Do emotion-induced blindness and the attentional blink share underlying mechanisms? An event-related potential study of emotionally-arousing words.

PubMed

MacLeod, Jeffrey; Stewart, Brandie M; Newman, Aaron J; Arnell, Karen M

2017-06-01

When two targets are presented within approximately 500 ms of each other in the context of rapid serial visual presentation (RSVP), participants' ability to report the second target is reduced compared to when the targets are presented further apart in time. This phenomenon is known as the attentional blink (AB). The AB is increased in magnitude when the first target is emotionally arousing. Emotionally arousing stimuli can also capture attention and create an AB-like effect even when these stimuli are presented as to-be-ignored distractor items in a single-target RSVP task. This phenomenon is known as emotion-induced blindness (EIB). The phenomenological similarity in the behavioral results associated with the AB with an emotional T1 and EIB suggest that these effects may result from similar underlying mechanisms - a hypothesis that we tested using event-related electrical brain potentials (ERPs). Behavioral results replicated those reported previously, demonstrating an enhanced AB following an emotionally arousing target and a clear EIB effect. In both paradigms highly arousing taboo/sexual words resulted in an increased early posterior negativity (EPN) component that has been suggested to represent early semantic activation and selection for further processing in working memory. In both paradigms taboo/sexual words also produced an increased late positive potential (LPP) component that has been suggested to represent consolidation of a stimulus in working memory. Therefore, ERP results provide evidence that the EIB and emotion-enhanced AB effects share a common underlying mechanism.

Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

NASA Astrophysics Data System (ADS)

Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

2014-05-01

The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology.

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms.

PubMed

Thijssen, Dick H J; Maxwell, Joseph; Green, Daniel J; Cable, N Timothy; Jones, Helen

2016-06-01

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact

Potential Mechanisms of Cancer Prevention by Weight Control

NASA Astrophysics Data System (ADS)

Jiang, Yu; Wang, Weiqun

Weight control via dietary caloric restriction and/or physical activity has been demonstrated in animal models for cancer prevention. However, the underlying mechanisms are not fully understood. Body weight loss due to negative energy balance significantly reduces some metabolic growth factors and endocrinal hormones such as IGF-1, leptin, and adiponectin, but enhances glucocorticoids, that may be associated with anti-cancer mechanisms. In this review, we summarized the recent studies related to weight control and growth factors. The potential molecular targets focused on those growth factors- and hormones-dependent cellular signaling pathways are further discussed. It appears that multiple factors and multiple signaling cascades, especially for Ras-MAPK-proliferation and PI3K-Akt-anti-apoptosis, could be involved in response to weight change by dietary calorie restriction and/or exercise training. Considering prevalence of obesity or overweight that becomes apparent over the world, understanding the underlying mechanisms among weight control, endocrine change and cancer risk is critically important. Future studies using "-omics" technologies will be warrant for a broader and deeper mechanistic information regarding cancer prevention by weight control.

Gaussian effective potential: Quantum mechanics

NASA Astrophysics Data System (ADS)

Stevenson, P. M.

1984-10-01

We advertise the virtues of the Gaussian effective potential (GEP) as a guide to the behavior of quantum field theories. Much superior to the usual one-loop effective potential, the GEP is a natural extension of intuitive notions familiar from quantum mechanics. A variety of quantum-mechanical examples are studied here, with an eye to field-theoretic analogies. Quantum restoration of symmetry, dynamical mass generation, and "quantum-mechanical resuscitation" are among the phenomena discussed. We suggest how the GEP could become the basis of a systematic approximation procedure. A companion paper will deal with scalar field theory.

Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

PubMed

Qamar, Hafiz Misbah-Ud-Din; Qayyum, Rahila; Salma, Umme; Khan, Shamim; Khan, Taous; Shah, Abdul Jabbar

2018-12-01

Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium. The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

PubMed Central

Freeman, John H.; Steinmetz, Adam B.

2011-01-01

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning. PMID:21969489

Mechanisms of astrocytic K(+) clearance and swelling under high extracellular K(+) concentrations.

PubMed

Murakami, Shingo; Kurachi, Yoshihisa

2016-03-01

In response to the elevation of extracellular K(+) concentration ([K(+)]out), astrocytes clear excessive K(+) to maintain conditions necessary for neural activity. K(+) clearance in astrocytes occurs via two processes: K(+) uptake and K(+) spatial buffering. High [K(+)]out also induces swelling in astrocytes, leading to edema and cell death in the brain. Despite the importance of astrocytic K(+) clearance and swelling, the underlying mechanisms remain unclear. Here, we report results from a simulation analysis of astrocytic K(+) clearance and swelling. Astrocyte models were constructed by incorporating various mechanisms such as intra/extracellular ion concentrations of Na(+), K(+), and Cl(-), cell volume, and models of Na,K-ATPase, Na-K-Cl cotransporter (NKCC), K-Cl cotransporter, inwardly-rectifying K(+) (KIR) channel, passive Cl(-) current, and aquaporin channel. The simulated response of astrocyte models under the uniform distribution of high [K(+)]out revealed significant contributions of NKCC and Na,K-ATPase to increases of intracellular K(+) and Cl(-) concentrations, and swelling. Moreover, we found that, under the non-uniform distribution of high [K(+)]out, KIR channels localized at synaptic clefts absorbed excess K(+) by depolarizing the equivalent potential of K(+) (E K) above membrane potential, while K(+) released through perivascular KIR channels was enhanced by hyperpolarizing E K and depolarizing membrane potential. Further analysis of simulated drug effects revealed that astrocyte swelling was modulated by blocking each of the ion channels and transporters. Our simulation analysis revealed controversial mechanisms of astrocytic K(+) clearance and swelling resulting from complex interactions among ion channels and transporters.

Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

PubMed

Wei, Min; Li, Song; Le, Weidong

2017-10-25

Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

Developmental mechanisms underlying variation in craniofacial disease and evolution.

PubMed

Fish, Jennifer L

2016-07-15

Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. Copyright © 2015 Elsevier Inc. All rights reserved.

Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

NASA Astrophysics Data System (ADS)

Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

2018-07-01

Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

NASA Astrophysics Data System (ADS)

Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

2018-03-01

Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

Mechanisms underlying the wound healing potential of propolis based on its in vitro antioxidant activity.

PubMed

Cao, Xue-Ping; Chen, Yi-Fan; Zhang, Jiang-Lin; You, Meng-Meng; Wang, Kai; Hu, Fu-Liang

2017-10-15

Propolis is a resinous substance collected by honeybees, Apis mellifera, from various plant sources. Having various pharmacological and biological activities, it has been used in folk medicine and complementary therapies since ancient times. To evaluate the effects and underlying mechanism of the protective effects of the ethanol extract of Chinese propolis (EECP) on L929 cells injured by hydrogen peroxide (H 2 O 2 ). The wound healing activities of EECP in L929 cells with H 2 O 2 -induced damage were investigated. The main components of EECP were analyzed by RP-HPLC, and the free radical scavenging capacity and reducing power were also measured. The effects of EECP on the expression of antioxidant-related genes in fibroblast L929 cells were determined using qRT-PCR and western blotting. EECP had significant protective effects against cell death induced by H 2 O 2 and significantly inhibited the decline of collagen mRNA expression caused by H 2 O 2 in L929 cells. EECP induced the expression of antioxidant-related genes, such as HO-1, GCLM, and GCLC, which has great implications for the potential of propolis to alleviate oxidative stress in wound tissues. The protective effects of propolis have great implications for using propolis as a wound healing regent. Copyright © 2017 Elsevier GmbH. All rights reserved.

Endocochlear potential depends on Cl− channels: mechanism underlying deafness in Bartter syndrome IV

PubMed Central

Rickheit, Gesa; Maier, Hannes; Strenzke, Nicola; Andreescu, Corina E; De Zeeuw, Chris I; Muenscher, Adrian; Zdebik, Anselm A; Jentsch, Thomas J

2008-01-01

Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a β-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K+-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd−/− mice thus demonstrate a novel function of Cl− channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV. PMID:18833191

Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

NASA Astrophysics Data System (ADS)

Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

2017-03-01

Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

Potential fluid mechanic pathways of platelet activation.

PubMed

Shadden, Shawn C; Hendabadi, Sahar

2013-06-01

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.

Potential fluid mechanic pathways of platelet activation

PubMed Central

Shadden, Shawn C.; Hendabadi, Sahar

2012-01-01

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport. PMID:22782543

Music listening after stroke: beneficial effects and potential neural mechanisms.

PubMed

Särkämö, Teppo; Soto, David

2012-04-01

Music is an enjoyable leisure activity that also engages many emotional, cognitive, and motor processes in the brain. Here, we will first review previous literature on the emotional and cognitive effects of music listening in healthy persons and various clinical groups. Then we will present findings about the short- and long-term effects of music listening on the recovery of cognitive function in stroke patients and the underlying neural mechanisms of these music effects. First, our results indicate that listening to pleasant music can have a short-term facilitating effect on visual awareness in patients with visual neglect, which is associated with functional coupling between emotional and attentional brain regions. Second, daily music listening can improve auditory and verbal memory, focused attention, and mood as well as induce structural gray matter changes in the early poststroke stage. The psychological and neural mechanisms potentially underlying the rehabilitating effect of music after stroke are discussed. © 2012 New York Academy of Sciences.

Different underlying mechanisms for face emotion and gender processing during feature-selective attention: Evidence from event-related potential studies.

PubMed

Wang, Hailing; Ip, Chengteng; Fu, Shimin; Sun, Pei

2017-05-01

Face recognition theories suggest that our brains process invariant (e.g., gender) and changeable (e.g., emotion) facial dimensions separately. To investigate whether these two dimensions are processed in different time courses, we analyzed the selection negativity (SN, an event-related potential component reflecting attentional modulation) elicited by face gender and emotion during a feature selective attention task. Participants were instructed to attend to a combination of face emotion and gender attributes in Experiment 1 (bi-dimensional task) and to either face emotion or gender in Experiment 2 (uni-dimensional task). The results revealed that face emotion did not elicit a substantial SN, whereas face gender consistently generated a substantial SN in both experiments. These results suggest that face gender is more sensitive to feature-selective attention and that face emotion is encoded relatively automatically on SN, implying the existence of different underlying processing mechanisms for invariant and changeable facial dimensions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms and therapeutic potential of microRNAs in hypertension

PubMed Central

Shi, Lijun; Liao, Jingwen; Liu, Bailin; Zeng, Fanxing; Zhang, Lubo

2015-01-01

Hypertension is the major risk factor for the development of stroke, coronary artery disease, heart failure and renal disease. The underlying cellular and molecular mechanisms of hypertension are complex and remain largely elusive. MicroRNAs (miRNAs) are short, noncoding RNA fragments of 22–26 nucleotides and regulate protein expression post-transcriptionally by targeting the 3′-untranslated region of mRNA. A growing body of recent research indicates that miRNAs are important in the pathogenesis of arterial hypertension. Herein, we summarize the current knowledge regarding the mechanisms of miRNAs in cardiovascular remodeling, focusing specifically on hypertension. We also review recent progress of the miRNA-based therapeutics including pharmacological and nonpharmacological therapies (such as exercise training) and their potential applications in the management of hypertension. PMID:26004493

Simulated airplane headache: a proxy towards identification of underlying mechanisms.

PubMed

Bui, Sebastian Bao Dinh; Petersen, Torben; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

2017-12-01

Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E 2 (PGE 2 ), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE 2 , cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE 2 , and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

Mechanism underlying berberine's effects on HSP70/TNFα under heat stress: Correlation with the TATA boxes.

PubMed

Jiang, Jing-Fei; Lei, Fan; Yuan, Zhi-Yi; Wang, Yu-Gang; Wang, Xin-Pei; Yan, Xiao-Jin; Yu, Xuan; Xing, Dong-Ming; DU, Li-Jun

2017-03-01

Heat stress can stimulate an increase in body temperature, which is correlated with increased expression of heat shock protein 70 (HSP70) and tumor necrosis factor α (TNFα). The exact mechanism underlying the HSP70 and TNFα induction is unclear. Berberine (BBR) can significantly inhibit the temperature rise caused by heat stress, but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated. The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions, using in vivo and in vitro models. The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses. The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions (40 °C). HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature, but knockdown of HSP70 could not down-regulate the level of TNFα. Furthermore, TNFα could not influence the expression of HSP70 under normal and heat conditions. BBR targeted both HSP70 and TNFα by suppressing their gene transcription, thereby decreasing body temperature under heat conditions. In conclusion, BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation.

PubMed

Allavena, Giulia; Boyd, Caroline; Oo, Kyaw Soe; Maellaro, Emilia; Zhivotovsky, Boris; Kaminskyy, Vitaliy O

2016-11-01

Macroautophagy/autophagy is a well-organized process of intracellular degradation, which is rapidly activated under starvation conditions. Recent data demonstrate a transcriptional upregulation of several autophagy genes as a mechanism that controls autophagy in response to starvation. Here we report that despite the significant upregulation of mRNA of the essential autophagy initiation gene ULK1, its protein level is rapidly reduced under starvation. Although both autophagic and proteasomal systems contribute to the degradation of ULK1, under prolonged nitrogen deprivation, its level was still reduced in ATG7 knockout cells, and only initially stabilized in cells treated with the lysosomal or proteasomal inhibitors. We demonstrate that under starvation, protein translation is rapidly diminished and, similar to treatments with the proteosynthesis inhibitors cycloheximide or anisomycin, is associated with a significant reduction of ULK1. Furthermore, it was found that inhibition of the mitochondrial respiratory complexes or the mitochondrial ATP synthase function that could also take place in the absence of substrates, promote upregulation of ULK1 mRNA and protein expression in an AMPK-dependent manner in U1810 lung cancer cells growing in complete culture medium. These inhibitors could also drastically increase the ULK1 protein in U1810 cells with knockout of ATG13, where the ULK1 expression is significantly diminished. However, such upregulation of ULK1 protein is negligible under starvation conditions, further signifying the contribution of translation and suggesting that transcriptional upregulation of ULK1 protein will be diminished under such conditions. Thus, we propose a model where inhibition of protein translation, together with the degradation systems, limit autophagy during starvation.

Semiclassical stochastic mechanics for the Coulomb potential with applications to modelling dark matter

NASA Astrophysics Data System (ADS)

Neate, Andrew; Truman, Aubrey

2016-05-01

Little is known about dark matter particles save that their most important interactions with ordinary matter are gravitational and that, if they exist, they are stable, slow moving and relatively massive. Based on these assumptions, a semiclassical approximation to the Schrödinger equation under the action of a Coulomb potential should be relevant for modelling their behaviour. We investigate the semiclassical limit of the Schrödinger equation for a particle of mass M under a Coulomb potential in the context of Nelson's stochastic mechanics. This is done using a Freidlin-Wentzell asymptotic series expansion in the parameter ɛ = √{ ħ / M } for the Nelson diffusion. It is shown that for wave functions ψ ˜ exp((R + iS)/ɛ2) where R and S are real valued, the ɛ = 0 behaviour is governed by a constrained Hamiltonian system with Hamiltonian Hr and constraint Hi = 0 where the superscripts r and i denote the real and imaginary parts of the Bohr correspondence limit of the quantum mechanical Hamiltonian, independent of Nelson's ideas. Nelson's stochastic mechanics is restored in dealing with the nodal surface singularities and by computing (correct to first order in ɛ) the relevant diffusion process in terms of Jacobi fields thereby revealing Kepler's laws in a new light. The key here is that the constrained Hamiltonian system has just two solutions corresponding to the forward and backward drifts in Nelson's stochastic mechanics. We discuss the application of this theory to modelling dark matter particles under the influence of a large gravitating point mass.

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.

Spurious heat conduction behavior of finite-size graphene nanoribbon under extreme uniaxial strain caused by the AIREBO potential

NASA Astrophysics Data System (ADS)

Yang, Xueming; Wu, Sihan; Xu, Jiangxin; Cao, Bingyang; To, Albert C.

2018-02-01

Although the AIREBO potential can well describe the mechanical and thermal transport of the carbon nanostructures under normal conditions, previous studies have shown that it may overestimate the simulated mechanical properties of carbon nanostructures in extreme strains near fracture. It is still unknown whether such overestimation would also appear in the thermal transport of nanostructrues. In this paper, the mechanical and thermal transport of graphene nanoribbon under extreme deformation conditions are studied by MD simulations using both the original and modified AIREBO potential. Results show that the cutoff function of the original AIREBO potential produces an overestimation on thermal conductivity in extreme strains near fracture stage. Spurious heat conduction behavior appears, e.g., the thermal conductivity of GNRs does not monotonically decrease with increasing strain, and even shows a ;V; shaped reversed and nonphysical trend. Phonon spectrum analysis show that it also results in an artificial blue shift of G peak and phonon stiffening of the optical phonon modes. The correlation between spurious heat conduction behavior and overestimation of mechanical properties near the fracture stage caused by the original AIREBO potential are explored and revealed.

Selenium and Anticarcinogenesis: Underlying Mechanisms

USDA-ARS?s Scientific Manuscript database

The manuscript discusses recent research related to anticarcinogenic mechanisms of selenium (Se) action in light of the underlying chemical/biochemical functions of the selenium species likely to be executors of those effects. Recent studies in a variety of model systems have increased understanding...

Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

NASA Astrophysics Data System (ADS)

Saloman, Jami L.

Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

Mechanisms underlying ICU muscle wasting and effects of passive mechanical loading

PubMed Central

2012-01-01

Introduction Critically ill ICU patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life for survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model show that the mechanical silencing associated with CIM is the primary triggering factor. This study aims to unravel the mechanisms underlying CIM, and to evaluate the effects of a specific intervention aiming at reducing mechanical silencing in sedated and mechanically ventilated ICU patients. Methods Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading for 10 hours per day (2.5 hours, four times) for 9 ± 1 days. Results These patients developed a phenotype considered pathognomonic of CIM; that is, severe muscle wasting and a preferential myosin loss (P < 0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of neuronal nitric oxide synthase. Passive mechanical loading for 9 ± 1 days resulted in a 35% higher specific force (P < 0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass. Conclusion Mechanical silencing is suggested to be a primary mechanism underlying CIM; that is

Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

PubMed

Weng, Z Y; Liu, Z Q; Ritchie, R O; Jiao, D; Li, D S; Wu, H L; Deng, L H; Zhang, Z F

2016-12-01

The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acupuncture for Visceral Pain: Neural Substrates and Potential Mechanisms

PubMed Central

Chen, Shuping; Wang, Shubin; Rong, Peijing; Wang, Junying; Qiao, Lina; Feng, Xiumei; Liu, Junling

2014-01-01

Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. Despite much advances, the pathophysiological mechanism is still poorly understood comparing with its somatic counterpart and, as a result, the therapeutic efficacy is usually unsatisfactory. Acupuncture has long been used for the management of numerous disorders in particular pain and visceral pain, characterized by the high therapeutic benefits and low adverse effects. Previous findings suggest that acupuncture depresses pain via activation of a number of neurotransmitters or modulators including opioid peptides, serotonin, norepinephrine, and adenosine centrally and peripherally. It endows us, by advancing the understanding of the role of ion channels and gut microbiota in pain process, with novel perspectives to probe the mechanisms underlying acupuncture analgesia. In this review, after describing the visceral innervation and the relevant afferent pathways, in particular the ion channels in visceral nociception, we propose three principal mechanisms responsible for acupuncture induced benefits on visceral pain. Finally, potential topics are highlighted regarding the future studies in this field. PMID:25614752

Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

NASA Technical Reports Server (NTRS)

Rosenthal, Nadia A.

1999-01-01

The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

Peeling mechanism of tomato under infrared heating

USDA-ARS?s Scientific Manuscript database

Critical behaviors of peeling tomatoes using infrared heat are thermally induced peel loosening and subsequent cracking. However, the mechanism of peel loosening and cracking due to infrared heating remains unclear. This study aimed at investigating the mechanism of peeling tomatoes under infrared h...

Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimer’s Disease – Potential Benefits and Underlying Mechanisms

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2014-01-01

Alzheimer’s disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research. PMID:24795656

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

Salicylic acid-induced abiotic stress tolerance and underlying mechanisms in plants

PubMed Central

Khan, M. Iqbal R.; Fatma, Mehar; Per, Tasir S.; Anjum, Naser A.; Khan, Nafees A.

2015-01-01

Abiotic stresses (such as metals/metalloids, salinity, ozone, UV-B radiation, extreme temperatures, and drought) are among the most challenging threats to agricultural system and economic yield of crop plants. These stresses (in isolation and/or combination) induce numerous adverse effects in plants, impair biochemical/physiological and molecular processes, and eventually cause severe reductions in plant growth, development and overall productivity. Phytohormones have been recognized as a strong tool for sustainably alleviating adverse effects of abiotic stresses in crop plants. In particular, the significance of salicylic acid (SA) has been increasingly recognized in improved plant abiotic stress-tolerance via SA-mediated control of major plant-metabolic processes. However, the basic biochemical/physiological and molecular mechanisms that potentially underpin SA-induced plant-tolerance to major abiotic stresses remain least discussed. Based on recent reports, this paper: (a) overviews historical background and biosynthesis of SA under both optimal and stressful environments in plants; (b) critically appraises the role of SA in plants exposed to major abiotic stresses; (c) cross-talks potential mechanisms potentially governing SA-induced plant abiotic stress-tolerance; and finally (d) briefly highlights major aspects so far unexplored in the current context. PMID:26175738

Gas Bubble Dynamics under Mechanical Vibrations

NASA Astrophysics Data System (ADS)

Mohagheghian, Shahrouz; Elbing, Brian

2017-11-01

The scientific community has a limited understanding of the bubble dynamics under mechanical oscillations due to over simplification of Navier-Stockes equation by neglecting the shear stress tensor and not accounting for body forces when calculating the acoustic radiation force. The current work experimental investigates bubble dynamics under mechanical vibration and resulting acoustic field by measuring the bubble size and velocity using high-speed imaging. The experimental setup consists of a custom-designed shaker table, cast acrylic bubble column, compressed air injection manifold and an optical imaging system. The mechanical vibrations resulted in accelerations between 0.25 to 10 times gravitational acceleration corresponding to frequency and amplitude range of 8 - 22Hz and 1 - 10mm respectively. Throughout testing the void fraction was limited to <5%. The bubble size is larger than resonance size and smaller than acoustic wavelength. The amplitude of acoustic pressure wave was estimated using the definition of Bjerknes force in combination with Rayleigh-Plesset equation. Physical behavior of the system was capture and classified. Bubble size, velocity as well as size and spatial distribution will be presented.

Deformation Mechanisms of Gum Metals Under Nanoindentation

NASA Astrophysics Data System (ADS)

Sankaran, Rohini Priya

Gum Metal is a set of multi-component beta-Ti alloys designed and developed by Toyota Central R&D Labs in 2003 to have a nearly zero shear modulus in the direction. After significant amounts of cold-work (>90%), these alloys were found to have yield strengths at a significant fraction of the predicted ideal strengths and exhibited very little work hardening. It has been speculated that this mechanical behavior may be realized through an ideal shear mechanism as opposed to conventional plastic deformation mechanisms, such as slip, and that such a mechanism may be realized through a defect structure termed "nanodisturbance". It is furthermore theorized that for near ideal strength to be attained, dislocations need to be pinned at sufficiently high stresses. It is the search for these defects and pinning points that motivates the present study. However, the mechanism of plastic deformation and the true origin of specific defect structures unique to gum metals is still controversial, mainly due to the complexity of the beta-Ti alloy system and the heavily distorted lattice exhibited in cold worked gum metals, rendering interpretation of images difficult. Accordingly, the first aim of this study is to clarify the starting as-received microstructures of gum metal alloys through conventional transmission electron microscopy (TEM) and aberration-corrected high resolution scanning transmission electron microscopy with high-angle annular dark field detector (HAADF-HRSTEM) imaging. To elucidate the effects of beta-stability and starting microstructure on the deformation behavior of gum metals and thus to provide adequate context for potentially novel deformation structures, we investigate three alloy conditions: gum metal that has undergone solution heat treatment (STGM), gum metal that has been heavily cold worked (CWGM), and a solution treated alloy of nominal gum metal composition, but leaner in beta-stabilizing content (ST Ref-1). In order to directly relate observed

Sirtuins in neurodegenerative diseases: an update on potential mechanisms

PubMed Central

Min, Sang-Won; Sohn, Peter D.; Cho, Seo-Hyun; Swanson, Raymond A.; Gan, Li

2013-01-01

Silent information regulator 2 proteins (sirtuins or SIRTs) are a group of deacetylases (or deacylases) whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Compelling evidence supports that sirtuins play major roles in many aspects of physiology, especially in pathways related to aging – the predominant and unifying risk factor for neurodegenerative diseases. In this review, we highlight the molecular mechanisms underlying the protective effects of sirtuins in neurodegenerative diseases, focusing on protein homeostasis, neural plasticity, mitochondrial function, and sustained chronic inflammation. We will also examine the potential and challenges of targeting sirtuin pathways to block these pathogenic pathways. PMID:24093018

Effects of triclosan on hormones and reproductive axis in female Yellow River carp (Cyprinus carpio): Potential mechanisms underlying estrogen effect.

PubMed

Wang, Fan; Guo, Xiangmeng; Chen, Wanguang; Sun, Yaowen; Fan, Chaojie

2017-12-01

Triclosan (TCS), a member of the class of compounds called pharmaceutical and personal care products (PPCPs), is a broad antibacterial and antifungal agent found in a lot of consumer products. However, TCS hormone effect mechanism in teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were exposed to 1/20, 1/10 and 1/5 LC 50 TCS (96h LC 50 of TCS to carp) under semi-static conditions for 42days. Vitellogenin (Vtg), 17β-estradiol (E 2 ), testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-β, GnRH, and Er by quantitative real-time PCR (qRT-PCR). The results indicated that 1/5 LC 50 TCS induced Vtg in hepatopancreas of female carps by interference with the hypothalamic-pituitary-gonadal (HPG) axis at multiple potential loci through three mechanisms: (a) TCS exposure enhanced the mRNA expression of hypothalamus and gonadal aromatase which converts androgens into estrogens, subsequently increasing serum concentrations of E 2 to induce Vtg in hepatopancreas; (b) TCS treatment increased GnRH and GtH-β mRNA expression and secretion, causing the disturbance of reproductive endocrine and the increase of E 2 to induce Vtg in hepatopancreas; (c) TCS exposure enhanced synthesis and secretion of Er, then it bound to Er to active Vtg synthesis. These mechanisms showed that TCS may induce Vtg production in female Yellow River carp by Er-mediated and non-Er-mediated pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential of isotope analysis (C, Cl) to identify dechlorination mechanisms

NASA Astrophysics Data System (ADS)

Cretnik, Stefan; Thoreson, Kristen; Bernstein, Anat; Ebert, Karin; Buchner, Daniel; Laskov, Christine; Haderlein, Stefan; Shouakar-Stash, Orfan; Kliegman, Sarah; McNeill, Kristopher; Elsner, Martin

2013-04-01

Chloroethenes are commonly used in industrial applications, and detected as carcinogenic contaminants in the environment. Their dehalogenation is of environmental importance in remediation processes. However, a detailed understanding frequently accounted problem is the accumulation of toxic degradation products such as cis-dichloroethylene (cis-DCE) at contaminated sites. Several studies have addressed the reductive dehalogenation reactions using biotic and abiotic model systems, but a crucial question in this context has remained open: Do environmental transformations occur by the same mechanism as in their corresponding in vitro model systems? The presented study shows the potential to close this research gap using the latest developments in compound specific chlorine isotope analysis, which make it possible to routinely measure chlorine isotope fractionation of chloroethenes in environmental samples and complex reaction mixtures.1,2 In particular, such chlorine isotope analysis enables the measurement of isotope fractionation for two elements (i.e., C and Cl) in chloroethenes. When isotope values of both elements are plotted against each other, different slopes reflect different underlying mechanisms and are remarkably insensitive towards masking. Our results suggest that different microbial strains (G. lovleyi strain SZ, D. hafniense Y51) and the isolated cofactor cobalamin employ similar mechanisms of reductive dechlorination of TCE. In contrast, evidence for a different mechanism was obtained with cobaloxime cautioning its use as a model for biodegradation. The study shows the potential of the dual isotope approach as a tool to directly compare transformation mechanisms of environmental scenarios, biotic transformations, and their putative chemical lab scale systems. Furthermore, it serves as an essential reference when using the dual isotope approach to assess the fate of chlorinated compounds in the environment.

Simulation of fatigue damage in ferroelectric polycrystals under mechanical/electrical loading

NASA Astrophysics Data System (ADS)

Kozinov, S.; Kuna, M.

2018-07-01

The reliability of smart-structures made of ferroelectric ceramics is essentially reduced by the formation of cracks under the action of external electrical and/or mechanical loading. In the current research a numerical model for low-cycle fatigue in ferroelectric mesostructures is proposed. In the finite element simulations a combination of two user element routines is utilized. The first one is used to model a micromechanical ferroelectric domain switching behavior inside the grains. The second one is used to simulate fatigue damage of grain boundaries by a cohesive zone model (EMCCZM) based on an electromechanical cyclic traction-separation law (TSL). For numerical simulations a scanning electron microscope image of the ceramic's grain structure was digitalized and meshed. The response of this mesostructure to cyclic electrical or mechanical loading is systematically analyzed. As a result of the simulations, the distribution of electric potential, field, displacement and polarization as well as mechanical stresses and deformations inside the grains are obtained. At the grain boundaries, the formation and evolution of damage are analyzed until final failure and induced degradation of electric permittivity. It is found that the proposed model correctly mimics polycrystalline behavior during poling processes and progressive damage under cyclic electromechanical loading. To the authors' knowledge, it is the first model and numerical analysis of ferroelectric polycrystals taking into account both domain reorientation and cohesive modeling of intergranular fracture. It can help to understand failure mechanisms taking place in ferroelectrics during fatigue processes.

Mechanisms underlying perceptual learning of contrast detection in adults with anisometropic amblyopia

PubMed Central

Huang, Chang-Bing; Lu, Zhong-Lin; Zhou, Yifeng

2010-01-01

What underlies contrast sensitivity improvements in adults with anisometropic amblyopia following perceptual learning in grating contrast detection? In this paper, we adopted the external noise approach (Z.-L. Lu & B. A. Dosher, 1998) to identify the mechanisms underlying perceptual learning in adults with anisometropic amblyopia. By measuring contrast thresholds in a range of external noise conditions at two performance levels (79.3% and 70.7%), we found that a mixture of internal additive noise reduction and external noise exclusion underlay training induced contrast sensitivity improvements in adults with anisometropic amblyopia. In comparison, normal adults exhibited only small amount of external noise exclusion under the same training conditions. The results suggest that neural plasticity may be more robust in amblyopia, lending further support of perceptual learning as a potential treatment for adult amblyopia. PMID:20053087

Mechanical behaviour of TWIP steel under shear loading

NASA Astrophysics Data System (ADS)

Vincze, G.; Butuc, M. C.; Barlat, F.

2016-08-01

Twinning induced plasticity steels (TWIP) are very good candidate for automotive industry applications because they potentially offer large energy absorption before failure due to their exceptional strain hardening capability and high strength. However, their behaviour is drastically influenced by the loading conditions. In this work, the mechanical behaviour of a TWIP steel sheet sample was investigated at room temperature under monotonic and reverse simple shear loading. It was shown that all the expected features of load reversal such as Bauschinger effect, transient strain hardening with high rate and permanent softening, depend on the prestrain level. This is in agreement with the fact that these effects, which occur during reloading, are related to the rearrangement of the dislocation structure induced during the predeformation. The homogeneous anisotropic hardening (HAH) approach proposed by Barlat et al. (2011) [1] was successfully employed to predict the experimental results.

INSULIN RESISTANCE POST-BURN: UNDERLYING MECHANISMS AND CURRENT THERAPEUTIC STRATEGIES

PubMed Central

Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

2014-01-01

The profound hypermetabolic response to burn injury is associated with insulin resistance and hyperglycemia, significantly contributing to the incidence of morbidity and mortality in this patient population. These responses are present in all trauma, surgical, or critically ill patients, but the severity, length, and magnitude is unique for burn patients. Although advances in therapeutic strategies to attenuate the post-burn hypermetabolic response have significantly improved the clinical outcome of these patients over the past years, therapeutic approaches to overcome stress-induced hyperglycemia have remained challenging. Intensive insulin therapy has been shown to significantly reduce morbidity and mortality in critically ill patients. High incidence of hypoglycemic events and difficult blood glucose titrations have led to investigation of alternative strategies, including the use of metformin, a biguanide, or fenofibrate, a PPAR-γ agonist. Nevertheless, weaknesses and potential side affects of these drugs reinforces the need for better understanding of the molecular mechanisms underlying insulin resistance post-burn that may lead to novel therapeutic strategies further improving the prognosis of these patients. This review aims to discuss the mechanisms underlying insulin resistance induced hyperglycemia post-burn and outlines current therapeutic strategies that are being used to modulate hyperglycemia following thermal trauma. PMID:18695610

Bolted Double-Lap Composite Joints Under Mechanical and Thermal Loading

NASA Technical Reports Server (NTRS)

Kradinov, V.; Barut, A.; Madenci, E.; Walker, Sandra P. (Technical Monitor)

2000-01-01

This study concerns the determination of the contact stresses and contact region around bolt holes and the bolt load distribution in single- and double-lap joints of composite laminates with arbitrarily located bolts under general mechanical loading conditions and uniform temperature change. The unknown contact stress distribution and contact region between the bolt and laminates and the interaction among the bolts require the bolt load distribution, as well as the contact stresses, to be as part of the solution. The present method is based on the complex potential theory and the variational formulation in order to account for bolt stiffness, bolt-hole clearance, and finite geometry of the composite laminates.

Potential mechanisms linking probiotics to diabetes: a narrative review of the literature.

PubMed

Miraghajani, Maryam; Dehsoukhteh, Somayeh Shahraki; Rafie, Nahid; Hamedani, Sahar Golpour; Sabihi, Sima; Ghiasvand, Reza

2017-01-01

Some studies have suggested a wide range of possible mechanisms through which probiotics may play a role in diabetes prevention and treatment. However, the underlying mechanisms are not fully understood. We conducted this study to review the potential mechanisms suggested for the effect of probiotics in diabetes. Narrative review conducted at the Food Security Research Center of Isfahan. A search in the electronic databases MEDLINE (PubMed), Cochrane Library, Web of Science and Google scholar was performed up to October 2016. The initial search yielded 1214 reports. After removing duplicates, 704 titles and abstracts were screened. Finally, out of 83 full-text articles that were reviewed for eligibility, 30 articles were included in the final analysis. The anti-diabetic mechanisms for probiotics reported encompass intraluminal and direct effects on the intestinal mucosa and microbiota (n = 13), anti-inflammatory and immunomodulatory effects (n = 10), antioxidative effects (n = 5), effects on endoplasmic reticulum (ER) stress and expression of genes involved in glucose homeostasis and insulin resistance (n = 6), with some studies pointing to more than one mechanism. The results may throw some light on the capacity of probiotics as a novel approach towards controlling diabetes. However, further human studies are warranted to elucidate and confirm the potential role of probiotics in diabetes prevention and treatment. Also, it needs to be ascertained whether the effectiveness of probiotics in diabetes prevention and treatment is dependent on the strain of the microorganisms.

The electrical potential difference through the foot epithelium of the snail Achatina achatina, Lameere during mechanical and chemical stimulation.

PubMed

Tyrakowski, Tomasz; Hołyńska, Iga; Lampka, Magdalena; Kaczorowski, Piotr

2006-01-01

An important electrophysiological variable--the transepithelial potential difference reflects the electrogenic transepithelial ion currents, which are produced and modified by ion transport processes in polarized cells of epithelium. These processes result from coordinated function of transporters in apical and basolateral cell membranes and have been observed in all epithelial tissues studied so far. The experiments were performed on isolated specimens of snail foot. In the experiments, the baseline transepithelial electrical potential difference--PD, changes of transepithelial difference during mechanical stimulation--dPD and the transepithelial resistance were measured with an Ussing apparatus. A total of 60 samples of foot ventral surface of 28 snails were studied. The transepithelial electrical potential difference of isolated foot ranged from -6.0 to 10.0 mV under different experimental conditions. Mechanical stimulation of foot ventral surface caused changes of electrogenic ion transport, observed as transient hyperpolarization (electrical potential difference became more positive). When the transepithelial electrical potential difference decreased during stimulation, the reaction was described as depolarization. When amiloride and bumetanide were added to the stimulating fluid so that the sodium and chloride ion transport pathways were inhibited, prolonged depolarization occurred. Under the influence of different stimuli: mechanical (gentle rinsing), chemical (changes of ion concentrations) and pharmacological (application of ion inhibitors), transient changes of potential difference (dPD) were evoked, ranging from about -0.7 to almost 2.0 mV. Changes in transepithelial potential difference of the pedal surface of the snail's foot related to these physiological stimuli are probably involved in the locomotion of the animal and are under control of the part of the nervous system in which tachykinin related peptides (TRP) act as transmitters.

Transformations of organic compounds under the action of mechanical stress

NASA Astrophysics Data System (ADS)

Dubinskaya, Aleksandra M.

1999-08-01

Transformations of organic compounds (monomeric and polymeric) under the action of mechanical stress are considered. Two types of processes occur under these conditions. The first type involves disordering and amorphisation of crystal structure and conformational transformations as a result of rupture of intermolecular bonds. The second type includes mechanochemical reactions activated by deformation of valence bonds and angles under mechanical stress, namely, the rupture of bonds, oxidation and hydrolysis. Data on the organic mechanochemical synthesis of new compounds or molecular complexes are systematised and generalised. It is demonstrated that mechanical treatment ensures mass transfer and the contact of reacting species in these reactions. Proteins are especially sensitive to mechanical stress and undergo denaturation; enzymes are inactivated. The bibliography includes 115 references.

Transcriptome analysis reveals potential mechanisms underlying differential heart development in fast- and slow-growing broilers under heat stress.

PubMed

Zhang, Jibin; Schmidt, Carl J; Lamont, Susan J

2017-04-13

Modern fast-growing broilers are susceptible to heart failure under heat stress because their relatively small hearts cannot meet increased need of blood pumping. To improve the cardiac tolerance to heat stress in modern broilers through breeding, we need to find the important genes and pathways that contribute to imbalanced cardiac development and frequent occurrence of heat-related heart dysfunction. Two broiler lines - Ross 708 and Illinois - were included in this study as a fast-growing model and a slow-growing model respectively. Each broiler line was separated to two groups at 21 days posthatch. One group was subjected to heat stress treatment in the range of 35-37 °C for 8 h per day, and the other was kept in thermoneutral condition. Body and heart weights were measured at 42 days posthatch, and gene expression in left ventricles were compared between treatments and broiler lines through RNA-seq analysis. Body weight and normalized heart weight were significantly reduced by heat stress only in Ross broilers. RNA-seq results of 44 genes were validated using Biomark assay. A total of 325 differentially expressed (DE) genes were detected between heat stress and thermoneutral in Ross 708 birds, but only 3 in Illinois broilers. Ingenuity pathway analysis (IPA) predicted dramatic changes in multiple cellular activities especially downregulation of cell cycle. Comparison between two lines showed that cell cycle activity is higher in Ross than Illinois in thermoneutral condition but is decreased under heat stress. Among the significant pathways (P < 0.01) listed for different comparisons, "Mitotic Roles of Polo-like Kinases" is always ranked first. The increased susceptibility of modern broilers to cardiac dysfunction under heat stress compared to slow-growing broilers could be due to diminished heart capacity related to reduction in relative heart size. The smaller relative heart size in Ross heat stress group than in Ross thermoneutral group is suggested

Mechanical model testing of rebreathing potential in infant bedding materials

PubMed Central

Carleton, J.; Donoghue, A.; Porter, W.

1998-01-01

Rebreathing of expired air may be a lethal hazard for prone sleeping infants. This paper describes a mechanical model to simulate infant breathing, and examines the effects of bedding on exhaled air retention. Under simulated rebreathing conditions, the model allows the monitoring of raised carbon dioxide (CO2) inside an artificial lung-trachea system. Resulting levels of CO2 (although probably exaggerated in the mechanical model compared with an infant, due to the model's fixed breathing rate and volume) suggest that common bedding materials vary widely in inherent rebreathing potential. In face down tests, maximum airway CO2 ranged from less than 5% on sheets and waterproof mattresses to over 25% on sheepskins, bean bag cushions, and some pillows and comforters. Concentrations of CO2 decreased with increasing head angle of the doll, away from the face down position. Recreations of 29infant death scenes also showed large CO2 increases on some bedding materials, suggesting these infants could have died while rebreathing.

 PMID:9623394

Deciphering the underlying mechanisms of Diesun Miaofang in traumatic injury from a systems pharmacology perspective

PubMed Central

ZHENG, CHUN-SONG; FU, CHANG-LONG; PAN, CAI-BIN; BAO, HONG-JUAN; CHEN, XING-QIANG; YE, HONG-ZHI; YE, JIN-XIA; WU, GUANG-WEN; LI, XI-HAI; XU, HUI-FENG; XU, XIAO-JIE; LIU, XIAN-XIANG

2015-01-01

Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmcological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine. PMID:25891262

Quantum mechanics without potential function

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

Alhaidari, A. D., E-mail: haidari@sctp.org.sa; Ismail, M. E. H.

2015-07-15

In the standard formulation of quantum mechanics, one starts by proposing a potential function that models the physical system. The potential is then inserted into the Schrödinger equation, which is solved for the wavefunction, bound states energy spectrum, and/or scattering phase shift. In this work, however, we propose an alternative formulation in which the potential function does not appear. The aim is to obtain a set of analytically realizable systems, which is larger than in the standard formulation and may or may not be associated with any given or previously known potential functions. We start with the wavefunction, which ismore » written as a bounded infinite sum of elements of a complete basis with polynomial coefficients that are orthogonal on an appropriate domain in the energy space. Using the asymptotic properties of these polynomials, we obtain the scattering phase shift, bound states, and resonances. This formulation enables one to handle not only the well-known quantum systems but also previously untreated ones. Illustrative examples are given for two- and three-parameter systems.« less

Hyperglycemia Augments the Adipogenic Transdifferentiation Potential of Tenocytes and Is Alleviated by Cyclic Mechanical Stretch.

PubMed

Wu, Yu-Fu; Huang, Yu-Ting; Wang, Hsing-Kuo; Yao, Chung-Chen Jane; Sun, Jui-Sheng; Chao, Yuan-Hung

2017-12-28

Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes. Specifically, non-tenogenic gene expression, adipogenic potential, cell migration rate, filamentous actin expression, and the activation of signaling pathways were analyzed in tenocytes treated with high glucose, followed by the presence or absence of mechanical stretch. We analyzed tenocyte phenotype in vivo by immunohistochemistry using an STZ (streptozotocin)-induced long-term diabetic mouse model. High glucose-treated tenocytes expressed higher levels of the adipogenic transcription factors PPAR γ and C/EBPs. PPARγ was also highly expressed in diabetic tendons. In addition, increased adipogenic differentiation and decreased cell migration induced by high glucose implicated a fibroblast-to-adipocyte phenotypic change. By applying mechanical stretch to tenocytes in high-glucose conditions, adipogenic differentiation was repressed, while cell motility was enhanced, and fibroblastic morphology and gene expression profiles were strengthened. In part, these effects resulted from a stretch-induced activation of ERK (extracellular signal-regulated kinases) and a concomitant inactivation of Akt. Our results show that mechanical stretch alleviates the augmented adipogenic transdifferentiation potential of high glucose-treated tenocytes and helps maintain their fibroblastic characteristics. The alterations induced by high glucose highlight possible pathological mechanisms for diabetic tendinopathy

A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

PubMed

Christen, Patrik; Ito, Keita; van Rietbergen, Bert

2015-03-01

Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations. © 2015 Anatomical Society.

Increasing potential for intense tropical and subtropical thunderstorms under global warming.

PubMed

Singh, Martin S; Kuang, Zhiming; Maloney, Eric D; Hannah, Walter M; Wolding, Brandon O

2017-10-31

Intense thunderstorms produce rapid cloud updrafts and may be associated with a range of destructive weather events. An important ingredient in measures of the potential for intense thunderstorms is the convective available potential energy (CAPE). Climate models project increases in summertime mean CAPE in the tropics and subtropics in response to global warming, but the physical mechanisms responsible for such increases and the implications for future thunderstorm activity remain uncertain. Here, we show that high percentiles of the CAPE distribution (CAPE extremes) also increase robustly with warming across the tropics and subtropics in an ensemble of state-of-the-art climate models, implying strong increases in the frequency of occurrence of environments conducive to intense thunderstorms in future climate projections. The increase in CAPE extremes is consistent with a recently proposed theoretical model in which CAPE depends on the influence of convective entrainment on the tropospheric lapse rate, and we demonstrate the importance of this influence for simulated CAPE extremes using a climate model in which the convective entrainment rate is varied. We further show that the theoretical model is able to account for the climatological relationship between CAPE and a measure of lower-tropospheric humidity in simulations and in observations. Our results provide a physical basis on which to understand projected future increases in intense thunderstorm potential, and they suggest that an important mechanism that contributes to such increases may be present in Earth's atmosphere. Published under the PNAS license.

A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association.

PubMed

Cross, Amanda J; Ferrucci, Leah M; Risch, Adam; Graubard, Barry I; Ward, Mary H; Park, Yikyung; Hollenbeck, Albert R; Schatzkin, Arthur; Sinha, Rashmi

2010-03-15

Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P(trend) < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P(trend) = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P(trend) = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P(trend) = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P(trend) < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P(trend) <0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations.

Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

PubMed Central

Cohignac, Vanessa; Landry, Marion Julie; Boczkowski, Jorge; Lanone, Sophie

2014-01-01

The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s) still remain(s) unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity. PMID:28344236

Music and literature: are there shared empathy and predictive mechanisms underlying their affective impact?

PubMed Central

Omigie, Diana

2015-01-01

It has been suggested that music and language had a shared evolutionary precursor before becoming mainly responsible for the communication of emotive and referential meaning respectively. However, emphasis on potential differences between music and language may discourage a consideration of the commonalities that music and literature share. Indeed, one possibility is that common mechanisms underlie their affective impact, and the current paper carefully reviews relevant neuroscientific findings to examine such a prospect. First and foremost, it will be demonstrated that considerable evidence of a common role of empathy and predictive processes now exists for the two domains. However, it will also be noted that an important open question remains: namely, whether the mechanisms underlying the subjective experience of uncertainty differ between the two domains with respect to recruitment of phylogenetically ancient emotion areas. It will be concluded that a comparative approach may not only help to reveal general mechanisms underlying our responses to music and literature, but may also help us better understand any idiosyncrasies in their capacity for affective impact. PMID:26379583

Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

PubMed

Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

2013-03-01

Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

Molecular Mechanics: The Method and Its Underlying Philosophy.

ERIC Educational Resources Information Center

Boyd, Donald B.; Lipkowitz, Kenny B.

1982-01-01

Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

Mechanisms underlying subunit independence in pyramidal neuron dendrites

PubMed Central

Behabadi, Bardia F.; Mel, Bartlett W.

2014-01-01

Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate local spikes, which has led to the proposal that their dendrites act as independent computational subunits within a multilayered processing scheme. However, when a PN is strongly activated, back-propagating action potentials (bAPs) sweeping outward from the soma synchronize dendritic membrane potentials many times per second. How PN dendrites maintain the independence of their voltage-dependent computations, despite these repeated voltage resets, remains unknown. Using a detailed compartmental model of a layer 5 PN, and an improved method for quantifying subunit independence that incorporates a more accurate model of dendritic integration, we first established that the output of each dendrite can be almost perfectly predicted by the intensity and spatial configuration of its own synaptic inputs, and is nearly invariant to the rate of bAP-mediated “cross-talk” from other dendrites over a 100-fold range. Then, through an analysis of conductance, voltage, and current waveforms within the model cell, we identify three biophysical mechanisms that together help make independent dendritic computation possible in a firing neuron, suggesting that a major subtype of neocortical neuron has been optimized for layered, compartmentalized processing under in-vivo–like spiking conditions. PMID:24357611

Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation.

PubMed

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

2017-09-29

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

Lifelong bilingualism and neural reserve against Alzheimer's disease: a review of findings and potential mechanisms.

PubMed

Gold, Brian T

2015-03-15

Alzheimer's disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

Plant-Microbial Interactions Define Potential Mechanisms of Organic Matter Priming in the Rhizosphere

NASA Astrophysics Data System (ADS)

Zhalnina, K.; Cho, H. J.; Hao, Z.; Mansoori, N.; Karaoz, U.; Jenkins, S.; White, R. A., III; Lipton, M. S.; Deng, K.; Zhou, J.; Pett-Ridge, J.; Northen, T.; Firestone, M. K.; Brodie, E.

2015-12-01

In the rhizosphere, metabolic processes of plants and microorganisms are closely coupled, and together with soil minerals, their interactions regulate the turnover of soil organic C (SOC). Plants provide readily assimilable metabolites for microorganisms through exudation, and it has been hypothesized that increasing concentrations of exudate C may either stimulate or suppress rates of SOC mineralization (rhizosphere priming). Both positive and negative rhizosphere priming has been widely observed, however the underlying mechanisms remain poorly understood. To begin to identify the molecular mechanisms underlying rhizosphere priming, we isolated a broad range of soil bacteria from a Mediterranean grassland dominated by annual grass. Thirty-nine heterotrophic bacteria were selected for genome sequencing and both rRNA gene analysis and metagenome coverage suggest that these isolates represent naturally abundant strain variants. We analyzed their genomes for potential metabolic traits related to life in the rhizosphere and the decomposition of polymeric SOC. While the two dominant groups, Alphaproteobacteria and Actinobacteria, were enriched in polymer degrading enzymes, Alphaproteobacterial isolates contained greater gene copies of transporters related to amino acid, organic acid and auxin uptake or export, suggesting an enhanced metabolic potential for life in the root zone. To verify this metabolic potential, we determined the enzymatic activities of these isolates and revealed preferences of strains to degrade certain polymers (xylan, cellulose or lignin). Fourier Transform Infrared spectroscopy is being used to determine which polymeric components of plant roots are targeted by specific strains and how exudates may impact their degradation. To verify the potential of isolates to assimilate root exudates and export key metabolites we are using LC-MS/MS based exometabolomic profiling. The traits hypothesized and verified here (transporters, enzymes, exudate uptake

Priming of Short-Term Potentiation and Synaptic Tagging/Capture Mechanisms by Ryanodine Receptor Activation in Rat Hippocampal CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Li, Qin; Abraham, Wickliffe C.; Xiao, Zhi Cheng

2009-01-01

Activity-dependent changes in synaptic strength such as long-term potentiation (LTP) and long-term depression (LTD) are considered to be cellular mechanisms underlying learning and memory. Strengthening of a synapse for a few seconds or minutes is termed short-term potentiation (STP) and is normally unable to take part in the processes of synaptic…

DNA under Force: Mechanics, Electrostatics, and Hydration.

PubMed

Li, Jingqiang; Wijeratne, Sithara S; Qiu, Xiangyun; Kiang, Ching-Hwa

2015-02-25

Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

Cadmium transfer and detoxification mechanisms in a soil-mulberry-silkworm system: phytoremediation potential.

PubMed

Zhou, Lingyun; Zhao, Ye; Wang, Shuifeng

2015-11-01

Phytoremediation has been proven to be an environmentally sound alternative for the recovery of contaminated soils, and the economic profit that comes along with the process might stimulate its field use. This study investigated cadmium (Cd) transfer and detoxification mechanisms in a soil-mulberry-silkworm system to estimate the suitability of the mulberry and silkworm as an alternative method for the remediation of Cd-polluted soil; it also explored the underlying mechanisms regulating the trophic transfer of Cd. The results show that both the mulberry and silkworm have high Cd tolerance. The transfer factor suggests that the mulberry has high potential for Cd extraction from polluted soil. The subcellular distribution and chemical forms of Cd in mulberry leaves show that cell wall deposition and vacuolar compartmentalization play important role in Cd tolerance. In the presence of increasing Cd concentrations in silkworm food, detoxification mechanisms (excretion and homeostasis) were activated so that excess Cd was excreted in fecal balls, and metallothionein levels in the mid-gut, the posterior of the silk gland, and the fat body of silkworms were enhanced. And, the Cd concentrations in silk are at a low level, ranging from 0.02 to 0.21 mg kg(-1). Therefore, these mechanisms of detoxification can regulate Cd trophic transfer, and mulberry planting and silkworm breeding has high phytoremediation potential for Cd-contaminated soil.

Effects of early-life malnutrition on neurodevelopment and neuropsychiatric disorders and the potential mechanisms.

PubMed

Yan, Xintian; Zhao, Xinzhi; Li, Juxue; He, Lin; Xu, Mingqing

2018-04-20

Lines of evidence have demonstrated that early-life malnutrition is highly correlated with neurodevelopment and adulthood neuropsychiatric disorders, while some findings are conflicting with each other. In addition, the biological mechanisms are less investigated. We systematically reviewed the evidence linking early-life nutrition status with neurodevelopment and clinical observations in human and animal models. We summarized the effects of special nutritious on neuropsychiatric disorders and explored the underlying potential mechanisms. The further understanding of the biological regulation of early-life nutritional status on neurodevelopment might shed light on precision nutrition at an integrative systems biology framework. Copyright © 2018 Elsevier Inc. All rights reserved.

Relative refractoriness of left ventricular contraction underlies human tachycardia-induced mechanical and electrical alternans.

PubMed

Kashimura, Takeshi; Kodama, Makoto; Watanabe, Tohru; Tanaka, Komei; Hayashi, Yuka; Ohno, Yukako; Obata, Hiroaki; Ito, Masahiro; Hirono, Satoru; Hanawa, Haruo; Minamino, Tohru

2014-02-01

Mechanical alternans (MA) and electrical alternans (EA) are predictors of cardiac events. Experimental studies have suggested that refractoriness of calcium cycling underlies these cardiac alternans. However, refractoriness of left ventricular contraction has not been examined in patients with cardiac alternans. In 51 patients with miscellaneous heart diseases, incremental right atrial pacing was performed to induce MA and EA. MA was quantified by alternans amplitude (AA: the difference between left ventricular dP/dt of a strong beat and that of a weak beat), and AA at 100/min (AA100) and maximal AA (AAmax) were measured. EA was defined as alternation of T wave morphology in 12-lead electrocardiogram. Relative refractoriness of left ventricular contraction was examined by drawing the mechanical restitution curve under a basal coupling interval (BCL) of 600 ms (100/min) and was assessed by the slope at BCL (Δmechanical restitution). Postextrasystolic potentiation (PESP) was also examined and the slope of PESP curve (ΔPESP) was assessed as a property to alternate strong and weak beats. MA and EA were induced in 19 patients and in none at 100/min or less, and at any heart rate in 32 and in 10, respectively. AA100 and AAmax correlated positively with Δmechanical restitution and negatively with ΔPESP. Patients with EA had a significantly larger Δmechanical restitution and a significantly larger absolute value of ΔPESP than those without. In patients with MA and EA, the left ventricular contractile force during tachycardia is under relative refractoriness and prone to cause large fluctuation of contractile force. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Preterm Infant Weight Gain is Increased by Massage Therapy and Exercise Via Different Underlying Mechanisms

PubMed Central

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

2014-01-01

Objective To compare the effects of massage therapy (moderate pressure stroking) and exercise (flexion and extension of limbs) on preterm infants’ weight gain and to explore potential underlying mechanisms for those effects. Methods Weight gain and parasympathetic nervous system activity were assessed in 30 preterm infants randomly assigned to a massage therapy group or to an exercise group. Infants received 10 minutes of moderate pressure massage or passive flexion and extension of the limbs 3 times per day for 5 days, and EKGs were collected during the first session to assess vagal activity. Results Both massage and exercise led to increased weight gain. However, while exercise was associated with increased calorie consumption, massage was related to increased vagal activity. Conclusion Taken together, these findings suggest that massage and exercise lead to increased preterm infant weight gain via different underlying mechanisms. PMID:24480603

Optimum design of bolted composite lap joints under mechanical and thermal loading

NASA Astrophysics Data System (ADS)

Kradinov, Vladimir Yurievich

A new approach is developed for the analysis and design of mechanically fastened composite lap joints under mechanical and thermal loading. Based on the combined complex potential and variational formulation, the solution method satisfies the equilibrium equations exactly while the boundary conditions are satisfied by minimizing the total potential. This approach is capable of modeling finite laminate planform dimensions, uniform and variable laminate thickness, laminate lay-up, interaction among bolts, bolt torque, bolt flexibility, bolt size, bolt-hole clearance and interference, insert dimensions and insert material properties. Comparing to the finite element analysis, the robustness of the method does not decrease when modeling the interaction of many bolts; also, the method is more suitable for parametric study and design optimization. The Genetic Algorithm (GA), a powerful optimization technique for multiple extrema functions in multiple dimensions search spaces, is applied in conjunction with the complex potential and variational formulation to achieve optimum designs of bolted composite lap joints. The objective of the optimization is to acquire such a design that ensures the highest strength of the joint. The fitness function for the GA optimization is based on the average stress failure criterion predicting net-section, shear-out, and bearing failure modes in bolted lap joints. The criterion accounts for the stress distribution in the thickness direction at the bolt location by applying an approach utilizing a beam on an elastic foundation formulation.

Herb pair Danggui-Honghua: mechanisms underlying blood stasis syndrome by system pharmacology approach

NASA Astrophysics Data System (ADS)

Yue, Shi-Jun; Xin, Lan-Ting; Fan, Ya-Chu; Li, Shu-Jiao; Tang, Yu-Ping; Duan, Jin-Ao; Guan, Hua-Shi; Wang, Chang-Yun

2017-01-01

Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.

Mechanism underlying impaired cardiac pacemaking rhythm during ischemia: A simulation study

NASA Astrophysics Data System (ADS)

Bai, Xiangyun; Wang, Kuanquan; Yuan, Yongfeng; Li, Qince; Dobrzynski, Halina; Boyett, Mark R.; Hancox, Jules C.; Zhang, Henggui

2017-09-01

Ischemia in the heart impairs function of the cardiac pacemaker, the sinoatrial node (SAN). However, the ionic mechanisms underlying the ischemia-induced dysfunction of the SAN remain elusive. In order to investigate the ionic mechanisms by which ischemia causes SAN dysfunction, action potential models of rabbit SAN and atrial cells were modified to incorporate extant experimental data of ischemia-induced changes to membrane ion channels and intracellular ion homeostasis. The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium. Using the multi-scale models, the functional impact of ischemia-induced electrical alterations on cardiac pacemaking action potentials (APs) and their conduction was investigated. The effects of vagal tone activity on the regulation of cardiac pacemaker activity in control and ischemic conditions were also investigated. The simulation results showed that at the cellular level ischemia slowed the SAN pacemaking rate, which was mainly attributable to the altered Na+-Ca2+ exchange current and the ATP-sensitive potassium current. In the 2D SAN-atrium tissue model, ischemia slowed down both the pacemaking rate and the conduction velocity of APs into the surrounding atrial tissue. Simulated vagal nerve activity, including the actions of acetylcholine in the model, amplified the effects of ischemia, leading to possible SAN arrest and/or conduction exit block, which are major features of the sick sinus syndrome. In conclusion, this study provides novel insights into understanding the mechanisms by which ischemia alters SAN function, identifying specific conductances as contributors to bradycardia and conduction block.

Mechanical and thermal buckling analysis of rectangular sandwich panels under different edge conditions

NASA Technical Reports Server (NTRS)

Ko, William L.

1994-01-01

The combined load (mechanical or thermal load) buckling equations were established for orthotropic rectangular sandwich panels under four different edge conditions by using the Rayleigh-Ritz method of minimizing the total potential energy of a structural system. Two-dimensional buckling interaction curves and three-dimensional buckling interaction surfaces were constructed for high-temperature honeycomb-core sandwich panels supported under four different edge conditions. The interaction surfaces provide overall comparison of the panel buckling strengths and the domains of symmetrical and antisymmetrical buckling associated with the different edge conditions. In addition, thermal buckling curves of these sandwich panels are presented. The thermal buckling conditions for the cases with and without thermal moments were found to be identical for the small deformation theory.

Insights into the mechanisms underlying colonic motor patterns

PubMed Central

Dinning, Phil G.; Brookes, Simon J.; Costa, Marcello

2016-01-01

Abstract In recent years there have been significant technical and methodological advances in our ability to record the movements of the gastrointestinal tract. This has led to significant changes in our understanding of the different types of motor patterns that exist in the gastrointestinal tract (particularly the large intestine) and in our understanding of the mechanisms underlying their generation. Compared with other tubular smooth muscle organs, a rich variety of motor patterns occurs in the large intestine. This reflects a relatively autonomous nervous system in the gut wall, which has its own unique population of sensory neurons. Although the enteric nervous system can function independently of central neural inputs, under physiological conditions bowel motility is influenced by the CNS: if spinal pathways are disrupted, deficits in motility occur. The combination of high resolution manometry and video imaging has improved our knowledge of the range of motor patterns and provided some insight into the neural and mechanical factors underlying propulsion of contents. The neural circuits responsible for the generation of peristalsis and colonic migrating motor complexes have now been identified to lie within the myenteric plexus and do not require inputs from the mucosa or submucosal ganglia for their generation, but can be modified by their activity. This review will discuss the recent advances in our understanding of the different patterns of propagating motor activity in the large intestine of mammals and how latest technologies have led to major changes in our understanding of the mechanisms underlying their generation. PMID:26990133

Escape rate of Brownian particles from a metastable potential well under time derivative Ornstein-Uhlenbeck noise

NASA Astrophysics Data System (ADS)

Bai, Zhan-Wu; Wang, Ping

2016-03-01

We investigate the escape rate of Brownian particles that move in a cubic metastable potential subjected to an internal time derivative Ornstein-Uhlenbeck noise (DOUN). This noise can induce the ballistic diffusion of force-free Brownian particles. Some new features are found. The escape rate for DOUN shows qualitative different dependence on potential well width compared with OUN which induces normal diffusion. As the potential barrier height decreases, the escape rate of DOUN deviates from Arrhenius law considerably earlier than that of Ornstein-Uhlenbeck noise (OUN). The Brownian particles escape faster under DOUN than that under OUN. A quasi-periodic oscillation occurs in transient state. A solvable case is presented to demonstrate the significant cancellation behavior in the barrier region that governs most of these phenomena. The physical mechanism of the findings can be clarified by the noise features. These characteristics should be common for internal noises that induce superdiffusion, especially the ballistic diffusion.

Potential mechanisms for chemotherapy-induced impairments in cognitive function.

PubMed

Jansen, Catherine; Miaskowski, Christine; Dodd, Marilyn; Dowling, Glenna; Kramer, Joel

2005-11-03

To review the domains of cognitive function and their corresponding neuroanatomic structures as well as present current evidence for neurotoxicity associated with specific chemotherapeutic agents and potential mechanisms for chemotherapy-induced cognitive impairments. Published research articles, review articles, and textbooks. Chemotherapy does not appear to cross the blood-brain barrier when given in standard doses; however, many chemotherapy drugs have the potential to cause cognitive impairments through more than one mechanism. In addition, patient factors may be protective or place individuals at higher risk for cognitive impairments. Although evidence of chemotherapy-induced impairments in cognitive function exists, no clinical studies have attempted to elucidate the mechanisms for chemotherapy-induced impairments in cognitive function. In addition, further studies are needed to determine predictive factors, potential biomarkers, and relevant assessment parameters. The ability to identify high-risk patients has important implications for practice in regard to informed consent, patient education about the effects of treatment, and preventive strategies.

Turing mechanism underlying a branching model for lung morphogenesis.

PubMed

Xu, Hui; Sun, Mingzhu; Zhao, Xin

2017-01-01

The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

Quantum mechanical streamlines. I - Square potential barrier

NASA Technical Reports Server (NTRS)

Hirschfelder, J. O.; Christoph, A. C.; Palke, W. E.

1974-01-01

Exact numerical calculations are made for scattering of quantum mechanical particles hitting a square two-dimensional potential barrier (an exact analog of the Goos-Haenchen optical experiments). Quantum mechanical streamlines are plotted and found to be smooth and continuous, to have continuous first derivatives even through the classical forbidden region, and to form quantized vortices around each of the nodal points. A comparison is made between the present numerical calculations and the stationary wave approximation, and good agreement is found between both the Goos-Haenchen shifts and the reflection coefficients. The time-independent Schroedinger equation for real wavefunctions is reduced to solving a nonlinear first-order partial differential equation, leading to a generalization of the Prager-Hirschfelder perturbation scheme. Implications of the hydrodynamical formulation of quantum mechanics are discussed, and cases are cited where quantum and classical mechanical motions are identical.

Lifelong Bilingualism and Neural Reserve against Alzheimer’s disease: A Review of Findings and Potential Mechanisms

PubMed Central

Gold, Brian T.

2014-01-01

Alzheimer’s disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. PMID:25496781

New potentials for conformal mechanics

NASA Astrophysics Data System (ADS)

Papadopoulos, G.

2013-04-01

We find under some mild assumptions that the most general potential of one-dimensional conformal systems with time-independent couplings is expressed as V = V0 + V1, where V0 is a homogeneous function with respect to a homothetic motion in configuration space and V1 is determined from an equation with source a homothetic potential. Such systems admit at most an SL(2,{R}) conformal symmetry which, depending on the couplings, is embedded in {Diff}({R}) in three different ways. In one case, SL(2,{R}) is also embedded in Diff(S1). Examples of such models include those with potential V = αx2 + βx-2 for arbitrary couplings α and β, the Calogero models with harmonic oscillator couplings and nonlinear models with suitable metrics and potentials. In addition, we give the conditions on the couplings for a class of gauge theories to admit a SL(2,{R}) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries that include the isometries of AdS2 × S3 and AdS2 × S3 × S3 which arise as backgrounds in AdS2/CFT1.

Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms.

PubMed

Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-31

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.

Advanced paternal age effects in neurodevelopmental disorders—review of potential underlying mechanisms

PubMed Central

Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-01

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders. PMID:28140401

Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

PubMed Central

Cha, Chae Young; Nakamura, Yasuhiko; Himeno, Yukiko; Wang, JianWu; Fujimoto, Shinpei; Inagaki, Nobuya; Earm, Yung E

2011-01-01

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings. PMID:21708953

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

PubMed Central

Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

2015-01-01

Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID:26136672

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation.

PubMed

Chervyakov, Alexander V; Chernyavsky, Andrey Yu; Sinitsyn, Dmitry O; Piradov, Michael A

2015-01-01

Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

Amount of fear extinction changes its underlying mechanisms.

PubMed

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-07-03

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

Mechanisms underlying the antihypertensive properties of Urtica dioica.

PubMed

Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

2016-09-01

Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

Mechanisms defining the electrotonic potential abnormalities in simulated amyotrophic lateral sclerosis.

PubMed

Stephanova, D I; Krustev, S M; Negrev, N

2012-06-01

Electrotonic potentials allow the accommodative processes to polarizing stimuli to be assessed. Electrotonic potential transients in response to applied polarizing stimuli are caused by the kinetics of underlying axonal conductances. Here, we study these transients using our multi-layered model of the human motor nerve, in three simulated cases of the motor neuron disease amyotrophic lateral sclerosis (ALS): ALS1, ALS2 and ALS3 are three consecutively greater degrees of uniform axonal dysfunctions along the human motor nerve fibre. The results show that the responses in the ALS1 case are quite similar to the normal case. In contrast, in the ALS2 and ALS3 cases, long-lasting (100 ms) subthreshold depolarizing stimuli activate the classical "transient" Na(+) channels in the nodal and in the internodal axolemma beneath the myelin sheath; this leads to action potential generation during the early parts of the electrotonic responses in all compartments along the fibre length. The results also show that the electrotonic potentials in response to long-lasting (100 ms) subthreshold hyperpolarizing stimuli in the ALS1 and ALS2 cases are quiet similar to those of the normal case. However, the current kinetics in the ALS3 case differs from the normal case after the termination of the long-lasting hyperpolarizing stimuli. In the most abnormal ALS3 case, the activation of the Na(+) channels in the nodal and in the internodal axolemma leads to repetitive action potential generation in the late parts (100-200 ms) of the hyperpolarizing electrotonic responses. The results show that the repetitive firing, due to the progressively increased nodal and internodal ion channel dysfunction, are consistent with the loss of functional potassium channels involving both the fast and the slow potassium channel types. The results confirm that the electrotonic potentials in the three simulated ALS cases are specific indicators for the motor neuron disease ALS. The mechanisms underlying the

Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

PubMed Central

Williams, Stephen R; Stuart, Greg J

1999-01-01

Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from

Skylab fluid mechanics simulations: Oscillation, rotation, collision and coalescence of water droplets under low-gravity environment

NASA Technical Reports Server (NTRS)

Vaughan, O. H., Jr.; Hung, R. J.

1975-01-01

Skylab 4 crew members performed a series of demonstrations showing the oscillations, rotations, as well as collision coalescence of water droplets which simulate various physical models of fluids under low gravity environment. The results from Skylab demonstrations provide information and illustrate the potential of an orbiting space-oriented research laboratory for the study of more sophisticated fluid mechanic experiments. Experiments and results are discussed.

Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon "Candidatus Nitrosotalea devanaterra".

PubMed

Lehtovirta-Morley, Laura E; Sayavedra-Soto, Luis A; Gallois, Nicolas; Schouten, Stefan; Stein, Lisa Y; Prosser, James I; Nicol, Graeme W

2016-05-01

Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer "Candidatus Nitrosotalea devanaterra" provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of "Ca Nitrosotalea devanaterra" reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that "Ca Nitrosotalea devanaterra" contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography-mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of "Ca Nitrosotalea devanaterra" were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. Copyright © 2016 Lehtovirta-Morley et al.

The costly filtering of potential distraction: evidence for a supramodal mechanism.

PubMed

Marini, Francesco; Chelazzi, Leonardo; Maravita, Angelo

2013-08-01

When dealing with significant sensory stimuli, performance can be hampered by distracting events. Attention mechanisms lessen such negative effects, enabling selection of relevant information while blocking potential distraction. Recent work shows that preparatory brain activity, occurring before a critical stimulus, may reflect mechanisms of attentional control aimed to filter upcoming distracters. However, it is unknown whether the engagement of these filtering mechanisms to counteract distraction in itself taxes cognitive-brain systems, leading to performance costs. Here we address this question and, specifically, seek the behavioral signature of a mechanism for the filtering of potential distraction within and between sensory modalities. We show that, in potentially distracting contexts, a filtering mechanism is engaged to cope with forthcoming distraction, causing a dramatic behavioral cost in no-distracter trials during a speeded tactile discrimination task. We thus demonstrate an impaired processing caused by a potential, yet absent, distracter. This effect generalizes across different sensory modalities, such as vision and audition, and across different manipulations of the context, such as the distracter's sensory modality and pertinence to the task. Moreover, activation of the filtering mechanism relies on both strategic and reactive processes, as shown by its dynamic dependence on probabilistic and cross-trial contingencies. Crucially, across participants, the observed strategic cost is inversely related to the interference exerted by a distracter on distracter-present trials. These results attest to a mechanism for the monitoring and filtering of potential distraction in the human brain. Although its activation is indisputably beneficial when distraction occurs, it leads to robust costs when distraction is actually expected but currently absent. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Mechanisms underlying REBT in mood disordered patients: predicting depression from the hybrid model of learning.

PubMed

Jackson, Chris J; Izadikah, Zahra; Oei, Tian P S

2012-06-01

Jackson's (2005, 2008a) hybrid model of learning identifies a number of learning mechanisms that lead to the emergence and maintenance of the balance between rationality and irrationality. We test a general hypothesis that Jackson's model will predict depressive symptoms, such that poor learning is related to depression. We draw comparisons between Jackson's model and Ellis' (2004) Rational Emotive Behavior Therapy and Theory (REBT) and thereby provide a set of testable learning mechanisms potentially underlying REBT. Results from 80 patients diagnosed with depression completed the learning styles profiler (LSP; Jackson, 2005) and two measures of depression. Results provide support for the proposed model of learning and further evidence that low rationality is a key predictor of depression. We conclude that the hybrid model of learning has the potential to explain some of the learning and cognitive processes related to the development and maintenance of irrational beliefs and depression. Copyright © 2011. Published by Elsevier B.V.

Students' Conceptual Difficulties in Quantum Mechanics: Potential Well Problems

ERIC Educational Resources Information Center

Ozcan, Ozgur; Didis, Nilufer; Tasar, Mehmet Fatih

2009-01-01

In this study, students' conceptual difficulties about some basic concepts in quantum mechanics like one-dimensional potential well problems and probability density of tunneling particles were identified. For this aim, a multiple choice instrument named Quantum Mechanics Conceptual Test has been developed by one of the researchers of this study…

Maize water status and physiological traits as affected by root endophytic fungus Piriformospora indica under combined drought and mechanical stresses.

PubMed

Hosseini, Fatemeh; Mosaddeghi, Mohammad Reza; Dexter, Anthony Roger; Sepehri, Mozhgan

2018-05-01

Under combined drought and mechanical stresses, mechanical stress primarily controlled physiological responses of maize. Piriformospora indica mitigated the adverse effects of stresses, and inoculated maize experienced less oxidative damage and had better adaptation to stressful conditions. The objective of this study was to investigate the effect of maize root colonization by an endophytic fungus P. indica on plant water status, physiological traits and root morphology under combined drought and mechanical stresses. Seedlings of inoculated and non-inoculated maize (Zea mays L., cv. single cross 704) were cultivated in growth chambers filled with moistened siliceous sand at a matric suction of 20 hPa. Drought stress was induced using PEG 6000 solution with osmotic potentials of 0, - 0.3 and - 0.5 MPa. Mechanical stress (i.e., penetration resistances of 1.05, 4.23 and 6.34 MPa) was exerted by placing weights on the surface of the sand medium. After 30 days, leaf water potential (LWP) and relative water content (RWC), root and shoot fresh weights, root volume (RV) and diameter (RD), leaf proline content, leaf area (LA) and catalase (CAT) and ascorbate peroxidase (APX) activities were measured. The results show that exposure to individual drought and mechanical stresses led to higher RD and proline content and lower plant biomass, RV and LA. Moreover, increasing drought and mechanical stress severity increased APX activity by about 1.9- and 3.1-fold compared with the control. When plants were exposed to combined stresses, mechanical stress played the dominant role in controlling plant responses. P. indica-inoculated plants are better adapted to individual and combined stresses. The inoculated plants had greater RV, LA, RWC, LWP and proline content under stressful conditions. In comparison with non-inoculated plants, inoculated plants showed lower CAT and APX activities which means that they experienced less oxidative stress induced by stressful conditions.

Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

PubMed

Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

2016-01-01

Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

Amount of fear extinction changes its underlying mechanisms

PubMed Central

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-01-01

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that. DOI: http://dx.doi.org/10.7554/eLife.25224.001 PMID:28671550

The mismatch negativity: A review of underlying mechanisms

PubMed Central

Garrido, Marta I.; Kilner, James M.; Stephan, Klaas E.; Friston, Karl J.

2009-01-01

The mismatch negativity (MMN) is a brain response to violations of a rule, established by a sequence of sensory stimuli (typically in the auditory domain) [Näätänen R. Attention and brain function. Hillsdale, NJ: Lawrence Erlbaum; 1992]. The MMN reflects the brain’s ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory learning and perceptual accuracy. Although the MMN has been studied extensively, the neurophysiological mechanisms underlying the MMN are not well understood. Several hypotheses have been put forward to explain the generation of the MMN; amongst these accounts, the “adaptation hypothesis” and the “model adjustment hypothesis” have received the most attention. This paper presents a review of studies that focus on neuronal mechanisms underlying the MMN generation, discusses the two major explanatory hypotheses, and proposes predictive coding as a general framework that attempts to unify both. PMID:19181570

Mechanical and thermal buckling analysis of sandwich panels under different edge conditions

NASA Technical Reports Server (NTRS)

Ko, William L.

1993-01-01

By using the Rayleigh-Ritz method of minimizing the total potential energy of a structural system, combined load (mechanical or thermal load) buckling equations are established for orthotropic rectangular sandwich panels supported under four different edge conditions. Two-dimensional buckling interaction curves and three dimensional buckling interaction surfaces are constructed for high-temperature honeycomb-core sandwich panels supported under four different edge conditions. The interaction surfaces provide easy comparison of the panel buckling strengths and the domains of symmetrical and antisymmetrical buckling associated with the different edge conditions. Thermal buckling curves of the sandwich panels also are presented. The thermal buckling conditions for the cases with and without thermal moments were found to be identical for the small deformation theory. In sandwich panels, the effect of transverse shear is quite large, and by neglecting the transverse shear effect, the buckling loads could be overpredicted considerably. Clamping of the edges could greatly increase buckling strength more in compression than in shear.

Experimental Analysis of the Mechanism of Hearing under Water

PubMed Central

Chordekar, Shai; Kishon-Rabin, Liat; Kriksunov, Leonid; Adelman, Cahtia; Sohmer, Haim

2015-01-01

The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC). PMID:26770975

Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure.

PubMed

de Steenhuijsen Piters, Wouter A A; Bogaert, Debby

2016-02-02

The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem-also called "microbiome"-is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. Copyright © 2016 de Steenhuijsen Piters and Bogaert.

Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure

PubMed Central

de Steenhuijsen Piters, Wouter A. A.

2016-01-01

ABSTRACT The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. PMID:26838716

Neural mechanisms underlying the integration of situational information into attribution outcomes.

PubMed

Brosch, Tobias; Schiller, Daniela; Mojdehbakhsh, Rachel; Uleman, James S; Phelps, Elizabeth A

2013-08-01

When forming impressions and trying to figure out why other people behave the way they do, we should take into account not only dispositional factors (i.e., personality traits) but also situational constraints as potential causes for a behavior. However, in their attributions, people often ignore the importance of situational factors. To investigate the neural mechanisms underlying the integration of situational information into attributions, we decomposed the attribution process by separately presenting information about behaviors and about the situational circumstances in which they occur. After reading the information, participants judged whether dispositional or situational causes explained the behavior (attribution), and how much they liked the person described in the scenario (affective evaluation). The dorsolateral prefrontal cortex showed increased blood oxygenation-level-dependent activation during the encoding of situational information when the resulting attribution was situational, relative to when the attribution was dispositional, potentially reflecting a controlled process that integrates situational information into attributions. Interestingly, attributions were strongly linked to subsequent affective evaluations, with the dorsomedial prefrontal cortex emerging as potential substrate of the integration of attributions and affective evaluations. Our findings demonstrate how top-down control processes regulate impression formation when situational information is taken into account to understand others.

Neural mechanisms underlying the integration of situational information into attribution outcomes

PubMed Central

Brosch, Tobias; Schiller, Daniela; Mojdehbakhsh, Rachel; Uleman, James S.; Phelps, Elizabeth A.

2013-01-01

When forming impressions and trying to figure out why other people behave the way they do, we should take into account not only dispositional factors (i.e. personality traits) but also situational constraints as potential causes for a behavior. However, in their attributions, people often ignore the importance of situational factors. To investigate the neural mechanisms underlying the integration of situational information into attributions, we decomposed the attribution process by separately presenting information about behaviors and about the situational circumstances in which they occur. After reading the information, participants judged whether dispositional or situational causes explained the behavior (attribution), and how much they liked the person described in the scenario (affective evaluation). The dorsolateral prefrontal cortex showed increased blood oxygenation-level-dependent activation during the encoding of situational information when the resulting attribution was situational, relative to when the attribution was dispositional, potentially reflecting a controlled process that integrates situational information into attributions. Interestingly, attributions were strongly linked to subsequent affective evaluations, with the dorsomedial prefrontal cortex emerging as potential substrate of the integration of attributions and affective evaluations. Our findings demonstrate how top-down control processes regulate impression formation when situational information is taken into account to understand others. PMID:23446840

The Challenge of Characterizing Operations in the Mechanisms Underlying Behavior

ERIC Educational Resources Information Center

Bechtel, William

2005-01-01

Neuroscience and cognitive science seek to explain behavioral regularities in terms of underlying mechanisms. An important element of a mechanistic explanation is a characterization of the operations of the parts of the mechanism. The challenge in characterizing such operations is illustrated by an example from the history of physiological…

Mechanisms underlying the association between insomnia, anxiety, and depression in adolescence: Implications for behavioral sleep interventions.

PubMed

Blake, Matthew J; Trinder, John A; Allen, Nicholas B

2018-05-28

There is robust evidence of an association between insomnia, anxiety, and depression in adolescence. The aim of this review is to describe and synthesize potential mechanisms underlying this association and explore implications for the design of adolescent behavioral sleep interventions. Specifically, we examine whether insomnia symptoms are a mechanism for the development of internalizing symptoms in adolescence and whether sleep interventions are an effective treatment for both insomnia and internalizing symptoms in adolescence because they target the shared mechanisms underlying these disorders. Research using different methodologies points to the role of sequential, parallel, and interacting mechanisms. In this paper, we review a wide range of relevant biological (i.e., polymorphisms and dysregulation in serotonin, dopamine, and circadian clock genes; alterations in corticolimbic and mesolimbic brain circuits; cortisol reactivity to stress; inflammatory cytokine dysregulation; biased memory consolidation; changes in sleep architecture), psychological (i.e., cognitive inflexibility, interpretational biases, judgment biases, negative attribution styles, worry, rumination, biased attention to threat, dysfunctional beliefs and attitudes about sleep, misperception of sleep deficit), and social mechanisms (i.e., reduced and impaired social interactions, unhelpful parenting behaviors, family stress) and propose an integrative multilevel model of how these phenomena may interact to increase vulnerability to both insomnia and internalizing disorders. Several 'biopsychosocial' mechanisms hold promise as viable treatment targets for adolescent behavioral sleep interventions, which may reduce both insomnia and internalizing symptoms. Copyright © 2018 Elsevier Ltd. All rights reserved.

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

PubMed

Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

2015-05-01

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The

Artificial Bee Colony Optimization of Capping Potentials for Hybrid Quantum Mechanical/Molecular Mechanical Calculations.

PubMed

Schiffmann, Christoph; Sebastiani, Daniel

2011-05-10

We present an algorithmic extension of a numerical optimization scheme for analytic capping potentials for use in mixed quantum-classical (quantum mechanical/molecular mechanical, QM/MM) ab initio calculations. Our goal is to minimize bond-cleavage-induced perturbations in the electronic structure, measured by means of a suitable penalty functional. The optimization algorithm-a variant of the artificial bee colony (ABC) algorithm, which relies on swarm intelligence-couples deterministic (downhill gradient) and stochastic elements to avoid local minimum trapping. The ABC algorithm outperforms the conventional downhill gradient approach, if the penalty hypersurface exhibits wiggles that prevent a straight minimization pathway. We characterize the optimized capping potentials by computing NMR chemical shifts. This approach will increase the accuracy of QM/MM calculations of complex biomolecules.

Molecular mechanisms underlying deoxy‐ADP.Pi activation of pre‐powerstroke myosin

PubMed Central

Nowakowski, Sarah G.

2017-01-01

Abstract Myosin activation is a viable approach to treat systolic heart failure. We previously demonstrated that striated muscle myosin is a promiscuous ATPase that can use most nucleoside triphosphates as energy substrates for contraction. When 2‐deoxy ATP (dATP) is used, it acts as a myosin activator, enhancing cross‐bridge binding and cycling. In vivo, we have demonstrated that elevated dATP levels increase basal cardiac function and rescues function of infarcted rodent and pig hearts. Here we investigate the molecular mechanism underlying this physiological effect. We show with molecular dynamics simulations that the binding of dADP.Pi (dATP hydrolysis products) to myosin alters the structure and dynamics of the nucleotide binding pocket, myosin cleft conformation, and actin binding sites, which collectively yield a myosin conformation that we predict favors weak, electrostatic binding to actin. In vitro motility assays at high ionic strength were conducted to test this prediction and we found that dATP increased motility. These results highlight alterations to myosin that enhance cross‐bridge formation and reveal a potential mechanism that may underlie dATP‐induced improvements in cardiac function. PMID:28097776

Potential Mechanisms for Enhanced Zika Epidemic and Disease.

PubMed

Xia, Hongjie; Xie, Xuping; Shan, Chao; Shi, Pei-Yong

2018-05-11

A number of mechanisms have driven the explosive epidemics and severe diseases of Zika virus since 2007. Here, we comment on how herd immunity, heterologous flavivirus preimmunity, and viral mutations could enhance the epidemic potential and disease severity of Zika virus in humans.

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

PubMed

Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon “Candidatus Nitrosotalea devanaterra”

PubMed Central

Sayavedra-Soto, Luis A.; Gallois, Nicolas; Schouten, Stefan; Stein, Lisa Y.; Prosser, James I.; Nicol, Graeme W.

2016-01-01

Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer “Candidatus Nitrosotalea devanaterra” provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of “Ca. Nitrosotalea devanaterra” reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that “Ca. Nitrosotalea devanaterra” contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography–mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of “Ca. Nitrosotalea devanaterra” were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. PMID:26896134

Comparison of Regulation Mechanisms of Five Mulberry Ingredients on Insulin Secretion under Oxidative Stress.

PubMed

Zheng, Yun-Chong; He, Hao; Wei, Xing; Ge, Sheng; Lu, Yan-Hua

2016-11-23

The effects of mulberry ingredients including 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) on insulin secretion under oxidative stress were investigated. The results revealed that they had distinct effects on insulin secretion in H 2 O 2 -induced MIN 6 cells, especially DNJ, C3G, and C3R, while RES and OXY showed modest effects in low dose (12.5 μM). The mechanisms were demonstrated in signal pathway that after treatment with DNJ, C3G, and C3R, the expressions of glucokinase (GK) were up-regulated, leading to intracellular ATP accumulation and insulin secretion. They also bound to glucagon-like peptide-1 receptor (GLP-1R), improved GLP-1R, duodenal homeobox factor-1 (PDX-1) expression, and stimulated insulin secretion. Moreover, ROS production was inhibited, followed by a decreasing apoptosis rate, while RES and OXY accelerated the apoptosis at high dose (50 μM). This work expounded the potential mechanisms of mulberry ingredients on insulin secretion, indicating the potential application in the intervention against hyperglycemia.

Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions

DTIC Science & Technology

2013-01-01

REPORT Friction Stir Weld Failure Mechanisms in Aluminum -Armor Structures Under Ballistic Impact Loading Conditions 14. ABSTRACT 16. SECURITY...Stir Weld Failure Mechanisms in Aluminum -Armor Structures Under Ballistic Impact Loading Conditions M. Grujicic, B. Pandurangan, A. Arakere, C-F. Yen...K.O. Pedersen, Fracture Mechanisms of Aluminum Alloy AA7075-T651 Under Various Loading Conditions , Int. J. Impact Eng., 2010, 37, p 537–551 24. T

Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

PubMed

Han, Xiaorui; Leng, Xiaoming; Zhao, Man; Wu, Mei; Chen, Amei; Hong, Guoju; Sun, Ping

2017-12-22

Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration. © 2017 The Author(s).

Biological Communities in Desert Varnish and Potential Implications for Varnish Formation Mechanisms

NASA Astrophysics Data System (ADS)

Lang-Yona, Naama; Maier, Stefanie; Macholdt, Dorothea; Rodriguez-Caballero, Emilio; Müller-Germann, Isabell; Yordanova, Petya; Jochum, Klaus-Peter; Andreae, Meinrat O.; Pöschl, Ulrich; Weber, Bettina; Fröhlich-Nowoisky, Janine

2017-04-01

Desert varnishes are thin, orange to black coatings found on rocks in arid and semi-arid environments on Earth. The formation mechanisms of rock varnish are still under debate and the involvement of microorganisms in this process remains unclear. In this work we aimed to identify the microbial community occurring in rock varnish to potentially gain insights into the varnish formation mechanism. For this purpose, rocks coated with desert varnish were collected from the Anza-Borrego Desert, California, USA, as well as soils from underneath the rocks. DNA from both varnish coatings and soil samples was extracted and subsequently used for metagenomic analysis, as well as for q-PCR analyses for specific species quantification. The element composition of the varnish coatings was analyzed and compared to the soil samples. Rock varnish shows similar depleted elements, compared to soil, but Mn and Pb are 50-60 times enriched compared to the soil samples, and about 100 times enriched compared to the upper continental crust. Our genomic analyses suggest unique populations and different protein functional groups occurring in the varnish compared to soil samples. We discuss these differences and try to shed light on the mechanism of Mn oxyhydroxide production in desert varnish formation.

Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

PubMed Central

Karshikoff, Bianka; Sundelin, Tina; Lasselin, Julie

2017-01-01

Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development. A description of the features of central fatigue is provided, and the current evidence describing the association between inflammation and fatigue in various medical conditions is reviewed. Additionally, the effect of inflammation on specific neuronal processes that may be involved in distinct fatigue dimensions is described. We suggest that the multidimensional aspects of fatigue should be assessed in future studies of inflammation-induced fatigue and that this would benefit the development of effective therapeutic interventions. PMID:28163706

Mechanism underlying the heart rate dependency of wave reflection in the aorta: a numerical simulation.

PubMed

Xiao, Hanguang; Tan, Isabella; Butlin, Mark; Li, Decai; Avolio, Alberto P

2018-03-01

Arterial wave reflection has been shown to have a significant dependence on heart rate (HR). However, the underlying mechanisms inherent in the HR dependency of wave reflection have not been well established. This study aimed to investigate the potential mechanisms and role of arterial viscoelasticity using a 55-segment transmission line model of the human arterial tree combined with a fractional viscoelastic model. At varying degrees of viscoelasticity modeled as fractional order parameter α, reflection magnitude (RM), reflection index (RI), augmentation index (AIx), and a proposed novel normalized reflection coefficient (Γ norm ) were estimated at different HRs from 60 to 100 beats/min with a constant mean flow of 70 ml/s. RM, RI, AIx, and Γ norm at the ascending aorta decreased linearly with increasing HR at all degrees of viscoelasticity. The means ± SD of the HR dependencies of RM, RI, AIx, and Γ norm were -0.042 ± 0.004, -0.018 ± 0.001, -1.93 ± 0.55%, and -0.037 ± 0.002 per 10 beats/min, respectively. There was a significant and nonlinear reduction in RM, RI, and Γ norm with increasing α at all HRs. In addition, HR and α have a more pronounced effect on wave reflection at the aorta than at peripheral arteries. The potential mechanism of the HR dependency of wave reflection was explained by the inverse dependency of the reflection coefficient on frequency, with the harmonics of the pulse waveform moving toward higher frequencies with increasing HR. This HR dependency can be modulated by arterial viscoelasticity. NEW & NOTEWORTHY This in silico study addressed the underlying mechanisms of how heart rate influences arterial wave reflection based on a transmission line model and elucidated the role of arterial viscoelasticity in the dependency of arterial wave reflection on heart rate. This study provides insights into wave reflection as a frequency-dependent phenomenon and demonstrates the validity of using reflection magnitude and

The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms.

PubMed

Zhang, Yifan; Xu, Jingwei; Zhang, Kun; Yang, Wei; Li, Bingjin

2018-01-01

Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy". As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

PubMed Central

Byrne, N. G.; Muir, T. C.

1985-01-01

The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is

Potential Mechanisms of Exercise in Gestational Diabetes

PubMed Central

Golbidi, Saeid; Laher, Ismail

2013-01-01

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first diagnosed during pregnancy. This condition shares same array of underlying abnormalities as occurs in diabetes outside of pregnancy, for example, genetic and environmental causes. However, the role of a sedentary lifestyle and/or excess energy intake is more prominent in GDM. Physically active women are less likely to develop GDM and other pregnancy-related diseases. Weight gain in pregnancy causes increased release of adipokines from adipose tissue; many adipokines increase oxidative stress and insulin resistance. Increased intramyocellular lipids also increase cellular oxidative stress with subsequent generation of reactive oxygen species. A well-planned program of exercise is an important component of a healthy lifestyle and, in spite of old myths, is also recommended during pregnancy. This paper briefly reviews the role of adipokines in gestational diabetes and attempts to shed some light on the mechanisms by which exercise can be beneficial as an adjuvant therapy in GDM. In this regard, we discuss the mechanisms by which exercise increases insulin sensitivity, changes adipokine profile levels, and boosts antioxidant mechanisms. PMID:23691290

Metabolic memory and chronic diabetes complications: potential role for epigenetic mechanisms.

PubMed

Intine, Robert V; Sarras, Michael P

2012-10-01

Recent estimates indicate that diabetes mellitus currently affects more than 10 % of the world's population. Evidence from both the laboratory and large scale clinical trials has revealed that prolonged hyperglycemia induces chronic complications which persist and progress unimpeded even when glycemic control is pharmaceutically achieved via the phenomenon of metabolic memory. The epigenome is comprised of all chromatin modifications including post translational histone modification, expression control via miRNAs and the methylation of cytosine within DNA. Modifications of these epigenetic marks not only allow cells and organisms to quickly respond to changing environmental stimuli but also confer the ability of the cell to "memorize" these encounters. As such, these processes have gained much attention as potential molecular mechanisms underlying metabolic memory and chronic diabetic complications. Here we present a review of the very recent literature published pertaining to this subject.

A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

PubMed Central

Westmark, Cara Jean

2014-01-01

Numerous neurological disorders including fragile X syndrome, Down syndrome, autism, and Alzheimer’s disease are co-morbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity, and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold. PMID:25232349

Underlying Mechanism of Antimicrobial Activity of Chitosan Microparticles and Implications for the Treatment of Infectious Diseases

PubMed Central

Jeon, Soo Jin; Oh, Manhwan; Yeo, Won-Sik; Galvão, Klibs N.; Jeong, Kwang Cheol

2014-01-01

The emergence of antibiotic resistant microorganisms is a great public health concern and has triggered an urgent need to develop alternative antibiotics. Chitosan microparticles (CM), derived from chitosan, have been shown to reduce E. coli O157:H7 shedding in a cattle model, indicating potential use as an alternative antimicrobial agent. However, the underlying mechanism of CM on reducing the shedding of this pathogen remains unclear. To understand the mode of action, we studied molecular mechanisms of antimicrobial activity of CM using in vitro and in vivo methods. We report that CM are an effective bactericidal agent with capability to disrupt cell membranes. Binding assays and genetic studies with an ompA mutant strain demonstrated that outer membrane protein OmpA of E. coli O157:H7 is critical for CM binding, and this binding activity is coupled with a bactericidal effect of CM. This activity was also demonstrated in an animal model using cows with uterine diseases. CM treatment effectively reduced shedding of intrauterine pathogenic E. coli (IUPEC) in the uterus compared to antibiotic treatment. Since Shiga-toxins encoded in the genome of bacteriophage is often overexpressed during antibiotic treatment, antibiotic therapy is generally not recommended because of high risk of hemolytic uremic syndrome. However, CM treatment did not induce bacteriophage or Shiga-toxins in E. coli O157:H7; suggesting that CM can be a potential candidate to treat infections caused by this pathogen. This work establishes an underlying mechanism whereby CM exert antimicrobial activity in vitro and in vivo, providing significant insight for the treatment of diseases caused by a broad spectrum of pathogens including antibiotic resistant microorganisms. PMID:24658463

Investigating the Mechanisms Underlying Neuronal Death in Ischemia Using In Vitro Oxygen-Glucose Deprivation: Potential Involvement of Protein SUMOylation

PubMed Central

CIMAROSTI, HELENA; HENLEY, JEREMY M.

2012-01-01

It is well established that brain ischemia can cause neuronal death via different signaling cascades. The relative importance and interrelationships between these pathways, however, remain poorly understood. Here is presented an overview of studies using oxygen-glucose deprivation of organotypic hippocampal slice cultures to investigate the molecular mechanisms involved in ischemia. The culturing techniques, setup of the oxygen-glucose deprivation model, and analytical tools are reviewed. The authors focus on SUMOylation, a posttranslational protein modification that has recently been implicated in ischemia from whole animal studies as an example of how these powerful tools can be applied and could be of interest to investigate the molecular pathways underlying ischemic cell death. PMID:19029060

Maternal childhood trauma, postpartum depression, and infant outcomes: Avoidant affective processing as a potential mechanism.

PubMed

Choi, Karmel W; Sikkema, Kathleen J; Vythilingum, Bavi; Geerts, Lut; Faure, Sheila C; Watt, Melissa H; Roos, Annerine; Stein, Dan J

2017-03-15

Women who have experienced childhood trauma may be at risk for postpartum depression, increasing the likelihood of negative outcomes among their children. Predictive pathways from maternal childhood trauma to child outcomes, as mediated by postpartum depression, require investigation. A longitudinal sample of South African women (N=150) was followed through pregnancy and postpartum. Measures included maternal trauma history reported during pregnancy; postpartum depression through six months; and maternal-infant bonding, infant development, and infant physical growth at one year. Structural equation models tested postpartum depression as a mediator between maternal experiences of childhood trauma and children's outcomes. A subset of women (N=33) also participated in a lab-based emotional Stroop paradigm, and their responses to fearful stimuli at six weeks were explored as a potential mechanism linking maternal childhood trauma, postpartum depression, and child outcomes. Women with childhood trauma experienced greater depressive symptoms through six months postpartum, which then predicted negative child outcomes at one year. Mediating effects of postpartum depression were significant, and persisted for maternal-infant bonding and infant growth after controlling for covariates and antenatal distress. Maternal avoidance of fearful stimuli emerged as a potential affective mechanism. Limitations included modest sample size, self-report measures, and unmeasured potential confounders. Findings suggest a mediating role of postpartum depression in the intergenerational transmission of negative outcomes. Perinatal interventions that address maternal trauma histories and depression, as well as underlying affective mechanisms, may help interrupt cycles of disadvantage, particularly in high-trauma settings such as South Africa. Copyright © 2017. Published by Elsevier B.V.

Formononetin protects TBI rats against neurological lesions and the underlying mechanism.

PubMed

Li, Zhengzhao; Dong, Xianhong; Zhang, Jianfeng; Zeng, Guang; Zhao, Huimin; Liu, Yun; Qiu, Rubiao; Mo, Linjian; Ye, Yu

2014-03-15

Traumatic brain injury (TBI) is a major cause of disability or death worldwide, especially in the young. Thus, effective medication with few side effects needs to be developed. This work aimed to explore the potential benefits of formononetin (FN) on TBI rodent model and to discuss the regarding mechanism. These findings showed that FN effectively increased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in brain tissue of TBI rats (P<0.01), while it reduced intracephalic malonaldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations (P<0.01). Meanwhile, the hydrocephalus in the TBI rat was alleviated, and the injured nerve cell of the lesioned brain was reduced as showed in hematoxylin-eosin (HE) staining assay. In addition, the endogenous mRNA level of cyclooxygenase-2 (COX-2) in the brain of the TBI rat was significantly down-regulated (P<0.01). Furthermore, the protein expression of nuclear factor E2-related factor 2 (Nrf2) was effectively up-regulated (P<0.01). Taken together, we conclude that formononetin mediates the promising anti-TBI effects against neurocyte damage, which the underlying mechanisms are associated with inhibiting intracephalic inflammatory response and oxidative stress for neuroprotection. Copyright © 2013 Elsevier B.V. All rights reserved.

Defect induced plasticity and failure mechanism of boron nitride nanotubes under tension

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

Anoop Krishnan, N. M., E-mail: anoopnm@civil.iisc.ernet.in; Ghosh, Debraj

2014-07-28

The effects of Stone-Wales (SW) and vacancy defects on the failure behavior of boron nitride nanotubes (BNNTs) under tension are investigated using molecular dynamics simulations. The Tersoff-Brenner potential is used to model the atomic interaction and the temperature is maintained close to 300 K. The effect of a SW defect is studied by determining the failure strength and failure mechanism of nanotubes with different radii. In the case of a vacancy defect, the effect of an N-vacancy and a B-vacancy is studied separately. Nanotubes with different chiralities but similar diameter is considered first to evaluate the chirality dependence. The variation ofmore » failure strength with the radius is then studied by considering nanotubes of different diameters but same chirality. It is observed that the armchair BNNTs are extremely sensitive to defects, whereas the zigzag configurations are the least sensitive. In the case of pristine BNNTs, both armchair and zigzag nanotubes undergo brittle failure, whereas in the case of defective BNNTs, only the zigzag ones undergo brittle failure. An interesting defect induced plastic behavior is observed in defective armchair BNNTs. For this nanotube, the presence of a defect triggers mechanical relaxation by bond breaking along the closest zigzag helical path, with the defect as the nucleus. This mechanism results in a plastic failure.« less

Biological mechanisms underlying the role of physical fitness in health and resilience

PubMed Central

Silverman, Marni N.; Deuster, Patricia A.

2014-01-01

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex. PMID:25285199

Biological mechanisms underlying the role of physical fitness in health and resilience.

PubMed

Silverman, Marni N; Deuster, Patricia A

2014-10-06

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex.

Study of mechanical behavior of AFM silicon tips under mechanical load

NASA Astrophysics Data System (ADS)

Kopycinska-Mueller, M.; Gluch, J.; Köhler, B.

2016-11-01

In this paper we address critical issues concerning calibration of AFM based methods used for nanoscale mechanical characterization of materials. It has been shown that calibration approaches based on macroscopic models for contact mechanics may yield excellent results in terms of the indentation modulus of the sample, but fail to provide a comprehensive and actual information concerning the tip-sample contact radius or the mechanical properties of the tip. Explanations for the severely reduced indentation modulus of the tip included the inadequacies of the models used for calculations of the tip-sample contact stiffness, discrepancies in the actual and ideal shape of the tip, presence of the amorphous silicon phase within the silicon tip, as well as negligence of the actual size of the stress field created in the tip during elastic interactions. To clarify these issues, we investigated the influence of the mechanical load applied to four AFM silicon tips on their crystalline state by exposing them to systematically increasing loads, evaluating the character of the tip-sample interactions via the load-unload stiffness curves, and assessing the state of the tips from HR-TEM images. The results presented in this paper were obtained in a series of relatively simple and basic atomic force acoustic microscopy (AFAM) experiments. The novel combination of TEM imaging of the AFM tips with the analysis of the load-unload stiffness curves gave us a detailed insight into their mechanical behavior under load conditions. We were able to identify the limits for the elastic interactions, as well as the hallmarks for phase transformation and dislocation formation and movement. The comparison of the physical dimensions of the AFM tips, geometry parameters determined from the values of the contact stiffness, and the information on the crystalline state of the tips allowed us a better understanding of the nanoscale contact.

Stellar performance: mechanisms underlying Milky Way orientation in dung beetles

PubMed Central

el Jundi, Basil; Smolka, Jochen; Khaldy, Lana; Nilsson, Dan-Eric; Byrne, Marcus J.; Dacke, Marie

2017-01-01

Nocturnal dung beetles (Scarabaeus satyrus) are currently the only animals that have been demonstrated to use the Milky Way for reliable orientation. In this study, we tested the capacity of S. satyrus to orient under a range of artificial celestial cues, and compared the properties of these cues with images of the Milky Way simulated for a beetle's visual system. We find that the mechanism that permits accurate stellar orientation under the Milky Way is based on an intensity comparison between different regions of the Milky Way. We determined the beetles' contrast sensitivity for this task in behavioural experiments in the laboratory, and found that the resulting threshold of 13% is sufficient to detect the contrast between the southern and northern arms of the Milky Way under natural conditions. This mechanism should be effective under extremely dim conditions and on nights when the Milky Way forms a near symmetrical band that crosses the zenith. These findings are discussed in the context of studies of stellar orientation in migratory birds and itinerant seals. This article is part of the themed issue ‘Vision in dim light’. PMID:28193823

Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

ERIC Educational Resources Information Center

Freeman, John H.; Steinmetz, Adam B.

2011-01-01

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

Emerging evidence of ozone metabolic effects and potential mechanisms

EPA Science Inventory

SOT 2014 Abstract: Invitational Emerging evidence of ozone metabolic effects and potential mechanisms U.P. Kodavanti NHEERL, USEPA, Research Triangle Park, NC Recent evidence suggests that air pollutants are linked to metabolic syndrome and impact several key metabolic proce...

Developmental mechanisms underlying variable, invariant and plastic phenotypes

PubMed Central

Abley, Katie; Locke, James C. W.; Leyser, H. M. Ottoline

2016-01-01

Background Discussions of phenotypic robustness often consider scenarios where invariant phenotypes are optimal and assume that developmental mechanisms have evolved to buffer the phenotypes of specific traits against stochastic and environmental perturbations. However, plastic plant phenotypes that vary between environments or variable phenotypes that vary stochastically within an environment may also be advantageous in some scenarios. Scope Here the conditions under which invariant, plastic and variable phenotypes of specific traits may confer a selective advantage in plants are examined. Drawing on work from microbes and multicellular organisms, the mechanisms that may give rise to each type of phenotype are discussed. Conclusion In contrast to the view of robustness as being the ability of a genotype to produce a single, invariant phenotype, changes in a phenotype in response to the environment, or phenotypic variability within an environment, may also be delivered consistently (i.e. robustly). Thus, for some plant traits, mechanisms have probably evolved to produce plasticity or variability in a reliable manner. PMID:27072645

Molecular and Microbial Mechanisms Increasing Soil C Storage Under Future Rates of Anthropogenic N Deposition

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

Zak, Donald R.

A growing body of evidence reveals that anthropogenic N deposition can reduce the microbial decay of plant detritus and increase soil C storage across a wide range of terrestrial ecosystems. This aspect of global change has the potential to constrain the accumulation of anthropogenic CO 2 in the Earth’s atmosphere, and hence slow the pace of climate warming. The molecular and microbial mechanisms underlying this biogeochemical response are not understood, and they are not a component of any coupled climate-biogeochemical model estimating ecosystem C storage, and hence, the future climate of an N-enriched Earth. Here, we report the use ofmore » genomic-enabled approaches to identify the molecular underpinnings of the microbial mechanisms leading to greater soil C storage in response to anthropogenic N deposition, thereby enabling us to better anticipate changes in soil C storage.« less

Underlying mechanisms for syntrophic metabolism of essential enzyme cofactors in microbial communities

PubMed Central

Romine, Margaret F; Rodionov, Dmitry A; Maezato, Yukari; Osterman, Andrei L; Nelson, William C

2017-01-01

Many microorganisms are unable to synthesize essential B vitamin-related enzyme cofactors de novo. The underlying mechanisms by which such microbes survive in multi-species communities are largely unknown. We previously reported the near-complete genome sequence of two ~18-member unicyanobacterial microbial consortia that maintain stable membership on defined medium lacking vitamins. Here we have used genome analysis and growth studies on isolates derived from the consortia to reconstruct pathways for biogenesis of eight essential cofactors and predict cofactor usage and precursor exchange in these communities. Our analyses revealed that all but the two Halomonas and cyanobacterial community members were auxotrophic for at least one cofactor. We also observed a mosaic distribution of salvage routes for a variety of cofactor precursors, including those produced by photolysis. Potentially bidirectional transporters were observed to be preferentially in prototrophs, suggesting a mechanism for controlled precursor release. Furthermore, we found that Halomonas sp. do not require cobalamin nor control its synthesis, supporting the hypothesis that they overproduce and export vitamins. Collectively, these observations suggest that the consortia rely on syntrophic metabolism of cofactors as a survival strategy for optimization of metabolic exchange within a shared pool of micronutrients. PMID:28186498

Convergent mechanisms underlying rapid antidepressant action

PubMed Central

Zanos, Panos; Thompson, Scott M.; Duman, Ronald S.; Zarate, Carlos A.; Gould, Todd D.

2018-01-01

Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal and anti-anhedonic actions following a single administration to depressed patients. Proposed mechanisms of ketamine’s antidepressant action include N-methyl-D-aspartate receptor (NMDAR) modulation, GABAergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergoing pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine - pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists (i.e. GLYX-13 (rapastinel)), metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment

Resonances in piecewise potentials and Supersymmetric Quantum Mechanics (SUSY-QM) for the construction of optical potentials

NASA Astrophysics Data System (ADS)

Orozco Cortés, Luis Fernando; Fernández García, Nicolás

2014-05-01

A method to obtain the general solution of any constant piecewise potential is presented, this is achieved by means of the analysis of the transfer matrices in each cutoff. The resonance phenomenon together with the supersymmetric quantum mechanics technique allow us to construct a wide family of complex potentials which can be used as theoretical models for optical systems. The method is applied to the particular case for which the potential function has six cutoff points.

Deformation and failure mechanisms of graphite/epoxy composites under static loading

NASA Technical Reports Server (NTRS)

Clements, L. L.

1981-01-01

The mechanisms of deformation and failure of graphite epoxy composites under static loading were clarified. The influence of moisture and temperature upon these mechanisms were also investigated. Because the longitudinal tensile properties are the most critical to the performance of the composite, these properties were investigated in detail. Both ultimate and elastic mechanical properties were investigated, but the study of mechanisms emphasized those leading to failure of the composite. The graphite epoxy composite selected for study was the system being used in several NASA sponsored flight test programs.

Dendritic mechanisms underlying the coupling of the dendritic with the axonal action potential initiation zone of adult rat layer 5 pyramidal neurons

PubMed Central

Larkum, M E; Zhu, J J; Sakmann, B

2001-01-01

Double, triple and quadruple whole-cell voltage recordings were made simultaneously from different parts of the apical dendritic arbor and the soma of adult layer 5 (L5) pyramidal neurons. We investigated the membrane mechanisms that support the conduction of dendritic action potentials (APs) between the dendritic and axonal AP initiation zones and their influence on the subsequent AP pattern. The duration of the current injection to the distal dendritic initiation zone controlled the degree of coupling with the axonal initiation zone and the AP pattern. Two components of the distally evoked regenerative potential were pharmacologically distinguished: a rapidly rising peak potential that was TTX sensitive and a slowly rising plateau-like potential that was Cd2+ and Ni2+ sensitive and present only with longer-duration current injection. The amplitude of the faster forward-propagating Na+-dependent component and the amplitude of the back-propagating AP fell into two classes (more distinctly in the forward-propagating case). Current injection into the dendrite altered propagation in both directions. Somatic current injections that elicited single Na+ APs evoked bursts of Na+ APs when current was injected simultaneously into the proximal apical dendrite. The mechanism did not depend on dendritic Na+–Ca2+ APs. A three-compartment model of a L5 pyramidal neuron is proposed. It comprises the distal dendritic and axonal AP initiation zones and the proximal apical dendrite. Each compartment contributes to the initiation and to the pattern of AP discharge in a distinct manner. Input to the three main dendritic arbors (tuft dendrites, apical oblique dendrites and basal dendrites) has a dominant influence on only one of these compartments. Thus, the AP pattern of L5 pyramids reflects the laminar distribution of synaptic activity in a cortical column. PMID:11389204

Failure Mechanisms of Brittle Rocks under Uniaxial Compression

NASA Astrophysics Data System (ADS)

Liu, Taoying; Cao, Ping

2017-09-01

The behaviour of a rock mass is determined not only by the properties of the rock matrix, but mostly by the presence and properties of discontinuities or fractures within the mass. The compression test on rock-like specimens with two prefabricated transfixion fissures, made by pulling out the embedded metal inserts in the pre-cured period was carried out on the servo control uniaxial loading tester. The influence of the geometry of pre-existing cracks on the cracking processes was analysed with reference to the experimental observation of crack initiation and propagation from pre-existing flaws. Based on the rock fracture mechanics and the stress-strain curves, the evolution failure mechanism of the fissure body was also analyzed on the basis of exploring the law of the compression-shear crack initiation, wing crack growth and rock bridge connection. Meanwhile, damage fracture mechanical models of a compression-shear rock mass are established when the rock bridge axial transfixion failure, tension-shear combined failure, or wing crack shear connection failure occurs on the specimen under axial compression. This research was of significance in studying the failure mechanism of fractured rock mass.

Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

PubMed

Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

2017-11-01

Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

Fatigue responses of lead zirconate titanate stacks under semibipolar electric cycling with mechanical preload

NASA Astrophysics Data System (ADS)

Wang, Hong; Cooper, Thomas A.; Lin, Hua-Tay; Wereszczak, Andrew A.

2010-10-01

Lead zirconate titanate (PZT) stacks that had an interdigital internal electrode configuration were tested to more than 108 cycles. A 100 Hz semibipolar sine wave with a field range of +4.5/-0.9 kV/mm was used in cycling with a concurrently-applied 20 MPa preload. Significant reductions in piezoelectric and dielectric responses were observed during the cycling depending on the measuring condition. Extensive partial discharges were also observed. These surface events resulted in the erosion of external electrode and the exposure of internal electrodes. Sections prepared by sequential polishing technique revealed a variety of damage mechanisms including delaminations, pores, and etch grooves. The scale of damage was correlated with the degree of fatigue-induced reduction in piezoelectric and dielectric responses. The results from this study demonstrate the feasibility of using a semibipolar mode to drive a PZT stack under a mechanical preload and illustrate the potential fatigue and damages of the stack in service.

Mechanisms Underlying Cytotoxicity Induced by Engineered Nanomaterials: A Review of In Vitro Studies

PubMed Central

Nogueira, Daniele R.; Mitjans, Montserrat; Rolim, Clarice M. B.; Vinardell, M. Pilar

2014-01-01

Engineered nanomaterials are emerging functional materials with technologically interesting properties and a wide range of promising applications, such as drug delivery devices, medical imaging and diagnostics, and various other industrial products. However, concerns have been expressed about the risks of such materials and whether they can cause adverse effects. Studies of the potential hazards of nanomaterials have been widely performed using cell models and a range of in vitro approaches. In the present review, we provide a comprehensive and critical literature overview on current in vitro toxicity test methods that have been applied to determine the mechanisms underlying the cytotoxic effects induced by the nanostructures. The small size, surface charge, hydrophobicity and high adsorption capacity of nanomaterial allow for specific interactions within cell membrane and subcellular organelles, which in turn could lead to cytotoxicity through a range of different mechanisms. Finally, aggregating the given information on the relationships of nanomaterial cytotoxic responses with an understanding of its structure and physicochemical properties may promote the design of biologically safe nanostructures. PMID:28344232

Deformation mechanisms of idealised cermets under multi-axial loading

NASA Astrophysics Data System (ADS)

Bele, E.; Goel, A.; Pickering, E. G.; Borstnar, G.; Katsamenis, O. L.; Pierron, F.; Danas, K.; Deshpande, V. S.

2017-05-01

The response of idealised cermets comprising approximately 60% by volume steel spheres in a Sn/Pb solder matrix is investigated under a range of axisymmetric compressive stress states. Digital volume correlation (DVC) anal`ysis of X-ray micro-computed tomography scans (μ-CT), and the measured macroscopic stress-strain curves of the specimens revealed two deformation mechanisms. At low triaxialities the deformation is granular in nature, with dilation occurring within shear bands. Under higher imposed hydrostatic pressures, the deformation mechanism transitions to a more homogeneous incompressible mode. However, DVC analyses revealed that under all triaxialities there are regions with local dilatory and compaction responses, with the magnitude of dilation and the number of zones wherein dilation occurs decreasing with increasing triaxiality. Two numerical models are presented in order to clarify these mechanisms: (i) a periodic unit cell model comprising nearly rigid spherical particles in a porous metal matrix and (ii) a discrete element model comprising a large random aggregate of spheres connected by non-linear normal and tangential "springs". The periodic unit cell model captured the measured stress-strain response with reasonable accuracy but under-predicted the observed dilation at the lower triaxialities, because the kinematic constraints imposed by the skeleton of rigid particles were not accurately accounted for in this model. By contrast, the discrete element model captured the kinematics and predicted both the overall levels of dilation and the simultaneous presence of both local compaction and dilatory regions with the specimens. However, the levels of dilation in this model are dependent on the assumed contact law between the spheres. Moreover, since the matrix is not explicitly included in the analysis, this model cannot be used to predict the stress-strain responses. These analyses have revealed that the complete constitutive response of cermets

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

Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading.

PubMed

Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

2016-09-06

The loss of glycosaminoglycan (GAG) content is a major biochemical change during intervertebral disc (IVD) degeneration. Abnormal mechanical loading is one of the major factors causing disc degeneration. In this study, a multiscale mathematical model was developed to quantify the effect of mechanical loading on GAG synthesis. This model was based on a recently developed cell volume dependent GAG synthesis theory that predicts the variation of GAG synthesis rate of a cell under the influence of mechanical stimuli, and the biphasic theory that describes the deformation of IVD under mechanical loading. The GAG synthesis (at the cell level) was coupled with the mechanical loading (at the tissue level) via a cell-matrix unit approach which established a relationship between the variation of cell dilatation and the local tissue dilatation. This multiscale mathematical model was used to predict the effect of static load (creep load) on GAG synthesis in bovine tail discs. The predicted results are in the range of experimental results. This model was also used to investigate the effect of static (0.2MPa) and diurnal loads (0.1/0.3MPa and 0.15/0.25MPa in 12/12 hours shift with an average of 0.2MPa over a cycle) on GAG synthesis. It was found that static load and diurnal loads have different effects on GAG synthesis in a diurnal cycle, and the diurnal load effects depend on the amplitude of the load. The model is important to understand the effect of mechanical loading at the tissue level on GAG synthesis at the cellular level, as well as to optimize the mechanical loading in growing engineered tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analytical solutions of the Dirac equation under Hellmann–Frost–Musulin potential

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

Onate, C.A., E-mail: oaclems14@physicist.net; Onyeaju, M.C.; Ikot, A.N.

2016-12-15

The approximate analytical solutions of the Dirac equation with Hellmann–Frost–Musulin potential have been studied by using the generalized parametric Nikiforov–Uvarov (NU) method for arbitrary spin–orbit quantum number k under the spin and pseudospin symmetries. The Hellmann–Frost–Musulin potential is a superposition potential that consists of Yukawa potential, Coulomb potential, and Frost–Musulin potential. As a particular case, we found the energy levels of the non-relativistic limit of the spin symmetry. The energy equation of Yukawa potential, Coulomb potential, Hellmann potential and Frost–Musulin potential are obtained. Energy values are generated for some diatomic molecules.

Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis.

PubMed

Halama, Anna; Kulinski, Michal; Dib, Shaima S; Zaghlool, Shaza B; Siveen, Kodappully S; Iskandarani, Ahmad; Zierer, Jonas; Prabhu, Kirti S; Satheesh, Noothan J; Bhagwat, Aditya M; Uddin, Shahab; Kastenmüller, Gabi; Elemento, Olivier; Gross, Steven S; Suhre, Karsten

2018-08-28

Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy. Simultaneously inhibiting glutaminolysis and either beta oxidation with trimetazidine or autophagy with chloroquine both induced cancer cell death. Here we identified metabolic escape mechanisms contributing to cancer cell survival under treatment and we suggest potentially translational strategy for combined cancer therapy, given that chloroquine is an FDA approved drug. Our findings are first to show efficiency of combined inhibition of glutaminolysis and beta oxidation as potential anti-cancer strategy as well as add to the evidence that combined inhibition of glutaminolysis and autophagy may be effective in glutamine-addicted cancers. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Epilepsy following cortical injury: Cellular and molecular mechanisms as targets for potential prophylaxis

PubMed Central

Prince, David A.; Parada, Isabel; Scalise, Karina; Graber, Kevin; Shen, Fran

2009-01-01

Summary The sequelae of traumatic brain injury, including posttraumatic epilepsy, represent a major societal problem. Significant resources are required to develop a better understanding of the underlying pathophysiologic mechanisms as targets for potential prophylactic therapies. Posttraumatic epilepsy undoubtedly involves numerous pathogenic factors that develop more or less in parallel. We have highlighted two potential “prime movers”: disinhibition and development of new functional excitatory connectivity, which occur in a number of animal models and some forms of epilepsy in humans. Previous experiments have shown that tetrodotoxin (TTX) applied to injured cortex during a critical period early after lesion placement can prevent epileptogenesis in the partial cortical (“undercut”) model of posttraumatic epilepsy. Here we show that such treatment markedly attenuates histologic indices of axonal and terminal sprouting and presumably associated aberrant excitatory connectivity. A second finding in the undercut model is a decrease in spontaneous inhibitory events. Current experiments show that this is accompanied by regressive alterations in fast-spiking γ-aminobutyric acid (GABA)ergic interneurons, including shrinkage of dendrites, marked decreases in axonal length, structural changes in inhibitory boutons, and loss of inhibitory synapses on pyramidal cells. Other data support the hypothesis that these anatomic abnormalities may result from loss of trophic support normally provided to interneurons by brain-derived neurotrophic factor (BDNF). Approaches that prevent these two pathophysiologic mechanisms may offer avenues for prophylaxis for posttraumatic epilepsy. However, major issues such as the role of these processes in functional recovery from injury and the timing of the critical period(s) for application of potential therapies in humans are critical and need to be resolved. PMID:19187292

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

PubMed Central

Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

2017-01-01

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

Mechanism for amorphization of boron carbide under complex stress conditions

NASA Astrophysics Data System (ADS)

Li, Jun; Xu, Shuang; Liu, Lisheng; Wang, Zhen; Zhang, Jinyong; Liu, Qiwen

2018-05-01

As an excellent material, the application of boron carbide (B4C) is limited by pressure-induced amorphization. To understand the mechanism for amorphization in B4C, first-principles methods based on density functional theory were employed to investigate the mechanical behaviors and the deformation process in B4C under complex stress conditions with six different biaxial perpendicular compression directions. The angle (θ) between one of the loading directions and the [0 0 0 1] c-axis ranged from 0° to 75° with every 15° interval. We found that the maximum stress at θ = 30° is 124.5 GPa, which is the lowest among six biaxial compressions. Simulation results show that the mechanism for amorphization in B4C under complex stress conditions is complicated. We take the θ = 30° biaxial compression as an example to explain the complicated deformation process. In the elastic deformation region, sudden bending of three-atom chains occurs and results in a stress fluctuation. Then the formation of new B–B bonds between the three-atom chains and the icosahedra leads to the first stress drop. After that, the B–C bonds in the chains are broken, resulting in the second stress drop. In this process, the icosahedra are partially destroyed. The stress increases continuously and then drops at the critical failure strain. Finally, the fully destruction of icosahedra leads to amorphization in B4C. However, under other five biaxial compressions, the B–C bonds in three-atom chains are not fractured before structural failure. Understanding the deformation mechanism for amorphization of B4C in real applications is prime important for proposing how to resist amorphization and enhance the toughness of B4C.

A representative-sandwich model for simultaneously coupled mechanical-electrical-thermal simulation of a lithium-ion cell under quasi-static indentation tests

DOE PAGES

Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.; ...

2015-08-29

The safety behavior of lithium-ion batteries under external mechanical crush is a critical concern, especially during large scale deployment. We previously presented a sequentially coupled mechanical-electrical-thermal modeling approach for studying mechanical abuse induced short circuit. Here in this work, we study different mechanical test conditions and examine the interaction between mechanical failure and electrical-thermal responses, by developing a simultaneous coupled mechanical-electrical-thermal model. The present work utilizes a single representative-sandwich (RS) to model the full pouch cell with explicit representations for each individual component such as the active material, current collector, separator, etc. Anisotropic constitutive material models are presented to describemore » the mechanical properties of active materials and separator. The model predicts accurately the force-strain response and fracture of battery structure, simulates the local failure of separator layer, and captures the onset of short circuit for lithium-ion battery cell under sphere indentation tests with three different diameters. Electrical-thermal responses to the three different indentation tests are elaborated and discussed. Lastly, numerical studies are presented to show the potential impact of test conditions on the electrical-thermal behavior of the cell after the occurrence of short circuit.« less

A representative-sandwich model for simultaneously coupled mechanical-electrical-thermal simulation of a lithium-ion cell under quasi-static indentation tests

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

Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.

The safety behavior of lithium-ion batteries under external mechanical crush is a critical concern, especially during large scale deployment. We previously presented a sequentially coupled mechanical-electrical-thermal modeling approach for studying mechanical abuse induced short circuit. Here in this work, we study different mechanical test conditions and examine the interaction between mechanical failure and electrical-thermal responses, by developing a simultaneous coupled mechanical-electrical-thermal model. The present work utilizes a single representative-sandwich (RS) to model the full pouch cell with explicit representations for each individual component such as the active material, current collector, separator, etc. Anisotropic constitutive material models are presented to describemore » the mechanical properties of active materials and separator. The model predicts accurately the force-strain response and fracture of battery structure, simulates the local failure of separator layer, and captures the onset of short circuit for lithium-ion battery cell under sphere indentation tests with three different diameters. Electrical-thermal responses to the three different indentation tests are elaborated and discussed. Lastly, numerical studies are presented to show the potential impact of test conditions on the electrical-thermal behavior of the cell after the occurrence of short circuit.« less

[Role of long-term potentiation in mechanism of the conditioned learning].

PubMed

Tsvetkov, E A; Suderevskaia, E I; Veselkin, N P

2011-01-01

The review analyzes the fundamental problem of study of the neuronal mechanisms underlying processes of learning and memory. As a neuronal models of these phenomena there was considered one of the cellular phenomena that has characteristics similar with those in the process of "remembering"--such as the long-term potentiation (LTP). LTP is easily reproduced in certain synapses of the central nervous system, specifically in synapses of hippocampus and amygdala. As to the behavioral model of learning, there was used the conditioned learning, in frames of which production of the context-dependent/independent conditioned reaction was considered. Analysis of literature data has allowed showing that various stages of LTP produced on synapses of hippocampus or amygdala can be comparable with certain phase of the process of learning. Based on the exposed material the authors conclude that plastic changes of synapses of hippocampus and amygdala can represent the morphological substrate of some kinds of learning and memory.

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

Divergence of water balance mechanisms and acclimation potential in body color morphs of Drosophila ananassae.

PubMed

Parkash, Ravi; Aggarwal, Dau Dayal; Lambhod, Chanderkala; Singh, Divya

2014-01-01

Drosophila ananassae is a desiccation sensitive species, but the physiological basis of its abundance in the drier subtropical areas is largely unknown. We tested the hypothesis whether body color morphs of D. ananassae differ in the mechanistic basis of water conservation as well as desiccation acclimation potential, consistent with their distribution under dry or wet habitats. We observed reduced rate of water loss consistent with the greater desiccation potential of dark morph as compared with light morph, despite lack of quantitative differences in cuticular lipid mass between them. Dark morph evidenced greater wet and dry mass (∼1.17-fold) as well as higher hemolymph content (∼1.70-fold) and (∼17%) dehydration tolerance to sustain longer survival under desiccation stress (LT50 17.5 hr) as compared with light morph (LT50 4.3 hr). We found significant differences in the storage of energy metabolites in the body color morphs of D. ananassae, that is, carbohydrate content was significantly higher (∼0.18 mg/mg dry mass) in the dark morph as compared to light morph, but greater (∼0.05 mg/mg dry mass) body lipid content was evident in the light morph. Under desiccation stress, dark and light morphs utilized mainly carbohydrates but also lipids to a lesser extent. However, the rate of utilization of energy metabolites did not vary between dark and light morphs. Further, the dark morph consumed higher energy content derived from carbohydrates under desiccation stress as compared with the light morph. Finally, we found contrasting patterns of acclimation to desiccation stress in the two body color morphs, that is, increase in desiccation survival (4.7 hr), as well as in dehydration tolerance (∼6%) due to acclimation of the dark morph but no such effects were observed in the light morph. Thus, divergence in water balance mechanisms as well as acclimation potential reflects evolved physiological adaptations of the dark morph under drier but of the

Effects of positive end-expiratory pressure on intracranial pressure in mechanically ventilated dogs under hyperbaric oxygenation.

PubMed

Sun, Qing; Wu, Di; Yu, Tao; Yang, Ying; Wei, Li; Lv, Fuxiang; Gao, Guangkai

2014-01-01

Mechanical ventilation with positive end-expiratory pressure (PEEP) has been advocated as an essential life support for critical patients. However, its side effect, which is demonstrated by an elevation of intracranial pressure (ICP) under normobaric (NBO2) conditions, is potentially detrimental to patients. Hyperbaric oxygen (HBO2) therapy, on the other hand, is frequently applied for the same group of patients, and its efficacy is shown by maintaining a higher PaO2 and a reduced ICP. Our study investigated the effect of HBO2 and NBO2 on ICP with or without PEEP ventilation on healthy dogs by comparing cerebrospinal fluid pressure (CSFP) and concluded that the elevation of PEEP resulted in a significant increase of ICP (CSFP) under both conditions (p < 0.05). HBO2 leads to a lower ICP increase compared to the NBO2 group. Under the same level of PEEP, the joint use of PEEP and HBO2 is safe and highly practical in clinical medicine.

The molecular mechanisms underlying lens fiber elongation

PubMed Central

Audette, Dylan S.; Scheiblin, David A.; Duncan, Melinda K.

2016-01-01

Lens fiber cells are highly elongated cells with complex membrane morphologies that are critical for the transparency of the ocular lens. Investigations into the molecular mechanisms underlying lens fiber cell elongation were first reported in the 1960s, however, our understanding of the process is still poor nearly 50 years later. This review summarizes what is currently hypothesized about the regulation of lens fiber cell elongation along with the available experimental evidence, and how this information relates to what is known about the regulation of cell shape/elongation in other cell types, particularly neurons. PMID:27015931

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®

Step-wise potential development across the lipid bilayer under external electric fields

NASA Astrophysics Data System (ADS)

Majhi, Amit Kumar

2018-04-01

Pore formation across the bilayers under external electric field is an important phenomenon, which has numerous applications in biology and bio-engineering fields. However, it is not a ubiquitous event under all field applications. To initiate a pore in the bilayer a particular threshold electric field is required. The electric field alters the intrinsic potential distribution across the bilayer as we as it enhances total potential drop across the bilayer, which causes the pore formation. The intrinsic potential profile has a maximum peak value, which is 0.8 V and it gets enhanced under application of external field, 0.43 V/nm. The peak value becomes 1.4 V when a pore appears in the bilayer and it continues to evolve as along as the external electric field remains switched on.

Mechanical Isolation of Highly Stable Antimonene under Ambient Conditions.

PubMed

Ares, Pablo; Aguilar-Galindo, Fernando; Rodríguez-San-Miguel, David; Aldave, Diego A; Díaz-Tendero, Sergio; Alcamí, Manuel; Martín, Fernando; Gómez-Herrero, Julio; Zamora, Félix

2016-08-01

Antimonene fabricated by mechanical exfoliation is highly stable under atmospheric conditions over periods of months and even when immersed in water. Density functional theory confirms the experiments and predicts an electronic gap of ≈1 eV. These results highlight the use of antimonene for optoelectronics applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First-principles investigation of mechanical and electronic properties of tetragonal NbAl3 under tension

NASA Astrophysics Data System (ADS)

Jiao, Zhen; Liu, Qi-Jun; Liu, Fu-Sheng; Tang, Bin

2018-06-01

Using the density functional theory calculations, the mechanical and electronic properties of NbAl3 under different tensile loads were investigated. The calculated lattice parameters, elastic constants and mechanical properties (bulk modulus, shear modulus, Young's modulus, Poisson's ratio, Pugh's criterion and Cauchy's pressure) indicated that our results were in agreement with the published experimental and theoretical data at zero tension. With respect to NbAl3 under tension in this paper, the crystal structure was changed from tetragonal to orthorhombic under tension along the [100] and [101] directions. The NbAl3 crystal has been classified as brittle material under tension from 0 to 20 GPa. The obtained Young's modulus and Debye temperature monotonically decreased with increasing tension stress. Combining with mechanical and electronic properties in detail, the decreased mechanical properties were mainly due to the weakening of covalency.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

PubMed

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Exploring the Mechanisms of Exercise-Induced Hypoalgesia Using Somatosensory and Laser Evoked Potentials

PubMed Central

Jones, Matthew D.; Taylor, Janet L.; Booth, John; Barry, Benjamin K.

2016-01-01

Exercise-induced hypoalgesia is well described, but the underlying mechanisms are unclear. The aim of this study was to examine the effect of exercise on somatosensory evoked potentials, laser evoked potentials, pressure pain thresholds and heat pain thresholds. These were recorded before and after 3-min of isometric elbow flexion exercise at 40% of the participant's maximal voluntary force, or an equivalent period of rest. Exercise-induced hypoalgesia was confirmed in two experiments (Experiment 1–SEPs; Experiment 2–LEPs) by increased pressure pain thresholds at biceps brachii (24.3 and 20.6% increase in Experiment 1 and 2, respectively; both d > 0.84 and p < 0.001) and first dorsal interosseous (18.8 and 21.5% increase in Experiment 1 and 2, respectively; both d > 0.57 and p < 0.001). In contrast, heat pain thresholds were not significantly different after exercise (forearm: 10.8% increase, d = 0.35, p = 0.10; hand: 3.6% increase, d = 0.06, p = 0.74). Contrasting effects of exercise on the amplitude of laser evoked potentials (14.6% decrease, d = −0.42, p = 0.004) and somatosensory evoked potentials (10.9% increase, d = −0.02, p = 1) were also observed, while an equivalent period of rest showed similar habituation (laser evoked potential: 7.3% decrease, d = −0.25, p = 0.14; somatosensory evoked potential: 20.7% decrease, d = −0.32, p = 0.006). The differential response of pressure pain thresholds and heat pain thresholds to exercise is consistent with relative insensitivity of thermal nociception to the acute hypoalgesic effects of exercise. Conflicting effects of exercise on somatosensory evoked potentials and laser evoked potentials were observed. This may reflect non-nociceptive contributions to the somatosensory evoked potential, but could also indicate that peripheral nociceptors contribute to exercise-induced hypoalgesia. PMID:27965587

Exploring the Mechanisms of Exercise-Induced Hypoalgesia Using Somatosensory and Laser Evoked Potentials.

PubMed

Jones, Matthew D; Taylor, Janet L; Booth, John; Barry, Benjamin K

2016-01-01

Exercise-induced hypoalgesia is well described, but the underlying mechanisms are unclear. The aim of this study was to examine the effect of exercise on somatosensory evoked potentials, laser evoked potentials, pressure pain thresholds and heat pain thresholds. These were recorded before and after 3-min of isometric elbow flexion exercise at 40% of the participant's maximal voluntary force, or an equivalent period of rest. Exercise-induced hypoalgesia was confirmed in two experiments (Experiment 1-SEPs; Experiment 2-LEPs) by increased pressure pain thresholds at biceps brachii (24.3 and 20.6% increase in Experiment 1 and 2, respectively; both d > 0.84 and p < 0.001) and first dorsal interosseous (18.8 and 21.5% increase in Experiment 1 and 2, respectively; both d > 0.57 and p < 0.001). In contrast, heat pain thresholds were not significantly different after exercise (forearm: 10.8% increase, d = 0.35, p = 0.10; hand: 3.6% increase, d = 0.06, p = 0.74). Contrasting effects of exercise on the amplitude of laser evoked potentials (14.6% decrease, d = -0.42, p = 0.004) and somatosensory evoked potentials (10.9% increase, d = -0.02, p = 1) were also observed, while an equivalent period of rest showed similar habituation (laser evoked potential: 7.3% decrease, d = -0.25, p = 0.14; somatosensory evoked potential: 20.7% decrease, d = -0.32, p = 0.006). The differential response of pressure pain thresholds and heat pain thresholds to exercise is consistent with relative insensitivity of thermal nociception to the acute hypoalgesic effects of exercise. Conflicting effects of exercise on somatosensory evoked potentials and laser evoked potentials were observed. This may reflect non-nociceptive contributions to the somatosensory evoked potential, but could also indicate that peripheral nociceptors contribute to exercise-induced hypoalgesia.

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

Synaptic mechanisms underlying persistent cocaine craving

PubMed Central

Wolf, Marina E.

2017-01-01

Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

Mechanisms underlying astringency: introduction to an oral tribology approach

NASA Astrophysics Data System (ADS)

Upadhyay, Rutuja; Brossard, Natalia; Chen, Jianshe

2016-03-01

Astringency is one of the predominant factors in the sensory experience of many foods and beverages ranging from wine to nuts. The scientific community is discussing mechanisms that explain this complex phenomenon, since there are no conclusive results which correlate well with sensory astringency. Therefore, the mechanisms and perceptual characteristics of astringency warrant further discussion and investigation. This paper gives a brief introduction of the fundamentals of oral tribology forming a basis of the astringency mechanism. It discusses the current state of the literature on mechanisms underlying astringency describing the existing astringency models. The review discusses the crucial role of saliva and its physiology which contributes significantly in astringency perception in the mouth. It also provides an overview of research concerned with the physiological and psychophysical factors that mediate the perception of this sensation, establishing the ground for future research. Thus, the overall aim of the review is to establish the critical roles of oral friction (thin-film lubrication) in the sensation of astringency and possibly of some other specific sensory features.

Protective role of Nrf2 against mechanical-stretch-induced apoptosis in mouse fibroblasts: a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence.

PubMed

Li, Qiannan; Li, Bingshu; Liu, Cheng; Wang, Linlin; Tang, Jianming; Hong, Li

2018-01-10

We investigated the protective effect and underlying molecular mechanism of nuclear factor-E2-related factor 2 (Nrf2) against mechanical-stretch-induced apoptosis in mouse fibroblasts. Normal cells, Nrf2 silencing cells, and Nrf2 overexpressing cells were respectively divided into two groups-nonintervention and cyclic mechanical strain (CMS)-subjected to CMS of 5333 μ (1.0 Hz for 4 h), six groups in total (control, CMS, shNfe212, shNfe212 + CMS, LV-shNfe212, and LV-shNfe212 + CMS). After treatment, cell apoptosis; cell-cycle distribution; expressions of Nrf2, Bax, Bcl-2, Cyt-C, caspase-3, caspase-9, cleaved-caspase-3, and cleaved-caspase-9; mitochondrial membrane potential (ΔΨm); reactive oxygen species (ROS); and malondialdehyde (MDA) levels were measured. Thirty virgin female C57BL/6 mice were divided into two groups: control (without intervention) and vaginal distension (VD) groups, which underwent VD for 1 h with an 8-mm dilator (0.3 ml saline). Leak-point pressure (LPP) was tested on day 7 after VD; Nrf2 expression, apoptosis, and MDA levels were then measured in urethra and anterior vaginal wall. Mechanical stretch decreased Nrf2 messenger RNA (mRNA) and protein expressions. Overexpression of Nrf2 alleviated mechanical-stretch-induced cell apoptosis; S-phase arrest of cell cycle; up-regulation of Bax, cytochrome C (Cyt-C), ROS, MDA, ratio of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9; and exacerbated the decrease of Bcl2 and ΔΨm in L929 cells. On the contrary, silencing of Nrf2 showed opposite effects. Besides, VD reduced LPP levels and Nrf2 expression and increased cell apoptosis and MDA generation in the urethra and anterior vaginal wall. Nrf2 exhibits a protective role against mechanical-stretch -induced apoptosis on mouse fibroblasts, which might indicate a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence (SUI).

Identification of the mechanism underlying a human chimera by SNP array analysis.

PubMed

Shin, So Youn; Yoo, Han-Wook; Lee, Beom Hee; Kim, Kun Suk; Seo, Eul-Ju

2012-09-01

Human chimerism resulting from the fusion of two different zygotes is a rare phenomenon. Two mechanisms of chimerism have been hypothesized: dispermic fertilization of an oocyte and its second polar body and dispermic fertilization of two identical gametes from parthenogenetic activation, and these can be identified and discriminated using DNA polymorphism. In the present study we describe a patient with chimerism presenting as a true hermaphrodite and applied single nucleotide polymorphism array analysis to demonstrate dispermic fertilization of two identical gametes from parthenogenetic activation as the underlying mechanism at the whole chromosome level. We suggest that application of genotyping array analysis to the diagnostic process in patients with disorders of sex development will help identify more human chimera patients and increase our understanding of the underlying mechanisms. Copyright © 2012 Wiley Periodicals, Inc.

Study on Mechanical Properties of Barite Concrete under Impact Load

NASA Astrophysics Data System (ADS)

Chen, Z. F.; Cheng, K.; Wu, D.; Gan, Y. C.; Tao, Q. W.

2018-03-01

In order to research the mechanical properties of Barite concrete under impact load, a group of concrete compression tests was carried out under the impact load by using the drop test machine. A high-speed camera was used to record the failure process of the specimen during the impact process. The test results show that:with the increase of drop height, the loading rate, the peak load, the strain under peak load, the strain rate and the dynamic increase factor (DIF) all increase gradually. The ultimate tensile strain is close to each other, and the time of impact force decreases significantly, showing significant strain rate effect.

Mechanisms of action of ligands of potential-dependent sodium channels.

PubMed

Tikhonov, D B

2008-06-01

Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

Yogurt and Cardiometabolic Diseases: A Critical Review of Potential Mechanisms.

PubMed

Fernandez, Melissa Anne; Panahi, Shirin; Daniel, Noémie; Tremblay, Angelo; Marette, André

2017-11-01

Associations between yogurt intake and risk of diet-related cardiometabolic diseases (CMDs) have been the subject of recent research in epidemiologic nutrition. A healthy dietary pattern has been identified as a pillar for the prevention of weight gain and CMDs. Epidemiologic studies suggest that yogurt consumption is linked to healthy dietary patterns, lifestyles, and reduced risk of CMDs, particularly type 2 diabetes. However, to our knowledge, few to no randomized controlled trials have investigated yogurt intake in relation to cardiometabolic clinical outcomes. Furthermore, there has been little attempt to clarify the mechanisms that underlie the potential beneficial effects of yogurt consumption on CMDs. Yogurt is a nutrient-dense dairy food and has been suggested to reduce weight gain and prevent CMDs by contributing to intakes of protein, calcium, bioactive lipids, and several other micronutrients. In addition, fermentation with bacterial strains generates bioactive peptides, resulting in a potentially greater beneficial effect of yogurt on metabolic health than nonfermented dairy products such as milk. To date, there is little concrete evidence that the mechanisms proposed in observational studies to explain positive results of yogurt on CMDs or parameters are valid. Many proposed mechanisms are based on assumptions that commercial yogurts contain strain-specific probiotics, that viable yogurt cultures are present in adequate quantities, and that yogurt provides a minimum threshold dose of nutrients or bioactive components capable of exerting a physiologic effect. Therefore, the primary objective of this review is to investigate the plausibility of potential mechanisms commonly cited in the literature in order to shed light on the inverse associations reported between yogurt intake and various cardiometabolic health parameters that are related to its nutrient profile, bacterial constituents, and food matrix. This article reviews current gaps and challenges

Hepatic and renal mechanisms underlying the osmopressor response

PubMed Central

Mai, Tu H.; Garland, Emily M.; Diedrich, André; Robertson, David

2017-01-01

Increased blood pressure (BP) is observed in patients with impaired baroreflexes after water drinking. The stimulus for this effect is low blood osmolality, and it has been termed the osmopressor response (OPR). The BP increase is associated with activation of the sympathetic nervous system and a requirement for transient receptor potential vanilloid 4 (TRPV4) channels. However, the mechanisms underlying the OPR are poorly understood. We tested the hypothesis that hypotonicity is sensed in the portal area to initiate the OPR. Sino-aortic denervated mice were used and BP was monitored for 30 min after fluid infusion while mice were under anesthesia. Infusion of hypotonic fluid (0.45% saline), but not of isotonic 0.9% saline, directly into the portal vein, produced an immediate OPR (increase in BP with saline 0.45%: 15 ± 13 vs. 0.9%: −7 ± 2 mm Hg, p = 0.003; AUC: 0.45%: 150 ± 99, n = 7 vs. 0.9%: −74 ± 60 mm Hg · min, n = 5, p = 0.003). However, 0.45% saline was not able to trigger a similar response in TRPV4−/− mice (ΔBPTRPV4: −2 ± 5 mm Hg, n = 8, p = 0.009). Hypotonic saline did not raise BP when infused at the same speed and volume into the jugular vein (jugular: −5 ± 6 mm Hg, p = 0.002, compared to portal). Denervation of the splanchnic nerve by celiac ganglionectomy (CGX) did not abolish the OPR (CGX: 15 ± 11 vs. Sham: 16 ± 6 mm Hg, p = 0.34). Renal denervation diminished the OPR elicited by duodenal water infusion (denervation: 9 ± 4 vs. sham: 31 ± 15 mm Hg, p = 0.016). Therefore, hypotonicity in the portal circulation, probably sensed by TRPV4 channels, triggers the OPR and intact renal nerves are needed for the full response. PMID:28143710

Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary Deafness

PubMed Central

Wingard, Jeffrey C.; Zhao, Hong-Bo

2015-01-01

Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. However, there is no apparent, demonstrable relationship between specific changes in connexin (channel) functions and the phenotypes of mutation-induced hearing loss. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Cx30 (GJB6), Cx29 (GJC3), Cx31 (GJB3), and Cx43 (GJA1) mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation-induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required. PMID:26074771

Mechanical properties of graphene nanoribbons under uniaxial tensile strain

NASA Astrophysics Data System (ADS)

Yoneyama, Kazufumi; Yamanaka, Ayaka; Okada, Susumu

2018-03-01

Based on the density functional theory with the generalized gradient approximation, we investigated the mechanical properties of graphene nanoribbons in terms of their edge shape under a uniaxial tensile strain. The nanoribbons with armchair and zigzag edges retain their structure under a large tensile strain, while the nanoribbons with chiral edges are fragile against the tensile strain compared with those with armchair and zigzag edges. The fracture started at the cove region, which corresponds to the border between the zigzag and armchair edges for the nanoribbons with chiral edges. For the nanoribbons with armchair edges, the fracture started at one of the cove regions at the edges. In contrast, the fracture started at the inner region of the nanoribbons with zigzag edges. The bond elongation under the tensile strain depends on the mutual arrangement of covalent bonds with respect to the strain direction.

Mechanical properties of a collagen fibril under simulated degradation.

PubMed

Malaspina, David C; Szleifer, Igal; Dhaher, Yasin

2017-11-01

Collagen fibrils are a very important component in most of the connective tissue in humans. An important process associated with several physiological and pathological states is the degradation of collagen. Collagen degradation is usually mediated by enzymatic and non-enzymatic processes. In this work we use molecular dynamics simulations to study the influence of simulated degradation on the mechanical properties of the collagen fibril. We applied tensile stress to the collagen fiber at different stages of degradation. We compared the difference in the fibril mechanical priorities due the removal of enzymatic crosslink, surface degradation and volumetric degradation. As anticipated, our results indicated that, regardless of the degradation scenario, fibril mechanical properties is reduced. The type of degradation mechanism (crosslink, surface or volumetric) expressed differential effect on the change in the fibril stiffness. Our simulation results showed dramatic change in the fibril stiffness with a small amount of degradation. This suggests that the hierarchical structure of the fibril is a key component for the toughness and is very sensitive to changes in the organization of the fibril. The overall results are intended to provide a theoretical framework for the understanding the mechanical behavior of collagen fibrils under degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A nonlinear electrostatic potential change in the T-system of skeletal muscle detected under passive recording conditions using potentiometric dyes

PubMed Central

1990-01-01

Voltage-sensing dyes were used to examine the electrical behavior of the T-system under passive recording conditions similar to those commonly used to detect charge movement. These conditions are designed to eliminate all ionic currents and render the T-system potential linear with respect to the command potential applied at the surface membrane. However, we found an unexpected nonlinearity in the relationship between the dye signal from the T-system and the applied clamp potential. An additional voltage- and time-dependent optical signal appears over the same depolarizing range of potentials where change movement and mechanical activation occur. This nonlinearity is not associated with unblocked ionic currents and cannot be attributed to lack of voltage clamp control of the T-system, which appears to be good under these conditions. We propose that a local electrostatic potential change occurs in the T-system upon depolarization. An electrostatic potential would not be expected to extend beyond molecular distances of the membrane and therefore would be sensed by a charged dye in the membrane but not by the voltage clamp, which responds solely to the potential of the bulk solution. Results obtained with different dyes suggest that the location of the phenomena giving rise to the extra absorbance change is either intramembrane or at the inner surface of the T-system membrane. PMID:2299329

Mechanical and tribological behaviour of molten salt processed self-lubricated aluminium composite under different treatments

NASA Astrophysics Data System (ADS)

Kannan, C.; Ramanujam, R.

2018-05-01

The aim of this research work is to evaluate the mechanical and tribological behaviour of Al 7075 based self-lubricated hybrid nanocomposite under different treated conditions viz. as-cast, T6 and deep cryo treated. In order to overcome the drawbacks associated with conventional stir casting, a combinational approach that consists of molten salt processing, ultrasonic assistance and optimized mechanical stirring is adopted in this study to fabricate the nanocomposite. The mechanical characterisation tests carried out on this nanocomposite reveals an improvement of about 39% in hardness and 22% in ultimate tensile strength possible under T6 condition. Under specific conditions, the wear rate can be reduced to the extent of about 63% through the usage of self-lubricated hybrid nanocomposite under T6 condition.

Molecular mechanics of silk nanostructures under varied mechanical loading.

PubMed

Bratzel, Graham; Buehler, Markus J

2012-06-01

Spider dragline silk is a self-assembling tunable protein composite fiber that rivals many engineering fibers in tensile strength, extensibility, and toughness, making it one of the most versatile biocompatible materials and most inviting for synthetic mimicry. While experimental studies have shown that the peptide sequence and molecular structure of silk have a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies, in particular, under variations of genetic sequences have been reported. In this study, atomistic-level structures of wildtype as well as modified MaSp1 protein from the Nephila clavipes spider dragline silk sequences, obtained using an in silico approach based on replica exchange molecular dynamics and explicit water molecular dynamics, are subjected to simulated nanomechanical testing using different force-control loading conditions including stretch, pull-out, and peel. The authors have explored the effects of the poly-alanine length of the N. clavipes MaSp1 peptide sequence and identify differences in nanomechanical loading conditions on the behavior of a unit cell of 15 strands with 840-990 total residues used to represent a cross-linking β-sheet crystal node in the network within a fibril of the dragline silk thread. The specific loading condition used, representing concepts derived from the protein network connectivity at larger scales, have a significant effect on the mechanical behavior. Our analysis incorporates stretching, pull-out, and peel testing to connect biochemical features to mechanical behavior. The method used in this study could find broad applications in de novo design of silk-like tunable materials for an array of applications. Copyright © 2011 Wiley Periodicals, Inc.

Molecular dynamics study of strengthening mechanism of nanolaminated graphene/Cu composites under compression.

PubMed

Weng, Shayuan; Ning, Huiming; Fu, Tao; Hu, Ning; Zhao, Yinbo; Huang, Cheng; Peng, Xianghe

2018-02-15

Molecular dynamics simulations of nanolaminated graphene/Cu (NGCu) and pure Cu under compression are conducted to investigate the underlying strengthening mechanism of graphene and the effect of lamella thickness. It is found that the stress-strain curves of NGCu undergo 3 regimes i.e. the elastic regime I, plastic strengthening regime II and plastic flow regime III. Incorporating graphene monolayer is proved to simultaneously contribute to the strength and ductility of the composites and the lamella thickness has a great effect on the mechanical properties of NGCu composites. Different strengthening mechanisms play main role in different regimes, the transition of mechanisms is found to be related to the deformation behavior. Graphene affected zone is developed and integrated with rule of mixtures and confined layer slip model to describe the elastic properties of NGCu and the strengthening effect of the incorporated graphene.

Two distinct neural mechanisms underlying indirect reciprocity.

PubMed

Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

2014-03-18

Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

Two distinct neural mechanisms underlying indirect reciprocity

PubMed Central

Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

2014-01-01

Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards. PMID:24591599

Computerized symbolic manipulation in structural mechanics Progress and potential

NASA Technical Reports Server (NTRS)

Noor, A. K.; Andersen, C. M.

1978-01-01

Status and recent applications of computerized symbolic manipulation to structural mechanics problems are summarized. The applications discussed include; (1) generation of characteristic arrays of finite elements; (2) evaluation of effective stiffness and mass coefficients of continuum models for repetitive lattice structures; and (3) application of Rayleigh-Ritz technique to free vibration analysis of laminated composite elliptic plates. The major advantages of using computerized symbolic manipulation in each of these applications are outlined. A number of problem areas which limit the realization of the full potential of computerized symbolic manipulation in structural mechanics are examined and some of the means of alleviating them are discussed.

Extreme mechanical properties of materials under extreme pressure and temperature conditions (Invited)

NASA Astrophysics Data System (ADS)

Kavner, A.; Armentrout, M. M.; Xie, M.; Weinberger, M.; Kaner, R. B.; Tolbert, S. H.

2010-12-01

A strong synergy ties together the high-pressure subfields of mineral physics, solid-state physics, and materials engineering. The catalog of studies measuring the mechanical properties of materials subjected to large differential stresses in the diamond anvil cell demonstrates a significant pressure-enhancement of strength across many classes of materials, including elemental solids, salts, oxides, silicates, and borides and nitrides. High pressure techniques—both radial diffraction and laser heating in the diamond anvil cell—can be used to characterize the behavior of ultrahard materials under extreme conditions, and help test hypotheses about how composition, structure, and bonding work together to govern the mechanical properties of materials. The principles that are elucidated by these studies can then be used to help design engineering materials to encourage desired properties. Understanding Earth and planetary interiors requires measuring equations of state of relevant materials, including oxides, silicates, and metals under extreme conditions. If these minerals in the diamond anvil cell have any ability to support a differential stress, the assumption of quasi-hydrostaticity no longer applies, with a resulting non-salubrious effect on attempts to measure equation of state. We illustrate these applications with the results of variety of studies from our laboratory and others’ that have used high-pressure radial diffraction techniques and also laser heating in the diamond anvil cell to characterize the mechanical properties of a variety of ultrahard materials, especially osmium metal, osmium diboride, rhenium diboride, and tungsten tetraboride. We compare ambient condition strength studies such as hardness testing with high-pressure studies, especially radial diffraction under differential stress. In addition, we outline criteria for evaluating mechanical properties of materials at combination high pressures and temperatures. Finally, we synthesize our

Cavitation behavior observed in three monoleaflet mechanical heart valves under accelerated testing conditions.

PubMed

Lo, Chi-Wen; Liu, Jia-Shing; Li, Chi-Pei; Lu, Po-Chien; Hwang, Ned H

2008-01-01

Accelerated testing provides a substantial amount of data on mechanical heart valve durability in a short period of time, but such conditions may not accurately reflect in vivo performance. Cavitation, which occurs during mechanical heart valve closure when local flow field pressure decreases below vapor pressure, is thought to play a role in valve damage under accelerated conditions. The underlying flow dynamics and mechanisms behind cavitation bubble formation are poorly understood. Under physiologic conditions, random perivalvular cavitation is difficult to capture. We applied accelerated testing at a pulse rate of 600 bpm and transvalvular pressure of 120 mm Hg, with synchronized videographs and high-frequency pressure measurements, to study cavitation of the Medtronic Hall Standard (MHS), Medtronic Hall D-16 (MHD), and Omni Carbon (OC) valves. Results showed cavitation bubbles between 340 and 360 micros after leaflet/housing impact of the MHS, MHD, and OC valves, intensified by significant leaflet rebound. Squeeze flow, Venturi, and water hammer effects each contributed to cavitation, depending on valve design.

Effect of nature-based sounds' intervention on agitation, anxiety, and stress in patients under mechanical ventilator support: a randomised controlled trial.

PubMed

Saadatmand, Vahid; Rejeh, Nahid; Heravi-Karimooi, Majideh; Tadrisi, Sayed Davood; Zayeri, Farid; Vaismoradi, Mojtaba; Jasper, Melanie

2013-07-01

Few studies have been conducted to investigate the effect of nature-based sounds (N-BS) on agitation, anxiety level and physiological signs of stress in patients under mechanical ventilator support. Non-pharmacological nursing interventions such as N-BS can be less expensive and efficient ways to alleviate anxiety and adverse effects of sedative medications in patients under mechanical ventilator support. This study was conducted to identify the effect of the nature-based sounds' intervention on agitation, anxiety level and physiological stress responses in patients under mechanical ventilation support. A randomized placebo-controlled trial design was used to conduct this study. A total of 60 patients aged 18-65 years under mechanical ventilation support in an intensive care unit were randomly assigned to the control and experimental groups. The patients in the intervention group received 90 min of N-BS. Pleasant nature sounds were played to the patients using media players and headphones. Patients' physiological signs were taken immediately before the intervention and at the 30th, 60th, 90th minutes and 30 min after the procedure had finished. The physiological signs of stress assessed were heart rate, respiratory rate, and blood pressure. Data were collected over eight months from Oct 2011 to June 2012. Anxiety levels and agitation were assessed using the Faces Anxiety Scale and Richmond Agitation Sedation Scale, respectively. The experimental group had significantly lower systolic blood pressure, diastolic blood pressure, anxiety and agitation levels than the control group. These reductions increased progressively in the 30th, 60th, 90th minutes, and 30 min after the procedure had finished indicating a cumulative dose effect. N-BS can provide an effective method of decreasing potentially harmful physiological responses arising from anxiety in mechanically ventilated patients. Nurses can incorporate N-BS intervention as a non-pharmacologic intervention into the

Effect of the fungus Piriformospora indica on physiological characteristics and root morphology of wheat under combined drought and mechanical stresses.

PubMed

Hosseini, Fatemeh; Mosaddeghi, Mohammad Reza; Dexter, Anthony Roger

2017-09-01

This study was done to evaluate the effects of the root-colonizing endophytic fungus Piriformospora indica on wheat growth under combined drought and mechanical stresses. Inoculated (colonized) and non-inoculated (uncolonized) wheat (Triticum aestivum L. cv. Chamran) seedlings were planted in growth chambers filled with moist sand (at a matric suction of 20 hPa). Slight, moderate and severe mechanical stresses (i.e., penetration resistance, Q p , of 1.17, 4.17 and 5.96 MPa, respectively) were produced by a dead-load technique (i.e., placing a weight on the sand surface) in the root medium. Slight, moderate and severe drought stresses were induced using PEG 6000 solutions with osmotic potentials of 0, -0.3 and -0.5 MPa, respectively. After 30 days, plant physiological characteristics and root morphology were measured. An increase in Q p from 1.17 to 5.96 MPa led to greater leaf proline concentration and root diameter, and lower relative water content (RWC), leaf water potential (LWP), chlorophyll contents and root volume. Moreover, severe drought stress decreased root and shoot fresh weights, root volume, leaf area, RWC, LWP and chlorophyll content compared to control. Catalase (CAT) and ascorbate peroxidase (APX) activities under severe drought stress were about 1.5 and 2.9 times greater than control. Interaction of the stresses showed that mechanical stress primarily controls plant water status and physiological responses. However, endophyte presence mitigated the adverse effects of individual and combined stresses on plant growth. Colonized plants were better adapted and had greater root length and volume, RWC, LWP and chlorophyll contents under stressful conditions due to higher absorption sites for water and nutrients. Compared with uncolonized plants, colonized plants showed lower CAT activity implying that wheat inoculated with P. indica was more tolerant and experienced less oxidative damage induced by drought and/or mechanical stress. Copyright �

Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

PubMed

Shen, Lin; Yang, Weitao

2016-04-12

We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

Theoretical foundations of the sound analog membrane potential that underlies coincidence detection in the barn owl

PubMed Central

Ashida, Go; Funabiki, Kazuo; Carr, Catherine E.

2013-01-01

A wide variety of neurons encode temporal information via phase-locked spikes. In the avian auditory brainstem, neurons in the cochlear nucleus magnocellularis (NM) send phase-locked synaptic inputs to coincidence detector neurons in the nucleus laminaris (NL) that mediate sound localization. Previous modeling studies suggested that converging phase-locked synaptic inputs may give rise to a periodic oscillation in the membrane potential of their target neuron. Recent physiological recordings in vivo revealed that owl NL neurons changed their spike rates almost linearly with the amplitude of this oscillatory potential. The oscillatory potential was termed the sound analog potential, because of its resemblance to the waveform of the stimulus tone. The amplitude of the sound analog potential recorded in NL varied systematically with the interaural time difference (ITD), which is one of the most important cues for sound localization. In order to investigate the mechanisms underlying ITD computation in the NM-NL circuit, we provide detailed theoretical descriptions of how phase-locked inputs form oscillating membrane potentials. We derive analytical expressions that relate presynaptic, synaptic, and postsynaptic factors to the signal and noise components of the oscillation in both the synaptic conductance and the membrane potential. Numerical simulations demonstrate the validity of the theoretical formulations for the entire frequency ranges tested (1–8 kHz) and potential effects of higher harmonics on NL neurons with low best frequencies (<2 kHz). PMID:24265616

Dissociation of neural mechanisms underlying orientation processing in humans

PubMed Central

Ling, Sam; Pearson, Joel; Blake, Randolph

2009-01-01

Summary Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and discovery of that property [1, 2] dramatically shaped how we conceptualize visual processing [3–6]. However, much remains unknown about the neural substrates of these basic building blocks of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS) to attenuate neural responses evoked by stimuli presented within a local region of the visual field. Previous physiological studies have shown that rTMS can significantly suppress the neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region [7, 8]. By suppressing neural activity with rTMS, we were able to dissociate components of the neural circuitry underlying two distinct aspects of orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened following rTMS. This dissociation implies that orientation processing relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is largely governed by the patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses contained within those orientation-selective cortical neurons. PMID:19682905

Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

PubMed

Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

2018-03-28

Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

Coping styles and behavioural flexibility: towards underlying mechanisms

PubMed Central

Coppens, Caroline M.; de Boer, Sietse F.; Koolhaas, Jaap M.

2010-01-01

A coping style (also termed behavioural syndrome or personality) is defined as a correlated set of individual behavioural and physiological characteristics that is consistent over time and across situations. This relatively stable trait is a fundamental and adaptively significant phenomenon in the biology of a broad range of species, i.e. it confers differential fitness consequences under divergent environmental conditions. Behavioural flexibility appears to be an important underlying attribute or feature of the coping style that might explain consistency across situations. Proactive coping is characterized by low flexibility expressed as rather rigid, routine-like behavioural tendencies and reduced impulse control (behavioural inhibition) in operant conditioning paradigms. This article summarizes some of the evidence that individual differentiation in behavioural flexibility emerges as a function of underlying variability in the activation of a brain circuitry that includes the prefrontal cortex and its key neurochemical signalling pathways (e.g. dopaminergic and serotonergic input). We argue that the multidimensional nature of animal personality and the terminology used for the various dimensions should reflect the differential pattern of activation of the underlying neuronal network and the behavioural control function of its components. Accordingly, unravelling the molecular mechanisms that give rise to individual differences in the coping style will be an important topic in biobehavioural neurosciences, ecology and evolutionary biology. PMID:21078654

Alterations in tendon microenvironment in response to mechanical load: potential molecular targets for treatment strategies

PubMed Central

Fouda, Mohamed B; Thankam, Finosh G; Dilisio, Matthew F; Agrawal, Devendra K

2017-01-01

Rotator cuff (RC) tendons could beinflicted in many ways with an eventual outcome of pain, weakness and disability, which represent a large burden on health care cost. However, optimal healing, either conservatively or with surgical intervention, remains an issue that needs further investigation. Disorders of the RC tendons may result from external factors like trauma, or internal factors through physiologic and metabolic derangement. Most RC tendon disorders may be asymptomatic and may result from an over-activity of the inflicted shoulder and its tendons. Such tendon disorders are poorly diagnosed since patients do not seek medical attention until pain or weakness ensue. Immunological and biochemical events in RC disorders due to mechanical intolerance have not been investigated. Generally, the mechanical load drives normal physiological properties of the tendon. But, mechanical overload/burden exerts stress on tenocytes, and disrupts the tendon microenvironment by triggering a multitude of signaling pathways leading to extracellular matrix remodeling, disorganization, alteration in collagen composition and apoptosis. These events result in weak tendon which is highly susceptible to rupture or tear. In this article, we critically reviewed the intrinsic signaling pathways that are excessively triggered by continuous mechanical load and the counteracting physiological responses and associated derangements. The elucidation of the molecular events underlying mechanical stress-induced symptomatic/asymptomatic tendinopathy could provide information on potential target sites for translational application in the management of rotator cuff disorders. PMID:29118899

Mechanisms of transient receptor potential vanilloid 1 activation and sensitization by allyl isothiocyanate.

PubMed

Gees, Maarten; Alpizar, Yeranddy A; Boonen, Brett; Sanchez, Alicia; Everaerts, Wouter; Segal, Andrei; Xue, Fenqin; Janssens, Annelies; Owsianik, Grzegorz; Nilius, Bernd; Voets, Thomas; Talavera, Karel

2013-09-01

Allyl isothiocyanate (AITC; aka, mustard oil) is a powerful irritant produced by Brassica plants as a defensive trait against herbivores and confers pungency to mustard and wasabi. AITC is widely used experimentally as an inducer of acute pain and neurogenic inflammation, which are largely mediated by the activation of nociceptive cation channels transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 (TRPV1). Although it is generally accepted that electrophilic agents activate these channels through covalent modification of cytosolic cysteine residues, the mechanism underlying TRPV1 activation by AITC remains unknown. Here we show that, surprisingly, AITC-induced activation of TRPV1 does not require interaction with cysteine residues, but is largely dependent on S513, a residue that is involved in capsaicin binding. Furthermore, AITC acts in a membrane-delimited manner and induces a shift of the voltage dependence of activation toward negative voltages, which is reminiscent of capsaicin effects. These data indicate that AITC acts through reversible interactions with the capsaicin binding site. In addition, we show that TRPV1 is a locus for cross-sensitization between AITC and acidosis in nociceptive neurons. Furthermore, we show that residue F660, which is known to determine the stimulation by low pH in human TRPV1, is also essential for the cross-sensitization of the effects of AITC and low pH. Taken together, these findings demonstrate that not all reactive electrophiles stimulate TRPV1 via cysteine modification and help understanding the molecular bases underlying the surprisingly large role of this channel as mediator of the algesic properties of AITC.

Neural Mechanisms Underlying Cross-Modal Phonetic Encoding.

PubMed

Shahin, Antoine J; Backer, Kristina C; Rosenblum, Lawrence D; Kerlin, Jess R

2018-02-14

Audiovisual (AV) integration is essential for speech comprehension, especially in adverse listening situations. Divergent, but not mutually exclusive, theories have been proposed to explain the neural mechanisms underlying AV integration. One theory advocates that this process occurs via interactions between the auditory and visual cortices, as opposed to fusion of AV percepts in a multisensory integrator. Building upon this idea, we proposed that AV integration in spoken language reflects visually induced weighting of phonetic representations at the auditory cortex. EEG was recorded while male and female human subjects watched and listened to videos of a speaker uttering consonant vowel (CV) syllables /ba/ and /fa/, presented in Auditory-only, AV congruent or incongruent contexts. Subjects reported whether they heard /ba/ or /fa/. We hypothesized that vision alters phonetic encoding by dynamically weighting which phonetic representation in the auditory cortex is strengthened or weakened. That is, when subjects are presented with visual /fa/ and acoustic /ba/ and hear /fa/ ( illusion-fa ), the visual input strengthens the weighting of the phone /f/ representation. When subjects are presented with visual /ba/ and acoustic /fa/ and hear /ba/ ( illusion-ba ), the visual input weakens the weighting of the phone /f/ representation. Indeed, we found an enlarged N1 auditory evoked potential when subjects perceived illusion-ba , and a reduced N1 when they perceived illusion-fa , mirroring the N1 behavior for /ba/ and /fa/ in Auditory-only settings. These effects were especially pronounced in individuals with more robust illusory perception. These findings provide evidence that visual speech modifies phonetic encoding at the auditory cortex. SIGNIFICANCE STATEMENT The current study presents evidence that audiovisual integration in spoken language occurs when one modality (vision) acts on representations of a second modality (audition). Using the McGurk illusion, we show

Alteration of Basaltic Glass to Mg/Fe-Smectite under Acidic Conditions: A Potential Smectite Formation Mechanism on Mars

NASA Technical Reports Server (NTRS)

Peretyazhko, Tanya; Sutter, Brad; Ming, Douglas W.

2014-01-01

Phyllosilicates of the smectite group including Mg- and Fe-saponite and Fe(III)-rich nontronite have been identified on Mars. Smectites are believed to be formed under neutral to alkaline conditions that prevailed on early Mars. This hypothesis is supported by the observation of smectite and carbonate deposits in Noachian terrain on Mars. However, smectite may have formed under mildly acidic conditions. Abundant smectite formations have been detected as layered deposits hundreds of meters thick in intracrater depositional fans and plains sediments, while no large deposits of carbonates are found. Development of mildly acidic conditions at early Mars might allow formation of smectite but inhibit widespread carbonate precipitation. Little is known regarding the mechanisms of smectite formation from basaltic glass under acidic conditions. The objective of this study was to test a hypothesis that Mars-analogue basaltic glass alters to smectite minerals under acidic conditions (pH 4). The effects of Mg and Fe concentrations and temperature on smectite formation from basaltic glass were evaluated. Phyllosilicate synthesis was performed in batch reactors (Parr acid digestion vessel) under reducing hydrothermal conditions at 200 C and 100 C. Synthetic basaltic glass with a composition similar to that of the Gusev crater rock Adirondack (Ground surface APXS measurement) was used in these experiments. Basaltic glass was prepared by melting and quenching procedures. X-ray diffraction (XRD) analysis indicated that the synthesized glass was composed of olivine, magnetite and X-ray amorphous phase. Samples were prepared by mixing 250 mg Adirondack with 0.1 M acetic acid (final pH 4). In order to study influence of Mg concentration on smectite formation, experiments were performed with addition of 0, 1 and 10 mM MgCl2. After 1, 7 and 14 day incubations the solution composition was analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and the altered glass and formed

Child Care Subsidy Use and Child Development: Potential Causal Mechanisms

ERIC Educational Resources Information Center

Hawkinson, Laura E.

2011-01-01

Research using an experimental design is needed to provide firm causal evidence on the impacts of child care subsidy use on child development, and on underlying causal mechanisms since subsidies can affect child development only indirectly via changes they cause in children's early experiences. However, before costly experimental research is…

Insights into the Mechanisms Underlying Boron Homeostasis in Plants

PubMed Central

Yoshinari, Akira; Takano, Junpei

2017-01-01

Boron is an essential element for plants but is toxic in excess. Therefore, plants must adapt to both limiting and excess boron conditions for normal growth. Boron transport in plants is primarily based on three transport mechanisms across the plasma membrane: passive diffusion of boric acid, facilitated diffusion of boric acid via channels, and export of borate anion via transporters. Under boron -limiting conditions, boric acid channels and borate exporters function in the uptake and translocation of boron to support growth of various plant species. In Arabidopsis thaliana, NIP5;1 and BOR1 are located in the plasma membrane and polarized toward soil and stele, respectively, in various root cells, for efficient transport of boron from the soil to the stele. Importantly, sufficient levels of boron induce downregulation of NIP5;1 and BOR1 through mRNA degradation and proteolysis through endocytosis, respectively. In addition, borate exporters, such as Arabidopsis BOR4 and barley Bot1, function in boron exclusion from tissues and cells under conditions of excess boron. Thus, plants actively regulate intracellular localization and abundance of transport proteins to maintain boron homeostasis. In this review, the physiological roles and regulatory mechanisms of intracellular localization and abundance of boron transport proteins are discussed. PMID:29204148

Electrochemical mechanism of tin membrane electrodeposition under ultrasonic waves.

PubMed

Nan, Tianxiang; Yang, Jianguang; Chen, Bing

2018-04-01

Tin was electrodeposited from chloride solutions using a membrane cell under ultrasonic waves. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CHR), and chronopotentiometry were applied to investigate the electrochemical mechanism of tin electrodeposition under ultrasonic field. Chronoamperometry curves showed that the initial process of tin electrodeposition followed the diffusion controlled three-dimensional nucleation and grain growth mechanism. The analysis of the cyclic voltammetry and linear sweep voltammetry diagrams showed that the application of ultrasound can change the tin membrane electro-deposition reaction from diffusion to electrochemical control, and the optimum parameters for tin electrodeposition were H + concentration 3.5 mol·L -1 , temperature 35 °C and ultrasonic power 100 W. The coupling ultrasonic field played a role in refining the grain in this process. The growth of tin crystals showed no orientation preferential, and the tin deposition showed a tendency to form a regular network structure after ultrasonic coupling. While in the absence of ultrasonic coupling, the growth of tin crystals has a high preferential orientation, and the tin deposition showed a tendency to form tin whiskers. Ultrasonic coupling was more favorable for obtaining a more compact and smoother cathode tin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanisms of microstructure formation under the influence of ultrasonic vibrations

NASA Astrophysics Data System (ADS)

Rakita, Milan

Positive effects of ultrasound on crystallization have been known for almost 90 years. Application of ultrasound has been very successful in many industries, most notably in chemistry, creating a new branch of science - sonochemistry. However, ultrasonication has not found wide commercial application in the solidification processing. The reason for that is the complexity of underlying phenomena and the lack of predicting models which correlate processing parameters with the properties of a product. The purpose of this study is to give some contribution toward better understanding of mechanisms that lead to changes in the solidifying microstructure. It has been found that, under experimental conditions used in this work, cavitation-induced nucleation is the major contributor to the grain refinement. Ultrasonication at minimal supercoolings is expected to give maximal grain refinement. Dendrite fragmentation has not shown to be a significant contributor to the grain refinement. Dendrite fragmentation is maximal if done by bubbles that come in contact with the solidifying phase, or that are created there. Alloys/solutions with long solidification interval, or wide mushy zone, are expected to exhibit more dendrite fragmentation. Bubbles are recognized as a crucial feature in ultrasonication. Their size distribution in the liquid phase prior to ultrasonication dictates the cavitation threshold and intensity of cavitation. For the first time, radiation pressure has been recognized as potentially significant factor in grain refinement. In the experimental setup used in this study, acoustic pressure at the main (driving) frequency is not substantial to cause significant fragmentation, and only dendrites close to the sonotrode were fragmented. However, application of ultrasound with frequencies that are several times higher than the current industrial practice could substantially increase dendrite fragmentation. Appearance of fractional harmonics has also been recognized

Coffee melanoidins: structures, mechanisms of formation and potential health impacts.

PubMed

Moreira, Ana S P; Nunes, Fernando M; Domingues, M Rosário; Coimbra, Manuel A

2012-09-01

During the roasting process, coffee bean components undergo structural changes leading to the formation of melanoidins, which are defined as high molecular weight nitrogenous and brown-colored compounds. As coffee brew is one of the main sources of melanoidins in the human diet, their health implications are of great interest. In fact, several biological activities, such as antioxidant, antimicrobial, anticariogenic, anti-inflammatory, antihypertensive, and antiglycative activities, have been attributed to coffee melanoidins. To understand the potential of coffee melanoidin health benefits, it is essential to know their chemical structures. The studies undertaken to date dealing with the structural characterization of coffee melanoidins have shown that polysaccharides, proteins, and chlorogenic acids are involved in coffee melanoidin formation. However, exact structures of coffee melanoidins and mechanisms involved in their formation are far to be elucidated. This paper systematizes the available information and provides a critical overview of the knowledge obtained so far about the structure of coffee melanoidins, mechanisms of their formation, and their potential health implications.

Thermal diodes, regulators, and switches: Physical mechanisms and potential applications

NASA Astrophysics Data System (ADS)

Wehmeyer, Geoff; Yabuki, Tomohide; Monachon, Christian; Wu, Junqiao; Dames, Chris

2017-12-01

Interest in new thermal diodes, regulators, and switches has been rapidly growing because these components have the potential for rich transport phenomena that cannot be achieved using traditional thermal resistors and capacitors. Each of these thermal components has a signature functionality: Thermal diodes can rectify heat currents, thermal regulators can maintain a desired temperature, and thermal switches can actively control the heat transfer. Here, we review the fundamental physical mechanisms of switchable and nonlinear heat transfer which have been harnessed to make thermal diodes, switches, and regulators. The review focuses on experimental demonstrations, mainly near room temperature, and spans the fields of heat conduction, convection, and radiation. We emphasize the changes in thermal properties across phase transitions and thermal switching using electric and magnetic fields. After surveying fundamental mechanisms, we present various nonlinear and active thermal circuits that are based on analogies with well-known electrical circuits, and analyze potential applications in solid-state refrigeration and waste heat scavenging.

Scaling laws and deformation mechanisms of nanoporous copper under adiabatic uniaxial strain compression

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

Yuan, Fuping, E-mail: fpyuan@lnm.imech.ac.cn; Wu, Xiaolei, E-mail: xlwu@imech.ac.cn

2014-12-15

A series of large-scale molecular dynamics simulations were conducted to investigate the scaling laws and the related atomistic deformation mechanisms of Cu monocrystal samples containing randomly placed nanovoids under adiabatic uniaxial strain compression. At onset of yielding, plastic deformation is accommodated by dislocations emitted from void surfaces as shear loops. The collapse of voids are observed by continuous emissions of dislocations from void surfaces and their interactions with further plastic deformation. The simulation results also suggest that the effect modulus, the yield stress and the energy aborption density of samples under uniaxial strain are linearly proportional to the relative densitymore » ρ. Moreover, the yield stress, the average flow stress and the energy aborption density of samples with the same relative density show a strong dependence on the void diameter d, expressed by exponential relations with decay coefficients much higher than -1/2. The corresponding atomistic mechanisms for scaling laws of the relative density and the void diameter were also presented. The present results should provide insights for understanding deformation mechanisms of nanoporous metals under extreme conditions.« less

Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy

PubMed Central

Palmar, Jim; Nava, Manuel; Tomey, Daniel; Garicano, Carlos

2018-01-01

Purpose of Review Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. Recent Findings Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus. They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. Summary Necroptosis, autophagy, and pyroptosis are molecular mechanisms that modulate the survival of the pancreatic beta cell, demonstrating the importance of the immune system in glucolipotoxicity processes and the potential role for immunometabolism as another component of what once known as the “ominous octet.” PMID:29670917

Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

PubMed Central

Xia, Kang; Zhan, Haifei; Hu, De’an; Gu, Yuantong

2016-01-01

The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft. PMID:27618989

Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

NASA Astrophysics Data System (ADS)

Xia, Kang; Zhan, Haifei; Hu, De'An; Gu, Yuantong

2016-09-01

The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.

Cadherin-11 modulates cell morphology and collagen synthesis in periodontal ligament cells under mechanical stress.

PubMed

Feng, Lishu; Zhang, Yimei; Kou, Xiaoxing; Yang, Ruili; Liu, Dawei; Wang, Xuedong; Song, Yang; Cao, Haifeng; He, Danqing; Gan, Yehua; Zhou, Yanheng

2017-03-01

To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed β-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time- and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed β-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation.

Environmental genotoxicity: Probing the underlying mechanisms

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

Shugart, L.; Theodorakis, C.

1993-12-31

Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort tomore » predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.« less

Change of plans: an evaluation of the effectiveness and underlying mechanisms of successful talent transfer.

PubMed

Collins, Rosie; Collins, Dave; MacNamara, Aine; Jones, Martin Ian

2014-01-01

Talent transfer (TT) is a recently formalised process used to identify and develop talented athletes by selecting individuals who have already succeeded in one sport and transferring them to another. Despite the increasing popularity of TT amongst national organisations and sport governing body professionals, however, there is little empirical evidence as to its efficacy or how it may be most efficiently employed. Accordingly, this investigation was designed to gain a deeper understanding of the effectiveness and underlying mechanisms of TT, achieved through a two-part study. Stage 1 provided a quantitative analysis of the incidence and distribution or, in this respect, epidemiology of TT, finding the most popular transfer to be sprinting to bobsleigh, with an average transfer age of 19 years. Stage 2 scrutinised the TT process and explored the specific cases revealed in stage 1 by examining the perceptions of four sport science support specialists who had worked in TT settings, finding several emergent themes which, they felt, could explain the TT processes. The most prominent theme was the psychosocial mechanism of TT, an aspect currently missing from TT initiatives, suggesting that current TT systems are poorly structured and should redress their approach to develop a more integrated scheme that encompasses all potential mechanisms of transfer.

Dual mechanisms regulate ecosystem stability under decade-long warming and hay harvest

PubMed Central

Shi, Zheng; Xu, Xia; Souza, Lara; Wilcox, Kevin; Jiang, Lifen; Liang, Junyi; Xia, Jianyang; García-Palacios, Pablo; Luo, Yiqi

2016-01-01

Past global change studies have identified changes in species diversity as a major mechanism regulating temporal stability of production, measured as the ratio of the mean to the standard deviation of community biomass. However, the dominant plant functional group can also strongly determine the temporal stability. Here, in a grassland ecosystem subject to 15 years of experimental warming and hay harvest, we reveal that warming increases while hay harvest decreases temporal stability. This corresponds with the biomass of the dominant C4 functional group being higher under warming and lower under hay harvest. As a secondary mechanism, biodiversity also explains part of the variation in temporal stability of production. Structural equation modelling further shows that warming and hay harvest regulate temporal stability through influencing both temporal mean and variation of production. Our findings demonstrate the joint roles that dominant plant functional group and biodiversity play in regulating the temporal stability of an ecosystem under global change. PMID:27302085

A potential biochemical mechanism underlying the influence of sterol deprivation stress on Caenorhabditis elegans longevity

USDA-ARS?s Scientific Manuscript database

To investigate the biochemical mechanism for sterol-mediated alteration in aging in Caenorhabditis elegans, we established sterol depletion conditions by treating worms with azacoprostane, which reduced mean lifespan of adult C. elegans by 35%. Proteomic analyses of egg proteins from treated and un...

Mechanisms Underlying Food-Drug Interactions: Inhibition of Intestinal Metabolism and Transport

PubMed Central

Won, Christina S.; Oberlies, Nicholas H.; Paine, Mary F.

2012-01-01

Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes. Commonly consumed fruit juices, teas, and alcoholic drinks contain phytochemicals that inhibit intestinal cytochrome P450 and phase II conjugation enzymes, as well as uptake and efflux transport proteins. Whereas myriad phytochemicals have been shown to inhibit these processes in vitro, translation to the clinic has been deemed insignificant or undetermined. An overlooked prerequisite for elucidating food effects on drug PK is thorough knowledge of causative bioactive ingredients. Substantial variability in bioactive ingredient composition and activity of a given dietary substance poses a challenge in conducting robust food-drug interaction studies. This confounding factor can be addressed by identifying and characterizing specific components, which could be used as marker compounds to improve clinical trial design and quantitatively predict food effects. Interpretation and integration of data from in vitro, in vivo, and in silico studies require collaborative expertise from multiple disciplines, from botany to clinical pharmacology (i.e., plant to patient). Development of more systematic methods and guidelines is needed to address the general lack of information on examining drug-dietary substance interactions prospectively. PMID:22884524

Underlying Mechanisms in the Relationship between Africentric Worldview and Depressive Symptoms

ERIC Educational Resources Information Center

Neblett, Enrique W., Jr.; Hammond, Wizdom Powell; Seaton, Eleanor K.; Townsend, Tiffany G.

2010-01-01

This study examines underlying mechanisms in the relationship between an Africentric worldview and depressive symptoms. Participants were 112 African American young adults. An Africentric worldview buffered the association between perceived stress and depressive symptoms. The relationship between an Africentric worldview and depressive symptoms…

Conception on the cell mechanisms of bone tissue loss under spase flight conditions

NASA Astrophysics Data System (ADS)

Rodionova, Natalia; Oganov, Victor; Kabitskaya, Olga

Basing on the analysis of available literature and the results of our own electron microscopic and radioautographic researches the data are presented about the morpho-functional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures under normal conditions and after exposure of animals (rats, monkeys, mice) to microgravity (SLS-2, Bion-11, BionM-1). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and surface osteocytes as well as to the bone-marrow stromal cells and to those lying on bone surfaces. As a response to the mechanical stimulus (microgravity) the system of stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, some of the osteoblasts undergo apoptosis. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts and bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn’t occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in these remodeling loci. These cell reactions are considered as adaptive-compensatory, but they don’t result

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

Off-axis mirror fabrication from spherical surfaces under mechanical stress

NASA Astrophysics Data System (ADS)

Izazaga-Pérez, R.; Aguirre-Aguirre, D.; Percino-Zacarías, M. E.; Granados-Agustín, Fermin-Salomon

2013-09-01

The preliminary results in the fabrication of off-axis optical surfaces are presented. The propose using the conventional polishing method and with the surface under mechanical stress at its edges. It starts fabricating a spherical surface using ZERODUR® optical glass with the conventional polishing method, the surface is deformed by applying tension and/or compression at the surface edges using a specially designed mechanical mount. To know the necessary deformation, the interferogram of the deformed surface is analyzed in real time with a ZYGO® Mark II Fizeau type interferometer, the mechanical stress is applied until obtain the inverse interferogram associated to the off-axis surface that we need to fabricate. Polishing process is carried out again until obtain a spherical surface, then mechanical stress in the edges are removed and compares the actual interferogram with the theoretical associated to the off-axis surface. To analyze the resulting interferograms of the surface we used the phase shifting analysis method by using a piezoelectric phase-shifter and Durango® interferometry software from Diffraction International™.

An analytical model of the mechanical properties of bulk coal under confined stress

USGS Publications Warehouse

Wang, G.X.; Wang, Z.T.; Rudolph, V.; Massarotto, P.; Finley, R.J.

2007-01-01

This paper presents the development of an analytical model which can be used to relate the structural parameters of coal to its mechanical properties such as elastic modulus and Poisson's ratio under a confined stress condition. This model is developed primarily to support process modeling of coalbed methane (CBM) or CO2-enhanced CBM (ECBM) recovery from coal seam. It applied an innovative approach by which stresses acting on and strains occurring in coal are successively combined in rectangular coordinates, leading to the aggregated mechanical constants. These mechanical properties represent important information for improving CBM/ECBM simulations and incorporating within these considerations of directional permeability. The model, consisting of constitutive equations which implement a mechanically consistent stress-strains correlation, can be used as a generalized tool to study the mechanical and fluid behaviors of coal composites. An example using the model to predict the stress-strain correlation of coal under triaxial confined stress by accounting for the elastic and brittle (non-elastic) deformations is discussed. The result shows a good agreement between the prediction and the experimental measurement. ?? 2007 Elsevier Ltd. All rights reserved.

Video analysis of concussion injury mechanism in under-18 rugby

PubMed Central

Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

2016-01-01

Background Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Methods Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative ‘control’ sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. Results All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact, 43% had a ‘down’ position, 29% the ‘up and forward’ and 29% the ‘away’ position (n=7). The speed of the injured tackler was observed as ‘slow’ in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of ‘support’ (n=2) or as the ‘jackal’ (n=1). Conclusions Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury. PMID:27900149

Disgust as a Mechanism for Decision Making Under Risk: Illuminating Sex Differences and Individual Risk-Taking Correlates of Disgust Propensity.

PubMed

Sparks, Adam Maxwell; Fessler, Daniel M T; Chan, Kai Qin; Ashokkumar, Ashwini; Holbrook, Colin

2018-02-01

The emotion disgust motivates costly behavioral strategies that mitigate against potentially larger costs associated with pathogens, sexual behavior, and moral transgressions. Because disgust thereby regulates exposure to harm, it is by definition a mechanism for calibrating decision making under risk. Understanding this illuminates two features of the demographic distribution of this emotion. First, this approach predicts and explains sex differences in disgust. Greater female disgust propensity is often reported and discussed in the literature, but, to date, conclusions have been based on informal comparisons across a small number of studies, while existing functionalist explanations are at best incomplete. We report the results of an extensive meta-analysis documenting this sex difference, arguing that key features of this pattern are best explained as one manifestation of a broad principle of the evolutionary biology of risk-taking: for a given potential benefit, males in an effectively polygynous mating system accept the risk of harm more willingly than do females. Second, viewing disgust as a mechanism for decision making under risk likewise predicts that individual differences in disgust propensity should correlate with individual differences in various forms of risky behavior, because situational and dispositional factors that influence valuation of opportunity and hazard are often correlated across multiple decision contexts. In two large-sample online studies, we find consistent associations between disgust and risk avoidance. We conclude that disgust and related emotions can be usefully examined through the theoretical lens of decision making under risk in light of human evolution. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Stabilization of solitons under competing nonlinearities by external potentials

NASA Astrophysics Data System (ADS)

Zegadlo, Krzysztof B.; Wasak, Tomasz; Malomed, Boris A.; Karpierz, Miroslaw A.; Trippenbach, Marek

2014-12-01

We report results of the analysis for families of one-dimensional (1D) trapped solitons, created by competing self-focusing (SF) quintic and self-defocusing (SDF) cubic nonlinear terms. Two trapping potentials are considered, the harmonic-oscillator (HO) and delta-functional ones. The models apply to optical solitons in colloidal waveguides and other photonic media, and to matter-wave solitons in Bose-Einstein condensates loaded into a quasi-1D trap. For the HO potential, the results are obtained in an approximate form, using the variational and Thomas-Fermi approximations, and in a full numerical form, including the ground state and the first antisymmetric excited one. For the delta-functional attractive potential, the results are produced in a fully analytical form, and verified by means of numerical methods. Both exponentially localized solitons and weakly localized trapped modes are found for the delta-functional potential. The most essential conclusions concern the applicability of competing Vakhitov-Kolokolov (VK) and anti-VK criteria to the identification of the stability of solitons created under the action of the competing SF and SDF terms.

Fatigue response of a PZT multilayer actuator under high-field electric cycling with mechanical preload

NASA Astrophysics Data System (ADS)

Wang, Hong; Wereszczak, Andrew A.; Lin, Hua-Tay

2009-01-01

An electric fatigue test system was developed for evaluating the reliability of piezoelectric actuators with a mechanical loading capability. Fatigue responses of a lead zirconate titanate (PZT) multilayer actuator with a platethrough electrode configuration were studied under an electric field (1.7 times that of the coercive field of PZT material) and a concurrent mechanical preload (30.0 MPa). A total of 109 cycles was carried out. Variations in charge density and mechanical strain under the high electric field and constant mechanical loads were observed during the fatigue test. The dc and the first harmonic (at 10 Hz) dielectric and piezoelectric coefficients were subsequently characterized using fast Fourier transformation. Both the dielectric and the piezoelectric coefficients exhibited a monotonic decrease prior to 2.86×108 cycles under certain preloading conditions, and then fluctuated. Both the dielectric loss tangent and the piezoelectric loss tangent also fluctuated after a decrease. The results are interpreted and discussed with respect to domain wall activities, microdefects, and other anomalies.

A heuristic model linking yoga philosophy and self-reflection to examine underlying mechanisms of add-on yoga treatment in schizophrenia.

PubMed

Rao, Naren; Menon, Sangeetha

2016-06-01

Preliminary evidence suggests efficacy of yoga as add-on treatment for schizophrenia, but the underlying mechanism by which yoga improves the symptoms of schizophrenia is not completely understood. Yoga improves self-reflection in healthy individuals, and self-reflection abnormalities are typically seen in schizophrenia. However, whether yoga treatment improves impairments in self-reflection typically seen in patients with schizophrenia is not examined. This paper discusses the potential mechanism of yoga in the treatment of schizophrenia and proposes a testable hypothesis for further empirical studies. It is proposed that self-reflection abnormalities in schizophrenia improve with yoga and the neurobiological changes associated with this can be examined using empirical behavioural measures and neuroimaging measures such as magnetic resonance imaging.

The Double-Well Potential in Quantum Mechanics: A Simple, Numerically Exact Formulation

ERIC Educational Resources Information Center

Jelic, V.; Marsiglio, F.

2012-01-01

The double-well potential is arguably one of the most important potentials in quantum mechanics, because the solution contains the notion of a state as a linear superposition of "classical" states, a concept which has become very important in quantum information theory. It is therefore desirable to have solutions to simple double-well potentials…

New Potentials for Old: The Darboux Transformation in Quantum Mechanics

ERIC Educational Resources Information Center

Williams, Brian Wesley; Celius, Tevye C.

2008-01-01

The Darboux transformation in quantum mechanics is reviewed at a basic level. Examples of how this transformation leads to exactly solvable potentials related to the "particle in a box" and the harmonic oscillator are shown in detail. The connection between the Darboux transformation and some modern operator based approaches to quantum mechanics…

Structural and Mechanical Properties of Intermediate Filaments under Extreme Conditions and Disease

NASA Astrophysics Data System (ADS)

Qin, Zhao

Intermediate filaments are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that intermediate filament proteins play key roles to reinforce cells subjected to large-deformation as well as participate in signal transduction. However, it is still poorly understood how the nanoscopic structure, as well as the biochemical properties of these protein molecules contribute to their biomechanical functions. In this research we investigate the material function of intermediate filaments under various extreme mechanical conditions as well as disease states. We use a full atomistic model and study its response to mechanical stresses. Learning from the mechanical response obtained from atomistic simulations, we build mesoscopic models following the finer-trains-coarser principles. By using this multiple-scale model, we present a detailed analysis of the mechanical properties and associated deformation mechanisms of intermediate filament network. We reveal the mechanism of a transition from alpha-helices to beta-sheets with subsequent intermolecular sliding under mechanical force, which has been inferred previously from experimental results. This nanoscale mechanism results in a characteristic nonlinear force-extension curve, which leads to a delocalization of mechanical energy and prevents catastrophic fracture. This explains how intermediate filament can withstand extreme mechanical deformation of > 1 00% strain despite the presence of structural defects. We combine computational and experimental techniques to investigate the molecular mechanism of Hutchinson-Gilford progeria syndrome, a premature aging disease. We find that the mutated lamin tail .domain is more compact and stable than the normal one. This altered structure and stability may enhance the association of intermediate filaments with the nuclear membrane, providing a molecular mechanism of the disease. We study the nuclear membrane association

Biochemical mechanisms of signaling: perspectives in plants under arsenic stress.

PubMed

Islam, Ejazul; Khan, Muhammad Tahir; Irem, Samra

2015-04-01

Plants are the ultimate food source for humans, either directly or indirectly. Being sessile in nature, they are exposed to various biotic and abiotic stresses because of changing climate that adversely effects their growth and development. Contamination of heavy metals is one of the major abiotic stresses because of anthropogenic as well as natural factors which lead to increased toxicity and accumulation in plants. Arsenic is a naturally occurring metalloid toxin present in the earth crust. Due to its presence in terrestrial and aquatic environments, it effects the growth of plants. Plants can tolerate arsenic using several mechanisms like phytochelation, vacuole sequestration and activation of antioxidant defense systems. Several signaling mechanisms have evolved in plants that involve the use of proteins, calcium ions, hormones, reactive oxygen species and nitric oxide as signaling molecules to cope with arsenic toxicity. These mechanisms facilitate plants to survive under metal stress by activating their defense systems. The pathways by which these stress signals are perceived and responded is an unexplored area of research and there are lots of gaps still to be filled. A good understanding of these signaling pathways can help in raising the plants which can perform better in arsenic contaminated soil and water. In order to increase the survival of plants in contaminated areas there is a strong need to identify suitable gene targets that can be modified according to needs of the stakeholders using various biotechnological techniques. This review focuses on the signaling mechanisms of plants grown under arsenic stress and will give an insight of the different sensory systems in plants. Furthermore, it provides the knowledge about several pathways that can be exploited to develop plant cultivars which are resistant to arsenic stress or can reduce its uptake to minimize the risk of arsenic toxicity through food chain thus ensuring food security. Copyright © 2015

Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

NASA Astrophysics Data System (ADS)

Xu, Yuan; Dai, Feng

2018-03-01

A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

PubMed Central

Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

2017-01-01

Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

Metabolic and transcriptional regulatory mechanisms underlying the anoxic adaptation of rice coleoptile

PubMed Central

Lakshmanan, Meiyappan; Mohanty, Bijayalaxmi; Lim, Sun-Hyung; Ha, Sun-Hwa; Lee, Dong-Yup

2014-01-01

The ability of rice to germinate under anoxia by extending the coleoptile is a highly unusual characteristic and a key feature underpinning the ability of rice seeds to establish in such a stressful environment. The process has been a focal point for research for many years. However, the molecular mechanisms underlying the anoxic growth of the coleoptile still remain largely unknown. To unravel the key regulatory mechanisms of rice germination under anoxic stress, we combined in silico modelling with gene expression data analysis. Our initial modelling analysis via random flux sampling revealed numerous changes in rice primary metabolism in the absence of oxygen. In particular, several reactions associated with sucrose metabolism and fermentation showed a significant increase in flux levels, whereas reaction fluxes across oxidative phosphorylation, the tricarboxylic acid cycle and the pentose phosphate pathway were down-regulated. The subsequent comparative analysis of the differences in calculated fluxes with previously published gene expression data under air and anoxia identified at least 37 reactions from rice central metabolism that are transcriptionally regulated. Additionally, cis-regulatory content analyses of these transcriptionally controlled enzymes indicate a regulatory role for transcription factors such as MYB, bZIP, ERF and ZnF in transcriptional control of genes that are up-regulated during rice germination and coleoptile elongation under anoxia. PMID:24894389

Mechanical remodeling of normally sized mammalian cells under a gravity vector.

PubMed

Zhang, Chen; Zhou, Lüwen; Zhang, Fan; Lü, Dongyuan; Li, Ning; Zheng, Lu; Xu, Yanhong; Li, Zhan; Sun, Shujin; Long, Mian

2017-02-01

Translocation of the dense nucleus along a gravity vector initiates mechanical remodeling of a cell, but the underlying mechanisms of cytoskeletal network and focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear. We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or edge-on-orientated substrate. Nucleus longitudinal translocation presents a high value in downward orientation at 24 h or in edge-on orientation at 72 h, which is consistent with orientation-dependent distribution of perinuclear actin stress fibers and vimentin cords. Redistribution of total FAC area and fractionized super mature adhesion number coordinates this dependence at short duration. This orientation-dependent remodeling is associated with nucleus flattering and lamin A/C phosphorylation. Actin depolymerization or Rho-associated protein kinase signaling inhibition abolishes the orientation dependence of nucleus translocation, whereas tubulin polymerization inhibition or vimentin disruption reserves the dependence. A biomechanical model is therefore proposed for integrating the mechanosensing of nucleus translocation with cytoskeletal remodeling and FAC reorganization induced by a gravity vector.-Zhang, C., Zhou, L., Zhang, F., Lü, D., Li, N., Zheng, L., Xu, Y., Li, Z., Sun, S., Long, M. Mechanical remodeling of normally sized mammalian cells under a gravity vector. © FASEB.

Is the primary mechanism underlying COPD: inflammation or ischaemia?

PubMed

Pearson, Michael

2013-08-01

The mechanisms underlying the majority of COPD cases have remained ill-defined. Cigarette smoke contains many toxic chemicals that certainly cause some inflammatory responses, but this article advances a hypothesis that the nicotine and similar compounds within the smoke acting as vasoconstrictors of bronchiolar arterioles may be more important via multiple small infarcts that eventually destroy lung tissue. The hypothesis can explain many of the known features of COPD and if accepted would significantly alter the approach to this condition.

A randomised-controlled trial investigating potential underlying mechanisms of a functionality-based approach to improving women's body image.

PubMed

Alleva, Jessica M; Diedrichs, Phillippa C; Halliwell, Emma; Martijn, Carolien; Stuijfzand, Bobby G; Treneman-Evans, Georgia; Rumsey, Nichola

2018-06-01

Focusing on body functionality is a promising technique for improving women's body image. This study replicates prior research in a large novel sample, tests longer-term follow-up effects, and investigates underlying mechanisms of these effects (body complexity and body-self integration). British women (N = 261) aged 18-30 who wanted to improve their body image were randomised to Expand Your Horizon (three online body functionality writing exercises) or an active control. Trait body image was assessed at Pretest, Posttest, 1-week, and 1-month Follow-Up. To explore whether changes in body complexity and body-self integration 'buffer' the impact of negative body-related experiences, participants also completed beauty-ideal media exposure. Relative to the control, intervention participants experienced improved appearance satisfaction, functionality satisfaction, body appreciation, and body complexity at Posttest, and at both Follow-Ups. Neither body complexity nor body-self integration mediated intervention effects. Media exposure decreased state body satisfaction among intervention and control participants, but neither body complexity nor body-self integration moderated these effects. The findings underscore the value of focusing on body functionality for improving body image and show that effects persist one month post-intervention. Copyright © 2018 Elsevier Ltd. All rights reserved.

Investigation on the interaction of catalase with sodium lauryl sulfonate and the underlying mechanisms.

PubMed

Wang, Jing; Jia, Rui; Wang, Jiaxi; Sun, Zhiqiang; Wu, Zitao; Liu, Rutao; Zong, Wansong

2018-02-01

As a classic type of anionic surfactants, sodium lauryl sulfonate (SLS) might change the structure and function of antioxidant enzyme catalase (CAT) through their direct interactions. However, the underlying molecular mechanism is still unknown. This study investigated the direct interaction of SLS with CAT molecule and the underlying mechanisms using multi-spectroscopic methods, isothermal titration calorimetry, and molecular docking studies. No obvious effects were observed on CAT structure and activity under low SLS concentration exposure. The particle size of CAT molecule decreased and CAT activity was slightly inhibited under high SLS concentration exposure. SLS prefers to bind to the interface of CAT mainly via van der Waals' forces and hydrogen bonds. Subsequently, SLS interacts with the amino acid residues around the heme groups of CAT via hydrophobic interactions and might inhibit CAT activity. © 2017 Wiley Periodicals, Inc.

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis

PubMed Central

2018-01-01

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words “pyro” and “ptosis” in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis. PMID:29706799

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis.

PubMed

Gao, Yu-Lei; Zhai, Jian-Hua; Chai, Yan-Fen

2018-01-01

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words " pyro " and " ptosis " in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.

Neurocomputational mechanisms underlying subjective valuation of effort costs

PubMed Central

Giehl, Kathrin; Sillence, Annie

2017-01-01

In everyday life, we have to decide whether it is worth exerting effort to obtain rewards. Effort can be experienced in different domains, with some tasks requiring significant cognitive demand and others being more physically effortful. The motivation to exert effort for reward is highly subjective and varies considerably across the different domains of behaviour. However, very little is known about the computational or neural basis of how different effort costs are subjectively weighed against rewards. Is there a common, domain-general system of brain areas that evaluates all costs and benefits? Here, we used computational modelling and functional magnetic resonance imaging (fMRI) to examine the mechanisms underlying value processing in both the cognitive and physical domains. Participants were trained on two novel tasks that parametrically varied either cognitive or physical effort. During fMRI, participants indicated their preferences between a fixed low-effort/low-reward option and a variable higher-effort/higher-reward offer for each effort domain. Critically, reward devaluation by both cognitive and physical effort was subserved by a common network of areas, including the dorsomedial and dorsolateral prefrontal cortex, the intraparietal sulcus, and the anterior insula. Activity within these domain-general areas also covaried negatively with reward and positively with effort, suggesting an integration of these parameters within these areas. Additionally, the amygdala appeared to play a unique, domain-specific role in processing the value of rewards associated with cognitive effort. These results are the first to reveal the neurocomputational mechanisms underlying subjective cost–benefit valuation across different domains of effort and provide insight into the multidimensional nature of motivation. PMID:28234892

Global wheat production potentials and management flexibility under the representative concentration pathways

NASA Astrophysics Data System (ADS)

Balkovič, Juraj; van der Velde, Marijn; Skalský, Rastislav; Xiong, Wei; Folberth, Christian; Khabarov, Nikolay; Smirnov, Alexey; Mueller, Nathaniel D.; Obersteiner, Michael

2014-11-01

Wheat is the third largest crop globally and an essential source of calories in human diets. Maintaining and increasing global wheat production is therefore strongly linked to food security. A large geographic variation in wheat yields across similar climates points to sizeable yield gaps in many nations, and indicates a regionally variable flexibility to increase wheat production. Wheat is particularly sensitive to a changing climate thus limiting management opportunities to enable (sustainable) intensification with potentially significant implications for future wheat production. We present a comprehensive global evaluation of future wheat yields and production under distinct Representative Concentration Pathways (RCPs) using the Environmental Policy Integrated Climate (EPIC) agro-ecosystem model. We project, in a geographically explicit manner, future wheat production pathways for rainfed and irrigated wheat systems. We explore agricultural management flexibility by quantifying the development of wheat yield potentials under current, rainfed, exploitable (given current irrigation infrastructure), and irrigated intensification levels. Globally, because of climate change, wheat production under conventional management (around the year 2000) would decrease across all RCPs by 37 to 52 and 54 to 103 Mt in the 2050s and 2090s, respectively. However, the exploitable and potential production gap will stay above 350 and 580 Mt, respectively, for all RCPs and time horizons, indicating that negative impacts of climate change can globally be offset by adequate intensification using currently existing irrigation infrastructure and nutrient additions. Future world wheat production on cropland already under cultivation can be increased by ~ 35% through intensified fertilization and ~ 50% through increased fertilization and extended irrigation, if sufficient water would be available. Significant potential can still be exploited, especially in rainfed wheat systems in Russia

Reliability-based optimization of maintenance scheduling of mechanical components under fatigue

PubMed Central

Beaurepaire, P.; Valdebenito, M.A.; Schuëller, G.I.; Jensen, H.A.

2012-01-01

This study presents the optimization of the maintenance scheduling of mechanical components under fatigue loading. The cracks of damaged structures may be detected during non-destructive inspection and subsequently repaired. Fatigue crack initiation and growth show inherent variability, and as well the outcome of inspection activities. The problem is addressed under the framework of reliability based optimization. The initiation and propagation of fatigue cracks are efficiently modeled using cohesive zone elements. The applicability of the method is demonstrated by a numerical example, which involves a plate with two holes subject to alternating stress. PMID:23564979

Contact force and mechanical loss of multistage cable under tension and bending

NASA Astrophysics Data System (ADS)

Ru, Yanyun; Yong, Huadong; Zhou, Youhe

2016-10-01

A theoretical model for calculating the stress and strain states of cabling structures with different loadings has been developed in this paper. We solve the problem for the first- and second-stage cable with tensile or bending strain. The contact and friction forces between the strands are presented by two-dimensional contact model. Several theoretical models have been proposed to verify the results when the triplet subjected to the tensile strain, including contact force, contact stresses, and mechanical loss. It is found that loadings will affect the friction force and the mechanical loss of the triplet. The results show that the contact force and mechanical loss are dependent on the twist pitch. A shorter twist pitch can lead to higher contact force, while the trend of mechanical loss with twist pitch is complicated. The mechanical loss may be reduced by adjusting the twist pitch reasonably. The present model provides a simple analysis method to investigate the mechanical behaviors in multistage-structures under different loads.

Characterization of interdigitated electrode piezoelectric fiber composites under high electrical and mechanical loading

NASA Astrophysics Data System (ADS)

Rodgers, John P.; Bent, Aaron A.; Hagood, Nesbitt W.

1996-05-01

The primary objective of this work is to develop a standard methodology for characterizing structural actuation systems intended for operation in high electrical and mechanical loading environments. The designed set of tests evaluates the performance of the active materials system under realistic operating conditions. The tests are also used to characterize piezoelectric fiber composites which have been developed as an alternative to monolithic piezoceramic wafers for structural actuation applications. The performance of this actuator system has been improved using an interdigitated electrode pattern, which orients the primary component of the electric field into the plane of the structure, enabling the use of the primary piezoelectric effect along the active fibers. One possible application of this technology is in the integral twist actuation of helicopter rotor blades for higher harmonic control. This application requires actuators which can withstand the harsh rotor blade operating environment. This includes large numbers of electrical and mechanical cycles with considerable centripetal and bending loads. The characterization tests include standard active material tests as well as application-driven tests which evaluate the performance of the actuators during simulated operation. Test results for several actuator configurations are provided, including S2 glass- reinforced and E-glass laminated actuators. The study concludes that the interdigitated electrode piezoelectric fiber composite actuator has great potential for high loading applications.

Packing properties of starch-based powders under mild mechanical stress.

PubMed

Zanardi, I; Gabbrielli, A; Travagli, V

2009-07-01

This study reports the ability to settle of commercial pharmaceutical grade starch samples, both native and pregelatinized. The experiments were carried out under different relative humidity (RH%) conditions and the packing properties were evaluated using both official pharmacopoeial monograph conditions and also modified conditions in order to give a deeper knowledge of tapping under mild mechanical stress. The technique adopted, simulating common pharmaceutical operating practices, appears to be useful to estimate some technologically relevant features of diluent powder materials. Moreover, a general mathematical function has been applied to the experimental data; this could be appropriate for adequately describing material settling patterns and offers practical parameters for characterizing starch powders within the context of a pharmaceutical quality system.

Human Cooperation and Its Underlying Mechanisms.

PubMed

Strang, Sabrina; Park, Soyoung Q

Cooperation is a uniquely human behavior and can be observed across cultures. In order to maintain cooperative behavior in society, people are willing to punish deviant behavior on their own expenses and even without any personal benefits. Cooperation has been object of research in several disciplines. Psychologists, economists, sociologists, biologists, and anthropologists have suggested several motives possibly underlying cooperative behavior. In recent years, there has been substantial progress in understanding neural mechanisms enforcing cooperation. Psychological as well as economic theories were tested for their plausibility using neuroscientific methods. For example, paradigms from behavioral economics were adapted to be tested in the magnetic resonance imaging (MRI) scanner. Also, related brain functions were modulated by using transmagnetic brain stimulation (TMS). While cooperative behavior has often been associated with positive emotions, noncooperative behavior was found to be linked to negative emotions. On a neural level, the temporoparietal junction (TPJ), the striatum, and other reward-related brain areas have been shown to be activated by cooperation, whereas noncooperation has mainly been associated with activity in the insula.

Antimicrobial resistance mechanisms and potential synthetic treatments.

PubMed

Ali, Junaid; Rafiq, Qasim A; Ratcliffe, Elizabeth

2018-04-01

Since the discovery of antibiotics by Sir Alexander Fleming they have been used throughout medicine and play a vital role in combating microorganisms. However, with their vast use, development of resistance has become more prevalent and their use is currently under threat. Antibiotic resistance poses a global threat to human and animal health, with many bacterial species having developed some form of resistance and in some cases within a year of first exposure to antimicrobial agents. This review aims to examine some of the mechanisms behind resistance. Additionally, re-engineering organisms, re-sensitizing bacteria to antibiotics and gene-editing techniques such as the clustered regularly interspaced short palindromic repeats-Cas9 system are providing novel approaches to combat bacterial resistance. To that extent, we have reviewed some of these novel and innovative technologies.

In situ investigation of Geobacillus stearothermophilus spore germination and inactivation mechanisms under moderate high pressure.

PubMed

Georget, Erika; Kapoor, Shobhna; Winter, Roland; Reineke, Kai; Song, Youye; Callanan, Michael; Ananta, Edwin; Heinz, Volker; Mathys, Alexander

2014-08-01

Bacterial spores are a major concern for food safety due to their high resistance to conventional preservation hurdles. Innovative hurdles can trigger bacterial spore germination or inactivate them. In this work, Geobacillus stearothermophilus spore high pressure (HP) germination and inactivation mechanisms were investigated by in situ infrared spectroscopy (FT-IR) and fluorometry. G. stearothermophilus spores' inner membrane (IM) was stained with Laurdan fluorescent dye. Time-dependent FT-IR and fluorescence spectra were recorded in situ under pressure at different temperatures. The Laurdan spectrum is affected by the lipid packing and level of hydration, and provided information on the IM state through the Laurdan generalized polarization. Changes in the -CH2 and -CH3 asymmetric stretching bands, characteristic of lipids, and in the amide I' band region, characteristic of proteins' secondary structure elements, enabled evaluation of the impact of HP on endospores lipid and protein structures. These studies were complemented by ex situ analyses (plate counts and microscopy). The methods applied showed high potential to identify germination mechanisms, particularly associated to the IM. Germination up to 3 log10 was achieved at 200 MPa and 55 °C. A molecular-level understanding of these mechanisms is important for the development and validation of multi-hurdle approaches to achieve commercial sterility. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Three-dimensional finite element analysis on cell culture membrane under mechanical load].

PubMed

Guo, Xin; Fan, Yubo; Song, Jinlin; Chen, Junkai

2002-01-01

A three-dimensional finite element model of the cell culture membrane was developed in the culture device under tension state made by us. The magnitude of tension and the displacement distribution in the membrane made of silicon rubber under different hydrostatic load were obtained by use of FEM analysis. A comparative study was made between the numerical and the experimental results. These results can serve as guides to the related cellular mechanical research.

Transcriptional Mechanisms Underlying Hemoglobin Synthesis

PubMed Central

Katsumura, Koichi R.; DeVilbiss, Andrew W.; Pope, Nathaniel J.; Johnson, Kirby D.; Bresnick, Emery H.

2013-01-01

The physiological switch in expression of the embryonic, fetal, and adult β-like globin genes has garnered enormous attention from investigators interested in transcriptional mechanisms and the molecular basis of hemoglobinopathies. These efforts have led to the discovery of cell type-specific transcription factors, unprecedented mechanisms of transcriptional coregulator function, genome biology principles, unique contributions of nuclear organization to transcription and cell function, and promising therapeutic targets. Given the vast literature accrued on this topic, this article will focus on the master regulator of erythroid cell development and function GATA-1, its associated proteins, and its frontline role in controlling hemoglobin synthesis. GATA-1 is a crucial regulator of genes encoding hemoglobin subunits and heme biosynthetic enzymes. GATA-1-dependent mechanisms constitute an essential regulatory core that nucleates additional mechanisms to achieve the physiological control of hemoglobin synthesis. PMID:23838521

Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

PubMed

Hara, Yusuke

2017-06-01

The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms

PubMed Central

Zilverstand, Anna; Parvaz, Muhammad A.; Moeller, Scott J.; Goldstein, Rita Z.

2016-01-01

Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain’s reward circuitry, and the recruitment and strengthening of the brain’s inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. PMID:26822363

Mechanical behavior, electronic and phonon properties of ZrB12 under pressure

NASA Astrophysics Data System (ADS)

Li, Xiao-Hong; Yong, Yong-Liang; Cui, Hong-Ling; Zhang, Rui-Zhou

2018-06-01

The mechanical, phonon and electronic properties of ZrB12 under pressure are investigated by first-principles calculations. The research shows that ZrB12 is mechanically and dynamically stable up to 100 GPa. The elastic constants, bulk modulus B, shear modulus G, hardness Hv, B/G ratio, Debye temperature under different pressures are systematically investigated. The calculation of electronic properties shows that ZrB12 has metallic character. The Zr-d states dominate the DOS at the Fermi level, and the total DOS and PDOS change slightly with the increasing pressure. DOS (Ef) first decreases, then increases with the increasing pressure. At 50 GPa, ZrB12 has less electron carriers. The analysis of electron localization function shows that the strong B-B and Zr-B covalent bonds may be responsible for the high hardness and stability.

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

PubMed

Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

2018-03-11

Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

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…

Synthetic oligorotaxanes exert high forces when folding under mechanical load

NASA Astrophysics Data System (ADS)

Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

2018-01-01

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells.

PubMed

Somasagara, Ranganatha R; Deep, Gagan; Shrotriya, Sangeeta; Patel, Manisha; Agarwal, Chapla; Agarwal, Rajesh

2015-04-01

Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcitabine-resistant (GR) and gemcitabine-sensitive (GS) PanC cells and underlying molecular mechanisms, together with efficacy of a natural agent bitter melon juice (BMJ). GR PanC cells showed distinct morphological features including spindle-shaped morphology and a decrease in E-cadherin expression. GR cells also showed higher ATP production with an increase in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Molecular studies showed higher expression of glucose transporters (GLUT1 and 4) suggesting an increase in glucose uptake by GR cells. Importantly, GR cells showed a significant increase in Akt and ERK1/2 phosphorylation and their inhibition decreased cell viability, suggesting their role in survival and drug resistance of these cells. Recently, we reported strong efficacy of BMJ against a panel of GS cells in culture and nude mice, which we expanded here and found that BMJ was also effective in decreasing both Akt and ERK1/2 phosphorylation and viability of GR PanC cells. Overall, we have identified novel mechanisms of gemcitabine resistance in PanC cells which are targeted by BMJ. Considering the short survival in PanC patients, our findings could have high translational potential in controlling this deadly malignancy.

Neural mechanisms underlying cognitive control of men with lifelong antisocial behavior.

PubMed

Schiffer, Boris; Pawliczek, Christina; Mu Ller, Bernhard; Forsting, Michael; Gizewski, Elke; Leygraf, Norbert; Hodgins, Sheilagh

2014-04-30

Results of meta-analyses suggested subtle deficits in cognitive control among antisocial individuals. Because almost all studies focused on children with conduct problems or adult psychopaths, however, little is known about cognitive control mechanisms among the majority of persistent violent offenders who present an antisocial personality disorder (ASPD). The present study aimed to determine whether offenders with ASPD, relative to non-offenders, display dysfunction in the neural mechanisms underlying cognitive control and to assess the extent to which these dysfunctions are associated with psychopathic traits and trait impulsivity. Participants comprised 21 violent offenders and 23 non-offenders who underwent event-related functional magnetic resonance imaging while performing a non-verbal Stroop task. The offenders, relative to the non-offenders, exhibited reduced response time interference and a different pattern of conflict- and error-related activity in brain areas involved in cognitive control, attention, language, and emotion processing, that is, the anterior cingulate, dorsolateral prefrontal, superior temporal and postcentral cortices, putamen, thalamus, and amygdala. Moreover, between-group differences in behavioural and neural responses revealed associations with core features of psychopathy and attentional impulsivity. Thus, the results of the present study confirmed the hypothesis that offenders with ASPD display alterations in the neural mechanisms underlying cognitive control and that those alterations relate, at least in part, to personality characteristics. Copyright © 2014. Published by Elsevier Ireland Ltd.

Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor

PubMed Central

Handforth, Adrian

2012-01-01

Background Harmaline and harmine are tremorigenic β-carbolines that, on administration to experimental animals, induce an acute postural and kinetic tremor of axial and truncal musculature. This drug-induced action tremor has been proposed as a model of essential tremor. Here we review what is known about harmaline tremor. Methods Using the terms harmaline and harmine on PubMed, we searched for papers describing the effects of these β-carbolines on mammalian tissue, animals, or humans. Results Investigations over four decades have shown that harmaline induces rhythmic burst-firing activity in the medial and dorsal accessory inferior olivary nuclei that is transmitted via climbing fibers to Purkinje cells and to the deep cerebellar nuclei, then to brainstem and spinal cord motoneurons. The critical structures required for tremor expression are the inferior olive, climbing fibers, and the deep cerebellar nuclei; Purkinje cells are not required. Enhanced synaptic norepinephrine or blockade of ionic glutamate receptors suppresses tremor, whereas enhanced synaptic serotonin exacerbates tremor. Benzodiazepines and muscimol suppress tremor. Alcohol suppresses harmaline tremor but exacerbates harmaline-associated neural damage. Recent investigations on the mechanism of harmaline tremor have focused on the T-type calcium channel. Discussion Like essential tremor, harmaline tremor involves the cerebellum, and classic medications for essential tremor have been found to suppress harmaline tremor, leading to utilization of the harmaline model for preclinical testing of antitremor drugs. Limitations are that the model is acute, unlike essential tremor, and only approximately half of the drugs reported to suppress harmaline tremor are subsequently found to suppress tremor in clinical trials. PMID:23440018

On the Physiological Modulation and Potential Mechanisms Underlying Parieto-Occipital Alpha Oscillations

PubMed Central

Lozano-Soldevilla, Diego

2018-01-01

The parieto-occipital alpha (8–13 Hz) rhythm is by far the strongest spectral fingerprint in the human brain. Almost 90 years later, its physiological origin is still far from clear. In this Research Topic I review human pharmacological studies using electroencephalography (EEG) and magnetoencephalography (MEG) that investigated the physiological mechanisms behind posterior alpha. Based on results from classical and recent experimental studies, I find a wide spectrum of drugs that modulate parieto-occipital alpha power. Alpha frequency is rarely affected, but this might be due to the range of drug dosages employed. Animal and human pharmacological findings suggest that both GABA enhancers and NMDA blockers systematically decrease posterior alpha power. Surprisingly, most of the theoretical frameworks do not seem to embrace these empirical findings and the debate on the functional role of alpha oscillations has been polarized between the inhibition vs. active poles hypotheses. Here, I speculate that the functional role of alpha might depend on physiological excitation as much as on physiological inhibition. This is supported by animal and human pharmacological work showing that GABAergic, glutamatergic, cholinergic, and serotonergic receptors in the thalamus and the cortex play a key role in the regulation of alpha power and frequency. This myriad of physiological modulations fit with the view that the alpha rhythm is a complex rhythm with multiple sources supported by both thalamo-cortical and cortico-cortical loops. Finally, I briefly discuss how future research combining experimental measurements derived from theoretical predictions based of biophysically realistic computational models will be crucial to the reconciliation of these disparate findings. PMID:29670518

Leaching of Zinc Sulfide by Thiobacillus ferrooxidans: Experiments with a Controlled Redox Potential Indicate No Direct Bacterial Mechanism

PubMed Central

Fowler, T. A.; Crundwell, F. K.

1998-01-01

The role of Thiobacillus ferrooxidans in bacterial leaching of mineral sulfides is controversial. Much of the controversy is due to the fact that the solution conditions, especially the concentrations of ferric and ferrous ions, change during experiments. The role of the bacteria would be more easily discernible if the concentrations of ferric and ferrous ions were maintained at set values throughout the experimental period. In this paper we report results obtained by using the constant redox potential apparatus described previously (P. I. Harvey and F. K. Crundwell, Appl. Environ. Microbiol. 63:2586–2592, 1997). This apparatus is designed to control the redox potential in the leaching compartment of an electrolytic cell by reduction or oxidation of dissolved iron. By controlling the redox potential the apparatus maintains the concentrations of ferrous and ferric ions at their initial values. Experiments were conducted in the presence of T. ferrooxidans and under sterile conditions. Analysis of the conversion of zinc sulfide in the absence of the bacteria and analysis of the conversion of zinc sulfate in the presence of the bacteria produced the same results. This indicates that the only role of the bacteria under the conditions used is regeneration of ferric ions in solution. In this work we found no evidence that there is a direct mechanism for bacterial leaching. PMID:9758769

Structural pierce into molecular mechanism underlying Clostridium perfringens Epsilon toxin function.

PubMed

Khalili, Saeed; Jahangiri, Abolfazl; Hashemi, Zahra Sadat; Khalesi, Bahman; Mard-Soltani, Maysam; Amani, Jafar

2017-03-01

Epsilon toxin of the Clostridium perfringens garnered a lot of attention due to its potential for toxicity in humans, extreme potency for cytotoxicity in mice and lack of any approved therapeutics prescribed for human. However, the intricacies of the Epsilon toxin action mechanism are yet to be understood. In this regard, various in silico tools have been exploited to model and refine the 3D structure of the toxin and its two receptors. The receptor proteins were embedded into designed lipid membranes within an aqueous and ionized environment. Thereafter, the modeled structures subjected to series of consecutive molecular dynamics runs to achieve the most natural like coordination for each model. Ultimately, protein-protein interaction analyses were performed to understand the probable action mechanism. The obtained results successfully confirmed the accuracy of employed methods to achieve high quality models for the toxin and its receptors within their lipid bilayers. Molecular dynamics analyses lead the structures to a more native like coordination. Moreover, the results of previous empirical studies were confirmed, while new insights for action mechanisms including the detailed roles of Hepatitis A virus cellular receptor 1 (HAVCR1) and Myelin and lymphocyte protein (MAL) proteins were achieved. In light of previous and our observations, we suggested novel models which elucidated the existing interplay between potential players of Epsilon toxin action mechanism with detailed structural evidences. These models would pave the way to have more robust understanding of the Epsilon toxin biology, more precise vaccine construction and more successful drug (inhibitor) design. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia.

PubMed

Cabral, Layla D M; Giusti-Paiva, Alexandre

2016-11-01

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid-1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)-induced lung injury in mice. For this, adult mice pre-treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS-challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre-treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre-treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Passive water collection with the integument: mechanisms and their biomimetic potential.

PubMed

Comanns, Philipp

2018-05-22

Several mechanisms of water acquisition have evolved in animals living in arid habitats to cope with limited water supply. They enable access to water sources such as rain, dew, thermally facilitated condensation on the skin, fog, or moisture from a damp substrate. This Review describes how a significant number of animals - in excess of 39 species from 24 genera - have acquired the ability to passively collect water with their integument. This ability results from chemical and structural properties of the integument, which, in each species, facilitate one or more of six basic mechanisms: increased surface wettability, increased spreading area, transport of water over relatively large distances, accumulation and storage of collected water, condensation, and utilization of gravity. Details are described for each basic mechanism. The potential for bio-inspired improvement of technical applications has been demonstrated in many cases, in particular for several wetting phenomena, fog collection and passive, directional transport of liquids. Also considered here are potential applications in the fields of water supply, lubrication, heat exchangers, microfluidics and hygiene products. These present opportunities for innovations, not only in product functionality, but also for fabrication processes, where resources and environmental impact can be reduced. © 2018. Published by The Company of Biologists Ltd.

Ultrasonographic measurement of the mechanical properties of the sole under the metatarsal heads.

PubMed

Wang, C L; Hsu, T C; Shau, Y W; Shieh, J Y; Hsu, K H

1999-09-01

The sole under the metatarsal heads functions as a shock absorber during walking and running. The mechanical properties of the sole provide the primary defense against the development of metatarsalgia and foot ulceration. However, limited information about these properties has been documented. In this study, we used ultrasonography to evaluate the mechanical properties, including unloaded thickness, compressibility index, elastic modulus, and energy dissipation ratio, of the sole in 20 healthy subjects. The unloaded thickness decreased progressively from the first to the fifth metatarsal heads, with values of 1.50, 1.36, 1.25, 1.14, and 1.04 cm. The sole under the first metatarsal head had the greatest values for the compressibility index and elastic modulus (55.9% and 1.39 kg/cm2), and the sole under the third metatarsal head had the smallest values (50.8% and 1.23 kg/cm2). The sole under the fifth metatarsal head had the greatest energy dissipation ratio (33.7%), followed by that under the third, second, first, and fourth metatarsal heads. Multivariate adjusted linear regression showed that the unloaded thickness, compressibility index, and elastic modulus values increased significantly with age and body weight (p < 0.05) and that the energy dissipation ratio increased significantly with body weight (p < 0.05)

Developmental origins of health and disease: current knowledge and potential mechanisms.

PubMed

Hoffman, Daniel J; Reynolds, Rebecca M; Hardy, Daniel B

2017-12-01

Epidemiologic and clinical research has provided a large body of evidence supporting the developmental origins of health and disease (DOHaD), but there has been a relative dearth of mechanistic studies in humans due to the complexity of working with large, longitudinal cohorts. Nonetheless, animal models of undernutrition have provided substantial evidence for the potential epigenetic, metabolic, and endocrine mechanisms behind DOHaD. Furthermore, recent research has explored the interaction between the environment and the gastrointestinal system by investigating how the gut microbial ecology may impact the capacity for nutrient processing and absorption in a manner that may limit growth. This review presents a summary of current research that supports the concept of DOHaD, as well as potential mechanisms and interactions that explain how nutrition in utero and during early childhood influences lifelong health. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

PubMed Central

Tarale, Prashant; Chakrabarti, Tapan; Sivanesan, Saravanadevi; Naoghare, Pravin; Bafana, Amit; Krishnamurthi, Kannan

2016-01-01

Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease. PMID:27314012

Feeding Problems and Their Underlying Mechanisms in the Esophageal Atresia–Tracheoesophageal Fistula Patient

PubMed Central

Mahoney, Lisa; Rosen, Rachel

2017-01-01

Feeding difficulties such as dysphagia, coughing, choking, or vomiting during meals, slow eating, oral aversion, food refusal, and stressful mealtimes are common in children with repaired esophageal atresia (EA) and the reasons for this are often multifactorial. The aim of this review is to describe the possible underlying mechanisms contributing to feeding difficulties in patients with EA and approaches to management. Underlying mechanisms for these feeding difficulties include esophageal dysphagia, oropharyngeal dysphagia and aspiration, and aversions related to prolonged gastrostomy tube feeding. The initial diagnostic evaluation for feeding difficulties in a patient with EA may involve an esophagram, videofluoroscopic imaging or fiberoptic endoscopic evaluation during swallowing, upper endoscopy with biopsies, pH-impedance testing, and/or esophageal motility studies. The main goal of management is to reduce the factors contributing to feeding difficulties and may include reducing esophageal stasis, maximizing reflux therapies, treating underlying lung disease, dilating strictures, and altering feeding methods, routes, or schedules. PMID:28620597

Ferroelastic domain switching dynamics under electrical and mechanical excitations.

PubMed

Gao, Peng; Britson, Jason; Nelson, Christopher T; Jokisaari, Jacob R; Duan, Chen; Trassin, Morgan; Baek, Seung-Hyub; Guo, Hua; Li, Linze; Wang, Yiran; Chu, Ying-Hao; Minor, Andrew M; Eom, Chang-Beom; Ramesh, Ramamoorthy; Chen, Long-Qing; Pan, Xiaoqing

2014-05-02

In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.

Ferroelastic domain switching dynamics under electrical and mechanical excitations

NASA Astrophysics Data System (ADS)

Gao, Peng; Britson, Jason; Nelson, Christopher T.; Jokisaari, Jacob R.; Duan, Chen; Trassin, Morgan; Baek, Seung-Hyub; Guo, Hua; Li, Linze; Wang, Yiran; Chu, Ying-Hao; Minor, Andrew M.; Eom, Chang-Beom; Ramesh, Ramamoorthy; Chen, Long-Qing; Pan, Xiaoqing

2014-05-01

In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.

[Study on mechanism of SOM stabilization of paddy soils under long-term fertilizations].

PubMed

Luo, Lu; Zhou, Ping; Tong, Cheng-Li; Shi, Hui; Wu, Jin-Shui; Huang, Tie-Ping

2013-02-01

Fourier transform infrared spectroscopy (FTIR) was applied to study the structure of soil organic matter (SOM) of paddy soils under long-term different fertilization treatments. The aim was to clarify the different distribution of SOM between different fertilization methods and between topsoil and subsoil, and to explore the stability mechanism of SOM under different fertilization treatments. The results showed that the content of topsoil organic carbon (SOC) was the highest under organic-inorganic fertilizations, with the increment of SOC by 18.5%, 12.9% and 18.4% under high organic manure (HOM), low organic manure (LOM) and straw returning (STW) respectively compared with no fertilization treatment (CK). The long-term fertilizations also changed the chemical structure of SOM. As compared with CK, different fertilization treatments increased the functional group absorbing intensity of chemical resistance compounds (aliphatic, aromaticity), carbohydrate and organo-silicon compounds, which was the most distinctive under treatments of HOM, LOM and STW. For example, the absorbing intensity of alkyl was 0.30, 0.25 and 0.29 under HOM, LOM and STW, respectively. These values were increased by 87% , 56% and 81% as compared with that under CK treatment. The functional group absorbing intensity of SOM in the topsoil was stronger than that in the subsoil, with the most distinctive difference under HOM, LOM and STW treatments. The present research indicated that the enhanced chemical resistance of functional group of SOM may contribute to the high contents of SOC in the paddy soils under long-term organic-inorganic fertilizations, which also suggested a chemical stabilization mechanism of SOM in the paddy soils.

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

PubMed

Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

2008-02-01

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

The Mechanism Underlying the Antibacterial Activity of Shikonin against Methicillin-Resistant Staphylococcus aureus

PubMed Central

Lee, Dae-Young; Kim, Yeon Bok; Lee, Sang-Won; Cha, Seon-Woo; Park, Hong-Woo; Kim, Geum-Soog; Kwon, Dong-Yeul; Lee, Min-Ho; Han, Sin-Hee

2015-01-01

Shikonin (SKN), a highly liposoluble naphthoquinone pigment isolated from the roots of Lithospermum erythrorhizon, is known to exert antibacterial, wound-healing, anti-inflammatory, antithrombotic, and antitumor effects. The aim of this study was to examine SKN antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The SKN was analyzed in combination with membrane-permeabilizing agents Tris and Triton X-100, ATPase inhibitors sodium azide and N,N′-dicyclohexylcarbodiimide, and S. aureus-derived peptidoglycan; the effects on MRSA viability were evaluated by the broth microdilution method, time-kill test, and transmission electron microscopy. Addition of membrane-permeabilizing agents or ATPase inhibitors together with a low dose of SKN potentiated SKN anti-MRSA activity, as evidenced by the reduction of MRSA cell density by 75% compared to that observed when SKN was used alone; in contrast, addition of peptidoglycan blocked the antibacterial activity of SKN. The results indicate that the anti-MRSA effect of SKN is associated with its affinity to peptidoglycan, the permeability of the cytoplasmic membrane, and the activity of ATP-binding cassette (ABC) transporters. This study revealed the potential of SKN as an effective natural antibiotic and of its possible use to substantially reduce the use of existing antibiotic may also be important for understanding the mechanism underlying the antibacterial activity of natural compounds. PMID:26265924

Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions

PubMed Central

Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A.; Decker, William; Manjili, Masoud H.; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A. Ivana; Raju, Jayadev; Hamid, Roslida A.; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K.; Ryan, Elizabeth P.; Brown, Dustin G.; Lowe, Leroy; Lyerly, H.Kim

2015-01-01

An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. PMID:26002081

General Anesthetics to Treat Major Depressive Disorder: Clinical Relevance and Underlying Mechanisms.

PubMed

Vutskits, Laszlo

2018-01-01

Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases. Clinical observations over the past few decades appear to confirm this possibility. Indeed, equipotency of general anesthesia alone in comparison with electroconvulsive therapy under general anesthesia has been demonstrated in several clinical trials. Importantly, in the past 15 years, intravenous administration of subanesthetic doses of ketamine have also been demonstrated to have rapid antidepressant effects. The molecular, cellular, and network mechanisms underlying these therapeutic effects have been partially identified. Although several important questions remain to be addressed, the ensemble of these experimental and clinical observations opens new therapeutic possibilities in the treatment of depressive disorders. Importantly, they also suggest a new therapeutic role for anesthetics that goes beyond their principal use in the perioperative period to facilitate surgery.

Research of mechanics of the compact bone microvolume and porous ceramics under uniaxial compression

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

Kolmakova, T. V., E-mail: kolmakova@ftf.tsu.ru; Buyakova, S. P., E-mail: sbuyakova@ispms.tsc.ru; Kul’kov, S. N., E-mail: kulkov@ms.tsc.ru

2015-11-17

The research results of the mechanics are presented and the effective mechanical characteristics under uniaxial compression of the simulative microvolume of the compact bone are defined subject to the direction of the collagen-mineral fibers, porosity and mineral content. The experimental studies of the mechanics are performed and the effective mechanical characteristics of the produced porous zirconium oxide ceramics are defined. The recommendations are developed on the selection of the ceramic samples designed to replace the fragment of the compact bone of a definite structure and mineral content.

Uncovering the mechanisms of Caenorhabditis elegans ageing from global quantification of the underlying landscape.

PubMed

Zhao, Lei; Wang, Jin

2016-11-01

Recent studies on Caenorhabditis elegans reveal that gene manipulations can extend its lifespan several fold. However, how the genes work together to determine longevity is still an open question. Here we construct a gene regulatory network for worm ageing and quantify its underlying potential and flux landscape. We found ageing and rejuvenation states can emerge as basins of attraction at certain gene expression levels. The system state can switch from one attractor to another driven by the intrinsic or external perturbations through genetics or the environment. Furthermore, we simulated gene silencing experiments and found that the silencing of longevity-promoting or lifespan-limiting genes leads to ageing or rejuvenation domination, respectively. This indicates that the difference in depths between ageing and the rejuvenation attractor is highly correlated with worm longevity. We further uncovered some key genes and regulations which have a strong influence on landscape basin stability. A dynamic landscape model is proposed to describe the whole process of ageing: the ageing attractor dominates when senescence progresses. We also uncovered the oscillation dynamics, and a similar behaviour was observed in the long-lived creature Turritopsis dohrnii Our landscape theory provides a global and physical approach to explore the underlying mechanisms of ageing. © 2016 The Author(s).

Investigation of the CH3Cl + CN(-) reaction in water: Multilevel quantum mechanics/molecular mechanics study.

PubMed

Xu, Yulong; Zhang, Jingxue; Wang, Dunyou

2015-06-28

The CH3Cl + CN(-) reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack SN2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show that the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ∼11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies.

Investigation of the CH3Cl + CN- reaction in water: Multilevel quantum mechanics/molecular mechanics study

NASA Astrophysics Data System (ADS)

Xu, Yulong; Zhang, Jingxue; Wang, Dunyou

2015-06-01

The CH3Cl + CN- reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack SN2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show that the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ˜11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies.

Implicit Misattribution as a Mechanism Underlying Evaluative Conditioning

PubMed Central

Jones, Christopher R.; Fazio, Russell H.; Olson, Michael A.

2009-01-01

Evaluative conditioning (EC) refers to the formation or change of an attitude towards an object following that object’s pairing with positively or negatively valenced stimuli. We provide evidence that EC can occur through an implicit misattribution mechanism in which an evaluative response evoked by a valenced stimulus is incorrectly and implicitly attributed to another stimulus, forming or changing an attitude towards this other stimulus. Five studies measured or manipulated variables related to the potential for the misattribution of an evaluation, or “source confusability.” Greater EC was observed when participants’ eye gaze shifted frequently between a valenced and neutral stimulus (Studies 1 & 2), when the two stimuli appeared in close spatial proximity (Study 3), and when the neutral stimulus was made more perceptually salient than the valenced stimulus due to its larger size (Study 4). In other words, conditions conducive to source confusability increased EC. Study 5 provided evidence for multiple mechanisms of EC by comparing the effects of mildly evocative valenced stimuli (those evoking responses that might more easily be misattributed to another object) to more strongly evocative stimuli. PMID:19379028

Age Differences in the Underlying Mechanisms of Stereotype Threat Effects

PubMed Central

Hess, Thomas M.

2015-01-01

Objectives. The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Method. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Results. Older adults’ performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. Conclusions. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. PMID:24077743

Simulation on the internal structure of three-dimensional proximal tibia under different mechanical environments.

PubMed

Fang, Juan; Gong, He; Kong, Lingyan; Zhu, Dong

2013-12-20

Bone can adjust its morphological structure to adapt to the changes of mechanical environment, i.e. the bone structure change is related to mechanical loading. This implies that osteoarthritis may be closely associated with knee joint deformity. The purposes of this paper were to simulate the internal bone mineral density (BMD) change in three-dimensional (3D) proximal tibia under different mechanical environments, as well as to explore the relationship between mechanical environment and bone morphological abnormity. The right proximal tibia was scanned with CT to reconstruct a 3D proximal tibia model in MIMICS, then it was imported to finite element software ANSYS to establish 3D finite element model. The internal structure of 3D proximal tibia of young normal people was simulated using quantitative bone remodeling theory in combination with finite element method, then based on the changing pattern of joint contact force on the tibial plateau in valgus knees, the mechanical loading was changed, and the simulated normal tibia structure was used as initial structure to simulate the internal structure of 3D proximal tibia for old people with 6° valgus deformity. Four regions of interest (ROIs) were selected in the proximal tibia to quantitatively analyze BMD and compare with the clinical measurements. The simulation results showed that the BMD distribution in 3D proximal tibia was consistent with clinical measurements in normal knees and that in valgus knees was consistent with the measurement of patients with osteoarthritis in clinics. It is shown that the change of mechanical environment is the main cause for the change of subchondral bone structure, and being under abnormal mechanical environment for a long time may lead to osteoarthritis. Besides, the simulation method adopted in this paper can more accurately simulate the internal structure of 3D proximal tibia under different mechanical environments. It helps to better understand the mechanism of

Simulation on the internal structure of three-dimensional proximal tibia under different mechanical environments

PubMed Central

2013-01-01

Background Bone can adjust its morphological structure to adapt to the changes of mechanical environment, i.e. the bone structure change is related to mechanical loading. This implies that osteoarthritis may be closely associated with knee joint deformity. The purposes of this paper were to simulate the internal bone mineral density (BMD) change in three-dimensional (3D) proximal tibia under different mechanical environments, as well as to explore the relationship between mechanical environment and bone morphological abnormity. Methods The right proximal tibia was scanned with CT to reconstruct a 3D proximal tibia model in MIMICS, then it was imported to finite element software ANSYS to establish 3D finite element model. The internal structure of 3D proximal tibia of young normal people was simulated using quantitative bone remodeling theory in combination with finite element method, then based on the changing pattern of joint contact force on the tibial plateau in valgus knees, the mechanical loading was changed, and the simulated normal tibia structure was used as initial structure to simulate the internal structure of 3D proximal tibia for old people with 6° valgus deformity. Four regions of interest (ROIs) were selected in the proximal tibia to quantitatively analyze BMD and compare with the clinical measurements. Results The simulation results showed that the BMD distribution in 3D proximal tibia was consistent with clinical measurements in normal knees and that in valgus knees was consistent with the measurement of patients with osteoarthritis in clinics. Conclusions It is shown that the change of mechanical environment is the main cause for the change of subchondral bone structure, and being under abnormal mechanical environment for a long time may lead to osteoarthritis. Besides, the simulation method adopted in this paper can more accurately simulate the internal structure of 3D proximal tibia under different mechanical environments. It helps to better

A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

NASA Astrophysics Data System (ADS)

Qin, Qing-Hua; Wang, Ya-Nan

2012-12-01

A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model), but also predict the realtime development pattern of BMC and BFE, as well as the dynamics of osteoblasts (OBA), osteoclasts (OCA), nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated. The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

Bound states of moving potential wells in discrete wave mechanics

NASA Astrophysics Data System (ADS)

Longhi, S.

2017-10-01

Discrete wave mechanics describes the evolution of classical or matter waves on a lattice, which is governed by a discretized version of the Schrödinger equation. While for a vanishing lattice spacing wave evolution of the continuous Schrödinger equation is retrieved, spatial discretization and lattice effects can deeply modify wave dynamics. Here we discuss implications of breakdown of exact Galilean invariance of the discrete Schrödinger equation on the bound states sustained by a smooth potential well which is uniformly moving on the lattice with a drift velocity v. While in the continuous limit the number of bound states does not depend on the drift velocity v, as one expects from the covariance of ordinary Schrödinger equation for a Galilean boost, lattice effects can lead to a larger number of bound states for the moving potential well as compared to the potential well at rest. Moreover, for a moving potential bound states on a lattice become rather generally quasi-bound (resonance) states.

Computational Identification of Diverse Mechanisms Underlying Transcription Factor-DNA Occupancy

PubMed Central

Cheng, Qiong; Kazemian, Majid; Pham, Hannah; Blatti, Charles; Celniker, Susan E.; Wolfe, Scot A.; Brodsky, Michael H.; Sinha, Saurabh

2013-01-01

ChIP-based genome-wide assays of transcription factor (TF) occupancy have emerged as a powerful, high-throughput method to understand transcriptional regulation, especially on a global scale. This has led to great interest in the underlying biochemical mechanisms that direct TF-DNA binding, with the ultimate goal of computationally predicting a TF's occupancy profile in any cellular condition. In this study, we examined the influence of various potential determinants of TF-DNA binding on a much larger scale than previously undertaken. We used a thermodynamics-based model of TF-DNA binding, called “STAP,” to analyze 45 TF-ChIP data sets from Drosophila embryonic development. We built a cross-validation framework that compares a baseline model, based on the ChIP'ed (“primary”) TF's motif, to more complex models where binding by secondary TFs is hypothesized to influence the primary TF's occupancy. Candidates interacting TFs were chosen based on RNA-SEQ expression data from the time point of the ChIP experiment. We found widespread evidence of both cooperative and antagonistic effects by secondary TFs, and explicitly quantified these effects. We were able to identify multiple classes of interactions, including (1) long-range interactions between primary and secondary motifs (separated by ≤150 bp), suggestive of indirect effects such as chromatin remodeling, (2) short-range interactions with specific inter-site spacing biases, suggestive of direct physical interactions, and (3) overlapping binding sites suggesting competitive binding. Furthermore, by factoring out the previously reported strong correlation between TF occupancy and DNA accessibility, we were able to categorize the effects into those that are likely to be mediated by the secondary TF's effect on local accessibility and those that utilize accessibility-independent mechanisms. Finally, we conducted in vitro pull-down assays to test model-based predictions of short-range cooperative interactions

[Progress of researches on mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage].

PubMed

Wang, Fan; Wang, Hai-qiao; Dong, Gui-rong

2011-04-01

In the present paper, the authors review the progress of researches on the mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage from experimental studies and research methods. The effects of acupuncture intervention mainly involve (1) lessening inflammatory reactions, (2) reducing impairment of free radicals and excitatory amino acids on cerebral neurons, (3) balancing release of vascular bioactive substances to increase regional cerebral blood flow, and (4) promoting repair and regeneration of the neural tissue, etc. In regard to the research methods, many new biological techniques such as biological molecular approaches, neuro-cellular chemical methods, reverse transcription-polymerase chain reaction (RT-PCR) or quantitative real time-PCR, situ hybridization, western blotting, electron microscope, etc., have been extensively applied to researches on the underlying mechanism of acupuncture therapy for cerebral infarction. In addition, the authors also pointed out that in spite of achieving some bigger progresses in experimental studies, most of the results basically reflect static, isolated and regional changes rather than dynamic and whole body changes. For this reason, more vivo research techniques and noninvasive research methods are highly recommended to be used in the future research on the underlying mechanisms of acupuncture therapy for acute cerebral ischemia.

Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

NASA Astrophysics Data System (ADS)

Rodionova, Natalia

Investigations on the space biosatellites has shown that the bone skeleton is one of the most im-portant targets of the effect space flight factors on the organism. Bone tissue cells were studied by electron microscopy in biosamples of rats' long bones flown on the board american station "SLS-2" and in experiments with modelling of microgravity ("tail suspension" method) with using autoradiography. The analysis of data permits to suppose that the processes of remod-eling in bone tissue at microgravity include the following succession of cell-to-cell interactions. Osteocytes as mechanosensory cells are first who respond to a changing "mechanical field". The next stage is intensification of osteolytic processes in osteocytes, leading to a volume en-largement of the osteocytic lacunae and removal of the "excess bone". Then mechanical signals have been transmitted through a system of canals and processes of the osteocytic syncitium to certain superficial bone zones and are perceived by osteoblasts and bone-lining cells (superficial osteocytes), as well as by the bone-marrow stromal cells. The sensitivity of stromal cells, pre-osteoblasts and osteoblasts, under microgravity was shown in a number of works. As a response to microgravity, the system of stromal cells -preosteoblasts -osteoblasts displays retardation of proliferation, differentiation and specific functions of osteogenetic cells. This is supported by the 3H-thymidine studies of the dynamics of differentiation of osteogenetic cells in remodeling zones. But unloading is not adequate and in part of the osteocytes are apoptotic changes as shown by our electron microscopic investigations. An osteocytic apoptosis can play the role in attraction the osteoclasts and in regulation of bone remodeling. The apoptotic bodies with a liquid flow through a system of canals are transferred to the bone surface, where they fulfil the role of haemoattractants for monocytes come here and form osteoclasts. The osteoclasts destroy

[Predictions of potential geographical distribution of Alhagi sparsifolia under climate change].

PubMed

Yang, Xia; Zheng, Jiang-Hua; Mu, Chen; Lin, Jun

2017-02-01

Specific information on geographic distribution of a species is important for its conservation. This study was conducted to determine the potential geographic distribution of Alhagi sparsifolia, which is a plant used in traditional Uighur medicine, and predict how climate change would affect its geographic range. The potential geographic distribution of A. sparsifolia under the current conditions in China was simulated with MaxEnt software based on species presence data at 42 locations and 19 climatic variables. The future distributions of A. sparsifolia were also projected in 2050 and 2070 under the climate change scenarios of RCP2.6 and RCP8.5 described in 5th Assessment Report of the Intergovernmental Panel on Climate Change (IPCC).The result showed that mean temperature of the coldest quarter, annual mean temperature, precipitation of the coldest quarter, annual precipitation, precipitation of the wettest month, mean temperature of the wettest quarter and the temperature annual range were the seven climatic factors influencing the geographic distribution of A. sparsifolia under current climate, the suitable habitats are mainly located in the Xinjiang, in the middle and north of Gansu, in the west of Neimeng, in the north of Nei Monggol. From 2050 to 2070, the model simulations indicated that the suitable habitats of A. sparsifolia would decrease under the climate change scenarios of RCP2.6 and scenarios of RCP8.5 on the whole. Copyright© by the Chinese Pharmaceutical Association.

Visualization of hot spot formation in energetic materials under periodic mechanical excitation using phosphor thermography

NASA Astrophysics Data System (ADS)

Casey, Alex; Fenoglio, Gabriel; Detrinidad, Humberto

2017-06-01

Under mechanical excitation, energy is known to localize within an energetic material resulting in `hot spot' formation. While many formation mechanisms have been proposed, additional insight to heat generation mechanisms, the effect of binder/crystal interfaces, and predication capabilities can be gained by quantifying the initiation and growth of the hot spots. Phosphor thermography is a well established temperature sensing technique wherein an object's temperature is obtained by collecting the temperature dependent luminescence of an optically excited phosphor. Herein, the phosphor thermography technique has been applied to Dow Corning Sylgard® 184/octahydro 1,3,5,7 tetranitro 1,3,5,7 tetrazocine (HMX) composite materials under mechanical excitation in order to visualize the evolution of the temperature field, and thus hot spot formation, within the binder. Funded by AFOSR. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

Distinct mechanisms coordinate transcription and translation under carbon and nitrogen starvation in Escherichia coli.

PubMed

Iyer, Sukanya; Le, Dai; Park, Bo Ryoung; Kim, Minsu

2018-05-14

Bacteria adapt to environmental stress by producing proteins that provide stress protection. However, stress can severely perturb the kinetics of gene expression, disrupting protein production. Here, we characterized how Escherichia coli mitigates such perturbations under nutrient stress through the kinetic coordination of transcription and translation. We observed that, when translation became limiting under nitrogen starvation, transcription elongation slowed accordingly. This slowdown was mediated by (p)ppGpp, the alarmone whose primary role is thought to be promoter regulation. This kinetic coordination by (p)ppGpp was critical for the robust synthesis of gene products. Surprisingly, under carbon starvation, (p)ppGpp was dispensable for robust synthesis. Characterization of the underlying kinetics revealed that under carbon starvation, transcription became limiting, and translation aided transcription elongation. This mechanism naturally coordinated transcription with translation, alleviating the need for (p)ppGpp as a mediator. These contrasting mechanisms for coordination resulted in the condition-dependent effects of (p)ppGpp on global protein synthesis and starvation survival. Our findings reveal a kinetic aspect of gene expression plasticity, establishing (p)ppGpp as a condition-dependent global effector of gene expression.

An Investigation of the Mechanism Underlying Teacher Aggression: Testing I[superscript 3] Theory and the General Aggression Model

ERIC Educational Resources Information Center

Montuoro, Paul; Mainhard, Tim

2017-01-01

Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression follows I[superscript 3] theory or General Aggression…

Mechanism of Small Current Generation under Impulse Voltage Applications in Vacuum

NASA Astrophysics Data System (ADS)

Aoki, Keita; Yasukawa, Hideaki; Kojima, Hiroki; Homma, Mitsutaka; Shioiri, Tetsu; Okubo, Hitoshi

Small discharge not to accompany breakdown can occur under high electric field in vacuum, however the mechanism is not well clarified. We have found that the current of small discharge decreases with repeated voltage applications, and leads to electrode conditioning effect of raising withstand voltage. The inception of the current is delayed with the decrease of current, and the inception time and waveform change by gap length. On the other hand, under low vacuum condition, the current increases and reaches saturation with repeated voltage applications. From these discussions, we concluded that the generating process of small current depended on the adsorption and absorption gas of electrodes.

Increasing potential for intense tropical and subtropical thunderstorms under global warming

PubMed Central

Kuang, Zhiming; Maloney, Eric D.; Hannah, Walter M.; Wolding, Brandon O.

2017-01-01

Intense thunderstorms produce rapid cloud updrafts and may be associated with a range of destructive weather events. An important ingredient in measures of the potential for intense thunderstorms is the convective available potential energy (CAPE). Climate models project increases in summertime mean CAPE in the tropics and subtropics in response to global warming, but the physical mechanisms responsible for such increases and the implications for future thunderstorm activity remain uncertain. Here, we show that high percentiles of the CAPE distribution (CAPE extremes) also increase robustly with warming across the tropics and subtropics in an ensemble of state-of-the-art climate models, implying strong increases in the frequency of occurrence of environments conducive to intense thunderstorms in future climate projections. The increase in CAPE extremes is consistent with a recently proposed theoretical model in which CAPE depends on the influence of convective entrainment on the tropospheric lapse rate, and we demonstrate the importance of this influence for simulated CAPE extremes using a climate model in which the convective entrainment rate is varied. We further show that the theoretical model is able to account for the climatological relationship between CAPE and a measure of lower-tropospheric humidity in simulations and in observations. Our results provide a physical basis on which to understand projected future increases in intense thunderstorm potential, and they suggest that an important mechanism that contributes to such increases may be present in Earth’s atmosphere. PMID:29078312

Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

PubMed

Dey-Rao, Rama; Sinha, Animesh A

2017-01-28

Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

Sulfated Glycans and Related Digestive Enzymes in the Zika Virus Infectivity: Potential Mechanisms of Virus-Host Interaction and Perspectives in Drug Discovery.

PubMed

Pomin, Vitor H

2017-01-01

As broadly reported, there is an ongoing Zika virus (ZIKV) outbreak in countries of Latin America. Recent findings have demonstrated that ZIKV causes severe defects on the neural development in fetuses in utero and newborns. Very little is known about the molecular mechanisms involved in the ZIKV infectivity. Potential therapeutic agents are also under investigation. In this report, the possible mechanisms of action played by glycosaminoglycans (GAGs) displayed at the surface proteoglycans of host cells, and likely in charge of interactions with surface proteins of the ZIKV, are highlighted. As is common for the most viruses, these sulfated glycans serve as receptors for virus attachment onto the host cells and consequential entry during infection. The applications of (1) exogenous sulfated glycans of different origins and chemical structures capable of competing with the virus attachment receptors (supposedly GAGs) and (2) GAG-degrading enzymes able to digest the virus attachment receptors on the cells may be therapeutically beneficial as anti-ZIKV. This communication attempts, therefore, to offer some guidance for the future research programs aimed to unveil the molecular mechanisms underlying the ZIKV infectivity and to develop therapeutics capable of decreasing the devastating consequences caused by ZIKV outbreak in the Americas.

Resizing procedure for structures under combined mechanical and thermal loading

NASA Technical Reports Server (NTRS)

Adelman, H. M.; Narayanaswami, R.

1976-01-01

The fully-stressed design (FSD) appears to be the most widely used approach for sizing of flight structures under strength and minimum-gage constraints. Almost all of the experience with FSD has been with structures primarily under mechanical loading as opposed to thermal loading. In this method the structural sizes are iterated with the step size, depending on the ratio of the total stress to the allowable stress. In this paper, the thermal fully-stressed design (TFSD) procedure developed for problems involving substantial thermal stress is extended to biaxial stress members using a Von Mises failure criterion. The TFSD resizing procedure for uniaxial stress is restated and the new procedure for biaxial stress members is developed. Results are presented for an application of the two procedures to size a simplified wing structure.

Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

PubMed Central

Beaudin, Anna E.; Stover, Patrick J.

2015-01-01

Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

In silico analysis of the potential mechanism of telocinobufagin on breast cancer MCF-7 cells.

PubMed

Dang, Yi-Wu; Lin, Peng; Liu, Li-Min; He, Rong-Quan; Zhang, Li-Jie; Peng, Zhi-Gang; Li, Xiao-Jiao; Chen, Gang

2018-05-01

The extractives from a ChanSu, traditional Chinese medicine, have been discovered to possess anti-inflammatory and tumor-suppressing abilities. However, the molecular mechanism of telocinobufagin, a compound extracted from ChanSu, on breast cancer cells has not been clarified. The aim of this study is to investigate the underlying mechanism of telocinobufagin on breast cancer cells. The differentially expressed genes after telocinobufagin treatment on breast cancer cells were searched and downloaded from Gene Expression Omnibus (GEO), ArrayExpress and literatures. Bioinformatics tools were applied to further explore the potential mechanism of telocinobufagin in breast cancer using the Kyoto Encyclopedia of genes and genomes (KEGG) pathway, Gene ontology (GO) enrichment, panther, and protein-protein interaction analyses. To better comprehend the role of telocinobufagin in breast cancer, we also queried the Connectivity Map using the gene expression profiles of telocinobufagin treatment. One GEO accession (GSE85871) provided 1251 differentially expressed genes after telocinobufagin treatment on MCF-7 cells. The pathway of neuroactive ligand-receptor interaction, cell adhesion molecules (CAMs), intestinal immune network for IgA production, hematopoietic cell lineage and calcium signaling pathway were the key pathways from KEGG analysis. IGF1 and KSR1, owning to higher protein levels in breast cancer tissues, IGF1 and KSR1 could be the hub genes related to telocinobufagin treatment. It was indicated that the molecular mechanism of telocinobufagin resembled that of fenspiride. Telocinobufagin might regulate neuroactive ligand-receptor interaction pathway to exert its influences in breast cancer MCF-7 cells, and its molecular mechanism might share some similarities with fenspiride. This study only presented a comprehensive picture of the role of telocinobufagin in breast cancer MCF-7 cells using big data. However, more thorough and deeper researches are required to add

The double crush syndrome revisited--a Delphi study to reveal current expert views on mechanisms underlying dual nerve disorders.

PubMed

Schmid, Annina B; Coppieters, Michel W

2011-12-01

A high prevalence of dual nerve disorders is frequently reported. How a secondary nerve disorder may develop following a primary nerve disorder remains largely unknown. Although still frequently cited, most explanatory theories were formulated many years ago. Considering recent advances in neuroscience, it is uncertain whether these theories still reflect current expert opinion. A Delphi study was conducted to update views on potential mechanisms underlying dual nerve disorders. In three rounds, seventeen international experts in the field of peripheral nerve disorders were asked to list possible mechanisms and rate their plausibility. Mechanisms with a median plausibility rating of ≥7 out of 10 were considered highly plausible. The experts identified fourteen mechanisms associated with a first nerve disorder that may predispose to the development of another nerve disorder. Of these fourteen mechanisms, nine have not previously been linked to double crush. Four mechanisms were considered highly plausible (impaired axonal transport, ion channel up or downregulation, inflammation in the dorsal root ganglia and neuroma-in-continuity). Eight additional mechanisms were listed which are not triggered by a primary nerve disorder, but may render the nervous system more vulnerable to multiple nerve disorders, such as systemic diseases and neurotoxic medication. Even though many mechanisms were classified as plausible or highly plausible, overall plausibility ratings varied widely. Experts indicated that a wide range of mechanisms has to be considered to better understand dual nerve disorders. Previously listed theories cannot be discarded, but may be insufficient to explain the high prevalence of dual nerve disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

[A study of complexity and power spectrum of cortical EEG and hippocampal potential in rats under different behavioral states].

PubMed

Feng, Zhou-yan; Zheng, Xiao-xiang

2002-08-01

Objective. To study the complexity and the power spectrum of cortical EEG and hippocampal potential in rats under waking and sleep states. Method. Cortical EEG and hippocampal potential were collected by implanted electrodes in freely moving rats. Algorithmic complexity (Kc), approximate entropy (ApEn), power spectral density (PSD) and gravity frequency of PSD of the potential waves were calculated. Result. The complexity of hippocampal potential was higher than that of cortical EEG under every state. The complexity of cortical EEG was lowest under the state of non rapid eye movement (NREM) sleep. The complexity of hippocampal potential was highest under waking state. The total power of both potentials in 0.5- 30 Hz frequency band showed their highest values under NREM state. Conclusion. The values of Kc and ApEn are closely related to the distributions of PSD. When there are evident peaks in PSD, the complexities of signals will decrease. The complexities may be used to distinguish the difference between cortical EEG and hippocampal potential, or large differences between the same kind of potentials under different behavioral states.

Cerebellar learning mechanisms

PubMed Central

Freeman, John H.

2014-01-01

The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: 1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and 2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. PMID:25289586

Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions.

PubMed

Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A; Decker, William; Manjili, Masoud H; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H; Lowe, Leroy; Lyerly, H Kim

2015-06-01

An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neural mechanisms underlying human consensus decision-making

PubMed Central

Suzuki, Shinsuke; Adachi, Ryo; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P.

2015-01-01

SUMMARY Consensus building in a group is a hallmark of animal societies, yet little is known about its underlying computational and neural mechanisms. Here, we applied a novel computational framework to behavioral and fMRI data from human participants performing a consensus decision-making task with up to five other participants. We found that participants reached consensus decisions through integrating their own preferences with information about the majority of group-members’ prior choices, as well as inferences about how much each option was stuck to by the other people. These distinct decision variables were separately encoded in distinct brain areas: the ventromedial prefrontal cortex, posterior superior temporal sulcus/temporoparietal junction and intraparietal sulcus, and were integrated in the dorsal anterior cingulate cortex. Our findings provide support for a theoretical account in which collective decisions are made through integrating multiple types of inference about oneself, others and environments, processed in distinct brain modules. PMID:25864634

Neural mechanisms underlying human consensus decision-making.

PubMed

Suzuki, Shinsuke; Adachi, Ryo; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P

2015-04-22

Consensus building in a group is a hallmark of animal societies, yet little is known about its underlying computational and neural mechanisms. Here, we applied a computational framework to behavioral and fMRI data from human participants performing a consensus decision-making task with up to five other participants. We found that participants reached consensus decisions through integrating their own preferences with information about the majority group members' prior choices, as well as inferences about how much each option was stuck to by the other people. These distinct decision variables were separately encoded in distinct brain areas-the ventromedial prefrontal cortex, posterior superior temporal sulcus/temporoparietal junction, and intraparietal sulcus-and were integrated in the dorsal anterior cingulate cortex. Our findings provide support for a theoretical account in which collective decisions are made through integrating multiple types of inference about oneself, others, and environments, processed in distinct brain modules. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

PubMed

Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

2017-11-01

Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Behavior of a Quasi-Isotropic Ply Metal Matrix Composite under Thermo-Mechanical and Isothermal Fatigue Loading

DTIC Science & Technology

1992-12-01

tensile strength of the composite (20:14). After the heat treatment was accomplished, polishing was performed. Using an automated MAXIMET polishing machine ...AD-A258 902 AFIT/GAE/.ENY/92D-05 Behavior of a Quasi-Isotropic Ply Metal Matrix Composite Under Thermo- Mechanical and Isothermal Fatigue Loading...115 AFIT/GAE/ENY/92D-05 Behavior of a Quasi-Isotropic Ply Metal Matrix Composite Under Thermo- Mechanical and Isothermal Fatigue Loading THESIS

Mechanisms Underlying Sexual Violence Exposure and Psychosocial Sequelae: A Theoretical and Empirical Review

PubMed Central

Walsh, Kate; Galea, Sandro; Koenen, Karestan C.

2015-01-01

Sexual violence is associated with a range of negative mental health and behavioral sequelae, including posttraumatic stress disorder (PTSD), depression, substance abuse/dependence, risky sexual behavior, and interpersonal relationship problems. However, mechanisms underlying these associations are not well understood. Identifying mechanisms that explain linkages between sexual violence and poor outcomes is of paramount importance in determining when and how to intervene to prevent or reduce the magnitude of these outcomes. This review focuses on theories that have been proposed to explain risk of negative outcomes among sexual violence victims, including the development of traumagenic dynamics and emotion dysregulation. We also review promising biological mechanisms that may explain the risk of negative outcomes among sexual violence victims, including studies concerned with epigenetic and neurobiological mechanisms. PMID:25762853

Dissociable cognitive mechanisms underlying human path integration.

PubMed

Wiener, Jan M; Berthoz, Alain; Wolbers, Thomas

2011-01-01

Path integration is a fundamental mechanism of spatial navigation. In non-human species, it is assumed to be an online process in which a homing vector is updated continuously during an outward journey. In contrast, human path integration has been conceptualized as a configural process in which travelers store working memory representations of path segments, with the computation of a homing vector only occurring when required. To resolve this apparent discrepancy, we tested whether humans can employ different path integration strategies in the same task. Using a triangle completion paradigm, participants were instructed either to continuously update the start position during locomotion (continuous strategy) or to remember the shape of the outbound path and to calculate home vectors on basis of this representation (configural strategy). While overall homing accuracy was superior in the configural condition, participants were quicker to respond during continuous updating, strongly suggesting that homing vectors were computed online. Corroborating these findings, we observed reliable differences in head orientation during the outbound path: when participants applied the continuous updating strategy, the head deviated significantly from straight ahead in direction of the start place, which can be interpreted as a continuous motor expression of the homing vector. Head orientation-a novel online measure for path integration-can thus inform about the underlying updating mechanism already during locomotion. In addition to demonstrating that humans can employ different cognitive strategies during path integration, our two-systems view helps to resolve recent controversies regarding the role of the medial temporal lobe in human path integration.

Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing

PubMed Central

Frässle, Stefan; Krach, Sören; Paulus, Frieder Michel; Jansen, Andreas

2016-01-01

While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization. PMID:27250879

Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing

NASA Astrophysics Data System (ADS)

Frässle, Stefan; Krach, Sören; Paulus, Frieder Michel; Jansen, Andreas

2016-06-01

While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization.

Continuing to illuminate the mechanisms underlying UV-mediated melanomagenesis

PubMed Central

Dellinger, Ryan W.; Liu-Smith, Feng; Meyskens, Frank L.

2014-01-01

The incidence of melanoma is one of the fastest growing of all tumor types in the United States and the number of cases worldwide has doubled in the past 30 years. Melanoma, which arises from melanocytes, is an extremely aggressive tumor that invades the vascular and lymphatic systems to establish tumors elsewhere in the body. Melanoma is a particularly resilient cancer and systemic therapy approaches have achieved minimal success against metastatic melanoma resulting in only a few FDA-approved treatments with limited benefit. Leading treatments offer minimal efficacy with response rates generally under 15% in the long term with no clear effect on melanoma-related mortality. Even the recent success of the specific BRAF mutant inhibitor vemurafenib has been tempered somewhat since acquired resistance is rapidly observed. Thus, understanding the mechanism(s) of melanoma carcinogenesis is paramount to combating this deadly disease. Not only for the treatment of melanoma but, ultimately, for prevention. In this report, we will summarize our work to date regarding the characterization of ultraviolet radiation (UVR)-mediated melanomagenesis and highlight several promising avenues of ongoing research. PMID:25022944

Coagulation-flocculation mechanisms in wastewater treatment plants through zeta potential measurements.

PubMed

López-Maldonado, E A; Oropeza-Guzman, M T; Jurado-Baizaval, J L; Ochoa-Terán, A

2014-08-30

Based on the polyelectrolyte-contaminant physical and chemical interactions at the molecular level, this article analyzed and discussed the coagulation-flocculation and chemical precipitation processes in order to improve their efficiency. Bench experiments indicate that water pH, polyelectrolyte (PE) dosing strategy and cationic polyelectrolyte addition are key parameters for the stability of metal-PE complexes. The coagulation-flocculation mechanism is proposed based on zeta potential (ζ) measurement as the criteria to define the electrostatic interaction between pollutants and coagulant-flocculant agents. Polyelectrolyte and wastewater dispersions are exposed to an electrophoretic effect to determine ζ. Finally, zeta potential values are compared at pH 9, suggesting the optimum coagulant dose at 162mg/L polydadmac and 67mg/L of flocculant, since a complete removal of TSS and turbidity is achieved. Based on the concentration of heavy metals (0.931mg/L Sn, 0.7mg/L Fe and 0.63mg/L Pb), treated water met the Mexican maximum permissible limits. In addition, the treated water has 45mg O2/L chemical oxygen demand (COD) and 45mg C/L total organic carbon (TOC). The coagulation-flocculation mechanism is proposed taking into account both: zeta potential (ζ)-pH measurement and chemical affinity, as the criteria to define the electrostatic and chemical interaction between pollutants and polyelectrolytes. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanisms Underlying Lexical Access in Native and Second Language Processing of Gender and Number Agreement

ERIC Educational Resources Information Center

Romanova, Natalia

2013-01-01

Despite considerable evidence suggesting that second language (L2) learners experience difficulties when processing morphosyntactic aspects of L2 in online tasks, the mechanisms underlying these difficulties remain unknown. The aim of this dissertation is to explore possible causes for the difficulties by comparing attentional mechanisms engaged…

Inhibitory effects and underlying mechanism of 7-hydroxyflavone phosphate ester in HeLa cells.

PubMed

Zhang, Ting; Du, Jiang; Liu, Liguo; Chen, Xiaolan; Yang, Fang; Jin, Qi

2012-01-01

Chrysin and its phosphate ester have previously been shown to inhibit cell proliferation and induce apoptosis in Hela cells; however, the underlying mechanism remains to be characterized. In the present study, we therefore synthesized diethyl flavon-7-yl phosphate (FP, C(19)H(19)O(6)P) by a simplified Atheron-Todd reaction, and explored its anti-tumor characteristics and mechanisms. Cell proliferation, cell cycle progression and apoptosis were measured by MTS, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling techniques, respectively in human cervical cancer HeLa cells treated with 7-hydroxyflavone (HF) and FP. p21, proliferating cell nuclear antigen (PCNA) and cAMP levels in Hela cells were analyzed by western blot and radioimmunoassay. Both HF and FP inhibited proliferation and induced apoptosis in HeLa cells via induction of PCNA/p21 expression, cleaved caspase-3/poly (ADP-ribose) polymerase (PARP)-1, elevation of cAMP levels, and cell cycle arrest with accumulation of cells in the G0/G1 fraction. The effects of FP were more potent than those of HF. The interactions of FP with Ca(2+)-calmodulin (CaM) and Ca(2+)-CaM-phosphodiesterase (PDE)1 were explored by electrospray ionization-mass spectrometry and fluorescence spectra. FP, but not HF, formed non-covalent complexes with Ca(2+)-CaM-PDE1, indicating that FP is an inhibitor of PDE1, and resulting in elevated cellular cAMP levels. It is possible that the elevated cAMP levels inhibit growth and induce apoptosis in Hela cells through induction of p21 and cleaved caspase-3/PARP-1 expression, and causing down-regulation of PCNA and cell cycle arrest with accumulation of cells in the G0/G1 and G2/M fractions. In conclusion, FP was shown to be a Ca(2+)-CaM-PDE inhibitor, which might account for its underlying anti-cancer mechanism in HeLa cells. These observations clearly demonstrate the special roles of phosphorylated flavonoids in biological processes, and suggest that FP might represent

Inhibitory Effects and Underlying Mechanism of 7-Hydroxyflavone Phosphate Ester in HeLa Cells

PubMed Central

Liu, Liguo; Chen, Xiaolan; Yang, Fang; Jin, Qi

2012-01-01

Chrysin and its phosphate ester have previously been shown to inhibit cell proliferation and induce apoptosis in Hela cells; however, the underlying mechanism remains to be characterized. In the present study, we therefore synthesized diethyl flavon-7-yl phosphate (FP, C19H19O6P) by a simplified Atheron-Todd reaction, and explored its anti-tumor characteristics and mechanisms. Cell proliferation, cell cycle progression and apoptosis were measured by MTS, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling techniques, respectively in human cervical cancer HeLa cells treated with 7-hydroxyflavone (HF) and FP. p21, proliferating cell nuclear antigen (PCNA) and cAMP levels in Hela cells were analyzed by western blot and radioimmunoassay. Both HF and FP inhibited proliferation and induced apoptosis in HeLa cells via induction of PCNA/p21 expression, cleaved caspase-3/poly (ADP-ribose) polymerase (PARP)-1, elevation of cAMP levels, and cell cycle arrest with accumulation of cells in the G0/G1 fraction. The effects of FP were more potent than those of HF. The interactions of FP with Ca2+-calmodulin (CaM) and Ca2+-CaM-phosphodiesterase (PDE)1 were explored by electrospray ionization-mass spectrometry and fluorescence spectra. FP, but not HF, formed non-covalent complexes with Ca2+-CaM-PDE1, indicating that FP is an inhibitor of PDE1, and resulting in elevated cellular cAMP levels. It is possible that the elevated cAMP levels inhibit growth and induce apoptosis in Hela cells through induction of p21 and cleaved caspase-3/PARP-1 expression, and causing down-regulation of PCNA and cell cycle arrest with accumulation of cells in the G0/G1 and G2/M fractions. In conclusion, FP was shown to be a Ca2+-CaM-PDE inhibitor, which might account for its underlying anti-cancer mechanism in HeLa cells. These observations clearly demonstrate the special roles of phosphorylated flavonoids in biological processes, and suggest that FP might represent a potential

A computerized test system for thermal-mechanical fatigue crack growth

NASA Technical Reports Server (NTRS)

Marchand, N.; Pelloux, R. M.

1986-01-01

A computerized testing system to measure fatigue crack growth under thermal-mechanical fatigue conditions is described. Built around a servohydraulic machine, the system is capable of a push-pull test under stress-controlled or strain-controlled conditions in the temperature range of 25 to 1050 C. Temperature and mechanical strain are independently controlled by the closed-loop system to simulate the complex inservice strain-temperature relationship. A d-c electrical potential method is used to measure crack growth rates. The correction procedure of the potential signal to take into account powerline and RF-induced noises and thermal changes is described. It is shown that the potential drop technique can be used for physical mechanism studies and for modelling crack tip processes.

Inspection Mechanism and Experimental Study of Prestressed Reverse Tension Method under PC Beam Bridge Anchorage

NASA Astrophysics Data System (ADS)

Peng, Zhang

2018-03-01

the prestress under anchorage is directly related to the structural security and performance of PC beam bridge. The reverse tension method is a kind of inspection which confirms the prestress by exerting reversed tension load on the exposed prestressing tendon of beam bridge anchoring system. The thesis elaborately expounds the inspection mechanism and mechanical effect of reverse tension method, theoretically analyzes the influential elements of inspection like tool anchorage deformation, compression of conjuncture, device glide, friction of anchorage loop mouth and elastic compression of concrete, and then presents the following formula to calculate prestress under anchorage. On the basis of model experiment, the thesis systematically studies some key issues during the reverse tension process of PC beam bridge anchorage system like the formation of stress-elongation curve, influential factors, judgment method of prestress under anchorage, variation trend and compensation scale, verifies the accuracy of mechanism analysis and demonstrates: the prestress under anchorage is less than or equal to 75% of the ultimate strength of prestressing tendon, the error of inspect result is less than 1%, which can meet with the demands of construction. The research result has provided theoretical basis and technical foundation for the promotion and application of reverse tension in bridge construction.

Laboratory and 3-D-distinct element analysis of failure mechanism of slope under external surcharge

NASA Astrophysics Data System (ADS)

Li, N.; Cheng, Y. M.

2014-09-01

Landslide is a major disaster resulting in considerable loss of human lives and property damages in hilly terrain in Hong Kong, China and many other countries. The factor of safety and the critical slip surface for slope stabilization are the main considerations for slope stability analysis in the past, while the detailed post-failure conditions of the slopes have not been considered in sufficient details. There are however increasing interest on the consequences after the initiation of failure which includes the development and propagation of the failure surfaces, the amount of failed mass and runoff and the affected region. To assess the development of slope failure in more details and to consider the potential danger of slopes after failure has initiated, the slope stability problem under external surcharge is analyzed by the distinct element method (DEM) and laboratory model test in the present research. A more refined study about the development of failure, microcosmic failure mechanism and the post-failure mechanism of slope will be carried out. The numerical modeling method and the various findings from the present work can provide an alternate method of analysis of slope failure which can give additional information not available from the classical methods of analysis.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Kinetics and mechanism of nickel ferrite formation under high temperature ultrasonic treatment.

PubMed

Baranchikov, Alexander Ye; Ivanov, Vladimir K; Tretyakov, Yuri D

2007-02-01

The effect of simultaneous ultrasonic and thermal treatment on kinetics and mechanism of nickel ferrite formation was studied. It was established that sonication leads to notable increase of the mean rate of this reaction and decrease of effective activation energy from 190+/-5 to 125+/-7 kJ/mol. XRD data show that ultrasonic treatment significantly affects the microstructure of both initial reagent (Fe(2)O(3)) and reaction product (NiFe(2)O(4)) thus promoting formation of well developed reaction zone. A general model of ferrite formation mechanism under high temperature ultrasonic treatment was proposed.

Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

PubMed

Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

2017-01-01

Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

Mechanisms of resistance change under pressure for AgNP-based conducting wires

NASA Astrophysics Data System (ADS)

Qian, Zhentao; Liu, Liping; Huang, Han; Cheng, Xiong; Zhu, Xiaobo; Gu, Wenhua

2018-02-01

The silver nanoparticle (AgNP) based conducting wire is a fundamental element of flexible electronic devices, especially in the printing electronics area. Its resistance change mechanisms under pressure is of both scientific interest and practical importance. AgNP-based conducting wires were fabricated on flexible substrates by electrospraying printing technology, and three possible resistance change mechanisms were studied: vertical deformation (VD) of the AgNP wire due to vertical pressure, horizontal wire elongation (HWE) along with the flexible substrate due to vertical pressure, and local micro deformation (LMD) at the touching edge. Analysis of the experiment data revealed that the resistance change due to VD was negligible, the resistance change due to PWE was one order of magnitude smaller than the measured value, and the resistance change due to PWE was the dominating mechanism.

Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional Chinese medicine.

PubMed

Zhou, Xuezhong; Li, Yubing; Peng, Yonghong; Hu, Jingqing; Zhang, Runshun; He, Liyun; Wang, Yinghui; Jiang, Lijie; Yan, Shiyan; Li, Peng; Xie, Qi; Liu, Baoyan

2014-09-01

Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

Neural Mechanisms Underlying Conscious and Unconscious Gaze-Triggered Attentional Orienting in Autism Spectrum Disorder

PubMed Central

Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshimura, Sayaka; Toichi, Motomi

2017-01-01

Impaired joint attention represents the core clinical feature of autism spectrum disorder (ASD). Behavioral studies have suggested that gaze-triggered attentional orienting is intact in response to supraliminally presented eyes but impaired in response to subliminally presented eyes in individuals with ASD. However, the neural mechanisms underlying conscious and unconscious gaze-triggered attentional orienting remain unclear. We investigated this issue in ASD and typically developing (TD) individuals using event-related functional magnetic resonance imaging. The participants viewed cue stimuli of averted or straight eye gaze direction presented either supraliminally or subliminally and then localized a target. Reaction times were shorter when eye-gaze cues were directionally valid compared with when they were neutral under the supraliminal condition in both groups; the same pattern was found in the TD group but not the ASD group under the subliminal condition. The temporo–parieto–frontal regions showed stronger activation in response to averted eyes than to straight eyes in both groups under the supraliminal condition. The left amygdala was more activated while viewing averted vs. straight eyes in the TD group than in the ASD group under the subliminal condition. These findings provide an explanation for the neural mechanisms underlying the impairment in unconscious but not conscious gaze-triggered attentional orienting in individuals with ASD and suggest possible neurological and behavioral interventions to facilitate their joint attention behaviors. PMID:28701942

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Pore closure in zeolitic imidazolate frameworks under mechanical pressure.

PubMed

Henke, Sebastian; Wharmby, Michael T; Kieslich, Gregor; Hante, Inke; Schneemann, Andreas; Wu, Yue; Daisenberger, Dominik; Cheetham, Anthony K

2018-02-14

We investigate the pressure-dependent mechanical behaviour of the zeolitic imidazolate framework ZIF-4 (M(im) 2 ; M 2+ = Co 2+ or Zn 2+ , im - = imidazolate) with high pressure, synchrotron powder X-ray diffraction and mercury intrusion measurements. A displacive phase transition from a highly compressible open pore ( op ) phase with continuous porosity (space group Pbca , bulk modulus ∼1.4 GPa) to a closed pore ( cp ) phase with inaccessible porosity (space group P 2 1 / c , bulk modulus ∼3.3-4.9 GPa) is triggered by the application of mechanical pressure. Over the course of the transitions, both ZIF-4 materials contract by about 20% in volume. However, the threshold pressure, the reversibility and the immediate repeatability of the phase transition depend on the metal cation. ZIF-4(Zn) undergoes the op-cp phase transition at a hydrostatic mechanical pressure of only 28 MPa, while ZIF-4(Co) requires about 50 MPa to initiate the transition. Interestingly, ZIF-4(Co) fully returns to the op phase after decompression, whereas ZIF-4(Zn) remains in the cp phase after pressure release and requires subsequent heating to switch back to the op phase. These variations in high pressure behaviour can be rationalised on the basis of the different electron configurations of the respective M 2+ ions (3d 10 for Zn 2+ and 3d 7 for Co 2+ ). Our results present the first examples of op-cp phase transitions ( i.e. breathing transitions) of ZIFs driven by mechanical pressure and suggest potential applications of these functional materials as shock absorbers, nanodampers, or in mechanocalorics.

Response mechanism of post-earthquake slopes under heavy rainfall

NASA Astrophysics Data System (ADS)

Qiu, Hong-zhi; Kong, Ji-ming; Wang, Ren-chao; Cui, Yun; Huang, Sen-wang

2017-07-01

This paper uses the catastrophic landslide that occurred in Zhongxing Town, Dujiangyan City, as an example to study the formation mechanism of landslides induced by heavy rainfall in the post-Wenchuan earthquake area. The deformation characteristics of a slope under seismic loading were investigated via a shaking table test. The results show that a large number of cracks formed in the slope due to the tensile and shear forces of the vibrations, and most of the cracks had angles of approximately 45° with respect to the horizontal. A series of flume tests were performed to show how the duration and intensity of rainfall influence the responses of the shaken and non-shaken slopes. Wetting fronts were recorded under different rainfall intensities, and the depth of rainfall infiltration was greater in the shaken slope than in the non-shaken slope because the former experienced a greater extreme rainfall intensity under the same early rainfall and rainfall duration conditions. At the beginning of the rainfall infiltration experiment, the pore water pressure in the slope was negative, and settling occurred at the top of the slope. With increasing rainfall, the pore water pressure changed from negative to positive, and cracks were observed on the back surface of the slope and the shear outlet of the landslide on the front of the slope. The shaken slope was more susceptible to crack formation than the non-shaken slope under the same rainfall conditions. A comparison of the responses of the shaken and non-shaken slopes under heavy rainfall revealed that cracks formed by earthquakes provided channels for infiltration. Soil particles in the cracks of slopes were washed away, and the pore water pressure increased rapidly, especially the transient pore water pressure in the slope caused by short-term concentrated rainfall which decreased rock strength and slope stability.

Rhinosinusitis in the intensive care unit patients: a review of the possible underlying mechanisms and proposals for the investigation of their potential role in functional treatment interventions.

PubMed

Riga, Maria; Danielidis, Vasilios; Pneumatikos, Ioannis

2010-03-01

Nosocomial rhinosinusitis (NS) is diagnosed in 2% to 26% of intubated patients and is associated with ventilator-associated pneumonia, septicemia, and fever of unknown etiology. The purpose of this study was to review the underlying pathogenetic mechanisms and the treatment options that derive from them. The pathogenesis of NS seems to be mainly a combination of the failure of the local defenses and self-clearance mechanisms and the development of topical factors, which favor the colonization of the nasal and antral cavities with pathogens. The systemic administration of antibiotics, which are the current treatment of NS, have a limited, if any, effect on any of the above pathophysiologic mechanisms. However, the review of the literature demonstrates that the research on functionally orientated treatment options has been limited to the effect of orotracheal vs nasotracheal intubation. There are no clinical trials investigating the effect, which combinations of pathophysiology-based measures may have on the prevalence and treatment of NS and ventilator-associated pneumonia. An update of the pathogenetic mechanisms demonstrates that the prevention and treatment of nosocomial rhinosinusitis may expand well beyond the systemic administration of antibiotics. Copyright 2010 Elsevier Inc. All rights reserved.

Novel failure mechanism and improvement for split-gate trench MOSFET with large current under unclamped inductive switch stress

NASA Astrophysics Data System (ADS)

Tian, Ye; Yang, Zhuo; Xu, Zhiyuan; Liu, Siyang; Sun, Weifeng; Shi, Longxing; Zhu, Yuanzheng; Ye, Peng; Zhou, Jincheng

2018-04-01

In this paper, a novel failure mechanism under unclamped inductive switch (UIS) for Split-Gate Trench Metal Oxide Semiconductor Field Effect Transistor (MOSFET) with large current is investigated. The device sample is tested and analyzed in detail. The simulation results demonstrate that the nonuniform potential distribution of the source poly should be responsible for the failure. Three structures are proposed and verified available to improve the device UIS ruggedness by TCAD simulation. The best one of the structures the device with source metal inserting into source poly through contacts in the field oxide is carried out and measured. The results demonstrate that the optimized structure can balance the trade-off between the UIS ruggedness and the static characteristics.

Plasma fibronectin stabilizes Borrelia burgdorferi–endothelial interactions under vascular shear stress by a catch-bond mechanism

PubMed Central

Niddam, Alexandra F.; Ebady, Rhodaba; Bansal, Anil; Koehler, Anne; Hinz, Boris

2017-01-01

Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with endothelia under vascular shear stress requires mechanically specialized interaction mechanisms, including force-strengthened catch bonds. However, the biomechanical mechanisms supporting vascular interactions of most bacterial pathogens are undefined. Fibronectin (Fn), a ubiquitous host molecule targeted by many pathogens, promotes vascular interactions of the Lyme disease spirochete Borrelia burgdorferi. Here, we investigated how B. burgdorferi exploits Fn to interact with endothelia under physiological shear stress, using recently developed live cell imaging and particle-tracking methods for studying bacterial–endothelial interaction biomechanics. We found that B. burgdorferi does not primarily target insoluble matrix Fn deposited on endothelial surfaces but, instead, recruits and induces polymerization of soluble plasma Fn (pFn), an abundant protein in blood plasma that is normally soluble and nonadhesive. Under physiological shear stress, caps of polymerized pFn at bacterial poles formed part of mechanically loaded adhesion complexes, and pFn strengthened and stabilized interactions by a catch-bond mechanism. These results show that B. burgdorferi can transform a ubiquitous but normally nonadhesive blood constituent to increase the efficiency, strength, and stability of bacterial interactions with vascular surfaces. Similar mechanisms may promote dissemination of other Fn-binding pathogens. PMID:28396443

New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

PubMed

Weinstein, Aviv; Lejoyeux, Michel

2015-03-01

There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

Mechanisms underlying different onset patterns of focal seizures

PubMed Central

Trevelyan, Andrew J; Valentin, Antonio; Alarcon, Gonzalo

2017-01-01

Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome. PMID:28472032

Determining polarizable force fields with electrostatic potentials from quantum mechanical linear response theory

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

Wang, Hao; Yang, Weitao, E-mail: weitao.yang@duke.edu; Department of Physics, Duke University, Durham, North Carolina 27708

We developed a new method to calculate the atomic polarizabilities by fitting to the electrostatic potentials (ESPs) obtained from quantum mechanical (QM) calculations within the linear response theory. This parallels the conventional approach of fitting atomic charges based on electrostatic potentials from the electron density. Our ESP fitting is combined with the induced dipole model under the perturbation of uniform external electric fields of all orientations. QM calculations for the linear response to the external electric fields are used as input, fully consistent with the induced dipole model, which itself is a linear response model. The orientation of the uniformmore » external electric fields is integrated in all directions. The integration of orientation and QM linear response calculations together makes the fitting results independent of the orientations and magnitudes of the uniform external electric fields applied. Another advantage of our method is that QM calculation is only needed once, in contrast to the conventional approach, where many QM calculations are needed for many different applied electric fields. The molecular polarizabilities obtained from our method show comparable accuracy with those from fitting directly to the experimental or theoretical molecular polarizabilities. Since ESP is directly fitted, atomic polarizabilities obtained from our method are expected to reproduce the electrostatic interactions better. Our method was used to calculate both transferable atomic polarizabilities for polarizable molecular mechanics’ force fields and nontransferable molecule-specific atomic polarizabilities.« less

Protective effect of erythropoietin against myocardial injury in rats with sepsis and its underlying mechanisms

PubMed Central

ZHANG, XINLIANG; DONG, SHIMIN; QIN, YANJUN; BIAN, XIAOHUA

2015-01-01

The aim of this study was to investigate the protective effect of erythropoietin (EPO) against acute myocardial injury and its underlying mechanisms. Mice (n=146) were randomly divided in a double-blind manner into four groups, sham, Rocephin, EPO and sepsis, and mortality was observed on the seventh day after cecal ligation and puncture. In addition, a total of 252 rats were randomly divided into three groups, sham, EPO and sepsis, and indicators of cardiac function, inflammatory mediators and serum creatine kinase levels were assessed. Mitochondrial membrane potential, cell apoptosis and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) p65 expression levels were detected using flow cytometry. Following intervention with EPO, the mortality rate in mice with sepsis was significantly reduced and the cardiac function of septic rats was significantly improved. In addition, the levels of inflammatory mediators, serum creatine kinase and apoptosis and the myocardial mitochondrial membrane potential and expression of NF-κB p65 in cardiac tissue were all improved following EPO treatment, and the differences between the results for the sepsis and EPO groups were statistically significant (P<0.05). These findings suggest that EPO reduces the myocardial inflammatory response in septic rats, attenuates the reduction in mitochondrial membrane potential and inhibits myocardial cell apoptosis by reducing NF-κB p65 expression, and therefore exerts a protective effect in the myocardium. PMID:25572660

Ablation characteristics and reaction mechanism of insulation materials under slag deposition condition

NASA Astrophysics Data System (ADS)

Guan, Yiwen; Li, Jiang; Liu, Yang

2017-07-01

Current understanding of the physical and chemical processes involved in the ablation of insulation materials by highly aluminized solid propellants is limited. The study on the heat transfer and ablation principle of ethylene propylene diene monomer (EPDM) materials under slag deposition condition is essential for future design or modification of large solid rocket motors (SRMs) for launch application. In this paper, the alumina liquid flow pattern and the deposition principle in full-scale SRM engines are discussed. The interaction mechanism between the alumina droplets and the wall are analyzed. Then, an experimental method was developed to simulate the insulation material ablation under slag deposition condition. Experimental study was conducted based on a laboratory-scale device. Meanwhile, from the analysis of the cross-sectional morphology and chemical composition of the charring layer after ablation, the reaction mechanism of the charring layer under deposition condition was discussed, and the main reaction equation was derived. The numerical simulation and experimental results show the following. (i) The alumina droplet flow in the deposition section of the laboratory-scale device is similar to that of a full-scale SRM. (ii) The charring layer of the EPDM insulator displays a porous tight/loose structure under high-temperature slag deposition condition. (iii) A seven-step carbothermal reduction in the alumina is derived and established under high-pressure and high-temperature environment in the SRM combustion chamber. (iv) The analysis using thermodynamic software indicates that the reaction of the alumina and charring layer initially forms Al4C3 during the operation. Then, Al element and Al2OC compound are subsequently produced with the reduction in the release of gas CO as well with continuous environmental heating.

A tool to assess potential for alien plant establishment and expansion under climate change.

PubMed

Roger, Erin; Duursma, Daisy Englert; Downey, Paul O; Gallagher, Rachael V; Hughes, Lesley; Steel, Jackie; Johnson, Stephen B; Leishman, Michelle R

2015-08-15

Predicting the influence of climate change on the potential distribution of naturalised alien plant species is an important and challenging task. While prioritisation of management actions for alien plants under current climatic conditions has been widely adopted, very few systems explicitly incorporate the potential of future changes in climate conditions to influence the distribution of alien plant species. Here, we develop an Australia-wide screening tool to assess the potential of naturalised alien plants to establish and spread under both current and future climatic conditions. The screening tool developed uses five spatially explicit criteria to establish the likelihood of alien plant population establishment and expansion under baseline climate conditions and future climates for the decades 2035 and 2065. Alien plants are then given a threat rating according to current and future threat to enable natural resource managers to focus on those species that pose the largest potential threat now and in the future. To demonstrate the screening tool, we present results for a representative sample of approximately 10% (n = 292) of Australia's known, naturalised alien plant species. Overall, most alien plant species showed decreases in area of habitat suitability under future conditions compared to current conditions and therefore the threat rating of most alien plant species declined between current and future conditions. Use of the screening tool is intended to assist natural resource managers in assessing the threat of alien plant establishment and spread under current and future conditions and thus prioritise detailed weed risk assessments for those species that pose the greatest threat. The screening tool is associated with a searchable database for all 292 alien plant species across a range of spatial scales, available through an interactive web-based portal at http://weedfutures.net/. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

PubMed Central

Wang, Shaogui; Ni, Hong-Min; Huang, Heqing

2014-01-01

Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy. PMID:25140315

Self-disgust as a potential mechanism underlying the association between PTSD and suicide risk.

PubMed

Brake, C Alex; Rojas, Sasha M; Badour, Christal L; Dutton, Courtney E; Feldner, Matthew T

2017-04-01

Suicide risk is highly prevalent among individuals with posttraumatic stress disorder (PTSD). Self-disgust, defined as disgust directed internally and comprised of disgust with oneself (disgusting self) and with one's behaviors (disgusting ways), may impact this increased risk. The present study examined self-disgust as a putative mechanism linking PTSD symptoms with suicide risk. A sample of 347 trauma-exposed undergraduates completed measures of PTSD symptoms, suicide risk, self-disgust, and depressive symptoms. Controlling for depressive symptoms, a process model indicated PTSD symptoms were positively linked to suicide risk via increased disgusting self but not disgusting ways. Process models examining individual PTSD symptom clusters revealed positive, indirect links between all PTSD symptom clusters except alterations in arousal and reactivity and suicide risk via disgusting self. These findings expand on growing literature documenting the importance of self-disgust in trauma-related pathology by identifying connections with suicide risk. Future directions and clinical considerations are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

American Society of Biomechanics Journal of Biomechanics Award 2013: Cortical bone tissue mechanical quality and biological mechanisms possibly underlying atypical fractures

PubMed Central

Geissler, Joseph R.; Bajaj, Devendra; Fritton, J. Christopher

2015-01-01

The biomechanics literature contains many well-understood mechanisms behind typical fracture types that have important roles in treatment planning. The recent association of “atypical” fractures with long-term use of drugs designed to prevent osteoporosis has renewed interest in the effects of agents on bone tissue-level quality. While this class of fracture was recognized prior to the introduction of the anti-resorptive bisphosphonate drugs and recently likened to stress fractures, the mechanism(s) that lead to atypical fractures have not been definitively identified. Thus, a causal relationship between these drugs and atypical fracture has not been established. Physicians, bioengineers and others interested in the biomechanics of bone are working to improve fracture-prevention diagnostics, and the design of treatments to avoid this serious side-effect in the future. This review examines the mechanisms behind the bone tissue damage that may produce the atypical fracture pattern observed increasingly with long-term bisphosphonate use. Our recent findings and those of others reviewed support that the mechanisms behind normal, healthy excavation and tunnel filling by bone remodeling units within cortical tissue strengthen mechanical integrity. The ability of cortical bone to resist the damage induced during cyclic loading may be altered by the reduced remodeling and increased tissue age resulting from long-term bisphosphonate treatment. Development of assessments for such potential fractures would restore confidence in pharmaceutical treatments that have the potential to spare millions in our aging population from the morbidity and death that often follow bone fracture. PMID:25683519

COMPUTATIONAL ANALYSIS OF SWALLOWING MECHANICS UNDERLYING IMPAIRED EPIGLOTTIC INVERSION

PubMed Central

Pearson, William G.; Taylor, Brandon K; Blair, Julie; Martin-Harris, Bonnie

2015-01-01

Objective Determine swallowing mechanics associated with the first and second epiglottic movements, that is, movement to horizontal and full inversion respectively, in order to provide a clinical interpretation of impaired epiglottic function. Study Design Retrospective cohort study. Methods A heterogeneous cohort of patients with swallowing difficulties was identified (n=92). Two speech-language pathologists reviewed 5ml thin and 5ml pudding videofluoroscopic swallow studies per subject, and assigned epiglottic component scores of 0=complete inversion, 1=partial inversion, and 2=no inversion forming three groups of videos for comparison. Coordinates mapping minimum and maximum excursion of the hyoid, pharynx, larynx, and tongue base during pharyngeal swallowing were recorded using ImageJ software. A canonical variate analysis with post-hoc discriminant function analysis of coordinates was performed using MorphoJ software to evaluate mechanical differences between groups. Eigenvectors characterizing swallowing mechanics underlying impaired epiglottic movements were visualized. Results Nineteen of 184 video-swallows were rejected for poor quality (n=165). A Goodman-Kruskal index of predictive association showed no correlation between epiglottic component scores and etiologies of dysphagia (λ=.04). A two-way analysis of variance by epiglottic component scores showed no significant interaction effects between sex and age (f=1.4, p=.25). Discriminant function analysis demonstrated statistically significant mechanical differences between epiglottic component scores: 1&2, representing the first epiglottic movement (Mahalanobis distance=1.13, p=.0007); and, 0&1, representing the second epiglottic movement (Mahalanobis distance=0.83, p=.003). Eigenvectors indicate that laryngeal elevation and tongue base retraction underlie both epiglottic movements. Conclusion Results suggest that reduced tongue base retraction and laryngeal elevation underlie impaired first and second

Oxotremorine-M potentiates NMDA receptors by muscarinic receptor dependent and independent mechanisms.

PubMed

Zwart, Ruud; Reed, Hannah; Sher, Emanuele

2018-01-01

Muscarinic acetylcholine M1 receptors play an important role in synaptic plasticity in the hippocampus and cortex. Potentiation of NMDA receptors as a consequence of muscarinic acetylcholine M1 receptor activation is a crucial event mediating the cholinergic modulation of synaptic plasticity, which is a cellular mechanism for learning and memory. In Alzheimer's disease, the cholinergic input to the hippocampus and cortex is severely degenerated, and agonists or positive allosteric modulators of M1 receptors are therefore thought to be of potential use to treat the deficits in cognitive functions in Alzheimer's disease. In this study we developed a simple system in which muscarinic modulation of NMDA receptors can be studied in vitro. Human M1 receptors and NR1/2B NMDA receptors were co-expressed in Xenopus oocytes and various muscarinic agonists were assessed for their modulatory effects on NMDA receptor-mediated responses. As expected, NMDA receptor-mediated responses were potentiated by oxotremorine-M, oxotremorine or xanomeline when the drugs were applied between subsequent NMDA responses, an effect which was fully blocked by the muscarinic receptor antagonist atropine. However, in oocytes expressing NR1/2B NMDA receptors but not muscarinic M1 receptors, oxotremorine-M co-applied with NMDA also resulted in a potentiation of NMDA currents and this effect was not blocked by atropine, demonstrating that oxotremorine-M is able to directly potentiate NMDA receptors. Oxotremorine, which is a close analogue of oxotremorine-M, and xanomeline, a chemically distinct muscarinic agonist, did not potentiate NMDA receptors by this direct mechanism. Comparing the chemical structures of the three different muscarinic agonists used in this study suggests that the tri-methyl ammonium moiety present in oxotremorine-M is important for the compound's interaction with NMDA receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Displacement and dissipation under the rotating tidal potential, in contrast to Love's geostationary potential

NASA Astrophysics Data System (ADS)

Bostrom, R. C.

The Earth rotates relative to the solunar gravity field. In consequence the M2, S2 tides are represented by permanent bulges, travelling westward around the Earth as distortion waves. The associated tidal stress ellipsoid progresses perpetually by rotation, without reversal. It is shown that under imperfect elasticity, in lieu of the body forces induced by Love's geostationary time-variant potential a rotating potential induces internal body couples, equally pervasive. Displacement is cumulative, and in the vortical mode formulated by Helmholtz (1858). Whereas in the geostationary formulation of Love cumulative distortion is nil, in actuality this motion is primary, and dimensionally capable of coupling with extant mantle convection. Unlike the marine tides, the bodily wave-tides proceed unhindered around the Earth unhindered by continental margins. Corrected for oceanic effects the complex Love numbers measure dissipation, as commonly supposed. However dissipation is the result of unmapped cumulative vortical displacement (a circulation component), rather than oscillatory forces having the form of a geographically stationary spheroidal eigenvibration. The characteristic period of the loss factor 1/Q is infinity rather than the period pertinent to seismicity or wobble, to which it is dimensionally unrelated. Although primary vorticity-induction is required by the existence of the rotating tidal potential, its tectonic consequences are a matter of speculation, treated elsewhere [1]. --- [1] Bostrom, R.C., 1998. Tectonic Consequences of the Earth's Rotation. Oxfo rd University Press.

Biological mechanisms underlying evolutionary origins of psychotic and mood disorders.

PubMed

Goto, Yukiori; Lee, Young-A; Yamaguchi, Yoshie; Jas, Emanuel

2016-10-01

Psychotic and mood disorders are brain dysfunctions that are caused by gene environment interactions. Although these disorders are disadvantageous and involve behavioral phenotypes that decrease the reproductive success of afflicted individuals in the modern human society, the prevalence of these disorders have remained constant in the population. Here, we propose several biological mechanisms by which the genes associated with psychotic and mood disorders could be selected for in specific environmental conditions that provide evolutionary bases for explanations of when, why, and where these disorders emerged and have been maintained in humans. We discuss the evolutionary origins of psychotic and mood disorders with specific focuses on the roles of dopamine and serotonin in the conditions of social competitiveness/hierarchy and maternal care and other potential mechanisms, such as social network homophily and symbiosis. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Bio-Energy Retains Its Mitigation Potential Under Elevated CO2

PubMed Central

Bellassen, Valentin; Njakou Djomo, Sylvestre; Lukac, Martin; Calfapietra, Carlo; Janssens, Ivan A.; Hoosbeek, Marcel R.; Viovy, Nicolas; Churkina, Galina; Scarascia-Mugnozza, Giuseppe; Ceulemans, Reinhart

2010-01-01

Background If biofuels are to be a viable substitute for fossil fuels, it is essential that they retain their potential to mitigate climate change under future atmospheric conditions. Elevated atmospheric CO2 concentration [CO2] stimulates plant biomass production; however, the beneficial effects of increased production may be offset by higher energy costs in crop management. Methodology/Main Findings We maintained full size poplar short rotation coppice (SRC) systems under both current ambient and future elevated [CO2] (550 ppm) and estimated their net energy and greenhouse gas balance. We show that a poplar SRC system is energy efficient and produces more energy than required for coppice management. Even more, elevated [CO2] will increase the net energy production and greenhouse gas balance of a SRC system with 18%. Managing the trees in shorter rotation cycles (i.e., 2 year cycles instead of 3 year cycles) will further enhance the benefits from elevated [CO2] on both the net energy and greenhouse gas balance. Conclusions/Significance Adapting coppice management to the future atmospheric [CO2] is necessary to fully benefit from the climate mitigation potential of bio-energy systems. Further, a future increase in potential biomass production due to elevated [CO2] outweighs the increased production costs resulting in a northward extension of the area where SRC is greenhouse gas neutral. Currently, the main part of the European terrestrial carbon sink is found in forest biomass and attributed to harvesting less than the annual growth in wood. Because SRC is intensively managed, with a higher turnover in wood production than conventional forest, northward expansion of SRC is likely to erode the European terrestrial carbon sink. PMID:20657833

Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss.

PubMed

Rupasinghe, H P Vasantha; Sekhon-Loodu, Satvir; Mantso, Theodora; Panayiotidis, Mihalis I

2016-09-01

Excessive accumulation of fat as the result of more energy intake and less energy expenditure is known as obesity. Lipids are essential components in the human body and are vital for maintaining homeostasis and physiological as well as cellular metabolism. Fatty acid synthesis and catabolism (by fatty acid oxidation) are normal part of basic fuel metabolism in animals. Fatty acids are degraded in the mitochondria by a biochemical process called β-oxidation in which two-carbon fragments are produced in each cycle. The increase in fatty acid β-oxidation is negatively correlated with body mass index. Although healthy life style, avoiding Western diet, dieting and strenuous exercise are the commonly used methods to lose weight, they are not considered a permanent solution in addition to risk attenuation of basal metabolic rate (BMR). Pharmacotherapy offers benefits of weight loss by altering the satiety and lowering absorption of fat from the food; however, its side effects may outweigh the benefits of weight loss. Alternatively, dietary phytochemicals and natural health products offer great potential as an efficient weight loss strategy by modulating lipid metabolism and/or increasing BMR and thermogenesis. Specifically, polyphenols such as citrus flavonoids, green tea epigallocatechin gallate, resveratrol, capsaicin and curcumin, have been reported to increase lipolysis and induce fatty acid β-oxidation through modulation of hormone sensitive lipase, acetyl-coA carboxylase, carnitine acyl transferase and peroxisome proliferator-activated receptor gamma coactivator-1. In this review article, we discuss selected phytochemicals in relation to their integrated functionalities and specific mechanisms for weight loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Thermal optimality of net ecosystem exchange of carbon dioxide and underlying mechanisms.

PubMed

Niu, Shuli; Luo, Yiqi; Fei, Shenfeng; Yuan, Wenping; Schimel, David; Law, Beverly E; Ammann, Christof; Arain, M Altaf; Arneth, Almut; Aubinet, Marc; Barr, Alan; Beringer, Jason; Bernhofer, Christian; Black, T Andrew; Buchmann, Nina; Cescatti, Alessandro; Chen, Jiquan; Davis, Kenneth J; Dellwik, Ebba; Desai, Ankur R; Etzold, Sophia; Francois, Louis; Gianelle, Damiano; Gielen, Bert; Goldstein, Allen; Groenendijk, Margriet; Gu, Lianhong; Hanan, Niall; Helfter, Carole; Hirano, Takashi; Hollinger, David Y; Jones, Mike B; Kiely, Gerard; Kolb, Thomas E; Kutsch, Werner L; Lafleur, Peter; Lawrence, David M; Li, Linghao; Lindroth, Anders; Litvak, Marcy; Loustau, Denis; Lund, Magnus; Marek, Michal; Martin, Timothy A; Matteucci, Giorgio; Migliavacca, Mirco; Montagnani, Leonardo; Moors, Eddy; Munger, J William; Noormets, Asko; Oechel, Walter; Olejnik, Janusz; Kyaw Tha Paw U; Pilegaard, Kim; Rambal, Serge; Raschi, Antonio; Scott, Russell L; Seufert, Günther; Spano, Donatella; Stoy, Paul; Sutton, Mark A; Varlagin, Andrej; Vesala, Timo; Weng, Ensheng; Wohlfahrt, Georg; Yang, Bai; Zhang, Zhongda; Zhou, Xuhui

2012-05-01

• It is well established that individual organisms can acclimate and adapt to temperature to optimize their functioning. However, thermal optimization of ecosystems, as an assemblage of organisms, has not been examined at broad spatial and temporal scales. • Here, we compiled data from 169 globally distributed sites of eddy covariance and quantified the temperature response functions of net ecosystem exchange (NEE), an ecosystem-level property, to determine whether NEE shows thermal optimality and to explore the underlying mechanisms. • We found that the temperature response of NEE followed a peak curve, with the optimum temperature (corresponding to the maximum magnitude of NEE) being positively correlated with annual mean temperature over years and across sites. Shifts of the optimum temperature of NEE were mostly a result of temperature acclimation of gross primary productivity (upward shift of optimum temperature) rather than changes in the temperature sensitivity of ecosystem respiration. • Ecosystem-level thermal optimality is a newly revealed ecosystem property, presumably reflecting associated evolutionary adaptation of organisms within ecosystems, and has the potential to significantly regulate ecosystem-climate change feedbacks. The thermal optimality of NEE has implications for understanding fundamental properties of ecosystems in changing environments and benchmarking global models. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Metabolic imaging in obesity: underlying mechanisms and consequences in the whole body.

PubMed

Iozzo, Patricia

2015-09-01

Obesity is a phenotype resulting from a series of causative factors with a variable risk of complications. Etiologic diversity requires personalized prevention and treatment. Imaging procedures offer the potential to investigate the interplay between organs and pathways underlying energy intake and consumption in an integrated manner, and may open the perspective to classify and treat obesity according to causative mechanisms. This review illustrates the contribution provided by imaging studies to the understanding of human obesity, starting with the regulation of food intake and intestinal metabolism, followed by the role of adipose tissue in storing, releasing, and utilizing substrates, including the interconversion of white and brown fat, and concluding with the examination of imaging risk indicators related to complications, including type 2 diabetes, liver pathologies, cardiac and kidney diseases, and sleep disorders. The imaging modalities include (1) positron emission tomography to quantify organ-specific perfusion and substrate metabolism; (2) computed tomography to assess tissue density as an indicator of fat content and browning/ whitening; (3) ultrasounds to examine liver steatosis, stiffness, and inflammation; and (4) magnetic resonance techniques to assess blood oxygenation levels in the brain, liver stiffness, and metabolite contents (triglycerides, fatty acids, glucose, phosphocreatine, ATP, and acetylcarnitine) in a variety of organs. © 2015 New York Academy of Sciences.

Age differences in the underlying mechanisms of stereotype threat effects.

PubMed

Popham, Lauren E; Hess, Thomas M

2015-03-01

The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Older adults' performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms.

PubMed

Nohe, Christoph; Hertel, Guido

2017-01-01

Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms

PubMed Central

Nohe, Christoph; Hertel, Guido

2017-01-01

Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB. PMID:28848478

The influence of the electrochemical stressing (potential step and potential-static holding) on the degradation of polymer electrolyte membrane fuel cell electrocatalysts

NASA Astrophysics Data System (ADS)

Shao, Yuyan; Kou, Rong; Wang, Jun; Viswanathan, Vilayanur V.; Kwak, Ja Hun; Liu, Jun; Wang, Yong; Lin, Yuehe

The understanding of the degradation mechanisms of electrocatalysts is very important for developing durable electrocatalysts for polymer electrolyte membrane (PEM) fuel cells. The degradation of Pt/C electrocatalysts under potential-static holding conditions (at 1.2 V and 1.4 V vs. RHE) and potential step conditions with the upper potential of 1.4 V for 150 s and lower potential limits (0.85 V and 0.60 V) for 30 s in each period [denoted as Pstep(1.4V_150s-0.85V_30s) and Pstep(1.4V_150s-0.60V_30s), respectively] were investigated. The electrocatalysts and support were characterized with electrochemical voltammetry, transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). Pt/C degrades much faster under Pstep conditions than that under potential-static holding conditions. Pt/C degrades under the Pstep(1.4V_150s-0.85V_30s) condition mainly through the coalescence process of Pt nanoparticles due to the corrosion of carbon support, which is similar to that under the conditions of 1.2 V- and 1.4 V-potential-static holding; however, Pt/C degrades mainly through the dissolution/loss and dissolution/redeposition process if stressed under Pstep(1.4V_150s-0.60V_30s). The difference in the degradation mechanisms is attributed to the chemical states of Pt nanoparticles: Pt dissolution can be alleviated by the protective oxide layer under the Pstep(1.4V_150s-0.85V_30s) condition and the potential-static holding conditions. These findings are very important for understanding PEM fuel cell electrode degradation and are also useful for developing fast test protocol for screening durable catalyst support materials.

Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

PubMed Central

Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

2012-01-01

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

Solid-State Solvation and Enhanced Exciton Diffusion in Doped Organic Thin Films under Mechanical Pressure.

PubMed

Chang, Wendi; Akselrod, Gleb M; Bulović, Vladimir

2015-04-28

Direct modification of exciton energy has been previously used to optimize the operation of organic optoelectronic devices. One demonstrated method for exciton energy modification is through the use of the solvent dielectric effects in doped molecular films. To gain a deeper appreciation of the underlying physical mechanisms, in this work we test the solid-state solvation effect in molecular thin films under applied external pressure. We observe that external mechanical pressure increases dipole-dipole interactions, leading to shifts in the Frenkel exciton energy and enhancement of the time-resolved spectral red shift associated with the energy-transfer-mediated exciton diffusion. Measurements are performed on host:dopant molecular thin films, which show bathochromic shifts in photoluminescence (PL) under increasing pressure. This is in agreement with a simple solvation theory model of exciton energetics with a fitting parameter based on the mechanical properties of the host matrix material. We measure no significant change in exciton lifetime with increasing pressure, consistent with unchanged aggregation in molecular films under compression. However, we do observe an increase in exciton spectral thermalization rate for compressed molecular films, indicating enhanced exciton diffusion for increased dipole-dipole interactions under pressure. The results highlight the contrast between molecular energy landscapes obtained when dipole-dipole interactions are increased by the pressure technique versus the conventional dopant concentration variation methods, which can lead to extraneous effects such as aggregation at higher doping concentrations. The present work demonstrates the use of pressure-probing techniques in studying energy disorder and exciton dynamics in amorphous molecular thin films.

Solid-State Solvation and Enhanced Exciton Diffusion in Doped Organic Thin Films under Mechanical Pressure

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

Chang, Wendi; Akselrod, Gleb M.; Bulović, Vladimir

2015-04-28

Direct modification of exciton energy has been previously used to optimize the operation of organic optoelectronic devices. One demonstrated method for exciton energy modification is through the use of the solvent dielectric effects in doped molecular films. To gain a deeper appreciation of the underlying physical mechanisms, in this work we test the solid-state solvation effect in molecular thin films under applied external pressure. We observe that external mechanical pressure increases dipole–dipole interactions, leading to shifts in the Frenkel exciton energy and enhancement of the time-resolved spectral red shift associated with the energy-transfer-mediated exciton diffusion. Measurements are performed on host:dopantmore » molecular thin films, which show bathochromic shifts in photoluminescence (PL) under increasing pressure. This is in agreement with a simple solvation theory model of exciton energetics with a fitting parameter based on the mechanical properties of the host matrix material. We measure no significant change in exciton lifetime with increasing pressure, consistent with unchanged aggregation in molecular films under compression. However, we do observe an increase in exciton spectral thermalization rate for compressed molecular films, indicating enhanced exciton diffusion for increased dipole–dipole interactions under pressure. The results highlight the contrast between molecular energy landscapes obtained when dipole–dipole interactions are increased by the pressure technique versus the conventional dopant concentration variation methods, which can lead to extraneous effects such as aggregation at higher doping concentrations. The present work demonstrates the use of pressure-probing techniques in studying energy disorder and exciton dynamics in amorphous molecular thin films.« less

Closed-form analysis of fiber-matrix interface stresses under thermo-mechanical loadings

NASA Technical Reports Server (NTRS)

Naik, Rajiv A.; Crews, John H., Jr.

1992-01-01

Closed form techniques for calculating fiber matrix (FM) interface stresses, using repeating square and diamond regular arrays, were presented for a unidirectional composite under thermo-mechanical loadings. An Airy's stress function micromechanics approach from the literature, developed for calculating overall composite moduli, was extended in the present study to compute FM interface stresses for a unidirectional graphite/epoxy (AS4/3501-6) composite under thermal, longitudinal, transverse, transverse shear, and longitudinal shear loadings. Comparison with finite element results indicate excellent agreement of the FM interface stresses for the square array. Under thermal and longitudinal loading, the square array has the same FM peak stresses as the diamond array. The square array predicted higher stress concentrations under transverse normal and longitudinal shear loadings than the diamond array. Under transverse shear loading, the square array had a higher stress concentration while the diamond array had a higher radial stress concentration. Stress concentration factors under transverse shear and longitudinal shear loadings were very sensitive to fiber volume fraction. The present analysis provides a simple way to calculate accurate FM interface stresses for both the square and diamond array configurations.

Physiological Traits Associated with Wheat Yield Potential and Performance under Water-Stress in a Mediterranean Environment

PubMed Central

del Pozo, Alejandro; Yáñez, Alejandra; Matus, Iván A.; Tapia, Gerardo; Castillo, Dalma; Sanchez-Jardón, Laura; Araus, José L.

2016-01-01

Different physiological traits have been proposed as key traits associated with yield potential as well as performance under water stress. The aim of this paper is to examine the genotypic variability of leaf chlorophyll, stem water-soluble carbohydrate content and carbon isotope discrimination (Δ13C), and their relationship with grain yield (GY) and other agronomical traits, under contrasting water conditions in a Mediterranean environment. The study was performed on a large collection of 384 wheat genotypes grown under water stress (WS, rainfed), mild water stress (MWS, deficit irrigation), and full irrigation (FI). The average GY of two growing seasons was 2.4, 4.8, and 8.9 Mg ha−1 under WS, MWS, and FI, respectively. Chlorophyll content at anthesis was positively correlated with GY (except under FI in 2011) and the agronomical components kernels per spike (KS) and thousand kernel weight (TKW). The WSC content at anthesis (WSCCa) was negatively correlated with spikes per square meter (SM2), but positively correlated with KS and TKW under WS and FI conditions. As a consequence, the relationships between WSCCa with GY were low or not significant. Therefore, selecting for high stem WSC would not necessary lead to genotypes of GY potential. The relationship between Δ13C and GY was positive under FI and MWS but negative under severe WS (in 2011), indicating higher water use under yield potential and MWS conditions. PMID:27458470

Physiological Traits Associated with Wheat Yield Potential and Performance under Water-Stress in a Mediterranean Environment.

PubMed

Del Pozo, Alejandro; Yáñez, Alejandra; Matus, Iván A; Tapia, Gerardo; Castillo, Dalma; Sanchez-Jardón, Laura; Araus, José L

2016-01-01

Different physiological traits have been proposed as key traits associated with yield potential as well as performance under water stress. The aim of this paper is to examine the genotypic variability of leaf chlorophyll, stem water-soluble carbohydrate content and carbon isotope discrimination (Δ(13)C), and their relationship with grain yield (GY) and other agronomical traits, under contrasting water conditions in a Mediterranean environment. The study was performed on a large collection of 384 wheat genotypes grown under water stress (WS, rainfed), mild water stress (MWS, deficit irrigation), and full irrigation (FI). The average GY of two growing seasons was 2.4, 4.8, and 8.9 Mg ha(-1) under WS, MWS, and FI, respectively. Chlorophyll content at anthesis was positively correlated with GY (except under FI in 2011) and the agronomical components kernels per spike (KS) and thousand kernel weight (TKW). The WSC content at anthesis (WSCCa) was negatively correlated with spikes per square meter (SM2), but positively correlated with KS and TKW under WS and FI conditions. As a consequence, the relationships between WSCCa with GY were low or not significant. Therefore, selecting for high stem WSC would not necessary lead to genotypes of GY potential. The relationship between Δ(13)C and GY was positive under FI and MWS but negative under severe WS (in 2011), indicating higher water use under yield potential and MWS conditions.

Potential mechanisms of resistance to venetoclax and strategies to circumvent it.

PubMed

Tahir, Stephen K; Smith, Morey L; Hessler, Paul; Rapp, Lisa Roberts; Idler, Kenneth B; Park, Chang H; Leverson, Joel D; Lam, Lloyd T

2017-06-02

Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges. In order to gain a more comprehensive insight into the nature of venetoclax resistance mechanisms, we evaluated the changes in the BCL-2 family members at the genetic and expression levels in seven different venetoclax-resistant derived leukemia and lymphoma cell lines. Gene and protein expression analyses identified a number of different alterations in the expression of pro- and anti-apoptotic BCL-2 family members. In the resistant derived cells, an increase in either or both the anti-apoptotic proteins BCL-X L or MCL-1, which are not targeted by venetoclax was observed, and either concomitant or exclusive with a decrease in one or more pro-apoptotic proteins. In addition, mutational analysis also revealed a mutation in the BH3 binding groove (F104L) that could potentially interfere with venetoclax-binding. Not all changes may be causally related to venetoclax resistance and may only be an epiphenomenon. For resistant cell lines showing elevations in BCL-X L or MCL-1, strong synergistic cell killing was observed when venetoclax was combined with either BCL-X L - or MCL-1-selective inhibitors, respectively. This highlights the importance of BCL-X L - and MCL-1 as causally contributing to venetoclax resistance. Overall our study identified numerous changes in multiple resistant lines; the changes were neither mutually exclusive nor universal across the cell lines tested, thus exemplifying the complexity

Effects and underlying mechanisms of curcumin on the proliferation of vascular smooth muscle cells induced by Chol:M{beta}CD

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

Qin Li; Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001; Yang Yunbo

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of various cardiovascular diseases. Curcumin, extracted from Curcumae longae, has been shown a variety of beneficial effects on human health, including anti-atherosclerosis by mechanisms poorly understood. In the present study, we attempted to investigate whether curcumin has any effect on VSMCs proliferation and the potential mechanisms involved. Our data showed curcumin concentration-dependently abrogated the proliferation of primary rat VSMCs induced by Chol:M{beta}CD. To explore the underlying cellular and molecular mechanisms, we found that curcumin was capable of restoring caveolin-1 expression which was reduced by Chol:M{beta}CD treatment. Moreover, curcumin abrogatedmore » the increment of phospho-ERK1/2 and nuclear accumulation of ERK1/2 in primary rat VSMCs induced by Chol:M{beta}CD, which led to a suppression of AP-1 promoter activity stimulated by Chol:M{beta}CD. In addition, curcumin was able to reverse cell cycle progression induced by Chol:M{beta}CD, which was further supported by its down-regulation of cyclinD1 and E2F promoter activities in the presence of Chol:M{beta}CD. Taking together, our data suggest curcumin inhibits Chol:M{beta}CD-induced VSMCs proliferation via restoring caveolin-1 expression that leads to the suppression of over-activated ERK signaling and causes cell cycle arrest at G1/S phase. These novel findings support the beneficial potential of curcumin in cardiovascular disease.« less

Microcracking in composite laminates under thermal and mechanical loading. Thesis

NASA Technical Reports Server (NTRS)

Maddocks, Jason R.

1995-01-01

Composites used in space structures are exposed to both extremes in temperature and applied mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. The goal of the present investigation is to develop a predictive methodology to quantify microcracking in general composite laminates under both thermal and mechanical loading. This objective is successfully met through a combination of analytical modeling and experimental investigation. In the analysis, the stress and displacement distributions in the vicinity of a crack are determined using a shear lag model. These are incorporated into an energy based cracking criterion to determine the favorability of crack formation. A progressive damage algorithm allows the inclusion of material softening effects and temperature-dependent material properties. The analysis is implemented by a computer code which gives predicted crack density and degraded laminate properties as functions of any thermomechanical load history. Extensive experimentation provides verification of the analysis. AS4/3501-6 graphite/epoxy laminates are manufactured with three different layups to investigate ply thickness and orientation effects. Thermal specimens are cooled to progressively lower temperatures down to -184 C. After conditioning the specimens to each temperature, cracks are counted on their edges using optical microscopy and in their interiors by sanding to incremental depths. Tensile coupons are loaded monotonically to progressively higher loads until failure. Cracks are counted on the coupon edges after each loading. A data fit to all available results provides input parameters for the analysis and shows them to be material properties, independent of geometry and loading. Correlation between experiment and analysis is generally very good under both thermal and mechanical loading, showing the methodology to be a powerful, unified tool. Delayed crack initiation observed in a few cases is attributed to a

A connectionist modeling study of the neural mechanisms underlying pain's ability to reorient attention.

PubMed

Dowman, Robert; Ritz, Benjamin; Fowler, Kathleen

2016-08-01

Connectionist modeling was used to investigate the brain mechanisms responsible for pain's ability to shift attention away from another stimulus modality and toward itself. Different connectionist model architectures were used to simulate the different possible brain mechanisms underlying this attentional bias, where nodes in the model simulated the brain areas thought to mediate the attentional bias, and the connections between the nodes simulated the interactions between the brain areas. Mathematical optimization techniques were used to find the model parameters, such as connection strengths, that produced the best quantitative fits of reaction time and event-related potential data obtained in our previous work. Of the several architectures tested, two produced excellent quantitative fits of the experimental data. One involved an unexpected pain stimulus activating somatic threat detectors in the dorsal posterior insula. This threat detector activity was monitored by the medial prefrontal cortex, which in turn evoked a phasic response in the locus coeruleus. The locus coeruleus phasic response resulted in a facilitation of the cortical areas involved in decision and response processes time-locked to the painful stimulus. The second architecture involved the presence of pain causing an increase in general arousal. The increase in arousal was mediated by locus coeruleus tonic activity, which facilitated responses in the cortical areas mediating the sensory, decision, and response processes involved in the task. These two neural network architectures generated competing predictions that can be tested in future studies.

Extracellular Polymeric Matrix Production and Relaxation under Fluid Shear and Mechanical Pressure in Staphylococcus aureus Biofilms.

PubMed

Hou, Jiapeng; Veeregowda, Deepak H; van de Belt-Gritter, Betsy; Busscher, Henk J; van der Mei, Henny C

2017-10-20

The viscoelasticity of a biofilm's EPS (extracellular-polymeric-substance) matrix conveys protection against mechanical challenges, but adaptive responses of biofilm inhabitants to produce EPS are not well known. Here, we compare the response of a biofilm of an EPS producing (ATCC 12600) and non-EPS producing (5298) Staphylococcus aureus strain to fluid shear and mechanical challenge. Confocal-Laser-Scanning-Microscopy confirmed absence of calcofluorwhite-stainable EPS in biofilms of S. aureus 5298. ATR-FTIR spectroscopy combined with tribometry indicated that the polysaccharide production per bacterium in the initial adhering layer was higher during growth at high shear than at low shear and this increased EPS production extended to entire biofilms, as indicated by tribometrically measured coefficients of friction (CoF). CoFs of biofilms grown under high fluid shear were higher than when grown under low shear, likely due to wash-off of polysaccharides. Measurement of a biofilm's CoF implies application of mechanical pressure that yielded an immediate increase in polysaccharide band area of S. aureus ATCC 12600 biofilms due to their compression that decreased after relieving pressure to the level observed prior to mechanical pressure. For biofilms grown under high shear, this coincided with a higher %whiteness in Optical-Coherence-Tomography-images indicative of water outflow, returning back into the biofilm during stress relaxation. Biofilms grown under low shear however, were stimulated during tribometry to produce EPS, also after stress relieve. Knowledge of factors that govern EPS production and water flow in biofilms will allow better control of biofilms under mechanical challenge and understanding of the barrier properties of biofilms toward antimicrobial penetration. IMPORTANCE Adaptive responses of biofilm inhabitants in nature to environmental challenges such as fluid shear and mechanical pressure, often involve EPS production with the aim of protecting

Molecular mechanisms underlying PINK1 and Parkin catalyzed ubiquitylation of substrates on damaged mitochondria.

PubMed

Koyano, Fumika; Matsuda, Noriyuki

2015-10-01

PINK1 and Parkin are gene products that cause genetic recessive Parkinsonism. PINK1 is a protein kinase and Parkin is a ubiquitin ligase (E3) that links ubiquitin to a substrate. Importantly, under steady state conditions, the enzymatic activity of Parkin is completely suppressed, but is activated when mitochondria become abnormal. In 2013 and 2014, biochemical and structure-function analyses revealed a number of critical mechanistic insights. First, Parkin is a self-inhibitory E3 that suppresses its E3 activity via intramolecular interactions. Second, in response to a decrease in mitochondrial membrane potential, PINK1 phosphorylates Ser65 in both the Parkin ubiquitin-like domain and ubiquitin itself. These phosphorylation events cooperate to relieve the Parkin autoinhibition. Third, activated Parkin forms a ubiquitin-thioester bond at Cys431 to produce a reaction intermediate that catalyzes ubiquitylation of substrates on damaged mitochondria. While the molecular mechanism regulating Parkin enzymatic activity has largely eluded clarification, a complete picture is now emerging. Copyright © 2015 Elsevier B.V. All rights reserved.

Electrostrictive Polymers for Mechanical-to-Electrical Energy Harvesting

DTIC Science & Technology

usable electrical energy. Piezoelectric ceramic-based devices have long been used in energy harvesting for converting mechanical motion to electrical ...typically softer and more flexible, the translated electrical energy output is considerably higher under the same mechanical force. Currently...investigations in using electroactive polymers for energy harvesting, and mechanical-to- electrical energy conversion, are beginning to show potential for

Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications.

PubMed

Holmes, Emily A; Blackwell, Simon E; Burnett Heyes, Stephanie; Renner, Fritz; Raes, Filip

2016-01-01

Mental imagery is an experience like perception in the absence of a percept. It is a ubiquitous feature of human cognition, yet it has been relatively neglected in the etiology, maintenance, and treatment of depression. Imagery abnormalities in depression include an excess of intrusive negative mental imagery; impoverished positive imagery; bias for observer perspective imagery; and overgeneral memory, in which specific imagery is lacking. We consider the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions. Treatment advances capitalizing on the representational format of imagery (as opposed to its content) are reviewed, including imagery rescripting, positive imagery generation, and memory specificity training. Consideration of mental imagery can contribute to clinical assessment and imagery-focused psychological therapeutic techniques and promote investigation of underlying mechanisms for treatment innovation. Research into mental imagery in depression is at an early stage. Work that bridges clinical psychology and neuroscience in the investigation of imagery-related mechanisms is recommended.

Local Mechanical Response of Superelastic NiTi Shape-Memory Alloy Under Uniaxial Loading

NASA Astrophysics Data System (ADS)

Xiao, Yao; Zeng, Pan; Lei, Liping; Du, Hongfei

2015-11-01

In this paper, we focus on the local mechanical response of superelastic NiTi SMA at different temperatures under uniaxial loading. In situ DIC is applied to measure the local strain of the specimen. Based on the experimental results, two types of mechanical response, which are characterized with localized phase transformation and homogenous phase transformation, are identified, respectively. Motivated by residual strain accumulation phenomenon of the superelastic mechanical response, we conduct controlled experiments, and infer that for a given material point, all (or most) of the irreversibility is accumulated when the transformation front is traversing the material point. A robust constitutive model is established to explain the experimental phenomena and we successfully simulate the evolution of local strain that agrees closely with the experimental results.

Toward understanding the efficacy and mechanism of Opuntia spp. as a natural coagulant for potential application in water treatment.

PubMed

Miller, Sarah M; Fugate, Ezekiel J; Craver, Vinka Oyanedel; Smith, James A; Zimmerman, Julie B

2008-06-15

Historically, there is evidence to suggest that communities in the developing world have used plant-based materials as one strategy for purifying drinking water. In this study, the coagulant properties of Opuntia spp., a species of cactus, are quantitatively evaluated for the first time. Opuntia spp. was evaluated for turbidity removal from synthetic water samples, and steps were made toward elucidating the underlying coagulation mechanism. In model turbid water using kaolin clay particles at pH 10, Opuntia spp. reduced turbidity by 98% for a range of initial turbidities. This is similar to the observed coagulation activities previously described for Moringa oleifera, a widely studied natural coagulant. Although it has been reported that Moringa oleifera predominantly operates through charge neutralization, comparison of zeta potential measurements and transmission electron microscopy images of flocs formed by Opuntia spp. suggest that these natural coagulants operate through different mechanisms. It is suggested that Opuntia spp. operates predominantly through a bridging coagulation mechanism. Once optimized, application of these readily available plants as a part of point-of-use water treatment technology may offer a practical, inexpensive, and appropriate solution for producing potable water in some developing communities.

The potential role of neuropathic mechanisms in dry eye syndromes.

PubMed

Mcmonnies, Charles W

Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Betavoltaic effect in titanium dioxide nanotube arrays under build-in potential difference

NASA Astrophysics Data System (ADS)

Zhang, Qiang; Chen, Ranbin; San, Haisheng; Liu, Guohua; Wang, Kaiying

2015-05-01

We report the fabrication of sandwich-type metal/TiO2 nanotube (TNT) array/metal structures as well as their betavoltaic effects under build-in voltage through contact potential difference. The sandwiched structure is integrated by immobilized TNT arrays on Ti foil with radioisotope 63Ni planar source on Ni substrate (Ni-63Ni/TNT array/Ti). Under irradiation of the 63Ni source with activity of 8 mCi, the structure (TNT diameter ∼ 130 nm, length ∼ 11 μm) presents optimum energy conversion efficiency of 7.30% with open-circuit voltage of 1.54 V and short-circuit current of 12.43 nA. The TNT arrays exhibit a highly potential for developing betavoltaic batteries due to its wide band gap and nanotube array configuration. The TNT-betavoltaic concept offers a facile solution for micro/nano electronics with high efficiency and long life-time instead of conventional planar junction-type batteries.

Fracture Mechanical Analysis of Open Cell Ceramic Foams Under Thermal Shock Loading

NASA Astrophysics Data System (ADS)

Settgast, C.; Abendroth, M.; Kuna, M.

2016-11-01

Ceramic foams made by replica techniques containing sharp-edged cavities, which are potential crack initiators and therefore have to be analyzed using fracture mechanical methods. The ceramic foams made of novel carbon bonded alumina are used as filters in metal melt filtration applications, where the filters are exposed to a thermal shock. During the casting process the filters experience a complex thermo-mechanical loading, which is difficult to measure. Modern numerical methods allow the simulation of such complex processes. As a simplified foam structure an open Kelvin cell is used as a representative volume element. A three-dimensional finite element model containing realistic sharp-edged cavities and three-dimensional sub-models along these sharp edges are used to compute the transient temperature, stress and strain fields at the Kelvin foam. The sharp edges are evaluated using fracture mechanical methods like the J-integral technique. The results of this study describe the influence of the pore size, relative density of the ceramic foam, the heat transfer and selected material parameters on the fracture mechanical behaviour.

Modelling mechanical behaviour of limestone under reservoir conditions

NASA Astrophysics Data System (ADS)

Carvalho Coelho, Lúcia; Soares, Antonio Claudio; Ebecken, Nelson Francisco F.; Drummond Alves, José Luis; Landau, Luiz

2006-12-01

High porosity and low permeability limestone has presented pore collapse. As fluid is withdrawn from these reservoirs, the effective stresses acting on the rock increase. If the strength of the rock is overcome, pore collapse may occur, leading to irreversible compaction of porous media with permeability and porosity reduction. It impacts on fluid withdrawal. Most of reservoirs have been discovered in weak formations, which are susceptible to this phenomenon. This work presents a study on the mechanical behaviour of a porous limestone from a reservoir located in Campos Basin, offshore Brazil. An experimental program was undergone in order to define its elastic plastic behaviour. The tests reproduced the loading path conditions expected in a reservoir under production. Parameters of the cap model were fitted to these tests and numerical simulations were run. The numerical simulations presented a good agreement with the experimental tests. Copyright

Neurocognitive mechanisms of statistical-sequential learning: what do event-related potentials tell us?

PubMed Central

Daltrozzo, Jerome; Conway, Christopher M.

2014-01-01

Statistical-sequential learning (SL) is the ability to process patterns of environmental stimuli, such as spoken language, music, or one’s motor actions, that unfold in time. The underlying neurocognitive mechanisms of SL and the associated cognitive representations are still not well understood as reflected by the heterogeneity of the reviewed cognitive models. The purpose of this review is: (1) to provide a general overview of the primary models and theories of SL, (2) to describe the empirical research – with a focus on the event-related potential (ERP) literature – in support of these models while also highlighting the current limitations of this research, and (3) to present a set of new lines of ERP research to overcome these limitations. The review is articulated around three descriptive dimensions in relation to SL: the level of abstractness of the representations learned through SL, the effect of the level of attention and consciousness on SL, and the developmental trajectory of SL across the life-span. We conclude with a new tentative model that takes into account these three dimensions and also point to several promising new lines of SL research. PMID:24994975

Mechanical measurement of hydrogen bonded host-guest systems under non-equilibrium, near-physiological conditions.

PubMed

Naranjo, Teresa; Cerrón, Fernando; Nieto-Ortega, Belén; Latorre, Alfonso; Somoza, Álvaro; Ibarra, Borja; Pérez, Emilio M

2017-09-01

Decades after the birth of supramolecular chemistry, there are many techniques to measure noncovalent interactions, such as hydrogen bonding, under equilibrium conditions. As ensembles of molecules rapidly lose coherence, we cannot extrapolate bulk data to single-molecule events under non-equilibrium conditions, more relevant to the dynamics of biological systems. We present a new method that exploits the high force resolution of optical tweezers to measure at the single molecule level the mechanical strength of a hydrogen bonded host-guest pair out of equilibrium and under near-physiological conditions. We utilize a DNA reporter to unambiguously isolate single binding events. The Hamilton receptor-cyanuric acid host-guest system is used as a test bed. The force required to dissociate the host-guest system is ∼17 pN and increases with the pulling rate as expected for a system under non-equilibrium conditions. Blocking one of the hydrogen bonding sites results in a significant decrease of the force-to-break by 1-2 pN, pointing out the ability of the method to resolve subtle changes in the mechanical strength of the binding due to the individual H-bonding components. We believe the method will prove to be a versatile tool to address important questions in supramolecular chemistry.

A review of failure models for unidirectional ceramic matrix composites under monotonic loads

NASA Technical Reports Server (NTRS)

Tripp, David E.; Hemann, John H.; Gyekenyesi, John P.

1989-01-01

Ceramic matrix composites offer significant potential for improving the performance of turbine engines. In order to achieve their potential, however, improvements in design methodology are needed. In the past most components using structural ceramic matrix composites were designed by trial and error since the emphasis of feasibility demonstration minimized the development of mathematical models. To understand the key parameters controlling response and the mechanics of failure, the development of structural failure models is required. A review of short term failure models with potential for ceramic matrix composite laminates under monotonic loads is presented. Phenomenological, semi-empirical, shear-lag, fracture mechanics, damage mechanics, and statistical models for the fast fracture analysis of continuous fiber unidirectional ceramic matrix composites under monotonic loads are surveyed.

Consciousness, unconsciousness and death in the context of slaughter. Part I. Neurobiological mechanisms underlying stunning and killing.

PubMed

Terlouw, Claudia; Bourguet, Cécile; Deiss, Véronique

2016-08-01

This review describes the neurobiological mechanisms that are relevant for the stunning and killing process of animals in the abattoir. The mechanisms underlying the loss of consciousness depend on the technique used: mechanical, electrical or gas stunning. Direct exsanguination (without prior stun) causes also a loss of consciousness before inducing death. The underlying mechanisms may involve cerebral anoxia or ischemia, or the depolarisation, acidification and/or the destruction of brain neurons. These effects may be caused by shock waves, electrical fields, the reduction or arrest of the cerebral blood circulation, increased levels of CO2 or low levels of O2 in the inhaled air, or the mechanical destruction of neurons. The targeted brain structures are the reticular formation, the ascending reticular activating system or thalamus, or the cerebral hemispheres in a general manner. Some of the techniques, when properly used, induce an immediate loss of consciousness; other techniques a progressive loss of consciousness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physiological mechanisms contributing to the QTL-combination effects on improved performance of IR64 rice NILs under drought

PubMed Central

Henry, Amelia; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Torres, Rolando D.; Batoto, Tristram C.; Manalili, Mervin; Anantha, M. S.; Mandal, N. P.; Kumar, Arvind

2015-01-01

Characterizing the physiological mechanisms behind major-effect drought-yield quantitative trait loci (QTLs) can provide an understanding of the function of the QTLs—as well as plant responses to drought in general. In this study, we characterized rice (Oryza sativa L.) genotypes with QTLs derived from drought-tolerant traditional variety AdaySel that were introgressed into drought-susceptible high-yielding variety IR64, one of the most popular megavarieties in South Asian rainfed lowland systems. Of the different combinations of the four QTLs evaluated, genotypes with two QTLs (qDTY 2.2 + qDTY 4.1) showed the greatest degree of improvement under drought compared with IR64 in terms of yield, canopy temperature, and normalized difference vegetation index (NDVI). Furthermore, qDTY 2.2 and qDTY 4.1 showed a potential for complementarity in that they were each most effective under different severities of drought stress. Multiple drought-response mechanisms were observed to be conferred in the genotypes with the two-QTL combination: higher root hydraulic conductivity and in some cases greater root growth at depth. As evidenced by multiple leaf water status and plant growth indicators, these traits affected transpiration but not transpiration efficiency or harvest index. The results from this study highlight the complex interactions among major-effect drought-yield QTLs and the drought-response traits they confer, and the need to evaluate the optimal combinations of QTLs that complement each other when present in a common genetic background. PMID:25680791

Mechanical properties and microstructural change of W–Y2O3 alloy under helium irradiation

PubMed Central

Tan, Xiaoyue; Luo, Laima; Chen, Hongyu; Zhu, Xiaoyong; Zan, Xiang; Luo, Guangnan; Chen, Junling; Li, Ping; Cheng, Jigui; Liu, Dongping; Wu, Yucheng

2015-01-01

A wet-chemical method combined with spark plasma sintering was used to prepare a W–Y2O3 alloy. High-temperature tensile tests and nano-indentation microhardness tests were used to characterize the mechanical properties of the alloy. After He-ion irradiation, fuzz and He bubbles were observed on the irradiated surface. The irradiation embrittlement was reflected by the crack indentations formed during the microhardness tests. A phase transformation from α-W to γ-W was investigated by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Polycrystallization and amorphization were also observed in the irradiation damage layer. The W materials tended to exhibit lattice distortion, amorphization, polycrystallization and phase transformation under He-ion irradiation. The transformation mechanism predicted by the atomic lattice model was consistent with the available experimental observations. These findings clarify the mechanism of the structural transition of W under ion irradiation and provide a clue for identifying materials with greater irradiation resistance. PMID:26227480

Mechanical behavior of glass/epoxy composite laminate with varying amount of MWCNTs under different loadings

NASA Astrophysics Data System (ADS)

Singh, K. K.; Rawat, Prashant

2018-05-01

This paper investigates the mechanical response of three phased (glass/MWCNTs/epoxy) composite laminate under three different loadings. Flexural strength, short beam strength and low-velocity impact (LVI) testing are performed to find an optimum doping percentage value for maximum enhancement in mechanical properties. In this work, MWCNTs were used as secondary reinforcement for three-phased composite plate. MWCNT doping was done in a range of 0–4 wt% of the thermosetting matrix system. Symmetrical design eight layered glass/epoxy laminate with zero bending extension coupling laminate was fabricated using a hybrid method i.e. hand lay-up technique followed by vacuum bagging method. Ranging analysis of MWCNT mixing highlighted the enhancement in flexural, short beam strength and improvement in damage tolerance under LVI loading. While at higher doping wt%, agglomeration of MWCNTs are observed. Results of mechanical testing proposed an optimized doping value for maximum strength and damage resistance of the laminate.

Intercomparison of chemical mechanisms for air quality policy formulation and assessment under North American conditions.

PubMed

Derwent, Richard

2017-07-01

The intercomparison of seven chemical mechanisms for their suitability for air quality policy formulation and assessment is described. Box modeling techniques were employed using 44 sets of background environmental conditions covering North America to constrain the chemical development of the longer lived species. The selected mechanisms were modified to enable an unbiased assessment of the adequacy of the parameterizations of photochemical ozone production from volatile organic compound (VOC) oxidation in the presence of NO x . Photochemical ozone production rates responded differently to 30% NO x and VOC reductions with the different mechanisms, despite the striking similarities between the base-case ozone production rates. The 30% reductions in NO x and VOCs also produced changes in OH. The responses in OH to 30% reductions in NO x and VOCs appeared to be more sensitive to mechanism choice, compared with the responses in the photochemical ozone production rates. Although 30% NO x reductions generally led to decreases in OH, 30% reductions in VOCs led to increases in OH, irrespective of mechanism choice and background environmental conditions. The different mechanisms therefore gave different OH responses to NO x and VOC reductions and so would give different responses in terms of changes in the fate and behavior of air toxics, acidification and eutrophication, and fine particle formation compared with others, in response to ozone control strategies. Policymakers need to understand that there are likely to be inherent differences in the responses to ozone control strategies between different mechanisms, depending on background environmental conditions and the extents of NO x and VOC reductions under consideration. The purpose of this paper is to compare predicted ozone responses to NO x and VOC reductions with seven chemical mechanisms under North American conditions. The good agreement found between the tested mechanisms should provide some support for their

[Genetic mechanism and evolutionary significance of the origin of parthenogenetic insects].

PubMed

Wang, Cheng-Ye

2011-12-01

There is a high proportion of parthenogenesis in insecta, and the parthenogenetic potential of insects is an important but often ignored threaten factor for the agricultural and forestry production. The maintenance of parthenogenetic species is a puzzling issue in evolutionary biology. In recent years, although the cellular mechanisms during parthenogenesis in some species have been well studied, the underlying genetic mechanisms that cause the switch from sexual reproduction to parthenogenesis have not been defined. While, understanding the genetic mechanism and evolutionary significance of the origin of parthenogenetic insects is crucial for preventing the pests in agricultural and forestry production. Here we summarized recent studies aimed at identifying the underlying genetic mechanism of parthenogenesis in insects, and briefly discussed its potential application in this filed.

Supersymmetric quantum mechanics: Engineered hierarchies of integrable potentials and related orthogonal polynomials

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

Balondo Iyela, Daddy; Centre for Cosmology, Particle Physics and Phenomenology; Département de Physique, Université de Kinshasa

2013-09-15

Within the context of supersymmetric quantum mechanics and its related hierarchies of integrable quantum Hamiltonians and potentials, a general programme is outlined and applied to its first two simplest illustrations. Going beyond the usual restriction of shape invariance for intertwined potentials, it is suggested to require a similar relation for Hamiltonians in the hierarchy separated by an arbitrary number of levels, N. By requiring further that these two Hamiltonians be in fact identical up to an overall shift in energy, a periodic structure is installed in the hierarchy which should allow for its resolution. Specific classes of orthogonal polynomials characteristicmore » of such periodic hierarchies are thereby generated, while the methods of supersymmetric quantum mechanics then lead to generalised Rodrigues formulae and recursion relations for such polynomials. The approach also offers the practical prospect of quantum modelling through the engineering of quantum potentials from experimental energy spectra. In this paper, these ideas are presented and solved explicitly for the cases N= 1 and N= 2. The latter case is related to the generalised Laguerre polynomials, for which indeed new results are thereby obtained. In the context of dressing chains and deformed polynomial Heisenberg algebras, some partial results for N⩾ 3 also exist in the literature, which should be relevant to a complete study of the N⩾ 3 general periodic hierarchies.« less

Formation of the imidazolides of dinucleotides under potentially prebiotic conditions

NASA Technical Reports Server (NTRS)

Sleeper, H. L.; Lohrmann, R.; Orgel, L. E.

1978-01-01

Imidazolides of dinucleotides such as ImpApA can be formed from the corresponding dinucleotides in a two-stage process, which gives up to 15% yields under potentially prebiotic conditions. First a solution of the dinucleotide and sodium trimetaphosphate is dried out at constant temperature and humidity. This produces polyphosphates such as p(n)ApA in excellent yield (greater than or equal to 80%). The products are dissolved in water, imidazole is added, and the solution is dried out again. This yields the 5'-phosphorimidazolides.

Micro-mechanical damage of trabecular bone-cement interface under selected loading conditions: a finite element study.

PubMed

Zhang, Qing-Hang; Tozzi, Gianluca; Tong, Jie

2014-01-01

In this study, two micro finite element models of trabecular bone-cement interface developed from high resolution computed tomography (CT) images were loaded under compression and validated using the in situ experimental data. The models were then used under tension and shear to examine the load transfer between the bone and cement and the micro damage development at the bone-cement interface. In addition, one models was further modified to investigate the effect of cement penetration on the bone-cement interfacial behaviour. The simulated results show that the load transfer at the bone-cement interface occurred mainly in the bone cement partially interdigitated region, while the fully interdigitated region seemed to contribute little to the mechanical response. Consequently, cement penetration beyond a certain value would seem to be ineffective in improving the mechanical strength of trabecular bone-cement interface. Under tension and shear loading conditions, more cement failures were found in denser bones, while the cement damage is generally low under compression.

Skin transcriptome reveals the intrinsic molecular mechanisms underlying hair follicle cycling in Cashmere goats under natural and shortened photoperiod conditions.

PubMed

Yang, Min; Song, Shen; Dong, Kunzhe; Chen, XiaoFei; Liu, Xuexue; Rouzi, Marhaba; Zhao, Qianjun; He, Xiaohong; Pu, Yabin; Guan, Weijun; Ma, Yuehui; Jiang, Lin

2017-10-18

The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. However, the underlying molecular mechanism remains unclear. We profiled the skin transcriptome of six goats at seven time points during hair follicle cycling via RNA-seq. The six goats comprised three goats exposed to a natural photoperiod and three exposed to a shortened photoperiod. During hair cycle transition, 1713 genes showed differential expression, and 332 genes showed a pattern of periodic expression. Moreover, a short photoperiod induced the hair follicle to enter anagen early, and 246 genes overlapped with the periodic genes. Among these key genes, cold-shock domain containing C2 (CSDC2) was highly expressed in the epidermis and dermis of Cashmere goat skin, although its function in hair-follicle development remains unknown. CSDC2 silencing in mouse fibroblasts resulted in the decreased mRNA expression of two key hair-follicle factors, leading to reduced cell numbers and a lower cell density. Cashmere growth or molting might be controlled by a set of periodic regulatory genes. The appropriate management of short light exposure can induce hair follicles to enter full anagen early through the activation of these regulators. The CSDC2 gene is a potentially important transcription factor in the hair growth cycle.

High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief.

PubMed

Arle, Jeffrey E; Mei, Longzhi; Carlson, Kristen W; Shils, Jay L

2016-06-01

Spinal cord stimulation (SCS) treats neuropathic pain through retrograde stimulation of dorsal column axons and their inhibitory effects on wide dynamic range (WDR) neurons. Typical SCS uses frequencies from 50-100 Hz. Newer stimulation paradigms use high-frequency stimulation (HFS) up to 10 kHz and produce pain relief but without paresthesia. Our hypothesis is that HFS preferentially blocks larger diameter axons (12-15 µm) based on dynamics of ion channel gates and the electric potential gradient seen along the axon, resulting in inhibition of WDR cells without paresthesia. We input field potential values from a finite element model of SCS into an active axon model with ion channel subcomponents for fiber diameters 1-20 µm and simulated dynamics on a 0.001 msec time scale. Assuming some degree of wave rectification seen at the axon, action potential (AP) blockade occurs as hypothesized, preferentially in larger over smaller diameters with blockade in most medium and large diameters occurring between 4.5 and 10 kHz. Simulations show both ion channel gate and virtual anode dynamics are necessary. At clinical HFS frequencies and pulse widths, HFS preferentially blocks larger-diameter fibers and concomitantly recruits medium and smaller fibers. These effects are a result of interaction between ion gate dynamics and the "activating function" (AF) deriving from current distribution over the axon. The larger fibers that cause paresthesia in low-frequency simulation are blocked, while medium and smaller fibers are recruited, leading to paresthesia-free neuropathic pain relief by inhibiting WDR cells. © 2016 International Neuromodulation Society.

Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)

PubMed Central

2014-01-01

The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

[Analysis on risk factors of endotracheal cuff under inflation in mechanically ventilated patients].

PubMed

Fu, You; Xi, Xiuming

2014-12-01

To investigate the prevalent condition of endotracheal cuff pressure and risk factors for under inflation. A prospective cohort study was conducted. Patients admitted to the Department of Critical Care Medicine of Fuxing Hospital Affiliated to Capital Medical University, who were intubated with a high-volume low-pressure endotracheal tube, and had undergone mechanical ventilation for at least 48 hours, were enrolled. The endotracheal cuff pressure was determined every 8 hours by a manual manometer connected to the distal edge of the valve cuff at 07 : 00, 15 : 00, and 23 : 00. Measurement of the endotracheal cuff pressure was continued until the extubation of endotracheal or tracheostomy tube, or death of the patient. According to the incidence of under inflation of endotracheal cuff, patients were divided into the incidence of under inflation lower than 25% group (lower low cuff pressure group) and higher than 25% group (higher low cuff pressure group). The possible influencing factors were evaluated in the two groups, including body mass index (BMI), size of endotracheal tube, duration of intubation, use of sedative or analgesic, number of leaving from intensive care unit (ICU), the number of turning over the patients, and aspiration of sputum. Logistic regression analysis was used to determine risk factors for under-inflation of the endotracheal cuff. During the study period, 53 patients were enrolled. There were 812 measurements, and 46.3% of them was abnormal, and 204 times (25.1%) of under inflation of endotracheal cuff were found. There were 24 patients (45.3%) in whom the incidence of under inflation rate was higher than 25%. The average of under inflation was 7 (4, 10) times. Compared with the group with lower rate of low cuff pressure, a longer time for intubation was found in group with higher rate of low cuff pressure [hours: 162 (113, 225) vs. 118 (97, 168), Z=-2.034, P=0.042]. There were no differences between the two groups in other factors

Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

PubMed

Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

2017-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x

The underlying mechanism of action for various medicinal properties of Piper betle (betel).

PubMed

Haslan, H; Suhaimi, F H; Thent, Zar Chi; Das, S

2015-01-01

Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.

Oscillatory electroosmotic flow in a parallel-plate microchannel under asymmetric zeta potentials

NASA Astrophysics Data System (ADS)

Peralta, M.; Arcos, J.; Méndez, F.; Bautista, O.

2017-06-01

In this work, we conduct a theoretical analysis of the start-up of an oscillatory electroosmotic flow (EOF) in a parallel-plate microchannel under asymmetric zeta potentials. It is found that the transient evolution of the flow field is controlled by the parameters {R}ω , {R}\\zeta , and \\bar{κ }, which represent the dimensionless frequency, the ratio of the zeta potentials of the microchannel walls, and the electrokinetic parameter, which is defined as the ratio of the microchannel height to the Debye length. The analysis is performed for both low and high zeta potentials; in the former case, an analytical solution is derived, whereas in the latter, a numerical solution is obtained. These solutions provide the fundamental characteristics of the oscillatory EOFs for which, with suitable adjustment of the zeta potential and the dimensionless frequency, the velocity profiles of the fluid flow exhibit symmetric or asymmetric shapes.

Deciphering potential mechanisms of anaerobic soil disinfestation (ASD)-mediated control of Pratylenchus penetrans

USDA-ARS?s Scientific Manuscript database

Pratylenchus penetrans is a component of the apple replant disease (ARD) causal pathogen complex. The potential role for biological mechanisms contributing to ASD-mediated suppression of P. penetrans was examined in greenhouse study using orchard soil with a history of ARD. Populations of P. penetra...

Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.

PubMed

Brose, Stephen A; Golovko, Svetlana A; Golovko, Mikhail Y

2016-01-01

Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

PubMed Central

Brose, Stephen A.; Golovko, Svetlana A.; Golovko, Mikhail Y.

2016-01-01

Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on NADH2+/NAD+ and NADPH2+/NADP+ ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased NADH2+/NAD+ and NADPH2+/NADP+ ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke. PMID:27965531

Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

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

Kadhim, Munira A

2012-08-22

The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electronmore » track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell

Epigenetic mechanisms in heart development and disease.

PubMed

Martinez, Shannalee R; Gay, Maresha S; Zhang, Lubo

2015-07-01

Suboptimal intrauterine development has been linked to predisposition to cardiovascular disease in adulthood, a concept termed 'developmental origins of health and disease'. Although the exact mechanisms underlying this developmental programming are unknown, a growing body of evidence supports the involvement of epigenetic regulation. Epigenetic mechanisms such as DNA methylation, histone modifications and micro-RNA confer added levels of gene regulation without altering DNA sequences. These modifications are relatively stable signals, offering possible insight into the mechanisms underlying developmental origins of health and disease. This review will discuss the role of epigenetic mechanisms in heart development as well as aberrant epigenetic regulation contributing to cardiovascular disease. Additionally, we will address recent advances targeting epigenetic mechanisms as potential therapeutic approaches to cardiovascular disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models

PubMed Central

Davis, Brian W.; Seabury, Christopher M.; Brashear, Wesley A.; Li, Gang; Roelke-Parker, Melody; Murphy, William J.

2015-01-01

The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented “rule of speciation.” We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the “Large X-Effect” in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. PMID:26006188

Nano-opto-electro-mechanical systems

NASA Astrophysics Data System (ADS)

Midolo, Leonardo; Schliesser, Albert; Fiore, Andrea

2018-01-01

A new class of hybrid systems that couple optical, electrical and mechanical degrees of freedom in nanoscale devices is under development in laboratories worldwide. These nano-opto-electro-mechanical systems (NOEMS) offer unprecedented opportunities to control the flow of light in nanophotonic structures, at high speed and low power consumption. Drawing on conceptual and technological advances from the field of optomechanics, they also bear the potential for highly efficient, low-noise transducers between microwave and optical signals, in both the classical and the quantum domains. This Perspective discusses the fundamental physical limits of NOEMS, reviews the recent progress in their implementation and suggests potential avenues for further developments in this field.

Fracture Mechanisms of Zirconium Diboride Ultra-High Temperature Ceramics under Pulse Loading

NASA Astrophysics Data System (ADS)

Skripnyak, Vladimir V.; Bragov, Anatolii M.; Skripnyak, Vladimir A.; Lomunov, Andrei K.; Skripnyak, Evgeniya G.; Vaganova, Irina K.

2015-06-01

Mechanisms of failure in ultra-high temperature ceramics (UHTC) based on zirconium diboride under pulse loading were studied experimentally by the method of SHPB and theoretically using the multiscale simulation method. The obtained experimental and numerical data are evidence of the quasi-brittle fracture character of nanostructured zirconium diboride ceramics under compression and tension at high strain rates and the room temperatures. Damage of nanostructured porous zirconium diboride -based UHTC can be formed under stress pulse amplitude below the Hugoniot elastic limit. Fracture of nanostructured ultra-high temperature ceramics under pulse and shock-wave loadings is provided by fast processes of intercrystalline brittle fracture and relatively slow processes of quasi-brittle failure via growth and coalescence of microcracks. A decrease of the shear strength can be caused by nano-voids clusters in vicinity of triple junctions between ceramic matrix grains and ultrafine-grained ceramics. This research was supported by grants from ``The Tomsk State University Academic D.I. Mendeleev Fund Program'' and also N. I. Lobachevski State University of Nizhny Novgorod (Grant of post graduate mobility).

2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications

PubMed Central

Ardura, Juan Antonio; Corton, Marta; Fernández-Fernández, Beatriz; Aguilera, Oscar; Gomez-Guerrero, Carmen; Mas, Sebastián; Moreno, Juan Antonio; Ruiz-Ortega, Marta; Sanz, Ana Belen; Sanchez-Niño, Maria Dolores; Rojo, Federico; Vivanco, Fernando; Esbrit, Pedro; Ayuso, Carmen; Alvarez-Llamas, Gloria; Egido, Jesús; García-Foncillas, Jesús; Ortiz, Alberto

2017-01-01

Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer. PMID:28060743

Three-Month-Olds' Visual Preference for Faces and Its Underlying Visual Processing Mechanisms

ERIC Educational Resources Information Center

Turati, C.; Valenza, E.; Leo, I.; Simion, F.

2005-01-01

This study was aimed at investigating the face preference phenomenon and its underlying mechanisms at 3 months of age. Using an eye-tracker apparatus, Experiment 1 demonstrated that 3-month-olds prefer natural face images to unnatural ones, replicating and extending previous evidence obtained with schematic facelike stimuli. Experiments 2 and 3…

Potential mechanisms for low uric acid in Parkinson disease

PubMed Central

Young, Sarah; Rosen, Ami; Bernhard, Douglas; Millington, David; Factor, Stewart

2018-01-01

Several epidemiologic studies have described an association between low serum uric acid (UA) and Parkinson disease (PD). Uric acid is a known antioxidant, and one proposed mechanism of neurodegeneration in PD is oxidative damage of dopamine neurons. However, other complex metabolic pathways may contribute. The purpose of this study is to elucidate potential mechanisms of low serum UA in PD. Subjects who met diagnostic criteria for definite or probable PD (n = 20) and controls (n = 20) aged 55–80 years were recruited. Twenty-four hour urine samples were collected from all participants, and both uric acid and allantoin were measured and corrected for body mass index (BMI). Urinary metabolites were compared using a twoway ANOVA with diagnosis and sex as the explanatory variables. There were no significant differences between PD and controls for total UA (p = 0.60), UA corrected for BMI (p = 0.37), or in the interaction of diagnosis and sex on UA (p = 0.24). Similarly, there were no significant differences between PD and controls for allantoin (p = 0.47), allantoin corrected for BMI (p = 0.57), or in the interaction of diagnosis and sex on allantoin (p = 0.78). Allantoin/UA ratios also did not significantly differ by diagnosis (p = 0.99). Our results imply that low serum UA in PD may be due to an intrinsic mechanism that alters the homeostatic set point for serum UA in PD, and may contribute to relatively lower protection against oxidative damage. These findings provide indirect support for neuroprotection trials aimed at raising serum UA. PMID:26747026

Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

PubMed

Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

2016-01-26

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

Spin- and Valley-Dependent Electronic Structure in Silicene Under Periodic Potentials

NASA Astrophysics Data System (ADS)

Lu, Wei-Tao; Li, Yun-Fang; Tian, Hong-Yu

2018-03-01

We study the spin- and valley-dependent energy band and transport property of silicene under a periodic potential, where both spin and valley degeneracies are lifted. It is found that the Dirac point, miniband, band gap, anisotropic velocity, and conductance strongly depend on the spin and valley indices. The extra Dirac points appear as the voltage potential increases, the critical values of which are different for electron with different spins and valleys. Interestingly, the velocity is greatly suppressed due to the electric field and exchange field, other than the gapless graphene. It is possible to achieve an excellent collimation effect for a specific spin near a specific valley. The spin- and valley-dependent band structure can be used to adjust the transport, and perfect transmissions are observed at Dirac points. Therefore, a remarkable spin and valley polarization is achieved which can be switched effectively by the structural parameters. Importantly, the spin and valley polarizations are greatly enhanced by the disorder of the periodic potential.

Engineered Potentials and Dynamics of Ultracold Quantum Gases Under the Microscope

DTIC Science & Technology

2014-05-09

CONTRACT OR GRANT NUMBER: DESCRIPTION OF MATERIAL INSTITUTION: PRINCIPAL INVESTIGATOR: Paola Cappellaro TYPE REPORT: Ph.D. Dissertation PERIOD...CONTRACT NUMBER Engineered potentials and dynamics of ulu·acold quantum gases W911NF-11-1-0400 under the microscope Sb. GRANT NUMBER Sc. PROGRAM...Schnorrberger, M. Moreno- Cardoner , S. Fölling, and I. Bloch, “Counting atoms using interaction blockade in an optical superlat- tice,” Phys. Rev. Lett

Framework flexibility of ZIF-8 under liquid intrusion: discovering time-dependent mechanical response and structural relaxation.

PubMed

Sun, Yueting; Li, Yibing; Tan, Jin-Chong

2018-04-18

The structural flexibility of a topical zeolitic imidazolate framework with sodalite topology, termed ZIF-8, has been elucidated through liquid intrusion under moderate pressures (i.e. tens of MPa). By tracking the evolution of water intrusion pressure under cyclic conditions, we interrogate the role of the gate-opening mechanism controlling the size variation of the pore channels of ZIF-8. Interestingly, we demonstrate that its channel deformation is recoverable through structural relaxation over time, hence revealing the viscoelastic mechanical response in ZIF-8. We propose a simple approach employing a glycerol-water solution mixture, which can significantly enhance the sensitivity of intrusion pressure for the detection of structural deformation in ZIF-8. By leveraging the time-dependent gate-opening phenomenon in ZIF-8, we achieved a notable improvement (50%) in energy dissipation during multicycle mechanical deformation experiments.

First-principles predictions of structural, mechanical and electronic properties of βTiNb under high pressure

NASA Astrophysics Data System (ADS)

Wang, Z. P.; Fang, Q. H.; Li, J.; Liu, B.

2018-04-01

Structural, mechanical and electronic properties of βTiNb alloy under high pressure have been investigated based on the density functional theory (DFT). The dependences of dimensionless volume ratio, elastic constants, bulk modulus, Young's modulus, shear modulus, ductile/brittle, anisotropy and Poisson's ratio on applied pressure are all calculated successfully. The results reveal that βTiNb alloy is mechanically stable under pressure below 23.45 GPa, and the pressure-induced phase transformation could occur beyond this critical value. Meanwhile, the applied pressure can effectively promote the mechanical properties of βTiNb alloy, including the resistances to volume change, elastic deformation and shear deformation, as well as the material ductility and metallicity. Furthermore, the calculated electronic structures testify that βTiNb alloy performs the metallicity and the higher pressure reduces the structural stability of unit cell.