifically, we find that the zebrafish tailbud is viscoelastic (elastic below a few seconds and fluid after just one minute) and displays decreasing stiffness and increasing fluidity towards its posterior elongating region. This method opens new avenues to study mechanobiology in vivo, both in embryogenesis and in disease processes, including cancer. PMID:27918540

Mechanical properties experimental investigation of HTPB propellant after thermal accelerated aging

NASA Astrophysics Data System (ADS)

Yang, Xiaohong; Sun, Chaoxiang; Zhang, Junfa; Xu, Jinsheng; Tan, Bingdong

2017-04-01

To get accurate aging mechanical properties of aged HTPB propellant, the thermal accelerated aging experiment method is utilized and the uniaxial tensile experiments were conducted to obtain the mechanical data of aged HTPB propellants, and the maximum tensile strength, σm, maximum tensile strain, ɛm, and the fracture tensile strain, ɛb, of HTPB propellant with different aging time and various aging temperatures,were obtained, using universal material testing machine. The experimental results show that the σm of HTPB propellant initially increases, subsequently decreases and finally increases with aging time. The ɛm and ɛb generally decrease with increasing aging time, what's more, the decrease rate of both ɛm and ɛb reduce with the aging time. What's more, the postcure effect and oxidation reaction occurred inside HTPB matrix, including the chain degradation reaction and oxidation-induced crosslinking, were discussed to explain the mechanical aging rule of HTPB propellant.

Strengthening of Aluminum Alloy 2219 by Thermo-mechanical Treatment

NASA Astrophysics Data System (ADS)

Li, Xifeng; Lei, Kun; Song, Peng; Liu, Xinqin; Zhang, Fei; Li, Jianfei; Chen, Jun

2015-10-01

Strengthening of aluminum alloy 2219 by thermo-mechanical treatment has been compared with artificial aging. Three simple deformation modes including pre-stretching, compression, and rolling have been used in thermo-mechanical treatment. The tensile strength, elongation, fracture feature, and precipitated phase have been investigated. The results show that the strengthening effect of thermo-mechanical treatment is better than the one of artificial aging. Especially, the yield strength significantly increases with a small decrease of elongation. When the specimen is pre-stretched to 8.0%, the yield strength reaches 385.0 MPa and increases by 22.2% in comparison to the one obtained in aging condition. The maximum tensile strength of 472.4 MPa is achieved with 4.0% thickness reduction by compression. The fracture morphology reveals locally ductile and brittle failure mechanism, while the coarse second-phase particles distribute on the fracture surface. The intermediate phases θ″ or θ' orthogonally precipitate in the matrix after thermo-mechanical treatment. As compared to artificial aging, the cold plastic deformation increases distribution homogeneity and the volume fraction of θ'' or θ' precipitates. These result in a better strengthening effect.

Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model.

PubMed

Kerckhoffs, Roy C P; Omens, Jeffrey H; McCulloch, Andrew D; Mulligan, Lawrence J

2010-07-01

Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97+/-0.004, 0.010+/-0.002, and 78+/-1 milliseconds, respectively. With dilation alone, CURE decreased 2.0+/-0.07%, ISF increased 58+/-47%, and WTpeak increased 31+/-3%. With dyssynchronous activation alone, CURE decreased 15+/-0.6%, ISF increased 14-fold (+/-3), and WTpeak increased 121+/-4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23+/-0.8%, ISF increased 20-fold (+/-5), and WTpeak increased 147+/-5%. Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.

Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms

PubMed Central

Van Lieshout, Ryan J.; Voruganti, Lakshmi P.

2008-01-01

Objective To identify converging themes from the neurodevelopmental hypothesis of schizophrenia and the pathophysiology of diabetic pregnancy and to examine mechanisms by which diabetes mellitus in a pregnant mother may increase the risk of schizophrenia in offspring. Methods We reviewed relevant publications on clinical, epidemiologic and animal studies of diabetic pregnancy and the neurodevelopmental aspects of schizophrenia. Results Epidemiologic studies have shown that the offspring of mothers who experienced diabetes mellitus during their pregnancies are 7 times more likely to develop schizophrenia, compared with those who were not exposed to diabetic pregnancy. Maternal hyperglycemia during pregnancy could predispose to schizophrenia in adult life through at least 3 prenatal mechanisms: hypoxia, oxidative stress and increased inflammation. Hyperglycemia increases oxidative stress, alters lipid metabolism, affects mitochondrial structure, causes derangements in neural cell processes and neuronal architecture and results in premature specialization before neural tube closure. The molecular mechanisms underlying these processes include the generation of excess oxyradicals and lipid peroxide intermediates as well as reductions in levels of polyunsaturated fatty acids that are known to cause increased dopaminergic and lowered γ-aminobutyric acidergic activity. The combination of hyperglycemia and hypoxia in pregnancy also leads to altered immune function including increased tumour necrosis factor-α, C-reactive protein and upregulation of other proinflammatory cytokines. Finally, maternal hyperglycemia could have a lasting impact on fetal cellular physiology, resulting in increased vulnerability to stress and predisposition to schizophrenia via a mechanism known as programming. These prenatal events can also result in obstetric complications such as fetal growth abnormalities and increased susceptibility to prenatal infection, all of which are associated with a spectrum of neurodevelopmental anomalies and an enhanced risk of schizophrenia. Conclusion On the basis of the evidence presented and taking into consideration the projected increases in the rates of diabetes mellitus among younger women of child-bearing potential, it is imperative that the neurodevelopmental sequelae of diabetic pregnancy in general, and the increased risk for schizophrenia in particular, receive further study. PMID:18787655

Increased atmospheric carbon dioxide and climate feedback mechanisms

NASA Technical Reports Server (NTRS)

Cess, R. D.

1982-01-01

As a consequence of fossil fuel burning, the atmospheric concentration of carbon dioxide has increased from 314 ppm in 1958, when detailed measurements of this quantity began, to a present value of 335 ppm; and it is estimated that during the next century, the CO2 concentration will double relative to its assumed preindustrial value of 290 ppm. Since CO2 is an infrared-active gas, increases in its atmospheric concentration would lead to a larger infrared opacity for the atmospheric which, by normal logic, would result in a warmer Earth. A number of modeling endeavors suggest a 2 to 4 C increase in global mean surface temperature with doubling of the CO2 concentration. But such estimates of CO2-induced warming are highly uncertain because of a lack of knowledge of climate feedback mechanisms. Interactive influences upon the solar and infrared opacities of the Earth-atmosphere system can either amplify or damp a climate-forcing mechanism such as increasing CO2. Climate feedback mechanisms discussed include climate sensitivity, cloudiness-radiation feedback, climate change predictions, and interactive atmospheric chemistry.

How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.

PubMed

de Goeij, Moniek C M; Suhrcke, Marc; Toffolutti, Veronica; van de Mheen, Dike; Schoenmakers, Tim M; Kunst, Anton E

2015-04-01

Economic crises are complex events that affect behavioral patterns (including alcohol consumption) via opposing mechanisms. With this realist systematic review, we aimed to investigate evidence from studies of previous or ongoing crises on which mechanisms (How?) play a role among which individuals (Whom?). Such evidence would help understand and predict the potential impact of economic crises on alcohol consumption. Medical, psychological, social, and economic databases were used to search for peer-reviewed qualitative or quantitative empirical evidence (published January 1, 1990-May 1, 2014) linking economic crises or stressors with alcohol consumption and alcohol-related health problems. We included 35 papers, based on defined selection criteria. From these papers, we extracted evidence on mechanism(s), determinant, outcome, country-level context, and individual context. We found 16 studies that reported evidence completely covering two behavioral mechanisms by which economic crises can influence alcohol consumption and alcohol-related health problems. The first mechanism suggests that psychological distress triggered by unemployment and income reductions can increase drinking problems. The second mechanism suggests that due to tighter budget constraints, less money is spent on alcoholic beverages. Across many countries, the psychological distress mechanism was observed mainly in men. The tighter budget constraints mechanism seems to play a role in all population subgroups across all countries. For the other three mechanisms (i.e., deterioration in the social situation, fear of losing one's job, and increased non-working time), empirical evidence was scarce or absent, or had small to moderate coverage. This was also the case for important influential contextual factors described in our initial theoretical framework. This realist systematic review suggests that among men (but not among women), the net impact of economic crises will be an increase in harmful drinking. Such a different net impact between men and women could potentially contribute to growing gender-related health inequalities during a crisis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanical Signaling for Bone Modeling and Remodeling

PubMed Central

Robling, Alexander G.; Turner, Charles H.

2012-01-01

Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. The cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis. PMID:19817708

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

PubMed

Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

2017-08-01

The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

Optical measurement of arterial mechanical properties: from atherosclerotic plaque initiation to rupture

NASA Astrophysics Data System (ADS)

Nadkarni, Seemantini K.

2013-12-01

During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future.

Clinical and laboratory evaluation of microstructural changes in the physical, mechanical and chemical properties of dental filling materials under the influence of an electromagnetic field.

PubMed

Moiseeva, Natalia S; Kunin, Anatoly A

2018-03-01

Restorative filling materials used for dental caries prevention and treatment consist of various components including monomers or oligomers, which play a significant role in forming the main structure of these materials, as well as in characterising their physical, mechanical and chemical properties. The necessity for the development and improvement of structural characteristics of polymeric dental filling materials intended for caries prevention and their life duration increase served as the initiating factor of our research. According to the research purpose and challenges, we studied the changes in the physical, mechanical and chemical properties of composite filling materials with and without electromagnetic field influence. The investigations in vivo include the study of microstructural features of polymeric filling materials by scanning electron microscopy (SEM) and the investigations in vitro include the study of sealed and extracted human teeth chips by using X-ray spectral analysis. We also evaluated the changes in the strength characteristics of dental filling materials with and without electromagnetic field influence. The analysis of the obtained data indicates the presence of structural changes in polymeric dental filling materials, including the material microstructure condensation confirmed by the SEM results, an increase in the strength and adhesion characteristics and certain regularities of the chemical elemental composition concentration change in the area of hard tooth tissue and dental filling material. These scientific data will provide tooth caries prevention and promote the increase of treatment quality.

Mineralocorticoid-induced sodium appetite and renal salt retention: Evidence for common signaling and effector mechanisms

PubMed Central

Fu, Yiling; Vallon, Volker

2014-01-01

An increase in renal sodium chloride (salt) retention and an increase in sodium appetite is the body's response to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum-and-glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC. PMID:25376899

Mechanically dynamic PDMS substrates to investigate changing cell environments

PubMed Central

Yeh, Yi-Cheun; Corbin, Elise A.; Caliari, Steven R.; Ouyang, Liu; Vega, Sebastián L.; Truitt, Rachel; Han, Lin; Margulies, Kenneth B.; Burdick, Jason A.

2018-01-01

Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ~1300 to 1900 μm2 and from ~2700 to 4600 μm2 for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ~2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM. PMID:28843064

Mechanically dynamic PDMS substrates to investigate changing cell environments.

PubMed

Yeh, Yi-Cheun; Corbin, Elise A; Caliari, Steven R; Ouyang, Liu; Vega, Sebastián L; Truitt, Rachel; Han, Lin; Margulies, Kenneth B; Burdick, Jason A

2017-11-01

Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ∼1300 to 1900 μm 2 and from ∼2700 to 4600 μm 2 for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ∼2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sources, factors, mechanisms and possible solutions to pollutants in marine ecosystems.

PubMed

Mostofa, Khan M G; Liu, Cong-Qiang; Vione, Davide; Gao, Kunshan; Ogawa, Hiroshi

2013-11-01

Algal toxins or red-tide toxins produced during algal blooms are naturally-derived toxic emerging contaminants (ECs) that may kill organisms, including humans, through contaminated fish or seafood. Other ECs produced either naturally or anthropogenically ultimately flow into marine waters. Pharmaceuticals are also an important pollution source, mostly due to overproduction and incorrect disposal. Ship breaking and recycle industries (SBRIs) can also release various pollutants and substantially deteriorate habitats and marine biodiversity. Overfishing is significantly increasing due to the global food crisis, caused by an increasing world population. Organic matter (OM) pollution and global warming (GW) are key factors that exacerbate these challenges (e.g. algal blooms), to which acidification in marine waters should be added as well. Sources, factors, mechanisms and possible remedial measures of these challenges to marine ecosystems are discussed, including their eventual impact on all forms of life including humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gastroesophageal reflux disease and non-digestive tract diseases.

PubMed

Chen, Ying

2015-05-01

Over the past decade, incidence of gastroesophageal reflux disease (GERD) showed an increasing trend resulting from factors, including lifestyle and dietary habits; however, both etiology and pathological mechanisms remain controversial. GERD occurs as a result of a variety of mechanisms and there is no single factor. Symptoms of GERD are often non-typical, with a likelihood of being overlooked by non-gastroenterology professionals. Therefore, improving GERD awareness in non-gastroenterology practitioners, along with early diagnosis and treatment, provide potential benefit to clinicians and patients alike. Increasing evidence suggests GERD has specific connections with a variety of non-digestive tract conditions, may contribute an aggravating compounding effect on other diseases, prolong hospitalization, and increase subsequent medical costs. This review considers and emphasizes the association between GERD and non-digestive tract conditions, including atrial fibrillation, chronic obstructive pulmonary disease, primary pulmonary fibrosis and energy metabolism related to diet.

The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant

PubMed Central

Yu, Lu; Yang, Fei; Luo, Hao; Liu, Feng-Yu; Han, Ji-Sheng; Xing, Guo-Gang; Wan, You

2008-01-01

Background The present study aims to investigate the role of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons in chronic pain including thermal hyperalgesia and mechanical allodynia. Chronic inflammatory nociception of rats was produced by intraplantar injection of complete Freund's adjuvant (CFA) and data was collected until day 28 following injection. Results Thermal hyperalgesia was evident from day 1 to day 28 with peak at day 7, while mechanical allodynia persisted from day 1 to day 14 and was greatest at day 7. Intrathecal administration of AMG 9810 at day 7, a selective TRPV1 antagonist, significantly reduced thermal hyperalgesia and mechanical allodynia. TRPV1 expression in DRG detected by Western blotting was increased relative to baseline throughout the observation period. Double labeling of TRPV1 with neuronal marker neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4) was used to distinguish different subtypes of DRG neurons. TRPV1 expression was increased in the medium-sized myelinated A fiber (NF200 positive) neurons and in small non-peptidergic (IB4 positive) neurons from day 1 to day 14 and was increased in small peptidergic (CGRP positive) neurons from day 1 to day 28. Conclusion TRPV1 expression increases in all three types of DRG neurons after CFA injection and plays a role in CFA-induced chronic inflammatory pain including thermal hyperalgesia and mechanical allodynia. PMID:19055783

Mechanisms of diabetes mellitus-induced bone fragility.

PubMed

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D; Abrahamsen, Bo; Schwartz, Ann V; Ferrari, Serge L

2017-04-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

The antimicrobial activity of nanoparticles: present situation and prospects for the future

PubMed Central

Wang, Linlin; Hu, Chen; Shao, Longquan

2017-01-01

Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed. PMID:28243086

Quorum sensing and microbial drug resistance.

PubMed

Chen, Yu-fan; Liu, Shi-yin; Liang, Zhi-bin; Lv, Ming-fa; Zhou, Jia-nuan; Zhang, Lian-hui

2016-10-20

Microbial drug resistance has become a serious problem of global concern, and the evolution and regulatory mechanisms of microbial drug resistance has become a hotspot of research in recent years. Recent studies showed that certain microbial resistance mechanisms are regulated by quorum sensing system. Quorum sensing is a ubiquitous cell-cell communication system in the microbial world, which associates with cell density. High-density microbial cells produce sufficient amount of small signal molecules, activating a range of downstream cellular processes including virulence and drug resistance mechanisms, which increases bacterial drug tolerance and causes infections on host organisms. In this review, the general mechanisms of microbial drug resistance and quorum-sensing systems are summarized with a focus on the association of quorum sensing and chemical signaling systems with microbial drug resistance mechanisms, including biofilm formation and drug efflux pump. The potential use of quorum quenching as a new strategy to control microbial resistance is also discussed.

Microfluidic strategies for understanding the mechanics of cells and cell-mimetic systems

PubMed Central

Dahl, Joanna B.; Lin, Jung-Ming G.; Muller, Susan J.; Kumar, Sanjay

2016-01-01

Microfluidic systems are attracting increasing interest for the high-throughput measurement of cellular biophysical properties and for the creation of engineered cellular microenvironments. Here we review recent applications of microfluidic technologies to the mechanics of living cells and synthetic cell-mimetic systems. We begin by discussing the use of microfluidic devices to dissect the mechanics of cellular mimics such as capsules and vesicles. We then explore applications to circulating cells, including erythrocytes and other normal blood cells, and rare populations with potential disease diagnostic value, such as circulating tumor cells. We conclude by discussing how microfluidic devices have been used to investigate the mechanics, chemotaxis, and invasive migration of adherent cells. In these ways, microfluidic technologies represent an increasingly important toolbox for investigating cellular mechanics and motility at high throughput and in a format that lends itself to clinical translation. PMID:26134738

Mechanochemical activation and patterning of an adhesive surface toward nanoparticle deposition.

PubMed

Baytekin, H Tarik; Baytekin, Bilge; Huda, Sabil; Yavuz, Zelal; Grzybowski, Bartosz A

2015-02-11

Mechanical pulling of adhesive tape creates radicals on the tape's surface. These radicals are capable of reducing metal salts to the corresponding metal nanoparticles. In this way, the mechanically activated tape can be decorated with various types of nanoparticles, including Au, Ag, Pd, or Cu. While retaining their mechanical properties and remaining "sticky," the tapes can exhibit new properties derived from the presence of metal nanoparticles (e.g., bacteriostaticity, increased electrical conductivity). They can also be patterned with nanoparticles only at selective locations of mechanical activation.

Efficacy of mechanical fuel treatments for reducing wildfire hazard

Treesearch

Robert J. Jr. Huggett; Karen L. Abt; Wayne Shepperd

2008-01-01

Mechanical fuel treatments are increasingly being used for wildfire hazard reduction in the western U.S. However, the efficacy of these treatments for reducing wildfire hazard at a landscape scale is difficult to quantify, especially when including growth following treatment. A set of uneven- and even-aged treatments designed to reduce fire hazard were simulated on 0.8...

The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

ERIC Educational Resources Information Center

Cheng, Ying; Shao, Can; Lathrop, Quinn N.

2016-01-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

Assessment of Mechanisms for Jovian Synchrotron Variability Associated with Comet SL-9

NASA Technical Reports Server (NTRS)

Bolton, S. J.; Thorne, R. M.

1995-01-01

The impact comet SL-9 with Jupiter induced a number of variations in Jupiter's synchrotron radiation, including an increase in emission intensity, spectral changes, and a possible broadening in the latitudinal distribution of the emission. Considered are three potential mechanisms for inducing such effects (electron acceleration, radial diffusion, and pitch-angle scattering), and their consequences.

Preterm Infant Massage Therapy Research: A Review

PubMed Central

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

2010-01-01

In this paper, preterm infant massage therapy studies are reviewed. Massage therapy has led to weight gain in preterm infants when moderate pressure massage was provided. In studies on passive movement of the limbs, preterm infants also gained significantly more weight, and their bone density also increased. Research on ways of delivering the massage is also explored including using mothers versus therapists and the added effects of using oils. The use of mothers as therapists was effective in at least one study. The use of oils including coconut oil and safflower oil enhanced the average weight gain, and the transcutaneous absorption of oil also increased triglycerides. In addition, the use of synthetic oil increased vagal activity, which may indirectly contribute to weight gain. The weight gain was associated with shorter hospital stays and, thereby, significant hospital cost savings. Despite these benefits, preterm infant massage is only practiced in 38% of neonatal intensive care units. This may relate to the underlying mechanisms not being well understood. The increases noted in vagal activity, gastric motility, insulin and IGF-1 levels following moderate pressure massage are potential underlying mechanisms. However, those variables combined do not explain all of the variance in weight gain, highlighting the need for additional mechanism studies. PMID:20137814

Thigmomorphogenesis: anatomical, morphological and mechanical analysis of genetically different sibs of Pinus taeda in response to mechanical perturbation.

PubMed

Telewski, F W; Jaffe, M J

1986-01-01

Twenty-three open pollinated families (half-sibs) and four controlled pollinated families (full-sibs) of Pinus taeda L. (loblolly pine) were grown in a greenhouse and analyzed for changes induced by mechanical perturbation (MP). These changes included inhibition of stem and needle elongation, bracing of branch nodes, and increased radial growth in the direction of the MP. Inhibition of stem elongation was the least variable feature measured. Leaf extension and stem diameter were highly variable between half-sibs. MP induced increased drag in greenhouse grown P. taeda in wind-tunnel tests. In P. taeda, MP induced decreased flexibility and increased elasticity and plasticity of the stem. The increased radial growth of the stems overrode the increase in elasticity, resulting in an overall decrease in flexibility. MP trees had a higher rupture point than non-MP controls. Increased radial growth is a result of more rapid cell divisions of the vascular cambium, resulting in increased numbers of tracheids. The decreased leader growth is partly due to a decreased tracheid length in response to MP.

Thigmomorphogenesis: anatomical, morphological and mechanical analysis of genetically different sibs of Pinus taeda in response to mechanical perturbation

NASA Technical Reports Server (NTRS)

Telewski, F. W.; Jaffe, M. J.

1986-01-01

Twenty-three open pollinated families (half-sibs) and four controlled pollinated families (full-sibs) of Pinus taeda L. (loblolly pine) were grown in a greenhouse and analyzed for changes induced by mechanical perturbation (MP). These changes included inhibition of stem and needle elongation, bracing of branch nodes, and increased radial growth in the direction of the MP. Inhibition of stem elongation was the least variable feature measured. Leaf extension and stem diameter were highly variable between half-sibs. MP induced increased drag in greenhouse grown P. taeda in wind-tunnel tests. In P. taeda, MP induced decreased flexibility and increased elasticity and plasticity of the stem. The increased radial growth of the stems overrode the increase in elasticity, resulting in an overall decrease in flexibility. MP trees had a higher rupture point than non-MP controls. Increased radial growth is a result of more rapid cell divisions of the vascular cambium, resulting in increased numbers of tracheids. The decreased leader growth is partly due to a decreased tracheid length in response to MP.

Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: emerging translational approaches that bridge biology and behavior.

PubMed

Feldstein Ewing, Sarah W; Chung, Tammy

2013-06-01

Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real-time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examine brain-based mechanisms of change, whereas others examine brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors. 2013 APA, all rights reserved

Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: Emerging translational approaches that bridge biology and behavior

PubMed Central

Feldstein Ewing, Sarah W.; Chung, Tammy

2013-01-01

Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examined brain-based mechanisms of change, whereas others examined brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors. PMID:23815447

Dissipation effects in mechanics and thermodynamics

NASA Astrophysics Data System (ADS)

Güémez, J.; Fiolhais, M.

2016-07-01

With the discussion of three examples, we aim at clarifying the concept of energy transfer associated with dissipation in mechanics and in thermodynamics. The dissipation effects due to dissipative forces, such as the friction force between solids or the drag force in motions in fluids, lead to an internal energy increase of the system and/or to heat transfer to the surroundings. This heat flow is consistent with the second law, which states that the entropy of the universe should increase when those forces are present because of the irreversibility always associated with their actions. As far as mechanics is concerned, the effects of the dissipative forces are included in Newton’s equations as impulses and pseudo-works.

Tracheo-bronchitis and pneumonia associated with mechanical ventilation by Chryseobacterium indologenes.

PubMed

González-Castro, A; Alsasua, A; Peñasco, Y; Rodríguez, J C; Duerto, J

2017-05-01

The development of nosocomial infections by germs resistant to carbapenems inherently increases mortality, and causes an increase in health spending. The knowledge and study of these infections is important in improving epidemiological and therapeutic performance protocols. We present a descriptive study of eight patients diagnosed with tracheobronchitis (TAVM) and pneumonia (NAVM) associated with mechanical ventilation Chryseobacterium indologenes (CBI), over a period of five years. CBI isolation occurred at 11 days on average (rank 7-18) of remaining patients connected to mechanical ventilation. The average length of patients on mechanical ventilation was 36 days (range 10-140). The average ICU stay was 49 days (range 14-180). There was no death at 28 days, but the intra-hospital mortality was 2 cases (25%). Nosocomial respiratory infection secondary to CBI in mechanically ventilated patients has increased in recent years, so that should be included in the differential diagnostic of NAMV. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

A multifaceted knowledge translation strategy can increase compliance with guideline recommendations for mechanical bowel preparation.

PubMed

Eskicioglu, Cagla; Pearsall, Emily; Victor, J Charles; Aarts, Mary-Anne; Okrainec, Allan; McLeod, Robin S

2015-01-01

The successful transfer of evidence into clinical practice is a slow and haphazard process. We report the outcome of a 5-year knowledge translation (KT) strategy to increase adherence with a clinical practice guideline (CPG) for mechanical bowel preparation (MBP) for elective colorectal surgery patients. A locally tailored CPG recommending MBP practices was developed. Data on MBP practices were collected at six University of Toronto hospitals before CPG implementation as well as after two separate KT strategies. KT strategy #1 included development of the CPG, education by opinion leaders, reminder cards, and presentations of data. KT strategy #2 included selection of hospital champions, development of communities of practice, education, reminder cards, electronic updates, pre-printed standardized orders, and audit and feedback. A total of 744 patients (400 males, 344 females, mean age 57.0) were included. Compliance increased from 58.6 to 70.4% after KT strategy #1 and to 81.1% after KT strategy #2 (p < 0.001). Using a tailored KT strategy, increased compliance was observed with CPG recommendations over time suggesting that a longitudinal KT strategy is required to increase and sustain compliance with recommendations. Furthermore, different strategies may be required at different times (i.e., educational sessions initially and reminders and standardized orders to maintain adherence).

The evolution of the science of Bear Brook Watershed in Maine, USA.

PubMed

Norton, S A; Fernandez, I J; Kahl, J S; Rustad, L E; Navrátil, Tomás; Almquist, H

2010-12-01

The Bear Brook Watershed in Maine (BBWM), USA is a paired watershed study with chemical manipulation of one watershed (West Bear = WB) while the other watershed (East Bear = EB) serves as a reference. Characterization of hydrology and chemical fluxes occurred in 1987-1989 and demonstrated the similarity of the ca. 10 ha adjacent forested watersheds. From 1989-2010, we have added 1,800 eq (NH(4))(2)SO(4) ha(-1) y(-1) to WB. EB runoff has slowly acidified even as atmospheric deposition of SO4(-2) has declined. EB acidification included decreasing pH, base cation concentrations, and alkalinity, and increasing inorganic Al concentration, as SO4(-2) declined. Organic Al increased. WB has acidified more rapidly, including a 6-year period of increasing leaching of base cations, followed by a long-term decline of base cations, although still elevated over pretreatment values, as base saturation declined in the soils. Sulfate in WB has not increased to a new steady state because of increased anion adsorption accompanying soil acidification. Dissolved Al has increased dramatically in WB; increased export of particulate Al and P has accompanied the acidification in both watersheds, WB more than EB. Nitrogen retention in EB increased after 3 years of study, as did many watersheds in the northeastern USA. Nitrogen retention in WB still remains at over 80%, in spite of 20+ years of N addition. The 20-year chemical treatment with continuous measurements of critical variables in both watersheds has enabled the identification of decadal-scale processes, including ecosystem response to declining SO4(-2) in ambient precipitation in EB and evolving mechanisms of treatment response in WB. The study has demonstrated soil mechanisms buffering pH, declines in soil base saturation, altered P biogeochemistry, unexpected mechanisms of storage of S, and continuous high retention of treatment N.

Obesity, Inflammation, and Cancer.

PubMed

Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A

2016-05-23

Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.

Thermal and Mechanical Buckling and Postbuckling Responses of Selected Curved Composite Panels

NASA Technical Reports Server (NTRS)

Breivik, Nicole L.; Hyer, Michael W.; Starnes, James H., Jr.

1998-01-01

The results of an experimental and numerical study of the buckling and postbuckling responses of selected unstiffened curved composite panels subjected to mechanical end shortening and a uniform temperature increase are presented. The uniform temperature increase induces thermal stresses in the panel when the axial displacement is constrained. An apparatus for testing curved panels at elevated temperature is described, numerical results generated by using a geometrically nonlinear finite element analysis code are presented. Several analytical modeling refinements that provide more accurate representation of the actual experimental conditions, and the relative contribution of each refinement, are discussed. Experimental results and numerical predictions are presented and compared for three loading conditions including mechanical end shortening alone, heating the panels to 250 F followed by mechanical end shortening, and heating the panels to 400 F. Changes in the coefficients of thermal expansion were observed as temperature was increased above 330 F. The effects of these changes on the experimental results are discussed for temperatures up to 400 F.

Control of skeletal muscle perfusion at the onset of dynamic exercise

NASA Technical Reports Server (NTRS)

Delp, M. D.

1999-01-01

At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

A review of numerical techniques approaching microstructures of crystalline rocks

NASA Astrophysics Data System (ADS)

Zhang, Yahui; Wong, Louis Ngai Yuen

2018-06-01

The macro-mechanical behavior of crystalline rocks including strength, deformability and failure pattern are dominantly influenced by their grain-scale structures. Numerical technique is commonly used to assist understanding the complicated mechanisms from a microscopic perspective. Each numerical method has its respective strengths and limitations. This review paper elucidates how numerical techniques take geometrical aspects of the grain into consideration. Four categories of numerical methods are examined: particle-based methods, block-based methods, grain-based methods, and node-based methods. Focusing on the grain-scale characters, specific relevant issues including increasing complexity of micro-structure, deformation and breakage of model elements, fracturing and fragmentation process are described in more detail. Therefore, the intrinsic capabilities and limitations of different numerical approaches in terms of accounting for the micro-mechanics of crystalline rocks and their phenomenal mechanical behavior are explicitly presented.

Modeling the mechanics of cells in the cell-spreading process driven by traction forces

NASA Astrophysics Data System (ADS)

Fang, Yuqiang; Lai, King W. C.

2016-04-01

Mechanical properties of cells and their mechanical interaction with the extracellular environments are main factors influencing cellular function, thus indicating the progression of cells in different disease states. By considering the mechanical interactions between cell adhesion molecules and the extracellular environment, we developed a cell mechanical model that can characterize the mechanical changes in cells during cell spreading. A cell model was established that consisted of various main subcellular components, including cortical cytoskeleton, nuclear envelope, actin filaments, intermediate filaments, and microtubules. We demonstrated the structural changes in subcellular components and the changes in spreading areas during cell spreading driven by traction forces. The simulation of nanoindentation tests was conducted by integrating the indenting force to the cell model. The force-indentation curve of the cells at different spreading states was simulated, and the results showed that cell stiffness increased with increasing traction forces, which were consistent with the experimental results. The proposed cell mechanical model provides a strategy to investigate the mechanical interactions of cells with the extracellular environments through the adhesion molecules and to reveal the cell mechanical properties at the subcellular level as cells shift from the suspended state to the adherent state.

Modeling the mechanics of cells in the cell-spreading process driven by traction forces.

PubMed

Fang, Yuqiang; Lai, King W C

2016-04-01

Mechanical properties of cells and their mechanical interaction with the extracellular environments are main factors influencing cellular function, thus indicating the progression of cells in different disease states. By considering the mechanical interactions between cell adhesion molecules and the extracellular environment, we developed a cell mechanical model that can characterize the mechanical changes in cells during cell spreading. A cell model was established that consisted of various main subcellular components, including cortical cytoskeleton, nuclear envelope, actin filaments, intermediate filaments, and microtubules. We demonstrated the structural changes in subcellular components and the changes in spreading areas during cell spreading driven by traction forces. The simulation of nanoindentation tests was conducted by integrating the indenting force to the cell model. The force-indentation curve of the cells at different spreading states was simulated, and the results showed that cell stiffness increased with increasing traction forces, which were consistent with the experimental results. The proposed cell mechanical model provides a strategy to investigate the mechanical interactions of cells with the extracellular environments through the adhesion molecules and to reveal the cell mechanical properties at the subcellular level as cells shift from the suspended state to the adherent state.

Flux pinning mechanism in codoped-MgB2 with Al2O3 and SiC

NASA Astrophysics Data System (ADS)

Kiafiroozkoohi, Narjess Sadat; Ghorbani, Shaban Reza; Arabi, Hadi

2018-05-01

MgB2 superconductor samples, co-doped with 0.02 wt of Al2O3 and 0.02 wt SiC, have been examined by M-H loop measurements and calculation of the critical current density based on the Bean model. Normalized volume pinning force, f = F/Fmax, as a function of the reduced magnetic field, h = H/Hmax has been obtained at each temperature. Hughochi flux pinning model, which was included the normal point pinning, the normal surface pinning, and the pinning based on spatial variation in the Ginzburg-Landau parameter, was used to study the flux pinning mechanisms. It was found that the Δκ effect and the normal point pinning mechanisms play the main role in the flux pinning at the magnetic field lower than Hmax and the contribution of the Δκ mechanism increases with the increasing temperature, while the contribution of normal point pinning mechanism decreases. At magnetic field larger than Hmax, the only mechanism that acts as the flux pinning was the normal surface pinning mechanism.

Comparative Study of Hardening Mechanisms During Aging of a 304 Stainless Steel Containing α'-Martensite

NASA Astrophysics Data System (ADS)

Jeong, S. W.; Kang, U. G.; Choi, J. Y.; Nam, W. J.

2012-09-01

Strain aging and hardening behaviors of a 304 stainless steel containing deformation-induced martensite were investigated by examining mechanical properties and microstructural evolution for different aging temperature and time. Introduced age hardening mechanisms of a cold rolled 304 stainless steel were the additional formation of α'-martensite, hardening of α'-martensite, and hardening of deformed austenite. The increased amount of α'-martensite at an aging temperature of 450 °C confirmed the additional formation of α'-martensite as a hardening mechanism in a cold rolled 304 stainless steel. Additionally, the increased hardness in both α'-martensite and austenite phases with aging temperature proved that hardening of both α'-martensite and austenite phases would be effective as hardening mechanisms in cold rolled and aged 304 stainless steels. The results suggested that among hardening mechanisms, hardening of an α'-martensite phase, including the diffusion of interstitial solute carbon atoms to dislocations and the precipitation of fine carbide particles would become a major hardening mechanism during aging of cold rolled 304 stainless steels.

Influence of temperature on patch residence time in parasitoids: physiological and behavioural mechanisms

NASA Astrophysics Data System (ADS)

Moiroux, Joffrey; Abram, Paul K.; Louâpre, Philippe; Barrette, Maryse; Brodeur, Jacques; Boivin, Guy

2016-04-01

Patch time allocation has received much attention in the context of optimal foraging theory, including the effect of environmental variables. We investigated the direct role of temperature on patch time allocation by parasitoids through physiological and behavioural mechanisms and its indirect role via changes in sex allocation and behavioural defences of the hosts. We compared the influence of foraging temperature on patch residence time between an egg parasitoid, Trichogramma euproctidis, and an aphid parasitoid, Aphidius ervi. The latter attacks hosts that are able to actively defend themselves, and may thus indirectly influence patch time allocation of the parasitoid. Patch residence time decreased with an increase in temperature in both species. The increased activity levels with warming, as evidenced by the increase in walking speed, partially explained these variations, but other mechanisms were involved. In T. euproctidis, the ability to externally discriminate parasitised hosts decreased at low temperature, resulting in a longer patch residence time. Changes in sex allocation with temperature did not explain changes in patch time allocation in this species. For A. ervi, we observed that aphids frequently escaped at intermediate temperature and defended themselves aggressively at high temperature, but displayed few defence mechanisms at low temperature. These defensive behaviours resulted in a decreased patch residence time for the parasitoid and partly explained the fact that A. ervi remained for a shorter time at the intermediate and high temperatures than at the lowest temperature. Our results suggest that global warming may affect host-parasitoid interactions through complex mechanisms including both direct and indirect effects on parasitoid patch time allocation.

Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood.

PubMed

Sullivan, Elinor L; Smith, M Susan; Grove, Kevin L

2011-01-01

The perinatal environment plays an important role in programming many aspects of physiology and behavior including metabolism, body weight set point, energy balance regulation and predisposition to mental health-related disorders such as anxiety, depression and attention deficit hyperactivity disorder. Maternal health and nutritional status heavily influence the early environment and have a long-term impact on critical central pathways, including the melanocortinergic, serotonergic system and dopaminergic systems. Evidence from a variety of animal models including rodents and nonhuman primates indicates that exposure to maternal high-fat diet (HFD) consumption programs offspring for increased risk of adult obesity. Hyperphagia and increased preference for fatty and sugary foods are implicated as mechanisms for the increased obesity risk. The effects of maternal HFD consumption on energy expenditure are unclear, and future studies need to address the impact of perinatal HFD exposure on this important component of energy balance regulation. Recent evidence from animal models also indicates that maternal HFD consumption increases the risk of offspring developing mental health-related disorders such as anxiety. Potential mechanisms for perinatal HFD programming of neural pathways include circulating factors, such as hormones (leptin, insulin), nutrients (fatty acids, triglycerides and glucose) and inflammatory cytokines. As maternal HFD consumption and obesity are common and rapidly increasing, we speculate that future generations will be at increased risk for both metabolic and mental health disorders. Thus, it is critical that future studies identify therapeutic strategies that are effective at preventing maternal HFD-induced malprogramming. Copyright © 2010 S. Karger AG, Basel.

Viral entry mechanisms: the increasing diversity of paramyxovirus entry

PubMed Central

Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

2009-01-01

The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

Visual system manifestations of Alzheimer's disease.

PubMed

Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

2017-12-01

Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review.

PubMed

Oscarsson, Jan; Hurt-Camejo, Eva

2017-08-10

Epidemiological and genetic studies suggest that elevated triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hypertriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies. We conducted a review, using systematic methodology, of studies in humans assessing the mechanisms of action of EPA and DHA on apolipoprotein B-containing lipoproteins, including TG-rich lipoproteins and low-density lipoproteins (LDLs). A systematic search of PubMed retrieved 55 articles, of which 30 were used in the review; 35 additional arrticles were also included. In humans, dietary DHA is retroconverted to EPA, while production of DHA from EPA is not observed. Dietary DHA is preferentially esterified into TGs, while EPA is more evenly esterified into TGs, cholesterol esters and phospholipids. The preferential esterification of DHA into TGs likely explains the higher turnover of DHA than EPA in plasma. The main effects of both EPA and DHA are decreased fasting and postprandial serum TG levels, through reduction of hepatic very-low-density lipoprotein (VLDL)-TG production. The exact mechanism for reduced VLDL production is not clear but does not include retention of lipids in the liver; rather, increased hepatic fatty acid oxidation is likely. The postprandial reduction in TG levels is caused by increased lipoprotein lipase activity and reduced serum VLDL-TG concentrations, resulting in enhanced chylomicron clearance. Overall, no clear differences between the effects of EPA and DHA on TG levels, or on turnover of TG-rich lipoproteins, have been observed. Effects on LDL are complex and may be influenced by genetics, such as APOE genotype. EPA and DHA diminish fasting circulating TG levels via reduced production of VLDL. The mechanism of reduced VLDL production does not involve hepatic retention of lipids. Lowered postprandial TG levels are also explained by increased chylomicron clearance. Little is known about the specific cellular and biochemical mechanisms underlying the TG-lowering effects of EPA and DHA in humans.

Cellular and Molecular Mechanisms of Sexual Differentiation in the Mammalian Nervous System

PubMed Central

Forger, Nancy G.; Strahan, J. Alex; Castillo-Ruiz, Alexandra

2016-01-01

Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to rethink often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

[The Stigma-discrimination Complex Associated With Mental Disorder as a Risk Factor for Suicide].

PubMed

Campo-Arias, Adalberto; Herazo, Edwin

2015-01-01

The concept stigma-discrimination complex associated with mental disorder (SDCAMD) is proposed to encompass the terms used in the attribution theory: stigma, stereotype, prejudice and discrimination. SDCAMD is one of the most frequent disorders worldwide. Internalized and perceived SDCAMD may explain a number of suicide cases. To update the factors that may explain the association between SDCAMD and suicide, and postulate possible underlying mechanisms. Articles were identified in MEDLINE using the descriptors for "stigma", "mental disorders" and "suicide" or "suicide rate". Articles published between January 2000 and June 2014 were included. Reviews and case studies were not considered. The two included studies showed that stigma increased the risk of suicidal behaviors. It was evident that people who meet criteria for mental disorder and reported high self-stigma made a greater number of suicide attempts, and countries with high stigma in the general population have a higher suicide rate. It was considered that the relationship between SDCAMD and suicide is established by a set of interrelated mechanisms. A "direct" mechanism involving perceived stigma and is configured as a barrier to access mental health services, and an "indirect" mechanism involving the self-stigma, which increases the vulnerability to depressive episodes and repeated self-injurious behaviors that ultimately end in suicide. The SDCAMD impacts negatively on the quality of life of people who meet criteria for mental disorders, and accounts for a significant number of suicides. One way is related to the perceived stigma that is configured as a barrier to access mental health services and, the second one includes repeated self-injurious behaviors that reduce self-esteem and increases perceived stress. Further research is required to increase the knowledge of this association. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Increased global transcription activity as a mechanism of replication stress in cancer

PubMed Central

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M.; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-01-01

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer. PMID:27725641

Increased global transcription activity as a mechanism of replication stress in cancer.

PubMed

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-10-11

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS V12 , elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.

Obstructive sleep apnea as an independent stroke risk factor: possible mechanisms.

PubMed

Godoy, Jaime; Mellado, Patricio; Tapia, Jorge; Santín, Julia

2009-03-01

Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, increased levels of proinflammatory nuclear transcription factor kappa B, decreased circulating nitric oxide, elevation of vascular adhesion molecules and vascular endothelial growth factor. In addition, several authors have described that Continuous Positive Airway Pressure, the standard OSA therapy, reverts these abnormalities. Further research is needed in order to better clarify the complex mechanisms that underlie the relation between OSA, atherogenesis and CVD which most likely will have significant clinical impact.

Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments

NASA Astrophysics Data System (ADS)

Baker, Brendon M.; Trappmann, Britta; Wang, William Y.; Sakar, Mahmut S.; Kim, Iris L.; Shenoy, Vivek B.; Burdick, Jason A.; Chen, Christopher S.

2015-12-01

To investigate how cells sense stiffness in settings structurally similar to native extracellular matrices, we designed a synthetic fibrous material with tunable mechanics and user-defined architecture. In contrast to flat hydrogel surfaces, these fibrous materials recapitulated cell-matrix interactions observed with collagen matrices including stellate cell morphologies, cell-mediated realignment of fibres, and bulk contraction of the material. Increasing the stiffness of flat hydrogel surfaces induced mesenchymal stem cell spreading and proliferation; however, increasing fibre stiffness instead suppressed spreading and proliferation for certain network architectures. Lower fibre stiffness permitted active cellular forces to recruit nearby fibres, dynamically increasing ligand density at the cell surface and promoting the formation of focal adhesions and related signalling. These studies demonstrate a departure from the well-described relationship between material stiffness and spreading established with hydrogel surfaces, and introduce fibre recruitment as a previously undescribed mechanism by which cells probe and respond to mechanics in fibrillar matrices.

The role of Myc-induced protein synthesis in cancer

PubMed Central

Ruggero, Davide

2009-01-01

Deregulation in different steps of translational control is an emerging mechanism for cancer formation. One example of an oncogene with a direct role in control of translation is the Myc transcription factor. Myc directly increases protein synthesis rates by controlling the expression of multiple components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, Pol III and rDNA. However, the contribution of Myc-dependent increases in protein synthesis towards the multi-step process leading to cancer has remained unknown. Recent evidence strongly suggests that Myc oncogenic signaling may monopolize the translational machinery to elicit cooperative effects on cell growth, cell cycle progression, and genome instability as a mechanism for cancer initiation. Moreover, new genetic tools to restore aberrant increases in protein synthesis control are now available, which should enable the dissection of important mechanisms in cancer that rely on the translational machinery. PMID:19934336

Development of novel dental nanocomposites reinforced with polyhedral oligomeric silsesquioxane (POSS).

PubMed

Wu, Xiaorong; Sun, Yi; Xie, Weili; Liu, Yanju; Song, Xueyu

2010-05-01

It has been the focus to develop low shrinkage dental composite resins in recent ten years. A major difficulty in developing low shrinkage dental materials is that their deficiency in mechanical properties cannot satisfy the clinical purpose. The aim of this study is to develop novel dental nanocomposites incorporated with polyhedral oligomeric silsesquioxane (POSS). It is especially interesting to evaluate the volumetric shrinkage and mechanical properties, improve the shrinkage, working performances and service life of dental composite resins. The effect of added POSS on the composites' mechanical properties has been evaluated. The weight percentages of added POSS are 0, 2, 5, 10 and 15wt% respectively. Fourier-transform infra-red spectroscopy and X-ray diffraction were used to characterize their microstructures. Physico-mechanical properties that were investigated included volumetric shrinkage, flexural strength, flexural modulus, compressive strength, compressive modulus, Viker's hardness and fracture energy. Furthermore, the possible reinforced mechanism has been discussed. The shrinkage of novel nanocomposites decreased from 3.53% to 2.18%. The nanocomposites incorporated with POSS showed greatly improved mechanical properties, for example, with only 2wt% POSS added, the nanocompsite's flexural strength increased 15%, compressive strength increased 12%, hardness increased 15% and uncommonly, even the toughness of resins was obviously increased. With 5wt% POSS polymerized, compressive strength increased from 192MPa to 251MPa and compressive modulus increased from 3.93GPa to 6.62GPa, but flexure strength began to decline from 87MPa to 75MPa. This finding indicated that the reinforcing mechanism of flexure state maybe different from that of compressive state. The mechanical properties and volumetric shrinkage of dental composite resins polymerized with POSS can be improved significantly. In current study, the nanocomposite with 2wt% POSS incorporated is observed to achieve the best improved effects. 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Mechanical efficiency of two commercial lever-propulsion mechanisms for manual wheelchair locomotion.

PubMed

Lui, Jordon; MacGillivray, Megan K; Sheel, A William; Jeyasurya, Jeswin; Sadeghi, Mahsa; Sawatzky, Bonita Jean

2013-01-01

The purpose of this study was to (1) evaluate the mechanical efficiency (ME) of two commercially available lever-propulsion mechanisms for wheelchairs and (2) compare the ME of lever propulsion with hand rim propulsion within the same wheelchair. Of the two mechanisms, one contained a torsion spring while the other used a roller clutch design. We hypothesized that the torsion spring mechanism would increase the ME of propulsion due to a passive recovery stroke enabled by the mechanism. Ten nondisabled male participants with no prior manual wheeling experience performed submaximal exercise tests using both lever-propulsion mechanisms and hand rim propulsion on two different wheelchairs. Cardiopulmonary parameters including oxygen uptake (VO2), heart rate (HR), and energy expenditure (En) were determined. Total external power (Pext) was measured using a drag test protocol. ME was determined by the ratio of Pext to En. Results indicated no significant effect of lever-propulsion mechanism for all physiological measures tested. This suggests that the torsion spring did not result in a physiological benefit compared with the roller clutch mechanism. However, both lever-propulsion mechanisms showed decreased VO2 and HR and increased ME (as a function of slope) compared with hand rim propulsion (p < 0.001). This indicates that both lever-propulsion mechanisms tested are more mechanically efficient than conventional hand rim propulsion, especially when slopes are encountered.

Overcoming Stigma: Involving Families in Medical Student and Psychiatric Residency Education

ERIC Educational Resources Information Center

Schmetzer, Alan D.; Lafuze, Joan E.

2008-01-01

Objective: The primary purpose of this article is to present a possible mechanism for increasing communication about psychiatric matters such as diagnoses, treatment, and stigma between the physicians, including psychiatrists, and the families of persons with mental illness through a NAMI presentation. Methods: Included are a description of a…

Neighborhood and Family Environment of Expectans Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example

EPA Science Inventory

Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as an indirect mechanism that operates through coping behaviors, including adult smoking, or through increased toxic exposures during childhood. Little is known about pote...

Programmable Positioner For Spot Welding

NASA Technical Reports Server (NTRS)

Roden, William A.

1989-01-01

Welding station mechanized by installing preset indexing system and gear drive. Mechanism includes a low-cost, versatile, single-axis motion control and motor drive to provide fully-automatic weld sequencing and spot-to-spot spacing. Welding station relieves operator of some difficult, tedious tasks and increases both productivity and quality of welds. Results in welds of higher quality and greater accuracy, fewer weld defects, and faster welding operation.

Damping control of micromachined lowpass mechanical vibration isolation filters using electrostatic actuation with electronic signal processing

NASA Astrophysics Data System (ADS)

Dean, Robert; Flowers, George; Sanders, Nicole; MacAllister, Ken; Horvath, Roland; Hodel, A. S.; Johnson, Wayne; Kranz, Michael; Whitley, Michael

2005-05-01

Some harsh environments, such as those encountered by aerospace vehicles and various types of industrial machinery, contain high frequency/amplitude mechanical vibrations. Unfortunately, some very useful components are sensitive to these high frequency mechanical vibrations. Examples include MEMS gyroscopes and resonators, oscillators and some micro optics. Exposure of these components to high frequency mechanical vibrations present in the operating environment can result in problems ranging from an increased noise floor to component failure. Passive micromachined silicon lowpass filter structures (spring-mass-damper) have been demonstrated in recent years. However, the performance of these filter structures is typically limited by low damping (especially if operated in near-vacuum environments) and a lack of tunability after fabrication. Active filter topologies, such as piezoelectric, electrostrictive-polymer-film and SMA have also been investigated in recent years. Electrostatic actuators, however, are utilized in many micromachined silicon devices to generate mechanical motion. They offer a number of advantages, including low power, fast response time, compatibility with silicon micromachining, capacitive position measurement and relative simplicity of fabrication. This paper presents an approach for realizing active micromachined mechanical lowpass vibration isolation filters by integrating an electrostatic actuator with the micromachined passive filter structure to realize an active mechanical lowpass filter. Although the electrostatic actuator can be used to adjust the filter resonant frequency, the primary application is for increasing the damping to an acceptable level. The physical size of these active filters is suitable for use in or as packaging for sensitive electronic and MEMS devices, such as MEMS vibratory gyroscope chips.

A Drosophila model for developmental nicotine exposure

PubMed Central

2017-01-01

Despite the known health risks of tobacco smoking, many people including pregnant women continue smoking. The effects of developmental nicotine exposure are known, but the underlying mechanisms are not well understood. Drosophila melanogaster is a model organism that can be used for uncovering genetic and molecular mechanisms for drugs of abuse. Here I show that Drosophila can be a model to elucidate the mechanisms for nicotine’s effects on a developing organism. Drosophila reared on nicotine food display developmental and behavioral effects similar to those in mammals including decreased survival and weight, increased developmental time, and decreased sensitivity to acute nicotine and ethanol. The Drosophila nicotinic acetylcholine receptor subunit alpha 7 (Dα7) mediates some of these effects. A novel role for Dα7 on ethanol sedation in Drosophila is also shown. Future research taking advantage of the genetic and molecular tools for Drosophila will allow additional discovery of the mechanisms behind the effects of nicotine during development. PMID:28498868

Progressive Damage Analysis of Bonded Composite Joints

NASA Technical Reports Server (NTRS)

Leone, Frank A., Jr.; Girolamo, Donato; Davila, Carlos G.

2012-01-01

The present work is related to the development and application of progressive damage modeling techniques to bonded joint technology. The joint designs studied in this work include a conventional composite splice joint and a NASA-patented durable redundant joint. Both designs involve honeycomb sandwich structures with carbon/epoxy facesheets joined using adhesively bonded doublers.Progressive damage modeling allows for the prediction of the initiation and evolution of damage within a structure. For structures that include multiple material systems, such as the joint designs under consideration, the number of potential failure mechanisms that must be accounted for drastically increases the complexity of the analyses. Potential failure mechanisms include fiber fracture, intraply matrix cracking, delamination, core crushing, adhesive failure, and their interactions. The bonded joints were modeled using highly parametric, explicitly solved finite element models, with damage modeling implemented via custom user-written subroutines. Each ply was discretely meshed using three-dimensional solid elements. Layers of cohesive elements were included between each ply to account for the possibility of delaminations and were used to model the adhesive layers forming the joint. Good correlation with experimental results was achieved both in terms of load-displacement history and the predicted failure mechanism(s).

Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors

PubMed Central

2012-01-01

Background Sickle cell disease (SCD) is associated with both acute vaso-occlusive painful events as well as chronic pain syndromes, including heightened sensitivity to touch. We have previously shown that mice with severe SCD (HbSS mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have sensitized nociceptors, which contribute to increased mechanical sensitivity. Yet, the hypersensitivity in these neural populations alone may not fully explain the mechanical allodynia phenotype in mouse and humans. Findings Using the Light Touch Behavioral Assay, we found HbSS mice exhibited increased responses to repeated application of both innocuous punctate and dynamic force compared to control HbAA mice (100% normal human hemoglobin). HbSS mice exhibited a 2-fold increase in percent response to a 0.7mN von Frey monofilament when compared to control HbAA mice. Moreover, HbSS mice exhibited a 1.7-fold increase in percent response to the dynamic light touch “puffed” cotton swab stimulus. We further investigated the mechanisms that drive this behavioral phenotype by focusing on the cutaneous sensory neurons that primarily transduce innocuous, light touch. Low threshold cutaneous afferents from HbSS mice exhibited sensitization to mechanical stimuli that manifested as an increase in the number of evoked action potentials to suprathreshold force. Rapidly adapting (RA) Aβ and Aδ D-hair fibers showed the greatest sensitization, each with a 75% increase in suprathreshold firing compared to controls. Slowly adapting (SA) Aβ afferents had a 25% increase in suprathreshold firing compared to HbAA controls. Conclusions These novel findings demonstrate mice with severe SCD exhibit mechanical allodynia to both punctate and dynamic light touch and suggest that this behavioral phenotype may be mediated in part by the sensitization of light touch cutaneous afferent fibers to suprathreshold force. These findings indicate that Aβ fibers can be sensitized to mechanical force and should potentially be examined for sensitization in other tissue injury and disease models. PMID:22963123

Mechanisms of load dependency of myocardial ischemia reperfusion injury

PubMed Central

Mozaffari, Mahmood S; Liu, Jun Yao; Abebe, Worku; Baban, Babak

2013-01-01

Coronary artery disease and associated ischemic heart disease are prevalent disorders worldwide. Further, systemic hypertension is common and markedly increases the risk for heart disease. A common denominator of systemic hypertension of various etiologies is increased myocardial load/mechanical stress. Thus, it is likely that high pressure/mechanical stress attenuates the contribution of cardioprotective but accentuates the contribution of cardiotoxic pathways thereby exacerbating the outcome of an ischemia reperfusion insult to the heart. Critical events which contribute to cardiomyocyte injury in the ischemic-reperfused heart include cellular calcium overload and generation of reactive oxygen/nitrogen species which, in turn, promote the opening of the mitochondrial permeability transition pore, an important event in cell death. Increasing evidence also indicates that the myocardium is capable of mounting a robust inflammatory response which contributes importantly to tissue injury. On the other hand, cardioprotective maneuvers of ischemic preconditioning and postconditioning have led to identification of complex web of signaling pathways (e.g., reperfusion injury salvage kinase) which ultimately converge on the mitochondria to exert cytoprotection. The present review is intended to briefly describe mechanisms of cardiac ischemia reperfusion injury followed by a discussion of our work focused on how pressure/mechanical stress modulates endogenous cardiotoxic and cardioprotective mechanisms to ultimately exacerbate ischemia reperfusion injury. PMID:24224132

Mechanical properties, microstructural and thermal evolution of Mg65Ni20Y15-xSix (X = 1, 2, 3) alloys by mechanical alloying

NASA Astrophysics Data System (ADS)

Kursun, Celal; Gogebakan, Musa; Eskalen, Hasan

2018-03-01

We report on a work of the influence of the mechanical alloying on the microstructure, thermal and mechanical features of Mg65Ni20Y15-xSix (X = 1, 2, 3) alloys. The Mg-based alloys were produced by mechanical alloying technique from mixtures of pure crystalline Mg, Ni, Y and Si powders. These alloys were investigated using a variety of analytical techniques including x-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrometry (EDX) and differential scanning calorimetry (DSC). The mechanical properties of the alloys were investigated by Vickers microhardness (HV) tester. After 75 h of milling time, three different intermetallic phases were obtained. These phases were defined as Mg24Y5, Mg2Ni3Si and Mg2Ni by XRD data. The particle and crystallite sizes of the Mg-based alloys were decreased by increasing milling time and they were calculated 2 μm and ˜9 nm, respectively. From the EDX analysis, it was determined that compositional homogeneity of the Mg-based alloys was fairly high. The microhardness values of the Mg65Ni20Y15-xSix (X = 1, 2, 3) alloys increased by increasing Si into the alloys and were determined 101, 131 and 158 HV, respectively.

Civil propulsion technology for the next twenty-five years

NASA Technical Reports Server (NTRS)

Rosen, Robert; Facey, John R.

1987-01-01

The next twenty-five years will see major advances in civil propulsion technology that will result in completely new aircraft systems for domestic, international, commuter and high-speed transports. These aircraft will include advanced aerodynamic, structural, and avionic technologies resulting in major new system capabilities and economic improvements. Propulsion technologies will include high-speed turboprops in the near term, very high bypass ratio turbofans, high efficiency small engines and advanced cycles utilizing high temperature materials for high-speed propulsion. Key fundamental enabling technologies include increased temperature capability and advanced design methods. Increased temperature capability will be based on improved composite materials such as metal matrix, intermetallics, ceramics, and carbon/carbon as well as advanced heat transfer techniques. Advanced design methods will make use of advances in internal computational fluid mechanics, reacting flow computation, computational structural mechanics and computational chemistry. The combination of advanced enabling technologies, new propulsion concepts and advanced control approaches will provide major improvements in civil aircraft.

Activation of the mitogen-activated protein kinase pathway by bone sialoprotein regulates osteoblast differentiation.

PubMed

Gordon, Jonathan A R; Hunter, Graeme K; Goldberg, Harvey A

2009-01-01

Bone sialoprotein (BSP) is an abundant protein in the extracellular matrix of bone that has been suggested to have several different physiological functions, including the nucleation of hydroxyapatite (HA), promotion of cell attachment and binding of collagen. Studies in our lab have demonstrated that increased expression of BSP in osteoblast cells can increase expression of the osteoblast-related genes Runx2 and Osx as well as alkaline phosphatase and osteocalcin and increase matrix mineralization. To determine the molecular mechanisms responsible for the BSP-mediated increase in osteoblastic differentiation, several functional domain mutants of BSP were expressed in primary rat bone osteoblastic cells, including the contiguous glutamic acid sequences (polyGlu) and the arginine-glycine-aspartic acid (RGD) motif. Markers of osteoblast differentiation, including matrix mineralization and alkaline phosphatase staining, were increased in cells expressing BSP mutants of the polyGlu sequences but not in cells expressing RGD-mutated BSP. We also determined the dependence on integrin-associated pathways in promoting BSP-mediated differentiation responses in osteoblasts by demonstrating the activation of focal adhesion kinase, MAP kinase-associated proteins ERK1/2, ribosomal s6 kinase 2 and the AP-1 protein cFos. Thus, the mechanism regulating osteoblast differentiation by BSP was determined to be dependent on integrin-mediated intracellular signaling pathways. Copyright 2008 S. Karger AG, Basel.

Effect of Cold Rolling on Age Hardening in Excess Mg-Type Al-Mg-Si Alloys Including Some Minor Elements

NASA Astrophysics Data System (ADS)

Ogawa, Yurie; Matsuda, Kenji; Kawabata, Tokimasa; Uetani, Yasuhiro; Ikeno, Susumu

It has been known that transition metals improve the mechanical property of Al-Mg-Si alloy. The thermo-mechanical treatment is also effective to improve the strength of Al-Mg-Si alloy. In this work, the aging behavior of deformed excess Mg-type Al-Mg-Si alloy including Ag,Cu,Pt was investigated by hardness test and TEM observation. The value of the maximum hardness increased and the aging time to the maximum hardness became shorter by increasing the amount of the deformation. The age-hardening ability (ΔHV) was decreased with increasing amount of the deformation. The effect of additional element on AHV was also similar to the result of the deformation described above. Comparing the value of the maximum hardness for the alloys aged at 423-523 K, the ex. Mg-Cu alloy was the highest, the ex. Mg-Ag alloy was middle, and the ex. Mg and ex. Mg-Pt alloys were the lowest because of total amounts of added elements.

DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.

PubMed

Park, Sung-Jun; Gavrilova, Oksana; Brown, Alexandra L; Soto, Jamie E; Bremner, Shannon; Kim, Jeonghan; Xu, Xihui; Yang, Shutong; Um, Jee-Hyun; Koch, Lauren G; Britton, Steven L; Lieber, Richard L; Philp, Andrew; Baar, Keith; Kohama, Steven G; Abel, E Dale; Kim, Myung K; Chung, Jay H

2017-05-02

Hallmarks of aging that negatively impact health include weight gain and reduced physical fitness, which can increase insulin resistance and risk for many diseases, including type 2 diabetes. The underlying mechanism(s) for these phenomena is poorly understood. Here we report that aging increases DNA breaks and activates DNA-dependent protein kinase (DNA-PK) in skeletal muscle, which suppresses mitochondrial function, energy metabolism, and physical fitness. DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism. Decreasing DNA-PK activity increases AMPK activity and prevents weight gain, decline of mitochondrial function, and decline of physical fitness in middle-aged mice and protects against type 2 diabetes. In conclusion, DNA-PK is one of the drivers of the metabolic and fitness decline during aging, and therefore DNA-PK inhibitors may have therapeutic potential in obesity and low exercise capacity. Published by Elsevier Inc.

Mechanism of DNA binding enhancement by hepatitis B virus protein pX.

PubMed

Palmer, C R; Gegnas, L D; Schepartz, A

1997-12-09

At least three hundred million people worldwide are infected with the hepatitis B virus (HBV), and epidemiological studies show a clear correlation between chronic HBV infection and the development of hepatocellular carcinoma. HBV encodes a protein, pX, which abducts the cellular transcriptional machinery in several ways including direct interactions with bZIP transcription factors. These interactions increase the DNA affinities of target bZIP proteins in a DNA sequence-dependent manner. Here we use a series of bZIP peptide models to explore the mechanism by which pX interacts with bZIP proteins. Our results suggest that pX increases bZIP.DNA stability by increasing the stability of the bZIP dimer as well as the affinity of the dimer for DNA. Additional experiments provide evidence for a mechanism in which pX recognizes the composite structure of the peptide.DNA complex, not simply the primary peptide sequence. These experiments provide a framework for understanding how pX alters the patterns of transcription within the nucleus. The similarities between the mechanism proposed for pX and the mechanism previously proposed for the human T-cell leukemia virus protein Tax are discussed.

PASSIVE MECHANICAL PROPERTIES AND RELATED PROTEINS CHANGE WITH BOTULINUM NEUROTOXIN A INJECTION OF NORMAL SKELETAL MUSCLE

PubMed Central

Thacker, Bryan E.; Tomiya, Akihito; Hulst, Jonah B.; Suzuki, Kentaro P.; Bremner, Shannon N.; Gastwirt, Randy F.; Greaser, Marion L.; Lieber, Richard L.; Ward, Samuel R.

2011-01-01

Summary The effects of botulinum neurotoxin A on the passive mechanical properties of skeletal muscle have not been investigated, but may have significant impact in the treatment of neuromuscular disorders including spasticity. Single fiber and fiber bundle passive mechanical testing was performed on rat muscles treated with botulinum neurotoxin A. Myosin heavy chain and titin composition of single fibers was determined by gel electrophoresis. Muscle collagen content was determined using a hydroxyproline assay. Neurotoxin-treated single fiber passive elastic modulus was reduced compared to control fibers (53.00 kPa versus 63.43 kPa). Fiber stiffness and slack sarcomere length were also reduced compared to control fibers and myosin heavy chain composition shifted from faster to slower isoforms. Average titin molecular weight increased 1.77% after treatment. Fiber bundle passive elastic modulus increased following treatment (168.83 kPa versus 75.14 kPa). Bundle stiffness also increased while collagen content per mass of muscle tissue increased 38%. Injection of botulinum neurotoxin A produces an effect on the passive mechanical properties of normal muscle that is opposite to the changes observed in spastic muscles. PMID:21853457

Passive mechanical properties and related proteins change with botulinum neurotoxin A injection of normal skeletal muscle.

PubMed

Thacker, Bryan E; Tomiya, Akihito; Hulst, Jonah B; Suzuki, Kentaro P; Bremner, Shannon N; Gastwirt, Randy F; Greaser, Marion L; Lieber, Richard L; Ward, Samuel R

2012-03-01

The effects of botulinum neurotoxin A on the passive mechanical properties of skeletal muscle have not been investigated, but may have significant impact in the treatment of neuromuscular disorders including spasticity. Single fiber and fiber bundle passive mechanical testing was performed on rat muscles treated with botulinum neurotoxin A. Myosin heavy chain and titin composition of single fibers was determined by gel electrophoresis. Muscle collagen content was determined using a hydroxyproline assay. Neurotoxin-treated single fiber passive elastic modulus was reduced compared to control fibers (53.00 kPa vs. 63.43 kPa). Fiber stiffness and slack sarcomere length were also reduced compared to control fibers and myosin heavy chain composition shifted from faster to slower isoforms. Average titin molecular weight increased 1.77% after treatment. Fiber bundle passive elastic modulus increased following treatment (168.83  kPa vs. 75.14 kPa). Bundle stiffness also increased while collagen content per mass of muscle tissue increased 38%. Injection of botulinum neurotoxin A produces an effect on the passive mechanical properties of normal muscle that is opposite to the changes observed in spastic muscles. Copyright © 2011 Orthopaedic Research Society.

Sexual Experience in Female Rodents: Cellular Mechanisms and Functional Consequences

PubMed Central

Meisel, Robert L.; Mullins, Amanda J.

2007-01-01

The neurobiology of female sexual behavior has largely focused on mechanisms of hormone action on nerve cells and how these effects translate into the display of copulatory motor patterns. Of equal importance, though less studied, are some of the consequences of engaging in sexual behavior, including the rewarding properties of sexual interactions and how sexual experience alters copulatory efficiency. This review summarizes the effects of sexual experience on reward processes and copulation in female Syrian hamsters. Neural correlates of these sexual interactions include long-term cellular changes in dopamine transmission and postsynaptic signaling pathways related to neuronal plasticity (e.g., dendritic spine formation). Taken together, these studies suggest that sexual experience enhances the reinforcing properties of sexual behavior, which has the coincident outcome of increasing copulatory efficiency in a way that can increase reproductive success. PMID:16978593

A high dose of intravenous immunoglobulin increases CD94 expression on natural killer cells in women with recurrent spontaneous abortion.

PubMed

Shimada, Shigeki; Takeda, Masamitsu; Nishihira, Jun; Kaneuchi, Masanori; Sakuragi, Noriaki; Minakami, Hisanori; Yamada, Hideto

2009-11-01

A high dose of intravenous immunoglobulin (HIVIg) therapy is effective in various diseases such as autoimmune diseases, and also is expected to have efficacy in recurrent spontaneous abortion (RSA). The aim of this study was to understand immunological mechanisms of this therapy. By flowcytometric analyses, we examined phenotypic changes of a variety of immunological cells including natural killer (NK) cells, cytotoxic T cells, regulatory T cells and macrophages in peripheral blood of RSA women with HIVIg therapy (n = 8). Expression percentages of inhibitory CD94 on NK cells significantly (P = 0.01) increased after the therapy (58.8 +/- 21.4% versus 71.0 +/- 17.6%). Mechanisms of possible efficacy of HIVIg therapy for RSA may include enhancement of CD94 expression and subsequent suppression of NK cell cytotoxicity.

High pressure ceramic joint

DOEpatents

Ward, M.E.; Harkins, B.D.

1993-11-30

Many recuperators have components which react to corrosive gases and are used in applications where the donor fluid includes highly corrosive gases. These recuperators have suffered reduced life, increased service or maintenance, and resulted in increased cost. The present joint when used with recuperators increases the use of ceramic components which do not react to highly corrosive gases. Thus, the present joint used with the present recuperator increases the life, reduces the service and maintenance, and reduces the increased cost associated with corrosive action of components used to manufacture recuperators. The present joint is comprised of a first ceramic member, a second ceramic member, a mechanical locking device having a groove defined in one of the first ceramic member and the second ceramic member. The joint and the mechanical locking device is further comprised of a refractory material disposed in the groove and contacting the first ceramic member and the second ceramic member. The present joint mechanically provides a high strength load bearing joint having good thermal cycling characteristics, good resistance to a corrosive environment and good steady state strength at elevated temperatures. 4 figures.

High pressure ceramic joint

DOEpatents

Ward, Michael E.; Harkins, Bruce D.

1993-01-01

Many recuperators have components which react to corrosive gases and are used in applications where the donor fluid includes highly corrosive gases. These recuperators have suffered reduced life, increased service or maintenance, and resulted in increased cost. The present joint when used with recuperators increases the use of ceramic components which do not react to highly corrosive gases. Thus, the present joint used with the present recuperator increases the life, reduces the service and maintenance, and reduces the increased cost associated with corrosive action of components used to manufacture recuperators. The present joint is comprised of a first ceramic member, a second ceramic member, a mechanical locking device having a groove defined in one of the first ceramic member and the second ceramic member. The joint and the mechanical locking device is further comprised of a refractory material disposed in the groove and contacting the first ceramic member and the second ceramic member. The present joint mechanically provides a high strength load bearing joint having good thermal cycling characteristics, good resistance to a corrosive environment and good steady state strength at elevated temperatures.

Numerical Modeling of Flow through Phloem Considering Active Loading

NASA Astrophysics Data System (ADS)

Liu, Jin; Sze, Tsun-Kay Jackie; Dutta, Prashanta

2013-11-01

Transport through phloem is of significant interest in engineering applications including self-powered microfluidic pumps. We present a phloem model, combining protein level mechanics with cellular level fluid transport. Fluid flow and sucrose transport through a petiole sieve tube are simulated using the Nernst-Planck, Navier-Stokes, and continuity equations. Governing equations are solved using the finite volume method with dynamically calculated boundary conditions. Sieve tube cell structure consisting of sieve plates is included in a two dimensional model by computational cell blocking. Sucrose transport is incorporated as a boundary condition through a six-state model, bringing in active loading mechanisms with consideration of physical plant properties. The effects of reaction rates and leaf sucrose concentration are investigated to understand the transport mechanism in petiole sieve tubes. Numerical results show that increasing forward reactions of the proton sucrose transporter significantly promotes the pumping ability. A lower leaf sieve sucrose concentration results in a lower wall inflow velocity, but yields a higher inflow of water due to the active loading mechanism. The overall effect is higher outflow velocity for lower leaf sieve sucrose concentration because the increase in inflow velocity outweighs wall velocity. This new phloem model provides new insights on mechanisms potentially useful for fluidic pumping in self-powered microfluidic pumps. This work is supported in part by the National Science Fundation grant CBET-1250107.

Extra permeability is required to model dynamic oxygen measurements: evidence for functional recruitment?

PubMed Central

Barrett, Matthew JP; Suresh, Vinod

2013-01-01

Neural activation triggers a rapid, focal increase in blood flow and thus oxygen delivery. Local oxygen consumption also increases, although not to the same extent as oxygen delivery. This ‘uncoupling' enables a number of widely-used functional neuroimaging techniques; however, the physiologic mechanisms that govern oxygen transport under these conditions remain unclear. Here, we explore this dynamic process using a new mathematical model. Motivated by experimental observations and previous modeling, we hypothesized that functional recruitment of capillaries has an important role during neural activation. Using conventional mechanisms alone, the model predictions were inconsistent with in vivo measurements of oxygen partial pressure. However, dynamically increasing net capillary permeability, a simple description of functional recruitment, led to predictions consistent with the data. Increasing permeability in all vessel types had the same effect, but two alternative mechanisms were unable to produce predictions consistent with the data. These results are further evidence that conventional models of oxygen transport are not sufficient to predict dynamic experimental data. The data and modeling suggest that it is necessary to include a mechanism that dynamically increases net vascular permeability. While the model cannot distinguish between the different possibilities, we speculate that functional recruitment could have this effect in vivo. PMID:23673433

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria.

PubMed

Gong, Lauren; Parikh, Sunil; Rosenthal, Philip J; Greenhouse, Bryan

2013-09-11

Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria.

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria

PubMed Central

2013-01-01

Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria. PMID:24025776

Home Mechanical Ventilation: A 12-Year Population-Based Retrospective Cohort Study.

PubMed

Povitz, Marcus; Rose, Louise; Shariff, Salimah Z; Leonard, Sean; Welk, Blayne; Jenkyn, Krista Bray; Leasa, David J; Gershon, Andrea S

2018-04-01

Increasing numbers of individuals are being initiated on home mechanical ventilation, including noninvasive (bi-level) and invasive mechanical ventilation delivered via tracheostomy due to chronic respiratory failure to enable symptom management and promote quality of life. Given the high care needs of these individuals, a better understanding of the indications for home mechanical ventilation, and health-care utilization is needed. We performed a retrospective cohort study using provincial health administrative data from Ontario, Canada (population ∼13,000,000). Home mechanical ventilation users were characterized using health administrative data to determine the indications for home mechanical ventilation, the need for acute care at the time of ventilation approval, and their health service use and mortality rates following approval. The annual incidence of home mechanical ventilation approval rose from 1.8/100,000 in 2000 to 5.0/100,000 in 2012, or an annual increase of approximately 0.3/100,000 persons/y. The leading indications were neuromuscular disease, thoracic restriction, and COPD. The indication for the remainder could not be determined due to limitations of the administrative databases. Of the 4,670 individuals, 23.0% commenced home mechanical ventilation following an acute care hospitalization. Among individuals who survived at least 1 y, fewer required hospitalization in the year that followed home mechanical ventilation approval (29.9% vs 39.8%) as compared with the year prior. Utilization of home mechanical ventilation is increasing in Ontario, Canada, and further study is needed to clarify the factors contributing to this and to further optimize utilization of health-care resources. Copyright © 2018 by Daedalus Enterprises.

Fiber-Reinforced Reactive Nano-Epoxy Composites

NASA Technical Reports Server (NTRS)

Zhong, Wei-Hong

2011-01-01

An ultra-high-molecular-weight polyethylene/ matrix interface based on the fabrication of a reactive nano-epoxy matrix with lower surface energy has been improved. Enhanced mechanical properties versus pure epoxy on a three-point bend test include: strength (25 percent), modulus (20 percent), and toughness (30 percent). Increased thermal properties include higher Tg (glass transition temperature) and stable CTE (coefficient of thermal expansion). Improved processability for manufacturing composites includes faster wetting rates on macro-fiber surfaces, lower viscosity, better resin infusion rates, and improved rheological properties. Improved interfacial adhesion properties with Spectra fibers by pullout tests include initial debonding force of 35 percent, a maximum pullout force of 25 percent, and energy to debond at 65 percent. Improved mechanical properties of Spectra fiber composites (tensile) aging resistance properties include hygrothermal effects. With this innovation, high-performance composites have been created, including carbon fibers/nano-epoxy, glass fibers/nano-epoxy, aramid fibers/ nano-epoxy, and ultra-high-molecularweight polyethylene fiber (UHMWPE).

Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases

PubMed Central

Gil-Campos, Mercedes

2018-01-01

The pediatric population is continually at risk of developing infectious and inflammatory diseases. The treatment for infections, particularly gastrointestinal conditions, focuses on oral or intravenous rehydration, nutritional support and, in certain case, antibiotics. Over the past decade, the probiotics and synbiotics administration for the prevention and treatment of different acute and chronic infectious diseases has dramatically increased. Probiotic microorganisms are primarily used as treatments because they can stimulate changes in the intestinal microbial ecosystem and improve the immunological status of the host. The beneficial impact of probiotics is mediated by different mechanisms. These mechanisms include the probiotics’ capacity to increase the intestinal barrier function, to prevent bacterial transferation and to modulate inflammation through immune receptor cascade signaling, as well as their ability to regulate the expression of selected host intestinal genes. Nevertheless, with respect to pediatric intestinal diseases, information pertaining to these key mechanisms of action is scarce, particularly for immune-mediated mechanisms of action. In the present work, we review the biochemical and molecular mechanisms of action of probiotics and synbiotics that affect the immune system. PMID:29303974

Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes.

PubMed

Bramlett, Helen M; Dietrich, W Dalton

2015-12-01

Traumatic brain injury (TBI) is a significant clinical problem with few therapeutic interventions successfully translated to the clinic. Increased importance on the progressive, long-term consequences of TBI have been emphasized, both in the experimental and clinical literature. Thus, there is a need for a better understanding of the chronic consequences of TBI, with the ultimate goal of developing novel therapeutic interventions to treat the devastating consequences of brain injury. In models of mild, moderate, and severe TBI, histopathological and behavioral studies have emphasized the progressive nature of the initial traumatic insult and the involvement of multiple pathophysiological mechanisms, including sustained injury cascades leading to prolonged motor and cognitive deficits. Recently, the increased incidence in age-dependent neurodegenerative diseases in this patient population has also been emphasized. Pathomechanisms felt to be active in the acute and long-term consequences of TBI include excitotoxicity, apoptosis, inflammatory events, seizures, demyelination, white matter pathology, as well as decreased neurogenesis. The current article will review many of these pathophysiological mechanisms that may be important targets for limiting the chronic consequences of TBI.

Experiments with suspended cells on the Space Shuttle

NASA Technical Reports Server (NTRS)

Morrison, D. R.; Chapes, S. K.; Guikema, J. A.; Spooner, B. S.; Lewis, M. L.

1992-01-01

Spaceflight experiments since 1981 have demonstrated that certain cell functions are altered by micro-g. Biophysical models suggest that cell membranes and organelles should not be affected directly by gravity, however, the chemical microenvironment surrounding the cell and molecular transport could be altered by reduced gravity. Most experiments have used suspended live cells in small chambers without stirring or medium exchange. Flight results include increased attachment of anchorage-dependent human cells to collagen coated microcarriers, reduced secretion of growth hormone from pituitary cells, decreased mitogenic response of lymphocytes, increased Interferon-alpha by lymphocytes, increased Interleukin-1 and Tumor Necrosis Factor secretion by macrophages. Related experiments on cells immediately postflight and on procaryotic cells have shown significant changes in secretory capacity, cell proliferation, differentiation and development. Postulated mechanism include altered cell-cell interactions, altered calcium ion transport, effects on cell cytoskeleton, transport of transmitters and interactions with receptors. The discussion includes use of new molecular methods, considerations for cell environmental control and a preview of several experiments planned for the Shuttle and Spacelab flights to study the basic effects of microgravity on cellular physiology and potential interactions of spaceflight with radiation damage and cellular repair mechanisms.

Molecular Mechanism of Betaine on Hepatic Lipid Metabolism: Inhibition of Forkhead Box O1 (FoxO1) Binding to Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).

PubMed

Kim, Dae Hyun; Lee, Bonggi; Kim, Min Jo; Park, Min Hi; An, Hye Jin; Lee, Eun Kyeong; Chung, Ki Wung; Park, June Whoun; Yu, Byung Pal; Choi, Jae Sue; Chung, Hae Young

2016-09-14

Betaine is a major water-soluble component of Lycium chinensis. Although there are reports about the protective effects of betaine on hepatic steatosis, the underlying mechanisms are unclear. We used db/db mice and HepG2 cells to examine the mechanism underlying betaine-mediated protection against hepatic steatosis. Here, we showed increased hepatic lipid accumulation in db/db mice, which is associated with increased activation of lipogenic transcription factors including forkhead box O1 (FoxO1) and peroxisome proliferator-activated receptor gamma (PPARγ), whereas betaine administration by oral gavage reversed these characteristics. We investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO1/PPARγ signaling in HepG2 cells. Although adenovirus-mediated FoxO1 overexpression notably increased mRNA expression levels of PPARγ and its target genes including FAS and ACC, betaine treatment reversed them. Furthermore, betaine inhibited FoxO1 binding to the PPARγ promoter and PPARγ transcriptional activity in HepG2 cells, which was previously shown to induce hepatic steatosis. We concluded that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the FoxO1 binding to PPARγ and their downstream lipogenic signaling cascade.

Elucidating a molecular mechanism that the deterioration of porcine meat quality responds to increased cortisol based on transcriptome sequencing.

PubMed

Wan, Xuebin; Wang, Dan; Xiong, Qi; Xiang, Hong; Li, Huanan; Wang, Hongshuai; Liu, Zezhang; Niu, Hongdan; Peng, Jian; Jiang, Siwen; Chai, Jin

2016-11-11

Stress response is tightly linked to meat quality. The current understanding of the intrinsic mechanism of meat deterioration under stress is limited. Here, male piglets were randomly assigned to cortisol and control groups. Our results showed that when serum cortisol level was significantly increased, the meat color at 1 h postmortem, muscle bundle ratio, apoptosis rate, and gene expression levels of calcium channel and cell apoptosis including SERCA1, IP3R1, BAX, Bcl-2, and Caspase-3, were notably increased. However, the value of drip loss at 24 h postmortem and serum CK were significantly decreased. Additionally, a large number of differentially expressed genes (DEGs) in GC regulation mechanism were screened out using transcriptome sequencing technology. A total of 223 DEGs were found, including 80 up-regulated genes and 143 down-regulated genes. A total of 204 genes were enriched in GO terms, and 140 genes annotated into in KEGG database. Numerous genes were primarily involved in defense, inflammatory and wound responses. This study not only identifies important genes and signalling pathways that may affect the meat quality but also offers a reference for breeding and feeding management to provide consumers with better quality pork products.

A study of optical, mechanical and electrical properties of poly(methacrylic acid)/TiO2 nanocomposite

NASA Astrophysics Data System (ADS)

AL-Baradi, Ateyyah M.; Al-Shehri, Samar F.; Badawi, Ali; Merazga, Amar; Atta, A. A.

2018-06-01

This work is concerned with the study of the effect of titanium dioxide (TiO2) nanofillers on the optical, mechanical and electrical properties of poly(methacrylic acid) (PMAA) networks as a function of TiO2 concentration and crosslink density. The structure of the prepared samples was investigated by X-ray diffractometry (XRD) and Transmittance Electron Microscope (TEM). XRD results showed a single phase for the nanocomposites indicating that no large TiO2 aggregates in the polymer matrix. The optical properties of the prepared samples including the absorption, transmittance, energy band gap and refractive index were explored using Spectrophotometer. These measurements showed that there is a red-shift in the absorption caused by the increase of TiO2 concentration. However, the crosslink density in the polymer plays no role in changing the absorption. The energy band gap (Eg) decreases with increasing the concentration of TiO2 in the polymer matrix; whereas Eg increases with increasing the crosslink density. Moreover, the mechanical properties of PMAA/TiO2 nanocomposites by Dynamic Mechanical Analysis (DMA) showed that the viscoelasticity of PMAA decreases with adding TiO2 nanoparticles and the glass transition temperature (Tg) was also found to drop from 130 °C to 114 °C. Finally, the DC conductivity of the obtained systems was found to increase with increasing TiO2 nanoparticles in the matrix.

Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics

PubMed Central

Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B.; Janmey, Paul A.; Wells, Rebecca G.

2016-01-01

Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G’ and G” and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver. PMID:26735954

Inspiratory muscle training increases inspiratory muscle strength in patients weaning from mechanical ventilation: a systematic review.

PubMed

Moodie, Lisa; Reeve, Julie; Elkins, Mark

2011-01-01

Does inspiratory muscle training improve inspiratory muscle strength and endurance, facilitate weaning, improve survival, and reduce the rate of reintubation and tracheostomy in adults receiving mechanical ventilation? Systematic review of randomised or quasi-randomised controlled trials. Adults over 16 years of age receiving mechanical ventilation. Inspiratory muscle training versus sham or no inspiratory muscle training. Data were extracted regarding inspiratory muscle strength and endurance, the duration of unassisted breathing periods, weaning success and duration, reintubation and tracheostomy, survival, adverse effects, and length of stay. Three studies involving 150 participants were included in the review. The studies varied in time to commencement of the training, the device used, the training protocol, and the outcomes measured. Inspiratory muscle training significantly increased inspiratory muscle strength over sham or no training (weighted mean difference 8 cmH(2)O, 95% CI 6 to 9). There were no statistically significant differences between the groups in weaning success or duration, survival, reintubation, or tracheostomy. Inspiratory muscle training was found to significantly increase inspiratory muscle strength in adults undergoing mechanical ventilation. Despite data from a substantial pooled cohort, it is not yet clear whether the increase in inspiratory muscle strength leads to a shorter duration of mechanical ventilation, improved weaning success, or improved survival. Further large randomised studies are required to clarify the impact of inspiratory muscle training on patients receiving mechanical ventilation. PROSPERO CRD42011001132. Copyright © 2011 Australian Physiotherapy Association. Published by .. All rights reserved.

Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise.

PubMed

Stöhr, Eric J; Stembridge, Mike; Shave, Rob; Samuel, T Jake; Stone, Keeron; Esformes, Joseph I

2017-10-01

To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist, and untwisting rate ("LV mechanics"). LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double-leg press exercise at two intensities (30% and 60% of maximum strength, one-repetition maximum). Speckle tracking analysis generated LV strain, twist, and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. Responses in both exercise trials were statistically similar (P > 0.05). During effort, stroke volume decreased, whereas SVR and LV wall stress increased (P < 0.05). Immediately after effort, stroke volume returned to baseline, whereas SVR and wall stress decreased (P < 0.05). Similarly, acute exercise was accompanied by a significant decrease in systolic parameters of LV muscle mechanics (P < 0.05). However, diastolic parameters, including LV untwisting rate, were statistically unaltered (P > 0.05). Immediately after exercise, systolic LV mechanics returned to baseline levels (P < 0.05) but LV untwisting rate increased significantly (P < 0.05). A single, acute bout of double-leg press resistance exercise transiently reduces systolic LV mechanics, but increases diastolic mechanics after exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes.

Disease-Induced Skeletal Muscle Atrophy and Fatigue

PubMed Central

Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

2016-01-01

Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal muscle weakness can increase the duration of hospitalization, result in exercise limitation, and contribute to a poor quality of life. Importantly, skeletal muscle atrophy is also associated with increased morbidity and mortality of patients. Therefore, improving our understanding of the mechanism(s) responsible for skeletal muscle weakness and fatigue in patients is a required first step to develop clinical protocols to prevent these skeletal muscle problems. This review will highlight the consequences and potential mechanisms responsible for skeletal muscle atrophy and fatigue in patients suffering from acute critical illness, cancer, chronic inflammatory diseases, and neurological disorders. PMID:27128663

Synthesis and Characterization of Nanodiamond Reinforced Chitosan for Bone Tissue Engineering

PubMed Central

Sun, Yu; Yang, Qiaoqin; Wang, Haidong

2016-01-01

Multifunctional tissue scaffold material nanodiamond (ND)/chitosan (CS) composites with different diamond concentrations from 1 wt % to 5 wt % were synthesized through a solution casting method. The microstructure and mechanical properties of the composites were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and nanoindentation. Compared with pristine CS, the addition of ND resulted in a significant improvement of mechanical properties, including a 239%, 276%, 321%, 333%, and 343% increase in Young’s modulus and a 68%, 96%, 114%, 118%, and 127% increase in hardness when the ND amount was 1 wt %, 2 wt %, 3 wt %, 4 wt %, and 5 wt %, respectively. The strong interaction between ND surface groups and the chitosan matrix plays an important role in improving mechanical properties. PMID:27649252

Increased Terpenoid Accumulation in Cotton (Gossypium hirsutum) Foliage is a General Wound Response

PubMed Central

Kunert, Grit; Gershenzon, Jonathan

2008-01-01

The subepidermal pigment glands of cotton accumulate a variety of terpenoid products, including monoterpenes, sesquiterpenes, and terpenoid aldehydes that can act as feeding deterrents against a number of insect herbivore species. We compared the effect of herbivory by Spodoptera littoralis caterpillars, mechanical damage by a fabric pattern wheel, and the application of jasmonic acid on levels of the major representatives of the three structural classes of terpenoids in the leaf foliage of 4-week-old Gossypium hirsutum plants. Terpenoid levels increased successively from control to mechanical damage, herbivory, and jasmonic acid treatments, with E-β-ocimene and heliocide H1 and H4 showing the highest increases, up to 15-fold. Herbivory or mechanical damage to older leaves led to terpenoid increases in younger leaves. Leaf-by-leaf analysis of terpenes and gland density revealed that higher levels of terpenoids were achieved by two mechanisms: (1) increased filling of existing glands with terpenoids and (2) the production of additional glands, which were found to be dependent on damage intensity. As the relative response of individual terpenoids did not differ substantially among herbivore, mechanical damage, and jasmonic acid treatments, the induction of terpenoids in cotton foliage appears to represent a non-specific wound response mediated by jasmonic acid. Electronic supplementary material The online version of this article (doi:10.1007/s10886-008-9453-z) contains supplementary material, which is available to authorized users. PMID:18386096

Fever as a risk factor for increased response to vitamin K antagonists: a review of the evidence and potential mechanisms.

PubMed

Self, Timothy H; Oliphant, Carrie S; Reaves, Anne B; Richardson, Amy M; Sands, Christopher W

2015-01-01

Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regarding the effect of fever on response to VKA, and to discuss possible mechanisms of this effect. We performed a search of the English literature from 1943 to June 2014, using the key words fever AND warfarin, acenocoumarol, phenprocoumon, coumarin anticoagulants and VKA; fever AND vitamin K dependent clotting factors II, VII, IX, and X. One animal investigation and 6 studies in humans suggest fever increases response to VKA, but one study did not find a significant effect. The magnitude of this effect is variable. Possible mechanisms for the increased effect of VKA associated with fever are increased catabolism of vitamin K dependent clotting factors, decreased vitamin K intake, and inhibition of VKA metabolism. More rigorous studies are needed to confirm that fever increases response to warfarin and other VKA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mindfulness Training Targets Neurocognitive Mechanisms of Addiction at the Attention-Appraisal-Emotion Interface

PubMed Central

Garland, Eric L.; Froeliger, Brett; Howard, Matthew O.

2014-01-01

Prominent neuroscience models suggest that addictive behavior occurs when environmental stressors and drug-relevant cues activate a cycle of cognitive, affective, and psychophysiological mechanisms, including dysregulated interactions between bottom-up and top-down neural processes, that compel the user to seek out and use drugs. Mindfulness-based interventions (MBIs) target pathogenic mechanisms of the risk chain linking stress and addiction. This review describes how MBIs may target neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Empirical evidence is presented suggesting that MBIs ameliorate addiction by enhancing cognitive regulation of a number of key processes, including: clarifying cognitive appraisal and modulating negative emotions to reduce perseverative cognition and emotional arousal; enhancing metacognitive awareness to regulate drug-use action schema and decrease addiction attentional bias; promoting extinction learning to uncouple drug-use triggers from conditioned appetitive responses; reducing cue-reactivity and increasing cognitive control over craving; attenuating physiological stress reactivity through parasympathetic activation; and increasing savoring to restore natural reward processing. Treatment and research implications of our neurocognitive framework are presented. We conclude by offering a temporally sequenced description of neurocognitive processes targeted by MBIs through a hypothetical case study. Our neurocognitive framework has implications for the optimization of addiction treatment with MBIs. PMID:24454293

The ins and outs of RND efflux pumps in Escherichia coli.

PubMed

Anes, João; McCusker, Matthew P; Fanning, Séamus; Martins, Marta

2015-01-01

Infectious diseases remain one of the principal causes of morbidity and mortality in the world. Relevant authorities including the WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. They have also reaffirmed the urgent need for investment in the discovery and development of new antibiotics and therapeutic approaches to treat multidrug resistant (MDR) bacteria. The extensive use of antimicrobial compounds in diverse environments, including farming and healthcare, has been identified as one of the main causes for the emergence of MDR bacteria. Induced selective pressure has led bacteria to develop new strategies of defense against these chemicals. Bacteria can accomplish this by several mechanisms, including enzymatic inactivation of the target compound; decreased cell permeability; target protection and/or overproduction; altered target site/enzyme and increased efflux due to over-expression of efflux pumps. Efflux pumps can be specific for a single substrate or can confer resistance to multiple antimicrobials by facilitating the extrusion of a broad range of compounds including antibiotics, heavy metals, biocides and others, from the bacterial cell. To overcome antimicrobial resistance caused by active efflux, efforts are required to better understand the fundamentals of drug efflux mechanisms. There is also a need to elucidate how these mechanisms are regulated and how they respond upon exposure to antimicrobials. Understanding these will allow the development of combined therapies using efflux inhibitors together with antibiotics to act on Gram-negative bacteria, such as the emerging globally disseminated MDR pathogen Escherichia coli ST131 (O25:H4). This review will summarize the current knowledge on resistance-nodulation-cell division efflux mechanisms in E. coli, a bacteria responsible for community and hospital-acquired infections, as well as foodborne outbreaks worldwide.

Endotoxin induces fibrosis in vascular endothelial cells through a mechanism dependent on transient receptor protein melastatin 7 activity.

PubMed

Echeverría, Cesar; Montorfano, Ignacio; Hermosilla, Tamara; Armisén, Ricardo; Velásquez, Luis A; Cabello-Verrugio, Claudio; Varela, Diego; Simon, Felipe

2014-01-01

The pathogenesis of systemic inflammatory diseases, including endotoxemia-derived sepsis syndrome, is characterized by endothelial dysfunction. It has been demonstrated that the endotoxin lipopolysaccharide (LPS) induces the conversion of endothelial cells (ECs) into activated fibroblasts through endothelial-to-mesenchymal transition mechanism. Fibrogenesis is highly dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the specific molecular identity of the calcium channel that mediates the Ca2+ influx during endotoxin-induced endothelial fibrosis is still unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel that is expressed in many cell types, including ECs. TRPM7 is involved in a number of crucial processes such as the conversion of fibroblasts into activated fibroblasts, or myofibroblasts, being responsible for the development of several characteristics of them. However, the role of the TRPM7 ion channel in endotoxin-induced endothelial fibrosis is unknown. Thus, our aim was to study whether the TRPM7 calcium channel participates in endotoxin-induced endothelial fibrosis. Using primary cultures of ECs, we demonstrated that TRPM7 is a crucial protein involved in endotoxin-induced endothelial fibrosis. Suppression of TRPM7 expression protected ECs from the fibrogenic process stimulated by endotoxin. Downregulation of TRPM7 prevented the endotoxin-induced endothelial markers decrease and fibrotic genes increase in ECs. In addition, TRPM7 downregulation abolished the endotoxin-induced increase in ECM proteins in ECs. Furthermore, we showed that intracellular Ca2+ levels were greatly increased upon LPS challenge in a mechanism dependent on TRPM7 expression. These results demonstrate that TRPM7 is a key protein involved in the mechanism underlying endotoxin-induced endothelial fibrosis.

Implications of mechanistic modeling of drought effects on growth and competition in forest landscape models

Treesearch

Eric J. Gustafson; Arjan M. G. De Bruijn; Brian R. Miranda; Brian R. Sturtevant; J. Thompson

2016-01-01

The incidence of drought is expected to increase worldwide as a factor structuring forested landscapes. Ecophysiological mechanisms are being added to Forest Landscape Models (FLMs) to increase their robustness to the novel environmental conditions of the future (including drought), but their behavior has not been evaluated for mixed temperate forests. We evaluated...

Increasing Special Library Collection Use in Very Computer Intensive Environments: Automatic Bibliographic Compilation and the Dissemination of Electronic Newsletters.

ERIC Educational Resources Information Center

Sanchez, James Joseph

This paper describes the development and implementation of an automatic bibliographic facility and an electronic newsletter created for a special collection of aerospace and mechanical engineering monographs and articles at the University of Arizona. The project included the development of an online catalog, increasing the depth of bibliographic…

(abstract) A Geomagnetic Contribution to Climate Change in this Century

NASA Technical Reports Server (NTRS)

Feynman, J.; Ruzmaikin, A.; Lawrence, J.

1996-01-01

There is a myth that all solar effects can be parameterized by the sun spot number. This is not true. For example, the level of geomagnetic activity during this century was not proportional to the sunspot number. Instead there is a large systematic increase in geomagnetic activity, not reflected in the sunspot number. This increase occurred gradually over at least 60 years. The 11 year solar cycle variation was superimposed on this systematic increase. Here we show that this systematic increase in activity is well correlated to the simultaneous increase in terrestrial temperature that occurred during the first half of this century. We discuss these findings in terms of mechanisms by which geomagnetics can be coupled to climate. These mechanisms include possible changes in weather patterns and cloud cover due to increased cosmic ray fluxes, or to increased fluxes of high energy electrons. We suggest that this systematic increase in geomagnetic activity contributed (along with anthropogenic effects and possible changes in solar irradiance) to the changes in climate recorded during this period.

The MOD-OA 200 kilowatt wind turbine generator design and analysis report

NASA Astrophysics Data System (ADS)

Andersen, T. S.; Bodenschatz, C. A.; Eggers, A. G.; Hughes, P. S.; Lampe, R. F.; Lipner, M. H.; Schornhorst, J. R.

1980-08-01

The project requirements, approach, system description, design requirements, design, analysis, system tests, installation safety considerations, failure modes and effects analysis, data acquisition, and initial performance for the MOD-OA 200 kw wind turbine generator are discussed. The components, the rotor, driven train, nacelle equipment, yaw drive mechanism and brake, tower, foundation, electrical system, and control systems are presented. The rotor includes the blades, hub and pitch change mechanism. The drive train includes the low speed shaft, speed increaser, high speed shaft, and rotor brake. The electrical system includes the generator, switchgear, transformer, and utility connection. The control systems are the blade pitch, yaw, and generator control, and the safety system. Manual, automatic, and remote control and Dynamic loads and fatigue are analyzed.

The MOD-OA 200 kilowatt wind turbine generator design and analysis report

NASA Technical Reports Server (NTRS)

Andersen, T. S.; Bodenschatz, C. A.; Eggers, A. G.; Hughes, P. S.; Lampe, R. F.; Lipner, M. H.; Schornhorst, J. R.

1980-01-01

The project requirements, approach, system description, design requirements, design, analysis, system tests, installation safety considerations, failure modes and effects analysis, data acquisition, and initial performance for the MOD-OA 200 kw wind turbine generator are discussed. The components, the rotor, driven train, nacelle equipment, yaw drive mechanism and brake, tower, foundation, electrical system, and control systems are presented. The rotor includes the blades, hub and pitch change mechanism. The drive train includes the low speed shaft, speed increaser, high speed shaft, and rotor brake. The electrical system includes the generator, switchgear, transformer, and utility connection. The control systems are the blade pitch, yaw, and generator control, and the safety system. Manual, automatic, and remote control and Dynamic loads and fatigue are analyzed.

Physiological Mechanisms of Eccentric Contraction and Its Applications: A Role for the Giant Titin Protein

PubMed Central

Hessel, Anthony L.; Lindstedt, Stan L.; Nishikawa, Kiisa C.

2017-01-01

When active muscles are stretched, our understanding of muscle function is stretched as well. Our understanding of the molecular mechanisms of concentric contraction has advanced considerably since the advent of the sliding filament theory, whereas mechanisms for increased force production during eccentric contraction are only now becoming clearer. Eccentric contractions play an important role in everyday human movements, including mobility, stability, and muscle strength. Shortly after the sliding filament theory of muscle contraction was introduced, there was a reluctant recognition that muscle behaved as if it contained an “elastic” filament. Jean Hanson and Hugh Huxley referred to this structure as the “S-filament,” though their concept gained little traction. This additional filament, the giant titin protein, was identified several decades later, and its roles in muscle contraction are still being discovered. Recent research has demonstrated that, like activation of thin filaments by calcium, titin is also activated in muscle sarcomeres by mechanisms only now being elucidated. The mdm mutation in mice appears to prevent activation of titin, and is a promising model system for investigating mechanisms of titin activation. Titin stiffness appears to increase with muscle force production, providing a mechanism that explains two fundamental properties of eccentric contractions: their high force and low energetic cost. The high force and low energy cost of eccentric contractions makes them particularly well suited for athletic training and rehabilitation. Eccentric exercise is commonly prescribed for treatment of a variety of conditions including sarcopenia, osteoporosis, and tendinosis. Use of eccentric exercise in rehabilitation and athletic training has exploded to include treatment for the elderly, as well as muscle and bone density maintenance for astronauts during long-term space travel. For exercise intolerance and many types of sports injuries, experimental evidence suggests that interventions involving eccentric exercise are demonstrably superior to conventional concentric interventions. Future work promises to advance our understanding of the molecular mechanisms that confer high force and low energy cost to eccentric contraction, as well as signaling mechanisms responsible for the beneficial effects of eccentric exercise in athletic training and rehabilitation. PMID:28232805

Aging effects on airflow dynamics and lung function in human bronchioles.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-01-01

The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies.

Aging effects on airflow dynamics and lung function in human bronchioles

PubMed Central

Kim, JongWon; Heise, Rebecca L.; Reynolds, Angela M.; Pidaparti, Ramana M.

2017-01-01

Background and objective The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Materials and methods Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. Findings The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Conclusion Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies. PMID:28846719

Upflow bioreactor with septum and pressure release mechanism

DOEpatents

Hansen, Conly L.; Hansen, Carl S.; Pack, Kevin; Milligan, John; Benefiel, Bradley C.; Tolman, C. Wayne; Tolman, Kenneth W.

2010-04-20

An upflow bioreactor includes a vessel having an inlet and an outlet configured for upflow operation. A septum is positioned within the vessel and defines a lower chamber and an upper chamber. The septum includes an aperture that provides fluid communication between the upper chamber and lower chamber. The bioreactor also includes means for releasing pressure buildup in the lower chamber. In one configuration, the septum includes a releasable portion having an open position and a closed position. The releasable portion is configured to move to the open position in response to pressure buildup in the lower chamber. In the open position fluid communication between the lower chamber and the upper chamber is increased. Alternatively the lower chamber can include a pressure release line that is selectively actuated by pressure buildup. The pressure release mechanism can prevent the bioreactor from plugging and/or prevent catastrophic damage to the bioreactor caused by high pressures.

OXIDATIVE DNA DAMAGE IN DIESEL BUS MECHANICS

EPA Science Inventory

Rationale:

Diesel exposure has been associated with adverse health effects, including susceptibility to asthma, allergy and cancer. Previous epidemiological studies demonstrated increased cancer incidence among workers exposed to diesel. This is likely due to oxid...

Thermal response of integral abutment bridges with mechanically stabilized earth walls.

DOT National Transportation Integrated Search

2013-03-01

The advantages of integral abutment bridges (IABs) include reduced maintenance costs and increased useful life spans. : However, improved procedures are necessary to account for the impacts of cyclic thermal displacements on IAB components, : includi...

Achondroplasia: Development, Pathogenesis, and Therapy

PubMed Central

Ornitz, David M.; Legeai-Mallet, Laurence

2016-01-01

Autosomal dominant mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) cause Achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include Hypochondroplasia (Hch), Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN), and Thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. PMID:27987249

Self-contained heat rejection module for future spacecraft

NASA Technical Reports Server (NTRS)

Fleming, M. L.; Williams, J. L.; Baskett, J. D.; Leach, J. W.

1975-01-01

This paper discusses development of a Self-Contained Heat Rejection Module (SHRM) which can be used on a wide variety of future spacecraft launched by the space shuttle orbiter. The SHRM contains radiators which are deployed by a scissor-mechanism and the flow equipment including pumps, accumulator, by-pass valves, and controllers necessary to reject heat from those radiators. Heat transfer between SHRM and the parent vehicle is effected by a contact heat exchanger. This device provides heat transfer between two separate flow loops through a mechanical connection. This approach reduces the time required to attach the SHRM to the payload, and increases the reliability of the SHRM flow loop since breaking into the fluid system in the field is not required. The SHRM concept also includes a refrigeration system to increase heat rejection capacity in adverse environments, or to provide for a lower return temperature, down to -23 C.

Control of mechanically activated polymersome fusion: Factors affecting fusion

DOE PAGES

Henderson, Ian M.; Paxton, Walter F.

2014-12-15

Previously we have studied the mechanically-activated fusion of extruded (200 nm) polymer vesicles into giant polymersomes using agitation in the presence of salt. In this study we have investigated several factors contributing to this phenomenon, including the effects of (i) polymer vesicle concentration, (ii) agitation speed and duration, and iii) variation of the salt and its concentration. It was found that increasing the concentration of the polymer dramatically increases the production of giant vesicles through the increased collisions of polymersomes. Our investigations also found that increasing the frequency of agitation increased the efficiency of fusion, though ultimately limited the sizemore » of vesicle which could be produced due to the high shear involved. Finally it was determined that salt-mediation of the fusion process was not limited to NaCl, but is instead a general effect facilitated by the presence of solvated ionic compounds, albeit with different salts initiating fusion at different concentration.« less

Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.

PubMed

Wadhwa, Renu; Konar, Arpita; Kaul, Sunil C

2016-05-01

Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mathematical modeling and computational prediction of cancer drug resistance.

PubMed

Sun, Xiaoqiang; Hu, Bin

2017-06-23

Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing. In this review, we first briefly summarize the current progress of experimentally revealed resistance mechanisms of targeted therapy, including genetic mechanisms, epigenetic mechanisms, posttranslational mechanisms, cellular mechanisms, microenvironmental mechanisms and pharmacokinetic mechanisms. Subsequently, we list several currently available databases and Web-based tools related to drug sensitivity and resistance. Then, we focus primarily on introducing some state-of-the-art computational methods used in drug resistance studies, including mechanism-based mathematical modeling approaches (e.g. molecular dynamics simulation, kinetic model of molecular networks, ordinary differential equation model of cellular dynamics, stochastic model, partial differential equation model, agent-based model, pharmacokinetic-pharmacodynamic model, etc.) and data-driven prediction methods (e.g. omics data-based conventional screening approach for node biomarkers, static network approach for edge biomarkers and module biomarkers, dynamic network approach for dynamic network biomarkers and dynamic module network biomarkers, etc.). Finally, we discuss several further questions and future directions for the use of computational methods for studying drug resistance, including inferring drug-induced signaling networks, multiscale modeling, drug combinations and precision medicine. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Psychological Stress Induces Temporary Masticatory Muscle Mechanical Sensitivity in Rats

PubMed Central

Huang, Fei; Zhang, Min; Chen, Yong-Jin; Li, Qiang; Wu, An-Zhen

2011-01-01

To explore the relationship between psychological stress and masticatory muscle pain, we created a communication stress animal model to determine whether psychological stress could induce increased mechanical sensitivity in masticatory muscles and to study the changes of mechanical nociceptive thresholds after stress removal. Forty-eight male Sprague-Dawley rats were divided into a control group (CON), a foot-shocked group (FS, including 3 subgroups recorded as FS-1, FS-2, and FS-3), a psychological stress group (PS), and a drug treatment group (DT). PS and DT rats were confined in a communication box for one hour a day to observe the psychological responses of neighboring FS rats.Measurements of the mechanical nociceptive thresholds of the bilateral temporal and masseter muscles showed a stimulus-response relationship between psychological stress and muscle mechanical sensitivity. The DT rats, who received a diazepam injection, showed almost the same mechanical sensitivity of the masticatory muscles to that of the control in response to psychological stress. Fourteen days after the psychological stressor was removed, the mechanical nociceptive thresholds returned to normal. These findings suggest that psychological stress is directly related to masticatory muscle pain. Removal of the stressor could be a useful method for relieving mechanical sensitivity increase induced by psychological stress. PMID:21331360

Rate Constants and Mechanisms of Protein–Ligand Binding

PubMed Central

Pang, Xiaodong; Zhou, Huan-Xiang

2017-01-01

Whereas protein–ligand binding affinities have long-established prominence, binding rate constants and binding mechanisms have gained increasing attention in recent years. Both new computational methods and new experimental techniques have been developed to characterize the latter properties. It is now realized that binding mechanisms, like binding rate constants, can and should be quantitatively determined. In this review, we summarize studies and synthesize ideas on several topics in the hope of providing a coherent picture of and physical insight into binding kinetics. The topics include microscopic formulation of the kinetic problem and its reduction to simple rate equations; computation of binding rate constants; quantitative determination of binding mechanisms; and elucidation of physical factors that control binding rate constants and mechanisms. PMID:28375732

Exposure to buffer solution alters tendon hydration and mechanics.

PubMed

Safa, Babak N; Meadows, Kyle D; Szczesny, Spencer E; Elliott, Dawn M

2017-08-16

A buffer solution is often used to maintain tissue hydration during mechanical testing. The most commonly used buffer solution is a physiological concentration of phosphate buffered saline (PBS); however, PBS increases the tissue's water content and decreases its tensile stiffness. In addition, solutes from the buffer can diffuse into the tissue and interact with its structure and mechanics. These bathing solution effects can confound the outcome and interpretation of mechanical tests. Potential bathing solution artifacts, including solute diffusion, and their effect on mechanical properties, are not well understood. The objective of this study was to measure the effects of long-term exposure of rat tail tendon fascicles to several concentrations (0.9-25%) of NaCl, sucrose, polyethylene glycol (PEG), and SPEG (NaCl+PEG) solutions on water content, solute diffusion, and mechanical properties. We found that with an increase in solute concentration the apparent water content decreased for all solution types. Solutes diffused into the tissue for NaCl and sucrose, however, no solute diffusion was observed for PEG or SPEG. The mechanical properties changed for both NaCl solutions, in particular after long-term (8h) incubation the modulus and equilibrium stress decreased compared to short-term (15min) for 25% NaCl, and the cross sectional area increased for 0.9% NaCl. However, the mechanical properties were unchanged for both PEG and SPEG except for minor alterations in stress relaxation parameters. This study shows that NaCl and sucrose buffer solutions are not suitable for long-term mechanical tests. We therefore propose using PEG or SPEG as alternative buffer solutions that after long-term incubation can maintain tissue hydration without solute diffusion and produce a consistent mechanical response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1.

PubMed

Hoppe, U C; Marbán, E; Johns, D C

2001-04-24

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, I(Kr), of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed I(Kr) without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.

Mindfulness-based cognitive therapy for depression: trends and developments.

PubMed

MacKenzie, Meagan B; Kocovski, Nancy L

2016-01-01

Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy.

The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients.

PubMed

Lo, Janet; Plutzky, Jorge

2012-06-01

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

Remote temperature-set-point controller

DOEpatents

Burke, W.F.; Winiecki, A.L.

1984-10-17

An instrument is described for carrying out mechanical strain tests on metallic samples with the addition of means for varying the temperature with strain. The instrument includes opposing arms and associated equipment for holding a sample and varying the mechanical strain on the sample through a plurality of cycles of increasing and decreasing strain within predetermined limits, circuitry for producing an output signal representative of the strain during the tests, apparatus including a a set point and a coil about the sample for providing a controlled temperature in the sample, and circuitry interconnected between the strain output signal and set point for varying the temperature of the sample linearly with strain during the tests.

Remote temperature-set-point controller

DOEpatents

Burke, William F.; Winiecki, Alan L.

1986-01-01

An instrument for carrying out mechanical strain tests on metallic samples with the addition of an electrical system for varying the temperature with strain, the instrument including opposing arms and associated equipment for holding a sample and varying the mechanical strain on the sample through a plurality of cycles of increasing and decreasing strain within predetermined limits, circuitry for producing an output signal representative of the strain during the tests, apparatus including a set point and a coil about the sample for providing a controlled temperature in the sample, and circuitry interconnected between the strain output signal and set point for varying the temperature of the sample linearly with strain during the tests.

Mechanical ventilatory constraints during incremental cycle exercise in human pregnancy: implications for respiratory sensation

PubMed Central

Jensen, Dennis; Webb, Katherine A; Davies, Gregory A L; O'Donnell, Denis E

2008-01-01

The aim of this study was to identify the physiological mechanisms of exertional respiratory discomfort (breathlessness) in pregnancy by comparing ventilatory (breathing pattern, airway function, operating lung volumes, oesophageal pressure (Poes)-derived indices of respiratory mechanics) and perceptual (breathlessness intensity) responses to incremental cycle exercise in 15 young, healthy women in the third trimester (TM3; between 34 and 38 weeks gestation) and again 4–5 months postpartum (PP). During pregnancy, resting inspiratory capacity (IC) increased (P < 0.01) and end-expiratory lung volume decreased (P < 0.001), with no associated change in total lung capacity (TLC) or static respiratory muscle strength. This permitted greater tidal volume (VT) expansion throughout exercise in TM3, while preserving the relationship between contractile respiratory muscle effort (tidal Poes swing expressed as a percentage of maximum inspiratory pressure (PImax)) and thoracic volume displacement (VT expressed as a percentage of vital capacity) and between breathlessness and ventilation (V̇E). At the highest equivalent work rate (HEWR = 128 ± 5 W) in TM3 compared with PP: V̇E, tidal Poes/PImax and breathlessness intensity ratings increased by 10.2 l min−1 (P < 0.001), 8.8%PImax (P < 0.05) and 0.9 Borg units (P < 0.05), respectively. Pulmonary resistance was not increased at rest or during exercise at the HEWR in TM3, despite marked increases in mean tidal inspiratory and expiratory flow rates, suggesting increased bronchodilatation. Dynamic mechanical constraints on VT expansion (P < 0.05) with associated increased breathlessness intensity ratings (P < 0.05) were observed near peak exercise in TM3 compared with PP. In conclusion: (1) pregnancy-induced increases in exertional breathlessness reflected the normal awareness of increased V̇E and contractile respiratory muscle effort; (2) mechanical adaptations of the respiratory system, including recruitment of resting IC and increased bronchodilatation, accommodated the increased VT while preserving effort–displacement and breathlessness–V̇E relationships; and (3) dynamic mechanical ventilatory constraints contributed to respiratory discomfort near the limits of tolerance in late gestation. PMID:18687714

Molecular Mechanisms of Antidiuretic Effect of Oxytocin

PubMed Central

Li, Chunling; Wang, Weidong; Summer, Sandra N.; Westfall, Timothy D.; Brooks, David P.; Falk, Sandor; Schrier, Robert W.

2008-01-01

Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying this effect are not completely understood. We infused oxytocin by osmotic minipump into vasopressin-deficient Brattleboro rats for five days and observed marked antidiuresis, increased urine osmolality, and increased solute-free water reabsorption. Administration of oxytocin also significantly increased the protein levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated increased AQP2 and p-AQP2 expression and trafficking to the apical plasma membrane of principal cells in the collecting duct, and increased AQP3 expression in the basolateral membrane. These oxytocin-induced effects were blocked by treatment with the vasopressin V2 receptor antagonist SR121463B, but not by treatment with the oxytocin receptor antagonist GW796679X. We conclude that vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3 protein expression. PMID:18057218

Mechanical Properties and Simulated Aging of Silicone Maxillofacial Elastomers: Advancements in the Past 45 Years.

PubMed

Hatamleh, Muhanad M; Polyzois, Gregory L; Nuseir, Amjad; Hatamleh, Khaldoun; Alnazzawi, Ahmad

2016-07-01

To identify and discuss the findings of publications on mechanical behavior of maxillofacial prosthetic materials published since 1969. Original experimental articles reporting on mechanical properties of maxillofacial prosthetic materials were included. A two-stage search of the literature, electronic and hand search, identified relevant published studies up to May 2015. An extensive electronic search was conducted of databases including PubMed, Embase, Scopus, and Google Scholar. Included primary studies (n = 63) reported on tensile strength, tear strength, and hardness of maxillofacial prosthetic materials at baseline and after aging. The search revealed 63 papers, with more than 28 papers being published in the past 10 years, which shows an increased number of publications when compared to only 6 papers published in the 1970s. The increase is linear with significant correlation (r = 0.85). Such an increase reflects great awareness and continued developments and warrants more research in the field of maxillofacial prosthetic materials properties; however, it is difficult to directly compare results, as studies varied in maxillofacial prosthetic materials tested with various silicone elastomers being heavily investigated, standards followed in preparing test specimens, experimental testing protocols, and parameters used in setting simulated aging conditionings. It is imperative to overcome the existing variability by establishing unified national or international standards/specifications for maxillofacial prosthetic materials. Standardization organizations or bodies, the scientific community, and academia need to be coordinated to achieve this goal. In the meantime and despite all of these theoretically significant alternatives, clinical practice still faces problems with serviceability of maxillofacial prostheses. © 2016 by the American College of Prosthodontists.

[Cancer immunotherapy. Importance of overcoming immune suppression].

PubMed

Malvicini, Mariana; Puchulo, Guillermo; Matar, Pablo; Mazzolini, Guillermo

2010-01-01

Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.

A 1D pulse wave propagation model of the hemodynamics of calf muscle pump function.

PubMed

Keijsers, J M T; Leguy, C A D; Huberts, W; Narracott, A J; Rittweger, J; van de Vosse, F N

2015-07-01

The calf muscle pump is a mechanism which increases venous return and thereby compensates for the fluid shift towards the lower body during standing. During a muscle contraction, the embedded deep veins collapse and venous return increases. In the subsequent relaxation phase, muscle perfusion increases due to increased perfusion pressure, as the proximal venous valves temporarily reduce the distal venous pressure (shielding). The superficial and deep veins are connected via perforators, which contain valves allowing flow in the superficial-to-deep direction. The aim of this study is to investigate and quantify the physiological mechanisms of the calf muscle pump, including the effect of venous valves, hydrostatic pressure, and the superficial venous system. Using a one-dimensional pulse wave propagation model, a muscle contraction is simulated by increasing the extravascular pressure in the deep venous segments. The hemodynamics are studied in three different configurations: a single artery-vein configuration with and without valves and a more detailed configuration including a superficial vein. Proximal venous valves increase effective venous return by 53% by preventing reflux. Furthermore, the proximal valves shielding function increases perfusion following contraction. Finally, the superficial system aids in maintaining the perfusion during the contraction phase and reduces the refilling time by 37%. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

The Eicosapentaenoic Acid Metabolite 15-Deoxy-δ12,14-Prostaglandin J3 Increases Adiponectin Secretion by Adipocytes Partly via a PPARγ-Dependent Mechanism

PubMed Central

Lefils-Lacourtablaise, Jennifer; Socorro, Mairobys; Géloën, Alain; Daira, Patricia; Debard, Cyrille; Loizon, Emmanuelle; Guichardant, Michel; Dominguez, Zury; Vidal, Hubert; Lagarde, Michel; Bernoud-Hubac, Nathalie

2013-01-01

The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ12,14-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation. PMID:23734181

Prooxidant Mechanisms in Iron Overload Cardiomyopathy

PubMed Central

Cheng, Ching-Feng; Lian, Wei-Shiung

2013-01-01

Iron overload cardiomyopathy (IOC), defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading. PMID:24350287

Compound mechanism hypothesis on +Gz induced brain injury and dysfunction of learning and memory

NASA Astrophysics Data System (ADS)

Sun, Xi-Qing; Li, Jin-Sheng; Cao, Xin-Sheng; Wu, Xing-Yu

2005-08-01

We systematically studied the effect of high- sustained +Gz on the brain and its mechanism in past ten years by animal centrifuge experiments. On the basis of the facts we observed and the more recent advances in acceleration physiology, we put forward a compound mechanism hypothesis to offer a possible explanation for +Gz-induced brain injury and dysfunction of learning and memory. It states that, ischemia during high G exposure might be the main factor accounting for +Gz-induced brain injury and dysfunction of learning and memory, including transient depression of brain energy metabolism, disturbance of ion homeostasis, increased blood-brain barrier permeability, increased brain nitric oxide synthase expression, and the protective effect of heat shock protein 70. In addition, the large rapid change of intracranial pressure and increased stress during +Gz exposure, and the hemorrheologic change after +Gz exposure might be one of the important factors accounting for +Gz-induced brain injury and dysfunction of learning and memory.

Resveratrol induces membrane and DNA disruption via pro-oxidant activity against Salmonella typhimurium.

PubMed

Lee, Wonjong; Lee, Dong Gun

2017-07-22

Resveratrol is a flavonoid found in various plants including grapes, which has been reported to be active against various pathogenic bacteria. However, antibacterial effects and mechanisms via pro-oxidant property of resveratrol remain unknown and speculative. This research investigated antibacterial mechanism of resveratrol against a food-borne human pathogen Salmonella typhimurium, and confirmed the cell death associated oxidative damage. Resveratrol increased outer membrane permeability and membrane depolarization. It also was observed DNA injury responses such as DNA fragmentation, increasing DNA contents and cell division inhibition. Intracellular ROS accumulation, GSH depletion and significant increased malondialdehyde levels were confirmed, which indicated pro-oxidant activity of resveratrol and oxidative stress. Furthermore, the observed lethal damages were reduced by antioxidant N-acetylcysteine treatment supported the view that resveratrol-induced oxidative stress stimulated S. typhimurium cell death. In conclusion, this study expands understanding on role of pro-oxidant property and insight into previously unrecognized oxygen-dependent anti-Salmonella mechanism on resveratrol. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulatory RNAs and control of epigenetic mechanisms: expectations for cognition and cognitive dysfunction.

PubMed

Butler, Anderson A; Webb, William M; Lubin, Farah D

2016-01-01

The diverse functions of noncoding RNAs (ncRNAs) can influence virtually every aspect of the transcriptional process including epigenetic regulation of genes. In the CNS, regulatory RNA networks and epigenetic mechanisms have broad relevance to gene transcription changes involved in long-term memory formation and cognition. Thus, it is becoming increasingly clear that multiple classes of ncRNAs impact neuronal development, neuroplasticity, and cognition. Currently, a large gap exists in our knowledge of how ncRNAs facilitate epigenetic processes, and how this phenomenon affects cognitive function. In this review, we discuss recent findings highlighting a provocative role for ncRNAs including lncRNAs and piRNAs in the control of epigenetic mechanisms involved in cognitive function. Furthermore, we discuss the putative roles for these ncRNAs in cognitive disorders such as schizophrenia and Alzheimer's disease.

Constructivist Simultaneous Treatment of Borderline Personality Disorder, Trauma, and Addiction Comorbidity: A Qualitative Case Study.

PubMed

Johansen, Ayna B; Tavakoli, Shedeh; Bjelland, Ingerid; Lumley, Mark

2017-01-01

This qualitative case study explored one client's recovery from borderline personality disorder, trauma, and problem gambling. The client attended 18 months of integrative treatment and was followed for 5 years. The study included 106 data points of both client and therapist data. We identified three phases to treatment. First, alliance formation and normalization appeared as mechanisms, and the client experienced dependence. Second, working alliance and countertransference appeared as mechanisms, and the client experienced reduced gambling and suicidal ideation. Third, external controls and increased opportunity appeared as mechanisms, and "moving into the world" was the client experience. The findings give preliminary support to a phase-based constructivist treatment including trauma assessment to normalize self-feelings, countertransference work to support motivation for restraint, and case management principles to support continuity of change efforts. © The Author(s) 2015.

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Cannabis and psychosis: an update on course and biological plausible mechanisms.

PubMed

Linszen, Don; van Amelsvoort, Therese

2007-03-01

Cannabis use is the most commonly abused illicit substance. Its relation with psychosis remains a topic of debate. Epidemiological studies suggest that cannabis is a component cause accounting for approximately 10% of cases. An increasing number of studies have been published on neurobiological effects of cannabis and vulnerability of psychosis. Acute cannabis administration can induce memory impairments, sometimes persisting months following abstinence. There is no evidence that residual effects on cognition remain after years of abstinence. The scarce literature on neuro-imaging mainly done in nonpsychotic populations, show little evidence that cannabis has effects on brain anatomy. Acute effects of cannabis include increases of cerebral blood flow, whereas long-term effects of cannabis include attenuation of cerebral blood flow. In animals Delta9-tetrahydrocannabinol enhances dopaminergic neurotransmission in brain regions known to be implicated in psychosis. Studies in humans show that genetic vulnerability may add to increased risk of developing psychosis and cognitive impairments following cannabis consumption. Delta9-tetrahydrocannabinol induces psychotic like states and memory impairments in healthy volunteers. Simultaneously with increasing understanding of neurobiological cannabis effects, there is a lack of studies in people with psychosis. There are plausible mechanisms that might explain the psychotogenic effects of cannabis.

Electrical signals as mechanism of photosynthesis regulation in plants.

PubMed

Sukhov, Vladimir

2016-12-01

This review summarizes current works concerning the effects of electrical signals (ESs) on photosynthesis, the mechanisms of the effects, and its physiological role in plants. Local irritations of plants induce various photosynthetic responses in intact leaves, including fast and long-term inactivation of photosynthesis, and its activation. Irritation-induced ESs, including action potential, variation potential, and system potential, probably causes the photosynthetic responses in intact leaves. Probable mechanisms of induction of fast inactivation of photosynthesis are associated with Ca 2+ - and (or) H + -influxes during ESs generation; long-term inactivation of photosynthesis might be caused by Ca 2+ - and (or) H + -influxes, production of abscisic and jasmonic acids, and inactivation of phloem H + -sucrose symporters. It is probable that subsequent development of inactivation of photosynthesis is mainly associated with decreased CO 2 influx and inactivation of the photosynthetic dark reactions, which induces decreased photochemical quantum yields of photosystems I and II and increased non-photochemical quenching of photosystem II fluorescence and cyclic electron flow around photosystem I. However, other pathways of the ESs influence on the photosynthetic light reactions are also possible. One of them might be associated with ES-connected acidification of chloroplast stroma inducing ferredoxin-NADP + reductase accumulation at the thylakoids in Tic62 and TROL complexes. Mechanisms of ES-induced activation of photosynthesis require further investigation. The probable ultimate effect of ES-induced photosynthetic responses in plant life is the increased photosynthetic machinery resistance to stressors, including high and low temperatures, and enhanced whole-plant resistance to environmental factors at least during 1 h after irritation.

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

PubMed Central

Drengstig, Tormod; Ruoff, Peter

2014-01-01

The uptake of glucose and the nutrient coupled transcellular sodium traffic across epithelial cells in the small intestine has been an ongoing topic in physiological research for over half a century. Driving the uptake of nutrients like glucose, enterocytes must have regulatory mechanisms that respond to the considerable changes in the inflow of sodium during absorption. The Na-K-ATPase membrane protein plays a major role in this regulation. We propose the hypothesis that the amount of active Na-K-ATPase in enterocytes is directly regulated by the concentration of intracellular Na+ and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na+/K+ homeostasis. To explore these regulatory mechanisms, we present a mathematical model of the sodium coupled uptake of glucose in epithelial enterocytes. Our model integrates knowledge about individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase, and GLUT2, together with diffusion and membrane potentials. The intracellular concentrations of glucose, sodium, potassium, and chloride are modeled by nonlinear differential equations, and molecular flows are calculated based on experimental kinetic data from the literature, including substrate saturation, product inhibition, and modulation by membrane potential. Simulation results of the model without the addition of regulatory mechanisms fit well with published short-term observations, including cell depolarization and increased concentration of intracellular glucose and sodium during increased concentration of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K-ATPase and K permeability to the model show that our hypothesis predicts observed long-term ionic homeostasis. PMID:24898586

Bi-directional signaling: Extracellular Matrix and Integrin Regulation of Breast Tumor Progression

PubMed Central

Gehler, Scott; Ponik, Suzanne M.; Riching, Kristin M; Keely, Patricia J.

2016-01-01

Cell transformation and tumor progression involves a common set of acquired capabilities, including increased proliferation, failure of cell death, self-sufficiency in growth, angiogenesis, and tumor cell invasion and metastasis (1). The stromal environment consists of many cell types, including fibroblasts, macrophages, and endothelial cells, in addition to various extracellular matrix (ECM) proteins that function to support normal tissue maintenance, but have also been implicated in tumor progression (2). Both the chemical and mechanical properties of the ECM have been shown to influence normal and malignant cell behavior. For instance, mesenchymal stem cells differentiate into specific lineages that are dependent on matrix stiffness (3), while tumor cells undergo changes in cell behavior and gene expression in response to matrix stiffness (4). ECM remodeling is implicated in tumor progression and includes changes in both the chemical and mechanical properties of the ECM (5) that can be a result of 1.) increased deposition of stromal ECM, 2.) enhanced contraction of ECM fibrils, and 3.) altered collagen alignment and ECM stiffness. In addition, remodeling of the ECM may alter whether tumor cells employ proteolytic degradation mechanisms during invasion and metastasis. Tumor cells respond to such changes in ECM remodeling through altered intracellular signaling and cell cycle control that lead to enhanced proliferation, loss of normal tissue architecture, and local tumor cell migration and invasion into the surrounding stromal tissue (6). This review will focus on the bi-directional interplay between the mechanical properties of the ECM and changes in integrin-mediated signal transduction events in an effort to elucidate cell behaviors during tumor progression. PMID:23582036

Identification of potential biophysical and molecular signalling mechanisms underlying hyaluronic acid enhancement of cartilage formation

PubMed Central

Responte, Donald J.; Natoli, Roman M.; Athanasiou, Kyriacos A.

2012-01-01

This study determined the effects of exogenous hyaluronic acid (HA) on the biomechanical and biochemical properties of self-assembled bovine chondrocytes, and investigated biophysical and genetic mechanisms underlying these effects. The effects of HA commencement time, concentration, application duration and molecular weight were examined using histology, biomechanics and biochemistry. Additionally, the effects of HA application on sulphated glycosaminoglycan (GAG) retention were assessed. To investigate the influence of HA on gene expression, microarray analysis was conducted. HA treatment of developing neocartilage increased compressive stiffness onefold and increased sulphated GAG content by 35 per cent. These effects were dependent on HA molecular weight, concentration and application commencement time. Additionally, applying HA increased sulphated GAG retention within self-assembled neotissue. HA administration also upregulated 503 genes, including multiple genes associated with TGF-β1 signalling. Increased sulphated GAG retention indicated that HA could enhance compressive stiffness by increasing the osmotic pressure that negatively charged GAGs create. The gene expression data demonstrate that HA treatment differentially regulates genes related to TGF-β1 signalling, revealing a potential mechanism for altering matrix composition. These results illustrate the potential use of HA to improve cartilage regeneration efforts and better understand cartilage development. PMID:22809846

High-dose chlorogenic acid induces inflammation reactions and oxidative stress injury in rats without implication of mast cell degranulation.

PubMed

Du, Wen-Yuan; Chang, Cheng; Zhang, Yu; Liu, Yu-Ying; Sun, Kai; Wang, Chuan-She; Wang, Ming-Xia; Liu, Yuan; Wang, Fu; Fan, Jing-Yu; Li, Peng-Tao; Han, Jing-Yan

2013-05-02

Chlorogenic acid (CA) exits widely in those Chinese herbal injections that have antibacterial and antiphlogistic effects and belongs to the ethnopharmacological family of medicines. Chinese herbal injections containing high levels of CA have been reported to increase the adverse drug reactions, but the mechanism for which is still unclear. In this study, we investigated the mechanism of the CA derived adverse drug reactions. The present study was to explore the potential role of CA in initiating inflammatory reaction and the underlying mechanism. Male Wistar rats were treated with different dosages of CA for different time period. The variables examined included microcirculation by intravital microscopy, histology of ileum tissue, expression of adhesion molecules CD11b and CD18 on leukocytes by flow cytometry, myeloperoxidase activity and maleic dialdehyde content in ileum tissue by spectrophotometry, activity of superoxide dismutase and catalase in serum by ELISA, and expression of NADPH oxidase subunits by PCR and Western blot. High-dose CA increased the number of adherent leukocytes, generation of peroxides in the venular walls and induced albumin leakage from mesentery venules. High-dose CA induced changes also included an increase in maleic dialdehyde, myeloperoxidase, inflammatory cytokines and NADPH oxidase activities, and a decline in activity of superoxide dismutase and catalase. High-dose, but not Low-dose CA induced inflammation reaction, and in this process an imbalance between oxidant and antioxidant mechanism may be involved, providing more information for better understanding the rationale behind the adverse effects of CA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mechanical and biocompatible characterizations of a readily available multilayer vascular graft

PubMed Central

Madhavan, Krishna; Elliott, Winston H; Bonani, Walter; Monnet, Eric; Tan, Wei

2013-01-01

There is always a considerable clinical need for vascular grafts. Considering the availability, physical and mechanical properties, and regenerative potential, we have developed and characterized readily available, strong, and compliant multilayer grafts that support cell culture and ingrowth. The grafts were made from heterogeneous materials and structures, including a thin, dense, nanofibrous core composed of poly-ε-caprolactone (PCL), and a thick, porous, hydrogel sleeve composed of genipin-crosslinked collagen–chitosan (GCC). Because the difference in physicochemical properties between PCL and GCC caused layer separation, the layer adhesion was identified as a determinant to graft property and integrity under physiological conditions. Thus, strategies to modify the layer interface, including increasing porosity of the PCL surface, decreasing hydrophobicity, and increasing interlayer crosslinking, were developed. Results from microscopic images showed that increasing PCL porosity was characterized by improved layer adhesion. The resultant graft was characterized by high compliance (4.5%), and desired permeability (528 mL/cm2/min), burst strength (695 mmHg), and suture strength (2.38 N) for readily grafting. Results also showed that PCL mainly contributed to the graft mechanical properties, whereas GCC reduced the water permeability. In addition to their complementary contributions to physical and mechanical properties, the distinct graft layers also provided layer-specific structures for seeding and culture of vascular endothelial and smooth muscle cells in vitro. Acellular graft constructs were readily used to replace abdominal aorta of rabbits, resulting in rapid cell ingrowth and flow reperfusion. The multilayer constructs capable of sustaining physiological conditions and promoting cellular activities could serve as a platform for future development of regenerative vascular grafts. PMID:23165922

Computational Architecture of the Granular Layer of Cerebellum-Like Structures.

PubMed

Bratby, Peter; Sneyd, James; Montgomery, John

2017-02-01

In the adaptive filter model of the cerebellum, the granular layer performs a recoding which expands incoming mossy fibre signals into a temporally diverse set of basis signals. The underlying neural mechanism is not well understood, although various mechanisms have been proposed, including delay lines, spectral timing and echo state networks. Here, we develop a computational simulation based on a network of leaky integrator neurons, and an adaptive filter performance measure, which allows candidate mechanisms to be compared. We demonstrate that increasing the circuit complexity improves adaptive filter performance, and relate this to evolutionary innovations in the cerebellum and cerebellum-like structures in sharks and electric fish. We show how recurrence enables an increase in basis signal duration, which suggest a possible explanation for the explosion in granule cell numbers in the mammalian cerebellum.

Mechanical versus manual chest compressions for cardiac arrest.

PubMed

Brooks, Steven C; Hassan, Nizar; Bigham, Blair L; Morrison, Laurie J

2014-02-27

This is the first update of the Cochrane review on mechanical chest compression devices published in 2011 (Brooks 2011). Mechanical chest compression devices have been proposed to improve the effectiveness of cardiopulmonary resuscitation (CPR). To assess the effectiveness of mechanical chest compressions versus standard manual chest compressions with respect to neurologically intact survival in patients who suffer cardiac arrest. We searched the Cochrane Central Register of Controlled Studies (CENTRAL; 2013, Issue 12), MEDLINE Ovid (1946 to 2013 January Week 1), EMBASE (1980 to 2013 January Week 2), Science Citation abstracts (1960 to 18 November 2009), Science Citation Index-Expanded (SCI-EXPANDED) (1970 to 11 January 2013) on Thomson Reuters Web of Science, biotechnology and bioengineering abstracts (1982 to 18 November 2009), conference proceedings Citation Index-Science (CPCI-S) (1990 to 11 January 2013) and clinicaltrials.gov (2 August 2013). We applied no language restrictions. Experts in the field of mechanical chest compression devices and manufacturers were contacted. We included randomised controlled trials (RCTs), cluster RCTs and quasi-randomised studies comparing mechanical chest compressions versus manual chest compressions during CPR for patients with atraumatic cardiac arrest. Two review authors abstracted data independently; disagreement between review authors was resolved by consensus and by a third review author if consensus could not be reached. The methodologies of selected studies were evaluated by a single author for risk of bias. The primary outcome was survival to hospital discharge with good neurological outcome. We planned to use RevMan 5 (Version 5.2. The Nordic Cochrane Centre) and the DerSimonian & Laird method (random-effects model) to provide a pooled estimate for risk ratio (RR) with 95% confidence intervals (95% CIs), if data allowed. Two new studies were included in this update. Six trials in total, including data from 1166 participants, were included in the review. The overall quality of included studies was poor, and significant clinical heterogeneity was observed. Only one study (N = 767) reported survival to hospital discharge with good neurological function (defined as a Cerebral Performance Category score of one or two), demonstrating reduced survival with mechanical chest compressions when compared with manual chest compressions (RR 0.41, 95% CI 0.21 to 0.79). Data from four studies demonstrated increased return of spontaneous circulation, and data from two studies demonstrated increased survival to hospital admission with mechanical chest compressions as compared with manual chest compressions, but none of the individual estimates reached statistical significance. Marked clinical heterogeneity between studies precluded any pooled estimates of effect. Evidence from RCTs in humans is insufficient to conclude that mechanical chest compressions during cardiopulmonary resuscitation for cardiac arrest are associated with benefit or harm. Widespread use of mechanical devices for chest compressions during cardiac events is not supported by this review. More RCTs that measure and account for the CPR process in both arms are needed to clarify the potential benefit to be derived from this intervention.

Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs

PubMed Central

Hall, Matthew S.; Alisafaei, Farid; Ban, Ehsan; Feng, Xinzeng; Hui, Chung-Yuen; Shenoy, Vivek B.; Wu, Mingming

2016-01-01

In native states, animal cells of many types are supported by a fibrous network that forms the main structural component of the ECM. Mechanical interactions between cells and the 3D ECM critically regulate cell function, including growth and migration. However, the physical mechanism that governs the cell interaction with fibrous 3D ECM is still not known. In this article, we present single-cell traction force measurements using breast tumor cells embedded within 3D collagen matrices. We recreate the breast tumor mechanical environment by controlling the microstructure and density of type I collagen matrices. Our results reveal a positive mechanical feedback loop: cells pulling on collagen locally align and stiffen the matrix, and stiffer matrices, in return, promote greater cell force generation and a stiffer cell body. Furthermore, cell force transmission distance increases with the degree of strain-induced fiber alignment and stiffening of the collagen matrices. These findings highlight the importance of the nonlinear elasticity of fibrous matrices in regulating cell–ECM interactions within a 3D context, and the cell force regulation principle that we uncover may contribute to the rapid mechanical tissue stiffening occurring in many diseases, including cancer and fibrosis. PMID:27872289

Numerical analysis of effects of transglottal pressure change on fundamental frequency of phonation.

PubMed

Deguchi, Shinji; Matsuzaki, Yuji; Ikeda, Tadashige

2007-02-01

In humans, a decrease in transglottal pressure (Pt) causes an increase in the fundamental frequency of phonation (F0) only at a specific voice pitch within the modal register, the mechanism of which remains unclear. In the present study, numerical analyses were performed to investigate the mechanism of the voice pitch-dependent positive change of F0 due to Pt decrease. The airflow and the airway, including the vocal folds, were modeled in terms of mechanics of fluid and structure. Simulations of phonation using the numerical model indicated that Pt affects both the average position and the average amplitude magnitude of vocal fold self-excited oscillation in a non-monotonous manner. This effect results in voice pitch-dependent responses of F0 to Pt decreases, including the positive response of F0 as actually observed in humans. The findings of the present study highlight the importance of considering self-excited oscillation of the vocal folds in elucidation of the phonation mechanism.

Mechanisms of Memory Enhancement

PubMed Central

Stern, Sarah A.

2012-01-01

The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/NMDA receptor trafficking, neuromodulation (e.g. via dopamine, adrenaline, cortisol or acetylcholine) and metabolic processes (e.g. via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By capitalizing on this knowledge and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future. PMID:23151999

The influence of music during mechanical ventilation and weaning from mechanical ventilation: A review

PubMed Central

Hetland, Breanna; Lindquist, Ruth; Chlan, Linda L.

2015-01-01

Background Mechanical ventilation (MV) causes many distressing symptoms. Weaning, the gradual decrease in ventilator assistance leading to termination of MV, increases respiratory effort, which may exacerbate symptoms and prolong MV. Music, a non-pharmacological intervention without side effects may benefit patients during weaning from mechanical ventilatory support. Methods A narrative review of OVID Medline, PsychINFO, and CINAHL databases was conducted to examine the evidence for the use of music intervention in MV and MV weaning. Results Music intervention had a positive impact on ventilated patients; 16 quantitative and 2 qualitative studies were identified. Quantitative studies included randomized clinical trials (10), case controls (3), pilot studies (2) and a feasibility study. Conclusions Evidence supports music as an effective intervention that can lesson symptoms related to MV and promote effective weaning. It has potential to reduce costs and increase patient satisfaction. However, more studies are needed to establish its use during MV weaning. PMID:26227333

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

PubMed Central

Samal, Jasmine; Kandpal, Manish

2012-01-01

Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section. PMID:22232374

Increase in the Random Dopant Induced Threshold Fluctuations and Lowering in Sub 100 nm MOSFETs Due to Quantum Effects: A 3-D Density-Gradient Simulation Study

NASA Technical Reports Server (NTRS)

Asenov, Asen; Slavcheva, G.; Brown, A. R.; Davies, J. H.; Saini, S.

2000-01-01

In this paper we present a detailed simulation study of the influence of quantum mechanical effects in the inversion layer on random dopant induced threshold voltage fluctuations and lowering in sub 100 nm MOSFETs. The simulations have been performed using a 3-D implementation of the density gradient (DG) formalism incorporated in our established 3-D atomistic simulation approach. This results in a self-consistent 3-D quantum mechanical picture, which implies not only the vertical inversion layer quantisation but also the lateral confinement effects related to current filamentation in the 'valleys' of the random potential fluctuations. We have shown that the net result of including quantum mechanical effects, while considering statistical dopant fluctuations, is an increase in both threshold voltage fluctuations and lowering. At the same time, the random dopant induced threshold voltage lowering partially compensates for the quantum mechanical threshold voltage shift in aggressively scaled MOSFETs with ultrathin gate oxides.

2D simulations of orthogonal cutting of CFRP: Effect of tool angles on parameters of cut and chip morphology

NASA Astrophysics Data System (ADS)

Benhassine, Mehdi; Rivière-Lorphèvre, Edouard; Arrazola, Pedro-Jose; Gobin, Pierre; Dumas, David; Madhavan, Vinay; Aizpuru, Ohian; Ducobu, François

2018-05-01

Carbon-fiber reinforced composites (CFRP) are attractive materials for lightweight designs in applications needing good mechanical properties. Machining of such materials can be harder than metals due to their anisotropic behavior. In addition, the combination of the fibers and resin mechanical properties must also include the fiber orientation. In the case of orthogonal cutting, the tool inclination, rake angle or cutting angle usually influence the cutting process but such a detailed investigation is currently lacking in a 2D configuration. To address this issue, a model has been developed with Abaqus Explicit including Hashin damage. This model has been validated with experimental results from the literature. The effects of the tool parameters (rake angle, clearance angle) on the tool cutting forces, CFRP chip morphology and surface damage are herewith studied. It is shown that 90° orientation for the CFRP increases the surface damage. The rake angle has a minimal effect on the cutting forces but modifies the chip formation times. The feed forces are increased with increasing rake angle.

Neuromuscular Control Deficits and the Risk of Subsequent Injury after a Concussion: A Scoping Review.

PubMed

Howell, David R; Lynall, Robert C; Buckley, Thomas A; Herman, Daniel C

2018-05-01

An emerging area of research has identified that an increased risk of musculoskeletal injury may exist upon returning to sports after a sport-related concussion. The mechanisms underlying this recently discovered phenomenon, however, remain unknown. One theorized reason for this increased injury risk includes residual neuromuscular control deficits that remain impaired despite clinical recovery. Thus, the objectives of this review were: (1) to summarize the literature examining the relationship between concussion and risk of subsequent injury and (2) to summarize the literature for one mechanism with a theorized association with this increased injury risk, i.e., neuromuscular control deficits observed during gait after concussion under dual-task conditions. Two separate reviews were conducted consistent with both specified objectives. Studies published before 9 December, 2016 were identified using PubMed, Web of Science, and Academic Search Premier (EBSCOhost). Inclusion for the objective 1 search included dependent variables of quantitative measurements of musculoskeletal injury after concussion. Inclusion criteria for the objective 2 search included dependent variables pertaining to gait, dynamic balance control, and dual-task function. A total of 32 studies were included in the two reviews (objective 1 n = 10, objective 2 n = 22). According to a variety of study designs, athletes appear to have an increased risk of sustaining a musculoskeletal injury following a concussion. Furthermore, dual-task neuromuscular control deficits may continue to exist after patients report resolution of concussion symptoms, or perform normally on other clinical concussion tests. Therefore, musculoskeletal injury risk appears to increase following a concussion and persistent motor system and attentional deficits also seem to exist after a concussion. While not yet experimentally tested, these motor system and attentional deficits may contribute to the risk of sustaining a musculoskeletal injury upon returning to full athletic participation.

Mechanical properties and structure-function relationships of human chondrocyte-seeded cartilage constructs after in vitro culture.

PubMed

Middendorf, Jill M; Griffin, Darvin J; Shortkroff, Sonya; Dugopolski, Caroline; Kennedy, Stephen; Siemiatkoski, Joseph; Cohen, Itai; Bonassar, Lawrence J

2017-10-01

Autologous Chondrocyte Implantation (ACI) is a widely recognized method for the repair of focal cartilage defects. Despite the accepted use, problems with this technique still exist, including graft hypertrophy, damage to surrounding tissue by sutures, uneven cell distribution, and delamination. Modified ACI techniques overcome these challenges by seeding autologous chondrocytes onto a 3D scaffold and securing the graft into the defect. Many studies on these tissue engineered grafts have identified the compressive properties, but few have examined frictional and shear properties as suggested by FDA guidance. This study is the first to perform three mechanical tests (compressive, frictional, and shear) on human tissue engineered cartilage. The objective was to understand the complex mechanical behavior, function, and changes that occur with time in these constructs grown in vitro using compression, friction, and shear tests. Safranin-O histology and a DMMB assay both revealed increased sulfated glycosaminoglycan (sGAG) content in the scaffolds with increased maturity. Similarly, immunohistochemistry revealed increased lubricin localization on the construct surface. Confined compression and friction tests both revealed improved properties with increased construct maturity. Compressive properties correlated with the sGAG content, while improved friction coefficients were attributed to increased lubricin localization on the construct surfaces. In contrast, shear properties did not improve with increased culture time. This study suggests the various mechanical and biological properties of tissue engineered cartilage improve at different rates, indicating thorough mechanical evaluation of tissue engineered cartilage is critical to understanding the performance of repaired cartilage. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2298-2306, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Calcium in the Mechanism of Ammonia-Induced Astrocyte Swelling

PubMed Central

Jayakumar, A.R.; Rao, K.V. Rama; Tong, X.Y; Norenberg, M.D.

2016-01-01

Brain edema, due largely to astrocyte swelling, is an important clinical problem in patients with acute liver failure. While mechanisms underlying astrocyte swelling in this condition are not fully understood, ammonia and associated oxidative/nitrosative stress (ONS) appear to be involved. Mechanisms responsible for the increase in reactive oxygen/nitrogen species (RONS) and their role in ammonia-induced astrocyte swelling, however, are poorly understood. Recent studies have demonstrated a transient increase in intracellular Ca2+ in cultured astrocytes exposed to ammonia. As Ca2+ is a known inducer of RONS, we investigated potential mechanisms by which Ca2+ may be responsible for the production of RONS and cell swelling in cultured astrocytes after treatment with ammonia. Exposure of cultured astrocytes to ammonia (5 mM) increased the formation of free radicals, including nitric oxide, and such increase was significantly diminished by treatment with the Ca2+ chelator BAPTA-AM. We then examined the activity of Ca2+-dependent enzymes that are known to generate RONS and found that ammonia significantly increased the activities of NADPH oxidase (NOX), constitutive nitric oxide synthase (cNOS) and phospholipase A2 (PLA2) and such increases in activity were significantly diminished by BAPTA. Pretreatment of cultures with 7-nitroindazole, apocyanin and quinacrine, respective inhibitors of cNOS, NOX and PLA2, all significantly diminished RONS production. Additionally, treatment of cultures with BAPTA or with inhibitors of cNOS, NOX and PLA2 reduced ammonia-induced astrocyte swelling. These studies suggest that the ammonia-induced rise in intracellular Ca2+ activates free radical producing enzymes that ultimately contribute to the mechanism of astrocyte swelling. PMID:19393035

The Role of Psychobiological and Neuroendocrine Mechanisms in Appetite Regulation and Obesity

PubMed Central

Paspala, Ioanna; Katsiki, Niki; Kapoukranidou, Dorothea; Mikhailidis, Dimitri P; Tsiligiroglou-Fachantidou, Anna

2012-01-01

Obesity is a multifactorial disease. Among its causes are physical inactivity and overeating. In addition, other factors may play an important role in the development of overweight/obesity. For example, certain hormones including leptin, insulin and ghrelin, may influence appetite and consequently body weight. Obesity frequently co-exists with metabolic disorders including dyslipidemia, hypertension and insulin resistance, thus constituting the metabolic syndrome which is characterized by increased cardiovascular risk. Lack of comprehensive knowledge on obesity-related issues makes both prevention and treatment difficult. This review considers the psychobiological and neuroendocrine mechanisms of appetite and food intake. Whether these factors, in terms of obesity prevention and treatment, will prove to be relevant in clinical practice (including reducing the cardiovas-cular risk associated with obesity) remains to be established. PMID:23346258

Botanical modulation of menopausal symptoms: Mechanisms of action?

PubMed Central

Hajirahimkhan, Atieh; Dietz, Birgit M.; Bolton, Judy L.

2013-01-01

Menopausal women suffer from a variety of symptoms, including hot flashes and night sweats which can affect quality of life. Although hormone therapy (HT) has been the treatment of choice for relieving these symptoms, HT has been associated with increased breast cancer risk leading many women to search for natural, efficacious, and safe alternatives such as botanical supplements. Data from clinical trials suggesting that botanicals have efficacy for menopausal symptom relief, have been controversial and several mechanisms of action have been proposed including estrogenic, progestogenic, and serotonergic pathways. Plant extracts with potential estrogenic activities include soy, red clover, kudzu, hops, licorice, rhubarb, yam, and chasteberry. Botanicals with reported progestogenic activities are red clover, hops, yam, and chasteberry. Serotonergic mechanisms have also been proposed since women taking antidepressants often report reduction in hot flashes and night sweats. Black cohosh, kudzu, kava, licorice, and dong quai all either have reported 5-HT7 ligands or inhibit serotonin re-uptake, therefore have potential serotonergic activities. Understanding the mechanisms of action of these natural remedies used for women’s health, could lead to more efficacious formulations and to the isolation of active components which have the potential of becoming effective medications in the future. PMID:23408273

Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage

PubMed Central

Johnson, Anthea; Singhal, Naresh

2015-01-01

The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency. PMID:26512647

A Mechanistic Model of the Actin Cycle

PubMed Central

Bindschadler, M.; Osborn, E. A.; Dewey, C. F.; McGrath, J. L.

2004-01-01

We have derived a broad, deterministic model of the steady-state actin cycle that includes its major regulatory mechanisms. Ours is the first model to solve the complete nucleotide profile within filaments, a feature that determines the dynamics and geometry of actin networks at the leading edges of motile cells, and one that has challenged investigators developing models to interpret steady-state experiments. We arrived at the nucleotide profile through analytic and numerical approaches that completely agree. Our model reproduces behaviors seen in numerous experiments with purified proteins, but allows a detailed inspection of the concentrations and fluxes that might exist in these experiments. These inspections provide new insight into the mechanisms that determine the rate of actin filament treadmilling. Specifically, we find that mechanisms for enhancing Pi release from the ADP·Pi intermediate on filaments, for increasing the off rate of ADP-bound subunits at pointed ends, and the multiple, simultaneous functions of profilin, make unique and essential contributions to increased treadmilling. In combination, these mechanisms have a theoretical capacity to increase treadmilling to levels limited only by the amount of available actin. This limitation arises because as the cycle becomes more dynamic, it tends toward the unpolymerized state. PMID:15111391

Student views on the role of self-regulated learning in a surgery clerkship.

PubMed

Lyons-Warren, Ariel M; Kirby, John P; Larsen, Douglas P

2016-12-01

Self-regulated learning, including student-generated learning goals and flexibility in the learning structure are increasingly being used to enhance medical education. The role of these practices in surgical education of medical students has not been studied. We administered an 18-question electronic survey to all third-year medical students at Washington University in St. Louis School of Medicine. Of the 126 students invited, 64 responded and 56 were included in the analysis. We found that third-year medical students develop learning goals at the beginning of the surgery clerkship. Although these learning goals theoretically can be a mechanism for enhanced student-faculty engagement, students are not aware of formal mechanisms for sharing these goals with faculty members. Furthermore, students report a lack of flexibility within the surgery clerkship and discomfort with requesting specific learning opportunities. Finally, students report that they believe increased flexibility could improve student engagement, learning, and the overall clerkship experience. We therefore propose that a mechanism for students to share their learning goals with faculty and an infrastructure in which student learning experiences can be tailored to fit with these individualized goals would enhance student surgical learning. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes.

PubMed

Hobbs, Paul M; Johnson, William G; Graham, David Y

2016-08-06

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain.

CORTICOSTEROIDS AND MUSCLE WASTING ROLE OF TRANSCRIPTION FACTORS, NUCLEAR COFACTORS, AND HYPERACETYLATION

PubMed Central

Hasselgren, Per-Olof; Alamdari, Nima; Aversa, Zaira; Gonnella, Patricia; Smith, Ira J; Tizio, Steven

2010-01-01

Purpose of review The purpose of this review is to discuss novel insight into mechanisms of glucocorticoid-regulated muscle wasting, in particular the role of transcription factors and nuclear cofactors. In addition, novel strategies that may become useful in the treatment or prevention of glucocorticoid-induced muscle wasting are reviewed. Recent findings Studies suggest that glucocorticoid-induced upregulation of the transcription factors FOXO1 and C/EBPβ and downregulation of MyoD and myogenin are involved in glucocorticoid-induced muscle wasting. In addition, glucocorticoid-induced hyperacetylation caused by increased expression of the nuclear cofactor p300 and its histone acetyl transferase activity and decreased expression and activity of histone deacetylases (HDACs) plays an important role in glucocorticoid-induced muscle proteolysis and wasting. Other mechanisms may also be involved in glucocorticoid-induced muscle wasting, including insulin resistance and store-operated calcium entry. Novel potential strategies to prevent or treat glucocorticoid-induced muscle wasting include the use of small molecule HDAC activators, dissociated glucocorticoid receptor agonists, and 11β-hydroxysteroid dehydrogenase type 1 inhibitors. Summary An increased understanding of molecular mechanisms regulating glucocorticoid-induced muscle wasting will help develop new strategies to prevent and treat this debilitating condition. PMID:20473154

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes

PubMed Central

Hobbs, Paul M; Johnson, William G; Graham, David Y

2016-01-01

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain. PMID:27602238

Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

PubMed Central

Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

2014-01-01

This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-“aging gastropathy”-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications (e.g., NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically. PMID:24782600

Mechanical stress induces lung fibrosis by epithelial-mesenchymal transition.

PubMed

Cabrera-Benítez, Nuria E; Parotto, Matteo; Post, Martin; Han, Bing; Spieth, Peter M; Cheng, Wei-Erh; Valladares, Francisco; Villar, Jesús; Liu, Mingayo; Sato, Masaaki; Zhang, Haibo; Slutsky, Arthur S

2012-02-01

Many mechanically ventilated patients with acute respiratory distress syndrome develop pulmonary fibrosis. Stresses induced by mechanical ventilation may explain the development of fibrosis by a number of mechanisms (e.g., damage the alveolar epithelium, biotrauma). The objective of this study was t test the hypothesis that mechanical ventilation plays an important role in the pathogenesis of lung fibrosis. C57BL/6 mice were randomized into four groups: healthy controls; hydrochloric acid aspiration alone; vehicle control solution followed 24 hrs later by mechanical ventilation (peak inspiratory pressure 22 cm H(2)O and positive end-expiratory pressure 2 cm H(2)O for 2 hrs); and acid aspiration followed 24 hrs later by mechanical ventilation. The animals were monitored for up to 15 days after acid aspiration. To explore the direct effects of mechanical stress on lung fibrotic formation, human lung epithelial cells (BEAS-2B) were exposed to mechanical stretch for up to 48 hrs. Impaired lung mechanics after mechanical ventilation was associated with increased lung hydroxyproline content, and increased expression of transforming growth factor-β, β-catenin, and mesenchymal markers (α-smooth muscle actin and vimentin) at both the gene and protein levels. Expression of epithelial markers including cytokeratin-8, E-cadherin, and prosurfactant protein B decreased. Lung histology demonstrated fibrosis formation and potential epithelia-mesenchymal transition. In vitro direct mechanical stretch of BEAS-2B cells resulted in similar fibrotic and epithelia-mesenchymal transition formation. Mechanical stress induces lung fibrosis, and epithelia-mesenchymal transition may play an important role in mediating the ventilator-induced lung fibrosis.

Coexistence of Ureaplasma and chorioamnionitis is associated with prolonged mechanical ventilation.

PubMed

Jung, Euiseok; Choi, Chang Won; Kim, Su Yeong; Sung, Tae-Jung; Kim, Haeryoung; Park, Kyoung Un; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

2017-01-01

Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants. © 2016 Japan Pediatric Society.

Low‑level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling‑associated mechanism.

PubMed

Gao, Heqi; Zhai, Mingming; Wang, Pan; Zhang, Xuhui; Cai, Jing; Chen, Xiaofei; Shen, Guanghao; Luo, Erping; Jing, Da

2017-07-01

Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive. The current study systematically investigated the effect and potential molecular signaling mechanisms in mediating the effects of mechanical vibration (0.5 gn, 45 Hz) on primary osteoblasts in vitro. The results of the present study demonstrated that low‑level mechanical stimulation promoted osteoblastic proliferation and extracellular matrix mineralization. In addition, it was also revealed that mechanical vibration induced improved cytoskeleton arrangement in primary osteoblasts. Furthermore, mechanical vibration resulted in significantly increased gene expression of alkaline phosphatase, bone morphogenetic protein 2 and osteoprotegerin, and suppressed sclerostin gene expression, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses. Mechanical vibration was observed to upregulate gene and protein expression levels of osteogenesis‑associated biomarkers, including osteocalcin and Runt‑related transcription factor 2. In addition, RT‑qPCR and western blotting analysis demonstrated that mechanical vibration promoted gene and protein expression of canonical Wnt signaling genes, including Wnt3a, low‑density lipoprotein receptor‑related protein 6 and β‑catenin. In conclusion, the present study demonstrated that mechanical vibration stimulates osteoblastic activities and may function through a potential canonical Wnt signaling‑associated mechanism. These findings provided novel information that improves the understanding of the molecular mechanisms involved in osteoblastic activities in response to mechanical vibration, which may facilitate the scientific application of mechanical vibration for the treatment of osteoporosis in the clinic.

Towards a common framework of grounded action cognition: Relating motor control, perception and cognition.

PubMed

Gentsch, Antje; Weber, Arne; Synofzik, Matthis; Vosgerau, Gottfried; Schütz-Bosbach, Simone

2016-01-01

The relation between motor control and action cognition - including action-related thoughts and action-related perception - has been subject to controversial discussions in the last three decades. During these decades, cognitive neuroscience has been increasingly confronted with a huge variety of different accounts trying to understand and explain the relation between these systems, their interdependencies and the mediating mechanisms by establishing notions such as "internal models", "simulation" or "shared representation". These accounts, however, include a large array of partly overlapping, partly contradictory theories using similar terms for different mechanisms and different terms for similar mechanisms. In the absence of a systematic work-up and comparison, this array of accounts and theories leads to confusion in the field, duplication of experimental work, and unconnected parallelism of theory formation within and between different disciplines. Here we provide a systematic comparison of current models and prospective theories that deal with the relation between cognition, perception and motor control mechanisms. In a second step, we propose "grounded action cognition" as a comprehensive metatheoretical framework which defines different hypothetical possibilities of the relations between these domains, offers systematic insights into current models and theories and last but not least may help to increase comparability of empirical research in the domain of action and action cognition. Copyright © 2015 Elsevier B.V. All rights reserved.

Morphology and characterization of 3D micro-porous structured chitosan scaffolds for tissue engineering.

PubMed

Hsieh, Wen-Chuan; Chang, Chih-Pong; Lin, Shang-Ming

2007-06-15

This research studies the morphology and characterization of three-dimensional (3D) micro-porous structures produced from biodegradable chitosan for use as scaffolds for cells culture. The chitosan 3D micro-porous structures were produced by a simple liquid hardening method, which includes the processes of foaming by mechanical stirring without any chemical foaming agent added, and hardening by NaOH cross linking. The pore size and porosity were controlled with mechanical stirring strength. This study includes the morphology of chitosan scaffolds, the characterization of mechanical properties, water absorption properties and in vitro enzymatic degradation of the 3D micro-porous structures. The results show that chitosan 3D micro-porous structures were successfully produced. Better formation samples were obtained when chitosan concentration is at 1-3%, and concentration of NaOH is at 5%. Faster stirring rate would produce samples of smaller pore diameter, but when rotation speed reaches 4000 rpm and higher the changes in pore size is minimal. Water absorption would reduce along with the decrease of chitosan scaffolds' pore diameter. From stress-strain analysis, chitosan scaffolds' mechanical properties are improved when it has smaller pore diameter. From in vitro enzymatic degradation results, it shows that the disintegration rate of chitosan scaffolds would increase along with the processing time increase, but approaching equilibrium when the disintegration rate reaches about 20%.

Rebelling against the (Insulin) Resistance: A Review of the Proposed Insulin-Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds

PubMed Central

Zahradka, Peter

2018-01-01

Insulin resistance is a major risk factor for diseases such as type 2 diabetes and metabolic syndrome. Current methods for management of insulin resistance include pharmacological therapies and lifestyle modifications. Several clinical studies have shown that leguminous plants such as soybeans and pulses (dried beans, dried peas, chickpeas, lentils) are able to reduce insulin resistance and related type 2 diabetes parameters. However, to date, no one has summarized the evidence supporting a mechanism of action for soybeans and pulses that explains their ability to lower insulin resistance. While it is commonly assumed that the biological activities of soybeans and pulses are due to their antioxidant activities, these bioactive compounds may operate independent of their antioxidant properties and, thus, their ability to potentially improve insulin sensitivity via alternative mechanisms needs to be acknowledged. Based on published studies using in vivo and in vitro models representing insulin resistant states, the proposed mechanisms of action for insulin-sensitizing actions of soybeans, chickpeas, and their bioactive compounds include increasing glucose transporter-4 levels, inhibiting adipogenesis by down-regulating peroxisome proliferator-activated receptor-γ, reducing adiposity, positively affecting adipokines, and increasing short-chain fatty acid-producing bacteria in the gut. Therefore, this review will discuss the current evidence surrounding the proposed mechanisms of action for soybeans and certain pulses, and their bioactive compounds, to effectively reduce insulin resistance. PMID:29601521

Enhanced Biennial Variability in the Pacific due to Atlantic Capacitor Effect after the Early 1990s

NASA Astrophysics Data System (ADS)

WANG, L.; Yu, J. Y.; Paek, H.

2016-12-01

The El Niño-Southern Oscillation (ENSO) and Pacific subtropical highs (PSHs) have major impacts on social and ecological systems through their influences on severe natural hazards including tropical storms, coastal erosions, droughts and floods. The ability to forecast ENSO and PSHs requires an understanding of the underlying physical mechanisms that drive their variability. Here we present an Atlantic capacitor effect mechanism to suggest the Atlantic as a key pacemaker of the biennial variability in the Pacific including ENSO and PSHs in recent decades, while the pacemaker was previously considered to be mainly lied within the Pacific or Indian Oceans. The "charging" (i.e., ENSO imprinting the North Tropical Atlantic (NTA) sea surface temperature (SST) via an atmospheric bridge mechanism) and "discharging" (i.e., the NTA SST triggering the following ENSO via a subtropical teleconnection mechanism) process works alternately, generating the biennial rhythmic changes in the Pacific. After the early-1990s, the positive phase of the Atlantic Multidecadal Oscillation and global warming provides more favorable background states over the NTA that enable the Atlantic capacitor effect to operate more efficiently, giving rise to enhanced biennial variability in the Pacific which may increase the occurrence frequency of severe natural hazard events. The results highlight the increasing important role of the Atlantic-Pacific coupling as an important pacemaker of the ENSO cycle in recent decades.

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

Esfahani, M. Nasr; Yilmaz, M.; Sonne, M. R.

The trend towards nanomechanical resonator sensors with increasing sensitivity raises the need to address challenges encountered in the modeling of their mechanical behavior. Selecting the best approach in mechanical response modeling amongst the various potential computational solid mechanics methods is subject to controversy. A guideline for the selection of the appropriate approach for a specific set of geometry and mechanical properties is needed. In this study, geometrical limitations in frequency response modeling of flexural nanomechanical resonators are investigated. Deviation of Euler and Timoshenko beam theories from numerical techniques including finite element modeling and Surface Cauchy-Born technique are studied. The resultsmore » provide a limit beyond which surface energy contribution dominates the mechanical behavior. Using the Surface Cauchy-Born technique as the reference, a maximum error on the order of 50 % is reported for high-aspect ratio resonators.« less

Role of Oxidative Stress as Key Regulator of Muscle Wasting during Cachexia.

PubMed

Ábrigo, Johanna; Elorza, Alvaro A; Riedel, Claudia A; Vilos, Cristian; Simon, Felipe; Cabrera, Daniel; Estrada, Lisbell; Cabello-Verrugio, Claudio

2018-01-01

Skeletal muscle atrophy is a pathological condition mainly characterized by a loss of muscular mass and the contractile capacity of the skeletal muscle as a consequence of muscular weakness and decreased force generation. Cachexia is defined as a pathological condition secondary to illness characterized by the progressive loss of muscle mass with or without loss of fat mass and with concomitant diminution of muscle strength. The molecular mechanisms involved in cachexia include oxidative stress, protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction. Oxidative stress is one of the most common mechanisms of cachexia caused by different factors. It results in increased ROS levels, increased oxidation-dependent protein modification, and decreased antioxidant system functions. In this review, we will describe the importance of oxidative stress in skeletal muscles, its sources, and how it can regulate protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction involved in cachexia.

Trophic compensation reinforces resistance: herbivory absorbs the increasing effects of multiple disturbances.

PubMed

Ghedini, Giulia; Russell, Bayden D; Connell, Sean D

2015-02-01

Disturbance often results in small changes in community structure, but the probability of transitioning to contrasting states increases when multiple disturbances combine. Nevertheless, we have limited insights into the mechanisms that stabilise communities, particularly how perturbations can be absorbed without restructuring (i.e. resistance). Here, we expand the concept of compensatory dynamics to include countervailing mechanisms that absorb disturbances through trophic interactions. By definition, 'compensation' occurs if a specific disturbance stimulates a proportional countervailing response that eliminates its otherwise unchecked effect. We show that the compounding effects of disturbances from local to global scales (i.e. local canopy-loss, eutrophication, ocean acidification) increasingly promote the expansion of weedy species, but that this response is countered by a proportional increase in grazing. Finally, we explore the relatively unrecognised role of compensatory effects, which are likely to maintain the resistance of communities to disturbance more deeply than current thinking allows. © 2015 John Wiley & Sons Ltd/CNRS.

Developmental origins of NAFLD: a womb with a clue

PubMed Central

Wesolowski, Stephanie R.; El Kasmi, Karim C.; Jonscher, Karen R.; Friedman, Jacob E.

2017-01-01

Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation. PMID:27780972

Energy evolution mechanism in process of Sandstone failure and energy strength criterion

NASA Astrophysics Data System (ADS)

Wang, Yunfei; Cui, Fang

2018-07-01

To reveal the inherent relation between energy change and confining pressure during the process of sandstone damage, and its characteristics of energy storage and energy dissipation in different deformation stage. Obtaining the mechanical parameters by testing the Sandstone of two1 coal seam roof under uniaxial compression in Zhaogu coalmine, using Particle Flow Code (PFC) and fish program to get the meso-mechanical parameters, studying Sandstone energy evolution mechanism under different confining pressures, and deducing energy strength criterion based on energy principle of rock failure, some main researching results are reached as follows: with the increasing of confining pressure, the Sandstone yield stage and ductility increases, but brittleness decreases; Under higher confining pressure, the elastic strain energy of Sandstone before peak approximately keeps constant in a certain strain range, and rock absorbs all the energy which converts into surface energy required for internal damage development; Under lower confining pressure, Sandstone no longer absorbs energy with increasing strain after peak under lower confining pressure, while it sequentially absorbs energy under higher confining pressure; Under lower confining pressure, the energy Sandstone before peak absorbed mainly converts into elastic strain energy, while under higher confining pressure, dissipation energy significantly increases before peak, which indicates that the degree rock strength loss is higher under higher confining pressure; with the increasing of confining pressure, the limit of elastic strain energy increases and there exists a favourable linear variation relationship; At the peak point, the ratio of elastic strain energy to total energy of Sandstone nonlinearly decreases, while the ratio of dissipation energy to total energy nonlinearly increases with the increasing of confining pressure; According to energy evolution mechanism of rock failure, an energy strength criterion is derived. The criterion equation includes lithology constants and three principal stresses, and its physical meaning is clear. This criterion has an evident advantage than Hoek-Brown and Drucker-Prager criterion in calculation accuracy and can commendably describe rock failure characteristics.

Mechanically flexible organic electroluminescent device with directional light emission

DOEpatents

Duggal, Anil Raj; Shiang, Joseph John; Schaepkens, Marc

2005-05-10

A mechanically flexible and environmentally stable organic electroluminescent ("EL") device with directional light emission comprises an organic EL member disposed on a flexible substrate, a surface of which is coated with a multilayer barrier coating which includes at least one sublayer of a substantially transparent organic polymer and at least one sublayer of a substantially transparent inorganic material. The device includes a reflective metal layer disposed on the organic EL member opposite to the substrate. The reflective metal layer provides an increased external quantum efficiency of the device. The reflective metal layer and the multilayer barrier coating form a seal around the organic EL member to reduce the degradation of the device due to environmental elements.

Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study

USDA-ARS?s Scientific Manuscript database

Objective: To increase understanding of the biological mechanisms underlying this association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, beta-carotene, nitrate, folate,...

Nanotechnology as a therapeutic tool to combat microbial resistance.

PubMed

Pelgrift, Robert Y; Friedman, Adam J

2013-11-01

Use of nanoparticles is among the most promising strategies to overcome microbial drug resistance. This review article consists of three parts. The first part discusses the epidemiology of microbial drug resistance. The second part describes mechanisms of drug resistance used by microbes. The third part explains how nanoparticles can overcome this resistance, including the following: Nitric oxide-releasing nanoparticles (NO NPs), chitosan-containing nanoparticles (chitosan NPs), and metal-containing nanoparticles all use multiple mechanisms simultaneously to combat microbes, thereby making development of resistance to these nanoparticles unlikely. Packaging multiple antimicrobial agents within the same nanoparticle also makes development of resistance unlikely. Nanoparticles can overcome existing drug resistance mechanisms, including decreased uptake and increased efflux of drug from the microbial cell, biofilm formation, and intracellular bacteria. Finally, nanoparticles can target antimicrobial agents to the site of infection, so that higher doses of drug are given at the infected site, thereby overcoming resistance. © 2013.

Investigating the mechanism(s) underlying switching between states in bipolar disorder

PubMed Central

Young, Jared W.; Dulcis, Davide

2015-01-01

Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching. PMID:25814263

Effects of Inflorescence Stem Structure and Cell Wall Components on the Mechanical Strength of Inflorescence Stem in Herbaceous Peony

PubMed Central

Zhao, Daqiu; Han, Chenxia; Tao, Jun; Wang, Jing; Hao, Zhaojun; Geng, Qingping; Du, Bei

2012-01-01

Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but its poor inflorescence stem quality seriously constrains the development of the cut flower. Mechanical strength is an important characteristic of stems, which not only affects plant lodging, but also plays an important role in stem bend or break. In this paper, the mechanical strength, morphological indices and microstructure of P. lactiflora development inflorescence stems were measured and observed. The results showed that the mechanical strength of inflorescence stems gradually increased, and that the diameter of inflorescence stem was a direct indicator in estimating mechanical strength. Simultaneously, with the development of inflorescence stem, the number of vascular bundles increased, the vascular bundle was arranged more densely, the sclerenchyma cell wall thickened, and the proportion of vascular bundle and pith also increased. On this basis, cellulose and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated and their expression patterns were examined including PlPAL. The results showed that cellulose was not strictly correlated with the mechanical strength of inflorescence stem, and lignin had a significant impact on it. In addition, PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora and their functions were also different, but PlPAL and PlCCoAOMT regulated the lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT could be applied to improve the mechanical strength of P. lactiflora inflorescence stem in genetic engineering. PMID:22606025

Effects of inflorescence stem structure and cell wall components on the mechanical strength of inflorescence stem in herbaceous peony.

PubMed

Zhao, Daqiu; Han, Chenxia; Tao, Jun; Wang, Jing; Hao, Zhaojun; Geng, Qingping; Du, Bei

2012-01-01

Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but its poor inflorescence stem quality seriously constrains the development of the cut flower. Mechanical strength is an important characteristic of stems, which not only affects plant lodging, but also plays an important role in stem bend or break. In this paper, the mechanical strength, morphological indices and microstructure of P. lactiflora development inflorescence stems were measured and observed. The results showed that the mechanical strength of inflorescence stems gradually increased, and that the diameter of inflorescence stem was a direct indicator in estimating mechanical strength. Simultaneously, with the development of inflorescence stem, the number of vascular bundles increased, the vascular bundle was arranged more densely, the sclerenchyma cell wall thickened, and the proportion of vascular bundle and pith also increased. On this basis, cellulose and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated and their expression patterns were examined including PlPAL. The results showed that cellulose was not strictly correlated with the mechanical strength of inflorescence stem, and lignin had a significant impact on it. In addition, PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora and their functions were also different, but PlPAL and PlCCoAOMT regulated the lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT could be applied to improve the mechanical strength of P. lactiflora inflorescence stem in genetic engineering.

Asymmetries in reciprocal baroreflex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome.

PubMed

Davydov, D M; Naliboff, B; Shahabi, L; Shapiro, D

2018-02-01

Objective measures of pain severity remain ill defined, although its accurate measurement is critical. Reciprocal baroreflex mechanisms of blood pressure (BP) control were found to impact differently on pain regulation, and thus their asymmetry was hypothesized to also connect to chronic pain duration and severity. Seventy-eight female patients with irritable bowel syndrome (IBS) and 27 healthy women were assessed for IBS severity and chronicity, negative affect, and various measures of resting autonomic function including BP, heart rate and its variability (HRV), baroreceptor-sensitivity to activations and inhibitions, gains of brady- and tachy-cardiac baro-responses, gains of BP falls/rises, and BP start points for these spontaneous baroreflexes. IBS directly and indirectly (through increased negative affect) was associated with asymmetry between baroreceptor activations/inhibitions compared to symmetrical baroreflex reciprocity in the healthy women. In the IBS group, independently of specific IBS symptoms, pain chronicity was associated with (i) decreased BP falls coupled with either (a) decreased tachycardia associated with lower disease severity (earlier "pain resilience" mechanism), or (b) decreased bradycardia associated with higher disease severity (later "pain decompensation" mechanism), or (ii) increased BP start point for baroreceptor activations coupled with either (a) BP increase (delayed "pain adaptation" mechanism) or (b) affect-related HRV decrease (delayed "pain aggravation" mechanism). We anticipate the findings to be a starting point for validating these autonomic metrics of pain suffering and pain coping mechanisms in other chronic pain syndromes to suggest them as biomarkers of its severity and duration for profiling and correct management of chronic pain patients. © 2017 John Wiley & Sons Ltd.

Bovine versus Porcine Acellular Dermal Matrix: A Comparison of Mechanical Properties.

PubMed

Adelman, David M; Selber, Jesse C; Butler, Charles E

2014-05-01

Porcine and bovine acellular dermal matrices (PADM and BADM, respectively) are the most commonly used biologic meshes for ventral hernia repair. A previous study suggests a higher rate of intraoperative device failures using PADM than BADM. We hypothesize that this difference is, in part, related to intrinsic mechanical properties of the matrix substrate and source material. The following study directly compares these 2 matrices to identify any potential differences in mechanical properties that may relate to clinical outcomes. Sections of PADM (Strattice; Lifecell, Branchburg, N.J.) and BADM (SurgiMend; TEI Biosciences, Boston, Mass.) were subjected to a series of biomechanical tests, including suture retention, tear strength, and uniaxial tensile strength. Results were collected and compared statistically. In all parameters, BADM exhibited a superior mechanical strength profile compared with PADM of similar thickness. Increased BADM thickness correlated with increased mechanical strength. In suture tear-through testing with steel wire, failure of the steel wire occurred in the 4-mm-thick BADM, whereas the matrix material failed in all other thicknesses of BADM and PADM. Before implantation, BADM is inherently stronger than PADM at equivalent thicknesses and considerably stronger at increased thicknesses. These results corroborate clinical data from a previous study in which PADM was associated with a higher intraoperative device failure rate. Although numerous properties of acellular dermal matrix contribute to clinical outcomes, surgeons should consider initial mechanical strength properties when choosing acellular dermal matrices for load-bearing applications such as hernia repair.

A systematic review of the anti-obesity and weight lowering effect of ginger (Zingiber officinale Roscoe) and its mechanisms of action.

PubMed

Ebrahimzadeh Attari, Vahideh; Malek Mahdavi, Aida; Javadivala, Zeinab; Mahluji, Sepideh; Zununi Vahed, Sepideh; Ostadrahimi, Alireza

2018-04-01

Recently, the beneficial effects of ginger on obesity is taken into consideration. Albeit, it seems that the anti-obesity effect of ginger and its mechanism of action has not yet been reviewed. Therefore, the aim of this study was to systematically review the effect of Zingiber officinale Roscoe on obesity management. Databases including PubMed, Scopus, Google scholar, and Science Direct were searched from 1995 until May 2017 using the definitive keywords. Searching was limited to articles with English language. All of the relevant human and animal studies and also in vitro studies were included. Review articles, abstract in congress, and also other varieties of ginger were excluded. Eligibility of included articles were evaluated by 3 reviewers, which also extracted data. Articles were critically assessed individually for possible risk of bias. Twenty-seven articles (6 in vitro, 17 animal, and 4 human studies) were reviewed. Most of the experimental studies supported the weight lowering effect of ginger extract or powder in obese animal models, whereas the results of the available limited clinical studies showed no changes or slight changes of anthropometric measurements and body composition in subjects with obesity. Ginger could modulate obesity through various potential mechanisms including increasing thermogenesis, increasing lipolysis, suppression of lipogenesis, inhibition of intestinal fat absorption, and controlling appetite. This review article provides some convincing evidence to support the efficacy of ginger in obesity management and demonstrates the importance of future clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.

STRETCHING IMPACTS INFLAMMATION RESOLUTION IN CONNECTIVE TISSUE

PubMed Central

Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J.; Colas, Romain A.; Spite, Matthew; Serhan, Charles N.; Langevin, Helene M.

2016-01-01

Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. PMID:26588184

Gastro-esophageal reflux disease and obesity, where is the link?

PubMed

Emerenziani, Sara; Rescio, Maria Paola; Guarino, Michele Pier Luca; Cicala, Michele

2013-10-21

The confluence between the increased prevalence of gastro-esophageal reflux disease (GERD) and of obesity has generated great interest in the association between these two conditions. Several studies have addressed the potential relationship between GERD and obesity, but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined. A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter, thus exposing the esophageal mucosal to gastric content. Apart from the mechanical pressure, visceral fat is metabolically active and it has been strongly associated with serum levels of adipo-cytokines including interleukin-6 and tumor necrosis factor α, which may play a role in GERD or consequent carcinogenesis. This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity, and to better understand the possible role of weight loss as a therapeutic approach for GERD.

The serotonin axis: Shared mechanisms in seizures, depression and SUDEP

PubMed Central

Richerson, George B.; Buchanan, Gordon F.

2010-01-01

Summary There is a growing appreciation that patients with seizures are also affected by a number of co-morbid conditions, including an increase in prevalence of depression (Kanner, 2009), sleep apnea (Chihorek et al, 2007), and sudden death (Ryvlin et al, 2006; Tomson et al, 2008). The mechanisms responsible for these associations are unclear. Here we discuss the possibility that underlying pathology in the serotonin (5-HT) system of epilepsy patients lowers the threshold for seizures, while also increasing the risk of depression and sudden death. We propose that post-ictal dysfunction of 5-HT neurons causes depression of breathing and arousal in some epilepsy patients, and this can lead to sudden unexpected death in epilepsy (SUDEP). We further draw parallels between SUDEP and sudden infant death syndrome (SIDS), which may share pathophysiological mechanisms, and which have both been linked to defects in the 5-HT system. PMID:21214537

An extract from the Atlantic brown algae Saccorhiza polyschides counteracts diet-induced obesity in mice via a gut related multi-factorial mechanisms.

PubMed

Huebbe, Patricia; Nikolai, Sibylle; Schloesser, Anke; Herebian, Diran; Campbell, Graeme; Glüer, Claus-Christian; Zeyner, Annette; Demetrowitsch, Tobias; Schwarz, Karin; Metges, Cornelia C; Roeder, Thomas; Schultheiss, Gerhard; Ipharraguerre, Ignacio R; Rimbach, Gerald

2017-09-26

In this study we addressed the questions whether an Atlantic brown algae extract (BAE) affects diet induced obesity in mice and which would be the primary targets and underlying key mechanisms. Male C57 BL/6 mice were fed a hypercaloric diet, referred to as high fat diet (HFD), supplemented with a freeze-dried aqueous BAE from Saccorhiza polyschides (5 %) for 8 months. Compared to the control group, dietary BAE supplementation significantly attenuated increase in body weight and fat mass. We observed apparent metabolic improvement including normalization of blood glucose, reduced plasma leptin, reduced fecal bile salt hydrolase activity with lower microbial production of toxic bile acid metabolites in the gut and increased systemic bile acid circulation in BAE-fed mice counteracting adverse effects of long term HFD feeding. Survival of mice receiving dietary BAE supplementation appeared slightly enhanced; however, median and maximal life spans as well as hepatic mTOR activation were not significantly different between BAE and control mice. We suggest that the beneficial metabolic effects of our BAE are at least partly mediated by alterations in gut microbiota associated with fermentation of indigestible polysaccharides that are major components of brown algae such as alginates and fucoidans. We moreover propose a multi-factorial mechanism that involves profound alterations in bile acid homeostasis, changes in intestinal and systemic glucose metabolism likely including increased intestinal gluconeogenesis, increased activity of the intestinally derived hormone GLP-1 contributing to promote systemic insulin sensitivity, and inhibition of α-amylase activity, which expectably limits dietary carbohydrate digestion and glucose release.

Synergistic effects from graphene and carbon nanotubes endow ordered hierarchical structure foams with a combination of compressibility, super-elasticity and stability and potential application as pressure sensors

NASA Astrophysics Data System (ADS)

Kuang, Jun; Dai, Zhaohe; Liu, Luqi; Yang, Zhou; Jin, Ming; Zhang, Zhong

2015-05-01

Nanostructured carbon material based three-dimensional porous architectures have been increasingly developed for various applications, e.g. sensors, elastomer conductors, and energy storage devices. Maintaining architectures with good mechanical performance, including elasticity, load-bearing capacity, fatigue resistance and mechanical stability, is prerequisite for realizing these functions. Though graphene and CNT offer opportunities as nanoscale building blocks, it still remains a great challenge to achieve good mechanical performance in their microarchitectures because of the need to precisely control the structure at different scales. Herein, we fabricate a hierarchical honeycomb-like structured hybrid foam based on both graphene and CNT. The resulting materials possess excellent properties of combined high specific strength, elasticity and mechanical stability, which cannot be achieved in neat CNT and graphene foams. The improved mechanical properties are attributed to the synergistic-effect-induced highly organized, multi-scaled hierarchical architectures. Moreover, with their excellent electrical conductivity, we demonstrated that the hybrid foams could be used as pressure sensors in the fields related to artificial skin.Nanostructured carbon material based three-dimensional porous architectures have been increasingly developed for various applications, e.g. sensors, elastomer conductors, and energy storage devices. Maintaining architectures with good mechanical performance, including elasticity, load-bearing capacity, fatigue resistance and mechanical stability, is prerequisite for realizing these functions. Though graphene and CNT offer opportunities as nanoscale building blocks, it still remains a great challenge to achieve good mechanical performance in their microarchitectures because of the need to precisely control the structure at different scales. Herein, we fabricate a hierarchical honeycomb-like structured hybrid foam based on both graphene and CNT. The resulting materials possess excellent properties of combined high specific strength, elasticity and mechanical stability, which cannot be achieved in neat CNT and graphene foams. The improved mechanical properties are attributed to the synergistic-effect-induced highly organized, multi-scaled hierarchical architectures. Moreover, with their excellent electrical conductivity, we demonstrated that the hybrid foams could be used as pressure sensors in the fields related to artificial skin. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00841g

Advances in helical stent design and fabrication thermal treatment and structural interaction studies of the simulated plaque-laden artery

NASA Astrophysics Data System (ADS)

Welch, Tre Raymond

Advancements in processing biomaterials have lead to the development of bioresorbable PLLA drug-loaded stents with different geometric configurations. To further advance the technology, systematic studies have been carried out. This dissertation consists of five specific aims: (1) To characterize the effects of thermal annealing on the mechanical characteristics of PLLA helical stent, (2) To characterize the mechanical characteristics of a PLLA double helix stent, (3) To characterize the physical and chemical properties of PLLA films impregnated with niacin and curcumin, (4) To characterize the mechanical interaction of expanded stent and vascular wall with both model simulation and experimental studies using PDMS phantom arteries, (5) To simulate the stent-plaque-artery interactions using computer models. Results and their significances in bioresorbable PLLA drug-loaded stents technology as well as clinical prospects will be presented. For Aim1, thermal annealing is shown to improve mechanical characteristics of the helical stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Differential scanning calorimetric analysis of stent fiber reveals that thermal annealing contribute to increased percent crystallinity, thus enhanced mechanical characteristics of the stent. For Aim 2, the new double helix design was shown to leads to improved mechanical characteristics of stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Further, it was found to lead to an increased percent crystallinity and reduced degradation rate. For Aim 3, the changes in mechanical properties, crystallinity in PLLA polymer loaded with curcumin, or niacin, or both from that of control are clearly delineated. Results from Aim 4 shed lights on the mechanical disturbance in the vicinity of deployed stent and vascular wall as well as the abnormal shear stresses on the vascular endothelium. Their implications in triggering thrombi formation are discussed. Results from Aim 5 provided insights on the stent-plaque-artery mechanical interaction and how the altered mechanical environment after stent deployment could affect vascular remodeling and factors lead to re-stenosis. The significances of this work in advancing the bioresorbable PLLA drug-loaded stents technology as well as its clinical prospects are presented.

Modifying the mechanics of healing infarcts: Is better the enemy of good?

PubMed

Clarke, Samantha A; Richardson, William J; Holmes, Jeffrey W

2016-04-01

Myocardial infarction (MI) is a major source of morbidity and mortality worldwide, with over 7 million people suffering infarctions each year. Heart muscle damaged during MI is replaced by a collagenous scar over a period of several weeks, and the mechanical properties of that scar tissue are a key determinant of serious post-MI complications such as infarct rupture, depression of heart function, and progression to heart failure. Thus, there is increasing interest in developing therapies that modify the structure and mechanics of healing infarct scar. Yet most prior attempts at therapeutic scar modification have failed, some catastrophically. This article reviews available information about the mechanics of healing infarct scar and the functional impact of scar mechanical properties, and attempts to infer principles that can better guide future attempts to modify scar. One important conclusion is that collagen structure, mechanics, and remodeling of healing infarct scar vary so widely among experimental models that any novel therapy should be tested across a range of species, infarct locations, and reperfusion protocols. Another lesson from past work is that the biology and mechanics of healing infarcts are sufficiently complex that the effects of interventions are often counterintuitive; for example, increasing infarct stiffness has little effect on heart function, and inhibition of matrix metalloproteases (MMPs) has little effect on scar collagen content. Computational models can help explain such counterintuitive results, and are becoming an increasingly important tool for integrating known information to better identify promising therapies and design experiments to test them. Moving forward, potentially exciting new opportunities for therapeutic modification of infarct mechanics include modulating anisotropy and promoting scar compaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolic mechanisms of drug-nutrient interactions.

PubMed

Hathcock, J N

1985-01-01

Metabolic mechanisms of nutrition and drug interactions include 1) the effects of diet on drug metabolism and action and 2) the effects of drugs on nutritional processes. The type, amount, and timing of foods consumed influence drug dissolution, absorption, distribution, metabolism, and excretion. High-fat meals enhance the absorption of griseofulvin and some other drugs. Milk and other sources of calcium inhibit absorption of tetracycline. High-fat meals increase plasma concentrations of free fatty acids and thereby displace many drugs from binding sites on plasma albumin. High-protein diets increase the activity of the mixed-function oxidase system and enhance the metabolism of numerous drugs. High-electrolyte intakes increase excretion of lithium and also diminish the action of diuretic agents. Bile acid sequestrants and some laxatives decrease lipid digestion and absorption, as well as absorption of the fat-soluble vitamins. Numerous drugs, including tetracycline and cholestyramine, bind iron and decrease its absorption. Coumarins inhibit the function of vitamin K. Phenobarbital and other anticonvulsants are inducers of cytochrome P-450 and the mixed-function oxidase system. Long-term treatment with these inducers can cause excessive metabolism and deficiency of vitamin D. Prooxidant drugs such as chloroquine, drugs detoxified by conjugation with glutathione, and alcohol can deplete reduced glutathione with consequent effects on amino acid transport and the redox status of cells. Acid-forming foods acidify the urine and increase the loss of alkaline drugs such as the amphetamines. Base-forming drugs increase the loss of acidic drugs such as barbiturates. The range of metabolic interactions of drugs and nutrients includes the full scope of physiological processes to which drugs and nutrients are subject.

Induced defense mechanisms in an aquatic angiosperm to insect herbivory.

PubMed

Fornoff, Felix; Gross, Elisabeth M

2014-05-01

In terrestrial angiosperms, defense and resistance mechanisms against herbivores have been studied extensively; yet this topic is poorly understood in aquatic angiosperms. We investigated induced response mechanisms in Myriophyllum spicatum to the generalist insect herbivore Acentria ephemerella in three independent experiments. Various morphological and chemical response variables were examined in grazed apical shoots and compared to undamaged controls. We further estimated plant palatability of induced and non-induced apices in choice assays, and assessed the growth response of Acentria larvae in no-choice feeding assays. Leaves of induced apices were splayed out horizontally and changed in color from green to red. The dry matter content and thus plant toughness increased by up to 19%, but silica levels stayed constant. Induced apices exhibited a decline in chlorophyll content of up to 34%, reflected also by a 10% decrease in nitrogen levels, while nitrogen increased by 14% in lower parts of grazed shoots. Also, herbivore-deterring total phenolic compounds increased by up to 20% in apices. In choice trials, Acentria larvae strongly avoided grazed tips, and growth was reduced by 25% on induced apices. In total, we observed five different induced resistance and defensive traits in grazed apices: changes in appearance, increased plant toughness, delocalization of N-containing metabolites, increased polyphenols, and reduced nutritional value. The observed changes prevent herbivore damage and loss of apical tissue, which are most valuable for plant fitness. Our study presents the first evidence of multiple, parallel defense strategies including constitutive and induced defense mechanisms in a freshwater angiosperm.

Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F

2016-09-01

Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®

Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

1990-01-01

The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

Influence of Coherent Tunneling and Incoherent Hopping on the Charge Transfer Mechanism in Linear Donor-Bridge-Acceptor Systems.

PubMed

Li, Guangqi; Govind, Niranjan; Ratner, Mark A; Cramer, Christopher J; Gagliardi, Laura

2015-12-17

The mechanism of charge transfer has been observed to change from tunneling to hopping with increasing numbers of DNA base pairs in polynucleotides and with the length of molecular wires. The aim of this paper is to investigate this transition by examining the population dynamics using a tight-binding Hamiltonian with model parameters to describe a linear donor-bridge-acceptor (D-B-A) system. The model includes a primary vibration and an electron-vibration coupling at each site. A further coupling of the primary vibration with a secondary phonon bath allows the system to dissipate energy to the environment and reach a steady state. We apply the quantum master equation (QME) approach, based on second-order perturbation theory in a quantum dissipative system, to examine the dynamical processes involved in charge-transfer and follow the population transfer rate at the acceptor, ka, to shed light on the transition from tunneling to hopping. With a small tunneling parameter, V, the on-site population tends to localize and form polarons, and the hopping mechanism dominates the transfer process. With increasing V, the population tends to be delocalized and the tunneling mechanism dominates. The competition between incoherent hopping and coherent tunneling governs the mechanism of charge transfer. By varying V and the total number of sites, we also examine the onset of the transition from tunneling to hopping with increasing length.

Thyrotoxicosis.

PubMed

Seigel, Stuart C; Hodak, Steven P

2012-03-01

Hyperthyroidism describes the sustained increase in thyroid hormone biosynthesis and secretion by a thyroid gland with increased metabolism. Although the use of radioiodine scanning serves as a useful surrogate that may help characterize the cause of thyrotoxicosis, it only indirectly addresses the underlying physiologic mechanism driving the increase in serum thyroid hormones. In this article, thyrotoxic states are divided into increased or decreased thyroid metabolic function. In addition to the diagnosis, clinical presentation, and treatment of the various causes of hyperthyroidism, a section on functional imaging and appropriate laboratory testing is included. Copyright © 2012 Elsevier Inc. All rights reserved.

Mechanical forces and their second messengers in stimulating cell growth in vitro

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.

1992-01-01

Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative 'mechanogenic' second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.

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

Xie, Miao; Mohammadi, Reza; Turner, Christopher L.

In this paper, we explore the hardening mechanisms in WB4-based solid solutions upon addition of Ta, Mn, and Cr using in situ radial X-ray diffraction techniques under nonhydrostatic pressure. By examining the lattice-supported differential strain, we provide insights into the mechanism for hardness increase in binary solid solutions at low dopant concentrations. Speculations on the combined effects of electronic structure and atomic size in ternary WB 4 solid solutions containing Ta with Mn or Cr are also included to understand the extremely high hardness of these materials.

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

Xie, Miao; Turner, Christopher L.; Mohammadi, Reza

In this work, we explore the hardening mechanisms in WB{sub 4}-based solid solutions upon addition of Ta, Mn, and Cr using in situ radial X-ray diffraction techniques under non-hydrostatic pressure. By examining the lattice-supported differential strain, we provide insights into the mechanism for hardness increase in binary solid solutions at low dopant concentrations. Speculations on the combined effects of electronic structure and atomic size in ternary WB{sub 4} solid solutions containing Ta with Mn or Cr are also included to understand the extremely high hardness of these materials.

Melittin induces apoptotic features in Candida albicans

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

Park, Cana; Lee, Dong Gun, E-mail: dglee222@knu.ac.kr

2010-03-26

Melittin is a well-known antimicrobial peptide with membrane-active mechanisms. In this study, it was found that Melittin exerted its antifungal effect via apoptosis. Candida albicans exposed to Melittin showed the increased reactive oxygen species (ROS) production, measured by DHR-123 staining. Fluorescence microscopy staining with FITC-annexin V, TUNEL and DAPI further confirmed diagnostic markers of yeast apoptosis including phosphatidylserine externalization, and DNA and nuclear fragmentation. The current study suggests that Melittin possesses an antifungal effect with another mechanism promoting apoptosis.

The Effect of UVC Irradiation on the Mechanical Properties of Chitosan Membrane in Sterilization Process

NASA Astrophysics Data System (ADS)

Rupiasih, N. N.; Sumadiyasa, M.; Putra, I. K.

2018-04-01

The present study, we report about the effect of UVC irradiation on the mechanical properties of chitosan membrane in the sterilization process. The membrane used was chitosan membrane 2% which prepared by a casting method using chitosan as matrix and acetic acid 1% as a solvent. The UVC source used was germicidal ultraviolet (UVG) which widely used for sterilization purposes. Variation doses were done by the varying time of irradiation, e.g. 5 min, 15 min, 30 min, and 60 min. Those samples are named as S1, S2, S3, and S4, respectively. Chitosan membrane before irradiation namely S0 also used for comparative study. The effect of UVC irradiation on the mechanical properties of membranes has been examined by different techniques including FTIR, DMA, and the water uptake capability. The results showed that ultimate tensile strength (UTS) and moduli of elasticity (E) were increased by increasing the irradiation time. From FTIR analysis obtained that no new molecules were formed in irradiated membranes. The water uptakes capability of the membranes after irradiation was smaller compared with before irradiation, and among the irradiated membranes, the water uptake capabilities were increased by increasing the exposure time. These observations suggested that more care should be taken during the sterilization process and outdoor used of the membrane. The other side, the UVC irradiation can improve the mechanical properties of the membranes.

Extensibility of the hamstrings is best explained by mechanical components of muscle contraction, not behavioral measures in individuals with chronic low back pain.

PubMed

Marshall, Paul W M; Mannion, Jamie; Murphy, Bernadette A

2009-08-01

To examine the relationship between hamstring extensibility by use of the instrumented straight leg raise; mechanical components of muscle contraction, including muscle recruitment, passive torque measures of tissue stiffness, and eccentric strength; and self-reported measures of pain and disability. Cross-sectional study. University laboratory. Twenty-one individuals with chronic nonspecific axial lower back pain and 15 healthy control subjects. Instrumented straight leg raise, concentric and eccentric hamstring strength, self-reported measures of pain, disability, fear avoidance, general health and well-being Objective measures included hamstring extensibility, hamstring muscle stiffness, absolute and relative concentric/eccentric strength, concentric/eccentric strength ratios. Self-reported measures included Oswestry disability index, visual analog pain scale, fear avoidance beliefs, and general health and well being. Patients with lower back pain had lower range of motion, greater changes in muscle stiffness, and impaired concentric-to-eccentric strength levels. Stepwise regression identified measures of stiffness as significantly predicting hamstring extensibility (adjusted r(2) = 0.58, F = 23.76, P < .001). Self-reported measures were not associated with extensibility. Gender differences were noted for passive stiffness and absolute strength. For women, later onset of the medial hamstrings also was associated with greater hamstring extensibility. Decreased extensibility of the hamstrings was associated with increased passive stiffness during the common range of motion (20 to 50 degrees ). Impaired stretch tolerance is associated with actual mechanical restriction, not behavioral measures indicating increased pain or fear-avoidant behavior. With no relationship to actual disability and contradictory findings in the literature for the relationship of the hamstrings to the mechanics of the low back, it is unclear whether decreased hamstring extensibility should be targeted in rehabilitation programs for axial lower back pain.

The role of protein O-linked beta-N-acetylglucosamine in mediating cardiac stress responses.

PubMed

Chatham, John C; Marchase, Richard B

2010-02-01

The modification of serine and threonine residues of nuclear and cytoplasmic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) has emerged as a highly dynamic post-translational modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O-GlcNAc on cellular function has been in the context of its adverse effects in mediating a range of chronic disease processes, including diabetes, cancer and neurodegenerative diseases. However, at the cellular level it has been shown that O-GlcNAc levels are increased in response to stress; augmentation of this response improved cell survival while attenuation decreased cell viability. Thus, it has become apparent that strategies that augment O-GlcNAc levels are pro-survival, whereas those that reduce O-GlcNAc levels decrease cell survival. There is a long history demonstrating the effectiveness of acute glucose-insulin-potassium (GIK) treatment and to a lesser extent glutamine in protecting against a range of stresses, including myocardial ischemia. A common feature of these approaches for metabolic cardioprotection is that they both have the potential to stimulate O-GlcNAc synthesis. Consequently, here we examine the links between metabolic cardioprotection with the ischemic cardioprotection associated with acute increases in O-GlcNAc levels. Some of the protective mechanisms associated with activation of O-GlcNAcylation appear to be transcriptionally mediated; however, there is also strong evidence to suggest that transcriptionally independent mechanisms also play a critical role. In this context we discuss the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis including the role of non-voltage gated, capacitative calcium entry as a potential mechanism contributing to this protection. Copyright 2009 Elsevier B.V. All rights reserved.

Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

PubMed

Brzozowski, Tomasz; Magierowska, Katarzyna; Magierowski, Marcin; Ptak-Belowska, Agata; Pajdo, Robert; Kwiecien, Slawomir; Olszanecki, Rafal; Korbut, Ryszard

2017-01-01

Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anaemia: can we define haemoglobin thresholds for impaired oxygen homeostasis and suggest new strategies for treatment?

PubMed

Hare, Gregory M T; Tsui, Albert K Y; Ozawa, Sherri; Shander, Aryeh

2013-03-01

Observational clinical studies in perioperative medicine have defined a progressive increase in mortality that is proportional to both chronic preoperative anaemia and acute interpretative reductions in haemoglobin concentration (Hb). However, this knowledge has not yet helped to define the critical Hb threshold for organ injury and mortality in specific patient populations or in individual patients. Nor has this knowledge enabled us to develop effective treatment strategies for anaemia, as evident from the lack of a demonstrable improvement in survival in patients randomised to higher Hb levels by various treatment strategies including allogeneic red blood cell transfusion, erythropoiesis-stimulating agents (ESAs) and haemoglobin-based oxygen carriers (HBOCs). These findings emphasise the need for a clearer understanding of the mechanism of anaemia-induced mortality. Towards achieving this goal, experimental studies have defined adaptive mechanism by which oxygen homeostasis is maintained during acute anaemia. The mechanisms include: (1) effective sensing of anaemia-induced tissue hypoxia; (2) adaptive cardiovascular responses to maintain adequate tissue oxygen delivery; (3) heterogeneity of organ-specific oxygen delivery to preferentially sustain vital organs which are essential for acute survival (heart and brain); (4) evidence of increased vital organ injury with interruption of cardiovascular responses to anaemia and (5) evidence of activation of adaptive cellular responses to maintain oxygen homeostasis and support survival during acute anaemia. Understanding these mechanisms may allow us to define treatment thresholds and novel treatment strategies for acute anaemia based on biological markers of tissue hypoxia. The overall goal of these approaches is to improve patient outcomes, including event-free perioperative survival. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development and Characterization of a Small Spacecraft Electro-Optic Scanner for Free-Space Laser Communications

NASA Technical Reports Server (NTRS)

Davis, Scott; Lichter, Michael; Raible, Daniel

2016-01-01

Emergent data-intensive missions coupled with dramatic reductions in spacecraft size plus an increasing number of space-based missions necessitates new high performance, compact and low cost communications technology. Free space optical communications offer advantages including orders of magnitude increase for data rate performance, increased security, immunity to jamming and lack of frequency allocation requirements when compared with conventional radio frequency (RF) means. The spatial coherence and low divergence associated with the optical frequencies of laser communications lends themselves to superior performance, but this increased directionality also creates one of the primary technical challenges in establishing a laser communications link by repeatedly and reliably pointing the beam onto the receive aperture. Several solutions have emerged from wide angle (slow) mechanical articulation systems, fine (fast) steering mirrors and rotating prisms, inertial compensation gyros and vibration isolation cancellation systems, but each requires moving components and imparts a measured amount of burden on the host platform. The complexity, cost and size of current mechanically scanned solutions limits their platform applicability, and restricts the feasibility of deploying optical communications payloads on very compact spacecraft employing critical systems. A high speed, wide angle, non-mechanical solution is therefore desirable. The purpose of this work is to share the development, testing, and demonstration of a breadboard prototype electro-optic (EO) scanned laser-communication link (see Figure 1). This demonstration is a step toward realizing ultra-low Size, Weight and Power (SWaP) SmallSat/MicroSat EO non-mechanical laser beam steering modules for high bandwidth ( greater than Gbps) free-space data links operating in the 1550 nm wavelength bands. The elimination of all moving parts will dramatically reduce SWaP and cost, increase component lifetime and reliability, and simplify the system design of laser communication modules. This paper describes the target mission architectures and requirements (few cubic centimeters of volume, 10's of grams of weight with milliwatts of power) and design of the beam steering module. Laboratory metrology is used to determine the component performance including horizontal and vertical resolution (20urad) as a function of control voltage (see Figure 2), transition time (0.1-1ms), pointing repeatability and optic insertion loss. A test bed system demonstration, including a full laser communications link, is conducted. The capabilities of this new EO beam steerer provide an opportunity to dramatically improve space communications through increased utilization of laser technology on smaller platforms than were previously attainable.

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

PubMed Central

Tchou-Wong, Kam-Meng; Kluz, Thomas; Arita, Adriana; Smith, Phillip R.; Brown, Stuart; Costa, Max

2011-01-01

Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3), a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s) underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq) and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq). The effect of NiCl2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs) on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl2. This study may provide insights into the epigenetic mechanism(s) underlying the carcinogenicity of nickel compounds. PMID:21455298

Effects of ventilation on hearing loss in preterm neonates: Nasal continuous positive pressure does not increase the risk of hearing loss in ventilated neonates.

PubMed

Rastogi, Shantanu; Mikhael, Michel; Filipov, Panayot; Rastogi, Deepa

2013-03-01

There is increased risk of hearing loss in preterm neonates. This risk is further increased by environmental noise exposure especially from life support equipment such as ventilation. Nasal continuous positive airway pressure (NCPAP) used for respiratory support of preterm neonates is known to be associated with prolonged exposure to high levels of noise. However, there is paucity of information on the effect of NCPAP as compared to mechanical ventilation on hearing loss among preterm neonates. A retrospective chart review was performed on neonates with birth weight (BW) <1500g. Association of clinical factors including the use of NCPAP and mechanical ventilation with failure of hearing screen were studied. Those who failed hearing screen were followed for 2 years to observe long term effects of NCPAP on the hearing loss. Of 344 neonates included in the study, 61 failed hearing screen. Gestational age (p=0.008), BW (p=0.03), ventilation (p=0.02), intrauterine growth retardation (p=0.02), necrotizing enterocolitis (NEC) (p=0.02), apnea (p<0.001), use of vancomycin (p=0.01) and furosemide (p=0.01) were associated with failure of hearing screen. On multivariate analysis, ventilation (OR 4.56, p=0.02), apnea (OR 2.2, p<0.001) and NEC (OR 2.4, p=0.02) were predictors of failed hearing screen. As compared to those not ventilated, the odds of failing hearing screen was 4.53 (p<0.01) and 4.59 (p<0.01) for those treated with NCPAP and mechanical ventilation respectively, with there being no difference between these two ventilatory modalities. Of the 61 neonates, 42 were followed for 2 years, of which 19 had confirmed hearing loss. Among these 19 neonates, there was no difference (p=0.12) between those who were treated with NCPAP or with mechanical ventilation. There is no increase in the hearing loss in preterm neonates treated with NCPAP as compared to mechanical ventilation despite being exposed to higher environmental noise generated by the NCPAP. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Impact of end effector technology on telemanipulation performance

NASA Technical Reports Server (NTRS)

Bejczy, A. K.; Szakaly, Z.; Ohm, T.

1990-01-01

Generic requirements for end effector design are briefly summarized as derived from generic functional and operational requirements. Included is a brief summary of terms and definitions related to end effector technology. The second part contains a brief overview of end effector technology work as JPL during the past ten years, with emphasis on the evolution of new mechanical, sensing and control capabilities of end effectors. The third and major part is devoted to the description of current end effector technology. The ongoing work addresses mechanical, sensing and control details with emphasis on mechanical ruggedness, increased resolution in sensing, and close electronic and control integration with overall telemanipulator control system.

Effect of Exposure on the Mechanical Properties of Gamma MET PX

NASA Technical Reports Server (NTRS)

Draper, S. L.; Lerch, B. A.; Locci, I. E.; Shazly, M.; Prakash, V.

2004-01-01

The effect of a service environment exposure on the mechanical properties of a high Nb content TiAl alloy, Gamma MET PX , was assessed. Gamma MET PX, like other TiAl alloys, experiences a reduction of ductility following high temperature exposure. Exposure in Ar, air, and high-purity oxygen all resulted in a loss of ductility with the ductility reduction increasing with oxygen content in the exposure atmosphere. Embrittling mechanisms, including bulk microstructural changes, moisture induced environmental embrittlement, and near surface effects were investigated. The embrittlement has been shown to be a near-surface effect, most likely due to the diffusion of oxygen into the alloy.

Real-Time Dynamic Observation of Micro-Friction on the Contact Interface of Friction Lining

PubMed Central

Zhang, Dekun; Chen, Kai; Guo, Yongbo

2018-01-01

This paper aims to investigate the microscopic friction mechanism based on in situ microscopic observation in order to record the deformation and contact situation of friction lining during the frictional process. The results show that friction coefficient increased with the shear deformation and energy loss of the surfacee, respectively. Furthermore, the friction mechanism mainly included adhesive friction in the high-pressure and high-speed conditions, whereas hysteresis friction was in the low-pressure and low-speed conditions. The mixed-friction mechanism was in the period when the working conditions varied from high pressure and speed to low pressure and speed. PMID:29498677

Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma☆

PubMed Central

Norian, John M.; Owen, Carter M.; Taboas, Juan; Korecki, Casey; Tuan, Rocky; Malik, Minnie; Catherino, William H.; Segars, James H.

2012-01-01

Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor’s inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells. PMID:21983114

The Need for Systematic Identification of Stakeholders for Public Engagement with Environmental Research

EPA Science Inventory

Despite the increasing promotion of stakeholder engagement in science contributing to environmental decision making, the mechanisms for identifying which stakeholders should be included are rarely strategic or documented. When documented, many of these efforts use ad hoc and/or ...

Systematic Identification of Stakeholders for Engagement with Systems Modeling Efforts in the Snohomish Basin, Washington, USA

EPA Science Inventory

Even as stakeholder engagement in systems dynamic modeling efforts is increasingly promoted, the mechanisms for identifying which stakeholders should be included are rarely documented. Accordingly, for an Environmental Protection Agency’s Triple Value Simulation (3VS) mode...

Effects of computerized cognitive training on neuroimaging outcomes in older adults: a systematic review.

PubMed

Ten Brinke, Lisanne F; Davis, Jennifer C; Barha, Cindy K; Liu-Ambrose, Teresa

2017-07-10

Worldwide, the population is aging and the number of individuals diagnosed with dementia is rising rapidly. Currently, there are no effective pharmaceutical cures. Hence, identifying lifestyle approaches that may prevent, delay, or treat cognitive impairment and dementia in older adults is becoming increasingly important. Computerized Cognitive Training (CCT) is a promising strategy to combat cognitive decline. Yet, the underlying mechanisms of the effect of CCT on cognition remain poorly understood. Hence, the primary objective of this systematic review was to examine peer-reviewed literature ascertaining the effect of CCT on both structural and functional neuroimaging measures among older adults to gain insight into the underlying mechanisms by which CCT may benefit cognitive function. In accordance with PRISMA guidelines, we used the following databases: MEDLINE, EMBASE, and CINAHL. Two independent reviewers abstracted data using pre-defined terms. These included: main study characteristics such as the type of training (i.e., single- versus multi-domain), participant demographics (age ≥ 50 years; no psychiatric conditions), and the inclusion of neuroimaging outcomes. The Physiotherapy Evidence Database (PEDro) scale was used to assess quality of all studies included in this systematic review. Nine studies were included in this systematic review, with four studies including multiple MRI sequences. Results of this systematic review are mixed: CCT was found to increase and decrease both brain structure and function in older adults. In addition, depending on region of interest, both increases and decreases in structure and function were associated with behavioural performance. Of all studies included in this systematic review, results from the highest quality studies, which were two randomized controlled trials, demonstrated that multi-domain CCT could lead to increases in hippocampal functional connectivity. Further high quality studies that include an active control, a sample size calculation, and an appropriate training dosage, are needed to confirm these findings and their relation to cognition.

Achondroplasia: Development, pathogenesis, and therapy.

PubMed

Ornitz, David M; Legeai-Mallet, Laurence

2017-04-01

Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

Thin Gauge Twin-Roll Casting, Process Capabilities and Product Quality

NASA Astrophysics Data System (ADS)

Daaland, O.; Espedal, A. B.; Nedreberg, M. L.; Alvestad, I.

Traditionally industrial twin roll casters have been operated at gauges 6-10 mm, depending on the type of caster and the final product requirements. Over the past few years it has become apparent that a significant increase in productivity can be achieved when the casting gauge is reduced. Hydro Aluminium embarked on an extensive research and development, thin gauge casting programme, in the beginning of the 1990's and this paper presents some results from a five year lasting project (joint programme between Hydro Aluminium a.s. and Lauener Engineering). Based on more than 400 casting trials the major benefits and limitations of casting at reduced gauge and increased speed are outlined. Important aspects related to process development and product quality are discussed including: productivity and limitations, surface defects, microstructural characteristics, cooling rates and dendrite structure, segregation behaviour and mechanical properties after thermo-mechanical processing. Results for casting of several alloys are given. Additionally, numerical modelling results of the strip casting process are included.

Neuropeptides in tendinopathy

PubMed Central

Scott, Alexander; Bahr, Roald

2014-01-01

Tendinopathy is a clinical syndrome of pain, tendon thickening, and increased blood flow. The current review highlights evidence supporting an underlying role of neuropeptides in the etiology, clinical presentation, and treatment of painful overuse tendinopathy. Painful tendons demonstrate an increased presence of Substance P-containing nerves which are strongly implicated as a potential source of pain, but which also play important roles in the tendon’s attempt to self-repair. Recent findings have identified potential roles of additional sensory and autonomic neuropeptides which regulate pain, tissue remodeling, and vascular flow, including acetylcholine, noradrenaline and neuropeptide Y. Neuropeptide production within tendons is stimulated by mechanical load and exercise, and both direct and indirect neuropeptide effects may be responsible for the potential benefits of heavy-load eccentric loading. A model is presented which delineates the physiologic basis for signalling pathways between tenocytes, mast cells and sensory and autonomic nerves, with implications for understanding the mechanisms of traditional as well as emerging treatment strategies including sclerosing therapy and nitric oxide. PMID:19273194

Interaction Between Allergy and Middle Ear Infection.

PubMed

Oh, Jeong-Hoon; Kim, Woo Jin

2016-09-01

Recent studies have attempted to identify interactions among the causes of otitis media with effusion (OME). This review discusses the interaction between allergy and infection with regard to host and environmental factors in terms of the development of OME. Protection of the upper airway against microbial invasion requires active interaction between the defense mechanisms of the respiratory epithelium, including innate and adaptive immunity, and mechanical factors. The impairment of these defenses due to allergy and/or increased bacterial resistance may lead to increased susceptibility to infectious organisms in the respiratory tract and middle ear mucosa. Recent genetic studies have provided valuable information about the association of Toll-like receptor signaling variations with clinical phenotypes and the risk of infection in the middle ear. Among the causal factors of OME, allergy not only induces an inflammatory reaction in the middle ear cavity but also facilitates the invasion of infectious pathogens. There is also evidence that allergy can affect the susceptibility of patients to infection of the upper respiratory tract, including the middle ear cavity.

Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

PubMed

Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

2015-10-01

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cardiovascular benefits of dietary fiber.

PubMed

Satija, Ambika; Hu, Frank B

2012-12-01

The relationship between dietary fiber and risk of cardiovascular disease (CVD) has been extensively studied. There is considerable epidemiological evidence indicating an inverse association between dietary fiber intake and CVD risk. The association has been found to be stronger for cereal fiber than for fruit or vegetable fiber, and several studies have also found increased whole grain consumption to be associated with CVD risk reduction. In light of this evidence, recent US dietary guidelines have endorsed increased consumption of fiber rich whole grains. Regular consumption of dietary fiber, particularly fiber from cereal sources, may improve CVD health through multiple mechanisms including lipid reduction, body weight regulation, improved glucose metabolism, blood pressure control, and reduction of chronic inflammation. Future research should focus on various food sources of fiber, including different types of whole grains, legumes, fruits, vegetables, and nuts, as well as resistant starch in relation to CVD risk and weight control; explore the biological mechanisms underlying the cardioprotective effect of fiber-rich diets; and study different ethnic groups and populations with varying sources of dietary fiber.

Emotion Dysregulation as a Mechanism Linking Stress Exposure to Adolescent Aggressive Behavior

PubMed Central

McLaughlin, Katie A.; Hatzenbuehler, Mark L.

2012-01-01

Exposure to stress is associated with a wide range of internalizing and externalizing problems in adolescents, including aggressive behavior. Extant research examining mechanisms underlying the associations between stress and youth aggression has consistently identified social information processing pathways that are disrupted by exposure to violence and increase risk of aggressive behavior. In the current study, we use longitudinal data to examine emotion dysregulation as a potential mechanism linking a broader range of stressful experiences to aggressive behavior in a diverse sample of early adolescents (N=1065). Specifically, we examined the longitudinal associations of peer victimization and stressful life events with emotion dysregulation and aggressive behavior. Structural equation modeling was used to create latent constructs of emotion dysregulation and aggression. Both stressful life events and peer victimization predicted subsequent increases in emotion dysregulation over a 4-month period. These increases in emotion dysregulation, in turn, were associated with increases in aggression over the subsequent 3 months. Longitudinal mediation models showed that emotion dysregulation mediated the relationship of both peer victimization (z=2.35, p=0.019) and stressful life events (z=2.32, p=0.020) with aggressive behavior. Increasing the use of adaptive emotion regulation strategies is an important target for interventions aimed at preventing the onset of adolescent aggressive behavior. PMID:22466516

Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg.

PubMed

Messere, Alessandro; Ceravolo, Gianluca; Franco, Walter; Maffiodo, Daniela; Ferraresi, Carlo; Roatta, Silvestro

2017-12-01

The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions ( n = 3-6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1 ) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2 ) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3 ) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4 ) the extent of attenuation negatively correlates with tissue oxygenation ( r  = -0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1 ) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2 ) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3 ) the extent of attenuation of the compression-induced hyperemia is proportional to the level of oxygenation achieved in the tissue. The results support the concept that tissue oxygenation is a key variable in blood flow regulation. Copyright © 2017 the American Physiological Society.

Sedentary behavior and sleep: paradoxical effects in association with childhood obesity.

PubMed

Must, A; Parisi, S M

2009-04-01

Sedentary behavior and sleep may be working in concert to increase the likelihood of a child becoming overweight, but in paradoxical ways. Reduction of sedentary behavior (that is, media screen time) has been extensively researched and touted as an intervention target. Inadequate sleep as a putative risk factor for obesity is only beginning to be explored. In this paper, we review the current state of research regarding these factors, and describe the existing evidence and mechanisms proposed to explain these relationships. Whereas the association between weight and sedentary behavior has been consistently shown in observational studies, effect sizes are small, and multiple mechanisms appear to be operating. Recent cross-sectional and longitudinal evidence suggests a link between short sleep duration and weight. Possible mechanisms here include direct metabolic effects as well as indirect behavioral pathways, including the presence of electronic media in children's bedrooms. Measurement issues present a challenge to both areas of research. Prospective studies that include more accurate measures of both sedentary behavior and of sleep will be needed to clarify causal pathways.

Mechanisms of resistance to linalool in Salmonella Senftenberg and their role in survival on basil.

PubMed

Kalily, Emmanuel; Hollander, Amit; Korin, Ben; Cymerman, Itamar; Yaron, Sima

2016-11-01

Fresh produce contaminated with human pathogens raises vital and ecological questions about bacterial survival strategies. Such occurrence was basil harboring Salmonella enterica serovar Senftenberg that caused an outbreak in 2007. This host was unanticipated due to its production of antibacterial substances, including linalool. We show that linalool perforates bacterial membranes, resulting in increased permeability and leakage of vital molecules. It also inhibits cell motility and causes bacterial aggregation. Linalool-resistance was investigated by identification and characterization of S. Senftenberg mutants that perform altered resistance. Resistance mechanisms include selective permeability, regulated efflux/influx and chemotaxis-controlled motility. Moreover, survival of S. Senftenberg on basil leaves was substantially affected by McpL, a putative chemotaxis-related receptor, and RfaG, a component of the lipopolysaccharide production pathway, both have a role in resistance to linalool. Results reveal that adaptation to linalool occurs in nature by concurrent mechanisms. This adaption raises concerns about pathogens adaptation to new hosts including antimicrobial-compound-producing plants. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer.

PubMed

Abdel-Hafiz, Hany A

2017-07-06

Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs). It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics.

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA.

PubMed

Al-Turkmani, M Rabie; Andersson, Charlotte; Alturkmani, Ragheed; Katrangi, Waddah; Cluette-Brown, Joanne E; Freedman, Steven D; Laposata, Michael

2008-09-01

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation.

Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

PubMed Central

Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

2015-01-01

Abstract. Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation. PMID:25562608

Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

NASA Astrophysics Data System (ADS)

Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

2015-05-01

Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing.

PubMed

Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R; Berns, Michael W

2015-05-01

Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

The mechanism of phloem loading in rice (Oryza sativa).

PubMed

Eom, Joon-Seob; Choi, Sang-Bong; Ward, John M; Jeon, Jong-Seong

2012-05-01

Carbohydrates, mainly sucrose, that are synthesized in source organs are transported to sink organs to support growth and development. Phloem loading of sucrose is a crucial step that drives long-distance transport by elevating hydrostatic pressure in the phloem. Three phloem loading strategies have been identified, two active mechanisms, apoplastic loading via sucrose transporters and symplastic polymer trapping, and one passive mechanism. The first two active loading mechanisms require metabolic energy, carbohydrate is loaded into the phloem against a concentration gradient. The passive process, diffusion, involves equilibration of sucrose and other metabolites between cells through plasmodesmata. Many higher plant species including Arabidopsis utilize the active loading mechanisms to increase carbohydrate in the phloem to higher concentrations than that in mesophyll cells. In contrast, recent data revealed that a large number of plants, especially woody species, load sucrose passively by maintaining a high concentration in mesophyll cells. However, it still remains to be determined how the worldwide important cereal crop, rice, loads sucrose into the phloem in source organs. Based on the literature and our results, we propose a potential strategy of phloem loading in rice. Elucidation of the phloem loading mechanism should improve our understanding of rice development and facilitate its manipulation towards the increase of crop productivity.

Childhood Asthma Hospitalizations in the United States, 2000-2009

PubMed Central

Hasegawa, Kohei; Tsugawa, Yusuke; Brown, David F.M.; Camargo, Carlos A.

2013-01-01

Objectives To examine temporal trends in the US incidence of childhood asthma hospitalizations, inhospital mortality, mechanical ventilation use, and hospital charges between 2000 and 2009. Study design A serial, cross-sectional analysis of a nationally-representative sample of children hospitalized with acute asthma. The Kids Inpatient Database was used to identify children <18 years of age with asthma by International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx. Outcome Measures were asthma hospitalization incidence, in-hospital mortality, mechanical ventilation use, and hospital charges. We examined temporal trends of each outcome, accounting for sampling weights. Hospital charges were adjusted for inflation to 2009 US dollars. Results The four separated years (2000, 2003, 2006, and 2009) of national discharge data included 592 805 weighted discharges with asthma. Between 2000 and 2009, asthma hospitalization incidence decreased from 21.1 to 18.4 per 10 000 person-years among all US children (13% decrease; Ptrend<.001). Mortality declined significantly after adjusting for confounders (OR for comparison of 2009 with 2000, 0.37; 95%CI, 0.17-0.79). By contrast, there was an increase in mechanical ventilation use (0.8% to 1.0%; 28% increase; Ptrend<.001). Nationwide hospital charges also increased from $1.27 billion to $1.59 billion (26% increase; Ptrend<.001); this increase was driven by a rise in the geometric mean of hospital charges per discharge, from $5940 to $8410 (42% increase; Ptrend<.001). Conclusions Between 2000 and 2009, we found significant declines in asthma hospitalization and in-hospital mortality among US children. By contrast, mechanical ventilation use and hospital charges for asthma significantly increased over this same period. PMID:23769497

Mechanisms of physiological and pathological cardiac hypertrophy.

PubMed

Nakamura, Michinari; Sadoshima, Junichi

2018-04-19

Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.

Functional bacterial amyloid increases Pseudomonas biofilm hydrophobicity and stiffness

PubMed Central

Zeng, Guanghong; Vad, Brian S.; Dueholm, Morten S.; Christiansen, Gunna; Nilsson, Martin; Tolker-Nielsen, Tim; Nielsen, Per H.; Meyer, Rikke L.; Otzen, Daniel E.

2015-01-01

The success of Pseudomonas species as opportunistic pathogens derives in great part from their ability to form stable biofilms that offer protection against chemical and mechanical attack. The extracellular matrix of biofilms contains numerous biomolecules, and it has recently been discovered that in Pseudomonas one of the components includes β-sheet rich amyloid fibrils (functional amyloid) produced by the fap operon. However, the role of the functional amyloid within the biofilm has not yet been investigated in detail. Here we investigate how the fap-based amyloid produced by Pseudomonas affects biofilm hydrophobicity and mechanical properties. Using atomic force microscopy imaging and force spectroscopy, we show that the amyloid renders individual cells more resistant to drying and alters their interactions with hydrophobic probes. Importantly, amyloid makes Pseudomonas more hydrophobic and increases biofilm stiffness 20-fold. Deletion of any one of the individual members of in the fap operon (except the putative chaperone FapA) abolishes this ability to increase biofilm stiffness and correlates with the loss of amyloid. We conclude that amyloid makes major contributions to biofilm mechanical robustness. PMID:26500638

Functional bacterial amyloid increases Pseudomonas biofilm hydrophobicity and stiffness.

PubMed

Zeng, Guanghong; Vad, Brian S; Dueholm, Morten S; Christiansen, Gunna; Nilsson, Martin; Tolker-Nielsen, Tim; Nielsen, Per H; Meyer, Rikke L; Otzen, Daniel E

2015-01-01

The success of Pseudomonas species as opportunistic pathogens derives in great part from their ability to form stable biofilms that offer protection against chemical and mechanical attack. The extracellular matrix of biofilms contains numerous biomolecules, and it has recently been discovered that in Pseudomonas one of the components includes β-sheet rich amyloid fibrils (functional amyloid) produced by the fap operon. However, the role of the functional amyloid within the biofilm has not yet been investigated in detail. Here we investigate how the fap-based amyloid produced by Pseudomonas affects biofilm hydrophobicity and mechanical properties. Using atomic force microscopy imaging and force spectroscopy, we show that the amyloid renders individual cells more resistant to drying and alters their interactions with hydrophobic probes. Importantly, amyloid makes Pseudomonas more hydrophobic and increases biofilm stiffness 20-fold. Deletion of any one of the individual members of in the fap operon (except the putative chaperone FapA) abolishes this ability to increase biofilm stiffness and correlates with the loss of amyloid. We conclude that amyloid makes major contributions to biofilm mechanical robustness.

TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion

PubMed Central

Osborne, Lukas D.; Li, George Z.; How, Tam; O'Brien, E. Tim; Blobe, Gerard C.; Superfine, Richard; Mythreye, Karthikeyan

2014-01-01

Recent studies implicate a role for cell mechanics in cancer progression. The epithelial-to-mesenchymal transition (EMT) regulates the detachment of cancer cells from the epithelium and facilitates their invasion into stromal tissue. Although classic EMT hallmarks include loss of cell–cell adhesions, morphology changes, and increased invasion capacity, little is known about the associated mechanical changes. Previously, force application on integrins has been shown to initiate cytoskeletal rearrangements that result in increased cell stiffness and a stiffening response. Here we demonstrate that transforming growth factor β (TGF-β)–induced EMT results in decreased stiffness and loss of the normal stiffening response to force applied on integrins. We find that suppression of the RhoA guanine nucleotide exchange factors (GEFs) LARG and GEF-H1 through TGF-β/ALK5–enhanced proteasomal degradation mediates these changes in cell mechanics and affects EMT-associated invasion. Taken together, our results reveal a functional connection between attenuated stiffness and stiffening response and the increased invasion capacity acquired after TGF-β–induced EMT. PMID:25143398

Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging

PubMed Central

O’Donovan, Aoife; Slavich, George M; Epel, Elissa S.; Neylan, Thomas C

2015-01-01

Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals. PMID:23127296

Auditory rhythmic cueing in movement rehabilitation: findings and possible mechanisms

PubMed Central

Schaefer, Rebecca S.

2014-01-01

Moving to music is intuitive and spontaneous, and music is widely used to support movement, most commonly during exercise. Auditory cues are increasingly also used in the rehabilitation of disordered movement, by aligning actions to sounds such as a metronome or music. Here, the effect of rhythmic auditory cueing on movement is discussed and representative findings of cued movement rehabilitation are considered for several movement disorders, specifically post-stroke motor impairment, Parkinson's disease and Huntington's disease. There are multiple explanations for the efficacy of cued movement practice. Potentially relevant, non-mutually exclusive mechanisms include the acceleration of learning; qualitatively different motor learning owing to an auditory context; effects of increased temporal skills through rhythmic practices and motivational aspects of musical rhythm. Further considerations of rehabilitation paradigm efficacy focus on specific movement disorders, intervention methods and complexity of the auditory cues. Although clinical interventions using rhythmic auditory cueing do not show consistently positive results, it is argued that internal mechanisms of temporal prediction and tracking are crucial, and further research may inform rehabilitation practice to increase intervention efficacy. PMID:25385780

The Influence of Welding Parameters on the Nugget Formation of Resistance Spot Welding of Inconel 625 Sheets

NASA Astrophysics Data System (ADS)

Rezaei Ashtiani, Hamid Reza; Zarandooz, Roozbeh

2015-09-01

A 2D axisymmetric electro-thermo-mechanical finite element (FE) model is developed to investigate the effect of current intensity, welding time, and electrode tip diameter on temperature distributions and nugget size in resistance spot welding (RSW) process of Inconel 625 superalloy sheets using ABAQUS commercial software package. The coupled electro-thermal analysis and uncoupled thermal-mechanical analysis are used for modeling process. In order to improve accuracy of simulation, material properties including physical, thermal, and mechanical properties have been considered to be temperature dependent. The thickness and diameter of computed weld nuggets are compared with experimental results and good agreement is observed. So, FE model developed in this paper provides prediction of quality and shape of the weld nuggets and temperature distributions with variation of each process parameter, suitably. Utilizing this FE model assists in adjusting RSW parameters, so that expensive experimental process can be avoided. The results show that increasing welding time and current intensity lead to an increase in the nugget size and electrode indentation, whereas increasing electrode tip diameter decreases nugget size and electrode indentation.

The effect of oxidation on the mechanical response and microstructure of porcine aortas.

PubMed

Stephen, Elizabeth A; Venkatasubramaniam, Arundhathi; Good, Theresa A; Topoleski, L D Timmie

2014-09-01

Reactive oxygen species (ROS), a product of many cellular functions, has been implicated in many age-related pathophysiological processes, including cardiovascular disease. The arterial proteins collagen and elastin may also undergo structural and functional changes due to damage caused by ROS. This study examined the effect of oxidation on the mechanical response of porcine aortas and aorta elastin and the associated changes in structural protein ultrastructure as a step in exploring the role of molecular changes in structural proteins with aging on elastic artery function. We examined the change in mechanical properties of aorta samples after various oxidation times as a first step in understanding how the oxidative environment associated with aging could impact mechanical properties of arterial structural proteins. We used confocal microscopy to visualize how the microstructure of isolated elastin changed with oxidation. We find that short term oxidation of elastin isolated from aortas leads to an increase in material stiffness, but also an increase in the fiber diameter, increase in void space in the matrix, and a decrease in the fiber orientation, possibly due to fiber cross-linking. The short term effects of oxidation on arterial collagen is more complex, with increase in material stiffness seen in the collagen region of the stress stretch curve at low extents of oxidation, but not at high levels of oxidation. These results may provide insight into the relationship between oxidative damage to tissue associated with aging and disease, structure of the arterial proteins elastin and collagen, and arterial mechanical properties and function. © 2013 Wiley Periodicals, Inc.

OBESITY-INDUCED HYPERTENSION: INTERACTION OF NEUROHUMORAL AND RENAL MECHANISMS

PubMed Central

Hall, John E.; do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Hall, Michael E.

2015-01-01

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65–75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include 1) physical compression of the kidneys by fat in and around the kidneys, 2) activation of the renin-angiotensin-aldosterone system (RAAS), and 3) increased sympathetic nervous system (SNS) activity. Activation of the RAAS system is likely due, in part, to renal compression as well as SNS activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for SNS activation in obesity have not been fully elucidated but appear to require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes, and inflammation. Unless effective anti-obesity drugs are developed, the impact of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein

PubMed Central

Francica, Joseph R.; Varela-Rohena, Angel; Medvec, Andrew; Plesa, Gabriela; Riley, James L.; Bates, Paul

2010-01-01

Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection. PMID:20844579

A review of mechanisms and modelling procedures for landslide tsunamis

NASA Astrophysics Data System (ADS)

Løvholt, Finn; Harbitz, Carl B.; Glimsdal, Sylfest

2017-04-01

Landslides, including volcano flank collapses or volcanically induced flows, constitute the second-most important cause of tsunamis after earthquakes. Compared to earthquakes, landslides are more diverse with respect to how they generation tsunamis. Here, we give an overview over the main tsunami generation mechanisms for landslide tsunamis. In the presentation, a mix of results using analytical models, numerical models, laboratory experiments, and case studies are used to illustrate the diversity, but also to point out some common characteristics. Different numerical modelling techniques for the landslide evolution, and the tsunami generation and propagation, as well as the effect of frequency dispersion, are also briefly discussed. Basic tsunami generation mechanisms for different types of landslides, including large submarine translational landslide, to impulsive submarine slumps, and violent subaerial landslides and volcano flank collapses, are reviewed. The importance of the landslide kinematics is given attention, including the interplay between landslide acceleration, landslide velocity to depth ratio (Froude number) and dimensions. Using numerical simulations, we demonstrate how landslide deformation and retrogressive failure development influence tsunamigenesis. Generation mechanisms for subaerial landslides, are reviewed by means of scaling relations from laboratory experiments and numerical modelling. Finally, it is demonstrated how the different degree of complexity in the landslide tsunamigenesis needs to be reflected by increased sophistication in numerical models.

Closed-form solutions for linear regulator design of mechanical systems including optimal weighting matrix selection

NASA Technical Reports Server (NTRS)

Hanks, Brantley R.; Skelton, Robert E.

1991-01-01

Vibration in modern structural and mechanical systems can be reduced in amplitude by increasing stiffness, redistributing stiffness and mass, and/or adding damping if design techniques are available to do so. Linear Quadratic Regulator (LQR) theory in modern multivariable control design, attacks the general dissipative elastic system design problem in a global formulation. The optimal design, however, allows electronic connections and phase relations which are not physically practical or possible in passive structural-mechanical devices. The restriction of LQR solutions (to the Algebraic Riccati Equation) to design spaces which can be implemented as passive structural members and/or dampers is addressed. A general closed-form solution to the optimal free-decay control problem is presented which is tailored for structural-mechanical system. The solution includes, as subsets, special cases such as the Rayleigh Dissipation Function and total energy. Weighting matrix selection is a constrained choice among several parameters to obtain desired physical relationships. The closed-form solution is also applicable to active control design for systems where perfect, collocated actuator-sensor pairs exist.

Longitudinal spread of mechanical excitation through tectorial membrane traveling waves

PubMed Central

Sellon, Jonathan B.; Farrahi, Shirin; Ghaffari, Roozbeh; Freeman, Dennis M.

2015-01-01

The mammalian inner ear separates sounds by their frequency content, and this separation underlies important properties of human hearing, including our ability to understand speech in noisy environments. Studies of genetic disorders of hearing have demonstrated a link between frequency selectivity and wave properties of the tectorial membrane (TM). To understand these wave properties better, we developed chemical manipulations that systematically and reversibly alter TM stiffness and viscosity. Using microfabricated shear probes, we show that (i) reducing pH reduces TM stiffness with little change in TM viscosity and (ii) adding PEG increases TM viscosity with little change in TM stiffness. By applying these manipulations in measurements of TM waves, we show that TM wave speed is determined primarily by stiffness at low frequencies and by viscosity at high frequencies. Both TM viscosity and stiffness affect the longitudinal spread of mechanical excitation through the TM over a broad range of frequencies. Increasing TM viscosity or decreasing stiffness reduces longitudinal spread of mechanical excitation, thereby coupling a smaller range of best frequencies and sharpening tuning. In contrast, increasing viscous loss or decreasing stiffness would tend to broaden tuning in resonance-based TM models. Thus, TM wave and resonance mechanisms are fundamentally different in the way they control frequency selectivity. PMID:26438861

Analytical Characterization of Internet Security Attacks

ERIC Educational Resources Information Center

Sellke, Sarah H.

2010-01-01

Internet security attacks have drawn significant attention due to their enormously adverse impact. These attacks includes Malware (Viruses, Worms, Trojan Horse), Denial of Service, Packet Sniffer, and Password Attacks. There is an increasing need to provide adequate defense mechanisms against these attacks. My thesis proposal deals with analytical…

Welfare Entitlements: Addressing New Realities.

ERIC Educational Resources Information Center

Belcher, Jon R.; Fandetti, Donald V.

1995-01-01

Because welfare entitlements are increasingly unpopular, social work advocates need to place greater emphasis on job growth and alternate mechanisms for wealth redistribution, including refundable tax credits for working poor people. The Internal Revenue Code can be an effective weapon in combating poverty if antipoverty approaches in the code are…

Practical Help for the Long-Term Learning Disabled Adolescent.

ERIC Educational Resources Information Center

Schirmer, Terry A.; George, Michael P.

1983-01-01

An alternative program offers learning disabled secondary students with histories of academic failure a curriculum emphasizing career awareness and life skills. A work station setup provides experience in such areas as drafting, consumer awareness, mechanics, and transportation. Results include increased attendance, improved self esteem, and…

Transcriptional profiling of mechanically and genetically sink-limited soybeans

USDA-ARS?s Scientific Manuscript database

The absence of a reproductive sink causes physiological and morphological changes in soybean plants. These include increased accumulation of nitrogen and starch in the leaves and delayed leaf senescence. To identify transcriptional changes that occur in leaves of these sink-limited plants, we used R...

Against Captivity: Black Girls and School Discipline Policies in the Afterlife of Slavery

ERIC Educational Resources Information Center

Wun, Connie

2016-01-01

Multilayered disciplinary policies including sophisticated surveillance mechanisms and harsh punitive practices increasingly characterize schools in the United States. Researchers contend that these modalities funnel students into prisons and produce "prison-like" conditions and/or militarized spaces. Most studies have examined the…

Exercise Training-Induced Adaptations Associated with Increases in Skeletal Muscle Glycogen Content

PubMed Central

Manabe, Yasuko; Gollisch, Katja S.C.; Holton, Laura; Kim, Young–Bum; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.

2012-01-01

Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism for increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4, or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. Compared to sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase 3 (GSK3). Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1, GSK3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks and may function as a negative feedback to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase and PP1activity. PMID:23206309

Depression in dementia: epidemiology, mechanisms, and treatment.

PubMed

Enache, Daniela; Winblad, Bengt; Aarsland, Dag

2011-11-01

Depression in people with dementia has important implications, such as reduced quality of life of patients and carers, and is associated with increased costs and reduced cognition. Here, we review recent studies of the epidemiology, course, mechanisms and treatment of depression in people with dementia. Depression is both a risk factor and a prodrome of Alzheimer's disease. Depression is a common occurrence in all types of dementias and at all disease stages, including in mild cognitive impairment (MCI). Many studies have explored whether depression in MCI increased the conversion rate to dementia, but findings are inconsistent. Studies of the mechanisms are relatively few and findings inconsistent, but inflammatory, trophic and cerebrovascular factors may contribute, in addition to monoamine deficiency and severity of plaques and tangle pathology. Studies of antidepressants for depression in dementia are inconclusive, with several negative findings reported in recent large studies, suggesting that antidepressant may not confer benefit over placebo. Depression is a common risk factor, prodrome, and accompanying symptom of people with Alzheimer's dementia. The mechanisms are unknown, and there is little evidence of effective therapies.

Role of Plant Growth Promoting Rhizobacteria in Agricultural Sustainability-A Review.

PubMed

Vejan, Pravin; Abdullah, Rosazlin; Khadiran, Tumirah; Ismail, Salmah; Nasrulhaq Boyce, Amru

2016-04-29

Plant growth promoting rhizobacteria (PGPR) shows an important role in the sustainable agriculture industry. The increasing demand for crop production with a significant reduction of synthetic chemical fertilizers and pesticides use is a big challenge nowadays. The use of PGPR has been proven to be an environmentally sound way of increasing crop yields by facilitating plant growth through either a direct or indirect mechanism. The mechanisms of PGPR include regulating hormonal and nutritional balance, inducing resistance against plant pathogens, and solubilizing nutrients for easy uptake by plants. In addition, PGPR show synergistic and antagonistic interactions with microorganisms within the rhizosphere and beyond in bulk soil, which indirectly boosts plant growth rate. There are many bacteria species that act as PGPR, described in the literature as successful for improving plant growth. However, there is a gap between the mode of action (mechanism) of the PGPR for plant growth and the role of the PGPR as biofertilizer-thus the importance of nano-encapsulation technology in improving the efficacy of PGPR. Hence, this review bridges the gap mentioned and summarizes the mechanism of PGPR as a biofertilizer for agricultural sustainability.

Monitoring the mechanical properties of healing bone.

PubMed

Claes, L E; Cunningham, J L

2009-08-01

Fracture healing is normally assessed through an interpretation of radiographs, clinical evaluation, including pain on weight bearing, and a manual assessment of the mobility of the fracture. These assessments are subjective and their accuracy in determining when a fracture has healed has been questioned. Viewed in mechanical terms, fracture healing represents a steady increase in strength and stiffness of a broken bone and it is only when these values are sufficiently high to support unrestricted weight bearing that a fracture can be said to be healed. Information on the rate of increase of the mechanical properties of a healing bone is therefore valuable in determining both the rate at which a fracture will heal and in helping to define an objective and measurable endpoint of healing. A number of techniques have been developed to quantify bone healing in mechanical terms and these are described and discussed in detail. Clinical studies, in which measurements of fracture stiffness have been used to identify a quantifiable end point of healing, compare different treatment methods, predictably determine whether a fracture will heal, and identify factors which most influence healing, are reviewed and discussed.

Controlling weeds with fungi, bacteria and viruses: a review

PubMed Central

Harding, Dylan P.; Raizada, Manish N.

2015-01-01

Weeds are a nuisance in a variety of land uses. The increasing prevalence of both herbicide resistant weeds and bans on cosmetic pesticide use has created a strong impetus to develop novel strategies for controlling weeds. The application of bacteria, fungi and viruses to achieving this goal has received increasingly great attention over the last three decades. Proposed benefits to this strategy include reduced environmental impact, increased target specificity, reduced development costs compared to conventional herbicides and the identification of novel herbicidal mechanisms. This review focuses on examples from North America. Among fungi, the prominent genera to receive attention as bioherbicide candidates include Colletotrichum, Phoma, and Sclerotinia. Among bacteria, Xanthomonas and Pseudomonas share this distinction. The available reports on the application of viruses to controlling weeds are also reviewed. Focus is given to the phytotoxic mechanisms associated with bioherbicide candidates. Achieving consistent suppression of weeds in field conditions is a common challenge to this control strategy, as the efficacy of a bioherbicide candidate is generally more sensitive to environmental variation than a conventional herbicide. Common themes and lessons emerging from the available literature in regard to this challenge are presented. Additionally, future directions for this crop protection strategy are suggested. PMID:26379687

Characterization Methods of Encapsulates

NASA Astrophysics Data System (ADS)

Zhang, Zhibing; Law, Daniel; Lian, Guoping

Food active ingredients can be encapsulated by different processes, including spray drying, spray cooling, spray chilling, spinning disc and centrifugal co-extrusion, extrusion, fluidized bed coating and coacervation (see Chap. 2 of this book). The purpose of encapsulation is often to stabilize an active ingredient, control its release rate and/or convert a liquid formulation into a solid which is easier to handle. A range of edible materials can be used as shell materials of encapsulates, including polysaccharides, fats, waxes and proteins (see Chap. 3 of this book). Encapsulates for typical industrial applications can vary from several microns to several millimetres in diameter although there is an increasing interest in preparing nano-encapsulates. Encapsulates are basically particles with a core-shell structure, but some of them can have a more complex structure, e.g. in a form of multiple cores embedded in a matrix. Particles have physical, mechanical and structural properties, including particle size, size distribution, morphology, surface charge, wall thickness, mechanical strength, glass transition temperature, degree of crystallinity, flowability and permeability. Information about the properties of encapsulates is very important to understanding their behaviours in different environments, including their manufacturing processes and end-user applications. E.g. encapsulates for most industrial applications should have desirable mechanical strength, which should be strong enough to withstand various mechanical forces generated in manufacturing processes, such as mixing, pumping, extrusion, etc., and may be required to be weak enough in order to release the encapsulated active ingredients by mechanical forces at their end-user applications, such as release rate of flavour by chewing. The mechanical strength of encapsulates and release rate of their food actives are related to their size, morphology, wall thickness, chemical composition, structure etc. Hence, reliable methods which can be used to characterize these properties of encapsulates are vital. In this chapter, the state-of-art of these methods, their principles and applications, and release mechanisms are described as follows.

Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

PubMed

You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

2013-04-01

Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals.

The Probiotic Mixture VSL#3 Accelerates Gastric Ulcer Healing by Stimulating Vascular Endothelial Growth Factor

PubMed Central

Dharmani, Poonam; De Simone, Claudio; Chadee, Kris

2013-01-01

Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6×109 bacteria) or high (1.2×1010 bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF. PMID:23484048

Vaccine adjuvants: Why and how.

PubMed

Christensen, Dennis

2016-10-02

Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.

The Potential Neural Mechanisms of Acute Indirect Vibration

PubMed Central

2011-01-01

There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception suggesting neural enhancement. Nevertheless, the neural mechanism(s) of vibration and its potentiating effect have received little attention. One proposal suggests that spinal reflexes enhance muscle contraction through a reflex activity known as tonic vibration stretch reflex (TVR), which increases muscle activation. However, TVR is based on direct, brief, and high frequency vibration (>100 Hz) which differs to indirect vibration, which is applied to the whole body or body parts at lower vibration frequency (5-45 Hz). Likewise, muscle tuning and neuromuscular aspects are other candidate mechanisms used to explain the vibration phenomenon. But there is much debate in terms of identifying which neural mechanism(s) are responsible for acute vibration; due to a number of studies using various vibration testing protocols. These protocols include: different methods of application, vibration variables, training duration, exercise types and a range of population groups. Therefore, the neural mechanism of acute vibration remain equivocal, but spinal reflexes, muscle tuning and neuromuscular aspects are all viable factors that may contribute in different ways to increasing muscular performance. Additional research is encouraged to determine which neural mechanism(s) and their contributions are responsible for acute vibration. Testing variables and vibration applications need to be standardised before reaching a consensus on which neural mechanism(s) occur during and post-vibration. Key points There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception, but little attention has been given to the neural mechanism(s) of acute indirect vibration. Current findings suggest that acute vibration exposure may cause a neural response, but there is little consensus on identifying which neural mechanism(s) are specifically responsible. This is due to a number of studies using various vibration testing protocols (i.e.varying frequencies, amplitudes, durations, and methods of application). Spinal reflexes, muscle tuning and neuromuscular aspects and central motor command are all viable neuromechanical factors that may contribute at different stages to transiently increasing muscular performance. Additional research is encouraged to determine when (pre, during and post) the different neural mechanism(s) respond to direct and indirect vibration stimuli. PMID:24149291

Injuries and medical issues in softball.

PubMed

Briskin, Susannah M

2012-01-01

Softball is enjoyed by millions of female and male athletes of all ages and competitive levels. Windmill pitchers are at risk for developing overuse injuries in the throwing arm. Improper mechanics and lack of pitch counts may increase the risk for developing a pitching-related injury. Softball-related overuse injuries include proximal biceps tendinitis, upper extremity stress fractures, and ulnar neuritis. Acute injuries commonly occur in the lower extremity and include both fractures and ligamentous injuries. Sliding injuries account for a significant number of these lower extremity injuries. The addition of breakaway bases and mandatory use of protective headgear by defensive players may decrease acute injuries commonly seen in softball. Off-season programs should stress proper throwing and sliding mechanics, core conditioning, and a lower extremity neuromuscular education program.

The radiation chemistry of ionic liquids: A review

DOE PAGES

Mincher, Bruce J.; Wishart, James F.

2014-07-03

Ionic liquids have received increasing attention as media for radiochemical separations. Recent literature includes examinations of the efficiencies and mechanisms of the solvent extraction of lanthanides, actinides and fission products into ionic liquid solutions. For radiochemical applications, including as replacement solvents for nuclear fuel reprocessing, a thorough understanding of the radiation chemistry of ionic liquids will be required. Such an understanding can be achieved based on a combination of steady-state radiolysis experiments coupled with post-irradiation product identification and pulse-radiolysis experiments to acquire kinetic information. These techniques allow for the elucidation of radiolytic mechanisms. This contribution reviews the current ionic liquidmore » radiation chemistry literature as it affects separations, with these considerations in mind.« less

Lactobacillus casei CCFM419 attenuates type 2 diabetes via a gut microbiota dependent mechanism.

PubMed

Wang, Gang; Li, Xiangfei; Zhao, Jianxin; Zhang, Hao; Chen, Wei

2017-09-20

Probiotics, as dietary supplements, transmit their major effects through the regulation of gut microbiota. According to a previous study, one possible mechanism of Lactobacillus casei CCFM419 protection against diabetes may involve gut flora. To test this hypothesis, high fat and streptozotocin-induced C57BL/6J mice were fed L. casei CCFM419 at 10 8 , 10 9 , and 10 10 colony forming units (CFU). Compared to untreated mice, 10 9 CFU of L. casei CCFM419 attenuated several symptoms of diabetes, including fasting blood glucose, postprandial blood glucose, glucose intolerance, and insulin resistance. In addition, this CFU level also decreased the levels of the inflammatory markers tumor necrosis factor-α and interleukin-6 and increased intestinal glucagon-like peptide-1 (GLP-1) levels, which are associated with the production of short chain fatty acids (SCFAs). The 16S rRNA gene sequencing of fecal samples demonstrated that 10 9 CFU of L. casei CCFM419 dramatically increased the abundance of Bacteroidetes and decreased the proportion of Firmicutes at the phylum level, and enriched Bifidobacterium, Lactobacillus, and SCFA-producing bacteria, including Allobaculum and Bacteroides. These findings suggested that L. casei CCFM419 modified the gut flora-SCFA-inflammation/GLP-1 mechanism to ameliorate type 2 diabetes.

Ultrasound-Mediated Transdermal Drug Delivery: Mechanisms, Scope, and Emerging Trends

PubMed Central

Polat, Baris E.; Hart, Douglas; Langer, Robert; Blankschtein, Daniel

2012-01-01

The use of ultrasound for the delivery of drugs to, or through, the skin is commonly known as sonophoresis or phonophoresis. The use of therapeutic and high frequencies of ultrasound (≥ 0.7 MHz) for sonophoresis (HFS) dates back to as early as the 1950s, while low-frequency sonophoresis (LFS, 20 – 100 kHz) has only been investigated significantly during the past two decades. Although HFS and LFS are similar because they both utilize ultrasound to increase the skin penetration of permeants, the mechanisms associated with each physical enhancer are different. Specifically, the location of cavitation and the extent to which each process can increase skin permeability are quite dissimilar. Although the applications of both technologies are different, they each have strengths that could allow them to improve current methods of local, regional, and systemic drug delivery. In this review, we will discuss the mechanisms associated with both HFS and LFS, specifically concentrating on the key mechanistic differences between these two skin treatment methods. Background on the relevant physics associated with ultrasound transmitted through aqueous media will also be discussed, along with implications of these phenomena on sonophoresis. Finally, a thorough review of the literature is included, dating back to the first published reports of sonophoresis, including a discussion of emerging trends in the field. PMID:21238514

Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation.

PubMed

Arenaza-Urquijo, Eider M; Bejanin, Alexandre; Gonneaud, Julie; Wirth, Miranka; La Joie, Renaud; Mutlu, Justine; Gaubert, Malo; Landeau, Brigitte; de la Sayette, Vincent; Eustache, Francis; Chételat, Gaël

2017-11-01

The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aβ) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aβ deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages. Copyright © 2017 Elsevier Inc. All rights reserved.

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

PubMed Central

Seminerio, Michael J.; Robson, Matthew J.; McCurdy, Christopher R.; Matsumoto, Rae R.

2013-01-01

Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced doseand time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression. PMID:22820108

Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development.

PubMed

Al-Gubory, Kaïs H

2014-07-01

Developmental toxicity caused by exposure to a mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviours, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase susceptibility of offspring to diseases. There is evidence to suggest that the developmental toxicological mechanisms of chemicals and lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased ROS generation overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Data on the involvement of oxidative stress in the mechanism of developmental toxicity following exposure to environmental pollutants are reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on post-natal development and health outcomes. Developmental toxicity caused by exposure to mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviors, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase the susceptibility of offspring to development complications and diseases. There is evidence to suggest that the developmental toxicological mechanisms of human-made chemicals and unhealthy lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased generation of ROS overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Exposure to various environmental pollutants induces synergic and cumulative dose-additive adverse effects on prenatal development, pregnancy outcomes and neonate health. Data from the literature on the involvement of oxidative stress in the mechanism of developmental toxicity following in vivo exposure to environmental pollutants will be reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on postnatal development and health outcomes. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Pathogenesis and Prevention of Hepatic Steatosis

PubMed Central

Nassir, Fatiha; Rector, R. Scott; Hammoud, Ghassan M.

2015-01-01

Hepatic steatosis is defined as intrahepatic fat of at least 5% of liver weight. Simple accumulation of triacylglycerols in the liver could be hepatoprotective; however, prolonged hepatic lipid storage may lead to liver metabolic dysfunction, inflammation, and advanced forms of nonalcoholic fatty liver disease. Nonalcoholic hepatic steatosis is associated with obesity, type 2 diabetes, and dyslipidemia. Several mechanisms are involved in the accumulation of intrahepatic fat, including increased flux of fatty acids to the liver, increased de novo lipogenesis, and/or reduced clearance through β-oxidation or very-low-density lipoprotein secretion. This article summarizes the mechanisms involved in the accumulation of triacylglycerols in the liver, the clinical implications, and the prevention of hepatic steatosis, with a focus on the role of mitochondrial function and lifestyle modifications. PMID:27099587

Effects of pleural effusion drainage on oxygenation, respiratory mechanics, and hemodynamics in mechanically ventilated patients.

PubMed

Razazi, Keyvan; Thille, Arnaud W; Carteaux, Guillaume; Beji, Olfa; Brun-Buisson, Christian; Brochard, Laurent; Mekontso Dessap, Armand

2014-09-01

In mechanically ventilated patients, the effect of draining pleural effusion on oxygenation is controversial. We investigated the effect of large pleural effusion drainage on oxygenation, respiratory function (including lung volumes), and hemodynamics in mechanically ventilated patients after ultrasound-guided drainage. Arterial blood gases, respiratory mechanics (airway, pleural and transpulmonary pressures, end-expiratory lung volume, respiratory system compliance and resistance), and hemodynamics (blood pressure, heart rate, and cardiac output) were recorded before and at 3 and 24 hours (H24) after pleural drainage. The respiratory settings were kept identical during the study period. The mean volume of effusion drained was 1,579 ± 684 ml at H24. Uncomplicated pneumothorax occurred in two patients. Respiratory mechanics significantly improved after drainage, with a decrease in plateau pressure and a large increase in end-expiratory transpulmonary pressure. Respiratory system compliance, end-expiratory lung volume, and PaO2/FiO2 ratio all improved. Hemodynamics were not influenced by drainage. Improvement in the PaO2/FiO2 ratio from baseline to H24 was positively correlated with the increase in end-expiratory lung volume during the same time frame (r = 0.52, P = 0.033), but not with drained volume. A high value of pleural pressure or a highly negative transpulmonary pressure at baseline predicted limited lung expansion following effusion drainage. A lesser improvement in oxygenation occurred in patients with ARDS. Drainage of large (≥500 ml) pleural effusion in mechanically ventilated patients improves oxygenation and end-expiratory lung volume. Oxygenation improvement correlated with an increase in lung volume and a decrease in transpulmonary pressure, but was less so in patients with ARDS.

Mechanical properties of water desalination and wastewater treatment membranes

DOE PAGES

Wang, Kui; Abdalla, Ahmed A.; Khaleel, Mohammad A.; ...

2017-07-13

Applications of membrane technology in water desalination and wastewater treatment have increased significantly in the past fewdecades due to itsmany advantages over otherwater treatment technologies.Water treatment membranes provide high flux and contaminant rejection ability and require good mechanical strength and durability. Thus, assessing the mechanical properties of water treatment membranes is critical not only to their design, but also for studying their failure mechanisms, including the surface damage, mechanical and chemical ageing, delamination and loss of dimensional stability of the membranes. The various experimental techniques to assess themechanical properties ofwastewater treatment and desalinationmembranes are reviewed. Uniaxial tensile test, bending test,more » dynamic mechanical analysis, nanoindentation and bursting tests are the most widely used mechanical characterization methods for water treatment membranes. Mechanical degradations induced by fouling, chemical cleaning as well as membrane delamination are then discussed. Moreover, in order to study the membranesmechanical responses under similar loading conditions, the stress-state of the membranes are analyzed and advanced mechanical testing approaches are proposed. Lastly, some perspectives are highlighted to study the structure-properties relationship for wastewater treatment and water desalination membranes.« less

Flash memory management system and method utilizing multiple block list windows

NASA Technical Reports Server (NTRS)

Chow, James (Inventor); Gender, Thomas K. (Inventor)

2005-01-01

The present invention provides a flash memory management system and method with increased performance. The flash memory management system provides the ability to efficiently manage and allocate flash memory use in a way that improves reliability and longevity, while maintaining good performance levels. The flash memory management system includes a free block mechanism, a disk maintenance mechanism, and a bad block detection mechanism. The free block mechanism provides efficient sorting of free blocks to facilitate selecting low use blocks for writing. The disk maintenance mechanism provides for the ability to efficiently clean flash memory blocks during processor idle times. The bad block detection mechanism provides the ability to better detect when a block of flash memory is likely to go bad. The flash status mechanism stores information in fast access memory that describes the content and status of the data in the flash disk. The new bank detection mechanism provides the ability to automatically detect when new banks of flash memory are added to the system. Together, these mechanisms provide a flash memory management system that can improve the operational efficiency of systems that utilize flash memory.

Mechanical properties of water desalination and wastewater treatment membranes

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

Wang, Kui; Abdalla, Ahmed A.; Khaleel, Mohammad A.

Applications of membrane technology in water desalination and wastewater treatment have increased significantly in the past fewdecades due to itsmany advantages over otherwater treatment technologies.Water treatment membranes provide high flux and contaminant rejection ability and require good mechanical strength and durability. Thus, assessing the mechanical properties of water treatment membranes is critical not only to their design, but also for studying their failure mechanisms, including the surface damage, mechanical and chemical ageing, delamination and loss of dimensional stability of the membranes. The various experimental techniques to assess themechanical properties ofwastewater treatment and desalinationmembranes are reviewed. Uniaxial tensile test, bending test,more » dynamic mechanical analysis, nanoindentation and bursting tests are the most widely used mechanical characterization methods for water treatment membranes. Mechanical degradations induced by fouling, chemical cleaning as well as membrane delamination are then discussed. Moreover, in order to study the membranesmechanical responses under similar loading conditions, the stress-state of the membranes are analyzed and advanced mechanical testing approaches are proposed. Lastly, some perspectives are highlighted to study the structure-properties relationship for wastewater treatment and water desalination membranes.« less

On mechanical mechanism of damage evolution in articular cartilage.

PubMed

Men, Yu-Tao; Jiang, Yan-Long; Chen, Ling; Zhang, Chun-Qiu; Ye, Jin-Duo

2017-09-01

Superficial lesions of cartilage are the direct indication of osteoarthritis. To investigate the mechanical mechanism of cartilage with micro-defect under external loading, a new plain strain numerical model with micro-defect was proposed and damage evolution progression in cartilage over time has been simulated, the parameter were studied including load style, velocity of load and degree of damage. The new model consists of the hierarchical structure of cartilage and depth-dependent arched fibers. The numerical results have shown that not only damage of the cartilage altered the distribution of the stress but also matrix and fiber had distinct roles in affecting cartilage damage, and damage in either matrix or fiber could promote each other. It has been found that the superficial cracks in cartilage spread preferentially along the tangent direction of the fibers. It is the arched distribution form of fibers that affects the crack spread of cartilage, which has been verified by experiment. During the process of damage evolution, its extension direction and velocity varied constantly with the damage degree. The rolling load could cause larger stress and strain than sliding load. Strain values of the matrix initially increased and then decreased gradually with the increase of velocity, and velocity had a greater effect on matrix than fibers. Damage increased steadily before reaching 50%, sharply within 50 to 85%, and smoothly and slowly after 85%. The finding of the paper may help to understand the mechanical mechanism why the cracks in cartilage spread preferentially along the tangent direction of the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

Massage Therapy Research Review

PubMed Central

Field, Tiffany

2017-01-01

Moderate pressure massage has contributed to many positive effects including increased weight gain in preterm infants, reduced pain in different syndromes including fibromyalgia and rheumatoid arthritis, enhanced attentiveness, reduced depression and enhanced immune function (increased natural killer cells and natural killer cell activity). Surprisingly, these recent studies have not been reviewed, highlighting the need for the current review. When moderate and light pressure massage have been compared in laboratory studies, moderate pressure massage reduced depression, anxiety and heart rate, and it altered EEG patterns, as in a relaxation response. Moderate pressure massage has also led to increased vagal activity and decreased cortisol levels. Functional magnetic resonance imaging data have suggested that moderate pressure massage was represented in several brain regions including the amygdala, the hypothalamus and the anterior cingulate cortex, all areas involved in stress and emotion regulation. Further research is needed to identify underlying neurophysiological and biochemical mechanisms associated with moderate pressure massage. PMID:25172313

Massage therapy research review.

PubMed

Field, Tiffany

2014-11-01

Moderate pressure massage has contributed to many positive effects including increased weight gain in preterm infants, reduced pain in different syndromes including fibromyalgia and rheumatoid arthritis, enhanced attentiveness, reduced depression and enhanced immune function (increased natural killer cells and natural killer cell activity).Surprisingly, these recent studies have not been reviewed, highlighting the need for the current review. When moderate and light pressure massage have been compared in laboratory studies, moderate pressure massage reduced depression, anxiety and heart rate, and it altered EEG patterns, as in a relaxation response. Moderate pressure massage has also led to increased vagal activity and decreased cortisol levels. Functional magnetic resonance imaging data have suggested that moderate pressure massage was represented in several brain regions including the amygdala, the hypothalamus and the anterior cingulate cortex, all areas involved in stress and emotion regulation. Further research is needed to identify underlying neurophysiological and biochemical mechanisms associated with moderate pressure massage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

PubMed Central

KIM, S. E.; CHANG, L.

2013-01-01

Background Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis. Purpose The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared. PMID:22863120

Productivity, embryo and eggshell characteristics, and contaminants in bald eagles from the Great Lakes, USA, 1986 to 2000

USGS Publications Warehouse

Best, David A.; Elliott, Kyle; Bowerman, William; Shieldcastle, Mark C.; Postupalsky, Sergej; Kubiak, Timothy J.; Tillitt, Donald E.; Elliott, John E.

2010-01-01

Chlorinated hydrocarbon concentrations in eggs of fish-eating birds from contaminated environments such as the Great Lakes of North America tend to be highly intercorrelated, making it difficult to elucidate mechanisms causing reproductive impairment, and to ascribe cause to specific chemicals. An information- theoretic approach was used on data from 197 salvaged bald eagle (Haliaeetus leucocephalus) eggs (159 clutches) that failed to hatch in Michigan and Ohio, USA (1986–2000). Contaminant levels declined over time while eggshell thickness increased, and by 2000 was at pre-1946 levels. The number of occupied territories and productivity increased during 1981 to 2004. For both the entire dataset and a subset of nests along the Great Lakes shoreline, polychlorinated biphenyls (ΣPCBs, fresh wet wt) were generally included in the most parsimonious models (lowest-Akaike's information criterion [AICs]) describing productivity, with significant declines in productivity observed above 26 µg/g ΣPCBs (fresh wet wt). Of 73 eggs with a visible embryo, eight (11%) were abnormal, including three with skewed bills, but they were not associated with known teratogens, including ΣPCBs. Eggs with visible embryos had greater concentrations of all measured contaminants than eggs without visible embryos; the most parsimonious models describing the presence of visible embryos incorporated dieldrin equivalents and dichlorodiphenyldichloroethylene (DDE). There were significant negative correlations between eggshell thickness and all contaminants, with ΣPCBs included in the most parsimonious models. There were, however, no relationships between productivity and eggshell thickness or Ratcliffe's index. The ΣPCBs and DDE were negatively associated with nest success of bald eagles in the Great Lakes watersheds, but the mechanism does not appear to be via shell quality effects, at least at current contaminant levels, while it is not clear what other mechanisms were involved.

Obesity: Current and potential pharmacotherapeutics and targets.

PubMed

Narayanaswami, Vidya; Dwoskin, Linda P

2017-02-01

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Obesity: Current and Potential Pharmacotherapeutics and Targets

PubMed Central

Narayanaswami, Vidya; Dwoskin, Linda P.

2016-01-01

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. PMID:27773782

Stress, depression, and cardiovascular dysregulation: A review of neurobiological mechanisms and the integration of research from preclinical disease models

PubMed Central

Grippo, Angela J.; Johnson, Alan Kim

2008-01-01

A bidirectional association between mood disorders such as depression, and cardiovascular diseases such as myocardial infarction and congestive heart failure, has been described; however, the precise neurobiological mechanisms that underlie these associations have not been fully elucidated. This review is focused on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders, with an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction including dopamine, norepinephrine and serotonin, and (e) behavioral changes including fatigue and physical inactivity. We also focus specifically on experimental investigations with preclinical disease models, conducted to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with the extensive literature describing findings from human research, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and can promote the development of better treatments and interventions for individuals with these co-morbid conditions. PMID:19116888

Reducing ultrafiltration membrane fouling during potable water reuse using pre-ozonation.

PubMed

Wang, Hui; Park, Minkyu; Liang, Heng; Wu, Shimin; Lopez, Israel J; Ji, Weikang; Li, Guibai; Snyder, Shane A

2017-11-15

Wastewater reclamation has increasingly become popular to secure potable water supply. Low-pressure membrane processes such as microfiltration (MF) and ultrafiltration (UF) play imperative roles as a barrier of macromolecules for such purpose, but are often limited by membrane fouling. Effluent organic matter (EfOM), including biopolymers and particulates, in secondary wastewater effluents have been known to be major foulants in low-pressure membrane processes. Hence, the primary aim of this study was to investigate the effects of pre-ozonation as a pre-treatment for UF on the membrane fouling caused by EfOM in secondary wastewater effluents for hydrophilic regenerated cellulose (RC) and hydrophobic polyethersulfone (PES) UF membranes. It was found that greater fouling reduction was achieved by pre-ozonation for the hydrophilic RC membrane than the hydrophobic PES membrane at increasing ozone doses. In addition, the physicochemical property changes of EfOM, including biopolymer fractions, by pre-ozonation were systemically investigated. The classical pore blocking model and the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theories were employed to scrutinize the fouling alleviation mechanism by pre-ozonation. As a result, the overarching mechanisms of fouling reduction were attributed to the following key reasons: (1) Ozone degraded macromolecules such as biopolymers like proteins and polysaccharides into smaller fractions, thereby increasing free energy of cohesion of EfOM and rendering them more hydrophilic and stable; (2) pre-ozonation augmented the interfacial free energy of adhesion between foulants and the RC/PES membranes, leading to the increase of repulsions and/or the decrease of attractions; and (3) pre-ozonation prolonged the transition from pore blocking to cake filtration that was a dominant fouling mechanism, thereby reducing fouling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arsenic-induced malignant transformation of human keratinocytes: Involvement of Nrf2

PubMed Central

Pi, Jingbo; Diwan, Bhalchandra A.; Sun, Yang; Liu, Jie; Qu, Wei; He, Yuying; Styblo, Miroslav; Waalkes, Michael P.

2009-01-01

Arsenic is a well-known human skin carcinogen but the underlying mechanisms of carcinogenesis are unclear. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism, and emerging data suggest that constitutive activation of Nrf2 contributes to malignant phenotype. In the present study when an immortalized, non-tumorigenic human keratinocyte cell line (HaCaT) was continuously exposed to environmentally relevant level of inorganic arsenite (100 nM) for 28 weeks, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. To investigate the mechanisms involved, a broad array of biomarkers for transformation were assessed in these arsenic-transformed cells (termed As-TM). In addition to increased secretion of matrix metalloproteinase-9 (MMP-9), a set of markers for squamous differentiation and skin keratinization, including keratin-1, keratin-10, involucrin, and loricrin, were significantly elevated in As-TM cells. Furthermore, As-TM cells showed increased intracellular glutathione, elevated expression of Nrf2 and its target genes, as well as generalized apoptotic resistance. In contrast to increased basal Nrf2 activity in As-TM cells, a diminished Nrf2-mediated antioxidant response induced by acute exposure to high dose of arsenite or tert-butyl hydroxyquinone occurred. The findings that multiple biomarkers for malignant transformation observed in As-TM cells, including MMP-9 and cytokeratins, are potentially regulated by Nrf2 suggest constitutive Nrf2 activation may be involved in arsenic carcinogenesis of skin. The weakened Nrf2 activation in response to oxidative stressors observed in As-TM cells, coupled with acquired apoptotic resistance, would potentially have increased the likelihood of transmittable oxidative DNA damage and fixation of mutational/DNA damage events. PMID:18572023

MR elastography of hydrocephalus

NASA Astrophysics Data System (ADS)

Pattison, Adam J.; Lollis, S. Scott; Perrinez, Phillip R.; Weaver, John B.; Paulsen, Keith D.

2009-02-01

Hydrocephalus occurs due to a blockage in the transmission of cerebrospinal fluid (CSF) in either the ventricles or subarachnoid space. Characteristics of this condition include increased intracranial pressure, which can result in neurologic deterioration [1]. Magnetic resonance elastography (MRE) is an imaging technique that estimates the mechanical properties of tissue in vivo. While some investigations of brain tissue have been performed using MRE [2,3,4,5], the effects due to changes in interstitial pressure and fluid content on the mechanical properties of the brain remain unknown. The purpose of this work is to assess the potential of MRE to differentiate between the reconstructed properties of normal and hydrocephalic brains. MRE data was acquired in 18 female feline subjects, 12 of which received kaolin injections resulting in an acute form of hydrocephalus. In each animal, four MRE scans were performed during the process including one pre-injection and three post-injection scans. The elastic parameters were obtained using a subzone-based reconstruction algorithm that solves Navier's equations for linearly elastic materials [6]. The remaining cats were used as controls, injected with saline instead of kaolin. To determine the state of hydrocephalus, ventricular volume was estimated from segmenting anatomical images. The mean ventricular volume of hydrocephalic cats significantly increased (P <~ 0.0001) between the first and second scans. The mean volume was not observed to increase (P >~ 0.5) for the control cats. Also, there was an observable increase in the recorded elastic shear modulus of brain tissue in the normal and hydrocephalic acquisitions. Results suggest that MRE is able to detect changes in the mechanical properties of brain tissue resulting from kaolin-induced hydrocephalus, indicating the need for further study.

Permanent-magnet-less machine having an enclosed air gap

DOEpatents

Hsu, John S [Oak Ridge, TN

2012-02-07

A permanent magnet-less, brushless synchronous system includes a stator that generates a magnetic rotating field when sourced by an alternating current. An uncluttered rotor disposed within the magnetic rotating field is spaced apart from the stator to form an air gap relative to an axis of rotation. A stationary excitation core spaced apart from the uncluttered rotor by an axial air gap and a radial air gap substantially encloses the stationary excitation core. Some permanent magnet-less, brushless synchronous systems include stator core gaps to reduce axial flux flow. Some permanent magnet-less, brushless synchronous systems include an uncluttered rotor coupled to outer laminations. The quadrature-axis inductance may be increased in some synchronous systems. Some synchronous systems convert energy such as mechanical energy into electrical energy (e.g., a generator); other synchronous systems may convert any form of energy into mechanical energy (e.g., a motor).

Permanent-magnet-less machine having an enclosed air gap

DOEpatents

Hsu, John S.

2013-03-05

A permanent magnet-less, brushless synchronous system includes a stator that generates a magnetic rotating field when sourced by an alternating current. An uncluttered rotor disposed within the magnetic rotating field is spaced apart from the stator to form an air gap relative to an axis of rotation. A stationary excitation core spaced apart from the uncluttered rotor by an axial air gap and a radial air gap substantially encloses the stationary excitation core. Some permanent magnet-less, brushless synchronous systems include stator core gaps to reduce axial flux flow. Some permanent magnet-less, brushless synchronous systems include an uncluttered rotor coupled to outer laminations. The quadrature-axis inductance may be increased in some synchronous systems. Some synchronous systems convert energy such as mechanical energy into electrical energy (e.g., a generator); other synchronous systems may convert any form of energy into mechanical energy (e.g., a motor).

National Trends (2009-2013) for Palliative Care Utilization for Patients Receiving Prolonged Mechanical Ventilation.

PubMed

Chatterjee, Kshitij; Goyal, Abhinav; Kakkera, Krishna; Harrington, Sarah; Corwin, Howard L

2018-05-04

Patients requiring mechanical ventilation have high morbidity and mortality. Providing palliative care services has been suggested as a way to improve comprehensive management of critically ill patients. We examined the trend in the utilization of palliative care among adults who require prolonged mechanical ventilation. Primary objectives were to determine the trend in palliative care utilization over time, predictors for palliative care utilization, and palliative care impact on hospital length of stay. Retrospective, cross-sectional study. The National Inpatient Sample data between 2009 and 2013 was used for this study. Adults (age ≥ 18 yr) who underwent prolonged mechanical ventilation (≥ 96 consecutive hr) were studied. Palliative care and mechanical ventilation were identified using the corresponding International Classification of Diseases, 9th revision, Clinical Modification, codes. A total of 1,751,870 hospitalizations with prolonged mechanical ventilation were identified between 2009 and 2013. The utilization of palliative care increased yearly from 6.5% in 2009 to 13.1% in 2013 (p < 0.001). Among the mechanically ventilated patients who died, palliative care increased from 15.9% in 2009 to 33.3% in 2013 (p < 0.001). Median hospital length of stay for patients with and without palliative care was 13 and 17 days, respectively (p < 0.001). Patients discharged to either short- or long-term care facilities had a shorter length of stay if palliative care was provided (15 vs 19 d; p < 0.001). The factors associated with a higher palliative care utilization included older age, malignancy, larger hospitals in urban areas, and teaching hospitals. Non-Caucasian race was associated with lower palliative care utilization. Among patients who undergo prolonged mechanical ventilation, palliative care utilization is increasing, particularly in patients who die during hospitalization. Using palliative care for mechanically ventilated patients who are discharged to either short- or long-term care facilities is associated with a shorter hospital length of stay.

A survey of unmanned ground vehicles with applications to agricultural and environmental sensing

USDA-ARS?s Scientific Manuscript database

Unmanned ground vehicles have been utilized in the last few decades in an effort to increase the efficiency of agriculture, in particular, by reducing labor needs. Unmanned vehicles have been used for a variety of purposes including: soil sampling, irrigation management, precision spraying, mechanic...

Preparing School Personnel to Implement Section 504

ERIC Educational Resources Information Center

Shaw, Stan F.; Madaus, Joseph W.

2008-01-01

Section 504 of the Rehabilitation Act of 1973 has become an increasingly important mechanism in providing services to students with disabilities in public schools. Because Section 504 is a civil rights law, responsibility for its implementation involves a range of school-based professionals, including administrators, general education teachers,…

NON-ADDITIVE INTERACTIONS OF AN ORGANOPHOSPHORUS PESTICIDE MIXTURE IN ADULT AND PREWEANLING RATS.

EPA Science Inventory

Critical features of risk assessment include the evaluation of risk following exposure to pesticide mixtures as well as the potential for increased sensitivity of the young. The US EPA is required to regulate pesticides acting via a common mechanism of action as a group, e.g.,...

Insults to the Developing Brain and Impact on Neurodevelopmental Outcome

ERIC Educational Resources Information Center

Adams-Chapman, Ira

2009-01-01

Premature infants have a disproportionately increased risk for brain injury based on several mechanisms including intraventricular hemorrhage, ischemia and the vulnerability of developing neuronal progenitor cells. Injury to the developing brain often results in neurologic abnormalities that can be correlated with a structural lesion; however more…

Autoimmunity and the Gut

PubMed Central

Campbell, Andrew W.

2014-01-01

Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity. PMID:24900918

Recurrent milk aspiration produces changes in airway mechanics, lung eosinophilia, and goblet cell hyperplasia in a murine model.

PubMed

Janahi, I A; Elidemir, O; Shardonofsky, F R; Abu-Hassan, M N; Fan, L L; Larsen, G L; Blackburn, M R; Colasurdo, G N

2000-12-01

Recurrent aspiration of milk into the respiratory tract has been implicated in the pathogenesis of a variety of inflammatory lung disorders including asthma. However, the lack of animal models of aspiration-induced lung injury has limited our knowledge of the pathophysiological characteristics of this disorder. This study was designed to evaluate the effects of recurrent milk aspiration on airway mechanics and lung cells in a murine model. Under light anesthesia, BALB/c mice received daily intranasal instillations of whole cow's milk (n = 7) or sterile physiologic saline (n = 9) for 10 d. Respiratory system resistance (Rrs) and dynamic elastance (Edyn,rs) were measured in anesthetized, tracheotomized, paralyzed and mechanically ventilated mice 24 h after the last aspiration of milk. Rrs and Edyn,rs were derived from transrespiratory and plethysmographic pressure signals. In addition, airway responses to increasing concentrations of i.v. methacholine (Mch) were determined. Airway responses were measured in terms of PD(100) (dose of Mch causing 100% increase from baseline Rrs) and Rrs,max (% increase from baseline at the maximal plateau response) and expressed as % control (mean +/- SE). We found recurrent milk aspiration did not affect Edyn and baseline Rrs values. However, airway responses to Mch were increased after milk aspiration when compared with control mice. These changes in airway mechanics were associated with an increased percentage of lymphocytes and eosinophils in the bronchoalveolar lavage, mucus production, and lung inflammation. Our findings suggest that recurrent milk aspiration leads to alterations in airway function, lung eosinophilia, and goblet cell hyperplasia in a murine model.

Experimental evaluation of multiscale tendon mechanics.

PubMed

Fang, Fei; Lake, Spencer P

2017-07-01

Tendon's primary function is a mechanical link between muscle and bone. The hierarchical structure of tendon and specific compositional constituents are believed to be critical for proper mechanical function. With increased appreciation for tendon importance and the development of various technological advances, this review paper summarizes recent experimental approaches that have been used to study multiscale tendon mechanics, includes an overview of studies that have evaluated the role of specific tissue constituents, and also proposes challenges/opportunities facing tendon study. Tendon has been demonstrated to have specific structural characteristics (e.g., multi-level hierarchy, crimp pattern, helix) and complex mechanical properties (e.g., non-linearity, anisotropy, viscoelasticity). Physical mechanisms including uncrimping, fiber sliding, and collagen reorganization have been shown to govern tendon mechanical responses under both static and dynamic loading. Several tendon constituents with relatively small quantities have been suggested to play a role in its mechanics, although some results are conflicting. Further research should be performed to understand the interplay and communication of tendon mechanical properties across levels of the hierarchical structure, and further show how each of these components contribute to tendon mechanics. The studies summarized and discussed in this review have helped elucidate important aspects of multiscale tendon mechanics, which is a prerequisite for analyzing stress/strain transfer between multiple scales and identifying key principles of mechanotransduction. This information could further facilitate interpreting the functional diversity of tendons from different species, different locations, and even different developmental stages, and then better understand and identify fundamental concepts related to tendon degeneration, disease, and healing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1353-1365, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Interface morphology and mechanical properties of Al-Cu-Al laminated composites fabricated by explosive welding and subsequent rolling process

NASA Astrophysics Data System (ADS)

Hoseini-Athar, M. M.; Tolaminejad, B.

2016-07-01

Explosive welding is a well-known solid state method for joining similar and dissimilar materials. In the present study, tri-layered Al-Cu-Al laminated composites with different interface morphologies were fabricated by explosive welding and subsequent rolling. Effects of explosive ratio and rolling thickness reduction on the morphology of interface and mechanical properties were evaluated through optical/scanning electron microscopy, micro-hardness, tensile and tensile-shear tests. Results showed that by increasing the thickness reduction, bonding strength of specimens including straight and wavy interfaces increases. However, bonding strength of the specimens with melted layer interface decreases up to a threshold thickness reduction, then rapidly increases by raising the reduction. Hardness Values of welded specimens were higher than those of original material especially near the interface and a more uniform hardness profile was obtained after rolling process.

The effect of anesthesia on body temperature control.

PubMed

Lenhardt, Rainer

2010-06-01

The human thermoregulatory system usually maintains core body temperature near 37 degrees C. This homeostasis is accomplished by thermoregulatory defense mechanisms such as vasoconstriction and shivering or sweating and vasodilatation. Thermoregulation is impaired during general anesthesia. Suppression of thermoregulatory defense mechanisms during general anesthesia is dose dependant and mostly results in perioperative hypothermia. Several adverse effects of hypothermia have been identified, including an increase in postoperative wound infection, perioperative coagulopathy and an increase of postoperative morbid cardiac events. Perioperative hypothermia can be avoided by warming patients actively during general anesthesia. Fever is a controlled increase of core body temperature. Various causes of perioperative fever are given. Fever is usually attenuated by general anesthesia. Typically, patients develop a fever of greater magnitude in the postoperative phase. Postoperative fever is fairly common. The incidence of fever varies with type and duration of surgery, patient's age, surgical site and preoperative inflammation.

ROLE OF SYMPATHETIC NERVOUS SYSTEM IN OBESITY RELATED HYPERTENSION

PubMed Central

da Silva, Alexandre; doCarmo, Jussara; Dubinion, John; Hall, John E.

2010-01-01

Obesity is recognized as a major, worldwide, health problem. Excess weight is a major cause of increased blood pressure in most patients with essential hypertension, and greatly increases the risk for diabetes, cardiovascular diseases, and end stage renal disease. Although the mechanisms by which obesity raises blood pressure are not completely understood, increased renal sodium reabsorption, impaired pressure natriuresis, and volume expansion appear to play important roles. Several potential mechanisms have been suggested to contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), and physical compression of the kidneys, especially when visceral obesity is present. Activation of the SNS in obesity may be due, in part, to hyperleptinemia and other factors secreted by adipocytes and the gastrointestinal tract, activation of the central nervous melanocortin pathway, and baroreceptor dysfunction. PMID:19442330

Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Chen, Dongquan; Stueckle, Todd A.; Luanpitpong, Sudjit; Rojanasakul, Yon; Lu, Yongju; Wang, Liying

2015-01-01

A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.

Presynaptic Active Zone Density during Development and Synaptic Plasticity.

PubMed

Clarke, Gwenaëlle L; Chen, Jie; Nishimune, Hiroshi

2012-01-01

Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

Presynaptic Active Zone Density during Development and Synaptic Plasticity

PubMed Central

Clarke, Gwenaëlle L.; Chen, Jie; Nishimune, Hiroshi

2012-01-01

Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated. PMID:22438837

Relationship between volume and survival in closed intensive care units is weak and apparent only in mechanically ventilated patients.

PubMed

Fernández, Rafael; Altaba, Susana; Cabre, Lluis; Lacueva, Victoria; Santos, Antonio; Solsona, Jose-Felipe; Añon, Jose-Manuel; Catalan, Rosa-Maria; Gutierrez, Maria-Jose; Fernandez-Cid, Ramon; Gomez-Tello, Vicente; Curiel, Emilio; Fernandez-Mondejar, Enrique; Oliva, Joan-Carles; Tizon, Ana Isabel; Gonzalez, Javier; Monedero, Pablo; Sanchez, Manuela Garcia; de la Torre, M Victoria; Ibañez, Pedro; Frutos, Fernando; Del Nogal, Frutos; Gomez, M Jesus; Marcos, Alfredo; Vera, Paula; Serrano, Jose Manuel; Umaran, Isabel; Carrillo, Andres; Lopez-Pueyo, M-Jose; Rascado, Pedro; Balerdi, Begoña; Suberviola, Borja; Hernandez, Gonzalo

2013-10-01

Recent studies have found an association between increased volume and increased intensive care unit (ICU) survival; however, this association might not hold true in ICUs with permanent intensivist coverage. Our objective was to determine whether ICU volume correlates with survival in the Spanish healthcare system. Post hoc analysis of a prospective study of all patients admitted to 29 ICUs during 3 months. At ICU discharge, the authors recorded demographic variables, severity score, and specific ICU treatments. Follow-up variables included ICU readmission and hospital mortality. Statistics include logistic multivariate analyses for hospital mortality according to quartiles of volume of patients. The authors studied 4,001 patients with a mean predicted risk of death of 23% (range at hospital level: 14-46%). Observed hospital mortality was 19% (range at hospital level: 11-35%), resulting in a standardized mortality ratio of 0.81 (range: 0.5-1.3). Among the 1,923 patients needing mechanical ventilation, the predicted risk of death was 32% (14-60%) and observed hospital mortality was 30% (12-61%), resulting in a standardized mortality ratio of 0.96 (0.5-1.7). The authors found no correlation between standardized mortality ratio and ICU volume in the entire population or in mechanically ventilated patients. Only mechanically ventilated patients in very low-volume ICUs had slightly worse outcome. In the currently studied healthcare system characterized by 24/7 intensivist coverage, the authors found wide variability in outcome among ICUs even after adjusting for severity of illness but no relationship between ICU volume and outcome. Only mechanically ventilated patients in very low-volume centers had slightly worse outcomes.

AGE-RAGE Stress, Stressors, and Antistressors in Health and Disease.

PubMed

Prasad, Kailash; Mishra, Manish

2018-03-01

Adverse effects of advanced glycation end-products (AGEs) on the tissues are through nonreceptor- and receptor-mediated mechanisms. In the receptor-mediated mechanism, interaction of AGEs with its cell-bound receptor of AGE (RAGE) increases generation of oxygen radicals, activates nuclear factor-kappa B, and increases expression and release of pro-inflammatory cytokines resulting in the cellular damage. The deleterious effects of AGE and AGE-RAGE interaction are coined as "AGE-RAGE stress." The body is equipped with defense mechanisms to counteract the adverse effects of AGE and RAGE through endogenous enzymatic (glyoxalase 1, glyoxalase 2) and AGE receptor-mediated (AGER1, AGER2) degradation of AGE, and through elevation of soluble receptor of AGE (sRAGE). Exogenous defense mechanisms include reduction in consumption of AGE, prevention of AGE formation, and downregulation of RAGE expression. We have coined AGE and RAGE as "stressors" and the defense mechanisms as "anti-stressors." AGE-RAGE stress is defined as a shift in the balance between stressors and antistressors in the favor of stressors. Measurements of stressors or antistressors alone would not assess AGE-RAGE stress. For true assessment of AGE-RAGE stress, the equation should include all the stressors and antistressors. The equation for AGE-RAGE stress, therefore, would be the ratio of AGE + RAGE/sRAGE + glyoxalase1 + glyoxalase 2 + AGER1 +AGER2. This is, however, not practical in patients. AGE-RAGE stress may be assessed simply by the ratio of AGE/sRAGE. A high ratio of AGE/sRAGE indicates a relative shift in stressors from antistressors, suggesting the presence of AGE-RAGE stress, resulting in tissue damage, initiation, and progression of the diseases and their complications.

Association of Central Adiposity With Adverse Cardiac Mechanics: Findings From the Hypertension Genetic Epidemiology Network Study.

PubMed

Selvaraj, Senthil; Martinez, Eva E; Aguilar, Frank G; Kim, Kwang-Youn A; Peng, Jie; Sha, Jin; Irvin, Marguerite R; Lewis, Cora E; Hunt, Steven C; Arnett, Donna K; Shah, Sanjiv J

2016-06-01

Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s'] and early diastolic [e'] tissue velocities). We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m(2), waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s' velocity, and e' velocity (P<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics. © 2016 American Heart Association, Inc.

Migraine and circle of Willis anomalies.

PubMed

Cucchiara, Brett; Detre, John

2008-01-01

Several mechanisms are currently thought to contribute to migraine pathogenesis, including interictal neuronal hyperexcitability, cortical spreading depression underlying the symptom of aura, and trigeminal nerve activation at a peripheral and central level. However, these mechanistic concepts incompletely explain migraine susceptibility in individual patients and do not fully account for the well documented association between migraine and ischemic cerebrovascular disease, including increased risk of both clinical stroke and subclinical brain lesions in migraine patients. The circle of Willis is a major source of collateral blood flow supply in the human brain, and developmental morphologic variants of the circle of Willis are extremely frequent. Altered cerebral blood flow (CBF) has been demonstrated in regions supplied by variant circle of Willis vessels. Our central hypothesis is that circle of Willis anomalies correlate with alterations in cerebral hemodynamics and contribute to migraine susceptibility and ischemic complications of migraine. Dysregulation of CBF may allow relative ischemia to develop in the setting of increased metabolic demand related to neuronal hyperexcitability, may trigger cortical spreading depression, and may predispose individuals with migraine to ischemic lesions and stroke. Identification of structural alterations in the cerebral vasculature in migraine patients would have several important pathophysiological and clinical implications. First, it would provide a developmental mechanism for migraine susceptibility that may lead to further insights into genetic predisposition to migraine. Second, it would expand understanding of potential mechanisms underlying migraine aura and linking migraine with both clinical and subclinical cerebral infarction. Third, it could help to identify the subpopulation of patients at risk of progressive cerebral ischemia so as to target preventative therapies appropriately. Fourth, it would suggest a role for further diagnostic evaluation to determine migraine mechanism in individual patients, analogous to the current paradigm in ischemic stroke in which determination of stroke mechanism is critical to therapeutic decision-making.

Yoga clinical research review.

PubMed

Field, Tiffany

2011-02-01

In this paper recent research is reviewed on the effects of yoga poses on psychological conditions including anxiety and depression, on pain syndromes, cardiovascular, autoimmune and immune conditions and on pregnancy. Further, the physiological effects of yoga including decreased heartrate and blood pressure and the physical effects including weight loss and increased muscle strength are reviewed. Finally, potential underlying mechanisms are proposed including the stimulation of pressure receptors leading to enhanced vagal activity and reduced cortisol. The reduction in cortisol, in turn, may contribute to positive effects such as enhanced immune function and a lower prematurity rate. Copyright © 2010 Elsevier Ltd. All rights reserved.

Sensitive periods in epigenetics: bringing us closer to complex behavioral phenotypes.

PubMed

Nagy, Corina; Turecki, Gustavo

2012-08-01

Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease, but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include DNA methylation, chromatin conformational changes through histone modifications, ncRNAs and, most recently, 5-hydroxymethylcytosine. Although DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods.

Sensitive Periods in Epigenetics: bringing us closer to complex behavioral phenotypes

PubMed Central

Nagy, Corina; Turecki, Gustavo

2017-01-01

Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include: DNA methylation, chromatin conformational changes through histone modifications, non-coding RNAs, and most recently, 5-hydroxymethylcytosine. Though DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods. PMID:22920183

Collaborative action around implementation in Collaborations for Leadership in Applied Health Research and Care: towards a programme theory.

PubMed

Rycroft-Malone, Jo; Wilkinson, Joyce; Burton, Christopher R; Harvey, Gill; McCormack, Brendan; Graham, Ian; Staniszewska, Sophie

2013-10-01

In theory, greater interaction between researchers and practitioners should result in increased potential for implementation. However, we know little about whether this is the case, or what mechanisms might operate to make it happen. This paper reports findings from a study that is identifying and tracking implementation mechanisms, processes, influences and impacts in real time, over time in the Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). This is a longitudinal, realist evaluation case study. The development of the conceptual framework and initial hypotheses involved literature reviewing and stakeholder consultation. Primary data were collected through interviews, observations and documents within three CLAHRCs, and analysed thematically against the framework and hypotheses. The first round of data collection shows that the mechanisms of collaborative action, relationship building, engagement, motivation, knowledge exchange and learning are important to the processes and outcomes of CLAHRCs' activity, including their capacity for implementation. These mechanisms operated in different contexts such as competing agendas, availability of resources and the CLAHRCs' brand. Contexts and mechanisms result in different impact, including the CLAHRCs' approach to implementation, quality of collaboration, commitment and ownership, and degree of sharing and managing knowledge. Emerging features of a middle range theory of implementation within collaboration include alignment in organizational structures and cognitive processes, history of partnerships, responsiveness and resilience in rapidly changing contexts. CLARHCs' potential to mobilize knowledge may be further realized by how they develop insights into their function as collaborative entities.

Reinforcement of SBR/waste rubber powder vulcanizate with in situ generated zinc dimethacrylate

NASA Astrophysics Data System (ADS)

Wang, X. P.; Cheng, B. K.; Zhang, X.; Jia, D. M.

2016-07-01

Methyl acrylic acid/zinc oxide (MAA/ZnO) was introduced to modify styrene- butadiene rubber/waste rubber powder (SBR/WRP) composites by blending. The enhanced mechanical properties and processing ability were presumably originated from improved compatibility and interfacial interaction between WRP and the SBR matrix by the in situ polymerization of zinc dimethacrylate (ZDMA). A refined interface of the modified SBR/WRP composite was observed by scanning electron microscopy. The formation of ZDMA significantly increased the ionic bond content in the vulcanizate, resulting in exceptional mechanical performance. The comprehensive mechanical properties including tensile strength, tear strength and dynamic heat-building performance reached optimum values with 16 phr MAA.

Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.

PubMed

Güldner, Andreas; Kiss, Thomas; Serpa Neto, Ary; Hemmes, Sabrine N T; Canet, Jaume; Spieth, Peter M; Rocco, Patricia R M; Schultz, Marcus J; Pelosi, Paolo; Gama de Abreu, Marcelo

2015-09-01

Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials.

Translocation of mineralo-organic nanoparticles from blood to urine: a new mechanism for the formation of kidney stones?

PubMed

Martel, Jan; Wu, Cheng-Yeu; Young, John D

2016-09-01

Recent studies indicate that mineralo-organic nanoparticles form in various human body fluids, including blood and urine. These nanoparticles may form within renal tubules and increase in size in supersaturated urine, eventually leading to the formation of kidney stones. Here, we present observations suggesting that mineralo-organic nanoparticles found in blood may induce kidney stone formation via an alternative mechanism in which the particles translocate through endothelial and renal epithelial cells to reach urine. We propose that this alternative mechanism of kidney stone formation and the study of mineralo-organic nanoparticles in general may provide novel strategies for the early detection and treatment of ectopic calcifications and kidney stones.

Mechanical and Electronic Approaches to Improve the Sensitivity of Microcantilever Sensors

PubMed Central

Mutyala, Madhu Santosh Ku; Bandhanadham, Deepika; Pan, Liu; Pendyala, Vijaya Rohini; Ji, Hai-Feng

2010-01-01

Advances in the field of Micro Electro Mechanical Systems (MEMS) and their uses now offer unique opportunities in the design of ultrasensitive analytical tools. The analytical community continues to search for cost-effective, reliable, and even portable analytical techniques that can give reliable and fast response results for a variety of chemicals and biomolecules. Microcantilevers (MCLs) have emerged as a unique platform for label-free biosensor or bioassay. Several electronic designs, including piezoresistive, piezoelectric, and capacitive approaches, have been applied to measure the bending or frequency change of the MCLs upon exposure to chemicals. This review summarizes mechanical, fabrication, and electronics approaches to increase the sensitivity of microcantilever (MCL) sensors. PMID:20975987

An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment

PubMed Central

Wu, Junzhen

2016-01-01

Inflamm-aging is a challenging and promising new branch of aging-related research fields that includes areas such as immunosenescence. Increasing evidence indicates that inflamm-aging is intensively associated with many aging diseases, such as Alzheimer's disease, atherosclerosis, heart disease, type II diabetes, and cancer. Mounting studies have focused on the role of inflamm-aging in disease progression and many advances have been made in the last decade. However, the underlying mechanisms by which inflamm-aging affects pathological changes and disease development are still unclear. Here, we review studies of inflamm-aging that explore the concept, pathological features, mechanisms, intervention, and the therapeutic strategies of inflamm-aging in disease progression. PMID:27493973

The mechanisms of cachexia underlying muscle dysfunction in COPD.

PubMed

Remels, A H V; Gosker, H R; Langen, R C J; Schols, A M W J

2013-05-01

Pulmonary cachexia is a prevalent, debilitating, and well-recognized feature of COPD associated with increased mortality and loss of peripheral and respiratory muscle function. The exact cause and underlying mechanisms of cachexia in COPD are still poorly understood. Increasing evidence, however, shows that pathological changes in intracellular mechanisms of muscle mass maintenance (i.e., protein turnover and myonuclear turnover) are likely involved. Potential factors triggering alterations in these mechanisms in COPD include oxidative stress, myostatin, and inflammation. In addition to muscle wasting, peripheral muscle in COPD is characterized by a fiber-type shift toward a more type II, glycolytic phenotype and an impaired oxidative capacity (collectively referred to as an impaired oxidative phenotype). Atrophied diaphragm muscle in COPD, however, displays an enhanced oxidative phenotype. Interestingly, intrinsic abnormalities in (lower limb) peripheral muscle seem more pronounced in either cachectic patients or weight loss-susceptible emphysema patients, suggesting that muscle wasting and intrinsic changes in peripheral muscle's oxidative phenotype are somehow intertwined. In this manuscript, we will review alterations in mechanisms of muscle mass maintenance in COPD and discuss the involvement of oxidative stress, inflammation, and myostatin as potential triggers of cachexia. Moreover, we postulate that an impaired muscle oxidative phenotype in COPD can accelerate the process of cachexia, as it renders muscle in COPD less energy efficient, thereby contributing to an energy deficit and weight loss when not dietary compensated. Furthermore, loss of peripheral muscle oxidative phenotype may increase the muscle's susceptibility to inflammation- and oxidative stress-induced muscle damage and wasting.

Acute reductions in blood flow restricted to the dorsomedial medulla induce a pressor response in rats.

PubMed

Waki, Hidefumi; Bhuiyan, Mohammad E R; Gouraud, Sabine S; Takagishi, Miwa; Hatada, Atsutoshi; Kohsaka, Akira; Paton, Julian F R; Maeda, Masanobu

2011-08-01

The brainstem nucleus of the solitary tract (nucleus tractus solitarii, NTS) is a pivotal region for regulating the set-point of arterial pressure, the mechanisms of which are not fully understood. Based on evidence that the NTS exhibits O2-sensing mechanisms, we examined whether a localized disturbance of blood supply, resulting in hypoxia in the NTS, would lead to an acute increase in arterial pressure. Male Wistar rats were used. Cardiovascular parameters were measured before and after specific branches of superficial dorsal medullary veins were occluded; we assumed these were drainage vessels from the NTS and would produce stagnant hypoxia. Hypoxyprobe-1, a marker for detecting cellular hypoxia in the post-mortem tissue, was used to reveal whether vessel occlusion induced hypoxia within the NTS. Following vessel occlusion, blood flow in the dorsal surface of the medulla oblongata including the NTS region showed an approximately 60% decrease and was associated with hypoxia in neurons located predominantly in the caudal part of the NTS as revealed using hypoxyprobe-1. Arterial pressure increased and this response was pronounced significantly in both magnitude and duration when baroreceptor reflex afferents were sectioned. These results suggest that localized hypoxia in the NTS increases arterial pressure. We suggest this represents a protective mechanism whereby the elevated systemic pressure is a compensatory mechanism to enhance cerebral perfusion. Whether this physiological mechanism has any relevance to neurogenic hypertension is discussed.

Vitamin D, Race, and Experimental Pain Sensitivity in Older Adults with Knee Osteoarthritis

PubMed Central

Glover, T.L.; Goodin, B.R.; Horgas, A.L.; Kindler, L.L.; King, C.D.; Sibille, K.T.; Peloquin, C.A.; Riley, J.L.; Staud, R.; Bradley, L.A.; Fillingim, R.B.

2012-01-01

Objective Low levels of serum circulating 25-hydroxyvitamin D have been correlated with many health conditions, including chronic pain. Recent clinical practice guidelines define vitamin D levels < 20 ng/mL as deficient and values of 21–29 ng/mL as insufficient. Vitamin D insufficiency, including the most severe levels of deficiency, is more prevalent in black Americans. Ethnic and race group differences have been reported in both clinical and experimental pain, with black Americans reporting increased pain. The purpose of this study was to examine whether variation in vitamin D levels contribute to race differences in knee osteoarthritic pain. Methods The sample consisted of 94 participants (75% female), including 45 blacks and 49 whites with symptomatic knee osteoarthritis. Average age was 55.8 years (range 45–71 years). Participants completed a questionnaire on knee osteoarthritic symptoms and underwent quantitative sensory testing, including measures of heat and mechanical pain sensitivity. Results Blacks had significantly lower levels of vitamin D compared to whites, demonstrated greater clinical pain, and showed greater sensitivity to mechanical and heat pain. Low levels of vitamin D predicted increased experimental pain sensitivity, but did not predict self-reported clinical pain. Group differences in vitamin D significantly predicted group differences in heat pain and pressure pain thresholds on the index knee and ipsilateral forearm. Conclusion These data demonstrate race differences in experimental pain are mediated by differences in vitamin D level. Vitamin D deficiency may be a risk factor for increased knee osteoarthritic pain in black Americans. PMID:23135697

Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection

PubMed Central

Marchesi, J.R.; Thursz, M.R.; Williams, H.R.T.

2015-01-01

Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem—the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond. PMID:25193538

Alternative mRNA polyadenylation in eukaryotes: an effective regulator of gene expression

PubMed Central

Lutz, Carol S.; Moreira, Alexandra

2010-01-01

Alternative RNA processing mechanisms, including alternative splicing and alternative polyadenylation, are increasingly recognized as important regulators of gene expression. This article will focus on what has recently been described about alternative polyadenylation in development, differentiation, and disease in higher eukaryotes. We will also describe how the evolving global methodologies for examining the cellular transcriptome, both experimental and bioinformatic, are revealing new details about the complex nature of alternative 3′ end formation, as well as interactions with other RNA-mediated and RNA processing mechanisms. PMID:21278855

Radiation Toxicity to the Cardiovascular System.

PubMed

Marmagkiolis, Konstantinos; Finch, William; Tsitlakidou, Despina; Josephs, Tyler; Iliescu, Cezar; Best, John F; Yang, Eric H

2016-03-01

Radiation therapy is an important component of cancer treatment, and today, it is applied to approximately 50% of malignancies, including valvular, myocardial, pericardial, coronary or peripheral vascular disease, and arrhythmias. An increased clinical suspicion and knowledge of those mechanisms is important to initiate appropriate screening for the optimal diagnosis and treatment. As the number of cancer survivors has been steadily increasing over the last decades, cardio-oncology, an evolving subspecialty of cardiology, will soon play a pivotal role in raising awareness of the increased cardiovascular risk and formulate strategies to optimally manage patients in this unique population.

[Effects of copper on biodegradation mechanism of trichloroethylene by mixed microorganisms].

PubMed

Gao, Yanhui; Zhao, Tiantao; Xing, Zhilin; He, Zhi; Zhang, Lijie; Peng, Xuya

2016-05-25

We isolated and enriched mixed microorganisms SWA1 from landfill cover soils supplemented with trichloroethylene (TCE). The microbial mixture could degrade TCE effectively under aerobic conditions. Then, we investigated the effect of copper ion (0 to 15 μmol/L) on TCE biodegradation. Results show that the maximum TCE degradation speed was 29.60 nmol/min with 95.75% degradation when copper ion was at 0.03 μmol/L. In addition, genes encoding key enzymes during biodegradation were analyzed by Real-time quantitative reverse transcription PCR (RT-qPCR). The relative expression abundance of pmoA gene (4.22E-03) and mmoX gene (9.30E-06) was the highest when copper ion was at 0.03 μmol/L. Finally, we also used MiSeq pyrosequencing to investigate the diversity of microbial community. Methylocystaceae that can co-metabolic degrade TCE were the dominant microorganisms; other microorganisms with the function of direct oxidation of TCE were also included in SWA1 and the microbial diversity decreased significantly along with increasing of copper ion concentration. Based on the above results, variation of copper ion concentration affected the composition of SWA1 and degradation mechanism of TCE. The degradation mechanism of TCE included co-metabolism degradation of methanotrophs and oxidation metabolism directly at copper ion of 0.03 μmol/L. When copper ion at 5 μmol/L (biodegradation was 84.75%), the degradation mechanism of TCE included direct-degradation and co-metabolism degradation of methanotrophs and microorganisms containing phenol hydroxylase. Therefore, biodegradation of TCE by microorganisms was a complicated process, the degradation mechanism included co-metabolism degradation of methanotrophs and bio-oxidation of non-methanotrophs.

Effect of sintering temperatures on the in vitro bioactivity, molecular structure and mechanical properties of titanium/carbonated hydroxyapatite nanobiocomposites

NASA Astrophysics Data System (ADS)

Youness, Rasha A.; Taha, Mohammed A.; Ibrahim, Medhat A.

2017-12-01

Titanium-containing carbonated hydroxyapatite (Ti-CHA) nanocomposite powders, with different CHA contents, have been prepared using high-energy ball milling method. The effect of sintering temperatures, 900, 1100 and 1300 °C on molecular structure and microstructure of these samples were examined by XRD; Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), respectively. Furthermore, their mechanical properties including hardness, longitudinal modulus, Young's modulus, shear modulus, bulk modulus and Poisson's ratio were measured by ultrasonic non-destructive technique. Moreover, bioactivity of sintered samples at different firing temperatures was assessed by immersing them in simulated body fluid at 37 ± 0.5 °C for 7 days and then, analyzed by FTIR spectroscopy. The results pointed out that increasing sintering temperature up to 1100 °C caused significant increases in densities and mechanical properties of these nanocomposite samples. However, further increase of firing temperature to 1300 °C was responsible for complete CHA decomposition and the resultant α-tricalcium (α-TCP) phase greatly affected these properties. On the contrary, better bioactivity was observed for sintered samples at 900 °C only. However, increase of sintering temperature of these samples up to 1300 °C led to severe decrease in their bioactivity due to the formation of highly soluble α-TCP phase.

Vibration training: could it enhance the strength, power, or speed of athletes?

PubMed

Wilcock, Ian M; Whatman, Chris; Harris, Nigel; Keogh, Justin W L

2009-03-01

The aim of this literature review was to determine whether vibration training could produce chronic improvements in the physical performance of trained athletes. Although the main objective was to analyze any performance benefits, a brief review of possible mechanisms linked to performance enhancement is also included. Vibration causes an increase in the g-forces acting on the muscles, increasing the loading parameters of any exercise. Increased loading should aid muscle hypertrophy, and some authors have suggested that vibration may enhance neuromuscular potentiation. Considering the 6 studies on trained athletes, there does seem to be some evidence to suggest that vibration may provide a small benefit to maximal strength (1-repetition maximum) and power (countermovement jumps) of trained athletes. Speed does not seem to be enhanced by vibration training. There is a lack of evidence to support the theory that long-term vibration training increases neuromuscular potentiation in trained athletes. What mechanism(s) could be responsible for possible strength and power enhancement is unclear. Because whole-body vibration does not seem to be detrimental to performance when used in a controlled manner, it could provide an additional training stimulus for athletes. However, further research is required to determine optimum vibration training protocols and to clarify whether vibration training produces performance benefits greater than those of traditional training methods.

Experimental measurements of energy augmentation for mechanical circulatory assistance in a patient-specific Fontan model.

PubMed

Chopski, Steven G; Rangus, Owen M; Moskowitz, William B; Throckmorton, Amy L

2014-09-01

A mechanical blood pump specifically designed to increase pressure in the great veins would improve hemodynamic stability in adolescent and adult Fontan patients having dysfunctional cavopulmonary circulation. This study investigates the impact of axial-flow blood pumps on pressure, flow rate, and energy augmentation in the total cavopulmonary circulation (TCPC) using a patient-specific Fontan model. The experiments were conducted for three mechanical support configurations, which included an axial-flow impeller alone in the inferior vena cava (IVC) and an impeller with one of two different protective stent designs. All of the pump configurations led to an increase in pressure generation and flow in the Fontan circuit. The increase in IVC flow was found to augment pulmonary arterial flow, having only a small impact on the pressure and flow in the superior vena cava (SVC). Retrograde flow was neither observed nor measured from the TCPC junction into the SVC. All of the pump configurations enhanced the rate of power gain of the cavopulmonary circulation by adding energy and rotational force to the fluid flow. We measured an enhancement of forward flow into the TCPC junction, reduction in IVC pressure, and only minimally increased pulmonary arterial pressure under conditions of pump support. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Post-transplantation Development of Food Allergies.

PubMed

Newman, Erik N; Firszt, Rafael

2018-01-29

The development of food allergies is increasingly being recognized as a post-solid organ transplant complication. In this article, we review the spectrum of post-transplant food allergy development and the proposed mechanisms for de novo food allergies and the clinical significance they pose. The development of new food allergies is disproportionately associated with pediatric liver transplants, where it occurs in up to 38% of select populations. The mechanism of food allergy development is not completely understood; however, it is likely promoted by unbalanced immune suppression. De novo food allergy development is a common complication of solid organ transplants with the highest risk occurring in pediatric liver transplant recipients. There are likely multiple mechanisms for food allergy development including passive transfer of membrane-bound IgE and lymphocytes from donor to recipient, as well as loss of food tolerance and active development of new food allergies. The optimal management of food allergies following organ transplants has not been well researched but may include changing the immune suppression regimen if the food allergy does not resolve without intervention.

Genetic Forms of Epilepsies and other Paroxysmal Disorders

PubMed Central

Olson, Heather E.; Poduri, Annapurna; Pearl, Phillip L.

2016-01-01

Genetic mechanisms explain the pathophysiology of many forms of epilepsy and other paroxysmal disorders such as alternating hemiplegia of childhood, familial hemiplegic migraine, and paroxysmal dyskinesias. Epilepsy is a key feature of well-defined genetic syndromes including Tuberous Sclerosis Complex, Rett syndrome, Angelman syndrome, and others. There is an increasing number of singe gene causes or susceptibility factors associated with several epilepsy syndromes, including the early onset epileptic encephalopathies, benign neonatal/infantile seizures, progressive myoclonus epilepsies, genetic generalized and benign focal epilepsies, epileptic aphasias, and familial focal epilepsies. Molecular mechanisms are diverse, and a single gene can be associated with a broad range of phenotypes. Additional features, such as dysmorphisms, head size, movement disorders, and family history may provide clues to a genetic diagnosis. Genetic testing can impact medical care and counseling. We discuss genetic mechanisms of epilepsy and other paroxysmal disorders, tools and indications for genetic testing, known genotype-phenotype associations, the importance of genetic counseling, and a look towards the future of epilepsy genetics. PMID:25192505

Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

PubMed Central

Karunaratne, A.; Xi, L.; Bentley, L.; Sykes, D.; Boyde, A.; Esapa, C.T.; Terrill, N.J.; Brown, S.D.M.; Cox, R.D.; Thakker, R.V.; Gupta, H.S.

2016-01-01

A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh− 120/+) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh− 120/+ mice. We also find a much larger fibril strain/tissue strain ratio in Crh− 120/+ mice (~ 1.5) compared to the wild-type mice (~ 0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis. PMID:26657825

Critical role of TRPP2 and TRPC1 channels in stretch-induced injury of blood-brain barrier endothelial cells.

PubMed

Berrout, Jonathan; Jin, Min; O'Neil, Roger G

2012-02-03

The microvessels of the brain are very sensitive to mechanical stresses such as observed in traumatic brain injury (TBI). Such stresses can quickly lead to dysfunction of the microvessel endothelial cells, including disruption of blood-brain barrier (BBB). It is now evident that elevation of cytosolic calcium levels ([Ca2+]i) can compromise the BBB integrity, however the mechanism by which mechanical injury can produce a [Ca2+]i increase in brain endothelial cells is unclear. To assess the effects of mechanical/stretch injury on [Ca2+]i signaling, mouse brain microvessel endothelial cells (bEnd3) were grown to confluency on elasticized membranes and [Ca2+]i monitored using fura 2 fluorescence imaging. Application of an injury, using a pressure/stretch pulse of 50 ms, induced a rapid transient increase in [Ca2+]i. In the absence of extracellular Ca2+, the injury-induced [Ca2+]i transient was greatly reduced, but not fully eliminated, while unloading of Ca2+ stores by thapsigargin treatment in the absence of extracellular Ca2+ abolished the injury transient. Application of LOE-908 and amiloride, TRPC and TRPP2 channel blockers, respectively, both reduced the transient [Ca2+]i increase. Further, siRNA knockdown assays directed at TRPC1 and TRPP2 expression also resulted in a reduction of the injury-induced [Ca2+]i response. In addition, stretch injury induced increases of NO production and actin stress fiber formation, both of which were markedly reduced upon treatment with LOE908 and/or amiloride. We conclude that mechanical injury of brain endothelial cells induces a rapid influx of calcium, mediated by TRPC1 and TRPP2 channels, which leads to NO synthesis and actin cytoskeletal rearrangement. Copyright © 2011. Published by Elsevier B.V.

Dynamic mechanical properties and anisotropy of synthetic shales with different clay minerals under confining pressure

NASA Astrophysics Data System (ADS)

Gong, Fei; Di, Bangrang; Wei, Jianxin; Ding, Pinbo; Shuai, Da

2018-03-01

The presence of clay minerals can alter the elastic behaviour of reservoir rocks significantly as the type of clay minerals, their volume and distribution, and their orientation control the shale's intrinsic anisotropic behaviours. Clay minerals are the most abundant materials in shale, and it has been proven extremely difficult to measure the elastic properties of natural shale by means of a single variable (in this case, the type of clay minerals), due to the influences of multiple factors, including water, TOC content and complex mineral compositions. We used quartz, clay (kaolinite, illite and smectite), carbonate and kerogen extract as the primary materials to construct synthetic shale with different clay minerals. Ultrasonic experiments were conducted to investigate the anisotropy of velocity and mechanical properties in dry synthetic and natural shale as a function of confining pressure. Velocities in synthetic shale are sensitive to the type of clay minerals, possibly due to the different structures of the clay minerals. The velocities increase with confining pressure and show higher rate of velocity increase at low pressures, and P-wave velocity is usually more sensitive than S-wave velocity to confining pressure according to our results. Similarly, the dynamic Young's modulus and Poisson's ratio increase with applied pressure, and the results also reveal that E11 is always larger than E33 and ν31 is smaller than ν12. Velocity and mechanical anisotropy decrease with increasing stress, and are sensitive to stress and the type of clay minerals. However, the changes of mechanical anisotropy with applied stress are larger compared with the velocity anisotropy, indicating that mechanical properties are more sensitive to the change of rock properties.

Recruitment of endosomal signaling mediates the forskolin modulation of guinea pig cardiac neuron excitability.

PubMed

Hardwick, Jean C; Clason, Todd A; Tompkins, John D; Girard, Beatrice M; Baran, Caitlin N; Merriam, Laura A; May, Victor; Parsons, Rodney L

2017-08-01

Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein-coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60% of the cardiac neurons. The forskolin-mediated increase in excitability was considered related to cAMP regulation of a cyclic nucleotide gated channel or via protein kinase A (PKA)/ERK signaling, mechanisms that have been linked to PAC1 receptor activation. However, unlike PACAP mechanisms, forskolin enhancement of excitability was not significantly reduced by treatment with cesium to block currents through hyperpolarization-activated nonselective cation channels ( I h ) or by treatment with PD98059 to block MEK/ERK signaling. In contrast, treatment with the clathrin inhibitor Pitstop2 or the dynamin inhibitor dynasore eliminated the forskolin-induced increase in excitability; treatments with the inactive Pitstop analog or PP2 treatment to inhibit Src-mediated endocytosis mechanisms were ineffective. The PKA inhibitor KT5702 significantly suppressed the forskolin-induced change in excitability; further, KT5702 and Pitstop2 reduced the forskolin-stimulated MEK/ERK activation in cardiac neurons. Collectively, the present results suggest that forskolin activation of AC/cAMP/PKA signaling leads to the recruitment of clathrin/dynamin-dependent endosomal transduction cascades, including MEK/ERK signaling, and that endosomal signaling is the critical mechanism underlying the forskolin-induced increase in cardiac neuron excitability. Copyright © 2017 the American Physiological Society.

Trends in reporting of mechanisms and incidence of hip injuries in males playing minor ice hockey in Canada: a cross-sectional study.

PubMed

Ayeni, Olufemi R; Kowalczuk, Marcin; Farag, Jordan; Farrokhyar, Forough; Chu, Raymond; Bedi, Asheesh; Willits, Kevin; Bhandari, Mohit

2014-01-01

There has been a noted increase in the diagnosis and reporting of sporting hip injuries and conditions in the medical literature but reporting at the minor hockey level is unknown. The purpose of this study is to investigate the trend of reporting hip injuries in amateur ice hockey players in Canada with a focus on injury type and mechanism. A retrospective review of the Hockey Canada insurance database was performed and data on ice hockey hip injuries reported between January 2005 and June 2011 were collected. The study population included all male hockey players from Peewee (aged 11-12 years) to Senior (aged 20+ years) participating in amateur level competition sanctioned by Hockey Canada. Reported cases of ice hockey hip injuries were analyzed according to age, mechanism of injury, and injury subtype. Annual injury reporting rates were determined and using a linear regression analysis trended to determine the change in ice hockey hip injury reporting rate over time. One hundred and six cases of ice hockey-related hip injuries were reported in total. The majority of injuries (75.5%) occurred in players aged 15-20 years playing at the Junior level. Most injuries were caused by a noncontact mechanism (40.6%) and strains were the most common subtype (50.0%). From 2005 to 2010, the number of reported hip injuries increased by 5.31 cases per year and the rate of reported hip injury per 1,000 registered players increased by 0.02 cases annually. Reporting of hip injuries in amateur ice hockey players is increasing. A more accurate injury reporting system is critical for future epidemiologic studies to accurately document the rate and mechanism of hip injury in amateur ice hockey players.

Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems.

PubMed

Mattson, Mark P; Wan, Ruiqian

2005-03-01

Intermittent fasting (IF; reduced meal frequency) and caloric restriction (CR) extend lifespan and increase resistance to age-related diseases in rodents and monkeys and improve the health of overweight humans. Both IF and CR enhance cardiovascular and brain functions and improve several risk factors for coronary artery disease and stroke including a reduction in blood pressure and increased insulin sensitivity. Cardiovascular stress adaptation is improved and heart rate variability is increased in rodents maintained on an IF or a CR diet. Moreover, rodents maintained on an IF regimen exhibit increased resistance of heart and brain cells to ischemic injury in experimental models of myocardial infarction and stroke. The beneficial effects of IF and CR result from at least two mechanisms--reduced oxidative damage and increased cellular stress resistance. Recent findings suggest that some of the beneficial effects of IF on both the cardiovascular system and the brain are mediated by brain-derived neurotrophic factor signaling in the brain. Interestingly, cellular and molecular effects of IF and CR on the cardiovascular system and the brain are similar to those of regular physical exercise, suggesting shared mechanisms. A better understanding of the cellular and molecular mechanisms by which IF and CR affect the blood vessels and heart and brain cells will likely lead to novel preventative and therapeutic strategies for extending health span.

Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

PubMed Central

Logan, Ellis Scott; Richman, Aliza

2014-01-01

Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

Mechanical Properties of High Entropy Alloy Al0.1CoCrFeNi for Peripheral Vascular Stent Application.

PubMed

Alagarsamy, Karthik; Fortier, Aleksandra; Komarasamy, Mageshwari; Kumar, Nilesh; Mohammad, Atif; Banerjee, Subhash; Han, Hai-Chao; Mishra, Rajiv S

2016-12-01

High entropy alloys (HEAs) are new class of metallic materials with five or more principal alloying elements. Due to this distinct concept of alloying, the HEAs exhibit unique properties compared to conventional alloys. The outstanding properties of HEAs include increased strength, superior wear resistance, high temperature stability, increased fatigue properties, good corrosion, and oxidation resistance. Such characteristics of HEAs have generated significant interest among the scientific community. However, their applications are yet to be explored. This paper discusses the mechanical behavior and microstructure of Al 0.1 CoCrFeNi HEA subjected to thermo-mechanical processing, and its potential application in peripheral vascular stent implants that are prone to high failure rates. Results show that Al 0.1 CoCrFeNi alloy possesses characteristics that compare well against currently used stent materials and it can potentially find use in peripheral vascular stent implants and extend their life-cycle.

Changes in permeability caused by transient stresses: field observations, experiments, and mechanisms

USGS Publications Warehouse

Manga, Michael; Beresnev, Igor; Brodsky, Emily E.; Elkhoury, Jean E.; Elsworth, Derek; Ingebritsen, Steve E.; Mays, David C.; Wang, Chi-Yuen

2012-01-01

Oscillations in stress, such as those created by earthquakes, can increase permeability and fluid mobility in geologic media. In natural systems, strain amplitudes as small as 10–6 can increase discharge in streams and springs, change the water level in wells, and enhance production from petroleum reservoirs. Enhanced permeability typically recovers to prestimulated values over a period of months to years. Mechanisms that can change permeability at such small stresses include unblocking pores, either by breaking up permeability-limiting colloidal deposits or by mobilizing droplets and bubbles trapped in pores by capillary forces. The recovery time over which permeability returns to the prestimulated value is governed by the time to reblock pores, or for geochemical processes to seal pores. Monitoring permeability in geothermal systems where there is abundant seismicity, and the response of flow to local and regional earthquakes, would help test some of the proposed mechanisms and identify controls on permeability and its evolution.

Accelerated Testing Methodology in Constant Stress-Rate Testing for Advanced Structural Ceramics: A Preloading Technique

NASA Technical Reports Server (NTRS)

Choi, Sung R.; Gyekenyesi, John P.; Huebert, Dean; Bartlett, Allen; Choi, Han-Ho

2001-01-01

Preloading technique was used as a means of an accelerated testing methodology in constant stress-rate ('dynamic fatigue') testing for two different brittle materials. The theory developed previously for fatigue strength as a function of preload was further verified through extensive constant stress-rate testing for glass-ceramic and CRT glass in room temperature distilled water. The preloading technique was also used in this study to identify the prevailing failure mechanisms at elevated temperatures, particularly at lower test rate in which a series of mechanisms would be associated simultaneously with material failure, resulting in significant strength increase or decrease. Two different advanced ceramics including SiC whisker-reinforced composite silicon nitride and 96 wt% alumina were used at elevated temperatures. It was found that the preloading technique can be used as an additional tool to pinpoint the dominant failure mechanism that is associated with such a phenomenon of considerable strength increase or decrease.

Accelerated Testing Methodology in Constant Stress-Rate Testing for Advanced Structural Ceramics: A Preloading Technique

NASA Technical Reports Server (NTRS)

Choi, Sung R.; Gyekenyesi, John P.; Huebert, Dean; Bartlett, Allen; Choi, Han-Ho

2001-01-01

Preloading technique was used as a means of an accelerated testing methodology in constant stress-rate (dynamic fatigue) testing for two different brittle materials. The theory developed previously for fatigue strength as a function of preload was further verified through extensive constant stress-rate testing for glass-ceramic and CRT glass in room temperature distilled water. The preloading technique was also used in this study to identify the prevailing failure mechanisms at elevated temperatures, particularly at lower test rates in which a series of mechanisms would be associated simultaneously with material failure, resulting in significant strength increase or decrease. Two different advanced ceramics including SiC whisker-reinforced composite silicon nitride and 96 wt% alumina were used at elevated temperatures. It was found that the preloading technique can be used as an additional tool to pinpoint the dominant failure mechanism that is associated with such a phenomenon of considerable strength increase or decrease.

Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus.

PubMed

Schoenfeld, Timothy J; Rada, Pedro; Pieruzzini, Pedro R; Hsueh, Brian; Gould, Elizabeth

2013-05-01

Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expression of the protein products of the immediate early genes c-fos and arc in new and mature granule neurons in sedentary mice, it has no such effect in runners. We further showed that running enhances local inhibitory mechanisms in the hippocampus, including increases in stress-induced activation of hippocampal interneurons, expression of vesicular GABA transporter (vGAT), and extracellular GABA release during cold water swim stress. Finally, blocking GABAA receptors in the ventral hippocampus, but not the dorsal hippocampus, with the antagonist bicuculline, reverses the anxiolytic effect of running. Together, these results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus.

Boron nitride nanotubes enhance properties of chitosan-based scaffolds.

PubMed

Emanet, Melis; Kazanç, Emine; Çobandede, Zehra; Çulha, Mustafa

2016-10-20

With their low toxicity, high mechanical strength and chemical stability, boron nitride nanotubes (BNNTs) are good candidates to enhance the properties of polymers, composites and scaffolds. Chitosan-based scaffolds are exhaustively investigated in tissue engineering because of their biocompatibility and antimicrobial activity. However, their spontaneous degradation prevents their use in a range of tissue engineering applications. In this study, hydroxylated BNNTs (BNNT-OH) were included into a chitosan scaffold and tested for their mechanical strength, swelling behavior and biodegradability. The results show that inclusion of BNNTs-OH into the chitosan scaffold increases the mechanical strength and pore size at values optimal for high cellular proliferation and adhesion. The chitosan/BNNT-OH scaffold was also found to be non-toxic to Human Dermal Fibroblast (HDF) cells due to its slow degradation rate. HDF cell proliferation and adhesion were increased as compared to the chitosan-only scaffold as observed by scanning electron microscopy (SEM) and fluorescent microscopy images. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical Homogenization Increases Bacterial Homogeneity in Sputum

PubMed Central

Stokell, Joshua R.; Khan, Ammad

2014-01-01

Sputum obtained from patients with cystic fibrosis (CF) is highly viscous and often heterogeneous in bacterial distribution. Adding dithiothreitol (DTT) is the standard method for liquefaction prior to processing sputum for molecular detection assays. To determine if DTT treatment homogenizes the bacterial distribution within sputum, we measured the difference in mean total bacterial abundance and abundance of Burkholderia multivorans between aliquots of DTT-treated sputum samples with and without a mechanical homogenization (MH) step using a high-speed dispersing element. Additionally, we measured the effect of MH on bacterial abundance. We found a significant difference between the mean bacterial abundances in aliquots that were subjected to only DTT treatment and those of the aliquots which included an MH step (all bacteria, P = 0.04; B. multivorans, P = 0.05). There was no significant effect of MH on bacterial abundance in sputum. Although our results are from a single CF patient, they indicate that mechanical homogenization increases the homogeneity of bacteria in sputum. PMID:24759710

The Effects of Temperature on Political Violence: Global Evidence at the Subnational Level

PubMed Central

Bollfrass, Alexander; Shaver, Andrew

2015-01-01

A number of studies have demonstrated an empirical relationship between higher ambient temperatures and substate violence, which have been extrapolated to make predictions about the security implications of climate change. This literature rests on the untested assumption that the mechanism behind the temperature-conflict link is that disruption of agricultural production provokes local violence. Using a subnational-level dataset, this paper demonstrates that the relationship: (1) obtains globally, (2) exists at the substate level — provinces that experience positive temperature deviations see increased conflict; and (3) occurs even in regions without significant agricultural production. Diminished local farm output resulting from elevated temperatures is unlikely to account for the entire increase in substate violence. The findings encourage future research to identify additional mechanisms, including the possibility that a substantial portion of the variation is brought about by the well-documented direct effects of temperature on individuals' propensity for violence or through macroeconomic mechanisms such as food price shocks. PMID:25992616

Microstructure and mechanical properties of Al/Cu/Mg laminated composite sheets produced by the ARB proces

NASA Astrophysics Data System (ADS)

Rahmatabadi, Davood; Tayyebi, Moslem; Hashemi, Ramin; Faraji, Ghader

2018-05-01

In the present study, an Al/Cu/Mg multi-layered composite was produced by accumulative roll bonding (ARB) through seven passes, and its microstructure and mechanical properties were evaluated. The microstructure investigations show that plastic instability occurred in both the copper and magnesium reinforcements in the primary sandwich. In addition, a composite with a perfectly uniform distribution of copper and magnesium reinforcing layers was produced during the last pass. By increasing the number of ARB cycles, the microhardness of the layers including aluminum, copper, and magnesium was significantly increased. The ultimate tensile strength of the sandwich was enhanced continually and reached a maximum value of 355.5 MPa. This strength value was about 3.2, 2, and 2.1 times higher than the initial strength values for the aluminum, copper, and magnesium sheets, respectively. Investigation of tensile fracture surfaces during the ARB process indicated that the fracture mechanism changed to shear ductile at the seventh pass.

Cellular and molecular mechanisms of repair in acute and chronic wound healing.

PubMed

Martin, P; Nunan, R

2015-08-01

A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments. © 2015 British Association of Dermatologists.

Increased vocal intensity due to the Lombard effect in speakers with Parkinson's disease: simultaneous laryngeal and respiratory strategies.

PubMed

Stathopoulos, Elaine T; Huber, Jessica E; Richardson, Kelly; Kamphaus, Jennifer; DeCicco, Devan; Darling, Meghan; Fulcher, Katrina; Sussman, Joan E

2014-01-01

The objective of the present study was to investigate whether speakers with hypophonia, secondary to Parkinson's disease (PD), would increases their vocal intensity when speaking in a noisy environment (Lombard effect). The other objective was to examine the underlying laryngeal and respiratory strategies used to increase vocal intensity. Thirty-three participants with PD were included for study. Each participant was fitted with the SpeechVive™ device that played multi-talker babble noise into one ear during speech. Using acoustic, aerodynamic and respiratory kinematic techniques, the simultaneous laryngeal and respiratory mechanisms used to regulate vocal intensity were examined. Significant group results showed that most speakers with PD (26/33) were successful at increasing their vocal intensity when speaking in the condition of multi-talker babble noise. They were able to support their increased vocal intensity and subglottal pressure with combined strategies from both the laryngeal and respiratory mechanisms. Individual speaker analysis indicated that the particular laryngeal and respiratory interactions differed among speakers. The SpeechVive™ device elicited higher vocal intensities from patients with PD. Speakers used different combinations of laryngeal and respiratory physiologic mechanisms to increase vocal intensity, thus suggesting that disease process does not uniformly affect the speech subsystems. Readers will be able to: (1) identify speech characteristics of people with Parkinson's disease (PD), (2) identify typical respiratory strategies for increasing sound pressure level (SPL), (3) identify typical laryngeal strategies for increasing SPL, (4) define the Lombard effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone and Skeletal Muscle: Key Players in Mechanotransduction and Potential Overlapping Mechanisms

PubMed Central

Goodman, Craig A.; Hornberger, Troy A.; Robling, Alexander G.

2015-01-01

The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists. PMID:26453495

Overview of Glenn Mechanical Components Branch Research

NASA Astrophysics Data System (ADS)

Zakrajsek, James

2002-09-01

Mr. James Zakrajsek, chief of the Mechanical Components Branch, gave an overview of research conducted by the branch. Branch members perform basic research on mechanical components and systems, including gears and bearings, turbine seals, structural and thermal barrier seals, and space mechanisms. The research is focused on propulsion systems for present and advanced aerospace vehicles. For rotorcraft and conventional aircraft, we conduct research to develop technology needed to enable the design of low noise, ultra safe geared drive systems. We develop and validate analytical models for gear crack propagation, gear dynamics and noise, gear diagnostics, bearing dynamics, and thermal analyses of gear systems using experimental data from various component test rigs. In seal research we develop and test advanced turbine seal concepts to increase efficiency and durability of turbine engines. We perform experimental and analytical research to develop advanced thermal barrier seals and structural seals for current and next generation space vehicles. Our space mechanisms research involves fundamental investigation of lubricants, materials, components and mechanisms for deep space and planetary environments.

Low frequency mechanical actuation accelerates reperfusion in-vitro

PubMed Central

2013-01-01

Background Rapid restoration of vessel patency after acute myocardial infarction is key to reducing myocardial muscle death and increases survival rates. Standard therapies include thrombolysis and direct PTCA. Alternative or adjunctive emergency therapies that could be initiated by minimally trained personnel in the field are of potential clinical benefit. This paper evaluates a method of accelerating reperfusion through application of low frequency mechanical stimulus to the blood carrying vessels. Materials and method We consider a stenosed, heparinized flow system with aortic-like pressure variations subject to direct vessel vibration at the occlusion site or vessel deformation proximal and distal to the occlusion site, versus a reference system lacking any form of mechanical stimulus on the vessels. Results The experimental results show limited effectiveness of the direct mechanical vibration method and a drastic increase in the patency rate when vessel deformation is induced. For vessel deformation at occlusion site 95% of clots perfused within 11 minutes of application of mechanical stimulus, for vessel deformation 60 centimeters from the occlusion site 95% percent of clots perfused within 16 minutes of stimulus application, while only 2.3% of clots perfused within 20 minutes in the reference system. Conclusion The presented in-vitro results suggest that low frequency mechanical actuation applied during the pre-hospitalization phase in patients with acute myocardial infarction have potential of being a simple and efficient adjunct therapy. PMID:24257116

Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation.

PubMed

Beurskens, Charlotte J; Brevoord, Daniel; Lagrand, Wim K; van den Bergh, Walter M; Vroom, Margreeth B; Preckel, Benedikt; Horn, Janneke; Juffermans, Nicole P

2014-01-01

Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2) diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical ventilation using low tidal volumes. Methods. This is an observational cohort substudy of a single arm intervention study. Twenty-four ICU patients were included, who were admitted after a cardiac arrest and mechanically ventilated for 3 hours with heliox (50% helium; 50% oxygen). A fixed protective ventilation protocol (6 mL/kg) was used, with prospective observation for changes in lung mechanics and gas exchange. Statistics was by Bonferroni post-hoc correction with statistical significance set at P < 0.017. Results. During heliox ventilation, respiratory rate decreased (25 ± 4 versus 23 ± 5 breaths min(-1), P = 0.010). Minute volume ventilation showed a trend to decrease compared to baseline (11.1 ± 1.9 versus 9.9 ± 2.1 L min(-1), P = 0.026), while reducing PaCO2 levels (5.0 ± 0.6 versus 4.5 ± 0.6 kPa, P = 0.011) and peak pressures (21.1 ± 3.3 versus 19.8 ± 3.2 cm H2O, P = 0.024). Conclusions. Heliox improved CO2 elimination while allowing reduced minute volume ventilation in adult patients during protective mechanical ventilation.

Mechanical responses, texture evolution, and yield loci of extruded AZ31 magnesium alloy under various loading conditions: Experiment and modeling

NASA Astrophysics Data System (ADS)

Kabirian, Farhoud

Mechanical responses and texture evolution of extruded AZ31 Mg are measured under uniaxial (tension-compression) and multiaxial (free-end torsion) loadings. Compression loading is carried out in three different directions at temperature and strain rate ranges of 77-423 K and 10-4 -3000 s -1, respectively. Texture evolution at different intermediate strains reveals that crystal reorientation is exhausted at smaller strains with increase in strain rate while increase in temperature retards twinning. In addition to the well-known tension-compression yield asymmetry, a strong anisotropy in strain hardening response is observed. Strain hardening during the compression experiment is intensified with decreasing and increasing temperature and strain rate, respectively. This complex behavior is explained through understanding the roles of deformation mechanisms using the Visco-Plastic Self Consistent (VPSC) model. In order to calibrate the VPSC model's constants as accurate as possible, a vast number of mechanical responses including stress-strain curves in tension, compression in three directions, and free-end torsion, texture evolution at different strains, lateral strains of compression samples, twin volume fraction, and axial strain during the torsion experiment. Modeling results show that depending on the number of measurements used for calibration, roles of different mechanisms in plastic deformation change significantly. In addition, a precise definition of yield is established for the extruded AZ31magnesium alloy after it is subjected to different loading conditions (uniaxial to multiaxial) at four different plastic strains. The yield response is measured in ?-? space. Several yield criteria are studied to predict yield response of extruded AZ31. This study proposes an asymmetrical fourth-order polynomial yield function. Material constants in this model can be directly calculated using mechanical measurements. Convexity of the proposed model is discussed, and domains of constants where convexity holds are determined. Effects of grain refinement induced by Equal Channel Angular Pressing, ECAP, on mechanical responses and texture evolution are investigated. Yield strength in compression increases after ECAP, however, strain-hardening rate drops with number of ECAP passes while failure strain increases. Texture measurements reveal the higher propensity to twinning in the extruded material compared with ECAPed magnesium. Calculated Schmid factor maps are utilized to connect the observed mechanical responses to the texture.

Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-β by affecting insulin-degrading enzyme.

PubMed

Grimm, Marcus O W; Mett, Janine; Stahlmann, Christoph P; Haupenthal, Viola J; Blümel, Tamara; Stötzel, Hannah; Grimm, Heike S; Hartmann, Tobias

2016-12-01

Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer's disease (AD). AD pathology is closely linked to an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques in the brain. Total Aβ levels are not only dependent on its production by proteolytic processing of the amyloid precursor protein (APP), but also on Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase Aβ-degradation by affecting insulin-degrading enzyme (IDE), the major Aβ-degrading enzyme secreted into the extracellular space of neuronal and microglial cells. The identification of the molecular mechanisms revealed that EPA directly increases IDE enzyme activity and elevates gene expression of IDE. DHA also directly stimulates IDE enzyme activity and affects IDE sorting by increasing exosome release of IDE, resulting in enhanced Aβ-degradation in the extracellular milieu. Apart from the known positive effect of DHA in reducing Aβ production, EPA and DHA might ameliorate AD pathology by increasing Aβ turnover.

Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis: Options and Challenges for Novel Bedside Technologies.

PubMed

Zonneveld, Rens; Molema, Grietje; Plötz, Frans B

2016-01-01

Alterations in neutrophil morphology (size, shape, and composition), mechanics (deformability), and motility (chemotaxis and migration) have been observed during sepsis. We combine summarizing features of neutrophil morphology, mechanics, and motility that change during sepsis with an investigation into their clinical utility as markers for sepsis through measurement with novel technologies. We performed an initial literature search in MEDLINE using search terms "neutrophil," "morphology," "mechanics," "dynamics," "motility," "mobility," "spreading," "polarization," "migration," and "chemotaxis." We then combined the results with "sepsis" and "septic shock." We scanned bibliographies of included articles to identify additional articles. Final selection was done after the authors reviewed recovered articles. We included articles based on their relevance for our review topic. When compared with resting conditions, sepsis causes an increase in circulating numbers of larger, more rigid neutrophils that show diminished granularity, migration, and chemotaxis. Combined measurement of these variables could provide a more complete view on neutrophil phenotype manifestation. For that purpose, sophisticated automated hematology analyzers, microscopy, and bedside microfluidic devices provide clinically feasible, high-throughput, and cost-limiting means. We propose that integration of features of neutrophil morphology, mechanics, and motility with these new analytical methods can be useful as markers for diagnosis, prognosis, and monitoring of sepsis and may even contribute to basic understanding of its pathophysiology.

RNA G-quadruplexes: emerging mechanisms in disease

PubMed Central

Cammas, Anne

2017-01-01

Abstract RNA G-quadruplexes (G4s) are formed by G-rich RNA sequences in protein-coding (mRNA) and non-coding (ncRNA) transcripts that fold into a four-stranded conformation. Experimental studies and bioinformatic predictions support the view that these structures are involved in different cellular functions associated to both DNA processes (telomere elongation, recombination and transcription) and RNA post-transcriptional mechanisms (including pre-mRNA processing, mRNA turnover, targeting and translation). An increasing number of different diseases have been associated with the inappropriate regulation of RNA G4s exemplifying the potential importance of these structures on human health. Here, we review the different molecular mechanisms underlying the link between RNA G4s and human diseases by proposing several overlapping models of deregulation emerging from recent research, including (i) sequestration of RNA-binding proteins, (ii) aberrant expression or localization of RNA G4-binding proteins, (iii) repeat associated non-AUG (RAN) translation, (iv) mRNA translational blockade and (v) disabling of protein–RNA G4 complexes. This review also provides a comprehensive survey of the functional RNA G4 and their mechanisms of action. Finally, we highlight future directions for research aimed at improving our understanding on RNA G4-mediated regulatory mechanisms linked to diseases. PMID:28013268

The infant food industry and international child health.

PubMed

Jelliffe, D B; Jelliffe, E F

1977-01-01

Declining breast-feeding, with accompanying increased marasmus and diarrhea, has occurred in developing countries because of many factors, including inappropriate health services, new urban life styles, and so forth. The infant food industry must bear a considerable burden of blame as a result of "unethical" advertising. Responses have most recently included various journalistic and legal actions. There is a need for revised roles for the infant food industry, and for mechanisms to monitor intrinsically harmful practices.

Restoration of tensile strength in bark samples of Ficus benjamina due to coagulation of latex during fast self-healing of fissures

PubMed Central

Bauer, Georg; Speck, Thomas

2012-01-01

Background and Aims The functions of plant latex have been discussed for a long time. Today, many studies support a defence mechanism as being its main function. A role as a self-healing mechanism was never attributed to the coagulation of latex. In this study we quantified the contribution of the coagulation of Ficus benjamina (weeping fig) latex to a restoration of the mechanical properties of the bark after external lesions. Methods Tensile tests of F. benjamina bark were conducted either immediately after injury or at various latency times after injury. Key Results A significant increase in the tensile strength of bark samples until 30 min after injury was found, and this effect could be attributed to the coagulation of plant latex alone. The tensile strength remains nearly constant until several hours or days after injury. Then, very probably due to other mechanisms such as cell growth and cell proliferation, the tensile strength begins to increase slightly again. Conclusions The coagulation of latex seals lesions and serves as a quick and effective pre-step of subsequent, more effective, long-lasting self-healing mechanisms such as cell growth and proliferation. Thus, a fast self-healing effect can be included in the list of functions of plant latex. PMID:22207613

Restoration of tensile strength in bark samples of Ficus benjamina due to coagulation of latex during fast self-healing of fissures.

PubMed

Bauer, Georg; Speck, Thomas

2012-03-01

The functions of plant latex have been discussed for a long time. Today, many studies support a defence mechanism as being its main function. A role as a self-healing mechanism was never attributed to the coagulation of latex. In this study we quantified the contribution of the coagulation of Ficus benjamina (weeping fig) latex to a restoration of the mechanical properties of the bark after external lesions. Tensile tests of F. benjamina bark were conducted either immediately after injury or at various latency times after injury. A significant increase in the tensile strength of bark samples until 30 min after injury was found, and this effect could be attributed to the coagulation of plant latex alone. The tensile strength remains nearly constant until several hours or days after injury. Then, very probably due to other mechanisms such as cell growth and cell proliferation, the tensile strength begins to increase slightly again. The coagulation of latex seals lesions and serves as a quick and effective pre-step of subsequent, more effective, long-lasting self-healing mechanisms such as cell growth and proliferation. Thus, a fast self-healing effect can be included in the list of functions of plant latex.

Mechanical exposure among general practice dentists in Sweden and possible implications of rationalisation.

PubMed

Jonker, D; Rolander, B; Balogh, I; Sandsjö, L; Ekberg, K; Winkel, J

2011-10-01

The present study investigates the dental work in terms of time distribution and mechanical exposure in value-adding work (VAW) and non-VAW. Further rationalisation of dental work would typically involve an increase in the proportion of VAW. Information on mechanical exposure within the classes of VAW and non-VAW may be used to predict possible implications of rationalisation. Sixteen dentists were investigated. Using a data logger, postures and movements were continuously recorded for each subject during the 4 h of work, which included the 45 min of video recording. Time distribution and mechanical exposure for the six different work activities identified were evaluated from the video recordings, using a loss analysis technique. VAW, which comprised 54% of the total working time, generally implied significantly more constrained mechanical exposures as compared with non-VAW. The results suggest that future rationalisation of dental work, involving a reduction of non-VAW, may increase the risk of developing musculoskeletal disorders. Statement of Relevance: The present study illustrates the potential effects of rationalisation on biomechanical exposures for dentists. The results highlight the significance of integrating ergonomic issues into the rationalisation process in dentistry in addition to ordinary workstation and tool design improvements performed by ergonomists.

Characterising the development of the understanding of human body systems in high-school biology students - a longitudinal study

NASA Astrophysics Data System (ADS)

Snapir, Zohar; Eberbach, Catherine; Ben-Zvi-Assaraf, Orit; Hmelo-Silver, Cindy; Tripto, Jaklin

2017-10-01

Science education today has become increasingly focused on research into complex natural, social and technological systems. In this study, we examined the development of high-school biology students' systems understanding of the human body, in a three-year longitudinal study. The development of the students' system understanding was evaluated using the Components Mechanisms Phenomena (CMP) framework for conceptual representation. We coded and analysed the repertory grid personal constructs of 67 high-school biology students at 4 points throughout the study. Our data analysis builds on the assumption that systems understanding entails a perception of all the system categories, including structures within the system (its Components), specific processes and interactions at the macro and micro levels (Mechanisms), and the Phenomena that present the macro scale of processes and patterns within a system. Our findings suggest that as the learning process progressed, the systems understanding of our students became more advanced, moving forward within each of the major CMP categories. Moreover, there was an increase in the mechanism complexity presented by the students, manifested by more students describing mechanisms at the molecular level. Thus, the 'mechanism' category and the micro level are critical components that enable students to understand system-level phenomena such as homeostasis.

Cardiovascular disease in recent onset diabetes mellitus.

PubMed

Yamagishi, Shoichi

2011-05-01

Diabetes is associated with a marked increased risk of atherosclerotic vascular disorders, including coronary, cerebrovascular, and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidemia, hypertension, smoking, obesity, lack of exercise, and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in the diabetic population. Furthermore, recently, macrovascular complications of diabetes have been shown to start before the onset of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since insulin resistance-related postprandial metabolic derangements are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial metabolic disturbance is a therapeutic target for the prevention of CVD in these high-risk patients. Therefore, in this paper, we review the molecular mechanisms for the increased risk of CVD in recent onset diabetes mellitus, especially focusing on postprandial dysmetabolism. We also discuss here the potential therapeutic strategies that specially target the mechanisms responsible for vascular alterations in diabetes. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

A novel cosmetic approach to treat thinning hair.

PubMed

Davis, M G; Thomas, J H; van de Velde, S; Boissy, Y; Dawson, T L; Iveson, R; Sutton, K

2011-12-01

Many of today's treatments associated with 'thinning hair', such as female pattern hair loss and telogen effluvium, are focused on two of the key aspects of the condition. Over-the-counter or prescription medications are often focused on improving scalp hair density while high-quality cosmetic products work to prevent further hair damage and minimize mid-fibre breakage. Fibre diameter is another key contributor to thinning hair, but it is less often the focus of medical or cosmetic treatments. To examine the ability of a novel leave-on technology combination [caffeine, niacinamide, panthenol, dimethicone and an acrylate polymer (CNPDA)] to affect the diameter and behaviour of individual terminal scalp hair fibres as a new approach to counteract decreasing fibre diameters. Testing methodology included fibre diameter measures via laser scan micrometer, assessment of fibre mechanical and behavioural properties via tensile break stress and torsion pendulum testing, and mechanistic studies including cryoscanning electron microscopy and autoradiographic analysis. CNPDA significantly increased the diameter of individual, existing terminal scalp hair fibres by 2-5 μm, which yields an increase in the cross-sectional area of approximately 10%. Beyond the diameter increase, the CNPDA-thickened fibres demonstrated the altered mechanical properties characteristic of thicker fibres: increased suppleness/pliability (decreased shear modulus) and better ability to withstand force without breaking (increased break stress). Although cosmetic treatments will not reverse the condition, this new approach may help to mitigate the effects of thinning hair. © 2011 Procter & Gamble. BJD © 2011 British Association of Dermatologists.

Fetal Programming and Cardiovascular Pathology

PubMed Central

Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

2016-01-01

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

Uric acid and cardiovascular disease.

PubMed

Ndrepepa, Gjin

2018-05-24

Uric acid (UA) is an end product of purine metabolism in humans and great apes. UA acts as an antioxidant and it accounts for 50% of the total antioxidant capacity of biological fluids in humans. When present in cytoplasm of the cells or in acidic/hydrophobic milieu in atherosclerotic plaques, UA converts into a pro-oxidant agent and promotes oxidative stress and through this mechanism participates in the pathophysiology of human disease including cardiovascular disease (CVD). Most epidemiological studies but not all of them suggested the existence of an association between elevated serum UA level and CVD, including coronary heart disease (CHD), stroke, congestive heart failure, arterial hypertension and atrial fibrillation as well as an increased risk for mortality due to CVD in general population and subjects with confirmed CHD. Evidence available also suggests an association between elevated UA and traditional cardiovascular risk factors, metabolic syndrome, insulin resistance, obesity, non-alcoholic fatty liver disease and chronic kidney disease. Experimental and clinical studies have evidenced several mechanisms through which elevated UA level exerts deleterious effects on cardiovascular health including increased oxidative stress, reduced availability of nitric oxide and endothelial dysfunction, promotion of local and systemic inflammation, vasoconstriction and proliferation of vascular smooth muscle cells, insulin resistance and metabolic dysregulation. Although the causality in the relationship between UA and CVD remains unproven, UA may be pathogenic and participate in the pathophysiology of CVD by serving as a bridging mechanism mediating (enabling) or potentiating the deleterious effects of cardiovascular risk factors on vascular tissue and myocardium. Copyright © 2018 Elsevier B.V. All rights reserved.

Genomic dissection of host-microbe and microbe-microbe interactions for advanced plant breeding.

PubMed

Kroll, Samuel; Agler, Matthew T; Kemen, Eric

2017-04-01

Agriculture faces many emerging challenges to sustainability, including limited nutrient resources, losses from diseases caused by current and emerging pathogens and environmental degradation. Microorganisms have great importance for plant growth and performance, including the potential to increase yields, nutrient uptake and pathogen resistance. An urgent need is therefore to understand and engineer plants and their associated microbial communities. Recent massive genomic sequencing of host plants and associated microbes offers resources to identify novel mechanisms of communal assembly mediated by the host. For example, host-microbe and microbe-microbe interactions are involved in niche formation, thereby contributing to colonization. By leveraging genomic resources, genetic traits underlying those mechanisms will become important resources to design plants selecting and hosting beneficial microbial communities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-Term Fragility of Y Chromosomes Is Dominated by Short-Term Resolution of Sexual Antagonism

PubMed Central

Blackmon, Heath; Brandvain, Yaniv

2017-01-01

The evolution of heteromorphic sex chromosomes has fascinated biologists, inspiring theoretical models, experimental studies, and studies of genome structure. This work has produced a clear model, in which heteromorphic sex chromosomes result from repeated fixations of inversions (or other recombination suppression mechanisms) that tether sexually antagonistic alleles to sex-determining regions, followed by the degeneration of these regions induced by the lack of sex chromosome recombination in the heterogametic sex. However, current models do not predict if inversions are expected to preferentially accumulate on one sex-chromosome or another, and do not address if inversions can accumulate even when they cause difficulties in pairing between heteromorphic chromosomes in the heterogametic sex increasing aneuploidy or meiotic arrest. To address these questions, we developed a population genetic model in which the sex chromosome aneuploidy rate is elevated when males carry an inversion on either the X or Y chromosome. We show that inversions fix more easily when male-beneficial alleles are dominant, and that inversions on the Y chromosome fix with lower selection coefficients than comparable X chromosome inversions. We further show that sex-chromosome inversions can often invade and fix despite causing a substantial increase in the risk of aneuploidy. As sexual antagonism can lead to the fixation of inversions that increase sex chromosomes aneuploidy (which underlies genetic diseases including Klinefelter and Turner syndrome in humans) selection could subsequently favor diverse mechanisms to reduce aneuploidy—including alternative meiotic mechanisms, translocations to, and fusions with, the sex chromosomes, and sex chromosome turnover. PMID:29021279

Effectiveness of demand generation interventions on use of modern contraceptives in low- and middle-income countries.

PubMed

Belaid, L; Dumont, A; Chaillet, N; Zertal, A; De Brouwere, V; Hounton, S; Ridde, V

2016-10-01

To synthesise evidence on the implementation, costs and cost-effectiveness of demand generation interventions and their effectiveness in improving uptake of modern contraception methods. A Cochrane systematic review was conducted. Searches were performed in electronic databases (MEDLINE, EMBASE) and the grey literature. Randomised controlled trials, cluster randomised trials and quasi-experimental studies, including controlled before-after studies (CBAs) and cost and cost-effectiveness studies that aimed to assess demand interventions (including community- and facility-based interventions, financial mechanisms and mass media campaigns) in low- and middle-income countries were considered. Meta-analyses and narrative synthesis were conducted. In total, 20 papers meeting the inclusion criteria were included in this review. Of those, 13 were used for meta-analysis. Few data were available on implementation and on the influence of context on demand interventions. Involving family members during counselling, providing education activities and increasing exposure to those activities could enhance the success of demand interventions. Demand generation interventions were positively associated with increases in current use (pooled OR 1.57; 95% CI: 1.46-1.69, P < 0.01). Financial mechanism interventions (vouchers) appeared effective to increase use of modern contraceptive methods (pooled OR 2.16; 95% CI: 1.91-2.45, P < 0.01; I 2 = 0%). Demand interventions improved knowledge (pooled OR 1.02; 95% CI 0.63-1.64, P = 0.93) and attitudes towards family planning and improved discussion with partners/husbands around modern contraceptive methods. However, given the limited number of studies included in each category of demand generation interventions, the dates of publication of the studies and their low quality, caution is advised in considering the results. Very limited evidence was available on costs; studies including data on costs were old and inconsistent. Demand generation interventions contribute to increases in modern contraceptive methods use. However, more studies with robust designs are needed to identify the most effective demand generation intervention to increase uptake of modern contraceptive methods. More evidence is also needed about implementation, costs and cost-effectiveness to inform decisions on sustainability and scaling-up. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Mechanism of SOA formation determines magnitude of radiative effects

NASA Astrophysics Data System (ADS)

Zhu, Jialei; Penner, Joyce E.; Lin, Guangxing; Zhou, Cheng; Xu, Li; Zhuang, Bingliang

2017-11-01

Secondary organic aerosol (SOA) nearly always exists as an internal mixture, and the distribution of this mixture depends on the formation mechanism of SOA. A model is developed to examine the influence of using an internal mixing state based on the mechanism of formation and to estimate the radiative forcing of SOA in the future. For the present day, 66% of SOA is internally mixed with sulfate, while 34% is internally mixed with primary soot. Compared with using an external mixture, the direct effect of SOA is decreased due to the decrease in total aerosol surface area and the increase of absorption efficiency. Aerosol number concentrations are sharply reduced, and this is responsible for a large decrease in the cloud albedo effect. Internal mixing decreases the radiative effect of SOA by a factor of >4 compared with treating SOA as an external mixture. The future SOA burden increases by 24% due to CO2 increases and climate change, leading to a total (direct plus cloud albedo) radiative forcing of ‑0.05 W m‑2. When the combined effects of changes in climate, anthropogenic emissions, and land use are included, the SOA forcing is ‑0.07 W m‑2, even though the SOA burden only increases by 6.8%. This is caused by the substantial increase of SOA associated with sulfate in the Aitken mode. The Aitken mode increase contributes to the enhancement of first indirect radiative forcing, which dominates the total radiative forcing.

Mechanism of SOA formation determines magnitude of radiative effects

DOE PAGES

Zhu, Jialei; Penner, Joyce E.; Lin, Guangxing; ...

2017-11-13

Secondary organic aerosol (SOA) nearly always exists as an internal mixture and the distribution of this mixture depends on the formation mechanism of SOA. A model is developed to examine the influence of using an internal mixing states based on the mechanism of formation and to estimate the radiative forcing of SOA in the future. For the present day, 66 % of SOA is internally mixed with sulfate, while 34 % is internally mixed with primary soot. When compared with using an external mixture, the direct effect of SOA is decreased, due to the decrease of total aerosol surface areamore » and the increase of absorption efficiency. Aerosol number concentrations are sharply reduced and this is responsible for a large decrease in the cloud albedo effect. In total, internal mixing suppresses the radiative effect of SOA by a factor of >4 compared to treating SOA as an external mixture. The future SOA burden increases by 24% due to CO2 increases and climate change, leading to a total (direct plus cloud albedo) radiative forcing of -0.05 W m-2. When the combined effects of changes in climate, anthropogenic emissions and land use are included, the SOA forcing is -0.07 W m-2, even though the SOA burden only increases by 6.8%. This is caused by the substantial increase of SOA associated with sulfate in the Aitken mode. The Aitken mode increase contributes to the enhancement of first indirect radiative forcing, which dominates the total radiative forcing.« less

Mechanism of SOA formation determines magnitude of radiative effects

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

Zhu, Jialei; Penner, Joyce E.; Lin, Guangxing

Secondary organic aerosol (SOA) nearly always exists as an internal mixture and the distribution of this mixture depends on the formation mechanism of SOA. A model is developed to examine the influence of using an internal mixing states based on the mechanism of formation and to estimate the radiative forcing of SOA in the future. For the present day, 66 % of SOA is internally mixed with sulfate, while 34 % is internally mixed with primary soot. When compared with using an external mixture, the direct effect of SOA is decreased, due to the decrease of total aerosol surface areamore » and the increase of absorption efficiency. Aerosol number concentrations are sharply reduced and this is responsible for a large decrease in the cloud albedo effect. In total, internal mixing suppresses the radiative effect of SOA by a factor of >4 compared to treating SOA as an external mixture. The future SOA burden increases by 24% due to CO2 increases and climate change, leading to a total (direct plus cloud albedo) radiative forcing of -0.05 W m-2. When the combined effects of changes in climate, anthropogenic emissions and land use are included, the SOA forcing is -0.07 W m-2, even though the SOA burden only increases by 6.8%. This is caused by the substantial increase of SOA associated with sulfate in the Aitken mode. The Aitken mode increase contributes to the enhancement of first indirect radiative forcing, which dominates the total radiative forcing.« less

Mechanism of SOA Formation Determines Magnitude of Radiative Effects

NASA Astrophysics Data System (ADS)

Zhu, J.; Penner, J.; Lin, G.; Zhou, C.

2017-12-01

Secondary organic aerosol (SOA) nearly always exists as an internal mixture and the distribution of this mixture depends on the formation mechanism of SOA. A model is developed to examine the influence of using an internal mixing states based on the mechanism of formation and to estimate the radiative forcing of SOA in the future. For the present day, 66 % of SOA is internally mixed with sulfate, while 34 % is internally mixed with primary soot. When compared with using an external mixture, the direct effect of SOA is decreased, due to the decrease of total aerosol surface area and the increase of absorption efficiency. Aerosol number concentrations are sharply reduced and this is responsible for a large decrease in the cloud albedo effect. In total, internal mixing suppresses the radiative effect of SOA by a factor of >4 compared to treating SOA as an external mixture. The future SOA burden increases by 24% due to CO2 increases and climate change, leading to a total (direct plus cloud albedo) radiative forcing of -0.05 W m-2. When the combined effects of changes in climate, anthropogenic emissions and land use are included, the SOA forcing is -0.07 W m-2, even though the SOA burden only increases by 6.8%. This is caused by the substantial increase of SOA associated with sulfate in the Aitken mode. The Aitken mode increase contributes to the enhancement of first indirect radiative forcing, which dominates the total radiative forcing.

Mechanism of SOA formation determines magnitude of radiative effects

PubMed Central

Penner, Joyce E.; Lin, Guangxing; Zhou, Cheng; Xu, Li; Zhuang, Bingliang

2017-01-01

Secondary organic aerosol (SOA) nearly always exists as an internal mixture, and the distribution of this mixture depends on the formation mechanism of SOA. A model is developed to examine the influence of using an internal mixing state based on the mechanism of formation and to estimate the radiative forcing of SOA in the future. For the present day, 66% of SOA is internally mixed with sulfate, while 34% is internally mixed with primary soot. Compared with using an external mixture, the direct effect of SOA is decreased due to the decrease in total aerosol surface area and the increase of absorption efficiency. Aerosol number concentrations are sharply reduced, and this is responsible for a large decrease in the cloud albedo effect. Internal mixing decreases the radiative effect of SOA by a factor of >4 compared with treating SOA as an external mixture. The future SOA burden increases by 24% due to CO2 increases and climate change, leading to a total (direct plus cloud albedo) radiative forcing of −0.05 W m−2. When the combined effects of changes in climate, anthropogenic emissions, and land use are included, the SOA forcing is −0.07 W m−2, even though the SOA burden only increases by 6.8%. This is caused by the substantial increase of SOA associated with sulfate in the Aitken mode. The Aitken mode increase contributes to the enhancement of first indirect radiative forcing, which dominates the total radiative forcing. PMID:29133426

Mechanism of SOA formation determines magnitude of radiative effects.

PubMed

Zhu, Jialei; Penner, Joyce E; Lin, Guangxing; Zhou, Cheng; Xu, Li; Zhuang, Bingliang

2017-11-28

Secondary organic aerosol (SOA) nearly always exists as an internal mixture, and the distribution of this mixture depends on the formation mechanism of SOA. A model is developed to examine the influence of using an internal mixing state based on the mechanism of formation and to estimate the radiative forcing of SOA in the future. For the present day, 66% of SOA is internally mixed with sulfate, while 34% is internally mixed with primary soot. Compared with using an external mixture, the direct effect of SOA is decreased due to the decrease in total aerosol surface area and the increase of absorption efficiency. Aerosol number concentrations are sharply reduced, and this is responsible for a large decrease in the cloud albedo effect. Internal mixing decreases the radiative effect of SOA by a factor of >4 compared with treating SOA as an external mixture. The future SOA burden increases by 24% due to CO 2 increases and climate change, leading to a total (direct plus cloud albedo) radiative forcing of -0.05 W m -2 When the combined effects of changes in climate, anthropogenic emissions, and land use are included, the SOA forcing is -0.07 W m -2 , even though the SOA burden only increases by 6.8%. This is caused by the substantial increase of SOA associated with sulfate in the Aitken mode. The Aitken mode increase contributes to the enhancement of first indirect radiative forcing, which dominates the total radiative forcing. Copyright © 2017 the Author(s). Published by PNAS.

Progressive Damage Modeling of Durable Bonded Joint Technology

NASA Technical Reports Server (NTRS)

Leone, Frank A.; Davila, Carlos G.; Lin, Shih-Yung; Smeltzer, Stan; Girolamo, Donato; Ghose, Sayata; Guzman, Juan C.; McCarville, Duglas A.

2013-01-01

The development of durable bonded joint technology for assembling composite structures for launch vehicles is being pursued for the U.S. Space Launch System. The present work is related to the development and application of progressive damage modeling techniques to bonded joint technology applicable to a wide range of sandwich structures for a Heavy Lift Launch Vehicle. The joint designs studied in this work include a conventional composite splice joint and a NASA-patented Durable Redundant Joint. Both designs involve a honeycomb sandwich with carbon/epoxy facesheets joined with adhesively bonded doublers. Progressive damage modeling allows for the prediction of the initiation and evolution of damage. For structures that include multiple materials, the number of potential failure mechanisms that must be considered increases the complexity of the analyses. Potential failure mechanisms include fiber fracture, matrix cracking, delamination, core crushing, adhesive failure, and their interactions. The joints were modeled using Abaqus parametric finite element models, in which damage was modeled with user-written subroutines. Each ply was meshed discretely, and layers of cohesive elements were used to account for delaminations and to model the adhesive layers. Good correlation with experimental results was achieved both in terms of load-displacement history and predicted failure mechanisms.

Update on Multiple Ovulations in Dairy Cattle

PubMed Central

Macmillan, Kira; Kastelic, John P.

2018-01-01

Simple Summary Multiple ovulations (MOV) in cattle can lead to twin pregnancies, which negatively affects the health, production, and reproduction of cows. Despite many studies, the causal mechanisms behind MOV are still not well understood. There is a general agreement that MOV are more likely during periods of low progesterone (P4), which may increase the luteinizing hormone (LH) release at the time of selection, resulting in more than one follicle becoming dominant. The MOV rate also increases in older cows and when the selection of a dominant follicle occurs concurrently with a high milk yield. Additional risk factors for MOV are ovarian cysts, diet, season, and genetics. A better understanding of the mechanisms underlying MOV may help to mitigate twinning, perhaps through the appropriate reproductive management protocols or genetic selection. Abstract This review updates the causal mechanisms and risk factors for multiple ovulations (MOV) in cattle. Clearly, MOV can lead to twin pregnancies, which negatively affects the health, production, and reproduction of cows. Therefore, a better understanding of the factors causing MOV may help to reduce twinning. Multiple ovulations occur after two or more follicles deviate and achieve codominance. The MOV rate is influenced by a complex network of hormones. For example, MOV is more common during periods of low progesterone (P4), that is, in anovulatory cattle or when luteolysis coincides with the selection of the future ovulatory follicle. There is also strong evidence for the luteinizing hormone (LH) being the primary factor leading to codominance, as high P4 concentrations suppress the transient LH surges and can reduce the ovulation rate in cattle or even inhibit deviation. Rates of MOV are increased in older and higher-producing dairy cows. Increased milk production and dry matter intake (DMI) increases hormone clearance, including P4; however, the association between milk yield and MOV has not been consistent. Additional risk factors for MOV include ovarian cysts, diet, season, and genetics. PMID:29695075

Thermally-driven Coupled THM Processes in Shales

NASA Astrophysics Data System (ADS)

Rutqvist, J.

2017-12-01

Temperature changes can trigger strongly coupled thermal-hydrological-mechanical (THM) processes in shales that are important to a number of subsurface energy applications, including geologic nuclear waste disposal and hydrocarbon extraction. These coupled processes include (1) direct pore-volume couplings, by thermal expansion of trapped pore-fluid that triggers instantaneous two-way couplings between pore fluid pressure and mechanical deformation, and (2) indirect couplings in terms of property changes, such as changes in mechanical stiffness, strength, and permeability. Direct pore-volume couplings have been studied in situ during borehole heating experiments in shale (or clay stone) formations at Mont Terri and Bure underground research laboratories in Switzerland and France. Typically, the temperature changes are accompanied with a rapid increase in pore pressure followed by a slower decrease towards initial (pre-heating) pore pressure. Coupled THM modeling of these heater tests shows that the pore pressure increases because the thermal expansion coefficient of the fluid is much higher than that of the porous clay stone. Such thermal pressurization induces fluid flow away from the pressurized area towards areas of lower pressure. The rate of pressure increase and magnitude of peak pressure depends on the rate of heating, pore-compressibility, and permeability of the shale. Modeling as well as laboratory experiments have shown that if the pore pressure increase is sufficiently large it could lead to fracturing of the shale or shear slip along pre-existing bedding planes. Another set of data and observations have been collected associated with studies related to concentrated heating and cooling of oil-shales and shale-gas formations. Heating may be used to enhance production from tight oil-shale, whereas thermal stimulation has been attempted for enhanced shale-gas extraction. Laboratory experiments on shale have shown that strength and elastic deformation modulus decreases with temperature while the rate creep deformations increase with temperature. Such temperature dependency also affects the well stability and zonal sealing across shale layers.

Negative extensibility metamaterials: phase diagram calculation

NASA Astrophysics Data System (ADS)

Klein, John T.; Karpov, Eduard G.

2017-12-01

Negative extensibility metamaterials are able to contract against the line of increasing external tension. A bistable unit cell exhibits several nonlinear mechanical behaviors including the negative extensibility response. Here, an exact form of the total mechanical potential is used based on engineering strain measure. The mechanical response is a function of the system parameters that specify unit cell dimensions and member stiffnesses. A phase diagram is calculated, which maps the response to regions in the diagram using the system parameters as the coordinate axes. Boundary lines pinpoint the onset of a particular mechanical response. Contour lines allow various material properties to be fine-tuned. Analogous to thermodynamic phase diagrams, there exist singular "triple points" which simultaneously satisfy conditions for three response types. The discussion ends with a brief statement about how thermodynamic phase diagrams differ from the phase diagram in this paper.

Wear mechanisms of the biotribological nanocomposite a-C : H coatings implanted by metallic nanoparticles.

PubMed

Major, L; Janusz, M; Lackner, J M; Kot, M; Dyner, M; Major, B

2017-10-01

Recently, to reduce the residual stress and increase the mechanical properties of a-C:H coatings, metallic nanoparticles have been implanted into their structure. In the present work, to improve the properties of the coating, metallic nanoparticles, including Cu, Nb, Ta, Zr, AgPt and Ag, were inserted into the a-C:H structure. The applied biological and mechanical analysis allowed the optimal biotribological parameters to be indicated for the potential application as protective coatings for metallic medical tools. Wear mechanisms operating at the small length of the designed biotribological coating, such as a-C:H implanted by Zr nanoparticles, were studied by means of transmission electron microscopy (TEM). The TEM analysis confirmed very good coating adhesion to the metallic substrate. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

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

Yin, Shengyong; Chen, Xinhua; Xie, Haiyang

Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatinmore » for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge.« less

Plausible Roles for RAGE in Conditions Exacerbated by Direct and Indirect (Secondhand) Smoke Exposure.

PubMed

Lewis, Joshua B; Hirschi, Kelsey M; Arroyo, Juan A; Bikman, Benjamin T; Kooyman, David L; Reynolds, Paul R

2017-03-17

Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure. Specifically, data are discussed relative to impaired lung physiology, cancer mechanisms, maternal-fetal complications, cardiometabolic, and joint disorders in the context of smoke exposure exacerbations. As a general unifying mechanism, the receptor for advanced glycation end-products (RAGE) and its signaling axis is increasingly considered central to smoke-related pathogenesis. RAGE is a multi-ligand cell surface receptor whose expression increases following cigarette smoke exposure. RAGE signaling participates in the underpinning of inflammatory mechanisms mediated by requisite cytokines, chemokines, and remodeling enzymes. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of lung disease and systemic complications that combine during the demise of those exposed.

Effects and Mechanisms of Tastants on the Gustatory-Salivary Reflex in Human Minor Salivary Glands.

PubMed

Satoh-Kuriwada, Shizuko; Shoji, Noriaki; Miyake, Hiroyuki; Watanabe, Chiyo; Sasano, Takashi

2018-01-01

The effects and mechanisms of tastes on labial minor salivary gland (LMSG) secretion were investigated in 59 healthy individuals. Stimulation with each of the five basic tastes (i.e., sweet, salty, sour, bitter, and umami) onto the tongue induced LMSG secretion in a dose-dependent manner. Umami and sour tastes evoked greater secretion than did the other tastes. A synergistic effect of umami on LMSG secretion was recognized: a much greater increase in secretion was observed by a mixed solution of monosodium glutamate and inosine 5'-monophosphate than by each separate stimulation. Blood flow (BF) in the nearby labial mucosa also increased following stimulation by each taste except bitter. The BF change and LMSG secretion in each participant showed a significant positive correlation with all tastes, including bitter. Administration of cevimeline hydrochloride hydrate to the labial mucosa evoked a significant increase in both LMSG secretion and BF, while adrenaline, atropine, and pirenzepine decreased LMSG secretion and BF. The change in LMSG secretion and BF induced by each autonomic agent was significantly correlated in each participant. These results indicate that basic tastes can induce the gustatory-salivary reflex in human LMSGs and that parasympathetic regulation is involved in this mechanism.

Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

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

Nagai, Rhoji; Murray, David B.; Metz, Thomas O.

2012-03-01

Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelatingmore » activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.« less

Mitigation of climate change impacts on raptors by behavioural adaptation: ecological buffering mechanisms

NASA Astrophysics Data System (ADS)

Wichmann, Matthias C.; Groeneveld, Jürgen; Jeltsch, Florian; Grimm, Volker

2005-07-01

The predicted climate change causes deep concerns on the effects of increasing temperatures and changing precipitation patterns on species viability and, in turn, on biodiversity. Models of Population Viability Analysis (PVA) provide a powerful tool to assess the risk of species extinction. However, most PVA models do not take into account the potential effects of behavioural adaptations. Organisms might adapt to new environmental situations and thereby mitigate negative effects of climate change. To demonstrate such mitigation effects, we use an existing PVA model describing a population of the tawny eagle ( Aquila rapax) in the southern Kalahari. This model does not include behavioural adaptations. We develop a new model by assuming that the birds enlarge their average territory size to compensate for lower amounts of precipitation. Here, we found the predicted increase in risk of extinction due to climate change to be much lower than in the original model. However, this "buffering" of climate change by behavioural adaptation is not very effective in coping with increasing interannual variances. We refer to further examples of ecological "buffering mechanisms" from the literature and argue that possible buffering mechanisms should be given due consideration when the effects of climate change on biodiversity are to be predicted.

Plausible Roles for RAGE in Conditions Exacerbated by Direct and Indirect (Secondhand) Smoke Exposure

PubMed Central

Lewis, Joshua B.; Hirschi, Kelsey M.; Arroyo, Juan A.; Bikman, Benjamin T.; Kooyman, David L.; Reynolds, Paul R.

2017-01-01

Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure. Specifically, data are discussed relative to impaired lung physiology, cancer mechanisms, maternal-fetal complications, cardiometabolic, and joint disorders in the context of smoke exposure exacerbations. As a general unifying mechanism, the receptor for advanced glycation end-products (RAGE) and its signaling axis is increasingly considered central to smoke-related pathogenesis. RAGE is a multi-ligand cell surface receptor whose expression increases following cigarette smoke exposure. RAGE signaling participates in the underpinning of inflammatory mechanisms mediated by requisite cytokines, chemokines, and remodeling enzymes. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of lung disease and systemic complications that combine during the demise of those exposed. PMID:28304347

Preparation and characterization of bionanocomposite films based on potato starch/halloysite nanoclay.

PubMed

Sadegh-Hassani, Fatemeh; Mohammadi Nafchi, Abdorreza

2014-06-01

In this research casting method was used to prepare potato starch based bio-nanocomposite films with halloysite nanoclay as the reinforcing materials. The composition included potato starch with 40% (w/w) of a mixture of sorbitol/glycerol (weight ratio of 3 to 1as plasticizer) with nanoclay (0-5% w/w). The films were dried under controlled conditions. Physicochemical properties such as solubility in water, water absorption capacity (WAC), water vapour permeability (WVP), oxygen permeability, and mechanical properties of the films were measured. Results showed that by increasing the concentration of nanoclay, mechanical properties of films were improved. Tensile strength was increased from 7.33 to 9.82MPa, and elongation at break decreased from 68.0 to 44.0%. Solubility in water decreased from 35 to 23%, and heat seal strength increased from 375 to 580N/m. Also incorporation of clay nanoparticles in the structure of biopolymer decreased permeability of the gaseous molecules. In summary, addition of halloysite nanoclay, improve the barrier and mechanical properties of potato starch films and this bionanocomposites have high potential to be used for food packaging purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

Autism spectrum disorder in children born preterm—role of exposure to perinatal inflammation

PubMed Central

Meldrum, Suzanne J.; Strunk, T.; Currie, A.; Prescott, S. L.; Simmer, K.; Whitehouse, A. J. O.

2013-01-01

Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm. PMID:23885233

NK cell recruitment and exercise: Potential immunotherapeutic role of shear stress and endothelial health.

PubMed

Evans, William

2017-11-01

Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium. Additionally, shear stress may play a role in improving NK cell function by decreasing oxidative stress. The relationship between shear stress and NK cell count and function can be tested by utilizing exercise and local heating with cuff inflation. If shear stress does play an important role, NK cell count and function will be improved in the non-cuffed exercise group, but not the cuffed limb. This paper will explore the mechanisms potentially explaining exercise-induced improvements in NK cell count and function, and propose a model for investigating these mechanisms. This mechanistic insight could aid in providing a novel, safe, relatively inexpensive, and non-invasive target for immunotherapy in cancer patients. Copyright © 2017. Published by Elsevier Ltd.

Intergenerational Neuroimaging of Human Brain Circuitry

PubMed Central

Ho, Tiffany C.; Sanders, Stephan J.; Gotlib, Ian H.; Hoeft, Fumiko

2016-01-01

Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed insight into the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here, we highlight recent intergenerational neuroimaging studies and provide recommendations for future work. PMID:27623194

Energy budget closure observed in paired Eddy Covariance towers with increased and continuous daily turbulence

USDA-ARS?s Scientific Manuscript database

The lack of energy closure has been a longstanding issue with Eddy Covariance (EC). Multiple mechanisms have been proposed to explain the discrepancies in energy balance including diurnal energy storage changes, advection of energy, and larger scale turbulent processes that cannot be resolved by fi...

Threats to Validity in the edTPA Video Component

ERIC Educational Resources Information Center

Choppin, Jeffrey; Meuwissen, Kevin

2017-01-01

The edTPA, a performance assessment designed to generate reliable and valid measures of teaching practice, increasingly is used as a gatekeeping mechanism for beginning teacher licensure in various states, including New York, Washington State, Wisconsin, and Georgia. One of the edTPA's key components is the demonstration of instructional practice…

Emotional Clarity as a Mechanism Linking Emotional Neglect and Depressive Symptoms during Early Adolescence

ERIC Educational Resources Information Center

Jessar, Allison J.; Hamilton, Jessica L.; Flynn, Megan; Abramson, Lyn Y.; Alloy, Lauren B.

2017-01-01

The present study examined whether emotional abuse and neglect differentially predicted decreases in emotional clarity, and whether emotional clarity, in turn, predicted increases in depressive symptoms. Participants included 204 early adolescents (52% African American; 54% female; M age = 12.85 years) who completed four assessments with measures…

Mechanism of resistance acquisition and potential associated fitness costs in navel orangeworm (Amyelois transitella) exposed to pyrethroid insecticides

USDA-ARS?s Scientific Manuscript database

The polyphagous navel orangeworm (Amyelois transitella) is the most destructive pest of nut crops, including almonds and pistachios, in California orchards. Management of this insect has typically been a combination of cultural controls and insecticide use, with the latter increasing substantially a...

Improving Internet Archive Service through Proxy Cache.

ERIC Educational Resources Information Center

Yu, Hsiang-Fu; Chen, Yi-Ming; Wang, Shih-Yong; Tseng, Li-Ming

2003-01-01

Discusses file transfer protocol (FTP) servers for downloading archives (files with particular file extensions), and the change to HTTP (Hypertext transfer protocol) with increased Web use. Topics include the Archie server; proxy cache servers; and how to improve the hit rate of archives by a combination of caching and better searching mechanisms.…

The Effectiveness of Academic Workload Models in an Institution: A Staff Perspective

ERIC Educational Resources Information Center

Kenny, John D. J.; Fluck, Andrew E.

2014-01-01

The demands on academic staff are increasing to the point where effective mechanisms for the allocation of their work are now necessary. Despite the inherent difficulties of categorising academic work, nearly all enterprise agreements at Australian universities include a clause designed to avoid work overload. Through a questionnaire, the…

Longitudinal Evaluation of a Scale-Up Model for Teaching Mathematics with Trajectories and Technologies: Mechanisms of Persistence of Effects

ERIC Educational Resources Information Center

Clements, Douglas H.

2011-01-01

The author and her colleagues' TRIAD model (Sarama, Clements, Starkey, Klein, & Wakeley, 2008), including the "Building Blocks" curriculum, have significantly and substantially increased preschooler's mathematical competence, both in previous studies (Clements & Sarama, 2008, g = 1.07) and in their present, largest implementation…

Supersonic Retropulsion Surface Preparation of Carbon Fiber Reinforced Epoxy Composites for Adhesive Bonding

NASA Technical Reports Server (NTRS)

Palmieri, Frank L.; Belcher, Marcus A.; Wohl, Christopher J.; Blohowiak, Kay Y.; Connell, John W.

2013-01-01

Surface preparation is widely recognized as a key step to producing robust and predictable bonds in a precise and reproducible manner. Standard surface preparation techniques, including grit blasting, manual abrasion, and peel ply, can lack precision and reproducibility, which can lead to variation in surface properties and subsequent bonding performance. The use of a laser to ablate composite surface resin can provide an efficient, precise, and reproducible means of preparing composite surfaces for adhesive bonding. Advantages include elimination of physical waste (i.e., grit media and sacrificial peel ply layers that ultimately require disposal), reduction in process variability due to increased precision (e.g. increased reproducibility), and automation of surface preparation, all of which improve reliability and process control. This paper describes a Nd:YAG laser surface preparation technique for composite substrates and the mechanical performance and failure modes of bonded laminates thus prepared. Additionally, bonded specimens were aged in a hot, wet environment for approximately one year and subsequently mechanically tested. The results of a one year hygrothermal aging study will be presented.

Catastrophic subsidence: An environmental hazard, shelby county, Alabama

NASA Astrophysics Data System (ADS)

Lamoreaux, Philip E.; Newton, J. G.

1986-03-01

Induced sinkholes (catastrophic subsidence) are those caused or accelerated by human activities These sinkholes commonly result from a water level decline due to pumpage Construction activities in a cone of depression greatly increases the likelihood of sinkhole occurrence Almost all occur where cavities develop in unconsolidated deposits overlying solution openings in carbonate rocks. Triggering mechanisms resulting from water level declines are (1) loss of buoyant support of the water, (2) increased gradient and water velocity, (3) water-level fluctuations, and (4) induced recharge Construction activities triggering sinkhole development include ditching, removing overburden, drilling, movement of heavy equipment, blasting and the diversion and impoundment of drainage Triggering mechanisms include piping, saturation, and loading Induced sinkholes resulting from human water development/management activities are most predictable in a youthful karst area impacted by groundwater withdrawals Shape, depth, and timing of catastrophic subsidence can be predicted in general terms Remote sensing techniques are used in prediction of locations of catastrophic subsidence. This provides a basis for design and relocation of structures such as a gas pipeline, dam, or building Utilization of techniques and a case history of the relocation of a pipeline are described

A Batch Feeder for Inhomogeneous Bulk Materials

NASA Astrophysics Data System (ADS)

Vislov, I. S.; Kladiev, S. N.; Slobodyan, S. M.; Bogdan, A. M.

2016-04-01

The work includes the mechanical analysis of mechanical feeders and batchers that find application in various technological processes and industrial fields. Feeders are usually classified according to their design features into two groups: conveyor-type feeders and non-conveyor feeders. Batchers are used to batch solid bulk materials. Less frequently, they are used for liquids. In terms of a batching method, they are divided into volumetric and weighting batchers. Weighting batchers do not provide for sufficient batching accuracy. Automatic weighting batchers include a mass controlling sensor and systems for automatic material feed and automatic mass discharge control. In terms of operating principle, batchers are divided into gravitational batchers and batchers with forced feed of material using conveyors and pumps. Improved consumption of raw materials, decreased loss of materials, ease of use in automatic control systems of industrial facilities allows increasing the quality of technological processes and improve labor conditions. The batch feeder suggested by the authors is a volumetric batcher that has no comparable counterparts among conveyor-type feeders and allows solving the problem of targeted feeding of bulk material batches increasing reliability and hermeticity of the device.

p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus

PubMed Central

Xia, Shuting; Zhou, Zikai; Leung, Celeste; Zhu, Yuehua; Pan, Xingxiu; Qi, Junxia; Morena, Maria; Hill, Matthew N; Xie, Wei; Jia, Zhengping

2016-01-01

PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders, including autism, but the underlying mechanisms remain elusive. We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic, but not phasic, secretion of endocannabinoids (eCB). Consistently, we found elevated levels of anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) following PAK1 disruption. This increased tonic AEA signaling is mediated by reduced cyclooxygenase-2 (COX-2), and COX-2 inhibitors recapitulate the effect of PAK1 deletion on GABAergic transmission in a CB1 receptor-dependent manner. These results establish a novel signaling process whereby PAK1 upregulates COX-2, reduces AEA and restricts tonic eCB-mediated processes. Because PAK1 and eCB are both critically involved in many other organ systems in addition to the brain, our findings may provide a unified mechanism by which PAK1 regulates these systems and their dysfunctions including cancers, inflammations and allergies. DOI: http://dx.doi.org/10.7554/eLife.14653.001 PMID:27296803

Genetic fine-mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

PubMed Central

Mahajan, Anubha; Locke, Adam; Rayner, N William; Robertson, Neil; Scott, Robert A; Prokopenko, Inga; Scott, Laura J; Green, Todd; Sparso, Thomas; Thuillier, Dorothee; Yengo, Loic; Grallert, Harald; Wahl, Simone; Frånberg, Mattias; Strawbridge, Rona J; Kestler, Hans; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Li, Man; Chen, Han; Fuchsberger, Christian; Kwan, Phoenix; Ma, Clement; Linderman, Michael; Lu, Yingchang; Thomsen, Soren K; Rundle, Jana K; Beer, Nicola L; van de Bunt, Martijn; Chalisey, Anil; Kang, Hyun Min; Voight, Benjamin F; Abecasis, Goncalo R; Almgren, Peter; Baldassarre, Damiano; Balkau, Beverley; Benediktsson, Rafn; Blüher, Matthias; Boeing, Heiner; Bonnycastle, Lori L; Borringer, Erwin P; Burtt, Noël P; Carey, Jason; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn C; Couper, David J; Crenshaw, Andrew T; van Dam, Rob M; Doney, Alex SF; Dorkhan, Mozhgan; Edkins, Sarah; Eriksson, Johan G; Esko, Tonu; Eury, Elodie; Fadista, João; Flannick, Jason; Fontanillas, Pierre; Fox, Caroline; Franks, Paul W; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Gottesman, Omri; Grant, George B; Grarup, Niels; Groves, Christopher J; Hassinen, Maija; Have, Christian T; Herder, Christian; Holmen, Oddgeir L; Hreidarsson, Astradur B; Humphries, Steve E; Hunter, David J; Jackson, Anne U; Jonsson, Anna; Jørgensen, Marit E; Jørgensen, Torben; Kerrison, Nicola D; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Kovacs, Peter; Kraft, Peter; Kravic, Jasmina; Langford, Cordelia; Leander, Karin; Liang, Liming; Lichtner, Peter; Lindgren, Cecilia M; Lindholm, Eero; Linneberg, Allan; Liu, Ching-Ti; Lobbens, Stéphane; Luan, Jian’an; Lyssenko, Valeriya; Männistö, Satu; McLeod, Olga; Meyer, Julia; Mihailov, Evelin; Mirza, Ghazala; Mühleisen, Thomas W; Müller-Nurasyid, Martina; Navarro, Carmen; Nöthen, Markus M; Oskolkov, Nikolay N; Owen, Katharine R; Palli, Domenico; Pechlivanis, Sonali; Perry, John RB; Platou, Carl GP; Roden, Michael; Ruderfer, Douglas; Rybin, Denis; van der Schouw, Yvonne T; Sennblad, Bengt; Sigurðsson, Gunnar; Stančáková, Alena; Steinbach, Gerald; Storm, Petter; Strauch, Konstantin; Stringham, Heather M; Sun, Qi; Thorand, Barbara; Tikkanen, Emmi; Tonjes, Anke; Trakalo, Joseph; Tremoli, Elena; Tuomi, Tiinamaija; Wennauer, Roman; Wood, Andrew R; Zeggini, Eleftheria; Dunham, Ian; Birney, Ewan; Pasquali, Lorenzo; Ferrer, Jorge; Loos, Ruth JF; Dupuis, Josée; Florez, Jose C; Boerwinkle, Eric; Pankow, James S; van Duijn, Cornelia; Sijbrands, Eric; Meigs, James B; Hu, Frank B; Thorsteinsdottir, Unnur; Stefansson, Kari; Lakka, Timo A; Rauramaa, Rainer; Stumvoll, Michael; Pedersen, Nancy L; Lind, Lars; Keinanen-Kiukaanniemi, Sirkka M; Korpi-Hyövälti, Eeva; Saaristo, Timo E; Saltevo, Juha; Kuusisto, Johanna; Laakso, Markku; Metspalu, Andres; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Ripatti, Samuli; Salomaa, Veikko; Ingelsson, Erik; Boehm, Bernhard O; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Koistinen, Heikki; Tuomilehto, Jaakko; Hveem, Kristian; Njølstad, Inger; Deloukas, Panagiotis; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; de Faire, Ulf; Hamsten, Anders; Illig, Thomas; Peters, Annette; Cauchi, Stephane; Sladek, Rob; Froguel, Philippe; Hansen, Torben; Pedersen, Oluf; Morris, Andrew D; Palmer, Collin NA; Kathiresan, Sekar; Melander, Olle; Nilsson, Peter M; Groop, Leif C; Barroso, Inês; Langenberg, Claudia; Wareham, Nicholas J; O’Callaghan, Christopher A; Gloyn, Anna L; Altshuler, David; Boehnke, Michael; Teslovich, Tanya M; McCarthy, Mark I; Morris, Andrew P

2015-01-01

We performed fine-mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in/near KCNQ1. “Credible sets” of variants most likely to drive each distinct signal mapped predominantly to non-coding sequence, implying that T2D association is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine-mapping implicated rs10830963 as driving T2D association. We confirmed that this T2D-risk allele increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D-risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease. PMID:26551672

Natural environments, nature relatedness and the ecological theater: connecting satellites and sequencing to shinrin-yoku.

PubMed

Craig, Jeffrey M; Logan, Alan C; Prescott, Susan L

2016-01-13

Recent advances in research concerning the public health value of natural environments have been remarkable. The growing interest in this topic (often housed under terms such as green and/or blue space) has been occurring in parallel with the microbiome revolution and an increased use of remote sensing technology in public health. In the context of biodiversity loss, rapid urbanization, and alarming rates of global non-communicable diseases (many associated with chronic, low-grade inflammation), discussions of natural vis-a-vis built environments are not merely fodder for intellectual curiosity. Here, we argue for increased interdisciplinary collaboration with the aim of better understanding the mechanisms-including aerobiological and epigenetic-that might help explain some of the noted positive health outcomes. It is our contention that some of these mechanisms are related to ecodiversity (i.e., the sum of biodiversity and geodiversity, including biotic and abiotic constituents). We also encourage researchers to more closely examine individual nature relatedness and how it might influence many outcomes that are at the interface of lifestyle habits and contact with ecodiversity.

Mediation of a Preventive Intervention’s Six-Year Effects on Health Risk Behaviors

PubMed Central

Soper, Ana C.; Wolchik, Sharlene A.; Tein, Jenn-Yun; Sandler, Irwin N.

2010-01-01

Using data from a 6-year longitudinal follow-up sample of 240 youth who participated in a randomized experimental trial of a preventive intervention for divorced families with children ages 9 -12, the current study tested mechanisms by which the intervention reduced substance use and risky sexual behavior in mid to late adolescence (15–19 years old). Mechanisms tested included parental monitoring, adaptive coping, and negative errors. Parental monitoring at 6-year follow-up mediated program effects to reduce alcohol and marijuana use, polydrug use, and other drug use for those with high pre-test risk for maladjustment. In the condition that included a program for mothers only, increases in youth adaptive coping at 6-year follow-up mediated program effects on risky sexual behavior for those with high pre-test risk for maladjustment. Contrary to expectation, program participation increased negative errors and decreased adaptive coping among low risk youth in some of the analyses. Ways in which this study furthers our understanding of pathways through which evidence-based preventive interventions affect health risk behaviors are discussed. PMID:20565156

The effect of helium-oxygen-assisted mechanical ventilation on chronic obstructive pulmonary disease exacerbation: A systemic review and meta-analysis.

PubMed

Wu, Xu; Shao, Chuan; Zhang, Liang; Tu, Jinjing; Xu, Hui; Lin, Zhihui; Xu, Shuguang; Yu, Biyun; Tang, Yaodong; Li, Shanqun

2018-03-01

Chronic obstructive pulmonary disease (COPD) is often accompanied by acute exacerbations. Patients of COPD exacerbation suffering from respiratory failure often need the support of mechanical ventilation. Helium-oxygen can be used to reduce airway resistance during mechanical ventilation. The aim of this study is to evaluate the effect of helium-oxygen-assisted mechanical ventilation on COPD exacerbation through a meta-analysis. A comprehensive literature search through databases of Pub Med (1966∼2016), Ovid MEDLINE (1965∼2016), Cochrane EBM (1991∼2016), EMBASE (1974∼2016) and Ovid MEDLINE was performed to identify associated studies. Randomized clinical trials met our inclusion criteria that focus on helium-oxygen-assisted mechanical ventilation on COPD exacerbation were included. The quality of the papers was evaluated after inclusion and information was extracted for meta-analysis. Six articles and 392 patients were included in total. Meta-analysis revealed that helium-oxygen-assisted mechanical ventilation reduced Borg dyspnea scale and increased arterial PH compared with air-oxygen. No statistically significant difference was observed between helium-oxygen and air-oxygen as regards to WOB, PaCO 2 , OI, tracheal intubation rates and mortality within hospital. Our study suggests helium-oxygen-assisted mechanical ventilation can help to reduce Borg dyspnea scale. In terms of the tiny change of PH, its clinical benefit is negligible. There is no conclusive evidence indicating the beneficial effect of helium-oxygen-assisted mechanical ventilation on clinical outcomes or prognosis of COPD exacerbation. © 2017 John Wiley & Sons Ltd.

Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

PubMed Central

Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

2012-01-01

Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

Resistance of Bacteria to Biocides.

PubMed

Maillard, Jean-Yves

2018-04-01

Biocides and formulated biocides are used worldwide for an increasing number of applications despite tightening regulations in Europe and in the United States. One concern is that such intense usage of biocides could lead to increased bacterial resistance to a product and cross-resistance to unrelated antimicrobials including chemotherapeutic antibiotics. Evidence to justify such a concern comes mostly from the use of health care-relevant bacterial isolates, although the number of studies of the resistance characteristics of veterinary isolates to biocides have increased the past few years. One problem remains the definition of "resistance" and how to measure resistance to a biocide. This has yet to be addressed globally, although the measurement of resistance is becoming more pressing, with regulators both in Europe and in the United States demanding that manufacturers provide evidence that their biocidal products will not impact on bacterial resistance. Alongside in vitro evidence of potential antimicrobial cross-resistance following biocide exposure, our understanding of the mechanisms of bacterial resistance and, more recently, our understanding of the effect of biocides to induce a mechanism(s) of resistance in bacteria has improved. This article aims to provide an understanding of the development of antimicrobial resistance in bacteria following a biocide exposure. The sections provide evidence of the occurrence of bacterial resistance and its mechanisms of action and debate how to measure bacterial resistance to biocides. Examples pertinent to the veterinary field are used where appropriate.

Mechatronics: the future of mechanical engineering; past, present, and a vision for the future

NASA Astrophysics Data System (ADS)

Ramasubramanian, M. K.

2001-08-01

Mechatronics is the synergistic integration of precision mechanical engineering, electronics, computational hardware and software in the design of products and processes. Mechatronics, the term coined in Japan in the '70s, has evolved to symbolize what mechanical design engineers do today worldwide. The revolutionary introduction of the microprocessor (or microcontroller) in the early '80s and ever increasing performance-cost ratio has changed the paradigm of mechanical design forever, and has broadened the original definition of mechatronics to include intelligent control and autonomous decision-making. Today, increasing number of new products is being developed at the intersection between traditional disciplines of Engineering, and Computer and Material Sciences. New developments in these traditional disciplines are being absorbed into mechatronics design at an ever-increasing pace. In this paper, a brief history of mechatronics, and several examples of this rapid adaptation of technologies into product design is presented. With the ongoing information technology revolution, especially in wireless communication, smart sensors design (enabled by MEMS technology), and embedded systems engineering, mechatronics design is going through another step change in capabilities and scope. The implications of these developments in mechatronics design in the near future are discussed. Finally, deficiencies in our engineering curriculum to address the needs of the industry to cope up with these rapid changes, and proposed remedies, will also be discussed.

Omega-3 fatty acids and dementia

PubMed Central

Cole, Greg M.; Ma, Qiu-Lan; Frautschy, Sally A.

2014-01-01

More than a dozen epidemiological studies have reported that reduced levels or intake of omega-3 fatty acids or fish consumption is associated with increased risk for age-related cognitive decline or dementia such as Alzheimer's disease (AD). Increased dietary consumption or blood levels of docosahexaenoic acid (DHA) appear protective for AD and other dementia in multiple epidemiological studies; however, three studies suggest that the ApoE4 genotype limits protection. DHA is broadly neuroprotective via multiple mechanisms that include neuroprotective DHA metabolites, reduced arachidonic acid metabolites, and increased trophic factors or downstream trophic signal transduction. DHA is also protective against several risk factors for dementia including head trauma, diabetes, and cardiovascular disease. DHA is specifically protective against AD via additional mechanisms: It limits the production and accumulation of the amyloid β peptide toxin that is widely believed to drive the disease; and it also suppresses several signal transduction pathways induced by Aβ, including two major kinases that phosphorylate the microtubule associated protein tau and promote neurofibrillary tangle pathology. Based on the epidemiological and basic research data, expert panels have recommended the need for clinical trials with omega-3 fatty acids, notably DHA, for the prevention or treatment of age-related cognitive decline—with a focus on the most prevalent cause, AD. Clinical trials are underway to prevent and treat AD. Results to-date suggest that DHA may be more effective if it is begun early or used in conjunction with antioxidants. PMID:19523795

Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.

PubMed

Garza-Lombó, Carla; Posadas, Yanahi; Quintanar, Liliana; Gonsebatt, María E; Franco, Rodrigo

2018-06-20

Essential metals such as copper, iron, manganese, and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our life span, humans are also exposed to xenobiotic metals from natural and anthropogenic sources, including aluminum, arsenic, cadmium, lead, and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals are linked to several neurological disorders, including neurodegeneration and neurodevelopmental alterations. Recent Advances: The redox activity of essential metals is key for neuronal homeostasis and brain function. Alterations in redox homeostasis and signaling are central to the pathological consequences of dysfunctional metal ion homeostasis and increased exposure to xenobiotic metals. Both redox-active and redox-inactive metals trigger oxidative stress and damage in the central nervous system, and the exact mechanisms involved are starting to become delineated. In this review, we aim to appraise the role of essential metals in determining the redox balance in the brain and the mechanisms by which alterations in the homeostasis of essential metals and exposure to xenobiotic metals disturb the cellular redox balance and signaling. We focus on recent literature regarding their transport, metabolism, and mechanisms of toxicity in neural systems. Delineating the specific mechanisms by which metals alter redox homeostasis is key to understand the pathological processes that convey chronic neuronal dysfunction in neurodegenerative and neurodevelopmental disorders. Antioxid. Redox Signal. 28, 1669-1703.

Biological mechanisms of non-linear dose-response for respirable mineral fibers.

PubMed

Cox, Louis Anthony Tony

2018-06-19

Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds. Copyright © 2018. Published by Elsevier Inc.

Fibrin Formation, Structure and Properties

PubMed Central

Weisel, John W.; Litvinov, Rustem I.

2017-01-01

Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules. The resulting half-staggered, double-stranded oligomers lengthen into protofibrils, which aggregate laterally to make fibers, which then branch to yield a three-dimensional network. Much is now known about the structural origins of clot mechanical properties, including changes in fiber orientation, stretching and buckling, and forced unfolding of molecular domains. Studies of congenital fibrinogen variants and post-translational modifications have increased our understanding of the structure and functions of fibrin(ogen). The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active proteolytic enzyme, plasmin, results in digestion of fibrin at specific lysine residues. In spite of a great increase in our knowledge of all these interconnected processes, much about the molecular mechanisms of the biological functions of fibrin(ogen) remains unknown, including some basic aspects of clotting, fibrinolysis, and molecular origins of fibrin mechanical properties. Even less is known concerning more complex (patho)physiological implications of fibrinogen and fibrin. PMID:28101869

Sorafenib enhances proteasome inhibitor-mediated cytotoxicity via inhibition of unfolded protein response and keratin phosphorylation

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

Honma, Yuichi; Harada, Masaru, E-mail: msrharada@med.uoeh-u.ac.jp

2013-08-15

Hepatocellular carcinoma (HCC) is highly resistant to conventional systemic therapies and prognosis for advanced HCC patients remains poor. Recent studies of the molecular mechanisms responsible for tumor initiation and progression have identified several potential molecular targets in HCC. Sorafenib is a multi-kinase inhibitor shown to have survival benefits in advanced HCC. It acts by inhibiting the serine/threonine kinases and the receptor type tyrosine kinases. In preclinical experiments sorafenib had anti-proliferative activity in hepatoma cells and it reduced tumor angiogenesis and increased apoptosis. Here, we demonstrate for the first time that the cytotoxic mechanisms of sorafenib include its inhibitory effects onmore » protein ubiquitination, unfolded protein response (UPR) and keratin phosphorylation in response to endoplasmic reticulum (ER) stress. Moreover, we show that combined treatment with sorafenib and proteasome inhibitors (PIs) synergistically induced a marked increase in cell death in hepatoma- and hepatocyte-derived cells. These observations may open the way to potentially interesting treatment combinations that may augment the effect of sorafenib, possibly including drugs that promote ER stress. Because sorafenib blocked the cellular defense mechanisms against hepatotoxic injury not only in hepatoma cells but also in hepatocyte-derived cells, we must be careful to avoid severe liver injury. -- Graphical abstract: Display Omitted -- Highlights: •We examined the cytotoxic mechanisms of sorafenib in hepatoma cells. •Sorafenib induces cell death via apoptotic and necrotic fashion. •Sorafenib inhibits protein ubiquitination and unfolded protein response. •Autophagy induced by sorafenib may affect its cytotoxicity. •Sorafenib inhibits keratin phosphorylation and cytoplasmic inclusion formation.« less

Effects of HfB2 and HfN Additions on the Microstructures and Mechanical Properties of TiB2-Based Ceramic Tool Materials

PubMed Central

An, Jing; Song, Jinpeng; Liang, Guoxing; Gao, Jiaojiao; Xie, Juncai; Cao, Lei; Wang, Shiying; Lv, Ming

2017-01-01

The effects of HfB2 and HfN additions on the microstructures and mechanical properties of TiB2-based ceramic tool materials were investigated. The results showed that the HfB2 additive not only can inhibit the TiB2 grain growth but can also change the morphology of some TiB2 grains from bigger polygons to smaller polygons or longer ovals that are advantageous for forming a relatively fine microstructure, and that the HfN additive had a tendency toward agglomeration. The improvement of flexural strength and Vickers hardness of the TiB2-HfB2 ceramics was due to the relatively fine microstructure; the decrease of fracture toughness was ascribed to the formation of a weaker grain boundary strength due to the brittle rim phase and the poor wettability between HfB2 and Ni. The decrease of the flexural strength and Vickers hardness of the TiB2-HfN ceramics was due to the increase of defects such as TiB2 coarse grains and HfN agglomeration; the enhancement of fracture toughness was mainly attributed to the decrease of the pore number and the increase of the rim phase and TiB2 coarse grains. The toughening mechanisms of TiB2-HfB2 ceramics mainly included crack bridging and transgranular fracture, while the toughening mechanisms of TiB2-HfN ceramics mainly included crack deflection, crack bridging, transgranular fracture, and the core-rim structure. PMID:28772821

Robotic Scaffolds for Tissue Engineering and Organ Growth

NASA Technical Reports Server (NTRS)

Stoica, Adrian

2011-01-01

The aim of tissue engineering (TE) is to restore tissue and organ functions with minimal host rejection. TE is seen as a future solution to solve the crisis of donor organs for transplant, which faces a shortage expected only to increase in the future. In this innovation, a flexible and configurable scaffold has been conceived that mechanically stresses cells that are seeded on it, stimulating them to increased growth. The influence of mechanical stress/ loading on cell growth has been observed on all forms of cells. For example, for cartilages, studies in animals, tissue explants, and engineered tissue scaffolds have all shown that cartilage cells (chondrocytes) modify their extracellular matrix in response to loading. The chondrocyte EMC production response to dynamics of the physical environment (in vivo cartilage development) illustrates a clear benefit (better growth) when stressed. It has been shown that static and dynamic compression regulates PRG4 biosynthesis by cartilage explants. Mechanical tissue stimulation is beneficial and (flexible) scaffolds with movable components, which are able to induce mechanical stimulation, offer advantages over the fixed, rigid scaffold design. In addition to improved cell growth from physical/mechanical stimulation, additional benefits include the ability to increase in size while preserving shape, or changing shape. By making scaffolds flexible, allowing relative movement between their components, adding sensing (e.g., for detecting response of cells to drug release and to mechanical actions), building controls for drug release and movement, and building even simple algorithms for mapping sensing to action, these structures can actually be made into biocompatible and biodegradable robots. Treating them as robots is a perspective shift that may offer advantages in the design and exploitation of these structures of the future.

A systematic review of the main mechanisms of heart failure disease management interventions.

PubMed

Clark, Alexander M; Wiens, Kelly S; Banner, Davina; Kryworuchko, Jennifer; Thirsk, Lorraine; McLean, Lianne; Currie, Kay

2016-05-01

To identify the main mechanisms of heart failure (HF) disease management programmes based in hospitals, homes or the community. Systematic review of qualitative and quantitative studies using realist synthesis. The search strategy incorporated general and specific terms relevant to the research question: HF, self-care and programmes/interventions for HF patients. To be included, papers had to be published in English after 1995 (due to changes in HF care over recent years) to May 2014 and contain specific data related to mechanisms of effect of HF programmes. 10 databases were searched; grey literature was located via Proquest Dissertations and Theses, Google and publications from organisations focused on HF or self-care. 33 studies (n=3355 participants, mean age: 65 years, 35% women) were identified (18 randomised controlled trials, three mixed methods studies, six pre-test post-test studies and six qualitative studies). The main mechanisms identified in the studies were associated with increased patient understanding of HF and its links to self-care, greater involvement of other people in this self-care, increased psychosocial well-being and support from health professionals to use technology. Future HF disease management programmes should seek to harness the main mechanisms through which programmes actually work to improve HF self-care and outcomes, rather than simply replicating components from other programmes. The most promising mechanisms to harness are associated with increased patient understanding and self-efficacy, involvement of other caregivers and health professionals and improving psychosocial well-being and technology use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

MYC Deregulation in Primary Human Cancers

PubMed Central

Kalkat, Manpreet; De Melo, Jason; Hickman, Katherine Ashley; Lourenco, Corey; Redel, Cornelia; Resetca, Diana; Tamachi, Aaliya; Tu, William B.; Penn, Linda Z.

2017-01-01

MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer. PMID:28587062

iTRAQ-Based Quantitative Proteomic Analysis of the Antimicrobial Mechanism of Peptide F1 against Escherichia coli.

PubMed

Miao, Jianyin; Chen, Feilong; Duan, Shan; Gao, Xiangyang; Liu, Guo; Chen, Yunjiao; Dixon, William; Xiao, Hang; Cao, Yong

2015-08-19

Antimicrobial peptides have received increasing attention in the agricultural and food industries due to their potential to control pathogens. However, to facilitate the development of novel peptide-based antimicrobial agents, details regarding the molecular mechanisms of these peptides need to be elucidated. The aim of this study was to investigate the antimicrobial mechanism of peptide F1, a bacteriocin found in Tibetan kefir, against Escherichia coli at protein levels using iTRAQ-based quantitative proteomic analysis. In response to treatment with peptide F1, 31 of the 280 identified proteins in E. coli showed alterations in their expression, including 10 down-regulated proteins and 21 up-regulated proteins. These 31 proteins all possess different molecular functions and are involved in different molecular pathways, as is evident in referencing the Kyoto Encyclopedia of Genes and Genomes pathways. Specifically, pathways that were significantly altered in E. coli in response to peptide F1 treatment include the tricarboxylic acid cycle, oxidative phosphorylation, glycerophospholipid metabolism, and the cell cycle-caulobacter pathways, which was also associated with inhibition of the cell growth, induction of morphological changes, and cell death. The results provide novel insights into the molecular mechanisms of antimicrobial peptides.

Application of Hydrogels in Heart Valve Tissue Engineering

PubMed Central

Zhang, Xing; Xu, Bin; Puperi, Daniel S.; Wu, Yan; West, Jennifer L.; Grande-Allen, K. Jane

2015-01-01

With an increasing number of patients requiring valve replacement, there is heightened interest in advancing heart valve tissue engineering (HVTE) to provide solutions to the many limitations of current surgical treatments. A variety of materials have been developed as scaffolds for HVTE including natural polymers, synthetic polymers, and decellularized valvular matrices. Among them, biocompatible hydrogels are generating growing interest. Natural hydrogels, such as collagen and fibrin, generally show good bioactivity, but poor mechanical durability. Synthetic hydrogels, on the other hand, have tunable mechanical properties; however, appropriate cell-matrix interactions are difficult to obtain. Moreover, hydrogels can be used as cell carriers when the cellular component is seeded into the polymer meshes or decellularized valve scaffolds. In this review, we discuss current research strategies for HVTE with an emphasis on hydrogel applications. The physicochemical properties and fabrication methods of these hydrogels, as well as their mechanical properties and bioactivities are described. Performance of some hydrogels including in vitro evaluation using bioreactors and in vivo tests in different animal models are also discussed. For future HVTE, it will be compelling to examine how hydrogels can be constructed from composite materials to replicate mechanical properties and mimic biological functions of the native heart valve. PMID:25955010

The role of blood flow distribution in the regulation of cerebral oxygen availability in fetal growth restriction.

PubMed

Luria, Oded; Bar, Jacob; Kovo, Michal; Malinger, Gustavo; Golan, Abraham; Barnea, Ofer

2012-04-01

Fetal growth restriction (FGR) elicits hemodynamic compensatory mechanisms in the fetal circulation. These mechanisms are complex and their effect on the cerebral oxygen availability is not fully understood. To quantify the contribution of each compensatory mechanism to the fetal cerebral oxygen availability, a mathematical model of the fetal circulation was developed. The model was based on cardiac-output distribution in the fetal circulation. The compensatory mechanisms of FGR were simulated and their effects on cerebral oxygen availability were analyzed. The mathematical analysis included the effects of cerebral vasodilation, placental resistance to blood flow, degree of blood shunting by the ductus venosus and the effect of maternal-originated placental insufficiency. The model indicated a unimodal dependency between placental blood flow and cerebral oxygen availability. Optimal cerebral oxygen availability was achieved when the placental blood flow was mildly reduced compared to the normal flow. This optimal ratio was found to increase as the hypoxic state of FGR worsens. The model indicated that cerebral oxygen availability is increasingly dependent on the cardiac output distribution as the fetus gains weight. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Shock Loading of Granular Ni/Al Composites. Part 1. Mechanics of Loading

DOE PAGES

Cherukara, Mathew J.; Germann, Timothy C.; Kober, Edward M.; ...

2014-10-16

We present molecular dynamics simulations of the thermomechanical response under shock loading of a granular material consisting of laminated Ni/Al grains. We observe two regimes: At low piston velocities (up ≲ 1km/s), the shock wave is diffuse, and the width of the shock front decreases with increasing piston velocity. Beyond a critical shock strength, however, the width remains relatively constant at approximately the mean grain radius. This change in behavior follows from an evolution of the mechanism of compaction with increasing insult strength. Furthermore, the mechanism evolves from plastic deformation-mediated pore collapse for relatively weak shocks, to solid extrusion andmore » fluid ejecta filling pores ahead of the shock front at intermediate strengths, and finally to atomic jetting into the pore for very strong shocks (up ≳ 2 km/s). High-energy fluid ejecta into pores leads to the formation of flow vorticity and can result in a large fraction of the input energy localizing into translational kinetic energy components including the formation of hot spots. This has implications for the mechanical mixing of Ni and Al in these reactive composites.« less

Genetics of Dyslipidemia and Ischemic Heart Disease.

PubMed

Sharma, Kavita; Baliga, Ragavendra R

2017-05-01

Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

Mechanical properties of steels with a microstructure of bainite/martensite and austenite islands

NASA Astrophysics Data System (ADS)

Syammach, Sami M.

Advanced high strength steels (AHSS) are continually being developed in order to reduce weight and improve safety for automotive applications. There is need for economic steels with improved strength and ductility combinations. These demands have led to research and development of third generation AHSS. Third generation AHSS include steel grades with a bainitic and tempered martensitic matrix with retained austenite islands. These steels may provide improved mechanical properties compared to first generation AHSS and should be more economical than second generation AHSS. There is a need to investigate these newer types of steels to determine their strength and formability properties. Understanding these bainitic and tempered martensitic steels is important because they likely can be produced using currently available production systems. If viable, these steels could be a positive step in the evolution of AHSS. The present work investigates the effect of the microstructure on the mechanical properties of steels with a microstructure of bainite, martensite, and retained austenite, so called TRIP aided bainitic ferrite (TBF) steels. The first step in this project was creating the desired microstructure. To create a microstructure of bainite, martensite, and austenite an interrupted austempering heat treatment was used. Varying the heat treatment times and temperatures produced microstructures of varying amounts of bainite, martensite, and austenite. Mechanical properties such as strength, ductility, strain hardening, and hole-expansion ratios were then evaluated for each heat treatment. Correlations between mechanical properties and microstructure were then evaluated. It was found that samples after each of the heat treatments exhibited strengths between 1050 MPa and 1350 MPa with total elongations varying from 8 pct to 16 pct. By increasing the bainite and austenite volume fraction the strength of the steel was found to decrease, but the ductility increased. Larger martensite volume fraction increased the strength of the steel. Strain hardening results showed that increasing the martensite volume fraction increased the strain hardening exponent while bainite decreased the strain hardening behavior. Austenite was found to slightly increase the strain hardening behavior. Hole-expansion tests showed hole expansion ratios ranging from 20 pct to 45 pct. Increasing the bainite volume fraction was found to increase the hole-expansion ratio. Increasing the martensite volume fraction was found to decrease the hole-expansion ratio. Overall, each of the heat treatments resulted in a steel with attractive properties, and the results showed how the microstructure of bainite, martensite, and austenite influences the mechanical properties of this type of steels.

The Role of Adaptation in Body Load-Regulating Mechanisms During Locomotion

NASA Technical Reports Server (NTRS)

Ruttley, Tara; Holt, Christopher; Mulavara, Ajitkumar; Bloomberg, Jacob

2010-01-01

Body loading is a fundamental parameter that modulates motor output during locomotion, and is especially important for controlling the generation of stepping patterns, dynamic balance, and termination of locomotion. Load receptors that regulate and control posture and stance in locomotion include the Golgi tendon organs and muscle spindles at the hip, knee, and ankle joints, and the Ruffini endings and the Pacinian corpuscles in the soles of the feet. Increased body weight support (BWS) during locomotion results in an immediate reorganization of locomotor control, such as a reduction in stance and double support duration and decreased hip, ankle, and knee angles during the gait cycle. Previous studies on the effect during exposure to increased BWS while walking showed a reduction in lower limb joint angles and gait cycle timing that represents a reorganization of locomotor control. Until now, no studies have investigated how locomotor control responds after a period of exposure to adaptive modification in the body load sensing system. The goal of this research was to determine the adaptive properties of body load-regulating mechanisms in locomotor control during locomotion. We hypothesized that body load-regulating mechanisms contribute to locomotor control, and adaptive changes in these load-regulating mechanisms require reorganization to maintain forward locomotion. Head-torso coordination, lower limb movement patterns, and gait cycle timing were evaluated before and after a 30-minute adaptation session during which subjects walked on a treadmill at 5.4 km/hr with 40% body weight support (BWS). Before and after the adaptation period, head-torso and lower limb 3D kinematic data were obtained while performing a goal directed task during locomotion with 0% BWS using a video-based motion analysis system, and gait cycle timing parameters were collected by foot switches positioned under the heel and toe of the subjects shoes. Subjects showed adaptive modification in the body load-regulating mechanisms that included increased head movement amplitude, increased knee and ankle flexion, and increased stance, stride, and double support time, with no change in the performance of the task with respect to that measured before exposure to BWS. These changes in locomotor control are opposite to that reported during 40% BWS exposure and indicative of an after-effect after removal of the adaptive stimulus. Therefore, it is evident that just 30 minutes of 40% BWS during locomotion was sufficient to induce adaptive modifications in the body load sensing systems that contribute to reorganization of sensory contributions to stable locomotor control.

Endocrine problems in children with Prader-Willi syndrome: special review on associated genetic aspects and early growth hormone treatment

PubMed Central

2012-01-01

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting) are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and postfertilization mitotic nondisjunction (Mit). Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH) receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS. PMID:22844316

Sociodemographic and cultural determinants of sleep deficiency: implications for cardiometabolic disease risk.

PubMed

Knutson, Kristen L

2013-02-01

Sleep is a biological imperative associated with cardiometabolic disease risk. As such, a thorough discussion of the sociocultural and demographic determinants of sleep is warranted, if not overdue. This paper begins with a brief review of the laboratory and epidemiologic evidence linking sleep deficiency, which includes insufficient sleep and poor sleep quality, with increased risk of chronic cardiometabolic diseases such as obesity, diabetes and hypertension. Identification of the determinants of sleep deficiency is the critical next step to understanding the role sleep plays in human variation in health and disease. Therefore, the majority of this paper describes the different biopsychosocial determinants of sleep, including age, gender, psychosocial factors (depression, stress and loneliness), socioeconomic position and race/ethnicity. In addition, because sleep duration is partly determined by behavior, it will be shaped by cultural values, beliefs and practices. Therefore, possible cultural differences that may impact sleep are discussed. If certain cultural, ethnic or social groups are more likely to experience sleep deficiency, then these differences in sleep could increase their risk of cardiometabolic diseases. Furthermore, if the mechanisms underlying the increased risk of sleep deficiency in certain populations can be identified, interventions could be developed to target these mechanisms, reduce sleep differences and potentially reduce cardiometabolic disease risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

Perspectives on fear generalization and its implications for emotional disorders.

PubMed

Jasnow, Aaron M; Lynch, Joseph F; Gilman, T Lee; Riccio, David C

2017-03-01

Although generalization to conditioned stimuli is not a new phenomenon, renewed interest in understanding its biological underpinning has stemmed from its association with a number of anxiety disorders. Generalization as it relates to fear processing is a temporally dynamic process in which animals, including humans, display fear in response to similar yet distinct cues or contexts as the time between training and testing increases. This Review surveys the literature on contextual fear generalization and its relation to several views of memory, including systems consolidation, forgetting, and transformation hypothesis, which differentially implicate roles of the hippocampus and neocortex in memory consolidation and retrieval. We discuss recent evidence on the neurobiological mechanisms contributing to the increase in fear generalization over time and how generalized responding may be modulated by acquisition, consolidation, and retrieval mechanisms. Whereas clinical perspectives of generalization emphasize a lack of fear inhibition to CS - cues or fear toward intermediate CS cues, the time-dependent nature of generalization and its relation to traditional views on memory consolidation and retrieval are often overlooked. Understanding the time-dependent increase in fear generalization has important implications not only for understanding how generalization contributes to anxiety disorders but also for understanding basic long-term memory function. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparative Proteomics Reveals Timely Transport into Cilia of Regulators or Effectors as a Mechanism Underlying Ciliary Disassembly.

PubMed

Wang, Limei; Gu, Lixiao; Meng, Dan; Wu, Qiong; Deng, Haiteng; Pan, Junmin

2017-07-07

Primary cilia are assembled and disassembled during cell cycle progression. During ciliary disassembly, ciliary axonemal microtubules (MTs) are depolymerized accompanied by extensive posttranslational protein modifications of ciliary proteins including protein phosphorylation, methylation, and ubiquitination. These events are hypothesized to involve transport of effectors or regulators into cilia at the time of ciliary disassembly from the cell body. To prove this hypothesis and identify new proteins involved in ciliary disassembly, we analyzed disassembling flagella in Chlamydomonas using comparative proteomics with TMT labeling. Ninety-one proteins were found to increase more than 1.4-fold in four replicates. The proteins of the IFT machinery not only increase but also exhibit stoichiometric changes. The other proteins that increase include signaling molecules, chaperones, and proteins involved in microtubule dynamics or stability. In particular, we have identified a ciliopathy protein C21orf2, the AAA-ATPase CDC48, that is involved in segregating polypeptides from large assemblies or cellular structures, FAP203 and FAP236, which are homologous to stabilizers of axonemal microtubules. Our data demonstrate that ciliary transport of effectors or regulators is one of the mechanisms underlying ciliary disassembly. Further characterization of the proteins identified will provide new insights into our understanding of ciliary disassembly and likely ciliopathy.

An update on cannabis research.

PubMed

Husain, S; Khan, I

1985-01-01

A symposium of over 125 scientists, held in August 1984 at the campus of Oxford University, considered the latest developments concerning cannabis research. Evidence on the mode of tetrahydrocannabinol action on the central nervous system indicates that acetylcholine turnover in the hippocampus through a GABA-ergic mechanism is of major importance, though the role of the dopaminergic or serotoninergic mechanism and involvement of prostaglandins and c-AMP is not ruled out. The use of cannabis causes prominent and predictable effects on the heart, including increased work-load, increased plasma volume and postural hypotension, which could impose threats to the cannabis users with hypertension, cerebrovascular disease or coronary arteriosclerosis. Cannabis or tetrahydrocannabinol has damaging effects on the endocrine functions in both male and female of all animal species tested. Among possible mechanisms of action, it is suggested that tetrahydrocannabinol disrupts gonadal functions by depriving the testicular cells of their energy reserves by inhibition of cellular energetics, and that it stimulates androgen-binding protein secretion, which may account for oligospermia seen in chronic cannabis smokers. In addition to these direct effects on gonads, tetrahydrocannabinol interferes with hormonal secretions from the pituitary, including luteinizing hormones, follicle-stimulating hormones and prolactin. Research findings indicate that maternal and paternal exposure to cannabinoids can influence developmental and reproductive functions in the offspring, but it is difficult to separate possible teratogenic effects from subsequent gametotoxic and mutagenic potentials of cannabinoids.

Transactivation of ErbB receptors by leptin in the cardiovascular system: mechanisms, consequences and target for therapy.

PubMed

Bełtowski, Jerzy; Jazmroz-Wiśniewska, Anna

2014-01-01

Many experimental and clinical studies have demonstrated that elevated leptin concentration in patients with obesity/metabolic syndrome contributes to the pathogenesis of cardiovascular disorders including arterial hypertension, atherosclerosis, restenosis after coronary angioplasty and myocardial hypertrophy. Receptor tyrosine kinases belonging to the ErbB family, especially ErbB1 (epidermal growth factor receptor) and ErbB2 are abundantly expressed in the blood vessels and the heart. EGFR is activated not only by its multiple peptide ligands but also by many other factors including angiotensin II, endothelin-1, norepinephrine, thrombin and prorenin; the phenomenon referred to as "transactivation". Augmented EGFR signaling contributes to abnormalities of vascular tone and renal sodium handling as well as vascular remodeling and myocardial hypertrophy through various intracellular mechanisms, in particular extracellular signal-regulated kinases (ERK) and phosphoinositide 3-kinase (PI3K). Recent experimental studies indicate that chronically elevated leptin transactivates the EGFR through the mechanisms requiring reactive oxygen species and cytosolic tyrosine kinase, c-Src. In addition, hyperleptinemia increases ErbB2 activity in the arterial wall. Stimulation of EGFR and ErbB2 downstream signaling pathways such as ERK and PI3K in the vascular wall and the kidney may contribute to the increase in vascular tone, enhanced tubular sodium reabsorption as well as vascular and renal lesions in hyperleptinemic obese subjects.

Carbonic Anhydrase-8 Regulates Inflammatory Pain by Inhibiting the ITPR1-Cytosolic Free Calcium Pathway

PubMed Central

Zhuang, Gerald Z.; Keeler, Benjamin; Grant, Jeff; Bianchi, Laura; Fu, Eugene S.; Zhang, Yan Ping; Erasso, Diana M.; Cui, Jian-Guo; Wiltshire, Tim; Li, Qiongzhen; Hao, Shuanglin; Sarantopoulos, Konstantinos D.; Candiotti, Keith; Wishnek, Sarah M.; Smith, Shad B.; Maixner, William; Diatchenko, Luda; Martin, Eden R.; Levitt, Roy C.

2015-01-01

Calcium dysregulation is causally linked with various forms of neuropathology including seizure disorders, multiple sclerosis, Huntington’s disease, Alzheimer’s, spinal cerebellar ataxia (SCA) and chronic pain. Carbonic anhydrase-8 (Car8) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates intracellular calcium release fundamental to critical cellular functions including neuronal excitability, neurite outgrowth, neurotransmitter release, mitochondrial energy production and cell fate. In this report we test the hypothesis that Car8 regulation of ITPR1 and cytoplasmic free calcium release is critical to nociception and pain behaviors. We show Car8 null mutant mice (MT) exhibit mechanical allodynia and thermal hyperalgesia. Dorsal root ganglia (DRG) from MT also demonstrate increased steady-state ITPR1 phosphorylation (pITPR1) and cytoplasmic free calcium release. Overexpression of Car8 wildtype protein in MT nociceptors complements Car8 deficiency, down regulates pITPR1 and abolishes thermal and mechanical hypersensitivity. We also show that Car8 nociceptor overexpression alleviates chronic inflammatory pain. Finally, inflammation results in downregulation of DRG Car8 that is associated with increased pITPR1 expression relative to ITPR1, suggesting a possible mechanism of acute hypersensitivity. Our findings indicate Car8 regulates the ITPR1-cytosolic free calcium pathway that is critical to nociception, inflammatory pain and possibly other neuropathological states. Car8 and ITPR1 represent new therapeutic targets for chronic pain. PMID:25734498

Coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis.

PubMed

Carlström, Mattias; Larsson, Susanna C

2018-06-01

Type 2 diabetes (T2D) is a major health problem worldwide that is associated with increased morbidity and mortality. There is increased interest in the value of different nutrition-based strategies for preventing the development of T2D. This review aims to cover current knowledge regarding the effects of coffee consumption on development of T2D or modulation of adverse complications. A meta-analysis on coffee consumption and the risk of T2D was conducted. Moreover, bioactive components in coffee, polymorphisms, and potential underlying mechanism(s) in relation to T2D and adverse complications are discussed. PubMed was searched up to December 1, 2017, and prospective cohort and nested case-control studies of the association between coffee consumption and T2D risk were selected. Two investigators independently extracted data from included studies. A total of 30 prospective studies with 1 185 210 participants and 53 018 incident T2D cases were included in the meta-analysis. The pooled relative risk (RR) was 0.71 (95% confidence interval [CI], 0.67-0.76) for the highest category of coffee consumption (median consumption, 5 cups/d) vs the lowest category (median consumption, 0 cups/d). The risk of T2D decreased by 6% (RR = 0.94; 95%CI, 0.93-0.95) for each cup-per-day increase in coffee consumption. Results were similar for caffeinated coffee consumption (per additional cup of coffee per day: RR = 0.93; 95%CI, 0.90-0.96) and decaffeinated coffee consumption (corresponding RR = 0.94; 95%CI, 0.90-0.98). Available evidence indicates that coffee consumption is inversely associated with risk of T2D. Possible mechanisms behind this association include thermogenic, antioxidative, and anti-inflammatory effects; modulation of adenosine receptor signaling; and microbiome content and diversity.

Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies.

PubMed

Planchart, Antonio; Green, Adrian; Hoyo, Cathrine; Mattingly, Carolyn J

2018-03-01

Metabolic syndrome (MS) describes the co-occurrence of conditions that increase one's risk for heart disease and other disorders such as diabetes and stroke. The worldwide increase in the prevalence of MS cannot be fully explained by lifestyle factors such as sedentary behavior and caloric intake alone. Environmental exposures, such as heavy metals, have been implicated, but results are conflicting and possible mechanisms remain unclear. To assess recent progress in determining a possible role between heavy metal exposure and MS, we reviewed epidemiological and model system data for cadmium (Cd), lead (Pb), and mercury (Hg) from the last decade. Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model system studies are needed to better assess potential causal links between heavy metal exposure and MS.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

PubMed

Kelly, Margaret; Gillies, Donna; Todd, David A; Lockwood, Catherine

2010-04-14

Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HME) are the most commonly used types of artificial humidification in this situation. To determine whether HHs or HMEs are more effective in preventing mortality and other complications in people who are mechanically ventilated. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials (RCTs). We included RCTs comparing heat and moisture exchangers (HMEs) to heated humidifiers (HHs) in mechanically ventilated adults and children. We included randomized crossover studies. We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analysed for individual outcomes. We included 33 trials with 2833 participants, 25 studies were parallel group design (n = 2710) and eight crossover design (n = 123). Only three included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HME may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the paediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

PubMed

Kelly, Margaret; Gillies, Donna; Todd, David A; Lockwood, Catherine

2010-10-01

Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HMEs) are the most commonly used types of artificial humidification in this situation. To determine whether HHs or HMES are more effective in preventing mortality and other complications in people who are mechanically ventilated. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials. We included randomized controlled trials comparing HMEs to HHs in mechanically ventilated adults and children. We included randomized crossover studies. We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analyzed for individual outcomes. We included 33 trials with 2833 participants; 25 studies were parallel group design (n = 2710) and 8 crossover design (n = 123). Only 3 included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HMEs may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the pediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

A Review of the Mechanical Properties of Concrete Containing Biofillers

NASA Astrophysics Data System (ADS)

Ezdiani Mohamad, Mazizah; Mahmood, Ali A.; Min, Alicia Yik Yee; Khalid, Nur Hafizah A.

2016-11-01

Sustainable construction is a rapidly increasing research area. Investigators of all backgrounds are using industrial and agro wastes to replace Portland cement in concrete to reduce greenhouse emissions and the corresponding decline in general health. Many types of wastes have been used as cement replacements in concrete including: fly ash, slag and rice husk ash in addition to others. This study investigates the possibility of producing a sustainable approach to construction through the partial replacement of concrete using biofillers. This will be achieved by studying the physical and mechanical properties of two widely available biological wastes in Malaysia; eggshell and palm oil fuel ash (POFA). The mechanical properties tests that were studied and compared are the compression, tensile and flexural tests.

Zinc finger proteins in cancer progression.

PubMed

Jen, Jayu; Wang, Yi-Ching

2016-07-13

Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression.

Plasma Cytokine Levels in Astronauts Before and after Spaceflight

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

2008-01-01

Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

Simulations of inorganic-bioorganic interfaces to discover new materials: insights, comparisons to experiment, challenges, and opportunities.

PubMed

Heinz, Hendrik; Ramezani-Dakhel, Hadi

2016-01-21

Natural and man-made materials often rely on functional interfaces between inorganic and organic compounds. Examples include skeletal tissues and biominerals, drug delivery systems, catalysts, sensors, separation media, energy conversion devices, and polymer nanocomposites. Current laboratory techniques are limited to monitor and manipulate assembly on the 1 to 100 nm scale, time-consuming, and costly. Computational methods have become increasingly reliable to understand materials assembly and performance. This review explores the merit of simulations in comparison to experiment at the 1 to 100 nm scale, including connections to smaller length scales of quantum mechanics and larger length scales of coarse-grain models. First, current simulation methods, advances in the understanding of chemical bonding, in the development of force fields, and in the development of chemically realistic models are described. Then, the recognition mechanisms of biomolecules on nanostructured metals, semimetals, oxides, phosphates, carbonates, sulfides, and other inorganic materials are explained, including extensive comparisons between modeling and laboratory measurements. Depending on the substrate, the role of soft epitaxial binding mechanisms, ion pairing, hydrogen bonds, hydrophobic interactions, and conformation effects is described. Applications of the knowledge from simulation to predict binding of ligands and drug molecules to the inorganic surfaces, crystal growth and shape development, catalyst performance, as well as electrical properties at interfaces are examined. The quality of estimates from molecular dynamics and Monte Carlo simulations is validated in comparison to measurements and design rules described where available. The review further describes applications of simulation methods to polymer composite materials, surface modification of nanofillers, and interfacial interactions in building materials. The complexity of functional multiphase materials creates opportunities to further develop accurate force fields, including reactive force fields, and chemically realistic surface models, to enable materials discovery at a million times lower computational cost compared to quantum mechanical methods. The impact of modeling and simulation could further be increased by the advancement of a uniform simulation platform for organic and inorganic compounds across the periodic table and new simulation methods to evaluate system performance in silico.

From favours to entitlements: community voice and action and health service quality in Zambia

PubMed Central

Topp, Stephanie M.; Ngulube, Moses

2017-01-01

Abstract Social accountability is increasingly invoked as a way of improving health services. This article presents a theory-driven qualitative study of the context, mechanisms and outcomes of a social accountability program, Citizen Voice and Action (CVA), implemented by World Vision (WV) in Zambia. Primary data were collected between November 2013 and January 2014. It included in-depth interviews and focus group discussions with program stakeholders. Secondary data were used iteratively—to inform the process for primary data collection, to guide primary data analysis and to contextualize findings from the primary data. CVA positively impacted the state, society, state–society relations and development coordination at the local level. Specifically, sustained improvements in some aspects of health system responsiveness, empowered citizens, the improved provision of public goods (health services) and increased consensus on development issues appeared to flow from CVA. The central challenge described by interviewees and FGD participants was the inability of CVA to address problems that required central level input. The mechanisms that generated these outcomes included productive state–society communication, enhanced trust, and state–society co-production of priorities and the provision of services. These mechanisms were activated in the context of existing structures for state–society interaction, willing political leaders, buy-in by traditional leaders, and WV’s strong reputation and access to resources. Prospective observational research in multiple contexts would shed more light on the context, mechanisms and outcomes of CVA programs. In addition to findings that are intuitive and well supported in the literature we identified new areas that are promising areas for future research. These include (1) the context of organizational reputation by the organization(s) spearheading social accountability efforts; (2) the potential relationship between social accountability efforts and making ambitious national programs operational at the frontlines of the health system and (3) the feasibility of scale up for certain types of local level responsiveness. PMID:28369410

The Molecular Mechanisms of the Antibacterial Effect of Picosecond Laser Generated Silver Nanoparticles and Their Toxicity to Human Cells

PubMed Central

Korshed, Peri; Li, Lin; Liu, Zhu; Wang, Tao

2016-01-01

Silver nanoparticles (Ag NPs) are known to have antibacterial properties. They are commonly produced by chemical synthesis which involves the use of harmful reducing agents. Contras, the laser technique is able to generate high-purity Ag NPs in water with specified surface charge characteristics. In the past, the molecular mechanisms contributing to the bactericidal effects of Ag NPs have been investigated extensively, but little is known of the antibacterial and toxic effects and mechanisms involved in laser-generated Ag NPs. In the current study Ag NPs were generated by picosecond laser ablation. Their antibacterial activity was determined on the gram-negative bacteria E. coli and Pseudomonas aeruginosa, and the gram positive bacteria Staphylococcus aureus including the methicillin resistant strain MRSA. Results showed that the laser generated Ag NPs exhibited strong dose-dependent antibacterial activity against all the three bacterial strains tested. Using E.coli as a model system, the laser Ag NPs treatment induced significantly high levels of reactive oxygen species (ROS). These ROS did not include detectable hydroxyl radicals, suggesting for the first time the selective ROS induction in bacterial cells by laser generated Ag NPs. The increased ROS was accompanied by significantly reduced cellular glutathione, and increased lipid peroxidation and permeability, suggesting ROS related bacterial cell damage. The laser generated Ag NPs exhibited low toxicity (within 72 hours) to five types of human cells although a weak significant decrease in cell survival was observed for endothelial cells and the lung cells. We conclude that picosecond laser generated Ag NPs have a broad spectrum of antibacterial effects against microbes including MRSA with minimal human cell toxicity. The oxidative stress is likely the key mechanism underlying the bactericidal effect, which leads to lipid peroxidation, depletion of glutathione, DNA damages and eventual disintegration of the cell membrane. PMID:27575485

The Molecular Mechanisms of the Antibacterial Effect of Picosecond Laser Generated Silver Nanoparticles and Their Toxicity to Human Cells.

PubMed

Korshed, Peri; Li, Lin; Liu, Zhu; Wang, Tao

2016-01-01

Silver nanoparticles (Ag NPs) are known to have antibacterial properties. They are commonly produced by chemical synthesis which involves the use of harmful reducing agents. Contras, the laser technique is able to generate high-purity Ag NPs in water with specified surface charge characteristics. In the past, the molecular mechanisms contributing to the bactericidal effects of Ag NPs have been investigated extensively, but little is known of the antibacterial and toxic effects and mechanisms involved in laser-generated Ag NPs. In the current study Ag NPs were generated by picosecond laser ablation. Their antibacterial activity was determined on the gram-negative bacteria E. coli and Pseudomonas aeruginosa, and the gram positive bacteria Staphylococcus aureus including the methicillin resistant strain MRSA. Results showed that the laser generated Ag NPs exhibited strong dose-dependent antibacterial activity against all the three bacterial strains tested. Using E.coli as a model system, the laser Ag NPs treatment induced significantly high levels of reactive oxygen species (ROS). These ROS did not include detectable hydroxyl radicals, suggesting for the first time the selective ROS induction in bacterial cells by laser generated Ag NPs. The increased ROS was accompanied by significantly reduced cellular glutathione, and increased lipid peroxidation and permeability, suggesting ROS related bacterial cell damage. The laser generated Ag NPs exhibited low toxicity (within 72 hours) to five types of human cells although a weak significant decrease in cell survival was observed for endothelial cells and the lung cells. We conclude that picosecond laser generated Ag NPs have a broad spectrum of antibacterial effects against microbes including MRSA with minimal human cell toxicity. The oxidative stress is likely the key mechanism underlying the bactericidal effect, which leads to lipid peroxidation, depletion of glutathione, DNA damages and eventual disintegration of the cell membrane.

Tracking implementation and (un)intended consequences: a process evaluation of an innovative peripheral health facility financing mechanism in Kenya

PubMed Central

Waweru, Evelyn; Goodman, Catherine; Kedenge, Sarah; Tsofa, Benjamin; Molyneux, Sassy

2016-01-01

In many African countries, user fees have failed to achieve intended access and quality of care improvements. Subsequent user fee reduction or elimination policies have often been poorly planned, without alternative sources of income for facilities. We describe early implementation of an innovative national health financing intervention in Kenya; the health sector services fund (HSSF). In HSSF, central funds are credited directly into a facility’s bank account quarterly, and facility funds are managed by health facility management committees (HFMCs) including community representatives. HSSF is therefore a finance mechanism with potential to increase access to funds for peripheral facilities, support user fee reduction and improve equity in access. We conducted a process evaluation of HSSF implementation based on a theory of change underpinning the intervention. Methods included interviews at national, district and facility levels, facility record reviews, a structured exit survey and a document review. We found impressive achievements: HSSF funds were reaching facilities; funds were being overseen and used in a way that strengthened transparency and community involvement; and health workers’ motivation and patient satisfaction improved. Challenges or unintended outcomes included: complex and centralized accounting requirements undermining efficiency; interactions between HSSF and user fees leading to difficulties in accessing crucial user fee funds; and some relationship problems between key players. Although user fees charged had not increased, national reduction policies were still not being adhered to. Finance mechanisms can have a strong positive impact on peripheral facilities, and HFMCs can play a valuable role in managing facilities. Although fiduciary oversight is essential, mechanisms should allow for local decision-making and ensure that unmanageable paperwork is avoided. There are also limits to what can be achieved with relatively small funds in contexts of enormous need. Process evaluations tracking (un)intended consequences of interventions can contribute to regional financing and decentralization debates. PMID:25920355

From favours to entitlements: community voice and action and health service quality in Zambia.

PubMed

Schaaf, Marta; Topp, Stephanie M; Ngulube, Moses

2017-07-01

Social accountability is increasingly invoked as a way of improving health services. This article presents a theory-driven qualitative study of the context, mechanisms and outcomes of a social accountability program, Citizen Voice and Action (CVA), implemented by World Vision (WV) in Zambia. Primary data were collected between November 2013 and January 2014. It included in-depth interviews and focus group discussions with program stakeholders. Secondary data were used iteratively-to inform the process for primary data collection, to guide primary data analysis and to contextualize findings from the primary data. CVA positively impacted the state, society, state-society relations and development coordination at the local level. Specifically, sustained improvements in some aspects of health system responsiveness, empowered citizens, the improved provision of public goods (health services) and increased consensus on development issues appeared to flow from CVA. The central challenge described by interviewees and FGD participants was the inability of CVA to address problems that required central level input. The mechanisms that generated these outcomes included productive state-society communication, enhanced trust, and state-society co-production of priorities and the provision of services. These mechanisms were activated in the context of existing structures for state-society interaction, willing political leaders, buy-in by traditional leaders, and WV's strong reputation and access to resources. Prospective observational research in multiple contexts would shed more light on the context, mechanisms and outcomes of CVA programs. In addition to findings that are intuitive and well supported in the literature we identified new areas that are promising areas for future research. These include (1) the context of organizational reputation by the organization(s) spearheading social accountability efforts; (2) the potential relationship between social accountability efforts and making ambitious national programs operational at the frontlines of the health system and (3) the feasibility of scale up for certain types of local level responsiveness. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Tracking implementation and (un)intended consequences: a process evaluation of an innovative peripheral health facility financing mechanism in Kenya.

PubMed

Waweru, Evelyn; Goodman, Catherine; Kedenge, Sarah; Tsofa, Benjamin; Molyneux, Sassy

2016-03-01

In many African countries, user fees have failed to achieve intended access and quality of care improvements. Subsequent user fee reduction or elimination policies have often been poorly planned, without alternative sources of income for facilities. We describe early implementation of an innovative national health financing intervention in Kenya; the health sector services fund (HSSF). In HSSF, central funds are credited directly into a facility's bank account quarterly, and facility funds are managed by health facility management committees (HFMCs) including community representatives. HSSF is therefore a finance mechanism with potential to increase access to funds for peripheral facilities, support user fee reduction and improve equity in access. We conducted a process evaluation of HSSF implementation based on a theory of change underpinning the intervention. Methods included interviews at national, district and facility levels, facility record reviews, a structured exit survey and a document review. We found impressive achievements: HSSF funds were reaching facilities; funds were being overseen and used in a way that strengthened transparency and community involvement; and health workers' motivation and patient satisfaction improved. Challenges or unintended outcomes included: complex and centralized accounting requirements undermining efficiency; interactions between HSSF and user fees leading to difficulties in accessing crucial user fee funds; and some relationship problems between key players. Although user fees charged had not increased, national reduction policies were still not being adhered to. Finance mechanisms can have a strong positive impact on peripheral facilities, and HFMCs can play a valuable role in managing facilities. Although fiduciary oversight is essential, mechanisms should allow for local decision-making and ensure that unmanageable paperwork is avoided. There are also limits to what can be achieved with relatively small funds in contexts of enormous need. Process evaluations tracking (un)intended consequences of interventions can contribute to regional financing and decentralization debates. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

A realist evaluation of patients’ decisions to deprescribe in the EMPOWER trial

PubMed Central

Martin, Philippe; Tannenbaum, Cara

2017-01-01

Background and objectives Successful mechanisms for engaging patients in the deprescribing process remain unknown but may include: (1) triggering motivation to deprescribe by increasing patients’ knowledge and concern about medications; (2) building capacity to taper by augmenting self-efficacy and (3) creating opportunities to discuss and receive support for deprescribing from a healthcare provider. We tested these mechanisms during theEliminating Medications through Patient Ownership of End Results (EMPOWER) () trial and investigated the contexts that led to positive and negative deprescribing outcomes. Design A realist evaluation using a sequential mixed methods approach, conducted alongside the EMPOWER randomised clinical trial. Setting Community, Quebec, Canada. Participants 261 older chronic benzodiazepine consumers, who received the EMPOWER intervention and had complete 6-month follow-up data. Intervention Mailed deprescribing brochure on benzodiazepines. Measurements Motivation (intent to discuss deprescribing; change in knowledge test score; change in beliefs about the risk–benefits of benzodiazepines, measured with the Beliefs about Medicines Questionnaire), capacity (self-efficacy for tapering) and opportunity (support from a physician or pharmacist). Results The intervention triggered the motivation to deprescribe among 167 (n=64%) participants (mean age 74.6 years±6.3, 72% women), demonstrated by improved knowledge (risk difference, 58.50% (95% CI 46.98% to 67.44%)) and increased concern about taking benzodiazepines (risk difference, 67.67% (95% CI 57.36% to 74.91%)). Those who attempted to taper exhibited increased self-efficacy (risk difference, 56.90% (95% CI 45.41% to 65.77%)). Contexts where the deprescribing mechanisms failed included lack of support from a healthcare provider, a focus on short-term quality of life, intolerance to withdrawal symptoms and perceived poor health. Conclusion Deprescribing mechanisms that target patient motivation and capacity to deprescribe yield successful outcomes in contexts where healthcare providers are supportive, and patients do not have internal competing desires to remain on drug therapy. Trial registration number ClinicalTrials.gov: NCT01148186. PMID:28473524

Prevention of non-contact anterior cruciate ligament injuries in soccer players. Part 1: Mechanisms of injury and underlying risk factors.

PubMed

Alentorn-Geli, Eduard; Myer, Gregory D; Silvers, Holly J; Samitier, Gonzalo; Romero, Daniel; Lázaro-Haro, Cristina; Cugat, Ramón

2009-07-01

Soccer is the most commonly played sport in the world, with an estimated 265 million active soccer players by 2006. Inherent to this sport is the higher risk of injury to the anterior cruciate ligament (ACL) relative to other sports. ACL injury causes the most time lost from competition in soccer which has influenced a strong research focus to determine the risk factors for injury. This research emphasis has afforded a rapid influx of literature defining potential modifiable and non-modifiable risk factors that increase the risk of injury. The purpose of the current review is to sequence the most recent literature that reports potential mechanisms and risk factors for non-contact ACL injury in soccer players. Most ACL tears in soccer players are non-contact in nature. Common playing situations precluding a non-contact ACL injury include: change of direction or cutting maneuvers combined with deceleration, landing from a jump in or near full extension, and pivoting with knee near full extension and a planted foot. The most common non-contact ACL injury mechanism include a deceleration task with high knee internal extension torque (with or without perturbation) combined with dynamic valgus rotation with the body weight shifted over the injured leg and the plantar surface of the foot fixed flat on the playing surface. Potential extrinsic non-contact ACL injury risk factors include: dry weather and surface, and artificial surface instead of natural grass. Commonly purported intrinsic risk factors include: generalized and specific knee joint laxity, small and narrow intercondylar notch width (ratio of notch width to the diameter and cross sectional area of the ACL), pre-ovulatory phase of menstrual cycle in females not using oral contraceptives, decreased relative (to quadriceps) hamstring strength and recruitment, muscular fatigue by altering neuromuscular control, decreased "core" strength and proprioception, low trunk, hip, and knee flexion angles, and high dorsiflexion of the ankle when performing sport tasks, lateral trunk displacement and hip adduction combined with increased knee abduction moments (dynamic knee valgus), and increased hip internal rotation and tibial external rotation with or without foot pronation. The identified mechanisms and risk factors for non-contact ACL injuries have been mainly studied in female soccer players; thus, further research in male players is warranted. Non-contact ACL injuries in soccer players likely has a multi-factorial etiology. The identification of those athletes at increased risk may be a salient first step before designing and implementing specific pre-season and in-season training programs aimed to modify the identified risk factors and to decrease ACL injury rates. Current evidence indicates that this crucial step to prevent ACL injury is the only option to effectively prevent the sequelae of osteoarthritis associated with this traumatic injury.

The use of systemic antibiotics in the treatment of refractory periodontitis: A systematic review.

PubMed

Santos, Rayane S; Macedo, Rodrigo F; Souza, Emmanuel A; Soares, Renata S C; Feitosa, Daniela S; Sarmento, Carlos F M

2016-07-01

The goal in treating refractory periodontitis (RP) is to arrest or slow disease progression, which usually has included the use of systemic antibiotics adjunct to conventional mechanical debridement. The aim of this systematic review was to evaluate the evidence that the association of systemic antibiotics with conventional mechanical debridement increases the efficacy of periodontal therapy in the treatment of RP. The authors searched for studies in PubMed MEDLINE, Cochrane Central Register of Controlled Trials, Thomson Reuters Web of Science, Scopus, Latin American and Caribbean Center on Health Sciences Information, and Scientific Electronic Library Online electronic databases by using selected key words from the earliest records up through October 31, 2014. Only clinical intervention studies in which investigators compared the treatment of participants with RP with either mechanical debridement alone or associated with systemic antibiotics were eligible for selection. Two authors independently assessed the risk of bias of each selected study. The authors identified 13 articles and included 6 of them. Investigators in all studies reported greater reductions in probing depth or in loss of clinical attachment level after adjunct systemic antibiotic therapy when compared with mechanical debridement alone. Antibiotics tested included metronidazole, clindamycin, tetracycline hydrochloride, amoxicillin, and amoxicillin and potassium clavulanate. Five studies presented a high risk of bias, and 1 study presented an unclear risk. The overall quality of the evidence does not allow the conclusion that adjunct systemic antibiotics are of additional benefit to conventional mechanical debridement alone. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Understanding the negative effects of depressive symptoms in patients with ESRD receiving hemodialysis.

PubMed

Khalil, Amani A; Lennie, Terry A; Frazier, Susan K

2010-01-01

Depressive symptoms are the most common psychological complication among patients with ESRD. Although depressive symptoms are a risk factor for increased morbidity and mortality, little is known about the mechanisms responsible for this association. Two pathways are described. The biological pathway involves interrelationships among depressive symptoms, inflammation, malnutrition, and atherosclerosis. The behavioral pathway includes the effects of depressive symptoms on dietary adherence. Recommendations include attention to therapeutic interventions that would influence these pathways to improve outcomes.

Validation of predicted patellofemoral mechanics in a finite element model of the healthy and cruciate-deficient knee.

PubMed

Ali, Azhar A; Shalhoub, Sami S; Cyr, Adam J; Fitzpatrick, Clare K; Maletsky, Lorin P; Rullkoetter, Paul J; Shelburne, Kevin B

2016-01-25

Healthy patellofemoral (PF) joint mechanics are critical to optimal function of the knee joint. Patellar maltracking may lead to large joint reaction loads and high stresses on the articular cartilage, increasing the risk of cartilage wear and the onset of osteoarthritis. While the mechanical sources of PF joint dysfunction are not well understood, links have been established between PF tracking and abnormal kinematics of the tibiofemoral (TF) joint, specifically following cruciate ligament injury and repair. The objective of this study was to create a validated finite element (FE) representation of the PF joint in order to predict PF kinematics and quadriceps force across healthy and pathological specimens. Measurements from a series of dynamic in-vitro cadaveric experiments were used to develop finite element models of the knee for three specimens. Specimens were loaded under intact, ACL-resected and both ACL and PCL-resected conditions. Finite element models of each specimen were constructed and calibrated to the outputs of the intact knee condition, and subsequently used to predict PF kinematics, contact mechanics, quadriceps force, patellar tendon moment arm and patellar tendon angle of the cruciate resected conditions. Model results for the intact and cruciate resected trials successfully matched experimental kinematics (avg. RMSE 4.0°, 3.1mm) and peak quadriceps forces (avg. difference 5.6%). Cruciate resections demonstrated either increased patellar tendon loads or increased joint reaction forces. The current study advances the standard for evaluation of PF mechanics through direct validation of cruciate-resected conditions including specimen-specific representations of PF anatomy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rare case-series of electrocautery burn following off-pump coronary artery bypass grafting

PubMed Central

Sabzi, Feridoun; Niazi, Mojtaba; Ahmadi, Alireza

2014-01-01

Abstract: With an increasing number of off-pump coronary artery surgery procedures in high-risk patients with coagulopathy, including renal failure, hepatic failure and anticoagulant drug-using patients, the frequency of related complications such as repeated exploration for bleeding is also increasing. The associated co-morbidity and repeated use of electrocautery in postoperative bleeding leaves patients susceptible to electrocautery ulcers. In this case series, rare cases of cautery burn with unique causative mechanisms are described. PMID:23669602

Oxygen-Free Welding Contact Tips

NASA Technical Reports Server (NTRS)

Pike, James F.

1993-01-01

Contact tips for gas/metal arc welding (GMAW) fabricated from oxygen-free copper. Prototype tips tested in robotic welding, for which application intended. Reduces electrical erosion, increases electrical conductivity, and reduces mechanical wear. Productivity of robotic welding increases while time during welding interrupted for removal and replacement of contact tips minimal. Improves alignment of joints and filler metal, reducing rate of rejection and repair of unacceptable weldments. Utility extends beyond aerospace industry to mass production of various types of hardware, including heavy off-highway construction equipment.

Using Physical Models for Anomaly Detection in Control Systems

NASA Astrophysics Data System (ADS)

Svendsen, Nils; Wolthusen, Stephen

Supervisory control and data acquisition (SCADA) systems are increasingly used to operate critical infrastructure assets. However, the inclusion of advanced information technology and communications components and elaborate control strategies in SCADA systems increase the threat surface for external and subversion-type attacks. The problems are exacerbated by site-specific properties of SCADA environments that make subversion detection impractical; and by sensor noise and feedback characteristics that degrade conventional anomaly detection systems. Moreover, potential attack mechanisms are ill-defined and may include both physical and logical aspects.

Involvement of SNARE complex in the hippocampus and prefrontal cortex of offspring with depression induced by prenatal stress.

PubMed

Cao, Yan Jun; Wang, Qiong; Zheng, Xing Xing; Cheng, Ying; Zhang, Yan

2018-08-01

Prenatal stress (PS) exposure can cause depression-like behavior in offspring, and maladaptive responses including physiological and neurobiological changes. Glutamate neurotransmission is implicated in effects of PS and in antidepressant mechanisms; however, the mechanisms underlying its involvement remain unclear. In the synapse, the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for vesicular docking and neurotransmitter release. To explore effects of PS on the SNARE complex, pregnant rats were assigned to a control or PS group. Both male and female offspring in each group were used in this study. PS rats were exposed to restraint stress three times daily for 45 min on days 14-20 of pregnancy. In the PS offspring, the expression of the SNARE protein SNAP-25, vesicle-associated membrane protein (VAMP)-2, and Syntaxin 1a was significantly increased in the hippocampus and prefrontal cortex. These observations were associated with increased levels of proteins that chaperone SNARE complex formation, including Munc-18, α-synuclein, CSPα, complexin1, and complexin2. Immunoblotting of hippocampal and prefrontal cortex homogenates revealed significantly increased SNARE complex formation. vGluT1 protein expression was also significantly increased in the offspring. Additionally, PS was associated with increased mRNA expression of VAMP1, VAMP2, SNAP25, Syntaxin1a, and Syntaxin1b in the hippocampus and prefrontal cortex. Increased monomeric SNARE proteins, SNARE complex formation, vesicle-associated proteins, and vGluT1 may explain the increase in glutamate and its downstream excitotoxicity. These results support the hypothesis that glutamate release and vesicular glutamate transporters play a role in PS-induced depression-like behavior of rat offspring. Copyright © 2018. Published by Elsevier B.V.

Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression

PubMed Central

Jagielska, Anna; Lowe, Alexis L.; Makhija, Ekta; Wroblewska, Liliana; Guck, Jochen; Franklin, Robin J. M.; Shivashankar, G. V.; Van Vliet, Krystyn J.

2017-01-01

Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10–15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes. This response to strain required specific interactions of OPCs with extracellular matrix ligands. Applied strain induced changes in nuclear shape, chromatin organization, and resulted in enhanced histone deacetylation, consistent with increased oligodendrocyte differentiation. This response was concurrent with increased mRNA levels of the epigenetic modifier histone deacetylase Hdac11. Inhibition of HDAC proteins eliminated the strain-mediated increase of OPC differentiation, demonstrating a role of HDACs in mechanotransduction of strain to chromatin. RNA sequencing revealed global changes in gene expression associated with strain. Specifically, expression of multiple genes associated with oligodendrocyte differentiation and axon-oligodendrocyte interactions was increased, including cell surface ligands (Ncam, ephrins), cyto- and nucleo-skeleton genes (Fyn, actinins, myosin, nesprin, Sun1), transcription factors (Sox10, Zfp191, Nkx2.2), and myelin genes (Cnp, Plp, Mag). These findings show how mechanical strain can be transmitted to the nucleus to promote oligodendrocyte differentiation, and identify the global landscape of signaling pathways involved in mechanotransduction. These data provide a source of potential new therapeutic avenues to enhance OPC differentiation in vivo. PMID:28473753

Renal Autoregulation in Health and Disease

PubMed Central

Carlström, Mattias; Wilcox, Christopher S.; Arendshorst, William J.

2015-01-01

Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]i occurs predominantly by Ca2+ influx through L-type voltage-operated Ca2+ channels (VOCC). Increased [Ca2+]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+ from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+ sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study. PMID:25834230