A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

PubMed

Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ Health Perspect 124:1034-1041; http://dx.doi.org/10.1289/ehp.1510308.

A generalized theory of preferential linking

NASA Astrophysics Data System (ADS)

Hu, Haibo; Guo, Jinli; Liu, Xuan; Wang, Xiaofan

2014-12-01

There are diverse mechanisms driving the evolution of social networks. A key open question dealing with understanding their evolution is: How do various preferential linking mechanisms produce networks with different features? In this paper we first empirically study preferential linking phenomena in an evolving online social network, find and validate the linear preference. We propose an analyzable model which captures the real growth process of the network and reveals the underlying mechanism dominating its evolution. Furthermore based on preferential linking we propose a generalized model reproducing the evolution of online social networks, and present unified analytical results describing network characteristics for 27 preference scenarios. We study the mathematical structure of degree distributions and find that within the framework of preferential linking analytical degree distributions can only be the combinations of finite kinds of functions which are related to rational, logarithmic and inverse tangent functions, and extremely complex network structure will emerge even for very simple sublinear preferential linking. This work not only provides a verifiable origin for the emergence of various network characteristics in social networks, but bridges the micro individuals' behaviors and the global organization of social networks.

Immunological mechanisms behind the cystic fibrosis-ABPA link.

PubMed

Hartl, Dominik

2009-01-01

Allergic bronchopulmonary aspergillosis (ABPA), a pulmonary hypersensitivity disease mediated by an allergic response to Aspergillus fumigatus (A. fumigatus), occurs preferentially in disease conditions with an impaired pulmonary immunity, especially in cystic fibrosis (CF) and allergic asthma. The pathophysiological mechanisms underlying the link between CF and ABPA are poorly understood. Animal and human data support a critical role for chemokines, especially CCL17 and its receptor CCR4, in ABPA. A summary and discussion of the immunological mechanism involved in the pathogenesis of ABPA with a focus on CF lung disease and the role of chemokines is presented here.

Effect of surface modification on protein retention and cell proliferation under strain.

PubMed

Dunkers, J P; Lee, H-J; Matos, M A; Pakstis, L M; Taboas, J M; Hudson, S D; Cicerone, M T

2011-07-01

When culturing cells on flexible surfaces, it is important to consider extracellular matrix treatments that will remain on the surface under mechanical strain. Here we investigate differences in laminin deposited on oxidized polydimethylsiloxane (PDMS) with plasma treatment (plasma-only) vs. plasma and aminopropyltrimethoxysilane treatment (silane-linked). We use specular X-ray reflectivity (SXR), transmission electron microscopy (TEM), and immunofluorescence to probe the quantity and uniformity of laminin. The surface coverage of laminin is approximately 45% for the plasma-only and 50% for the silane-linked treatment as determined by SXR. TEM and immunofluorescence reveal additional islands of laminin aggregates on the plasma-only PDMS compared with the relatively smooth and uniform silane-linked laminin surface. We also examine laminin retention under strain and vascular smooth muscle cell viability and proliferation under static and strain conditions. Equibiaxial stretching of the PDMS surfaces shows greatly improved retention of the silane-linked laminin over plasma-only. There are significantly more cells on the silane-linked surface after 4 days of equibiaxial strain. Published by Elsevier Ltd.

Chronic stress and illness in children: the role of allostatic load.

PubMed

Johnston-Brooks, C H; Lewis, M A; Evans, G W; Whalen, C K

1998-01-01

Recent studies of stress have highlighted the contributions of chronic psychological and environmental stressors to health and well-being. Children may be especially vulnerable to the negative effects of chronic stressors. Allostasis, the body's ability to adapt and adjust to environmental demands, has been proposed as an explanatory mechanism for the stress-health link, yet empirical evidence is minimal. This study tested the proposition that allostasis may be an underlying physiological mechanism linking chronic stress to poor health outcomes in school-aged children. Specifically, we examined whether allostasis would mediate or moderate the link between chronic stress and health. To test the hypothesis that allostasis contributes to the relation between chronic stress and poor health, we examined household density as a chronic environmental stressor, cardiovascular reactivity (CVR) as a marker of allostatic load, and number of school absences due to illness as the health outcome in a sample of 81 boys. Structural equation modeling indicated that the mediating model fit the data well, accounting for 17% of the variance in days ill. Results provide the first evidence that CVR may mediate the relation between household density and medical illness in children. More generally, these findings support the role of allostasis as an underlying mechanism in the link between chronic stress and health.

Post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon lithography [A post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon polymerization

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

Oakdale, James S.; Ye, Jianchao; Smith, William L.

Here, two photon polymerization (TPP) is a precise, reliable, and increasingly popular technique for rapid prototyping of micro-scale parts with sub-micron resolution. The materials of choice underlying this process are predominately acrylic resins cross-linked via free-radical polymerization. Due to the nature of the printing process, the derived parts are only partially cured and the corresponding mechanical properties, i.e. modulus and ultimate strength, are lower than if the material were cross-linked to the maximum extent. Herein, post-print curing via UV-driven radical generation, is demonstrated to increase the overall degree of cross-linking of low density, TPP-derived structures.

Post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon lithography [A post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon polymerization

DOE PAGES

Oakdale, James S.; Ye, Jianchao; Smith, William L.; ...

2016-11-28

Here, two photon polymerization (TPP) is a precise, reliable, and increasingly popular technique for rapid prototyping of micro-scale parts with sub-micron resolution. The materials of choice underlying this process are predominately acrylic resins cross-linked via free-radical polymerization. Due to the nature of the printing process, the derived parts are only partially cured and the corresponding mechanical properties, i.e. modulus and ultimate strength, are lower than if the material were cross-linked to the maximum extent. Herein, post-print curing via UV-driven radical generation, is demonstrated to increase the overall degree of cross-linking of low density, TPP-derived structures.

Intimate Partner Violence and Coparenting across the Transition to Parenthood

ERIC Educational Resources Information Center

Kan, Marni L.; Feinberg, Mark E.; Solmeyer, Anna R.

2012-01-01

Intimate partner violence (IPV) between parents has been linked to negative parenting and child maladjustment, yet the mechanisms underlying this association are not fully understood. Based on a theory that violence among parents disrupts the coparental alliance--which has been linked to parenting quality and child adjustment--the authors examined…

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

EPA Science Inventory

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying ...

Effect of fog on free-space optical links employing imaging receivers.

PubMed

Mahalati, Reza Nasiri; Kahn, Joseph M

2012-01-16

We analyze free-space optical links employing imaging receivers in the presence of misalignment and atmospheric effects, such as haze, fog or rain. We present a detailed propagation model based on the radiative transfer equation. We also compare the relative importance of two mechanisms by which these effects degrade link performance: signal attenuation and image blooming. We show that image blooming dominates over attenuation, except under medium-to-heavy fog conditions.

Translational control of aberrant stress responses as a hallmark of cancer.

PubMed

El-Naggar, Amal M; Sorensen, Poul H

2018-04-01

Altered mRNA translational control is emerging as a critical factor in cancer development and progression. Targeting specific elements of the translational machinery, such as mTORC1 or eIF4E, is emerging as a new strategy for innovative cancer therapy. While translation of most mRNAs takes place through cap-dependent mechanisms, a sub-population of cellular mRNA species, particularly stress-inducible mRNAs with highly structured 5'-UTR regions, are primarily translated through cap-independent mechanisms. Intriguingly, many of these mRNAs encode proteins that are involved in tumour cell adaptation to microenvironmental stress, and thus linked to aggressive behaviour including tumour invasion and metastasis. This necessitates a rigorous search for links between microenvironmental stress and aggressive tumour phenotypes. Under stress, cells block global protein synthesis to preserve energy while maintaining selective synthesis of proteins that support cell survival. One highly conserved mechanism to regulate protein synthesis under cell stress is to sequester mRNAs into cytosolic aggregates called stress granules (SGs), where their translation is silenced. SGs confer survival advantages and chemotherapeutic resistance to tumour cells under stress. Recently, it has been shown that genetically blocking SG formation dramatically reduces tumour invasive and metastatic capacity in vivo. Therefore, targeting SG formation might represent a potential treatment strategy to block cancer metastasis. Here, we present the critical link between selective mRNA translation, stress adaptation, SGs, and tumour progression. Further, we also explain how deciphering mechanisms of selective mRNA translation occurs under cell stress holds great promise for the identification of new targets in the treatment of cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Organically linked iron oxide nanoparticle supercrystals with exceptional isotropic mechanical properties.

PubMed

Dreyer, Axel; Feld, Artur; Kornowski, Andreas; Yilmaz, Ezgi D; Noei, Heshmat; Meyer, Andreas; Krekeler, Tobias; Jiao, Chengge; Stierle, Andreas; Abetz, Volker; Weller, Horst; Schneider, Gerold A

2016-05-01

It is commonly accepted that the combination of the anisotropic shape and nanoscale dimensions of the mineral constituents of natural biological composites underlies their superior mechanical properties when compared to those of their rather weak mineral and organic constituents. Here, we show that the self-assembly of nearly spherical iron oxide nanoparticles in supercrystals linked together by a thermally induced crosslinking reaction of oleic acid molecules leads to a nanocomposite with exceptional bending modulus of 114 GPa, hardness of up to 4 GPa and strength of up to 630 MPa. By using a nanomechanical model, we determined that these exceptional mechanical properties are dominated by the covalent backbone of the linked organic molecules. Because oleic acid has been broadly used as nanoparticle ligand, our crosslinking approach should be applicable to a large variety of nanoparticle systems.

Building Trust and Feeling Well: Examining Intraindividual and Interpersonal Outcomes and Underlying Mechanisms of Listening

ERIC Educational Resources Information Center

Lloyd, Karina J.; Boer, Diana; Kluger, Avraham N.; Voelpel, Sven C.

2015-01-01

We investigated perceived listening quality in relation to individual (self-clarity and emotional well-being) and dyadic variables (social attraction and trust). Specifically, we proposed that the link between perceived listening quality and emotional well-being is mediated by self-clarity, and that the link between perceived listening and trust…

Executive Function as a Mediator in the Link between Attention-Deficit/Hyperactivity Disorder and Social Problems

ERIC Educational Resources Information Center

Tseng, Wan-Ling; Gau, Susan Shur-Fen

2013-01-01

Background: Cognitive processes and mechanisms underlying the strong link between attention-deficit/hyperactivity disorder (ADHD) and social problems remain unclear. Limited knowledge also exists regarding a subgroup of youth with ADHD who do not have social problems. This study investigated the extent to which executive function (EF) mediated the…

School Segregation and Racial Academic Achievement Gaps. CEPA Working Paper No. 15-12

ERIC Educational Resources Information Center

Reardon, Sean F.

2015-01-01

Although it is clear that racial segregation is linked to academic achievement gaps, the mechanisms underlying this link have been debated since Coleman published his eponymous 1966 report. In this paper, I examine 16 distinct measures of segregation to determine which is most strongly associated with academic achievement gaps. I find very clear…

Unlocking the Black Box: Exploring the Link between High-Performance Work Systems and Performance

ERIC Educational Resources Information Center

Messersmith, Jake G.; Patel, Pankaj C.; Lepak, David P.

2011-01-01

With a growing body of literature linking systems of high-performance work practices to organizational performance outcomes, recent research has pushed for examinations of the underlying mechanisms that enable this connection. In this study, based on a large sample of Welsh public-sector employees, we explored the role of several individual-level…

Towards aging mechanisms of cross-linked polyethylene (XLPE) cable insulation materials in nuclear power plants

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

Liu, Shuaishuai; Fifield, Leonard S.; Bowler, Nicola

Cross-linked polyethylene (XLPE) cable insulation material undergoes simultaneous, accelerated thermal and gamma-radiation aging to simulate the long-term aging environment within nuclear power plants (NPPs). A variety of materials characterization tests, including scanning electron microscopy, thermo-gravimetric analysis, differential scanning calorimetry, oxidation induction time, gel-fraction and dielectric properties measurement, are conducted on pristine and differently aged XLPE samples. A preliminary model of one possible aging mechanism of XLPE cable insulation material under gamma radiation at elevated temperature of 115 °C is suggested.

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

ERIC Educational Resources Information Center

Herts, Kate L.; McLaughlin, Katie A.; Hatzenbuehler, Mark L.

2012-01-01

Exposure to stress is associated with a wide range of internalizing and externalizing problems in adolescents, including aggressive behavior. Extant research examining mechanisms underlying the associations between stress and youth aggression has consistently identified social information processing pathways that are disrupted by exposure to…

pH-Mediated Fluorescent Polymer Particles and Gel from Hyperbranched Polyethylenimine and the Mechanism of Intrinsic Fluorescence.

PubMed

Liu, Shi Gang; Li, Na; Ling, Yu; Kang, Bei Hua; Geng, Shuo; Li, Nian Bing; Luo, Hong Qun

2016-02-23

We report that fluorescence properties and morphology of hyperbranched polyethylenimine (hPEI) cross-linked with formaldehyde are highly dependent on the pH values of the cross-linking reaction. Under acidic and neutral conditions, water-soluble fluorescent copolymer particles (CPs) were produced. However, under basic conditions, white gels with weak fluorescence emission would be obtained. The water-soluble hPEI-formaldehyde (hPEI-F) CPs show strong intrinsic fluorescence without the conjugation to any classical fluorescent agents. By the combination of spectroscopy and microscopy techniques, the mechanism of fluorescence emission was discussed. We propose that the intrinsic fluorescence originates from the formation of a Schiff base in the cross-linking process between hPEI and formaldehyde. Schiff base bonds are the fluorescence-emitting moieties, and the compact structure of hPEI-F CPs plays an important role in their strong fluorescence emission. The exploration on fluorescence mechanism may provide a new strategy to prepare fluorescent polymer particles. In addition, the investigation shows that the hPEI-F CPs hold potential as a fluorescent probe for the detection of copper ions in aqueous media.

An investigation of the relationship between subjective sleep quality, loneliness and mood in an Australian sample: can daily routine explain the links?

PubMed

Smith, Simon Squire; Kozak, Nahum; Sullivan, Karen Anne

2012-03-01

Loneliness and low mood are associated with significant negative health outcomes including poor sleep, but the strength of the evidence underlying these associations varies. There is strong evidence that poor sleep quality and low mood are linked, but only emerging evidence that loneliness and poor sleep are associated. To independently replicate the finding that loneliness and poor subjective sleep quality are associated and to extend past research by investigating lifestyle regularity as a possible mediator of relationships, since lifestyle regularity has been linked to loneliness and poor sleep. Using a cross-sectional design, 97 adults completed standardized measures of loneliness, lifestyle regularity, subjective sleep quality and mood. Loneliness was a significant predictor of sleep quality. Lifestyle regularity was not a predictor of, nor associated with, mood, sleep quality or loneliness. This study provides an important independent replication of the association between poor sleep and loneliness. However, the mechanism underlying this link remains unclear. A theoretically plausible mechanism for this link, lifestyle regularity, does not explain the relationship between loneliness and poor sleep. The nexus between loneliness and poor sleep is unlikely to be broken by altering the social rhythm of patients who present with poor sleep and loneliness.

Observation of a ZZW female in a natural population: implications for avian sex determination.

PubMed Central

Arit, D; Bensch, S; Hansson, B; Hasselquist, D; Westerdahl, H

2004-01-01

Avian sex determination is chromosomal; however, the underlying mechanisms are not yet understood. There is no conclusive evidence for either of two proposed mechanisms: a dominant genetic switch or a dosage mechanism. No dominant sex-determining gene on the female-specific W chromosome has been found. Birds lack inactivation of one of the Z chromosomes in males, but seem to compensate for a double dose of Z-linked genes by other mechanisms. Recent studies showing female-specific expression of two genes may support an active role of the W chromosome. To resolve the question of avian sex determination the investigation of birds with a 2A: ZZW or 2A: ZO genotype would be decisive. Here, we report the case of an apparent 2A: ZZW great reed warbler (Acrocephalus arundinaceus) female breeding in a natural population, which was detected using Z-linked microsatellites. Our data strongly suggest a role of W-linked genes in avian sex determination. PMID:15252998

The Role of Inhibitory Control in the Production of Misinformation Effects

ERIC Educational Resources Information Center

MacLeod, Malcolm D.; Saunders, Jo

2005-01-01

Recent research has indicated a link between retrieval-induced forgetting and the production of misinformation effects (J. Saunders & M. D. MacLeod, 2002). The mechanism underlying this relationship, however, remains unclear. In an attempt to clarify this issue, the authors presented 150 participants with misinformation under conditions designed…

Attention Deficit Hyperactivity Disorder, Tic Disorder, and Allergy: Is There a Link? A Nationwide Population-Based Study

ERIC Educational Resources Information Center

Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Bai, Ya-Mei

2013-01-01

Background: Attention deficit hyperactivity disorder (ADHD) and tic disorder usually co-occur in the same individuals, but the underlying mechanisms remain unclear. Previous evidence has shown that a frequent coexistence of allergic diseases was noted in patients with ADHD or tic disorder. We attempted to investigate the possible link among ADHD,…

Kinetics versus thermodynamics in materials modeling: The case of the di-vacancy in iron

NASA Astrophysics Data System (ADS)

Djurabekova, F.; Malerba, L.; Pasianot, R. C.; Olsson, P.; Nordlund, K.

2010-07-01

Monte Carlo models are widely used for the study of microstructural and microchemical evolution of materials under irradiation. However, they often link explicitly the relevant activation energies to the energy difference between local equilibrium states. We provide a simple example (di-vacancy migration in iron) in which a rigorous activation energy calculation, by means of both empirical interatomic potentials and density functional theory methods, clearly shows that such a link is not granted, revealing a migration mechanism that a thermodynamics-linked activation energy model cannot predict. Such a mechanism is, however, fully consistent with thermodynamics. This example emphasizes the importance of basing Monte Carlo methods on models where the activation energies are rigorously calculated, rather than deduced from widespread heuristic equations.

Effect of link oriented self-healing on resilience of networks

NASA Astrophysics Data System (ADS)

Shang, Yilun

2016-08-01

Many real, complex systems, such as the human brain and skin with their biological networks or intelligent material systems consisting of composite functional liquids, exhibit a noticeable capability of self-healing. Here, we study a network model with arbitrary degree distributions possessing natural link oriented recovery mechanisms, whereby a failed link can be recovered if its two end nodes maintain a sufficient proportion of functional links. These mechanisms are pertinent for many spontaneous healing and manual repair phenomena, interpolating smoothly between complete healing and no healing scenarios. We show that the self-healing strategies have profound impact on resilience of homogeneous and heterogeneous networks employing a percolation threshold, fraction of giant cluster, and link robustness index. The self-healing effect induces distinct resilience characteristics for scale-free networks under random failures and intentional attacks, and a resilience crossover has been observed at certain level of self-healing. Our work highlights the significance of understanding the competition between healing and collapsing in the resilience of complex networks.

A Disease Mutation Causing Episodic Ataxia Type I in the S1 Links Directly to the Voltage Sensor and the Selectivity Filter in Kv Channels.

PubMed

Petitjean, Dimitri; Kalstrup, Tanja; Zhao, Juan; Blunck, Rikard

2015-09-02

The mutation F184C in Kv1.1 leads to development of episodic ataxia type I (EA1). Although the mutation has been said to alter activation kinetics and to lower expression, we show here that the underlying molecular mechanisms may be more complex. Although F184 is positioned in the "peripheral" S1 helix, it occupies a central position in the 3D fold. We show in cut-open oocyte voltage-clamp recordings of gating and ionic currents of the Shaker Kv channel expressed in Xenopus oocytes that F184 not only interacts directly with the gating charges of the S4, but also creates a functional link to the selectivity filter of the neighboring subunit. This link leads to impaired fast and slow inactivation. The effect on fast inactivation is of an allosteric nature considering that fast inactivation is caused by a linked cytosolic ball peptide. The extensive effects of F184C provide a new mechanism underlying EA. Episodic ataxia (EA) is an inherited disease that leads to occasional loss of motor control in combination with variable other symptoms such as vertigo or migraine. EA type I (EA1), studied here, is caused by mutations in a voltage-gated potassium channel that contributes to the generation of electrical signals in the brain. The mechanism by which mutations in voltage-gated potassium channels lead to EA is still unknown and there is no consistent pharmacological treatment. By studying in detail one disease-causing mutation in Kv1.1, we describe a novel molecular mechanism distinct from mechanisms described previously. This mechanism contributes to the understanding of potassium channel function in general and might lead to a better understanding of how EA develops. Copyright © 2015 the authors 0270-6474/15/3512198-09$15.00/0.

Obesity, Asthma, and Exercise in Child and Adolescent Health

PubMed Central

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

2018-01-01

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

Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state

PubMed Central

Verfaillie, Annelien; Imrichova, Hana; Atak, Zeynep Kalender; Dewaele, Michael; Rambow, Florian; Hulselmans, Gert; Christiaens, Valerie; Svetlichnyy, Dmitry; Luciani, Flavie; Van den Mooter, Laura; Claerhout, Sofie; Fiers, Mark; Journe, Fabrice; Ghanem, Ghanem-Elias; Herrmann, Carl; Halder, Georg; Marine, Jean-Christophe; Aerts, Stein

2015-01-01

Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading. Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event. This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively. Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors. Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma. Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance. PMID:25865119

Links between thermoregulation and aging in endotherms and ectotherms

PubMed Central

Flouris, Andreas D; Piantoni, Carla

2014-01-01

While the link between thermoregulation and aging is generally accepted, much further research, reflection, and debate is required to elucidate the physiological and molecular pathways that generate the observed thermal-induced changes in lifespan. Our aim in this review is to present, discuss, and scrutinize the thermoregulatory mechanisms that are implicated in the aging process in endotherms and ectotherms. Our analysis demonstrates that low body temperature benefits lifespan in both endothermic and ectothermic organisms. Research in endotherms has delved deeper into the physiological and molecular mechanisms linking body temperature and longevity. While research in ectotherms has been steadily increasing during the past decades, further mechanistic work is required in order to fully elucidate the underlying phenomena. What is abundantly clear is that both endotherms and ectotherms have a specific temperature zone at which they function optimally. This zone is defended through both physiological and behavioral means and plays a major role on organismal senescence. That low body temperature may be beneficial for lifespan is contrary to conventional medical theory where reduced body temperature is usually considered as a sign of underlying pathology. Regardless, this phenomenon has been targeted by scientists with the expectation that advancements may compress morbidity, as well as lower disease and mortality risk. The available evidence suggests that lowered body temperature may prolong life span, yet finding the key to temperature regulation remains the problem. While we are still far from a complete understanding of the mechanisms linking body temperature and longevity, we are getting closer. PMID:27226994

Barnacle cement: a polymerization model based on evolutionary concepts

PubMed Central

Dickinson, Gary H.; Vega, Irving E.; Wahl, Kathryn J.; Orihuela, Beatriz; Beyley, Veronica; Rodriguez, Eva N.; Everett, Richard K.; Bonaventura, Joseph; Rittschof, Daniel

2009-01-01

Summary Enzymes and biochemical mechanisms essential to survival are under extreme selective pressure and are highly conserved through evolutionary time. We applied this evolutionary concept to barnacle cement polymerization, a process critical to barnacle fitness that involves aggregation and cross-linking of proteins. The biochemical mechanisms of cement polymerization remain largely unknown. We hypothesized that this process is biochemically similar to blood clotting, a critical physiological response that is also based on aggregation and cross-linking of proteins. Like key elements of vertebrate and invertebrate blood clotting, barnacle cement polymerization was shown to involve proteolytic activation of enzymes and structural precursors, transglutaminase cross-linking and assembly of fibrous proteins. Proteolytic activation of structural proteins maximizes the potential for bonding interactions with other proteins and with the surface. Transglutaminase cross-linking reinforces cement integrity. Remarkably, epitopes and sequences homologous to bovine trypsin and human transglutaminase were identified in barnacle cement with tandem mass spectrometry and/or western blotting. Akin to blood clotting, the peptides generated during proteolytic activation functioned as signal molecules, linking a molecular level event (protein aggregation) to a behavioral response (barnacle larval settlement). Our results draw attention to a highly conserved protein polymerization mechanism and shed light on a long-standing biochemical puzzle. We suggest that barnacle cement polymerization is a specialized form of wound healing. The polymerization mechanism common between barnacle cement and blood may be a theme for many marine animal glues. PMID:19837892

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

PubMed

Nagy, Corina; Turecki, Gustavo

2012-08-01

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

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

PubMed Central

Nagy, Corina; Turecki, Gustavo

2017-01-01

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

Development and integration of high straightness flexure guiding mechanisms dedicated to the METAS watt balance Mark II

NASA Astrophysics Data System (ADS)

Cosandier, F.; Eichenberger, A.; Baumann, H.; Jeckelmann, B.; Bonny, M.; Chatagny, V.; Clavel, R.

2014-04-01

There is a firm will in the metrology community to redefine the kilogram in the International System of units by linking it to a fundamental physical constant. The watt balance is a promising way to link the mass unit to the Planck constant h. At the Federal Institute of Metrology METAS a second watt balance experiment is under development. A decisive part of the METAS Mark II watt balance is the mechanical linear guiding system. The present paper discusses the development and the metrological characteristics of two guiding systems that were conceived by the Laboratoire de Systèmes Robotiques of EPFL and built using flexure mechanical elements. Integration in the new setup is also described.

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility

PubMed Central

Lu, Xuemei; Shapiro, Joshua A.; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J.; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-01-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible. PMID:20511493

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility.

PubMed

Lu, Xuemei; Shapiro, Joshua A; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-08-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

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.

Structural Preferential Attachment: Network Organization beyond the Link

NASA Astrophysics Data System (ADS)

Hébert-Dufresne, Laurent; Allard, Antoine; Marceau, Vincent; Noël, Pierre-André; Dubé, Louis J.

2011-10-01

We introduce a mechanism which models the emergence of the universal properties of complex networks, such as scale independence, modularity and self-similarity, and unifies them under a scale-free organization beyond the link. This brings a new perspective on network organization where communities, instead of links, are the fundamental building blocks of complex systems. We show how our simple model can reproduce social and information networks by predicting their community structure and more importantly, how their nodes or communities are interconnected, often in a self-similar manner.

Common evolutionary trends underlie the four-bar linkage systems of sunfish and mantis shrimp.

PubMed

Hu, Yinan; Nelson-Maney, Nathan; Anderson, Philip S L

2017-05-01

Comparative biomechanics offers an opportunity to explore the evolution of disparate biological systems that share common underlying mechanics. Four-bar linkage modeling has been applied to various biological systems such as fish jaws and crustacean appendages to explore the relationship between biomechanics and evolutionary diversification. Mechanical sensitivity states that the functional output of a mechanical system will show differential sensitivity to changes in specific morphological components. We document similar patterns of mechanical sensitivity in two disparate four-bar systems from different phyla: the opercular four-bar system in centrarchid fishes and the raptorial appendage of stomatopods. We built dynamic linkage models of 19 centrarchid and 36 stomatopod species and used phylogenetic generalized least squares regression (PGLS) to compare evolutionary shifts in linkage morphology and mechanical outputs derived from the models. In both systems, the kinematics of the four-bar mechanism show significant evolutionary correlation with the output link, while travel distance of the output arm is correlated with the coupler link. This common evolutionary pattern seen in both fish and crustacean taxa is a potential consequence of the mechanical principles underlying four-bar systems. Our results illustrate the potential influence of physical principles on morphological evolution across biological systems with different structures, behaviors, and ecologies. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Chemo-physical properties of renal capsules under ultraviolet-c exposure

NASA Astrophysics Data System (ADS)

Baghapour, Sh.; Parvin, P.; Reyhani, A.; Mortazavi, S. Z.; Mokhtari, S.; Amjadi, A.

2014-08-01

The renal capsule tissue of lamb was irradiated with ultraviolet-C light and the treated samples were analyzed by uniaxial tensile test, dynamic mechanical analysis, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and contact angle measurements. It was shown that the skin cross-linking is dominant in low doses in accordance with the contact angle assessment. Conversely, the strong bulk degradation takes place at high doses. Similarly, the bulk cross-linking affects the mechanical tests as to enhance the stiffness at low doses, whereas strong degradation occurs at high doses that mainly arises from the strong bulk chain scission.

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

PubMed

Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

2017-01-01

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Multifunctional structural lithium ion batteries for electrical energy storage applications

NASA Astrophysics Data System (ADS)

Javaid, Atif; Zeshan Ali, Muhammad

2018-05-01

Multifunctional structural batteries based on carbon fiber-reinforced polymer composites are fabricated that can bear mechanical loads and act as electrochemical energy storage devices simultaneously. Structural batteries, containing woven carbon fabric anode; lithium cobalt oxide/graphene nanoplatelets coated aluminum cathode; filter paper separator and cross-linked polymer electrolyte, were fabricated through resin infusion under flexible tooling (RIFT) technique. Compression tests, dynamic mechanical thermal analysis, thermogravimetric analysis and impedance spectroscopy were done on the cross-linked polymer electrolytes while cyclic voltammetry, impedance spectroscopy, dynamic mechanical thermal analysis and in-plane shear tests were conducted on the fabricated structural batteries. A range of solid polymer electrolytes with increasing concentrations of lithium perchlorate salt in crosslinked polymer epoxies were formulated. Increased concentrations of electrolyte salt in cross-linked epoxy increased the ionic conductivity, although the compressive properties were compromised. A structural battery, exhibiting simultaneously a capacity of 0.16 mAh L‑1, an energy density of 0.32 Wh L‑1 and a shear modulus of 0.75 GPa have been reported.

The Preparation and Properties of Thermo-reversibly Cross-linked Rubber Via Diels-Alder Chemistry.

PubMed

Polgar, Lorenzo Massimo; van Duin, Martin; Picchioni, Francesco

2016-08-25

A method for using Diels Alder thermo-reversible chemistry as cross-linking tool for rubber products is demonstrated. In this work, a commercial ethylene-propylene rubber, grafted with maleic anhydride, is thermo-reversibly cross-linked in two steps. The pending anhydride moieties are first modified with furfurylamine to graft furan groups to the rubber backbone. These pendant furan groups are then cross-linked with a bis-maleimide via a Diels-Alder coupling reaction. Both reactions can be performed under a broad range of experimental conditions and can easily be applied on a large scale. The material properties of the resulting Diels-Alder cross-linked rubbers are similar to a peroxide-cured ethylene/propylene/diene rubber (EPDM) reference. The cross-links break at elevated temperatures (> 150 °C) via the retro-Diels-Alder reaction and can be reformed by thermal annealing at lower temperatures (50-70 °C). Reversibility of the system was proven with infrared spectroscopy, solubility tests and mechanical properties. Recyclability of the material was also shown in a practical way, i.e., by cutting a cross-linked sample into small parts and compression molding them into new samples displaying comparable mechanical properties, which is not possible for conventionally cross-linked rubbers.

Efficient control-channel multifailure management mechanism in GMPLS-based optical networks

NASA Astrophysics Data System (ADS)

Muñoz, Raül; Martínez, Ricardo; Junyent, Gabriel

2006-12-01

In generalized multiprotocol label switching (GMPLS) architecture, the control channels between each pair of optical nodes are not forced to use the same physical link as the data/transport channels. The problem arises when, due to the fact of allowing the control channels to be physically diverse from the associated data links, there may not be any active control channels available while data channels are still in use. Control-channel faults should not have a service impact on the existing connections; that is, a link that is carrying data traffic must not be torn down because the control channel is no longer available. But, due to the lack of the control channel, the active traffic that is using the data link may no longer be guaranteed with the same level of recovery service (protection or restoration). Under these circumstances the link must be considered to be in a degraded state. This means that routing and signaling should be notified that new connections are not accepted and the link is advertised with no unreserved resources. For this purpose, here we propose a control-channel multifailure management mechanism involving routing, signaling, and link management with extended GMPLS-based protocol extensions to keep the same level of service (in terms of provisioning and recovery) when a link is in the degraded state.

Bio-chemo-mechanical models of vascular mechanics

PubMed Central

Kim, Jungsil; Wagenseil, Jessica E.

2014-01-01

Models of vascular mechanics are necessary to predict the response of an artery under a variety of loads, for complex geometries, and in pathological adaptation. Classic constitutive models for arteries are phenomenological and the fitted parameters are not associated with physical components of the wall. Recently, microstructurally-linked models have been developed that associate structural information about the wall components with tissue-level mechanics. Microstructurally-linked models are useful for correlating changes in specific components with pathological outcomes, so that targeted treatments may be developed to prevent or reverse the physical changes. However, most treatments, and many causes, of vascular disease have chemical components. Chemical signaling within cells, between cells, and between cells and matrix constituents affects the biology and mechanics of the arterial wall in the short- and long-term. Hence, bio-chemo-mechanical models that include chemical signaling are critical for robust models of vascular mechanics. This review summarizes bio-mechanical and bio-chemo-mechanical models with a focus on large elastic arteries. We provide applications of these models and challenges for future work. PMID:25465618

Perception of a Naturalistic Stressor Interacts with 5-HTTLPR/rs25531 Genotype and Gender to Impact Reward Responsiveness

PubMed Central

Nikolova, Yuliya; Bogdan, Ryan; Pizzagalli, Diego A.

2011-01-01

Background Stressful life experiences frequently precede the onset of major depression; however, the mechanisms that underlie this link are poorly understood. Importantly, some individuals are more susceptible to the depressogenic effects of stress than others. Carriers of the S or LG allele of the 5-HTTLPR/rs25531 polymorphisms (S’ participants) have been found to be more prone to developing depression under stress relative to L or LA homozygotes (L’ participants). Moreover, emerging evidence indicates that stress-induced anhedonia may be a mechanism underlying links between stress and depression. Given these findings, we hypothesized that exposure to a naturalistic stressor (school final examinations) would disrupt reward responsiveness (a key behavioral component of anhedonia), and that this effect would be strongest in S’ participants. Methods To objectively assess reward responsiveness, we administered a probabilistic reward task to 70 Bulgarian high school students over two sessions in the 6-month period preceding school finals. For each participant, the two sessions were designated as the ‘stress’ and ‘control’ conditions based on self-reported perceived stress. Results A genotype × condition interaction emerged in males, with S’ participants showing larger stress-related reduction in reward responsiveness relative to L’ participants. Conclusion While in need of replication in a larger sample, our results indicate that stress associated with a real-life event is linked to reduced reward responsiveness, the susceptibility to which is modulated by 5-HTTLPR/rs25531 genotype. Although preliminary, these findings identify anhedonia as a promising mechanism linking 5-HTTLPR/rs25531 genotype and stress to depression. PMID:22094432

Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness.

PubMed

Nikolova, Yuliya; Bogdan, Ryan; Pizzagalli, Diego A

2012-01-01

Stressful life experiences frequently precede the onset of major depression; however, the mechanisms that underlie this link are poorly understood. Importantly, some individuals are more susceptible to the depressogenic effects of stress than others. Carriers of the S or LG allele of the 5-HTTLPR/rs25531 polymorphisms (S' participants) have been found to be more prone to developing depression under stress relative to L or LA homozygotes (L' participants). Moreover, emerging evidence indicates that stress-induced anhedonia may be a mechanism underlying links between stress and depression. Given these findings, we hypothesized that exposure to a naturalistic stressor (school final examinations) would disrupt reward responsiveness (a key behavioral component of anhedonia), and that this effect would be strongest in S' participants. To objectively assess reward responsiveness, we administered a probabilistic reward task to 70 Bulgarian high school students over two sessions in the 6-month period preceding school finals. For each participant, the two sessions were designated as the 'stress' and 'control' conditions based on self-reported perceived stress. A genotype×condition interaction emerged in males, with S' participants showing larger stress-related reduction in reward responsiveness relative to L' participants. While in need of replication in a larger sample, our results indicate that stress associated with a real-life event is linked to reduced reward responsiveness, the susceptibility to which is modulated by 5-HTTLPR/rs25531 genotype. Although preliminary, these findings identify anhedonia as a promising mechanism linking 5-HTTLPR/rs25531 genotype and stress to depression. Copyright © 2011 S. Karger AG, Basel.

Potential Theory for Directed Networks

PubMed Central

Zhang, Qian-Ming; Lü, Linyuan; Wang, Wen-Qiang; Zhou, Tao

2013-01-01

Uncovering factors underlying the network formation is a long-standing challenge for data mining and network analysis. In particular, the microscopic organizing principles of directed networks are less understood than those of undirected networks. This article proposes a hypothesis named potential theory, which assumes that every directed link corresponds to a decrease of a unit potential and subgraphs with definable potential values for all nodes are preferred. Combining the potential theory with the clustering and homophily mechanisms, it is deduced that the Bi-fan structure consisting of 4 nodes and 4 directed links is the most favored local structure in directed networks. Our hypothesis receives strongly positive supports from extensive experiments on 15 directed networks drawn from disparate fields, as indicated by the most accurate and robust performance of Bi-fan predictor within the link prediction framework. In summary, our main contribution is twofold: (i) We propose a new mechanism for the local organization of directed networks; (ii) We design the corresponding link prediction algorithm, which can not only testify our hypothesis, but also find out direct applications in missing link prediction and friendship recommendation. PMID:23408979

Disruptions in Emotion Regulation as a Mechanism Linking Community Violence Exposure to Adolescent Internalizing Problems

PubMed Central

Heleniak, Charlotte; King, Kevin M.; Monahan, Kathryn C.; McLaughlin, Katie A.

2017-01-01

Although community violence is an established risk factor for youth aggression, less research has examined its relation with internalizing psychopathology. This study examined associations of community violence exposure with internalizing symptoms, and state and trait emotion dysregulation as mechanisms underlying these associations, in 287 adolescents aged 16–17 (45.6% male; 40.8% White). Community violence exposure was associated with internalizing symptoms, negative affect during peer evaluation, trait emotional reactivity, and infrequent problem solving. Multiple emotion dysregulation indices were also associated with internalizing symptoms. In simultaneous multiple mediator models, indirect effects of community violence on internalizing problems were significantly explained by state and trait emotion dysregulation. Findings implicate emotion dysregulation as one mechanism linking community violence exposure to adolescent internalizing symptoms. PMID:28646545

The function and failure of sensory predictions.

PubMed

Bansal, Sonia; Ford, Judith M; Spering, Miriam

2018-04-23

Humans and other primates are equipped with neural mechanisms that allow them to automatically make predictions about future events, facilitating processing of expected sensations and actions. Prediction-driven control and monitoring of perceptual and motor acts are vital to normal cognitive functioning. This review provides an overview of corollary discharge mechanisms involved in predictions across sensory modalities and discusses consequences of predictive coding for cognition and behavior. Converging evidence now links impairments in corollary discharge mechanisms to neuropsychiatric symptoms such as hallucinations and delusions. We review studies supporting a prediction-failure hypothesis of perceptual and cognitive disturbances. We also outline neural correlates underlying prediction function and failure, highlighting similarities across the visual, auditory, and somatosensory systems. In linking basic psychophysical and psychophysiological evidence of visual, auditory, and somatosensory prediction failures to neuropsychiatric symptoms, our review furthers our understanding of disease mechanisms. © 2018 New York Academy of Sciences.

Metabolically programmed quality control system for dolichol-linked oligosaccharides

PubMed Central

Harada, Yoichiro; Nakajima, Kazuki; Masahara-Negishi, Yuki; Freeze, Hudson H.; Angata, Takashi; Taniguchi, Naoyuki; Suzuki, Tadashi

2013-01-01

The glycolipid Glc3Man9GlcNAc2-pyrophosphate-dolichol serves as the precursor for asparagine (N)-linked protein glycosylation in mammals. The biosynthesis of dolichol-linked oligosaccharides (DLOs) is arrested in low-glucose environments via unknown mechanisms, resulting in abnormal N-glycosylation. Here, we show that under glucose deprivation, DLOs are prematurely degraded during the early stages of DLO biosynthesis by pyrophosphatase, leading to the release of singly phosphorylated oligosaccharides into the cytosol. We identified that the level of GDP-mannose (Man), which serves as a donor substrate for DLO biosynthesis, is substantially reduced under glucose deprivation. We provide evidence that the selective shutdown of the GDP-Man biosynthetic pathway is sufficient to induce the release of phosphorylated oligosaccharides. These results indicate that glucose-regulated metabolic changes in the GDP-Man biosynthetic pathway cause the biosynthetic arrest of DLOs and facilitate their premature degradation by pyrophosphatase. We propose that this degradation system may avoid abnormal N-glycosylation with premature oligosaccharides under conditions that impair efficient DLO biosynthesis. PMID:24218558

The Dynamics of Finite-Dimensional Systems Under Nonconservative Position Forces

NASA Astrophysics Data System (ADS)

Lobas, L. G.

2001-01-01

General theorems on the stability of stationary states of mechanical systems subjected to nonconservative position forces are presented. Specific mechanical problems on gyroscopic systems, a double-link pendulum with a follower force and elastically fixed upper tip, multilink pneumowheel vehicles, a monorail car, and rail-guided vehicles are analyzed. Methods for investigation of divergent bifurcations and catastrophes of stationary states are described

Fast steering mirror for laser communication

NASA Astrophysics Data System (ADS)

Langenbach, Harald; Schmid, Manfred

2005-07-01

Future multimedia satellites require communication at large bandwidth which can be achieved by means of optical communication links. TESAT Spacecom is currently developing a Laser Communication Terminal (LCT) for such applications under DLR contract. EADS Astrium is developing and building the mechanisms for Pointing, Acquisition and Tracking (PAT) of the laser beam between two Laser Communication Terminals. Based on this development work the development of mechanism H/W to be flown on TerraSar X is currently under way. After a short description of the general arrangement of the Mechanisms inside the LCT, the paper describes the design of the fast steering mirrors (FSM) reflecting the critical requirements and the solutions how to achieve them.

Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA

PubMed Central

El Mendili, Mohamed-Mounir; Lenglet, Timothée; Stojkovic, Tanya; Behin, Anthony; Guimarães-Costa, Raquel; Salachas, François; Meininger, Vincent; Bruneteau, Gaelle; Le Forestier, Nadine; Laforêt, Pascal; Lehéricy, Stéphane; Benali, Habib; Pradat, Pierre-François

2016-01-01

Purpose The mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA) remain unknown. We investigated the profile of spinal cord atrophy (SCA) in SMN1-linked SMA, and its correlation with the topography of muscle weakness. Materials and Methods Eighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD) and cord cross-sectional area (CSA) measurements in SMA patients were compared to those in controls and correlated with strength and disability scores. Results CSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10−5). There were no correlations between atrophy measurements, strength and disability scores. Conclusions Spinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients. PMID:27089520

Longitudinal Links Between Gambling Participation and Academic Performance in Youth: A Test of Four Models.

PubMed

Vitaro, Frank; Brendgen, Mara; Girard, Alain; Dionne, Ginette; Boivin, Michel

2018-01-11

Gambling participation and low academic performance are related during adolescence, but the causal mechanisms underlying this link are unclear. It is possible that gambling participation impairs academic performance. Alternatively, the link between gambling participation and low academic performance could be explained by common underlying risk factors such as impulsivity and socio-family adversity. It could also be explained by other current correlated problem behaviors such as substance use. The goal of the present study was to examine whether concurrent and longitudinal links between gambling participation and low academic performance exist from age 14 to age 17 years, net of common antecedent factors and current substance use. A convenience sample of 766 adolescents (50.6% males) from a longitudinal twin sample participated in the study. Analyses revealed significant, albeit modest, concurrent links at both ages between gambling participation and academic performance. There was also a longitudinal link between gambling participation at age 14 and academic performance at age 17, which persisted after controlling for age 12 impulsivity and socio-family adversity as well as current substance use. Gambling participation predicts a decrease in academic performance during adolescence, net of concurrent and antecedent personal and familial risk factors.

Do common mechanisms of adaptation mediate color discrimination and appearance? Contrast adaptation

NASA Astrophysics Data System (ADS)

Hillis, James M.; Brainard, David H.

2007-08-01

Are effects of background contrast on color appearance and sensitivity controlled by the same mechanism of adaptation? We examined the effects of background color contrast on color appearance and on color-difference sensitivity under well-matched conditions. We linked the data using Fechner's hypothesis that the rate of apparent stimulus change is proportional to sensitivity and examined a family of parametric models of adaptation. Our results show that both appearance and discrimination are consistent with the same mechanism of adaptation.

Soil and public health: invisible bridges

USDA-ARS?s Scientific Manuscript database

Public health institutions, as ancient as civilizations itself, are intrinsically connected with soils. The massive body of the empirical knowledge about this connection has been accumulated. Recently unraveling the underlying mechanisms of this link has begun, and many of them appear to have the m...

Photouncaged Sequence-specific Interstrand DNA Cross-Linking with Photolabile 4-oxo-enal-modified Oligonucleotides

PubMed Central

Sun, Jingjing; Tang, Xinjing

2015-01-01

DNA cross-linking technology is an attractive tool for the detection, regulation, and manipulation of genes. In this study, a series of photolabile 4-oxo-enal-modified oligonucleotides functionalized with photosensitive ο-nitrobenzyl derivatives were rationally designed as a new kind of photocaged cross-linking agents. A comprehensive evaluation of cross-linking reactions for different nucleobases in complementary strands under different conditions suggested that the modified DNA oligonucleotides tended to form interstrand cross-linking to nucleobases with the potential of thymidine > guanosine » cytidine ~ adenosine. Different from previous literature reports that cytidine and adenosine were preferential cross-linked nucleobases with 4-oxo-enal moieties, our study represents the first example of DNA cross-linking for T and G selectivity using 4-oxo-enal moiety. The cross-linked adducts were identified and their cross-linking mechanism was also illustrated. This greatly expands the applications of 4-oxo-enal derivatives in the studies of DNA damage and RNA structure PMID:26020694

Photouncaged Sequence-specific Interstrand DNA Cross-Linking with Photolabile 4-oxo-enal-modified Oligonucleotides.

PubMed

Sun, Jingjing; Tang, Xinjing

2015-05-28

DNA cross-linking technology is an attractive tool for the detection, regulation, and manipulation of genes. In this study, a series of photolabile 4-oxo-enal-modified oligonucleotides functionalized with photosensitive ο-nitrobenzyl derivatives were rationally designed as a new kind of photocaged cross-linking agents. A comprehensive evaluation of cross-linking reactions for different nucleobases in complementary strands under different conditions suggested that the modified DNA oligonucleotides tended to form interstrand cross-linking to nucleobases with the potential of thymidine > guanosine » cytidine ~ adenosine. Different from previous literature reports that cytidine and adenosine were preferential cross-linked nucleobases with 4-oxo-enal moieties, our study represents the first example of DNA cross-linking for T and G selectivity using 4-oxo-enal moiety. The cross-linked adducts were identified and their cross-linking mechanism was also illustrated. This greatly expands the applications of 4-oxo-enal derivatives in the studies of DNA damage and RNA structure.

The Utilization of Plant Facilities on the International Space Station—The Composition, Growth, and Development of Plant Cell Walls under Microgravity Conditions

PubMed Central

Jost, Ann-Iren Kittang; Hoson, Takayuki; Iversen, Tor-Henning

2015-01-01

In the preparation for missions to Mars, basic knowledge of the mechanisms of growth and development of living plants under microgravity (micro-g) conditions is essential. Focus has centered on the g-effects on rigidity, including mechanisms of signal perception, transduction, and response in gravity resistance. These components of gravity resistance are linked to the evolution and acquisition of responses to various mechanical stresses. An overview is given both on the basic effect of hypergravity as well as of micro-g conditions in the cell wall changes. The review includes plant experiments in the US Space Shuttle and the effect of short space stays (8–14 days) on single cells (plant protoplasts). Regeneration of protoplasts is dependent on cortical microtubules to orient the nascent cellulose microfibrils in the cell wall. The space protoplast experiments demonstrated that the regeneration capacity of protoplasts was retarded. Two critical factors are the basis for longer space experiments: a. the effects of gravity on the molecular mechanisms for cell wall development, b. the availability of facilities and hardware for performing cell wall experiments in space and return of RNA/DNA back to the Earth. Linked to these aspects is a description of existing hardware functioning on the International Space Station. PMID:27135317

The Utilization of Plant Facilities on the International Space Station-The Composition, Growth, and Development of Plant Cell Walls under Microgravity Conditions.

PubMed

Jost, Ann-Iren Kittang; Hoson, Takayuki; Iversen, Tor-Henning

2015-01-20

In the preparation for missions to Mars, basic knowledge of the mechanisms of growth and development of living plants under microgravity (micro-g) conditions is essential. Focus has centered on the g-effects on rigidity, including mechanisms of signal perception, transduction, and response in gravity resistance. These components of gravity resistance are linked to the evolution and acquisition of responses to various mechanical stresses. An overview is given both on the basic effect of hypergravity as well as of micro-g conditions in the cell wall changes. The review includes plant experiments in the US Space Shuttle and the effect of short space stays (8-14 days) on single cells (plant protoplasts). Regeneration of protoplasts is dependent on cortical microtubules to orient the nascent cellulose microfibrils in the cell wall. The space protoplast experiments demonstrated that the regeneration capacity of protoplasts was retarded. Two critical factors are the basis for longer space experiments: a. the effects of gravity on the molecular mechanisms for cell wall development, b. the availability of facilities and hardware for performing cell wall experiments in space and return of RNA/DNA back to the Earth. Linked to these aspects is a description of existing hardware functioning on the International Space Station.

Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

PubMed

Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

2017-02-01

The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Deep space optical communications experiment

NASA Technical Reports Server (NTRS)

Kinman, P.; Katz, J.; Gagliardi, R.

1983-01-01

An optical communications experiment between a deep space vehicle and an earth terminal is under consideration for later in this decade. The experimental link would be incoherent (direct detection) and would employ two-way cooperative pointing. The deep space optical transceiver would ride piggyback on a spacecraft with an independent scientific objective. Thus, this optical transceiver is being designed for minimum spacecraft impact - specifically, low mass and low power. The choices of laser transmitter, coding/modulation scheme, and pointing mechanization are discussed. A representative telemetry link budget is presented.

Air Pollution Upregulates Endothelial Cell Procoagulant Activity Via Ultrafine Particle-Induced Oxidant Signaling and Tissue Factor Expression

EPA Science Inventory

Air pollution exposure is associated with cardiovascular events triggered by clot formation. Endothelial activation and initiation of coagulation are pathophysiological mechanisms that could link inhaled air pollutants to vascular events. Here we investigated the underlying mecha...

Effects of environmental pollutants on cellular iron homeostasis and ultimate links to human disease

EPA Science Inventory

Chronic disease has increased in the last several decades, and environmental pollutants have been implicated. The magnitude and variety of diseases indicate the malfunctioning of some basic mechanism underlying human health. Environmental pollutants demonstrate a capability to co...

JAXA-NASA Interoperability Demonstration for Application of DTN Under Simulated Rain Attenuation

NASA Technical Reports Server (NTRS)

Suzuki, Kiyoshisa; Inagawa, Shinichi; Lippincott, Jeff; Cecil, Andrew J.

2014-01-01

As is well known, K-band or higher band communications in space link segment often experience intermittent disruptions caused by heavy rainfall. In view of keeping data integrity and establishing autonomous operations under such situation, it is important to consider introducing a tolerance mechanism such as Delay/Disruption Tolerant Networking (DTN). The Consultative Committee for Space Data Systems (CCSDS) is studying DTN as part of the standardization activities for space data systems. As a contribution to CCSDS and a feasibility study for future utilization of DTN, Japan Aerospace Exploration Agency (JAXA) and National Aeronautics and Space Administration (NASA) conducted an interoperability demonstration for confirming its tolerance mechanism and capability of automatic operation using Data Relay Test Satellite (DRTS) space link and its ground terminals. Both parties used the Interplanetary Overlay Network (ION) open source software, including the Bundle Protocol, the Licklider Transmission Protocol, and Contact Graph Routing. This paper introduces the contents of the interoperability demonstration and its results.

Synthesis and characterisation of cross-linked chitosan composites functionalised with silver and gold nanoparticles for antimicrobial applications

NASA Astrophysics Data System (ADS)

Ryan, Catherine; Alcock, Emma; Buttimer, Finbarr; Schmidt, Michael; Clarke, David; Pemble, Martyn; Bardosova, Maria

2017-12-01

We present a study of a range of cross-linked chitosan composites with potential antimicrobial applications. They were formed by cross-linking chitosan and siloxane networks and by introducing silver and gold nanoparticles (NPs). The aim was to investigate whether adding the metal NPs to the chitosan-siloxane composite would lead to a material with enhanced antimicrobial ability as compared to chitosan itself. The composites were synthesised in hydrogel form with the metal NPs embedded in the cross-linked chitosan network. Spectroscopic and microscopic techniques were employed to investigate the structural properties of the composite and the tensile strength of the structures was measured. It was found that the addition of metal NPs did not influence the mechanical strength of the composite. A crystal violet attachment assay results displayed a significant reduction in the attachment of E. coli to the cross-linked chitosan surfaces. Release profile tests suggest that the metal NPs do not contribute to the overall antimicrobial activity under neutral conditions. The contribution to the mechanical and antimicrobial properties from cross-linking with siloxane is significant, giving rise to a versatile, durable, antimicrobial material suitable for thin film formation, wound dressings or the coating of various surfaces where robustness and antimicrobial control are required.

Synthesis and characterisation of cross-linked chitosan composites functionalised with silver and gold nanoparticles for antimicrobial applications

PubMed Central

Ryan, Catherine; Alcock, Emma; Buttimer, Finbarr; Schmidt, Michael; Clarke, David; Pemble, Martyn; Bardosova, Maria

2017-01-01

Abstract We present a study of a range of cross-linked chitosan composites with potential antimicrobial applications. They were formed by cross-linking chitosan and siloxane networks and by introducing silver and gold nanoparticles (NPs). The aim was to investigate whether adding the metal NPs to the chitosan-siloxane composite would lead to a material with enhanced antimicrobial ability as compared to chitosan itself. The composites were synthesised in hydrogel form with the metal NPs embedded in the cross-linked chitosan network. Spectroscopic and microscopic techniques were employed to investigate the structural properties of the composite and the tensile strength of the structures was measured. It was found that the addition of metal NPs did not influence the mechanical strength of the composite. A crystal violet attachment assay results displayed a significant reduction in the attachment of E. coli to the cross-linked chitosan surfaces. Release profile tests suggest that the metal NPs do not contribute to the overall antimicrobial activity under neutral conditions. The contribution to the mechanical and antimicrobial properties from cross-linking with siloxane is significant, giving rise to a versatile, durable, antimicrobial material suitable for thin film formation, wound dressings or the coating of various surfaces where robustness and antimicrobial control are required. PMID:28804527

Synthesis and characterisation of cross-linked chitosan composites functionalised with silver and gold nanoparticles for antimicrobial applications.

PubMed

Ryan, Catherine; Alcock, Emma; Buttimer, Finbarr; Schmidt, Michael; Clarke, David; Pemble, Martyn; Bardosova, Maria

2017-01-01

We present a study of a range of cross-linked chitosan composites with potential antimicrobial applications. They were formed by cross-linking chitosan and siloxane networks and by introducing silver and gold nanoparticles (NPs). The aim was to investigate whether adding the metal NPs to the chitosan-siloxane composite would lead to a material with enhanced antimicrobial ability as compared to chitosan itself. The composites were synthesised in hydrogel form with the metal NPs embedded in the cross-linked chitosan network. Spectroscopic and microscopic techniques were employed to investigate the structural properties of the composite and the tensile strength of the structures was measured. It was found that the addition of metal NPs did not influence the mechanical strength of the composite. A crystal violet attachment assay results displayed a significant reduction in the attachment of E. coli to the cross-linked chitosan surfaces. Release profile tests suggest that the metal NPs do not contribute to the overall antimicrobial activity under neutral conditions. The contribution to the mechanical and antimicrobial properties from cross-linking with siloxane is significant, giving rise to a versatile, durable, antimicrobial material suitable for thin film formation, wound dressings or the coating of various surfaces where robustness and antimicrobial control are required.

Differential regulation by ATP versus ADP further links CaMKII aggregation to ischemic conditions

PubMed Central

Vest, Rebekah S.; O’Leary, Heather; Bayer, K. Ulrich

2009-01-01

CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters under ischemic conditions. This study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by mimicking ischemic conditions: low pH (6.8 or less), Ca2+ (and calmodulin), and low ATP and/or high ADP concentration. Mutational analysis showed that high ATP prevented aggregation by a mechanism involving T286 auto-phosphorylation, and indicated requirement for nucleotide binding but not auto-phosphorylation also for extra-synaptic clustering within neurons. These results clarify a previously apparent paradox in the nucleotide and phosphorylation requirement of aggregation, and support a mechanism that involves inter-holoenzyme T286-region/T-site interaction. PMID:19840793

Integrative modelling reveals mechanisms linking productivity and plant species richness.

PubMed

Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

2016-01-21

How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

Dissecting the Role of Disturbed ER-Golgi Trafficking in Antivirals and Alcohol Abuse-Induced Pathogenesis of Liver Disorders.

PubMed

Ji, Cheng

2017-01-01

Antiviral drugs and alcohol abuse-induced organelle stresses have been linked to many disorders and the underlying molecular mechanisms are under intense investigations. This brief review communicates emerging evidence and research trends on how certain antivirals and alcohol affect ER-Golgi trafficking, which potentially impacts the function and integrity of the Golgi apparatus contributing to endoplasmic reticulum stress and cellular injury.

Regulation Mechanism of Salt Ions for Superlubricity of Hydrophilic Polymer Cross-Linked Networks on Ti6Al4V.

PubMed

Zhang, Caixia; Liu, Yuhong; Liu, Zhifeng; Zhang, Hongyu; Cheng, Qiang; Yang, Congbin

2017-03-07

Poly(vinylphosphonic acid) (PVPA) cross-linked networks on Ti 6 Al 4 V show superlubricity behavior when sliding against polytetrafluoroethylene in water-based lubricants. The superlubricity can occur but only with the existence of salt ions in the polymer cross-linked networks. This is different from the phenomenon in most polymer brushes. An investigation into the mechanism revealed that cations and anions in the lubricants worked together to yield the superlubricity even under harsh conditions. It is proposed that the preferential interactions of cations with PVPA molecules rather than water molecules are the main reason for the superlubricity in water-based lubricants. The interaction of anions with water molecules regulates the properties of the tribological interfaces, which influences the magnitude of the friction coefficient. Owing to the novel cross-linked networks and the interactions between cations and polymer molecules, their superlubricity can be maintained even at a high salt ion concentration of 5 M. These excellent properties make PVPA-modified Ti 6 Al 4 V a potential candidate for application in artificial implants.

Wired on sugar: the role of the CNS in the regulation of glucose homeostasis

PubMed Central

Grayson, Bernadette E.; Seeley, Randy J.; Sandoval, Darleen A.

2014-01-01

Obesity and type 2 diabetes mellitus (T2DM) — disorders of energy homeostasis and glucose homeostasis, respectively — are tightly linked and the incidences of both conditions are increasing in parallel. The CNS integrates information regarding peripheral nutrient and hormonal changes and processes this information to regulate energy homeostasis. Recent findings indicate that some of the neural circuits and mechanisms underlying energy balance are also essential for the regulation of glucose homeostasis. We propose that disruption of these overlapping pathways links the metabolic disturbances associated with obesity and T2DM. A better understanding of these converging mechanisms may lead to therapeutic strategies that target both T2DM and obesity. PMID:23232606

Diel growth dynamics in tree stems: linking anatomy and ecophysiology.

PubMed

Steppe, Kathy; Sterck, Frank; Deslauriers, Annie

2015-06-01

Impacts of climate on stem growth in trees are studied in anatomical, ecophysiological, and ecological disciplines, but an integrative framework to assess those impacts remains lacking. In this opinion article, we argue that three research efforts are required to provide that integration. First, we need to identify the missing links in diel patterns in stem diameter and stem growth and relate those patterns to the underlying mechanisms that control water and carbon balance. Second, we should focus on the understudied mechanisms responsible for seasonal impacts on such diel patterns. Third, information on stem anatomy and ecophysiology should be integrated in the same experiments and mechanistic plant growth models to capture both diel and seasonal scales. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bone as an endocrine organ relevant to diabetes

USDA-ARS?s Scientific Manuscript database

There are well-established associations between diabetes and fracture risk and yet the mechanism underlying these associations are controversial. Guided by a series of mouse studies, a specific form of the bone protein, osteocalcin, was proposed to be the mechanistic link between these two chronic d...

Psychopathology, Temperament and Unintentional Injury: Cross-Sectional and Longitudinal Relationships

ERIC Educational Resources Information Center

Rowe, Richard; Simonoff, Emily; Silberg, Judy L.

2007-01-01

Background: Growing evidence indicates a link between unintentional injury and both disruptive and emotional psychopathology. We present further evidence of these associations and address the underlying mechanisms. We also examine the genetic contribution to unintentional injury. Methods: The Virginia Twin Study of Adolescent Behavioral…

SNPs located at CpG sites modulate genome-epigenome interaction

USDA-ARS?s Scientific Manuscript database

DNA methylation is an important molecular-level phenotype that links genotypes and complex disease traits. Previous studies have found local correlation between genetic variants and DNA methylation levels (cis-meQTLs). However, general mechanisms underlying cis-meQTLs are unclear. We conducted a cis...

Calcium homeostasis in diabetes mellitus.

PubMed

Ahn, Changhwan; Kang, Ji-Houn; Jeung, Eui-Bae

2017-09-30

Diabetes mellitus (DM) is becoming a lifestyle-related pandemic disease. Diabetic patients frequently develop electrolyte disorders, especially diabetic ketoacidosis or nonketotic hyperglycemic hyperosmolar syndrome. Such patients show characteristic potassium, magnesium, phosphate, and calcium depletion. In this review, we discuss a homeostatic mechanism that links calcium and DM. We also provide a synthesis of the evidence in favor or against this linking mechanism by presenting recent clinical indications, mainly from veterinary research. There are consistent results supporting the use of calcium and vitamin D supplementation to reduce the risk of DM. Clinical trials support a marginal reduction in circulating lipids, and some meta-analyses support an increase in insulin sensitivity, following vitamin D supplementation. This review provides an overview of the calcium and vitamin D disturbances occurring in DM and describes the underlying mechanisms. Such elucidation will help indicate potential pathophysiology-based precautionary and therapeutic approaches and contribute to lowering the incidence of DM.

Interplay between social experiences and the genome: epigenetic consequences for behavior.

PubMed

Champagne, Frances A

2012-01-01

Social experiences can have a persistent effect on biological processes leading to phenotypic diversity. Variation in gene regulation has emerged as a mechanism through which the interplay between DNA and environments leads to the biological encoding of these experiences. Epigenetic modifications-molecular pathways through which transcription is altered without altering the underlying DNA sequence-play a critical role in the normal process of development and are being increasingly explored as a mechanism linking environmental experiences to long-term biobehavioral outcomes. In this review, evidence implicating epigenetic factors, such as DNA methylation and histone modifications, in the link between social experiences occurring during the postnatal period and in adulthood and altered neuroendocrine and behavioral outcomes will be highlighted. In addition, the role of epigenetic mechanisms in shaping variation in social behavior and the implications of epigenetics for our understanding of the transmission of traits across generations will be discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior.

PubMed

Tops, Sanne; Habel, Ute; Radke, Sina

2018-03-12

Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles. Copyright © 2018. Published by Elsevier Inc.

A process-based framework for soil ecosystem services study and management.

PubMed

Su, Changhong; Liu, Huifang; Wang, Shuai

2018-06-15

Soil provides various indispensable ecosystem services for human society. Soil's complex structure and property makes the soil ecological processes complicated and brings about tough challenges for soil ecosystem services study. Most of the current frameworks on soil services focus exclusively on services per se, neglecting the links and underlying ecological mechanisms. This article put forward a framework on soil services by stressing the underlying soil mechanisms and processes, which includes: 1) analyzing soil natural capital stock based on soil structure and property, 2) disentangling the underlying complex links and soil processes, 3) soil services valuation based on field investigation and spatial explicit models, and 4) enacting soil management strategy based on soil services and their driving factors. By application of this framework, we assessed the soil services of sediment retention, water yield, and grain production in the Upper-reach Fenhe Watershed. Based on the ecosystem services and human driving factors, the whole watershed was clustered into five groups: 1) municipal area, 2) typical coal mining area, 3) traditional farming area, 4) unsustainable urbanizing area, and 5) ecological conservation area. Management strategies on soils were made according to the clustering based soil services and human activities. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Kapustin, Eugene A.; Lee, Seungkyu; Alshammari, Ahmad S.

Despite numerous studies on chemical and thermal stability of metal-organic frameworks (MOFs), mechanical stability remains largely undeveloped. No strategy exists to control the mechanical deformation of MOFs under ultrahigh pressure, to date. We show that the mechanically unstable MOF-520 can be retrofitted by precise placement of a rigid 4,4'-biphenyldicarboxylate (BPDC) linker as a "girder" to afford a mechanically robust framework: MOF-520-BPDC. This retrofitting alters how the structure deforms under ultrahigh pressure and thus leads to a drastic enhancement of its mechanical robustness. While in the parent MOF-520 the pressure transmitting medium molecules diffuse into the pore and expand the structuremore » from the inside upon compression, the girder in the new retrofitted MOF-520-BPDC prevents the framework from expansion by linking two adjacent secondary building units together. As a result, the modified MOF is stable under hydrostatic compression in a diamond-anvil cell up to 5.5 gigapascal. The increased mechanical stability of MOF-520-BPDC prohibits the typical amorphization observed for MOFs in this pressure range. Direct correlation between the orientation of these girders within the framework and its linear strain was estimated, providing new insights for the design of MOFs with optimized mechanical properties.« less

Helicopter Pitch-Control Mechanism Reduces Vibration

NASA Technical Reports Server (NTRS)

Lemont, H.

1986-01-01

Large forces accommodated without increasing weight of helicopter structure. New mechanism yields stiffer control and improves accuracy of pitch changes under load. As result, heavy casting not for gearbox, nor extra reinforcing members needed for fuselage bulkheads, stringers, skin, and other parts. In new mechanism, reaction forces developed in rotor hub. Long load paths to gearbox and fuselage elminated. Reaction member rigidly attached to hub and rotates with it. At lower end of reaction member, bearing forms bridge to fuselage through stationary beam and antirotation link. Beam connected to reaction plate through rods.

The mechanical properties of polyimide films after exposure to high pH

NASA Technical Reports Server (NTRS)

Croall, Catharine I.; St.clair, Terry L.

1992-01-01

Wiring failures linked to insulation damage have drawn much attention in the aerospace industry and concerns have developed regarding the stability and safety of polyimide insulated electrical wire. Several polyimides were selected for evaluation for resistance to degradation by various aqueous alkaline solutions. The polyimides under evaluation include commercially available films such as Kapton (tk), Apical (tk), LaRC(tk)-TPI, and Upilex(tk)R and S, as well as a number of experimental films prepared by NASA Langley. Thermally imidized films were studied for their retention of mechanical properties after exposure to high pH solutions under stressed conditions.

Memory for Sequences of Events Impaired in Typical Aging

ERIC Educational Resources Information Center

Allen, Timothy A.; Morris, Andrea M.; Stark, Shauna M.; Fortin, Norbert J.; Stark, Craig E. L.

2015-01-01

Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to…

The Mediating Roles of Coping and Adjustment in the Relationship between Personality and Academic Achievement

ERIC Educational Resources Information Center

Perera, Harsha N.; McIlveen, Peter; Oliver, Mark E.

2015-01-01

Background: Existing literature has documented relationships between personality traits and academic achievement as well as some of the mechanisms underlying these links. However, the pathways by which personality traits are associated with achievement during stressful educational circumstances require further investigation. Aims: This study…

Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways

EPA Science Inventory

Background: Particulate matter is associated with adverse airway health effects; however, the underlying mechanism in disease initiation is still largely unknown. Recently, microRNAs (small noncoding RNAs) have been suggested as important in maintaining the lung in a disease free...

Evaluation and expression analysis of alfalfa genotypes in response to prolonged salt stress

USDA-ARS?s Scientific Manuscript database

Salinity is one of the most important abiotic stresses that adversely affect plant growth and productivity globally. In order to tackle this complex problem, it is important to link the biochemical and physiological responses with the underlying genetic mechanisms. In this study, we used 12 previous...

Dyadic Processes in Early Marriage: Attributions, Behavior, and Marital Quality

ERIC Educational Resources Information Center

Durtschi, Jared A.; Fincham, Frank D.; Cui, Ming; Lorenz, Frederick O.; Conger, Rand D.

2011-01-01

Marital processes in early marriage are important for understanding couples' future marital quality. Spouses' attributions about a partner's behavior have been linked to marital quality, yet the mechanisms underlying this association remain largely unknown. When we used couple data from the Family Transitions Project (N = 280 couples) across the…

Linking transcriptional responses to organismal tolerance reveals mechanisms of thermal sensitivity in a mesothermal endangered fish.

PubMed

Komoroske, Lisa M; Connon, Richard E; Jeffries, Ken M; Fangue, Nann A

2015-10-01

Forecasting species' responses to climate change requires understanding the underlying mechanisms governing environmental stress tolerance, including acclimation capacity and acute stress responses. Current knowledge of these physiological processes in aquatic ectotherms is largely drawn from eurythermal or extreme stenothermal species. Yet many species of conservation concern exhibit tolerance windows and acclimation capacities in between these extremes. We linked transcriptome profiles to organismal tolerance in a mesothermal endangered fish, the delta smelt (Hypomesus transpacificus), to quantify the cellular processes, sublethal thresholds and effects of thermal acclimation on acute stress responses. Delta smelt initiated rapid molecular changes in line with expectations of theoretical thermal limitation models, but also exhibited diminished capacity to modify the expression of some genes and cellular mechanisms key to coping with acute thermal stress found in eurytherms. Sublethal critical thresholds occurred 4-6 °C below their upper tolerance limits, and thermal acclimation shifted the onset of acute thermal stress and tolerance as predicted. However, we found evidence that delta smelt's limited thermal plasticity may be partially due to an inability of individuals to effectively make physiological adjustments to truly achieve new homoeostasis under heightened temperatures, resulting in chronic thermal stress. These findings provide insight into the physiological basis of the diverse patterns of thermal tolerances observed in nature. Moreover, understanding how underlying molecular mechanisms shape thermal acclimation capacity, acute stress responses and ultimately differential phenotypes contributes to a predictive framework to deduce species' responses in situ to changes in selective pressures due to climate change. © 2015 John Wiley & Sons Ltd.

Space Network Time Distribution and Synchronization Protocol Development for Mars Proximity Link

NASA Technical Reports Server (NTRS)

Woo, Simon S.; Gao, Jay L.; Mills, David

2010-01-01

Time distribution and synchronization in deep space network are challenging due to long propagation delays, spacecraft movements, and relativistic effects. Further, the Network Time Protocol (NTP) designed for terrestrial networks may not work properly in space. In this work, we consider the time distribution protocol based on time message exchanges similar to Network Time Protocol (NTP). We present the Proximity-1 Space Link Interleaved Time Synchronization (PITS) algorithm that can work with the CCSDS Proximity-1 Space Data Link Protocol. The PITS algorithm provides faster time synchronization via two-way time transfer over proximity links, improves scalability as the number of spacecraft increase, lowers storage space requirement for collecting time samples, and is robust against packet loss and duplication which underlying protocol mechanisms provide.

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.

Computational models of spatial updating in peri-saccadic perception

PubMed Central

Hamker, Fred H.; Zirnsak, Marc; Ziesche, Arnold; Lappe, Markus

2011-01-01

Perceptual phenomena that occur around the time of a saccade, such as peri-saccadic mislocalization or saccadic suppression of displacement, have often been linked to mechanisms of spatial stability. These phenomena are usually regarded as errors in processes of trans-saccadic spatial transformations and they provide important tools to study these processes. However, a true understanding of the underlying brain processes that participate in the preparation for a saccade and in the transfer of information across it requires a closer, more quantitative approach that links different perceptual phenomena with each other and with the functional requirements of ensuring spatial stability. We review a number of computational models of peri-saccadic spatial perception that provide steps in that direction. Although most models are concerned with only specific phenomena, some generalization and interconnection between them can be obtained from a comparison. Our analysis shows how different perceptual effects can coherently be brought together and linked back to neuronal mechanisms on the way to explaining vision across saccades. PMID:21242143

Mastery matters most: How mastery and positive relations link attachment avoidance and anxiety to negative emotions.

PubMed

Paech, Juliane; Schindler, Ines; Fagundes, Christopher P

2016-08-01

Attachment avoidance and anxiety are associated with negative emotions. However, the mechanisms underlying these associations are not fully understood. We investigated environmental mastery and positive relations with others as two mechanisms behind the attachment-emotion link in a sample of 343 adults. As predicted, attachment avoidance and anxiety were related to greater fear, hostility, envy and depression through lower mastery. Contrary to our hypothesis, positive relations mediated only the attachment-depression link. In addition, by adopting a moderated mediation approach, we were able to show that mastery mattered most for individuals high on avoidance: The indirect effect of avoidance through lack of mastery on fear, hostility and depression (but not on envy) increased with higher avoidance scores. Contrary to our predictions, poor relationships did not matter more as sources of negative emotions as anxiety increased. These findings underscore that the emotional life of avoidantly attached individuals is especially jeopardised by poor mastery.

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.

Direct mechanical stimulation of tip links in hair cells through DNA tethers

PubMed Central

Basu, Aakash; Lagier, Samuel; Vologodskaia, Maria; Fabella, Brian A; Hudspeth, AJ

2016-01-01

Mechanoelectrical transduction by hair cells commences with hair-bundle deflection, which is postulated to tense filamentous tip links connected to transduction channels. Because direct mechanical stimulation of tip links has not been experimentally possible, this hypothesis has not been tested. We have engineered DNA tethers that link superparamagnetic beads to tip links and exert mechanical forces on the links when exposed to a magnetic-field gradient. By pulling directly on tip links of the bullfrog's sacculus we have evoked transduction currents from hair cells, confirming the hypothesis that tension in the tip links opens transduction channels. This demonstration of direct mechanical access to tip links additionally lays a foundation for experiments probing the mechanics of individual channels. DOI: http://dx.doi.org/10.7554/eLife.16041.001 PMID:27331611

Unilateral occipital nerve stimulation for bilateral occipital neuralgia: a case report and literature review

PubMed Central

Liu, Aijun; Jiao, Yongcheng; Ji, Huijun; Zhang, Zhiwen

2017-01-01

Objectives The aim of this study is to present a case of successful relief of bilateral occipital neuralgia (ON) using unilateral occipital nerve stimulation (ONS) and to discuss the possible underlying mechanisms. Materials and methods We present the case of a 59-year-old female patient with severe bilateral ON treated with unilateral ONS. We systematically reviewed previous studies of ONS for ON, discussing the possible mechanisms of ONS in the relief of ON. Results The patient reported complete pain relief after consistent unilateral ONS during the follow-up period. The underlying mechanisms may be linked to the relationship between pain and several brain regions, including the pons, midbrain, and periaqueductal gray. Conclusion ONS is an effective and safe option for treating ON. Future studies will be required to clarify the mechanisms by which unilateral occipital stimulation provided relief for bilateral neuralgia in this case. PMID:28176938

Unilateral occipital nerve stimulation for bilateral occipital neuralgia: a case report and literature review.

PubMed

Liu, Aijun; Jiao, Yongcheng; Ji, Huijun; Zhang, Zhiwen

2017-01-01

The aim of this study is to present a case of successful relief of bilateral occipital neuralgia (ON) using unilateral occipital nerve stimulation (ONS) and to discuss the possible underlying mechanisms. We present the case of a 59-year-old female patient with severe bilateral ON treated with unilateral ONS. We systematically reviewed previous studies of ONS for ON, discussing the possible mechanisms of ONS in the relief of ON. The patient reported complete pain relief after consistent unilateral ONS during the follow-up period. The underlying mechanisms may be linked to the relationship between pain and several brain regions, including the pons, midbrain, and periaqueductal gray. ONS is an effective and safe option for treating ON. Future studies will be required to clarify the mechanisms by which unilateral occipital stimulation provided relief for bilateral neuralgia in this case.

Heat shrinkable behavior, physico-mechanical and structure properties of electron beam cross-linked blends of high-density polyethylene with acrylonitrile-butadiene rubber

NASA Astrophysics Data System (ADS)

Reinholds, Ingars; Kalkis, Valdis; Merijs-Meri, Remo; Zicans, Janis; Grigalovica, Agnese

2016-03-01

In this study, heat-shrinkable composites of electron beam irradiated high-density polyethylene (HDPE) composites with acrylonitrile-butadiene rubber (NBR) were investigated. HDPE/NBR blends at a ratio of components 100/0, 90/10, 80/20, 50/50 and 20/80 wt% were prepared using a two-roll mill. The compression molded films were irradiated high-energy (5 MeV) accelerated electrons up to irradiation absorbed doses of 100-300 kGy. The effect of electron beam induced cross-linking was evaluated by the changes of mechanical properties, gel content and by the differences of thermal properties, detected by differential scanning calorimetry. The thermo-shrinkage forces were determined as the kinetics of thermorelaxation and the residual shrinkage stresses of previously oriented (stretched up to 100% at above melting temperature of HDPE and followed by cooling to room temperature) specimens of irradiated HDPE/NBR blends under isometric heating-cooling mode. The compatibility between the both components was enhanced due to the formation of cross-linked sites at amorphous interphase. The results showed increase of mechanical stiffness of composites with increase of irradiation dose. The values of gel fraction compared to thermorelaxation stresses increased with the growth of irradiation dose level, as a result of formation cross-linked sites in amorphous PP/NBR interphase.

Flexible multimode polymer waveguides for high-speed short-reach communication links

NASA Astrophysics Data System (ADS)

Bamiedakis, N.; Shi, F.; Chu, D.; Penty, R. V.; White, I. H.

2018-02-01

Multimode polymer waveguides have attracted great interest for use in high-speed short-reach communication links as they can be cost-effectively integrated onto standard PCBs using conventional methods of the electronics industry and provide low loss (<0.04 dB/cm at 850 nm) and high bandwidth (>30 GHz×m) interconnection. The formation of such waveguides on flexible substrates can further provide flexible low-weight low-thickness interconnects and offer additional freedom in the implementation of high-speed short-reach optical links. These attributes make these flexible waveguides particularly attractive for use in low-cost detachable chip-to-chip links and in environments where weight and shape conformity become important, such as in cars and aircraft. However, the highly-multimoded nature of these waveguides raises important questions about their performance under severe flex due to mode loss and mode coupling. In this work therefore, we investigate the loss, crosstalk and bandwidth performance of such waveguides under out-of plane bending and in-plane twisting under different launch conditions and carry out data transmission tests at 40 Gb/s on a 1 m long spiral flexible waveguide under flexure. Excellent optical transmission characteristics are obtained while robust loss, crosstalk and bandwidth performance are demonstrated under flexure. Error-free (BER<10-12) 40 Gb/s data transmission is achieved over the 1 m long spiral waveguide for a 180° bend with a 4 mm radius. The obtained results demonstrate the excellent optical and mechanical properties of this technology and highlight its potential for use in real-world systems.

Characterization of rat leydig cell gonadotropin receptor structure by affinity cross-linking

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

Zhang, Q.Y.; Hwang, J.; Menon, K.M.J.

1986-05-01

The gonadotropin receptor from rat leydig cell has been characterized with respect to binding kinetics and physiological regulation. The present study was intended to examine the structure of the receptor. Leydig cell suspension was prepared by either collagenase digestion or by mechanical disruption of the testis. The cells were incubated with /sup 125/I-hCG and the unreacted hCG was removed by centrifugation. The /sup 125/I-hCG was then covalently linked to the cell surface receptor using cleavable (dithiobis (succinimidyl propionate)) and non-cleavable (disuccinimidyl suberate) cross-linking reagents. The extracted cross-linked membrane proteins were resolved on SDS-polyacrylamide gels under reducing and non-reducing conditions andmore » subjected to autoradiographic analysis. Under non-reducing conditions, two labeled species with M/sub r/ = 87,000 and 120,000 were detected. However, only one labeled band was detected under reducing conditions with M/sub r/ = 64,000. The binding of /sup 125/I-hCG to the receptor was inhibited by hCG and LH, but not by a number of peptides and proteins. The data suggest that hCG receptor in leydig cell is an oligomeric complex consisting of four subunits, ..cap alpha cap alpha beta gamma... The ..beta.. and ..gamma.. subunits are each linked to an ..cap alpha.. subunit through disulfide linkage and the hormone binds to each ..cap alpha.. subunit. The two dimers formed (..cap alpha beta cap alpha gamma..) are associated by noncovalent interactions.« less

A constructionist review of morality and emotions: no evidence for specific links between moral content and discrete emotions.

PubMed

Cameron, C Daryl; Lindquist, Kristen A; Gray, Kurt

2015-11-01

Morality and emotions are linked, but what is the nature of their correspondence? Many "whole number" accounts posit specific correspondences between moral content and discrete emotions, such that harm is linked to anger, and purity is linked to disgust. A review of the literature provides little support for these specific morality-emotion links. Moreover, any apparent specificity may arise from global features shared between morality and emotion, such as affect and conceptual content. These findings are consistent with a constructionist perspective of the mind, which argues against a whole number of discrete and domain-specific mental mechanisms underlying morality and emotion. Instead, constructionism emphasizes the flexible combination of basic and domain-general ingredients such as core affect and conceptualization in creating the experience of moral judgments and discrete emotions. The implications of constructionism in moral psychology are discussed, and we propose an experimental framework for rigorously testing morality-emotion links. © 2015 by the Society for Personality and Social Psychology, Inc.

Numerical Cognition Explains Age-Related Changes in Third-Party Fairness

ERIC Educational Resources Information Center

Chernyak, Nadia; Sandham, Beth; Harris, Paul L.; Cordes, Sara

2016-01-01

Young children share fairly and expect others to do the same. Yet little is known about the underlying cognitive mechanisms that support fairness. We investigated whether children's numerical competencies are linked with their sharing behavior. Preschoolers (aged 2.5-5.5) participated in third-party resource allocation tasks in which they split a…

Written Language Bursts Mediate the Relationship between Transcription Skills and Writing Performance

ERIC Educational Resources Information Center

Limpo, Teresa; Alves, Rui A.

2017-01-01

It is established that transcription skills (handwriting and spelling) constrain children's writing. Yet, little is known about the mechanism underlying this relationship. This study examined the mediating role of bursts and pauses on the link between transcription skills and writing fluency or text quality. For that, 174 second graders did the…

An Assessment of the Theoretical Underpinnings of Practical Participatory Evaluation

ERIC Educational Resources Information Center

Smits, Pernelle A.; Champagne, Francois

2008-01-01

This article is concerned with the underpinnings of practical participatory evaluation (PPE). Evaluation approaches have long been criticized because their results are often not used. It is believed that PPE addresses this drawback. The article focuses on the mechanisms underlying the links between activities and consequences in PPE. A PPE theory…

The Political Economy of Colonial Education: Mozambique, 1930-1975.

ERIC Educational Resources Information Center

Cross, Michael

1987-01-01

Under colonial fascism and during the revolutionary period leading to independence, the schooling of the African majority in Mozambique had no direct link with the economy, was more a mechanism of social control than of labor reproduction, and (in contrast to other African colonies) did not produce an African middle class supportive of the…

The Link between Maltreatment and Juvenile Firesetting: Correlates and Underlying Mechanisms

ERIC Educational Resources Information Center

Root, C.; MacKay, S.; Henderson, J.; Del Bove, G.; Warling, D.

2008-01-01

Objective: Despite the widely held belief that abuse is a risk factor for childhood firesetting, the role of maltreatment in firesetting is largely unexplored. This study reports on a sample of children and adolescents referred to a brief assessment and intervention program for juvenile firesetters. Firesetting histories of maltreated youth were…

Resistance training and older adults' beliefs about psychological benefits: the importance of self-efficacy and social interaction.

PubMed

Dionigi, Rylee

2007-12-01

The purpose of this study was to determine the perceived psychological benefits and explore the mechanisms underlying the link between exercise and psychological well-being for a group of older adults (65-72 years; 6 women; 4 men) who participated in a 12-week program of moderate-to-high intensity resistance training. They were interviewed in-depth at 1 week preintervention, 1 month after commencement, and 1 week after completion. The participants believed that resistance training enhanced their well-being, and they gave various physical, mental, and social reasons to explain this link. In particular, self-efficacy and social interaction were found to be key mechanisms underlying this relationship. This study exposed meaningful perceived improvements in psychological wellbeing that have not been uncovered in quantitative studies of healthy older people undertaking resistance training. The findings highlight the importance of using qualitative methods to enrich understandings of the positive effect of exercise on psychological well-being. The findings also have implications for designing effective resistance training interventions for older people.

[Ischemic strokes in young adults and illegal drugs].

PubMed

Barbieux, M; Véran, O; Detante, O

2012-01-01

One out of four ischemic strokes in France occurs in adults under 65 years old. About a third of them remain unexplained even after an extensive etiological assessment. A large part of these unexplained strokes could be linked to illegal drug abuse, and 10 % are estimated to be directly linked to illegal drugs in some international studies. The most frequently incriminated recreational drug remains cocaine, via several mechanisms. However, several other illegal drugs, some very commonly used such as cannabis, are suspected to have an important role in neurovascular diseases. In this article, we reviewed the epidemiological, pathophysiological and clinical studies, published in the international literature over the past 30 years. The drug-caused stroke epidemiology needs to be more precisely studied, as well as the underlying mechanisms depending on each drug. This is a public health issue that affects an economically active population, as stroke is the first cause of acquired handicap in adults. Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

RodZ links MreB to cell wall synthesis to mediate MreB rotation and robust morphogenesis

PubMed Central

Morgenstein, Randy M.; Bratton, Benjamin P.; Nguyen, Jeffrey P.; Ouzounov, Nikolay; Shaevitz, Joshua W.; Gitai, Zemer

2015-01-01

The rod shape of most bacteria requires the actin homolog, MreB. Whereas MreB was initially thought to statically define rod shape, recent studies found that MreB dynamically rotates around the cell circumference dependent on cell wall synthesis. However, the mechanism by which cytoplasmic MreB is linked to extracytoplasmic cell wall synthesis and the function of this linkage for morphogenesis has remained unclear. Here we demonstrate that the transmembrane protein RodZ mediates MreB rotation by directly or indirectly coupling MreB to cell wall synthesis enzymes. Furthermore, we map the RodZ domains that link MreB to cell wall synthesis and identify mreB mutants that suppress the shape defect of ΔrodZ without restoring rotation, uncoupling rotation from rod-like growth. Surprisingly, MreB rotation is dispensable for rod-like shape determination under standard laboratory conditions but is required for the robustness of rod shape and growth under conditions of cell wall stress. PMID:26396257

RodZ links MreB to cell wall synthesis to mediate MreB rotation and robust morphogenesis.

PubMed

Morgenstein, Randy M; Bratton, Benjamin P; Nguyen, Jeffrey P; Ouzounov, Nikolay; Shaevitz, Joshua W; Gitai, Zemer

2015-10-06

The rod shape of most bacteria requires the actin homolog, MreB. Whereas MreB was initially thought to statically define rod shape, recent studies found that MreB dynamically rotates around the cell circumference dependent on cell wall synthesis. However, the mechanism by which cytoplasmic MreB is linked to extracytoplasmic cell wall synthesis and the function of this linkage for morphogenesis has remained unclear. Here we demonstrate that the transmembrane protein RodZ mediates MreB rotation by directly or indirectly coupling MreB to cell wall synthesis enzymes. Furthermore, we map the RodZ domains that link MreB to cell wall synthesis and identify mreB mutants that suppress the shape defect of ΔrodZ without restoring rotation, uncoupling rotation from rod-like growth. Surprisingly, MreB rotation is dispensable for rod-like shape determination under standard laboratory conditions but is required for the robustness of rod shape and growth under conditions of cell wall stress.

Computational biomechanics changes our view on insect head evolution.

PubMed

Blanke, Alexander; Watson, Peter J; Holbrey, Richard; Fagan, Michael J

2017-02-08

Despite large-scale molecular attempts, the relationships of the basal winged insect lineages dragonflies, mayflies and neopterans, are still unresolved. Other data sources, such as morphology, suffer from unclear functional dependencies of the structures considered, which might mislead phylogenetic inference. Here, we assess this problem by combining for the first time biomechanics with phylogenetics using two advanced engineering techniques, multibody dynamics analysis and finite-element analysis, to objectively identify functional linkages in insect head structures which have been used traditionally to argue basal winged insect relationships. With a biomechanical model of unprecedented detail, we are able to investigate the mechanics of morphological characters under biologically realistic load, i.e. biting. We show that a range of head characters, mainly ridges, endoskeletal elements and joints, are indeed mechanically linked to each other. An analysis of character state correlation in a morphological data matrix focused on head characters shows highly significant correlation of these mechanically linked structures. Phylogenetic tree reconstruction under different data exclusion schemes based on the correlation analysis unambiguously supports a sistergroup relationship of dragonflies and mayflies. The combination of biomechanics and phylogenetics as it is proposed here could be a promising approach to assess functional dependencies in many organisms to increase our understanding of phenotypic evolution. © 2017 The Author(s).

A translational neuroscience perspective on mindfulness meditation as a prevention strategy.

PubMed

Tang, Yi-Yuan; Leve, Leslie D

2016-03-01

Mindfulness meditation research mainly focuses on psychological outcomes such as behavioral, cognitive, and emotional functioning. However, the neuroscience literature on mindfulness meditation has grown in recent years. This paper provides an overview of relevant neuroscience and psychological research on the effects of mindfulness meditation. We propose a translational prevention framework of mindfulness and its effects. Drawing upon the principles of prevention science, this framework integrates neuroscience and prevention research and postulates underlying brain regulatory mechanisms that explain the impact of mindfulness on psychological outcomes via self-regulation mechanisms linked to underlying brain systems. We conclude by discussing potential clinical and practice implications of this model and directions for future research.

Neuropharmacology of drugs and alcohol in mother and fetus.

PubMed

Pollard, Irina

2007-04-01

Epidemiological evidence suggests that an adverse prenatal environment can have profound long-term health consequences throughout postnatal life. This chapter discusses the underlying mechanisms implicated in the consumption of mood-altering recreational drugs and teratogenicity in the fetus. The way metabolic parameters in pregnancy influence the pharmacokinetic characteristics of drugs and alcohol and the developmental stage of neurotoxicity are reviewed. The general underlying mechanisms that link multifaceted interactions between drug characteristics, gene polymorphisms, dietary deficiencies, changed endocrine indices and fetal programming are outlined, with specific examples throughout the text. As developmental injury is of significant social concern, the final section questions whether society provides adequate support for making appropriate and informed lifestyle choices to alleviate preventable transgenerational harm.

Histone hyperacetylation and exon skipping: a calcium-mediated dynamic regulation in cardiomyocytes

PubMed Central

Sharma, Alok; Nguyen, Hieu; Cai, Lu; Lou, Hua

2015-01-01

In contrast to cell type-specific pre-mRNA alternative splicing, mechanisms controlling activity-dependent alternative splicing is under-studied and not well understood. In a recent study, we conducted a comprehensive analysis of calcium-mediated mechanism that regulates alternative exon skipping in mouse cardiomyocytes. Our results reveal a strong link between histone hyperacetylation and skipping of cassette exons, and provide support to the kinetic coupling model of the epigenetic regulation of alternative splicing at the chromatin level. PMID:26325491

Mechanisms and consequences of injury and repair in older organ transplants1

PubMed Central

Slegtenhorst, Bendix R; Dor, Frank JMF; Elkhal, Abdala; Rodriguez, Hector; Yang, Xiaoyong; Edtinger, Karoline; Quante, Markus; Chong, Anita S; Tullius, Stefan G

2014-01-01

Donor organ scarcity remains a significant clinical challenge in transplantation. Older organs, increasingly utilized to meet the growing demand for donor organs, have been linked to inferior transplant outcomes. Susceptibility to organ injury, reduced repair capacity, and increased immunogenicity are interrelated and impacted by physiological and pathological aging processes. Insights into the underlying mechanisms are needed to develop age-specific interventional strategies with regards to organ preservation, immunosuppression, and allocation. In this overview, we summarize current knowledge of injury and repair mechanisms and the effects of aging relevant to transplantation. PMID:24646769

An Overview of the State of the Art in Atomistic and Multiscale Simulation of Fracture

NASA Technical Reports Server (NTRS)

Saether, Erik; Yamakov, Vesselin; Phillips, Dawn R.; Glaessgen, Edward H.

2009-01-01

The emerging field of nanomechanics is providing a new focus in the study of the mechanics of materials, particularly in simulating fundamental atomic mechanisms involved in the initiation and evolution of damage. Simulating fundamental material processes using first principles in physics strongly motivates the formulation of computational multiscale methods to link macroscopic failure to the underlying atomic processes from which all material behavior originates. This report gives an overview of the state of the art in applying concurrent and sequential multiscale methods to analyze damage and failure mechanisms across length scales.

Chameleon-like elastomers with molecularly encoded strain-adaptive stiffening and coloration

NASA Astrophysics Data System (ADS)

Vatankhah-Varnosfaderani, Mohammad; Keith, Andrew N.; Cong, Yidan; Liang, Heyi; Rosenthal, Martin; Sztucki, Michael; Clair, Charles; Magonov, Sergei; Ivanov, Dimitri A.; Dobrynin, Andrey V.; Sheiko, Sergei S.

2018-03-01

Active camouflage is widely recognized as a soft-tissue feature, and yet the ability to integrate adaptive coloration and tissuelike mechanical properties into synthetic materials remains elusive. We provide a solution to this problem by uniting these functions in moldable elastomers through the self-assembly of linear-bottlebrush-linear triblock copolymers. Microphase separation of the architecturally distinct blocks results in physically cross-linked networks that display vibrant color, extreme softness, and intense strain stiffening on par with that of skin tissue. Each of these functional properties is regulated by the structure of one macromolecule, without the need for chemical cross-linking or additives. These materials remain stable under conditions characteristic of internal bodily environments and under ambient conditions, neither swelling in bodily fluids nor drying when exposed to air.

Molecular Retrofitting Adapts a Metal–Organic Framework to Extreme Pressure

DOE PAGES

Kapustin, Eugene A.; Lee, Seungkyu; Alshammari, Ahmad S.; ...

2017-06-07

Despite numerous studies on chemical and thermal stability of metal-organic frameworks (MOFs), mechanical stability remains largely undeveloped. No strategy exists to control the mechanical deformation of MOFs under ultrahigh pressure, to date. We show that the mechanically unstable MOF-520 can be retrofitted by precise placement of a rigid 4,4'-biphenyldicarboxylate (BPDC) linker as a "girder" to afford a mechanically robust framework: MOF-520-BPDC. This retrofitting alters how the structure deforms under ultrahigh pressure and thus leads to a drastic enhancement of its mechanical robustness. While in the parent MOF-520 the pressure transmitting medium molecules diffuse into the pore and expand the structuremore » from the inside upon compression, the girder in the new retrofitted MOF-520-BPDC prevents the framework from expansion by linking two adjacent secondary building units together. As a result, the modified MOF is stable under hydrostatic compression in a diamond-anvil cell up to 5.5 gigapascal. The increased mechanical stability of MOF-520-BPDC prohibits the typical amorphization observed for MOFs in this pressure range. Direct correlation between the orientation of these girders within the framework and its linear strain was estimated, providing new insights for the design of MOFs with optimized mechanical properties.« less

From Theory-Inspired to Theory-Based Interventions: A Protocol for Developing and Testing a Methodology for Linking Behaviour Change Techniques to Theoretical Mechanisms of Action.

PubMed

Michie, Susan; Carey, Rachel N; Johnston, Marie; Rothman, Alexander J; de Bruin, Marijn; Kelly, Michael P; Connell, Lauren E

2018-05-18

Understanding links between behaviour change techniques (BCTs) and mechanisms of action (the processes through which they affect behaviour) helps inform the systematic development of behaviour change interventions. This research aims to develop and test a methodology for linking BCTs to their mechanisms of action. Study 1 (published explicit links): Hypothesised links between 93 BCTs (from the 93-item BCT taxonomy, BCTTv1) and mechanisms of action will be identified from published interventions and their frequency, explicitness and precision documented. Study 2 (expert-agreed explicit links): Behaviour change experts will identify links between 61 BCTs and 26 mechanisms of action in a formal consensus study. Study 3 (integrated matrix of explicit links): Agreement between studies 1 and 2 will be evaluated and a new group of experts will discuss discrepancies. An integrated matrix of BCT-mechanism of action links, annotated to indicate strength of evidence, will be generated. Study 4 (published implicit links): To determine whether groups of co-occurring BCTs can be linked to theories, we will identify groups of BCTs that are used together from the study 1 literature. A consensus exercise will be used to rate strength of links between groups of BCT and theories. A formal methodology for linking BCTs to their hypothesised mechanisms of action can contribute to the development and evaluation of behaviour change interventions. This research is a step towards developing a behaviour change 'ontology', specifying relations between BCTs, mechanisms of action, modes of delivery, populations, settings and types of behaviour.

Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins.

PubMed

Bano, Fouzia; Tammi, Markku I; Kang, David W; Harris, Edward N; Richter, Ralf P

2018-06-19

The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Purines and Neuronal Excitability: Links to the Ketogenic Diet

PubMed Central

Masino, SA; Kawamura, M; Ruskin, DN; Geiger, JD; Boison, D

2011-01-01

ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

Unlocking the Constraints of Cyanobacterial Productivity: Acclimations Enabling Ultrafast Growth

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

Bernstein, Hans C.; McClure, Ryan S.; Hill, Eric A.

ABSTRACT Harnessing the metabolic potential of photosynthetic microbes for next-generation biotechnology objectives requires detailed scientific understanding of the physiological constraints and regulatory controls affecting carbon partitioning between biomass, metabolite storage pools, and bioproduct synthesis. We dissected the cellular mechanisms underlying the remarkable physiological robustness of the euryhaline unicellular cyanobacteriumSynechococcussp. strain PCC 7002 (Synechococcus7002) and identify key mechanisms that allow cyanobacteria to achieve unprecedented photoautotrophic productivities (~2.5-h doubling time). Ultrafast growth ofSynechococcus7002 was supported by high rates of photosynthetic electron transfer and linked to significantly elevated transcription of precursor biosynthesis and protein translation machinery. Notably, no growth or photosynthesis inhibition signaturesmore » were observed under any of the tested experimental conditions. Finally, the ultrafast growth inSynechococcus7002 was also linked to a 300% expansion of average cell volume. We hypothesize that this cellular adaptation is required at high irradiances to support higher cell division rates and reduce deleterious effects, corresponding to high light, through increased carbon and reductant sequestration. IMPORTANCEEfficient coupling between photosynthesis and productivity is central to the development of biotechnology based on solar energy. Therefore, understanding the factors constraining maximum rates of carbon processing is necessary to identify regulatory mechanisms and devise strategies to overcome productivity constraints. Here, we interrogate the molecular mechanisms that operate at a systems level to allow cyanobacteria to achieve ultrafast growth. This was done by considering growth and photosynthetic kinetics with global transcription patterns. We have delineated putative biological principles that allow unicellular cyanobacteria to achieve ultrahigh growth rates through photophysiological acclimation and effective management of cellular resource under different growth regimes.« less

Controlled manipulation of elastomers with radiation: Insights from multiquantum nuclear-magnetic-resonance data and mechanical measurements

NASA Astrophysics Data System (ADS)

Maiti, A.; Weisgraber, T.; Dinh, L. N.; Gee, R. H.; Wilson, T.; Chinn, S.; Maxwell, R. S.

2011-03-01

Filled and cross-linked elastomeric rubbers are versatile network materials with a multitude of applications ranging from artificial organs and biomedical devices to cushions, coatings, adhesives, interconnects, and seismic-isolation, thermal, and electrical barriers. External factors such as mechanical stress, temperature fluctuations, or radiation are known to create chemical changes in such materials that can directly affect the molecular weight distribution (MWD) of the polymer between cross-links and alter the structural and mechanical properties. From a materials science point of view it is highly desirable to understand, affect, and manipulate such property changes in a controlled manner. Unfortunately, that has not yet been possible due to the lack of experimental characterization of such networks under controlled environments. In this work we expose a known rubber material to controlled dosages of γ radiation and utilize a newly developed multiquantum nuclear-magnetic-resonance technique to characterize the MWD as a function of radiation. We show that such data along with mechanical stress-strain measurements are amenable to accurate analysis by simple network models and yield important insights into radiation-induced molecular-level processes.

Memory Dynamics in Cross-linked Actin Networks

NASA Astrophysics Data System (ADS)

Scheff, Danielle; Majumdar, Sayantan; Gardel, Margaret

Cells demonstrate the remarkable ability to adapt to mechanical stimuli through rearrangement of the actin cytoskeleton, a cross-linked network of actin filaments. In addition to its importance in cell biology, understanding this mechanical response provides strategies for creation of novel materials. A recent study has demonstrated that applied stress can encode mechanical memory in these networks through changes in network geometry, which gives rise to anisotropic shear response. Under later shear, the network is stiffer in the direction of the previously applied stress. However, the dynamics behind the encoding of this memory are unknown. To address this question, we explore the effect of varying either the rigidity of the cross-linkers or the length of actin filament on the time scales required for both memory encoding and over which it later decays. While previous experiments saw only a long-lived memory, initial results suggest another mechanism where memories relax relatively quickly. Overall, our study is crucial for understanding the process by which an external stress can impact network arrangement and thus the dynamics of memory formation.

Novel Polymer Aerogel toward High Dimensional Stability, Mechanical Property, and Fire Safety.

PubMed

Shang, Ke; Yang, Jun-Chi; Cao, Zhi-Jie; Liao, Wang; Wang, Yu-Zhong; Schiraldi, David A

2017-07-12

Inorganc silica-based aerogels, the earliest and widely used aerogels, have poorer mechanical properties than their organic substitutes, which are flammable. In this study, a novel polymeric aerogel with high strength, inherent flame retardancy, and cost-effectiveness, which is based on poly(vinyl alcohol) (PVA) cross-linked with melamine-formaldehyde (MF), was prepared under aqueous condition with an ecofriendly freeze-drying and postcuring process. Combined with the additional rigid MF network and benifited from the resulting unique infrastructure of inter-cross-linked flexible PVA segments and rigid MF segments, PVA-based aerogels exibited a significantly decreased degradation rate and sharply decreased peak heat release rate (PHRR) in cone calorimeter tests (by as much as 83%) compared with neat PVA. The polymer aerogels have a limiting oxygen index (LOI) as high as 36.5% and V-0 rating in UL-94 test. Furthermore, the aerogel samples exposured to harsh temperatures maintain their dimensions (<10% change), original mechanical strength and fire safety. Therefore, this work provides a novel stragegy for preparing pure organic polymeric aerogel materials with high mechanical strength, dimensional stability, and fire safety.

Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets

PubMed Central

Wang, James K. T.; Langfelder, Peter; Horvath, Steve; Palazzolo, Michael J.

2017-01-01

Huntington's disease (HD) is a progressive and autosomal dominant neurodegeneration caused by CAG expansion in the huntingtin gene (HTT), but the pathophysiological mechanism of mutant HTT (mHTT) remains unclear. To study HD using systems biological methodologies on all published data, we undertook the first comprehensive curation of two key PubMed HD datasets: perturbation genes that impact mHTT-driven endpoints and therefore are putatively linked causally to pathogenic mechanisms, and the protein interactome of HTT that reflects its biology. We perused PubMed articles containing co-citation of gene IDs and MeSH terms of interest to generate mechanistic gene sets for iterative enrichment analyses and rank ordering. The HD Perturbation database of 1,218 genes highly overlaps the HTT Interactome of 1,619 genes, suggesting links between normal HTT biology and mHTT pathology. These two HD datasets are enriched for protein networks of key genes underlying two mechanisms not previously implicated in HD nor in each other: exosome synaptic functions and homeostatic synaptic plasticity. Moreover, proteins, possibly including HTT, and miRNA detected in exosomes from a wide variety of sources also highly overlap the HD datasets, suggesting both mechanistic and biomarker links. Finally, the HTT Interactome highly intersects protein networks of pathogenic genes underlying Parkinson's, Alzheimer's and eight non-HD polyglutamine diseases, ALS, and spinal muscular atrophy. These protein networks in turn highly overlap the exosome and homeostatic synaptic plasticity gene sets. Thus, we hypothesize that HTT and other neurodegeneration pathogenic genes form a large interlocking protein network involved in exosome and homeostatic synaptic functions, particularly where the two mechanisms intersect. Mutant pathogenic proteins cause dysfunctions at distinct points in this network, each altering the two mechanisms in specific fashion that contributes to distinct disease pathologies, depending on the gene mutation and the cellular and biological context. This protein network is rich with drug targets, and exosomes may provide disease biomarkers, thus enabling drug discovery. All the curated datasets are made available for other investigators. Elucidating the roles of pathogenic neurodegeneration genes in exosome and homeostatic synaptic functions may provide a unifying framework for the age-dependent, progressive and tissue selective nature of multiple neurodegenerative diseases. PMID:28611571

Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets.

PubMed

Wang, James K T; Langfelder, Peter; Horvath, Steve; Palazzolo, Michael J

2017-01-01

Huntington's disease (HD) is a progressive and autosomal dominant neurodegeneration caused by CAG expansion in the huntingtin gene ( HTT ), but the pathophysiological mechanism of mutant HTT (mHTT) remains unclear. To study HD using systems biological methodologies on all published data, we undertook the first comprehensive curation of two key PubMed HD datasets: perturbation genes that impact mHTT-driven endpoints and therefore are putatively linked causally to pathogenic mechanisms, and the protein interactome of HTT that reflects its biology. We perused PubMed articles containing co-citation of gene IDs and MeSH terms of interest to generate mechanistic gene sets for iterative enrichment analyses and rank ordering. The HD Perturbation database of 1,218 genes highly overlaps the HTT Interactome of 1,619 genes, suggesting links between normal HTT biology and mHTT pathology. These two HD datasets are enriched for protein networks of key genes underlying two mechanisms not previously implicated in HD nor in each other: exosome synaptic functions and homeostatic synaptic plasticity. Moreover, proteins, possibly including HTT, and miRNA detected in exosomes from a wide variety of sources also highly overlap the HD datasets, suggesting both mechanistic and biomarker links. Finally, the HTT Interactome highly intersects protein networks of pathogenic genes underlying Parkinson's, Alzheimer's and eight non-HD polyglutamine diseases, ALS, and spinal muscular atrophy. These protein networks in turn highly overlap the exosome and homeostatic synaptic plasticity gene sets. Thus, we hypothesize that HTT and other neurodegeneration pathogenic genes form a large interlocking protein network involved in exosome and homeostatic synaptic functions, particularly where the two mechanisms intersect. Mutant pathogenic proteins cause dysfunctions at distinct points in this network, each altering the two mechanisms in specific fashion that contributes to distinct disease pathologies, depending on the gene mutation and the cellular and biological context. This protein network is rich with drug targets, and exosomes may provide disease biomarkers, thus enabling drug discovery. All the curated datasets are made available for other investigators. Elucidating the roles of pathogenic neurodegeneration genes in exosome and homeostatic synaptic functions may provide a unifying framework for the age-dependent, progressive and tissue selective nature of multiple neurodegenerative diseases.

Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease beta-amyloid.

PubMed

Barnham, Kevin J; Haeffner, Fredrik; Ciccotosto, Giuseppe D; Curtain, Cyril C; Tew, Deborah; Mavros, Christine; Beyreuther, Konrad; Carrington, Darryl; Masters, Colin L; Cherny, Robert A; Cappai, Roberto; Bush, Ashley I

2004-09-01

Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles and amyloid plaques, which are abnormal protein deposits. The major constituent of the plaques is the neurotoxic beta-amyloid peptide (Abeta); the genetics of familial AD support a direct role for this peptide in AD. Abeta neurotoxicity is linked to hydrogen peroxide formation. Abeta coordinates the redox active transition metals, copper and iron, to catalytically generate reactive oxygen species. The chemical mechanism underlying this process is not well defined. With the use of density functional theory calculations to delineate the chemical mechanisms that drive the catalytic production of H2O2 by Abeta/Cu, tyrosine10 (Y10) was identified as a pivotal residue for this reaction to proceed. The relative stability of tyrosyl radicals facilitates the electron transfers that are required to drive the reaction. Confirming the theoretical results, mutation of the tyrosine residue to alanine inhibited H2O2 production, Cu-induced radicalization, dityrosine cross-linking, and neurotoxicity.

Diagnostic reasoning and underlying knowledge of students with preclinical patient contacts in PBL.

PubMed

Diemers, Agnes D; van de Wiel, Margje W J; Scherpbier, Albert J J A; Baarveld, Frank; Dolmans, Diana H J M

2015-12-01

Medical experts have access to elaborate and integrated knowledge networks consisting of biomedical and clinical knowledge. These coherent knowledge networks enable them to generate more accurate diagnoses in a shorter time. However, students' knowledge networks are less organised and students have difficulties linking theory and practice and transferring acquired knowledge. Therefore we wanted to explore the development and transfer of knowledge of third-year preclinical students on a problem-based learning (PBL) course with real patient contacts. Before and after a 10-week PBL course with real patients, third-year medical students were asked to think out loud while diagnosing four types of paper patient problems (two course cases and two transfer cases), and explain the underlying pathophysiological mechanisms of the patient features. Diagnostic accuracy and time needed to think through the cases were measured. The think-aloud protocols were transcribed verbatim and different types of knowledge were coded and quantitatively analysed. The written pathophysiological explanations were translated into networks of concepts. Both the concepts and the links between concepts in students' networks were compared to model networks. Over the course diagnostic accuracy increased, case-processing time decreased, and students used less biomedical and clinical knowledge during diagnostic reasoning. The quality of the pathophysiological explanations increased: the students used more concepts, especially more model concepts, and they used fewer wrong concepts and links. The findings differed across course and transfer cases. The effects were generally less strong for transfer cases. Students' improved diagnostic accuracy and the improved quality of their knowledge networks suggest that integration of biomedical and clinical knowledge took place during a 10-week course. The differences between course and transfer cases demonstrate that transfer is complex and time-consuming. We therefore suggest offering students many varied patient contacts with the same underlying pathophysiological mechanism and encouraging students to link biomedical and clinical knowledge. © 2015 John Wiley & Sons Ltd.

Safety Harness For Work Under Suspended Load

NASA Technical Reports Server (NTRS)

Sunoo, Su Young

1994-01-01

Safety device protects worker under suspended engine or other heavy load. Mechanically linked with load so if load should fall, worker yanked safely away. Worker wears chest-plate vest with straps crossing eye on back. Lower safety cable connected to eye extends horizontally away from worker to nearby wall, wrapped on pulley and extends upward to motion amplifier or reducer. Safety cables transform any sudden downward motion of overhanging load into rapid sideways motion of worker. Net catches worker, preventing worker from bumping against wall.

The epigenetic impacts of social stress: how does social adversity become biologically embedded?

PubMed Central

Cunliffe, Vincent T

2016-01-01

Epigenetic mechanisms are implicated in the processes through which social stressors erode health in humans and other animals. Here I review progress in elucidating the biological pathways underlying the social gradient in health, with particular emphasis on how behavioral stresses influence epigenomic variation linked to health. The evidence that epigenetic changes are involved in embedding of social status-linked chronic stress is reviewed in the context of current knowledge about behavior within animal dominance hierarchies and the impacts of social position on behaviors that affect health. The roles of epigenetic mechanisms in responses to trauma and the evidence for their involvement in intergenerational transmission of the biological impacts of traumatic stress are also considered. Taken together, the emerging insights have important implications for development of strategies to improve societal health and well-being. PMID:27869483

N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

PubMed

O'Sullivan, J M; Aguila, S; McRae, E; Ward, S E; Rawley, O; Fallon, P G; Brophy, T M; Preston, R J S; Brady, L; Sheils, O; Chion, A; O'Donnell, J S

2016-12-01

Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF -/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate determinants expressed on VWF also play an unexpectedly important role in modulating in vivo clearance through both hepatic ASGPR-dependent and macrophage-dependent pathways. In addition, these data further support the hypothesis that variation in VWF glycosylation may be important in the pathophysiology underlying type 1C VWD. © 2016 International Society on Thrombosis and Haemostasis.

Strong and weak plasma response to dietary carotenoids identified by cluster analysis and linked to beta-carotene 15,15'-monooxygenase 1 single nucleotide polymorphisms

USDA-ARS?s Scientific Manuscript database

The mechanisms as well the genetics underlying bioavailability and metabolism of carotenoids in humans remains unclear. The individual temporal response of plasma carotenoids was analyzed in adults who consumed carotenoid-containing juices on a controlled-diet study using cluster analysis. Treatmen...

Mapping Language to the World: The Role of Iconicity in the Sign Language Input

ERIC Educational Resources Information Center

Perniss, Pamela; Lu, Jenny C.; Morgan, Gary; Vigliocco, Gabriella

2018-01-01

Most research on the mechanisms underlying referential mapping has assumed that learning occurs in ostensive contexts, where label and referent co-occur, and that form and meaning are linked by arbitrary convention alone. In the present study, we focus on "iconicity" in language, that is, resemblance relationships between form and…

29 CFR 1910.184 - Slings.

Code of Federal Regulations, 2013 CFR

2013-07-01

... under the load and has both ends, end attachments, eyes or handles on the hook or a single master link... lifting hook. Cable laid endless sling-mechanical joint is a wire rope sling made endless by joining the.... N-184-1.) Handle eye is an opening in a handle of a metal mesh sling shaped to accept a hook...

29 CFR 1910.184 - Slings.

Code of Federal Regulations, 2014 CFR

2014-07-01

... under the load and has both ends, end attachments, eyes or handles on the hook or a single master link... lifting hook. Cable laid endless sling-mechanical joint is a wire rope sling made endless by joining the.... N-184-1.) Handle eye is an opening in a handle of a metal mesh sling shaped to accept a hook...

29 CFR 1910.184 - Slings.

Code of Federal Regulations, 2012 CFR

2012-07-01

... under the load and has both ends, end attachments, eyes or handles on the hook or a single master link... lifting hook. Cable laid endless sling-mechanical joint is a wire rope sling made endless by joining the.... N-184-1.) Handle eye is an opening in a handle of a metal mesh sling shaped to accept a hook...

The Mediating Effects of Verbal Skills in the Relationship between Low Birth Weight and Childhood Aggressive Behaviour

ERIC Educational Resources Information Center

Vaske, Jamie; Newsome, Jamie; Boisvert, Danielle

2013-01-01

Prenatal and perinatal risk factors, such as low birth weight, have been linked to higher levels of aggressive and destructive behaviours during childhood. Although low birth weight is associated with childhood externalizing behaviour, the mechanisms underlying this relationship remain open to empirical investigation. The current study extends the…

Social Anxiety and Adolescents' Friendships: The Role of Social Withdrawal

ERIC Educational Resources Information Center

Biggs, Bridget K.; Vernberg, Eric M.; Wu, Yelena P.

2012-01-01

Research indicates social anxiety is associated with lower friendship quality, but little is known about the underlying mechanisms. This 2-month longitudinal study examined social withdrawal as a mediator of the social anxiety-friendship quality link in a sample of 214 adolescents (M[subscript age] = 13.1 years, SD = 0.73) that included an…

Epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes.

PubMed

Khan, Fazlullah; Momtaz, Saeideh; Niaz, Kamal; Hassan, Fatima Ismail; Abdollahi, Mohammad

2017-09-01

Exposure to inorganic arsenic (iAs) is a major threat to the human health worldwide. The consumption of arsenic in drinking water and other food products is associated with the risk of development of type-2 diabetes mellitus (T2DM). The available experimental evidence indicates that epigenetic alterations may play an important role in the development of diseases that are linked with exposure to environmental toxicants. iAs seems to be associated with the epigenetic modifications such as alterations in DNA methylation, histone modifications, and micro RNA (miRNA) abundance. This article reviewed epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes. Electronic databases such as PubMed, Scopus and Google scholar were searched for published literature from 1980 to 2017. Searched MESH terms were "Arsenic", "Epigenetic mechanism", "DNA methylation", "Histone modifications" and "Diabetes". There are various factors involved in the pathogenesis of T2DM but it is assumed that arsenic consumption causes the epigenetic alterations both at the gene-specific level and generalized genome level. The research indicates that exposure from low to moderate concentrations of iAs is linked with the epigenetic effects. In addition, it is evident that, arsenic can change the components of the epigenome and hence induces diabetes through epigenetic mechanisms, such as alterations in glucose transport and/or metabolism and insulin expression/secretion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanical response of common millet (Panicum miliaceum) seeds under quasi-static compression: Experiments and modeling.

PubMed

Hasseldine, Benjamin P J; Gao, Chao; Collins, Joseph M; Jung, Hyun-Do; Jang, Tae-Sik; Song, Juha; Li, Yaning

2017-09-01

The common millet (Panicum miliaceum) seedcoat has a fascinating complex microstructure, with jigsaw puzzle-like epidermis cells articulated via wavy intercellular sutures to form a compact layer to protect the kernel inside. However, little research has been conducted on linking the microstructure details with the overall mechanical response of this interesting biological composite. To this end, an integrated experimental-numerical-analytical investigation was conducted to both characterize the microstructure and ascertain the microscale mechanical properties and to test the overall response of kernels and full seeds under macroscale quasi-static compression. Scanning electron microscopy (SEM) was utilized to examine the microstructure of the outer seedcoat and nanoindentation was performed to obtain the material properties of the seedcoat hard phase material. A multiscale computational strategy was applied to link the microstructure to the macroscale response of the seed. First, the effective anisotropic mechanical properties of the seedcoat were obtained from finite element (FE) simulations of a microscale representative volume element (RVE), which were further verified from sophisticated analytical models. Then, macroscale FE models of the individual kernel and full seed were developed. Good agreement between the compression experiments and FE simulations were obtained for both the kernel and the full seed. The results revealed the anisotropic property and the protective function of the seedcoat, and showed that the sutures of the seedcoat play an important role in transmitting and distributing loads in responding to external compression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social Cognition and the Evolution of Language: Constructing Cognitive Phylogenies

PubMed Central

Fitch, W. Tecumseh; Huber, Ludwig; Bugnyar, Thomas

2015-01-01

Human language and social cognition are closely linked: advanced social cognition is necessary for children to acquire language, and language allows forms of social understanding (and, more broadly, culture) that would otherwise be impossible. Both “language” and “social cognition” are complex constructs, involving many independent cognitive mechanisms, and the comparative approach provides a powerful route to understanding the evolution of such mechanisms. We provide a broad comparative review of mechanisms underlying social intelligence in vertebrates, with the goal of determining which human mechanisms are broadly shared, which have evolved in parallel in other clades, and which, potentially, are uniquely developed in our species. We emphasize the importance of convergent evolution for testing hypotheses about neural mechanisms and their evolution. PMID:20346756

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

PubMed Central

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

2017-01-01

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

The Development of a Flexible Measuring System for Muscle Volume Using Ultrasonography

NASA Astrophysics Data System (ADS)

Fukumoto, Kiyotaka; Fukuda, Osamu; Tsubai, Masayoshi; Muraki, Satoshi

Quantification of muscle volume can be used as a means for the estimation of muscle strength. Its measuring process does not need the subject's muscular contractions so it is completely safe and particularly suited for elderly people. Therefore, we have developed a flexible measuring system for muscle volume using ultrasonography. In this system, an ultrasound probe is installed on a link mechanism which continuously scans fragmental images along the human body surface. These images are then measured and composed into a wide area cross-sectional image based on the spatial compounding method. The flexibility of the link mechanism enables the operator to measure the images under any body postures and body site. The spatial compounding method significantly reduces speckle and artifact noises from the composed cross-sectional image so that the operator can observe the individual muscles, such as Rectus femoris, Vastus intermedius, and so on, in detail. We conducted the experiments in order to examine the advantages of this system we have developed. The experimental results showed a high accuracy of the measuring position which was calculated using the link mechanism and presented the noise reduction effect based on the spatial compounding method. Finally, we confirmed high correlations between the MRI images and the ones of the developed system to verify the validity of the system.

Using an Adoption–Biological Family Design to Examine Associations Between Maternal Trauma, Maternal Depressive Symptoms, and Child Internalizing and Externalizing Behaviors

PubMed Central

Grabow, Aleksandria Perez; Khurana, Atika; Natsuaki, Misaki N.; Neiderhiser, Jenae M.; Harold, Gordon T.; Shaw, Daniel S.; Ganiban, Jody M.; Reiss, David; Leve, Leslie D.

2017-01-01

Maternal trauma is a complex risk factor that has been linked to adverse child outcomes, yet the mechanisms underlying this association are not well understood. This study, which included adoptive and biological families, examined the heritable and environmental mechanisms by which maternal trauma and associated depressive symptoms are linked to child internalizing and externalizing behaviors. Path analyses were used to analyze data from 541 adoptive mother–adopted child (AM–AC) dyads and 126 biological mother–biological child (BM–BC) dyads; the two family types were linked through the same biological mother. Rearing mother’s trauma was associated with child internalizing and externalizing behaviors in AM–AC and BM–BC dyads, and this association was mediated by rearing mothers’ depressive symptoms, with the exception of biological child externalizing behavior, for which biological mother trauma had a direct influence only. Significant associations between maternal trauma and child behavior in dyads that share only environment (i.e., AM–AC dyads) suggest an environmental mechanism of influence for maternal trauma. Significant associations were also observed between maternal depressive symptoms and child internalizing and externalizing behavior in dyads that were only genetically related, with no shared environment (i.e., BM–AC dyads), suggesting a heritable pathway of influence via maternal depressive symptoms. PMID:29162177

Using an adoption-biological family design to examine associations between maternal trauma, maternal depressive symptoms, and child internalizing and externalizing behaviors.

PubMed

Grabow, Aleksandria Perez; Khurana, Atika; Natsuaki, Misaki N; Neiderhiser, Jenae M; Harold, Gordon T; Shaw, Daniel S; Ganiban, Jody M; Reiss, David; Leve, Leslie D

2017-12-01

Maternal trauma is a complex risk factor that has been linked to adverse child outcomes, yet the mechanisms underlying this association are not well understood. This study, which included adoptive and biological families, examined the heritable and environmental mechanisms by which maternal trauma and associated depressive symptoms are linked to child internalizing and externalizing behaviors. Path analyses were used to analyze data from 541 adoptive mother-adopted child (AM-AC) dyads and 126 biological mother-biological child (BM-BC) dyads; the two family types were linked through the same biological mother. Rearing mother's trauma was associated with child internalizing and externalizing behaviors in AM-AC and BM-BC dyads, and this association was mediated by rearing mothers' depressive symptoms, with the exception of biological child externalizing behavior, for which biological mother trauma had a direct influence only. Significant associations between maternal trauma and child behavior in dyads that share only environment (i.e., AM-AC dyads) suggest an environmental mechanism of influence for maternal trauma. Significant associations were also observed between maternal depressive symptoms and child internalizing and externalizing behavior in dyads that were only genetically related, with no shared environment (i.e., BM-AC dyads), suggesting a heritable pathway of influence via maternal depressive symptoms.

Musical rhythm and reading development: does beat processing matter?

PubMed

Ozernov-Palchik, Ola; Patel, Aniruddh D

2018-05-20

There is mounting evidence for links between musical rhythm processing and reading-related cognitive skills, such as phonological awareness. This may be because music and speech are rhythmic: both involve processing complex sound sequences with systematic patterns of timing, accent, and grouping. Yet, there is a salient difference between musical and speech rhythm: musical rhythm is often beat-based (based on an underlying grid of equal time intervals), while speech rhythm is not. Thus, the role of beat-based processing in the reading-rhythm relationship is not clear. Is there is a distinct relation between beat-based processing mechanisms and reading-related language skills, or is the rhythm-reading link entirely due to shared mechanisms for processing nonbeat-based aspects of temporal structure? We discuss recent evidence for a distinct link between beat-based processing and early reading abilities in young children, and suggest experimental designs that would allow one to further methodically investigate this relationship. We propose that beat-based processing taps into a listener's ability to use rich contextual regularities to form predictions, a skill important for reading development. © 2018 New York Academy of Sciences.

The role of social relationships in the link between olfactory dysfunction and mortality.

PubMed

Leschak, Carrianne J; Eisenberger, Naomi I

2018-01-01

Recent work suggests that olfactory dysfunction is a strong predictor of five-year mortality in older adults. Based on past work showing: 1) that olfactory dysfunction impairs social functioning and 2) that social ties are linked with mortality, the current work explored whether impairments in social life mediated the relationship between olfactory dysfunction and mortality. Additionally, based on work showing gender differences in the social consequences of olfactory dysfunction, gender was assessed as a potential moderator of this association. Social network size mediated the olfactory-mortality link for females. To probe what feature of social networks was driving this effect, we investigated two subcomponents of social life: emotional closeness (e.g., perceived social support, loneliness) and physical closeness (e.g., physical contact, in-person socializing with others). Physical closeness significantly mediated the olfactory-mortality link for females, even after controlling for social network size. Emotional closeness did not mediate this link. Possible mechanisms underlying this relationship are discussed.

Predicting the evolution of complex networks via similarity dynamics

NASA Astrophysics Data System (ADS)

Wu, Tao; Chen, Leiting; Zhong, Linfeng; Xian, Xingping

2017-01-01

Almost all real-world networks are subject to constant evolution, and plenty of them have been investigated empirically to uncover the underlying evolution mechanism. However, the evolution prediction of dynamic networks still remains a challenging problem. The crux of this matter is to estimate the future network links of dynamic networks. This paper studies the evolution prediction of dynamic networks with link prediction paradigm. To estimate the likelihood of the existence of links more accurate, an effective and robust similarity index is presented by exploiting network structure adaptively. Moreover, most of the existing link prediction methods do not make a clear distinction between future links and missing links. In order to predict the future links, the networks are regarded as dynamic systems in this paper, and a similarity updating method, spatial-temporal position drift model, is developed to simulate the evolutionary dynamics of node similarity. Then the updated similarities are used as input information for the future links' likelihood estimation. Extensive experiments on real-world networks suggest that the proposed similarity index performs better than baseline methods and the position drift model performs well for evolution prediction in real-world evolving networks.

On the Formation and Properties of Interstrand DNA-DNA Cross-links Forged by Reaction of an Abasic Site With the Opposing Guanine Residue of 5′-CAp Sequences in Duplex DNA

PubMed Central

Johnson, Kevin M.; Price, Nathan E.; Wang, Jin; Fekry, Mostafa I.; Dutta, Sanjay; Seiner, Derrick R.; Wang, Yinsheng; Gates, Kent S.

2014-01-01

We recently reported that the aldehyde residue of an abasic (Ap) site in duplex DNA can generate an interstrand cross-link via reaction with a guanine residue on the opposing strand. This finding is intriguing because the highly deleterious nature of interstrand cross-links suggests that even small amounts of Ap-derived cross-links could make a significant contribution to the biological consequences stemming from the generation of Ap sites in cellular DNA. Incubation of 21-bp duplexes containing a central 5′-CAp sequence under conditions of reductive amination (NaCNBH3, pH 5.2) generated much higher yields of cross-linked DNA than reported previously. At pH 7, in the absence of reducing agents, these Ap-containing duplexes also produced cross-linked duplexes that were readily detected on denaturing polyacrylamide gels. Cross-link formation was not highly sensitive to reaction conditions and, once formed, the cross-link was stable to a variety of work-up conditions. Results of multiple experiments including MALDI-TOF mass spectrometry, gel mobility, methoxyamine capping of the Ap aldehyde, inosine-for-guanine replacement, hydroxyl radical footprinting, and LCMS/MS were consistent with a cross-linking mechanism involving reversible reaction of the Ap aldehyde residue with the N2-amino group of the opposing guanine residue in 5′-CAp sequences to generate hemiaminal, imine, or cyclic hemiaminal cross-links (7-10) that were irreversibly converted under conditions of reductive amination (NaCNBH3/pH 5.2) to a stable amine linkage. Further support for the importance of the exocyclic N2-amino group in this reaction was provided by an experiment showing that installation of a 2-aminopurine-thymine base pair at the cross-linking site produced high yields (15-30%) of a cross-linked duplex at neutral pH, in the absence of NaCNBH3. PMID:23215239

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

PubMed

Chatham, John C; Marchase, Richard B

2010-02-01

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

Linking ADHD to the Neural Circuitry of Attention

PubMed Central

Mueller, Adrienne; Hong, David S.; Shepard, Steven; Moore, Tirin

2017-01-01

ADHD is a complex condition with a heterogeneous presentation. Current diagnosis is primarily based on subjective experience and observer reports of behavioral symptoms – an approach that has significant limitations. Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks than neurotypical controls, and at least seven main functional domains appear implicated in ADHD. We discuss the underlying neural mechanisms of cognitive functions associated with ADHD with emphasis on the neural basis of selective attention, demonstrating the feasibility of basic research approaches for further understanding cognitive behavioral processes as they relate to human psychopathology. The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD. PMID:28483638

An ecological public health approach to understanding the relationships between sustainable urban environments, public health and social equity.

PubMed

Bentley, Michael

2014-09-01

The environmental determinants of public health and social equity present many challenges to a sustainable urbanism-climate change, water shortages and oil dependency to name a few. There are many pathways from urban environments to human health. Numerous links have been described but some underlying mechanisms behind these relationships are less understood. Combining theory and methods is a way of understanding and explaining how the underlying structures of urban environments relate to public health and social equity. This paper proposes a model for an ecological public health, which can be used to explore these relationships. Four principles of an ecological public health-conviviality, equity, sustainability and global responsibility-are used to derive theoretical concepts that can inform ecological public health thinking, which, among other things, provides a way of exploring the underlying mechanisms that link urban environments to public health and social equity. Theories of more-than-human agency inform ways of living together (conviviality) in urban areas. Political ecology links the equity concerns about environmental and social justice. Resilience thinking offers a better way of coming to grips with sustainability. Integrating ecological ethics into public health considers the global consequences of local urban living and thus attends to global responsibility. This way of looking at the relationships between urban environments, public health and social equity answers the call to craft an ecological public health for the twenty-first century by re-imagining public health in a way that acknowledges humans as part of the ecosystem, not separate from it, though not central to it. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Dynamic analysis of six-bar mechanical press for deep drawing

NASA Astrophysics Data System (ADS)

Mitsi, S.; Tsiafis, I.; Bouzakis, K. D.

2017-02-01

This paper analyzes the dynamical behavior of a six-bar linkage used in mechanical presses for metal forming such as deep drawing. In the under study mechanism, a four-bar linkage is connected to a slider through an articulated binary link. The motion of the six-bar linkage is studied by kinematic analysis developing an analytical method. Furthermore, using an iterative method and d’ Alembert’s principle, the joint forces and drive moment are evaluated considering joint frictions. The simulation results obtained with a MATLAB program are validated by comparing the theoretical values of the input moment with the ones obtained from the conservation of energy law.

mRNA localization: an orchestration of assembly, traffic and synthesis.

PubMed

Xing, Lei; Bassell, Gary J

2013-01-01

Asymmetrical mRNA localization and subsequent local translation provide efficient mechanisms for protein sorting in polarized cells. Defects in mRNA localization have been linked to developmental abnormalities and neurological diseases. Thus, it is critical to understand the machineries mediating and mechanisms underlying the asymmetrical distribution of mRNA and its regulation. The goal of this review is to summarize recent advances in the understanding of mRNA transport and localization, including the assembly and sorting of transport messenger ribonucleic protein (mRNP) granules, molecular mechanisms of active mRNP transport, cytoskeletal interactions and regulation of these events by extracellular signals. © 2012 John Wiley & Sons A/S.

Positive Attitude Toward Math Supports Early Academic Success: Behavioral Evidence and Neurocognitive Mechanisms.

PubMed

Chen, Lang; Bae, Se Ri; Battista, Christian; Qin, Shaozheng; Chen, Tianwen; Evans, Tanya M; Menon, Vinod

2018-03-01

Positive attitude is thought to impact academic achievement and learning in children, but little is known about its underlying neurocognitive mechanisms. Using a large behavioral sample of 240 children, we found that positive attitude toward math uniquely predicted math achievement, even after we accounted for multiple other cognitive-affective factors. We then investigated the neural mechanisms underlying the link between positive attitude and academic achievement in two independent cohorts of children (discovery cohort: n = 47; replication cohort: n = 28) and tested competing hypotheses regarding the differential roles of affective-motivational and learning-memory systems. In both cohorts, we found that positive attitude was associated with increased engagement of the hippocampal learning-memory system. Structural equation modeling further revealed that, in both cohorts, increased hippocampal activity and more frequent use of efficient memory-based strategies mediated the relation between positive attitude and higher math achievement. Our study is the first to elucidate the neurocognitive mechanisms by which positive attitude influences learning and academic achievement.

Towards force spectroscopy of single tip-link bonds

NASA Astrophysics Data System (ADS)

Koussa, Mounir A.; Sotomayor, Marcos; Wong, Wesley P.; Corey, David P.

2015-12-01

Inner-ear mechanotransduction relies on tip links, fine protein filaments made of cadherin-23 and protocadherin-15 that convey tension to mechanosensitive channels at the tips of hair-cell stereocilia. The tip-link cadherins are thought to form a heterotetrameric complex, with two cadherin-23 molecules forming the upper part of the filament and two protocadherin-15 molecules forming the lower end. The interaction between cadherin-23 and protocadherin-15 is mediated by their N-terminal tips. Missense mutations that modify the interaction interface impair binding and lead to deafness. Molecular dynamics simulations predict that the tip-link bond is mechanically strong enough to withstand forces in hair cells, but its experimentally determined strength is unknown. We have developed molecular tools to facilitate single-molecule force spectroscopy on the tip link bond. Self-assembling DNA nanoswitches are functionalized with the interacting tips of cadherin-23 and protocadherin-15 using the enzyme sortase under conditions that preserve protein function. These tip link nanoswitches are designed to provide a signature force-extension profile. This molecular signature should allow us to identify single-molecule rupture events in pulling experiments.

Isolation of Mouse Primary Gastric Epithelial Cells to Investigate the Mechanisms of Helicobacter pylori Associated Disease.

PubMed

Tran, Le Son; Ferrero, Richard L

2018-01-01

The gastrointestinal epithelium provides the first line of defense against invading pathogens, among which Helicobacter pylori is linked to numerous gastric pathologies, including chronic gastritis and cancer. Primary gastric epithelial cells represent a useful model for the investigation of the underlying molecular and cellular mechanisms involved in these H. pylori associated diseases. In this chapter, we describe a method for the isolation of primary gastric epithelial cells from mice and detection of epithelial cell adhesion molecule (EpCAM) expression in the isolated cells.

A mechanism for decoupling within the oceanic lithosphere revealed in the Troodos ophiolite

USGS Publications Warehouse

Agar, Susan M.; Klitgord, Kim D.

1995-01-01

Contrasting kinematic histories recorded in the sheeted dykes and underlying plutonic rocks of the Troodos ophiolite provide a new perspective on the mechanical evolution of oceanic spreading centres. The kinematic framework of the decoupling zone that partitions deformation between the sheeted dykes and plutonics contrasts with low-angle detachment models for slow-spreading ridges based on continental-rift analogues. A model for the generation of multiple, horizontal decoupling horizons, linked by planar normal faults, demonstrates new possibilities for the kinematic and rheological significance of seismic reflectors in oceanic lithosphere.

From quantum mechanics to finance: Microfoundations for jumps, spikes and high volatility phases in diffusion price processes

NASA Astrophysics Data System (ADS)

Henkel, Christof

2017-03-01

We present an agent behavior based microscopic model that induces jumps, spikes and high volatility phases in the price process of a traded asset. We transfer dynamics of thermally activated jumps of an unexcited/excited two state system discussed in the context of quantum mechanics to agent socio-economic behavior and provide microfoundations. After we link the endogenous agent behavior to price dynamics we establish the circumstances under which the dynamics converge to an Itô-diffusion price processes in the large market limit.

Dynamically Cross-linked Elastomer Hybrids with Light-Induced Rapid and Efficient Self-Healing Ability and Reprogrammable Shape Memory Behavior.

PubMed

Bai, Jing; Shi, Zixing

2017-08-16

Pristine carbon nanotubes (CNTs) were activated to exhibit Diels-Alder (DA) reactivity in a polymer matrix, which was modified with monomers containing furan groups. The DA-active polymer matrix was transferred into a dynamic reversible cross-linked inorganic-organic network via a Diels-Alder reaction with CNTs, where pristine CNTs were used as dienophile chemicals and furan-modified SBS acted as the macromolecular diene. In this system, the mechanical properties as well as resilience and solvent resistance were greatly improved even with the presence of only 1 wt % CNTs. Meanwhile, the hybrids retained recyclability and exhibited some smart behaviors, including self-healing and reprogrammable shape memory properties. Furthermore, due to the photothermal effect of CNTs, a retro-Diels-Alder (rDA) reaction was activated under laser irradiation, and healing of a crack on the hybrid surface was demonstrated in approximately 10 s with almost complete recovery of the mechanical properties. Such fast and efficient self-healing performance provides a new concept in designing self-healing nanocomposites with tunable structures and mechanical properties. Furthermore, the DA and rDA reactions could be combined to reprogram the shape memory behavior under laser irradiation or thermal treatment, wherein the temporary shape of the sample could be transferred to a permanent shape via the rDA reaction at high temperature.

Influence of cross-link structure, density and mechanical properties in the mesoscale deformation mechanisms of collagen fibrils

PubMed Central

Depalle, Baptiste; Qin, Zhao; Shefelbine, Sandra J.; Buehler, Markus J.

2015-01-01

Collagen is a ubiquitous protein with remarkable mechanical properties. It is highly elastic, shows large fracture strength and enables substantial energy dissipation during deformation. Most of the connective tissue in humans consists of collagen fibrils composed of a staggered array of tropocollagen molecules, which are connected by intermolecular cross-links. In this study, we report a three-dimensional coarse-grained model of collagen and analyze the influence of enzymatic cross-links on the mechanics of collagen fibrils. Two representatives immature and mature cross-links are implemented in the mesoscale model using a bottom-up approach. By varying the number, type and mechanical properties of cross-links in the fibrils and performing tensile test on the models, we systematically investigate the deformation mechanisms of cross-linked collagen fibrils. We find that cross-linked fibrils exhibit a three phase behavior, which agrees closer with experimental results than what was obtained using previous models. The fibril mechanical response is characterized by: (i) an initial elastic deformation corresponding to the collagen molecule uncoiling, (ii) a linear regime dominated by molecule sliding and (iii) the second stiffer elastic regime related to the stretching of the backbone of the tropocollagen molecules until the fibril ruptures. Our results suggest that both cross-link density and type dictate the stiffness of large deformation regime by increasing the number of interconnected molecules while cross-links mechanical properties determine the failure strain and strength of the fibril. These findings reveal that cross-links play an essential role in creating an interconnected fibrillar material of tunable toughness and strength. PMID:25153614

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

PubMed Central

2017-01-01

Introduction Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. Methods A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. Results The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Conclusion Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors. PMID:29077727

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

PubMed

Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

2017-01-01

Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.

31 CFR 1060.300 - Reporting obligations on foreign bank relationships with Iranian-linked financial institutions...

Code of Federal Regulations, 2012 CFR

2012-07-01

... relationships with Iranian-linked financial institutions designated under IEEPA and IRGC-linked persons... under IEEPA and IRGC-linked persons designated under IEEPA. (a) General. (1) Upon receiving a written... IRGC-linked person designated under IEEPA processed by such foreign bank within the preceding 90...

31 CFR 1060.300 - Reporting obligations on foreign bank relationships with Iranian-linked financial institutions...

Code of Federal Regulations, 2013 CFR

2013-07-01

... relationships with Iranian-linked financial institutions designated under IEEPA and IRGC-linked persons... under IEEPA and IRGC-linked persons designated under IEEPA. (a) General. (1) Upon receiving a written... IRGC-linked person designated under IEEPA processed by such foreign bank within the preceding 90...

31 CFR 1060.300 - Reporting obligations on foreign bank relationships with Iranian-linked financial institutions...

Code of Federal Regulations, 2014 CFR

2014-07-01

... relationships with Iranian-linked financial institutions designated under IEEPA and IRGC-linked persons... under IEEPA and IRGC-linked persons designated under IEEPA. (a) General. (1) Upon receiving a written... IRGC-linked person designated under IEEPA processed by such foreign bank within the preceding 90...

Symposium II: Mechanochemistry in Materials Science, MRS Fall Meeting, Nov 30-Dec 4, 2009, Boston, MA

DTIC Science & Technology

2010-09-02

Dynamic Mechanical Analysis (DMA). The fracture behavior of the mechanophore-linked polymer is also examined through the Double Cleavage Drilled ...multinary complex structures. Structural, microstructural, and chemical characterizations were explored by metrological tools to support this...simple hydrocarbons in order to quantitatively define structure-property relationships for reacting materials under shock compression. Embedded gauge

Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Background: The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat western diet, but the mechanism underlying this relationship remains to be determined. Objective: We tested the hypothesis that a high-fat diet promotes aberrant crypt (AC) format...

Developing Causal Understanding with Causal Maps: The Impact of Total Links, Temporal Flow, and Lateral Position of Outcome Nodes

ERIC Educational Resources Information Center

Jeong, Allan; Lee, Woon Jee

2012-01-01

This study examined some of the methodological approaches used by students to construct causal maps in order to determine which approaches help students understand the underlying causes and causal mechanisms in a complex system. This study tested the relationship between causal understanding (ratio of root causes correctly/incorrectly identified,…

Plant response to environmental conditions: assessing potential production, water demand, and negative effects of water deficit

PubMed Central

Tardieu, François

2013-01-01

This paper reviews methods for analyzing plant performance and its genetic variability under a range of environmental conditions. Biomass accumulation is linked every day to available light in the photosynthetically active radiation (PAR) domain, multiplied by the proportion of light intercepted by plants and by the radiation use efficiency. Total biomass is cumulated over the duration of the considered phase (e.g., plant cycle or vegetative phase). These durations are essentially constant for a given genotype provided that time is corrected for temperature (thermal time). Several ways of expressing thermal time are reviewed. Two alternative equations are presented, based either on the effect of transpiration, or on yield components. Their comparative interests and drawbacks are discussed. The genetic variability of each term of considered equations affects yield under water deficit, via mechanisms at different scales of plant organization and time. The effect of any physiological mechanism on yield of stressed plants acts via one of these terms, although the link is not always straightforward. Finally, I propose practical ways to compare the productivity of genotypes in field environments, and a “minimum dataset” of environmental data and traits that should be recorded for that. PMID:23423357

The Role of DNA Methylation in Cardiovascular Risk and Disease: Methodological Aspects, Study Design, and Data Analysis for Epidemiological Studies.

PubMed

Zhong, Jia; Agha, Golareh; Baccarelli, Andrea A

2016-01-08

Epidemiological studies have demonstrated that genetic, environmental, behavioral, and clinical factors contribute to cardiovascular disease development. How these risk factors interact at the cellular level to cause cardiovascular disease is not well known. Epigenetic epidemiology enables researchers to explore critical links between genomic coding, modifiable exposures, and manifestation of disease phenotype. One epigenetic link, DNA methylation, is potentially an important mechanism underlying these associations. In the past decade, there has been a significant increase in the number of epidemiological studies investigating cardiovascular risk factors and outcomes in relation to DNA methylation, but many gaps remain in our understanding of the underlying cause and biological implications. In this review, we provide a brief overview of the biology and mechanisms of DNA methylation and its role in cardiovascular disease. In addition, we summarize the current evidence base in epigenetic epidemiology studies relevant to cardiovascular health and disease and discuss the limitations, challenges, and future directions of the field. Finally, we provide guidelines for well-designed epigenetic epidemiology studies, with particular focus on methodological aspects, study design, and analytical challenges. © 2016 American Heart Association, Inc.

Spatiotemporal properties of microsaccades: Model predictions and experimental tests

NASA Astrophysics Data System (ADS)

Zhou, Jian-Fang; Yuan, Wu-Jie; Zhou, Zhao

2016-10-01

Microsaccades are involuntary and very small eye movements during fixation. Recently, the microsaccade-related neural dynamics have been extensively investigated both in experiments and by constructing neural network models. Experimentally, microsaccades also exhibit many behavioral properties. It’s well known that the behavior properties imply the underlying neural dynamical mechanisms, and so are determined by neural dynamics. The behavioral properties resulted from neural responses to microsaccades, however, are not yet understood and are rarely studied theoretically. Linking neural dynamics to behavior is one of the central goals of neuroscience. In this paper, we provide behavior predictions on spatiotemporal properties of microsaccades according to microsaccade-induced neural dynamics in a cascading network model, which includes both retinal adaptation and short-term depression (STD) at thalamocortical synapses. We also successfully give experimental tests in the statistical sense. Our results provide the first behavior description of microsaccades based on neural dynamics induced by behaving activity, and so firstly link neural dynamics to behavior of microsaccades. These results indicate strongly that the cascading adaptations play an important role in the study of microsaccades. Our work may be useful for further investigations of the microsaccadic behavioral properties and of the underlying neural dynamical mechanisms responsible for the behavioral properties.

Effect of proton pump inhibitors on magnesium balance: is there a link to cardiovascular risk?

PubMed

Pisani, Laura Francesca; Filippi, Elisabetta; Vavassori, Sara; Munizio, Nadia; Vecchi, Maurizio; Pastorelli, Luca

2016-03-01

Magnesium (Mg(2+)) is the second most copious element inside human cells and the fourth most abundant positively charged ion in the human body. It is of central importance for a broad variety of physiological processes, including intracellular signaling, neuronal excitability, muscle contraction, bone formation and enzyme activation. Its overall balance is tightly regulated by the concerted actions of the intestine, bones and kidneys. Disturbance of this balance can have serious consequences. Symptoms of hypomagnesaemia include tetany, seizures and cardiac arrhythmias, whereas hypermagnesaemia may cause cardiovascular and neuromuscular abnormalities. Drugs can interfere with Mg(2+) homoeostasis in several ways, and proton-pump inhibitors (PPIs) have been associated with hypomagnesaemia. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg(2+) balance will isuggest ideas for prevention and treatment, and might provide greater insight into Mg(2+) homoeostasis. This review gives an overview of the influence of PPIs on Mg(2+) homoeostasis and provides some understanding of the underlying physiological mechanisms. Moreover, we will discuss the potential link between PPI-induced changes in Mg(2+) homeostasis, and the reported cardiovascular risk observed in long-term PPI users.

How might contact with nature promote human health? Promising mechanisms and a possible central pathway.

PubMed

Kuo, Ming

2015-01-01

How might contact with nature promote human health? Myriad studies have linked the two; at this time the task of identifying the mechanisms underlying this link is paramount. This article offers: (1) a compilation of plausible pathways between nature and health; (2) criteria for identifying a possible central pathway; and (3) one promising candidate for a central pathway. The 21 pathways identified here include environmental factors, physiological and psychological states, and behaviors or conditions, each of which has been empirically tied to nature and has implications for specific physical and mental health outcomes. While each is likely to contribute to nature's impacts on health to some degree and under some circumstances, this paper explores the possibility of a central pathway by proposing criteria for identifying such a pathway and illustrating their use. A particular pathway is more likely to be central if it can account for the size of nature's impacts on health, account for nature's specific health outcomes, and subsume other pathways. By these criteria, enhanced immune functioning emerges as one promising candidate for a central pathway between nature and health. There may be others.

Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014.

PubMed

Denys, Marie-Astrid; Anding, Ralf; Tubaro, Andrea; Abrams, Paul; Everaert, Karel

2016-02-01

To investigate the link between lower urinary tract symptoms (LUTS) and metabolic disorders. This report results from presentations and subsequent discussions about LUTS and metabolic disorders at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2014. There are common pathophysiological determinants for the onset of LUTS and the metabolic syndrome (MetS). Both conditions are multifactorial, related to disorders in circadian rhythms and share common risk factors. As in men with erectile dysfunction, these potentially modifiable lifestyle factors may be novel targets to prevent and treat LUTS. The link between LUTS and metabolic disorders is discussed by using sleep, urine production and bladder function as underlying mechanisms that need to be further explored during future research. Recent findings indicate a bidirectional relationship between LUTS and the MetS. Future research has to explore underlying mechanisms to explain this relationship, in order to develop new preventive and therapeutic recommendations, such as weight loss and increasing physical activity. The second stage is to determine the effect of these new treatment approaches on the severity of LUTS and each of the components of the MetS. © 2016 Wiley Periodicals, Inc.

Fungal Exposure and Asthma: IgE and Non-IgE-Mediated Mechanisms.

PubMed

Zhang, Zhonghua; Reponen, Tiina; Hershey, Gurjit K Khurana

2016-11-01

Fungi are ubiquitous in indoor and outdoor environments and have been associated with respiratory disease including childhood and adult asthma. A growing body of evidence from human and animal studies has revealed a link between fungal exposure, especially indoor fungal exposure, with asthma initiation, persistence, and exacerbation. Despite the overwhelming evidence linking mold exposure and asthma, the mechanistic basis for the association has remained elusive. It is now clear that fungi need not be intact to impart negative health effects. Fungal components and fungal fragments are biologically active and contribute to asthma development and severity. Recent mechanistic studies have demonstrated that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. This paper will review the connection between fungal exposure and asthma with a focus on the immunological mechanisms underlying this relationship.

Nanoscale studies link amyloid maturity with polyglutamine diseases onset

NASA Astrophysics Data System (ADS)

Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

2016-08-01

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.

Social Isolation and Adult Mortality: The Role of Chronic Inflammation and Sex Differences

PubMed Central

Yang, Yang Claire; McClintock, Martha K.; Kozloski, Michael; Li, Ting

2014-01-01

The health and survival benefits of social embeddedness have been widely documented across social species, but the underlying biophysiological mechanisms have not been elucidated in the general population. We assessed the process by which social isolation increases the risk for all-cause and chronic disease mortality through proinflammatory mechanisms. Using the 18-year mortality follow-up data (n = 6,729) from the National Health and Nutrition Examination Survey (1988–2006) on Social Network Index and multiple markers of chronic inflammation, we conducted survival analyses and found evidence that supports the mediation role of chronic inflammation in the link between social isolation and mortality. A high-risk fibrinogen level and cumulative inflammation burden may be particularly important in this link. There are notable sex differences in the mortality effects of social isolation in that they are greater for men and can be attributed in part to their heightened inflammatory responses. PMID:23653312

Study on the friction of κ-carrageenan hydrogels in air and aqueous environments.

PubMed

Kozbial, Andrew; Li, Lei

2014-03-01

Understanding the friction mechanism of polysaccharide hydrogels, which is the key component of human cartilage that has very low friction coefficient, is critical to develop next generation artificial joint replacement materials. In this study, the friction of the polysaccharide κ-carrageenan hydrogel was investigated to elucidate the effect of external load, cross-linking density, velocity, and environment on friction. Our experimental results show that (1) coefficient of friction (COF) decreases with normal load in air and remains constant in water, (2) increasing cross-linking density concurrently increases friction and is proportional to Young's modulus, (3) COF increases with testing velocity in both air and water, and (4) friction is reduced in aqueous environment due to the lubricating effect of water. The underlying frictional mechanism is discussed on the basis of water transport from bulk to surface and a previously proposed "repulsion-adsorption" model. Copyright © 2013 Elsevier B.V. All rights reserved.

The molecular mechanism of thermal noise in rod photoreceptors.

PubMed

Gozem, Samer; Schapiro, Igor; Ferré, Nicolas; Olivucci, Massimo

2012-09-07

Spontaneous electrical signals in the retina's photoreceptors impose a limit on visual sensitivity. Their origin is attributed to a thermal, rather than photochemical, activation of the transduction cascade. Although the mechanism of such a process is under debate, the observation of a relationship between the maximum absorption wavelength (λ(max)) and the thermal activation kinetic constant (k) of different visual pigments (the Barlow correlation) indicates that the thermal and photochemical activations are related. Here we show that a quantum chemical model of the bovine rod pigment provides a molecular-level understanding of the Barlow correlation. The transition state mediating thermal activation has the same electronic structure as the photoreceptor excited state, thus creating a direct link between λ(max) and k. Such a link appears to be the manifestation of intrinsic chromophore features associated with the existence of a conical intersection between its ground and excited states.

Transglycosylation reactions, a main mechanism of phenolics incorporation in coffee melanoidins: Inhibition by Maillard reaction.

PubMed

Moreira, Ana S P; Nunes, Fernando M; Simões, Cristiana; Maciel, Elisabete; Domingues, Pedro; Domingues, M Rosário M; Coimbra, Manuel A

2017-07-15

Under roasting conditions, polysaccharides depolymerize and also are able to polymerize, forming new polymers through non-enzymatic transglycosylation reactions (TGRs). TGRs can also occur between carbohydrates and aglycones, such as the phenolic compounds present in daily consumed foods like coffee. In this study, glycosidically-linked phenolic compounds were quantified in coffee melanoidins, the polymeric nitrogenous brown-colored compounds formed during roasting, defined as end-products of Maillard reaction. One third of the phenolics present were in glycosidically-linked form. In addition, the roasting of solid-state mixtures mimicking coffee beans composition allowed the conclusion that proteins play a regulatory role in TGRs extension and, consequently, modulate melanoidins composition. Overall, the results obtained showed that TGRs are a main mechanism of phenolics incorporation in melanoidins and are inhibited by amino groups through Maillard reaction. Copyright © 2017 Elsevier Ltd. All rights reserved.

GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

PubMed Central

de Jonge, Jeroen C.; Vinkers, Christiaan H.; Hulshoff Pol, Hilleke E.; Marsman, Anouk

2017-01-01

Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic) neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS) offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course. PMID:28848455

Cross-generational influences on childhood anxiety disorders: pathways and mechanisms

PubMed Central

Leckman, James F.; Silverman, Wendy K.; Feldman, Ruth

2016-01-01

Anxiety disorders are common across the lifespan, cause severe distress and impairment, and usually have their onset in childhood. Substantial clinical and epidemiological research has demonstrated the existence of links between anxiety and its disorders in children and parents. Research on the pathways and mechanisms underlying these links has pointed to both behavioral and biological systems. This review synthesizes and summarizes several major aspects of this research. Behavioral systems include vicarious learning, social referencing, and modeling of parental anxiety; overly protective or critical parenting styles; and aspects of parental responses to child anxiety including family accommodation of the child’s symptoms. Biological systems include aspects of the prenatal environment affected by maternal anxiety, development and functioning of the oxytocinergic system, and genetic and epigenetic transmission. Implications for the prevention and treatment of child anxiety disorders are discussed, including the potential to enhance child anxiety treatment outcomes through biologically informed parent-based interventions. PMID:27145763

Cross-generational influences on childhood anxiety disorders: pathways and mechanisms.

PubMed

Lebowitz, Eli R; Leckman, James F; Silverman, Wendy K; Feldman, Ruth

2016-09-01

Anxiety disorders are common across the lifespan, cause severe distress and impairment, and usually have their onset in childhood. Substantial clinical and epidemiological research has demonstrated the existence of links between anxiety and its disorders in children and parents. Research on the pathways and mechanisms underlying these links has pointed to both behavioral and biological systems. This review synthesizes and summarizes several major aspects of this research. Behavioral systems include vicarious learning, social referencing, and modeling of parental anxiety; overly protective or critical parenting styles; and aspects of parental responses to child anxiety including family accommodation of the child's symptoms. Biological systems include aspects of the prenatal environment affected by maternal anxiety, development and functioning of the oxytocinergic system, and genetic and epigenetic transmission. Implications for the prevention and treatment of child anxiety disorders are discussed, including the potential to enhance child anxiety treatment outcomes through biologically informed parent-based interventions.

How does our brain constitute defense mechanisms? First-person neuroscience and psychoanalysis.

PubMed

Northoff, Georg; Bermpohl, Felix; Schoeneich, Frank; Boeker, Heinz

2007-01-01

Current progress in the cognitive and affective neurosciences is constantly influencing the development of psychoanalytic theory and practice. However, despite the emerging dialogue between neuroscience and psychoanalysis, the neuronal processes underlying psychoanalytic constructs such as defense mechanisms remain unclear. One of the main problems in investigating the psychodynamic-neuronal relationship consists in systematically linking the individual contents of first-person subjective experience to third-person observation of neuronal states. We therefore introduced an appropriate methodological strategy, 'first-person neuroscience', which aims at developing methods for systematically linking first- and third-person data. The utility of first-person neuroscience can be demonstrated by the example of the defense mechanism of sensorimotor regression as paradigmatically observed in catatonia. Combined psychodynamic and imaging studies suggest that sensorimotor regression might be associated with dysfunction in the neural network including the orbitofrontal, the medial prefrontal and the premotor cortices. In general sensorimotor regression and other defense mechanisms are psychoanalytic constructs that are hypothesized to be complex emotional-cognitive constellations. In this paper we suggest that specific functional mechanisms which integrate neuronal activity across several brain regions (i.e. neuronal integration) are the physiological substrates of defense mechanisms. We conclude that first-person neuroscience could be an appropriate methodological strategy for opening the door to a better understanding of the neuronal processes of defense mechanisms and their modulation in psychoanalytic psychotherapy. Copyright 2007 S. Karger AG, Basel.

A Glider-Assisted Link Disruption Restoration Mechanism in Underwater Acoustic Sensor Networks.

PubMed

Jin, Zhigang; Wang, Ning; Su, Yishan; Yang, Qiuling

2018-02-07

Underwater acoustic sensor networks (UASNs) have become a hot research topic. In UASNs, nodes can be affected by ocean currents and external forces, which could result in sudden link disruption. Therefore, designing a flexible and efficient link disruption restoration mechanism to ensure the network connectivity is a challenge. In the paper, we propose a glider-assisted restoration mechanism which includes link disruption recognition and related link restoring mechanism. In the link disruption recognition mechanism, the cluster heads collect the link disruption information and then schedule gliders acting as relay nodes to restore the disrupted link. Considering the glider's sawtooth motion, we design a relay location optimization algorithm with a consideration of both the glider's trajectory and acoustic channel attenuation model. The utility function is established by minimizing the channel attenuation and the optimal location of glider is solved by a multiplier method. The glider-assisted restoration mechanism can greatly improve the packet delivery rate and reduce the communication energy consumption and it is more general for the restoration of different link disruption scenarios. The simulation results show that glider-assisted restoration mechanism can improve the delivery rate of data packets by 15-33% compared with cooperative opportunistic routing (OVAR), the hop-by-hop vector-based forwarding (HH-VBF) and the vector based forward (VBF) methods, and reduce communication energy consumption by 20-58% for a typical network's setting.

A Glider-Assisted Link Disruption Restoration Mechanism in Underwater Acoustic Sensor Networks

PubMed Central

Wang, Ning; Su, Yishan; Yang, Qiuling

2018-01-01

Underwater acoustic sensor networks (UASNs) have become a hot research topic. In UASNs, nodes can be affected by ocean currents and external forces, which could result in sudden link disruption. Therefore, designing a flexible and efficient link disruption restoration mechanism to ensure the network connectivity is a challenge. In the paper, we propose a glider-assisted restoration mechanism which includes link disruption recognition and related link restoring mechanism. In the link disruption recognition mechanism, the cluster heads collect the link disruption information and then schedule gliders acting as relay nodes to restore the disrupted link. Considering the glider’s sawtooth motion, we design a relay location optimization algorithm with a consideration of both the glider’s trajectory and acoustic channel attenuation model. The utility function is established by minimizing the channel attenuation and the optimal location of glider is solved by a multiplier method. The glider-assisted restoration mechanism can greatly improve the packet delivery rate and reduce the communication energy consumption and it is more general for the restoration of different link disruption scenarios. The simulation results show that glider-assisted restoration mechanism can improve the delivery rate of data packets by 15–33% compared with cooperative opportunistic routing (OVAR), the hop-by-hop vector-based forwarding (HH-VBF) and the vector based forward (VBF) methods, and reduce communication energy consumption by 20–58% for a typical network’s setting. PMID:29414898

Deformation micromechanisms of collagen fibrils under uniaxial tension

PubMed Central

Tang, Yuye; Ballarini, Roberto; Buehler, Markus J.; Eppell, Steven J.

2010-01-01

Collagen, an essential building block of connective tissues, possesses useful mechanical properties due to its hierarchical structure. However, little is known about the mechanical properties of collagen fibril, an intermediate structure between the collagen molecule and connective tissue. Here, we report the results of systematic molecular dynamics simulations to probe the mechanical response of initially unflawed finite size collagen fibrils subjected to uniaxial tension. The observed deformation mechanisms, associated with rupture and sliding of tropocollagen molecules, are strongly influenced by fibril length, width and cross-linking density. Fibrils containing more than approximately 10 molecules along their length and across their width behave as representative volume elements and exhibit brittle fracture. Shorter fibrils experience a more graceful ductile-like failure. An analytical model is constructed and the results of the molecular modelling are used to find curve-fitted expressions for yield stress, yield strain and fracture strain as functions of fibril structural parameters. Our results for the first time elucidate the size dependence of mechanical failure properties of collagen fibrils. The associated molecular deformation mechanisms allow the full power of traditional material and structural engineering theory to be applied to our understanding of the normal and pathological mechanical behaviours of collagenous tissues under load. PMID:19897533

Purines and neuronal excitability: links to the ketogenic diet.

PubMed

Masino, S A; Kawamura, M; Ruskin, D N; Geiger, J D; Boison, D

2012-07-01

ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. Copyright © 2011 Elsevier B.V. All rights reserved.

Generator voltage stabilisation for series-hybrid electric vehicles.

PubMed

Stewart, P; Gladwin, D; Stewart, J; Cowley, R

2008-04-01

This paper presents a controller for use in speed control of an internal combustion engine for series-hybrid electric vehicle applications. Particular reference is made to the stability of the rectified DC link voltage under load disturbance. In the system under consideration, the primary power source is a four-cylinder normally aspirated gasoline internal combustion engine, which is mechanically coupled to a three-phase permanent magnet AC generator. The generated AC voltage is subsequently rectified to supply a lead-acid battery, and permanent magnet traction motors via three-phase full bridge power electronic inverters. Two complementary performance objectives exist. Firstly to maintain the internal combustion engine at its optimal operating point, and secondly to supply a stable 42 V supply to the traction drive inverters. Achievement of these goals minimises the transient energy storage requirements at the DC link, with a consequent reduction in both weight and cost. These objectives imply constant velocity operation of the internal combustion engine under external load disturbances and changes in both operating conditions and vehicle speed set-points. An electronically operated throttle allows closed loop engine velocity control. System time delays and nonlinearities render closed loop control design extremely problematic. A model-based controller is designed and shown to be effective in controlling the DC link voltage, resulting in the well-conditioned operation of the hybrid vehicle.

Comorbidity in Atopic Dermatitis.

PubMed

Simpson, Eric L

2012-03-01

The negative impact of atopic dermatitis (AD) often extends beyond the skin. Children with AD experience increased rates of infectious, mental health, and allergic diseases compared to their non-atopic peers. The mechanisms underlying these associations remain elusive. New insights from genetic and epidermal research pinpoint the skin barrier as a primary initiator of AD. Epicutaneous sensitization represents an intriguing new model which links a disrupted skin barrier to the later development of IgE-mediated diseases in patients with AD. Recent epidemiological studies have identified new comorbidities linked to AD as well, including several mental health disorders and obesity. This manuscript reviews the recent literature regarding both classic and newly described AD comorbidities.

Influence of cross-link structure, density and mechanical properties in the mesoscale deformation mechanisms of collagen fibrils.

PubMed

Depalle, Baptiste; Qin, Zhao; Shefelbine, Sandra J; Buehler, Markus J

2015-12-01

Collagen is a ubiquitous protein with remarkable mechanical properties. It is highly elastic, shows large fracture strength and enables substantial energy dissipation during deformation. Most of the connective tissue in humans consists of collagen fibrils composed of a staggered array of tropocollagen molecules, which are connected by intermolecular cross-links. In this study, we report a three-dimensional coarse-grained model of collagen and analyze the influence of enzymatic cross-links on the mechanics of collagen fibrils. Two representatives immature and mature cross-links are implemented in the mesoscale model using a bottom-up approach. By varying the number, type and mechanical properties of cross-links in the fibrils and performing tensile test on the models, we systematically investigate the deformation mechanisms of cross-linked collagen fibrils. We find that cross-linked fibrils exhibit a three phase behavior, which agrees closer with experimental results than what was obtained using previous models. The fibril mechanical response is characterized by: (i) an initial elastic deformation corresponding to the collagen molecule uncoiling, (ii) a linear regime dominated by molecule sliding and (iii) the second stiffer elastic regime related to the stretching of the backbone of the tropocollagen molecules until the fibril ruptures. Our results suggest that both cross-link density and type dictate the stiffness of large deformation regime by increasing the number of interconnected molecules while cross-links mechanical properties determine the failure strain and strength of the fibril. These findings reveal that cross-links play an essential role in creating an interconnected fibrillar material of tunable toughness and strength. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

RNA G-quadruplexes: emerging mechanisms in disease

PubMed Central

Cammas, Anne

2017-01-01

Abstract RNA G-quadruplexes (G4s) are formed by G-rich RNA sequences in protein-coding (mRNA) and non-coding (ncRNA) transcripts that fold into a four-stranded conformation. Experimental studies and bioinformatic predictions support the view that these structures are involved in different cellular functions associated to both DNA processes (telomere elongation, recombination and transcription) and RNA post-transcriptional mechanisms (including pre-mRNA processing, mRNA turnover, targeting and translation). An increasing number of different diseases have been associated with the inappropriate regulation of RNA G4s exemplifying the potential importance of these structures on human health. Here, we review the different molecular mechanisms underlying the link between RNA G4s and human diseases by proposing several overlapping models of deregulation emerging from recent research, including (i) sequestration of RNA-binding proteins, (ii) aberrant expression or localization of RNA G4-binding proteins, (iii) repeat associated non-AUG (RAN) translation, (iv) mRNA translational blockade and (v) disabling of protein–RNA G4 complexes. This review also provides a comprehensive survey of the functional RNA G4 and their mechanisms of action. Finally, we highlight future directions for research aimed at improving our understanding on RNA G4-mediated regulatory mechanisms linked to diseases. PMID:28013268

The pathogenic implication of abnormal interaction between apolipoprotein E isoforms, amyloid-beta peptides, and sulfatides in Alzheimer's disease.

PubMed

Han, Xianlin

2010-06-01

Alzheimer's disease (AD) is the most common cause of dementia in the aging population. Prior work has shown that the epsilon4 allele of apolipoprotein E (apoE4) is a major risk factor for "sporadic" AD, which accounts for >99% of AD cases without a defined underlying mechanism. Recently, we have demonstrated that sulfatides are substantially and specifically depleted at the very early stage of AD. To identify the mechanism(s) of sulfatide loss concurrent with AD onset, we have found that: (1) sulfatides are specifically associated with apoE-associated particles in cerebrospinal fluid (CSF); (2) apoE modulates cellular sulfatide levels; and (3) the modulation of sulfatide content is apoE isoform dependent. These findings not only lead to identification of the potential mechanisms underlying sulfatide depletion at the earliest stages of AD but also serve as mechanistic links to explain the genetic association of apoE4 with AD. Moreover, our recent studies further demonstrated that (1) apoE mediates sulfatide depletion in amyloid-beta precursor protein transgenic mice; (2) sulfatides enhance amyloid beta (Abeta) peptides binding to apoE-associated particles; (3) Abeta42 content notably correlates with sulfatide content in CSF; (4) sulfatides markedly enhance the uptake of Abeta peptides; and (5) abnormal sulfatide-facilitated Abeta uptake results in the accumulation of Abeta in lysosomes. Collectively, our studies clearly provide a link between apoE, Abeta, and sulfatides in AD and establish a foundation for the development of effective therapeutic interventions for AD.

An ecofeminist conceptual framework to explore gendered environmental health inequities in urban settings and to inform healthy public policy.

PubMed

Chircop, Andrea

2008-06-01

This theoretical exploration is an attempt to conceptualize the link between gender and urban environmental health. The proposed ecofeminist framework enables an understanding of the link between the urban physical and social environments and health inequities mediated by gender and socioeconomic status. This framework is proposed as a theoretical magnifying glass to reveal the underlying logic that connects environmental exploitation on the one hand, and gendered health inequities on the other. Ecofeminism has the potential to reveal an inherent, normative conceptual analysis and argumentative justification of western society that permits the oppression of women and the exploitation of the environment. This insight will contribute to a better understanding of the mechanisms underlying gendered environmental health inequities and inform healthy public policy that is supportive of urban environmental health, particularly for low-income mothers.

Defects in middle ear cavitation cause conductive hearing loss in the Tcof1 mutant mouse.

PubMed

Richter, Carol A; Amin, Susan; Linden, Jennifer; Dixon, Jill; Dixon, Michael J; Tucker, Abigail S

2010-04-15

Conductive hearing loss (CHL) is one of the most common forms of human deafness. Despite this observation, a surprising gap in our understanding of the mechanisms underlying CHL remains, particularly with respect to the molecular mechanisms underlying middle ear development and disease. Treacher Collins syndrome (TCS) is an autosomal dominant disorder of facial development that results from mutations in the gene TCOF1. CHL is a common feature of TCS but the causes of the hearing defect have not been studied. In this study, we have utilized Tcof1 mutant mice to dissect the developmental mechanisms underlying CHL. Our results demonstrate that effective cavitation of the middle ear is intimately linked to growth of the auditory bulla, the neural crest cell-derived structure that encapsulates all middle ear components, and that defects in these processes have a profoundly detrimental effect on hearing. This research provides important insights into a poorly characterized cause of human deafness, and provides the first mouse model for the study of middle ear cavity defects, while also being of direct relevance to a human genetic disorder.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo.

PubMed

Gouveia, Analuce; Marcelino, Hugo M; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P

2015-01-01

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo

PubMed Central

Gouveia, Analuce; Marcelino, Hugo M; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P

2015-01-01

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space. PMID:25602523

Critical realism: a practical ontology to explain the complexities of smoking and tobacco control in different resource settings

PubMed Central

Oladele, Dunsi; Clark, Alexander M.; Richter, Solina; Laing, Lory

2013-01-01

Background This paper presents critical realism (CR) as an innovative system for research in tobacco prevention and control. CR argues that underlying mechanisms are considered and explored to ensure effective implementation of any program/policy or intervention. Any intervention or program/policy that is transposed from one country to another or one setting to another is complex. Methods The research was undertaken and analyzed through a critical ethnography lens using CR as a philosophical underpinning. The study relied upon the following components: original fieldwork in Nigeria including participant observation of smokers, in-depth interviews and focus groups with smokers, and in-depth interviews with health professionals working in the area of tobacco control in Nigeria. Results Findings from this small ethnographic study in Nigeria, suggest that Critical Realism holds promise for addressing underlying mechanism that links complex influences on smoking. Conclusion This paper argues that understanding the underlying mechanisms associated with smoking in different societies will enable a platform for effective implementation of tobacco control policies that work in various settings. PMID:23561029

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)].

Downregulation of MicroRNA miR-526a by Enterovirus Inhibits RIG-I-Dependent Innate Immune Response

PubMed Central

Xu, Changzhi; He, Xiang; Zheng, Zirui; Zhang, Zhe; Wei, Congwen; Guan, Kai; Hou, Lihua; Zhang, Buchang; Zhu, Lin; Cao, Yuan; Zhang, Yanhong; Cao, Ye; Ma, Shengli; Wang, Penghao; Zhang, Pingping; Xu, Quanbin; Ling, Youguo

2014-01-01

ABSTRACT Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that induces type I interferon-mediated host-protective innate immunity against viral infection. Although cylindromatosis (CYLD) has been shown to negatively regulate innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. Here we show that RIG-I activity is regulated by inhibition of CYLD expression mediated by the microRNA miR-526a. We found that viral infection specifically upregulates miR-526a expression in macrophages via interferon regulatory factor (IRF)-dependent mechanisms. In turn, miR-526a positively regulates virus-triggered type I interferon (IFN-I) production, thus suppressing viral replication, the underlying mechanism of which is the enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR-526a expression inhibits the replication of EV71 virus. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and suggest a novel mechanism for the evasion of the innate immune response controlled by EV71. IMPORTANCE RNA virus infection upregulates the expression of miR-526a in macrophages through IRF-dependent pathways. In turn, miR-526a positively regulates virus-triggered type I IFN production and inhibits viral replication, the underlying mechanism of which is the enhancement of RIG-I K-63 ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein; cells with overexpressed miR-526a were highly resistant to EV71 infection. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and propose a novel mechanism for the evasion of the innate immune response controlled by EV71. PMID:25056901

Red blood cell dynamics: from cell deformation to ATP release.

PubMed

Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

2011-10-01

The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

Pathways from education to depression.

PubMed

Lee, Jinkook

2011-06-01

We examine educational gradients in depression and identify underlying mechanisms of how education might affect depression. We use a nationally representative sample of community-residing adults aged 45 and older from the 2006 Korean Longitudinal Study of Aging, which collected information about depressive symptoms and education. Using tobit regression, we estimate the effect of education on depression and examine what can explain the education gradients by controlling for proxy variables of different pathways linking education to depression. We found cognitive ability, economic resources, social status, social network, and health behavior explain all of the education gradients. Education affects depression through different underlying mechanisms, and the single most important pathway is through developing cognitive ability. Through these pathways, educational attainment influences not only depression for an individual but also for one's spouse, particularly for women, and parents.

Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health.

PubMed

Raichlen, David A; Alexander, Gene E

2017-07-01

The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise-brain connections are not well understood. We use an evolutionary neuroscience approach to develop the adaptive capacity model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: (i) what are the proximate and ultimate mechanisms underlying age-related brain atrophy, and (ii) how do lifestyle changes influence the trajectory of healthy and pathological aging? Copyright © 2017 Elsevier Ltd. All rights reserved.

Single molecular force across single integrins dictates cell spreading.

PubMed

Chowdhury, Farhan; Li, Isaac T S; Leslie, Benjamin J; Doğanay, Sultan; Singh, Rishi; Wang, Xuefeng; Seong, Jihye; Lee, Sang-Hak; Park, Seongjin; Wang, Ning; Ha, Taekjip

2015-10-01

Cells' ability to sense and interpret mechanical signals from the extracellular milieu modulates the degree of cell spreading. Yet how cells detect such signals and activate downstream signaling at the molecular level remain elusive. Herein, we utilize tension gauge tether (TGT) platform to investigate the underlying molecular mechanism of cell spreading. Our data from both differentiated cells of cancerous and non-cancerous origin show that for the same stiff underlying glass substrates and for same ligand density it is the molecular forces across single integrins that ultimately determine cell spreading responses. Furthermore, by decoupling molecular stiffness and molecular tension we demonstrate that molecular stiffness has little influence on cell spreading. Our data provide strong evidence that links molecular forces at the cell-substrate interface to the degree of cell spreading.

Importance of Gender and Attitudes about Violence in the Relationship between Exposure to Interparental Violence and the Perpetration of Teen Dating Violence

ERIC Educational Resources Information Center

Temple, Jeff R.; Shorey, Ryan C.; Tortolero, Susan R.; Wolfe, David A.; Stuart, Gregory L.

2013-01-01

Objective: Mounting evidence has demonstrated a link between exposure to family of origin violence and the perpetration of teen dating violence (TDV). However, only recently have mechanisms underlying this relationship been investigated and very few studies have differentiated between exposure to father-to-mother and mother-to-father violence.…

The GhTT2_A07 gene is linked to the brown colour and natural flame retardancy phenotypes of Lc1 cotton (Gossypium hirsutum L.) fibres

USDA-ARS?s Scientific Manuscript database

Some naturally-coloured brown cotton fibres from accessions of Gossypium hirsutum can be used to make textiles with enhanced flame retardancy (FR). Several independent brown fibre loci have been identified and mapped to chromosomes, but the underlying genes have yet to be identified, and the mechan...

Neurocognitive Mechanisms of Learning to Read: Print Tuning in Beginning Readers Related to Word-Reading Fluency and Semantics but Not Phonology

ERIC Educational Resources Information Center

Eberhard-Moscicka, Aleksandra K.; Jost, Lea B.; Raith, Margit; Maurer, Urs

2015-01-01

During reading acquisition children learn to recognize orthographic stimuli and link them to phonology and semantics. The present study investigated neurocognitive processes of learning to read after one year of schooling. We aimed to elucidate the cognitive processes underlying neural tuning for print that has been shown to play an important role…

Work stressors and partner social undermining: Comparing negative affect and psychological detachment as mechanisms.

PubMed

Meier, Laurenz L; Cho, Eunae

2018-05-14

With the mounting evidence that employees' work experiences spill over into the family domain and cross over to family members, it is important to understand the underlying mechanism through which work experiences affect the family domain and what factors may alleviate the adverse impact of work stress. Expanding previous research that mainly focused on the affect-based mechanism (negative affect), the present research investigated a resource-based mechanism (psychological detachment from work) in the relationship linking two work stressors (high workload and workplace incivility) with social undermining toward the partner at home. We also explored the relative strength of the mediating effects of the two mechanisms. In addition, we tested whether relationship satisfaction moderates the proposed effect of detachment on partner undermining. We tested these research questions using two studies with differing designs: a five-wave longitudinal study (N = 470) and a multisource study (N = 131). The results suggest that stressful work experiences affect the family domain via lack of detachment as well as negative affect, that the two pathways have comparable strength, and that high relationship satisfaction mitigates the negative effect of lack of detachment on partner undermining. In sum, this research extends the spillover-crossover model by establishing that poor psychological detachment from work during leisure time is an additional mechanism that links work and family. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Time-linked concurrence of sleep bruxism, periodic limb movements, and EEG arousals in sleep bruxers and healthy controls.

PubMed

van der Zaag, Jacques; Naeije, Machiel; Wicks, Darrel J; Hamburger, Hans L; Lobbezoo, Frank

2014-01-01

Sleep bruxism (SB) and periodic limb movements during sleep (PLMS) may have a common underlying neurophysiologic mechanism, especially in relation to the occurrence of sleep-related electroencephalographic (EEG) arousals. To test this hypothesis, three research questions were assessed. First, it was assessed whether PLMS events occur more frequently in SB patients than in individuals without SB. Second, the question was put forward whether the combined presence of SB and PLMS events is more common than that of isolated SB or PLMS events in a group of SB patients. Third, as to further unravel the possible role of EEG arousals in the underlying neurophysiologic mechanism of SB and PLMS, it was assessed in a group of SB patients whether combined SB/PLMS events with associated EEG arousals are more common than those without associated EEG arousals. Positive answers to these questions could suggest a common neurophysiological basis for both movement disorders. Seventeen SB patients and 11 healthy controls were polysomnographically studied. SB, PLMS, and EEG arousals were scored. An association was noted when the occurrence was within a 3-s association zone. The PLMS index was higher in SB patients than in healthy controls (P < 0.001). Within the group of SB patients, the combined SB/PLMS index was higher than the isolated SB index (P < 0.001) and the isolated PLMS index (P = 0.018). Similarly, the combined SB/PLMS index with EEG arousal was higher than the combined SB/PLMS index without EEG arousal in SB patients (P < 0.001). The results of this study indicate that SB, PLMS, and EEG arousals commonly concur during sleep in a time-linked manner. SB and PLMS probably have a common underlying neurophysiological 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.

49 CFR 238.207 - Link between coupling mechanism and car body.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Link between coupling mechanism and car body. 238.207 Section 238.207 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Requirements for Tier I Passenger Equipment § 238.207 Link between coupling mechanism and car body. All...

49 CFR 238.207 - Link between coupling mechanism and car body.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Link between coupling mechanism and car body. 238.207 Section 238.207 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Requirements for Tier I Passenger Equipment § 238.207 Link between coupling mechanism and car body. All...

49 CFR 238.207 - Link between coupling mechanism and car body.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Link between coupling mechanism and car body. 238.207 Section 238.207 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Requirements for Tier I Passenger Equipment § 238.207 Link between coupling mechanism and car body. All...

49 CFR 238.207 - Link between coupling mechanism and car body.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Link between coupling mechanism and car body. 238.207 Section 238.207 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Requirements for Tier I Passenger Equipment § 238.207 Link between coupling mechanism and car body. All...

49 CFR 238.207 - Link between coupling mechanism and car body.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Link between coupling mechanism and car body. 238.207 Section 238.207 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Requirements for Tier I Passenger Equipment § 238.207 Link between coupling mechanism and car body. All...

Exact and Optimal Quantum Mechanics/Molecular Mechanics Boundaries.

PubMed

Sun, Qiming; Chan, Garnet Kin-Lic

2014-09-09

Motivated by recent work in density matrix embedding theory, we define exact link orbitals that capture all quantum mechanical (QM) effects across arbitrary quantum mechanics/molecular mechanics (QM/MM) boundaries. Exact link orbitals are rigorously defined from the full QM solution, and their number is equal to the number of orbitals in the primary QM region. Truncating the exact set yields a smaller set of link orbitals optimal with respect to reproducing the primary region density matrix. We use the optimal link orbitals to obtain insight into the limits of QM/MM boundary treatments. We further analyze the popular general hybrid orbital (GHO) QM/MM boundary across a test suite of molecules. We find that GHOs are often good proxies for the most important optimal link orbital, although there is little detailed correlation between the detailed GHO composition and optimal link orbital valence weights. The optimal theory shows that anions and cations cannot be described by a single link orbital. However, expanding to include the second most important optimal link orbital in the boundary recovers an accurate description. The second optimal link orbital takes the chemically intuitive form of a donor or acceptor orbital for charge redistribution, suggesting that optimal link orbitals can be used as interpretative tools for electron transfer. We further find that two optimal link orbitals are also sufficient for boundaries that cut across double bonds. Finally, we suggest how to construct "approximately" optimal link orbitals for practical QM/MM calculations.

Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

PubMed

Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

2016-11-01

The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano- and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of end-group cross-linking on transport properties of sulfonated poly(phenylene sulfide nitrile)s for proton exchange membranes

NASA Astrophysics Data System (ADS)

Kang, Na Rae; Lee, So Young; Shin, Dong Won; Hwang, Doo Sung; Lee, Kang Hyuck; Cho, Doo Hee; Kim, Ji Hoon; Lee, Young Moo

2016-03-01

A series of end-group cross-linked membranes (Az-XESPSN) were prepared by click reaction to investigate the effects of cross-linking on the morphology and proton transport properties of proton exchange membranes. The morphological transformations resulting from thermal annealing and cross-linking were observed by means of atomic force microscopy (AFM) and transmission electron microscopy (TEM). Compared to the non-cross-linked ESPSN membranes, the Az-XESPSN membranes exhibited lower water uptake and improved mechanical and chemical stabilities. In addition, the Az-XESPSN membranes exhibited higher proton conductivities (0.018-0.028 S cm-1) compared to those of the ESPSN membranes (0.0044-0.0053 S cm-1) and Nafion 212 (0.0061 S cm-1), particularly in conditions of elevated temperature (120 °C) and low relative humidity (35%). Such enhancements can be attributed to a synergistic effect of well-defined hydrophilic ionic clusters and triazole groups that function as proton carriers under anhydrous conditions. Furthermore, the Az-XESPSN membranes exhibited significantly enhanced single cell performance and long-term stability compared to those of ESPSN membranes.

Processing and characterization of α-elastin electrospun membranes

NASA Astrophysics Data System (ADS)

Araujo, J.; Padrão, J.; Silva, J. P.; Dourado, F.; Correia, D. M.; Botelho, G.; Gomez Ribelles, J. L.; Lanceros-Méndez, S.; Sencadas, V.

2014-06-01

Elastin isolated from fresh bovine ligaments was dissolved in a mixture of 1,1,1,3,3,3-Hexafluoro-2-propanol and water were electrospun into fiber membranes under different processing conditions. Fiber mats of randomly and aligned fibers were obtained with fixed and rotating ground collectors and fibrils were composed by thin ribbons whose width depends on electrospinning conditions; fibrils with 721 nm up to 2.12 μm width were achieved. After cross-linking with glutaraldehyde, α-elastin can uptake as much as 1700 % of PBS solution and a slight increase on fiber thickness was observed. The glass transition temperature of electrospun fiber mats was found to occur at ˜80 °C. Moreover, α-Elastin showed to be a perfect elastomeric material, and no mechanical hysteresis was found in cycle mechanical measurements. The elastic modulus obtained for random and aligned fibers mats in a PBS solution was 330±10 kPa and 732±165 kPa, respectively. Finally, the electrospinning and cross-linking process does not inhibit MC-3T3-E1 cell adhesion. Cell culture results showed good cell adhesion and proliferation in the cross-linked elastin fiber mats.

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

Rivedal, Edgar; Leithe, Edward

Benzene is used at large volumes in many different human activities. Hematotoxicity and cancer-causation as a result of benzene exposure was recognized many years ago, but the mechanisms involved remain unclear. Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to both cancer induction and interference with normal hematopoietic development. We have previously suggested that inhibition of GJIC may play a role in benzene toxicity since benzene metabolites were found to block GJIC, the ring-opened trans,trans-muconaldehyde (MUC) being the most potent metabolite. In the present work we have studied the molecular mechanisms underlying the MUC-induced inhibition of gapmore » junctional communication. We show that MUC induces cross-linking of the gap junction protein connexin43 and that this is likely to be responsible for the induced inhibition of GJIC, as well as the loss of connexin43 observed in Western blots. We also show that glutaraldehyde possesses similar effects as MUC, and we compare the effects to that of formaldehyde. The fact that glutaraldehyde and formaldehyde have been associated with induction of leukemia as well as disturbance of hematopoiesis, strengthens the possible link between the effect of MUC on gap junctions, and the toxic effects of benzene.« less

Analysis of strategies to increase external fixator stiffness: is double stacking worth the cost?

PubMed

Strebe, Sara; Kim, Hyunchul; Russell, Joseph P; Hsieh, Adam H; Nascone, Jason; O'Toole, Robert V

2014-07-01

We compared the mechanical benefits and costs of 3 strategies that are commonly used to increase knee-spanning external fixator stiffness (resistance to deformation): double stacking, cross-linking, and use of an oblique pin. At our academic trauma centre and biomechanical testing laboratory, we used ultra-high-molecular-weight polyethylene bone models and commercially available external fixator components to simulate knee-spanning external fixation. The models were tested in anterior-posterior bending, medial-lateral bending, axial compression, and torsion. We recorded the construct stiffness for each strategy in all loading modes and assessed a secondary outcome of cost per 10% increase in stiffness. Double stacking significantly increased construct stiffness under anterior-posterior bending (109%), medial-lateral bending (22%), axial compression (150%), and torsion (41%) (p<0.05). Use of an oblique pin significantly increased stiffness under torsion (25%) (p<0.006). Cross-linking significantly increased stiffness only under torsion (29%) (p<0.002). Double stacking increased costs by 84%, cross-linking by 28%, and use of an oblique pin by 15% relative to a standard fixator. All 3 strategies increased stiffness under torsion to varying degrees, but only double stacking increased stiffness in all 4 testing modalities (p<0.05). Double stacking is most effective in increasing resistance to bending, particularly under anterior-posterior bending and axial compression, but requires a relatively high cost increase. Clinicians can use these data to help guide the most cost-effective strategy to increase construct stiffness based on the plane in which stiffness is needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Simulation of Delamination Under High Cycle Fatigue in Composite Materials Using Cohesive Models

NASA Technical Reports Server (NTRS)

Camanho, Pedro P.; Turon, Albert; Costa, Josep; Davila, Carlos G.

2006-01-01

A new thermodynamically consistent damage model is proposed for the simulation of high-cycle fatigue crack growth. The basis for the formulation is an interfacial degradation law that links Fracture Mechanics and Damage Mechanics to relate the evolution of the damage variable, d, with the crack growth rate da/dN. The damage state is a function of the loading conditions (R and (Delta)G) as well as the experimentally-determined crack growth rates for the material. The formulation ensures that the experimental results can be reproduced by the analysis without the need of additional adjustment parameters.

Retinoic Acid Signaling Affects Cortical Synchrony During Sleep

NASA Astrophysics Data System (ADS)

Maret, Stéphanie; Franken, Paul; Dauvilliers, Yves; Ghyselinck, Norbert B.; Chambon, Pierre; Tafti, Mehdi

2005-10-01

Delta oscillations, characteristic of the electroencephalogram (EEG) of slow wave sleep, estimate sleep depth and need and are thought to be closely linked to the recovery function of sleep. The cellular mechanisms underlying the generation of delta waves at the cortical and thalamic levels are well documented, but the molecular regulatory mechanisms remain elusive. Here we demonstrate in the mouse that the gene encoding the retinoic acid receptor beta determines the contribution of delta oscillations to the sleep EEG. Thus, retinoic acid signaling, which is involved in the patterning of the brain and dopaminergic pathways, regulates cortical synchrony in the adult.

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

PubMed

Javierre, Biola M; Burren, Oliver S; Wilder, Steven P; Kreuzhuber, Roman; Hill, Steven M; Sewitz, Sven; Cairns, Jonathan; Wingett, Steven W; Várnai, Csilla; Thiecke, Michiel J; Burden, Frances; Farrow, Samantha; Cutler, Antony J; Rehnström, Karola; Downes, Kate; Grassi, Luigi; Kostadima, Myrto; Freire-Pritchett, Paula; Wang, Fan; Stunnenberg, Hendrik G; Todd, John A; Zerbino, Daniel R; Stegle, Oliver; Ouwehand, Willem H; Frontini, Mattia; Wallace, Chris; Spivakov, Mikhail; Fraser, Peter

2016-11-17

Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cross Talk Between Brain Innate Immunity and Serotonin Signaling Underlies Depressive-Like Behavior Induced by Alzheimer's Amyloid-β Oligomers in Mice.

PubMed

Ledo, Jose Henrique; Azevedo, Estefania P; Beckman, Danielle; Ribeiro, Felipe C; Santos, Luis E; Razolli, Daniela S; Kincheski, Grasielle C; Melo, Helen M; Bellio, Maria; Teixeira, Antonio L; Velloso, Licio A; Foguel, Debora; De Felice, Fernanda G; Ferreira, Sergio T

2016-11-30

Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels. Inactivation or ablation of microglia blocked the increase in brain TNF-α and abolished depressive-like behavior induced by AβOs. Significantly, we identified serotonin as a negative regulator of microglial activation. Finally, AβOs failed to induce depressive-like behavior in Toll-like receptor 4-deficient mice and in mice harboring a nonfunctional TLR4 variant in myeloid cells. Results establish that AβOs trigger depressive-like behavior via a double impact on brain serotonin levels and microglial activation, unveiling a cross talk between brain innate immunity and serotonergic signaling as a key player in mood alterations in AD. Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia in the world. Brain accumulation of amyloid-β oligomers (AβOs) is a major feature in the pathogenesis of AD. Although clinical and epidemiological data suggest a strong connection between AD and depression, the underlying mechanisms linking these two disorders remain largely unknown. Here, we report that aberrant activation of the brain innate immunity and decreased serotonergic tonus in the brain are key players in AβO-induced depressive-like behavior in mice. Our findings may open up new possibilities for the development of effective therapeutics for AD and depression aimed at modulating microglial function. Copyright © 2016 the authors 0270-6474/16/3612106-11$15.00/0.

On heart rate variability and autonomic activity in homeostasis and in systemic inflammation.

PubMed

Scheff, Jeremy D; Griffel, Benjamin; Corbett, Siobhan A; Calvano, Steve E; Androulakis, Ioannis P

2014-06-01

Analysis of heart rate variability (HRV) is a promising diagnostic technique due to the noninvasive nature of the measurements involved and established correlations with disease severity, particularly in inflammation-linked disorders. However, the complexities underlying the interpretation of HRV complicate understanding the mechanisms that cause variability. Despite this, such interpretations are often found in literature. In this paper we explored mathematical modeling of the relationship between the autonomic nervous system and the heart, incorporating basic mechanisms such as perturbing mean values of oscillating autonomic activities and saturating signal transduction pathways to explore their impacts on HRV. We focused our analysis on human endotoxemia, a well-established, controlled experimental model of systemic inflammation that provokes changes in HRV representative of acute stress. By contrasting modeling results with published experimental data and analyses, we found that even a simple model linking the autonomic nervous system and the heart confound the interpretation of HRV changes in human endotoxemia. Multiple plausible alternative hypotheses, encoded in a model-based framework, equally reconciled experimental results. In total, our work illustrates how conventional assumptions about the relationships between autonomic activity and frequency-domain HRV metrics break down, even in a simple model. This underscores the need for further experimental work towards unraveling the underlying mechanisms of autonomic dysfunction and HRV changes in systemic inflammation. Understanding the extent of information encoded in HRV signals is critical in appropriately analyzing prior and future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

On heart rate variability and autonomic activity in homeostasis and in systemic inflammation

PubMed Central

Scheff, Jeremy D.; Griffel, Benjamin; Corbett, Siobhan A.; Calvano, Steve E.; Androulakis, Ioannis P.

2014-01-01

Analysis of heart rate variability (HRV) is a promising diagnostic technique due to the noninvasive nature of the measurements involved and established correlations with disease severity, particularly in inflammation-linked disorders. However, the complexities underlying the interpretation of HRV complicate understanding the mechanisms that cause variability. Despite this, such interpretations are often found in literature. In this paper we explored mathematical modeling of the relationship between the autonomic nervous system and the heart, incorporating basic mechanisms such as perturbing mean values of oscillating autonomic activities and saturating signal transduction pathways to explore their impacts on HRV. We focused our analysis on human endotoxemia, a well-established, controlled experimental model of systemic inflammation that provokes changes in HRV representative of acute stress. By contrasting modeling results with published experimental data and analyses, we found that even a simple model linking the autonomic nervous system and the heart confound the interpretation of HRV changes in human endotoxemia. Multiple plausible alternative hypotheses, encoded in a model-based framework, equally reconciled experimental results. In total, our work illustrates how conventional assumptions about the relationships between autonomic activity and frequency-domain HRV metrics break down, even in a simple model. This underscores the need for further experimental work towards unraveling the underlying mechanisms of autonomic dysfunction and HRV changes in systemic inflammation. Understanding the extent of information encoded in HRV signals is critical in appropriately analyzing prior and future studies. PMID:24680646

Allostery in the Hsp70 chaperone proteins

PubMed Central

Zuiderweg, Erik R.P.; Bertelsen, Eric B.; Rousaki, Aikaterini; Mayer, Matthias P.; Gestwicki, Jason E.; Ahmad, Atta

2013-01-01

Heat shock 70 kDa (Hsp70) chaperones are essential to in-vivo protein folding, protein transport and protein re-folding. They carry out these activities using repeated cycles of binding and release of client proteins. This process is under allosteric control of nucleotide binding and hydrolysis. X-ray crystallography, NMR spectroscopy and other biophysical techniques have contributed much to the understanding of the allosteric mechanism linking these activities and the effect of co-chaperones on this mechanism. In this chapter, these findings are critically reviewed. Studies on the allosteric mechanisms of Hsp70 have gained enhanced urgency, as recent studies have implicated this chaperone as a potential drug target in diseases such as Alzheimer's and cancer. Recent approaches to combat these diseases through interference with the Hsp70 allosteric mechanism are discussed. PMID:22576356

Output Error Analysis of Planar 2-DOF Five-bar Mechanism

NASA Astrophysics Data System (ADS)

Niu, Kejia; Wang, Jun; Ting, Kwun-Lon; Tao, Fen; Cheng, Qunchao; Wang, Quan; Zhang, Kaiyang

2018-03-01

Aiming at the mechanism error caused by clearance of planar 2-DOF Five-bar motion pair, the method of equivalent joint clearance of kinematic pair to virtual link is applied. The structural error model of revolute joint clearance is established based on the N-bar rotation laws and the concept of joint rotation space, The influence of the clearance of the moving pair is studied on the output error of the mechanis. and the calculation method and basis of the maximum error are given. The error rotation space of the mechanism under the influence of joint clearance is obtained. The results show that this method can accurately calculate the joint space error rotation space, which provides a new way to analyze the planar parallel mechanism error caused by joint space.

Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion.

PubMed

Weltens, N; Zhao, D; Van Oudenhove, L

2014-03-01

Food in general, and fatty foods in particular, have obtained intrinsic reward value throughout evolution. This reward value results from an interaction between exteroceptive signals from different sensory modalities, interoceptive hunger/satiety signals from the gastrointestinal tract to the brain, as well as ongoing affective and cognitive processes. Further evidence linking food to emotions stems from folk psychology ('comfort foods') and epidemiological studies demonstrating high comorbidity rates between disorders of food intake, including obesity, and mood disorders such as depression. This review paper aims to give an overview of current knowledge on the neurophysiological mechanisms underlying the link between (fatty) foods, their reward value, and emotional responses to (anticipation of) their intake in humans. Firstly, the influence of exteroceptive sensory signals, including visual, olfactory ('anticipatory food reward'), and gustatory ('consummatory food reward'), on the encoding of reward value in the (ventral) striatum and of subjective pleasantness in the cingulate and orbitofrontal cortex will be discussed. Differences in these pathways and mechanisms between lean and obese subjects will be highlighted. Secondly, recent studies elucidating the mechanisms of purely interoceptive fatty acid-induced signaling from the gastrointestinal tract to the brain, including the role of gut peptides, will be presented. These studies have demonstrated that such subliminal interoceptive stimuli may impact on hedonic circuits in the brain, and thereby influence the subjective and neural responses to negative emotion induction. This suggests that the effect of foods on mood may even occur independently from their exteroceptive sensory properties. © 2014 John Wiley & Sons Ltd.

Robust Adaptive Synchronization of Ring Configured Uncertain Chaotic FitzHugh–Nagumo Neurons under Direction-Dependent Coupling

PubMed Central

Iqbal, Muhammad; Rehan, Muhammad; Hong, Keum-Shik

2018-01-01

This paper exploits the dynamical modeling, behavior analysis, and synchronization of a network of four different FitzHugh–Nagumo (FHN) neurons with unknown parameters linked in a ring configuration under direction-dependent coupling. The main purpose is to investigate a robust adaptive control law for the synchronization of uncertain and perturbed neurons, communicating in a medium of bidirectional coupling. The neurons are assumed to be different and interconnected in a ring structure. The strength of the gap junctions is taken to be different for each link in the network, owing to the inter-neuronal coupling medium properties. Robust adaptive control mechanism based on Lyapunov stability analysis is employed and theoretical criteria are derived to realize the synchronization of the network of four FHN neurons in a ring form with unknown parameters under direction-dependent coupling and disturbances. The proposed scheme for synchronization of dissimilar neurons, under external electrical stimuli, coupled in a ring communication topology, having all parameters unknown, and subject to directional coupling medium and perturbations, is addressed for the first time as per our knowledge. To demonstrate the efficacy of the proposed strategy, simulation results are provided. PMID:29535622

A link-segment model of upright human posture for analysis of head-trunk coordination

NASA Technical Reports Server (NTRS)

Nicholas, S. C.; Doxey-Gasway, D. D.; Paloski, W. H.

1998-01-01

Sensory-motor control of upright human posture may be organized in a top-down fashion such that certain head-trunk coordination strategies are employed to optimize visual and/or vestibular sensory inputs. Previous quantitative models of the biomechanics of human posture control have examined the simple case of ankle sway strategy, in which an inverted pendulum model is used, and the somewhat more complicated case of hip sway strategy, in which multisegment, articulated models are used. While these models can be used to quantify the gross dynamics of posture control, they are not sufficiently detailed to analyze head-trunk coordination strategies that may be crucial to understanding its underlying mechanisms. In this paper, we present a biomechanical model of upright human posture that extends an existing four mass, sagittal plane, link-segment model to a five mass model including an independent head link. The new model was developed to analyze segmental body movements during dynamic posturography experiments in order to study head-trunk coordination strategies and their influence on sensory inputs to balance control. It was designed specifically to analyze data collected on the EquiTest (NeuroCom International, Clackamas, OR) computerized dynamic posturography system, where the task of maintaining postural equilibrium may be challenged under conditions in which the visual surround, support surface, or both are in motion. The performance of the model was tested by comparing its estimated ground reaction forces to those measured directly by support surface force transducers. We conclude that this model will be a valuable analytical tool in the search for mechanisms of balance control.

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS NATURALLY OCCURRING PHASIC DOPAMINE SIGNALING

PubMed Central

Howard, Christopher D.; Daberkow, David P.; Ramsson, Eric S.; Keefe, Kristen A.; Garris, Paul A.

2013-01-01

Methamphetamine (METH) is a highly addictive drug that is also neurotoxic to central dopamine (DA) systems. Although striatal DA depletions induced by METH are associated with behavioral and cognitive impairments, the link between these phenomena remains poorly understood. Previous work in both METH-pretreated animals and the 6-hydroxydopamine model of Parkinson’s disease suggests that a disruption of phasic DA signaling, which is important for learning and goal-directed behavior, may be such a link. However, prior studies used electrical stimulation to elicit phasic-like DA responses and were also performed under anesthesia, which alters DA neuron activity and presynaptic function. Here we investigated the consequences of METH-induced DA terminal loss on both electrically evoked phasic-like DA signals and so-called “spontaneous” phasic DA transients measured by voltammetry in awake rats. Not ostensibly attributable to discrete stimuli, these sub-second DA changes may play a role in enhancing reward-cue associations. METH-pretreatment reduced tissue DA content in the dorsomedial striatum and nucleus accumbens by ~55%. Analysis of phasic-like DA responses elicited by reinforcing stimulation revealed that METH pretreatment decreased their amplitude and underlying mechanisms for release and uptake to a similar degree as DA content in both striatal subregions. Most importantly, characteristics of DA transients were altered by METH-induced DA terminal loss, with amplitude and frequency decreased and duration increased. These results demonstrate for the first time that denervation of DA neurons alters naturally occurring DA transients and are consistent with diminished phasic DA signaling as a plausible mechanism linking METH-induced striatal DA depletions and cognitive deficits. PMID:23574406

Mechanics behind breast cancer prevention - focus on obesity, exercise and dietary fat.

PubMed

Alegre, Melissa Marie; Knowles, McKay Hovis; Robison, Richard A; O'Neill, Kim Leslie

2013-01-01

Cancer prevention is rapidly emerging as a major strategy to reduce cancer mortality. In the field of breast cancer, significant strides have recently been made in the understanding of underlying preventive mechanisms. Currently, three major strategies have been linked to an increase in breast cancer risk: obesity, lack of physical exercise, and high levels of saturated dietary fat. As a result, prevention strategies for breast cancer are usually centered on these lifestyle factors. Unfortunately, there remains controversy regarding epidemiological studies that seek to determine the benefit of these lifestyle changes. We have identified crucial mechanisms that may help clarify these conflicting studies. For example, recent reports with olive oil have demonstrated that it may influence crucial transcription factors and reduce breast tumor aggressiveness by targeting HER2. Similarly, physical exercise reduces sex hormone levels, which may help protect against breast cancer. Obesity promotes tumor cell growth and cell survival through upregulation of leptin and insulin-like growth factors. This review seeks to discuss these underlying mechanisms, and more behind the three major prevention strategies, as a means of understanding how breast cancer can be prevented.

Collective narcissism moderates the effect of in-group image threat on intergroup hostility.

PubMed

Golec de Zavala, Agnieszka; Cichocka, Aleksandra; Iskra-Golec, Irena

2013-06-01

Results of 4 experiments demonstrated that under in-group image threat collective narcissism predicts retaliatory intergroup hostility. Under in-group criticism (vs. praise) collective narcissists expressed intention to harm the offending out-group but not other, nonoffending out-groups. This effect was specific to collective narcissism and was replicated in studies that accounted for the overlap between collective narcissism and individual narcissism, in-group positivity (in-group identification, blind and constructive patriotism), social dominance orientation, and right wing authoritarianism. The link between collective narcissism and retaliatory intergroup hostility under in-group image threat was found in the context of national identity and international relations and in the context of a social identity defined by university affiliation. Study 4 demonstrated that the relationship between collective narcissism and intergroup hostility was mediated by the perception of in-group criticism as personally threatening. The results advance our understanding of the mechanism driving the link between collective narcissism and intergroup hostility. They indicate that threatened egotism theory can be extended into the intergroup domain. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

PubMed Central

Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

2016-01-01

The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

Stress--the battle for hearts and minds: links between depression, stress and ischemic heart disease.

PubMed

Korszun, Ania; Frenneaux, Michael P

2006-09-01

Depression and ischemic heart disease (IHD) are strongly related common disorders. Depression itself is an independent cardiac risk factor and is associated with a two- to threefold increase in IHD mortality. Attention has now shifted to identifying the common underlying mechanisms that could make individuals susceptible to both disorders. Abnormalities that have been implicated in this relationship include abnormal platelet activation, decreased baroreceptor sensitivity and endothelial dysfunction. Depression and IHD both have a high association with environmental stress, and depression is characterized by abnormalities of the stress-hormone axis. This review provides a brief overview of some recent developments in our understanding of the pathophysiological links between stress, depression and IHD.

Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?

PubMed Central

2014-01-01

Iodinated contrast agents are usually classified based upon their osmolality—high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some but not all patients resulting in loss of glomerular filtration rate. Over the past 30 years, nephrotoxicity has been linked to osmolality although the precise mechanism underlying such a link has been elusive. Improvements in our understanding of the pathogenesis of nephrotoxicity and prospective randomized clinical trials have attempted to further explore the relationship between osmolality and nephrotoxicity. In this review, the basis for our current understanding that there are little if any differences in nephrotoxic potential between low and isosmolar contrast media will be detailed using data from clinical studies. PMID:24587997

Percolation threshold determines the optimal population density for public cooperation

NASA Astrophysics Data System (ADS)

Wang, Zhen; Szolnoki, Attila; Perc, Matjaž

2012-03-01

While worldwide census data provide statistical evidence that firmly link the population density with several indicators of social welfare, the precise mechanisms underlying these observations are largely unknown. Here we study the impact of population density on the evolution of public cooperation in structured populations and find that the optimal density is uniquely related to the percolation threshold of the host graph irrespective of its topological details. We explain our observations by showing that spatial reciprocity peaks in the vicinity of the percolation threshold, when the emergence of a giant cooperative cluster is hindered neither by vacancy nor by invading defectors, thus discovering an intuitive yet universal law that links the population density with social prosperity.

S3QL: A distributed domain specific language for controlled semantic integration of life sciences data

PubMed Central

2011-01-01

Background The value and usefulness of data increases when it is explicitly interlinked with related data. This is the core principle of Linked Data. For life sciences researchers, harnessing the power of Linked Data to improve biological discovery is still challenged by a need to keep pace with rapidly evolving domains and requirements for collaboration and control as well as with the reference semantic web ontologies and standards. Knowledge organization systems (KOSs) can provide an abstraction for publishing biological discoveries as Linked Data without complicating transactions with contextual minutia such as provenance and access control. We have previously described the Simple Sloppy Semantic Database (S3DB) as an efficient model for creating knowledge organization systems using Linked Data best practices with explicit distinction between domain and instantiation and support for a permission control mechanism that automatically migrates between the two. In this report we present a domain specific language, the S3DB query language (S3QL), to operate on its underlying core model and facilitate management of Linked Data. Results Reflecting the data driven nature of our approach, S3QL has been implemented as an application programming interface for S3DB systems hosting biomedical data, and its syntax was subsequently generalized beyond the S3DB core model. This achievement is illustrated with the assembly of an S3QL query to manage entities from the Simple Knowledge Organization System. The illustrative use cases include gastrointestinal clinical trials, genomic characterization of cancer by The Cancer Genome Atlas (TCGA) and molecular epidemiology of infectious diseases. Conclusions S3QL was found to provide a convenient mechanism to represent context for interoperation between public and private datasets hosted at biomedical research institutions and linked data formalisms. PMID:21756325

S3QL: a distributed domain specific language for controlled semantic integration of life sciences data.

PubMed

Deus, Helena F; Correa, Miriã C; Stanislaus, Romesh; Miragaia, Maria; Maass, Wolfgang; de Lencastre, Hermínia; Fox, Ronan; Almeida, Jonas S

2011-07-14

The value and usefulness of data increases when it is explicitly interlinked with related data. This is the core principle of Linked Data. For life sciences researchers, harnessing the power of Linked Data to improve biological discovery is still challenged by a need to keep pace with rapidly evolving domains and requirements for collaboration and control as well as with the reference semantic web ontologies and standards. Knowledge organization systems (KOSs) can provide an abstraction for publishing biological discoveries as Linked Data without complicating transactions with contextual minutia such as provenance and access control.We have previously described the Simple Sloppy Semantic Database (S3DB) as an efficient model for creating knowledge organization systems using Linked Data best practices with explicit distinction between domain and instantiation and support for a permission control mechanism that automatically migrates between the two. In this report we present a domain specific language, the S3DB query language (S3QL), to operate on its underlying core model and facilitate management of Linked Data. Reflecting the data driven nature of our approach, S3QL has been implemented as an application programming interface for S3DB systems hosting biomedical data, and its syntax was subsequently generalized beyond the S3DB core model. This achievement is illustrated with the assembly of an S3QL query to manage entities from the Simple Knowledge Organization System. The illustrative use cases include gastrointestinal clinical trials, genomic characterization of cancer by The Cancer Genome Atlas (TCGA) and molecular epidemiology of infectious diseases. S3QL was found to provide a convenient mechanism to represent context for interoperation between public and private datasets hosted at biomedical research institutions and linked data formalisms.

On justification of efficient Energy-Force parameters of Hydraulic-excavator main mechanisms

NASA Astrophysics Data System (ADS)

Komissarov, Anatoliy; Lagunova, Yuliya; Shestakov, Viktor; Lukashuk, Olga

2018-03-01

The article formulates requirements for energy-efficient designs of the operational equipment of a hydraulic excavator (its boom, stick and bucket) and defines, for a mechanism of that equipment, a new term “performance characteristic”. The drives of main rotation mechanisms of the equipment are realized by hydraulic actuators (hydraulic cylinders) and transmission (leverage) mechanisms, with the actuators (the cylinders themselves, their pistons and piston rods) also acting as links of the leverage. Those drives are characterized by the complexity of translating mechanical-energy parameters of the actuators into energy parameters of the driven links (a boom, a stick and a bucket). Relations between those parameters depend as much on the types of mechanical characteristics of the hydraulic actuators as on the types of structural schematics of the transmission mechanisms. To assess how energy-force parameters of the driven links change when a typical operation is performed, it was proposed to calculate performance characteristics of the main mechanisms as represented by a set of values of transfer functions, i.e. by functional dependences between driven links and driving links (actuators). Another term “ideal performance characteristic” of a mechanism was introduced. Based on operation-emulating models for the main mechanisms of hydraulic excavators, analytical expressions were derived to calculate kinematic and force transfer functions of the main mechanisms.

Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII.

PubMed

Rijken, D C; Abdul, S; Malfliet, J J M C; Leebeek, F W G; Uitte de Willige, S

2016-07-01

Essentials Factor XIIIa inhibits fibrinolysis by forming fibrin-fibrin and fibrin-inhibitor cross-links. Conflicting studies about magnitude and mechanisms of inhibition have been reported. Factor XIIIa most strongly inhibits lysis of mechanically compacted or retracted plasma clots. Cross-links of α2-antiplasmin to fibrin prevent the inhibitor from being expelled from the clot. Background Although insights into the underlying mechanisms of the effect of factor XIII on fibrinolysis have improved considerably in the last few decades, in particular with the discovery that activated FXIII (FXIIIa) cross-links α2 -antiplasmin to fibrin, the topic remains a matter of debate. Objective To elucidate the mechanisms of the antifibrinolytic effect of FXIII. Methods and Results Platelet-poor plasma clot lysis, induced by the addition of tissue-type plasminogen activator, was measured in the presence or absence of a specific FXIIIa inhibitor. Both in a turbidity assay and in a fluorescence assay, the FXIIIa inhibitor had only a small inhibitory effect: 1.6-fold less tissue-type plasminogen activator was required for 50% clot lysis in the presence of the FXIIIa inhibitor. However, when the plasma clot was compacted by centrifugation, the FXIIIa inhibitor had a strong inhibitory effect, with 7.7-fold less tissue-type plasminogen activator being required for 50% clot lysis in the presence of the FXIIIa inhibitor. In both experiments, the effects of the FXIIIa inhibitor were entirely dependent on the cross-linking of α2 -antiplasmin to fibrin. The FXIIIa inhibitor reduced the amount of α2 -antiplasmin present in the compacted clots from approximately 30% to < 4%. The results were confirmed with experiments in which compaction was achieved by platelet-mediated clot retraction. Conclusions Compaction or retraction of fibrin clots reveals the strong antifibrinolytic effect of FXIII. This is explained by the cross-linking of α2 -antiplasmin to fibrin by FXIIIa, which prevents the plasmin inhibitor from being fully expelled from the clot during compaction/retraction. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Psychological Pathways Linking Social Support to Health Outcomes: A Visit with the “Ghosts” of Research Past, Present, and Future

PubMed Central

Uchino, Bert N.; Bowen, Kimberly; Carlisle, McKenzie; Birmingham, Wendy

2012-01-01

Contemporary models postulate the importance of psychological mechanisms linking perceived and received social support to physical health outcomes. In this review, we examine studies that directly tested the potential psychological mechanisms responsible for links between social support and health-relevant physiological processes (1980s to 2010). Inconsistent with existing theoretical models, no evidence was found that psychological mechanisms such as depression, perceived stress, and other affective processes are directly responsible for links between support and health. We discuss the importance of considering statistical/design issues, emerging conceptual perspectives, and limitations of our existing models for future research aimed at elucidating the psychological mechanisms responsible for links between social support and physical health outcomes. PMID:22326104

Self-control and its relation to joint developmental trajectories of cannabis use and depressive mood symptoms.

PubMed

Otten, Roy; Barker, Edward D; Maughan, Barbara; Arseneault, Louise; Engels, Rutger C M E

2010-12-01

Cannabis use and depressive mood symptoms in adolescence have been found to co-occur. In exploring the nature of this relationship and in the search for mechanisms that explain this link, scholars have postulated the idea for a 'common liability model'. According to this model, the link between cannabis use and depressive symptoms can be explained by an underlying risk factor. One important candidate for this underlying risk factor may be self-control, as a reflection of immature self-regulatory systems in adolescence. In the present study, we will test the extent to which joint development of cannabis use and depressive symptoms can be explained as an expression of self-control. A total of 428 adolescents participated in a five-wave longitudinal design. Main study outcomes were self-reports of self-control (age 12) and cannabis use and depressive symptoms (ages 12-16). We established six trajectories of joint development of cannabis use and depressive symptoms. Conditional probabilities indicated that cannabis use and depressive symptoms were symmetrically related. Levels of self-control were lowest for adolescents following the joint developmental pathway of cannabis use and high depressive symptoms. Low levels of self-control are predictive of joint development of cannabis use and depressive symptoms. Future studies should concentrate on the role of self-control in co-occurrence of other health risk behaviors and on psychological and physiological mechanisms underlying self-control and its relation to co-occurrence. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Comparison of the properties of collagen-chitosan scaffolds after γ-ray irradiation and carbodiimide cross-linking.

PubMed

Chen, Zihao; Du, Tianming; Tang, Xiangyu; Liu, Changjun; Li, Ruixin; Xu, Cheng; Tian, Feng; Du, Zhenjie; Wu, Jimin

2016-07-01

The property of collagen-chitosan porous scaffold varies according to cross-linking density and scaffold composition. This study was designed to compare the properties of collagen-chitosan porous scaffolds cross-linked with γ-irradiation and carbodiimide (CAR) for the first time. Eleven sets of collagen-chitosan scaffolds containing different concentrations of chitosan at a 5% increasing gradient were fabricated. Fourier transform infrared spectroscopy was performed to confirm the success of cross-linking in the scaffolds. The scaffold morphology was evaluated under scanning electron microscope (SEM). SEM revealed that chitosan was an indispensable material for the fabrication of γ-ray irradiation scaffold. The microstructure of γ-ray irradiation scaffold was less stable than those of alternative scaffolds. Based upon swelling ratio, porosity factor, and collagenase degradation, γ-ray irradiation scaffold was less stable than CAR and 25% proportion of chitosan scaffolds. Mechanical property determines the orientation in γ-irradiation and CAR scaffold. In vitro degradation test indicated that γ-irradiation and CAR cross-linking can elevate the scaffold biocompatibility. Compared with γ-ray irradiation, CAR cross-linked scaffold containing 25% chitosan can more significantly enhance the bio-stability and biocompatibility of collagen-chitosan scaffolds. CAR cross-linked scaffold may be the best choice for future tissue engineering.

Spectrin-ankyrin interaction mechanics: A key force balance factor in the red blood cell membrane skeleton.

PubMed

Saito, Masakazu; Watanabe-Nakayama, Takahiro; Machida, Shinichi; Osada, Toshiya; Afrin, Rehana; Ikai, Atsushi

2015-01-01

As major components of red blood cell (RBC) cytoskeleton, spectrin and F-actin form a network that covers the entire cytoplasmic surface of the plasma membrane. The cross-linked two layered structure, called the membrane skeleton, keeps the structural integrity of RBC under drastically changing mechanical environment during circulation. We performed force spectroscopy experiments on the atomic force microscope (AFM) as a means to clarify the mechanical characteristics of spectrin-ankyrin interaction, a key factor in the force balance of the RBC cytoskeletal structure. An AFM tip was functionalized with ANK1-62k and used to probe spectrin crosslinked to mica surface. A force spectroscopy study gave a mean unbinding force of ~30 pN under our experimental conditions. Two energy barriers were identified in the unbinding process. The result was related to the well-known flexibility of spectrin tetramer and participation of ankyrin 1-spectrin interaction in the overall balance of membrane skeleton dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.

The roles of hydraulic and carbon stress in a widespread climate-induced forest die-off

PubMed Central

Anderegg, William R. L.; Berry, Joseph A.; Smith, Duncan D.; Sperry, John S.; Anderegg, Leander D. L.; Field, Christopher B.

2012-01-01

Forest ecosystems store approximately 45% of the carbon found in terrestrial ecosystems, but they are sensitive to climate-induced dieback. Forest die-off constitutes a large uncertainty in projections of climate impacts on terrestrial ecosystems, climate–ecosystem interactions, and carbon-cycle feedbacks. Current understanding of the physiological mechanisms mediating climate-induced forest mortality limits the ability to model or project these threshold events. We report here a direct and in situ study of the mechanisms underlying recent widespread and climate-induced trembling aspen (Populus tremuloides) forest mortality in western North America. We find substantial evidence of hydraulic failure of roots and branches linked to landscape patterns of canopy and root mortality in this species. On the contrary, we find no evidence that drought stress led to depletion of carbohydrate reserves. Our results illuminate proximate mechanisms underpinning recent aspen forest mortality and provide guidance for understanding and projecting forest die-offs under climate change. PMID:22167807

Opportunities and Challenges for the Emerging Field of Positive Emotion Regulation: A Commentary on the Special Edition on Positive Emotions and Cognitions in Clinical Psychology.

PubMed

Dunn, Barnaby D

2017-01-01

The importance of developing a better understanding of positive emotion regulation in both healthy and clinical populations is now recognised. This special edition brings together leading figures in the positive emotion regulation field and has contributions characterizing positive phenomena, differentiating them from negative phenomena, and evaluating underlying psychological mechanisms that drive these phenomena. This commentary reviews these articles to highlight challenges and opportunities for this emerging field, including the need to better characterize positive phenomena, to be more explicit about how the links between negative and positive phenomena are conceptualised, to evaluate more robustly underlying mechanisms, to standardize measurement of positive constructs, and to ensure that these scientific findings lead to meaningful changes in real-world policy and practice.

An in situ tensile test apparatus for polymers in high pressure hydrogen

DOE PAGES

Alvine, Kyle J.; Kafentzis, Tyler A.; Pitman, Stan G.; ...

2014-10-31

Degradation of material properties by high-pressure hydrogen is an important factor in determining the safety and reliability of materials used in high-pressure hydrogen storage and delivery. Hydrogen damage mechanisms have a time dependence that is linked to hydrogen outgassing after exposure to the hydrogen atmosphere that makes ex situ measurements of mechanical properties problematic. Designing in situ measurement instruments for high-pressure hydrogen is challenging due to known hydrogen incompatibility with many metals and standard high-power motor materials like Nd. Here we detail the design and operation of a solenoid based in situ tensile tester under high-pressure hydrogen environments up tomore » 5,000 psi. Here, modulus data from high-density polyethylene (HDPE) samples tested under high-pressure hydrogen are also reported as compared to baseline measurements taken in air.« less

A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses.

PubMed

Oshiumi, Hiroyuki; Miyashita, Moeko; Matsumoto, Misako; Seya, Tsukasa

2013-01-01

The innate immune system is essential for controlling viral infections, but several viruses have evolved strategies to escape innate immunity. RIG-I is a cytoplasmic viral RNA sensor that triggers the signal to induce type I interferon production in response to viral infection. RIG-I activation is regulated by the K63-linked polyubiquitin chain mediated by Riplet and TRIM25 ubiquitin ligases. TRIM25 is required for RIG-I oligomerization and interaction with the IPS-1 adaptor molecule. A knockout study revealed that Riplet was essential for RIG-I activation. However the molecular mechanism underlying RIG-I activation by Riplet remains unclear, and the functional differences between Riplet and TRIM25 are also unknown. A genetic study and a pull-down assay indicated that Riplet was dispensable for RIG-I RNA binding activity but required for TRIM25 to activate RIG-I. Mutational analysis demonstrated that Lys-788 within the RIG-I repressor domain was critical for Riplet-mediated K63-linked polyubiquitination and that Riplet was required for the release of RIG-I autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling. We investigated the biological importance of this mechanism in human cells and found that hepatitis C virus (HCV) abrogated this mechanism. Interestingly, HCV NS3-4A proteases targeted the Riplet protein and abrogated endogenous RIG-I polyubiquitination and association with TRIM25 and TBK1, emphasizing the biological importance of this mechanism in human antiviral innate immunity. In conclusion, our results establish that Riplet-mediated K63-linked polyubiquitination released RIG-I RD autorepression, which allowed the access of positive factors to the RIG-I protein.

A Distinct Role of Riplet-Mediated K63-Linked Polyubiquitination of the RIG-I Repressor Domain in Human Antiviral Innate Immune Responses

PubMed Central

Oshiumi, Hiroyuki; Miyashita, Moeko; Matsumoto, Misako; Seya, Tsukasa

2013-01-01

The innate immune system is essential for controlling viral infections, but several viruses have evolved strategies to escape innate immunity. RIG-I is a cytoplasmic viral RNA sensor that triggers the signal to induce type I interferon production in response to viral infection. RIG-I activation is regulated by the K63-linked polyubiquitin chain mediated by Riplet and TRIM25 ubiquitin ligases. TRIM25 is required for RIG-I oligomerization and interaction with the IPS-1 adaptor molecule. A knockout study revealed that Riplet was essential for RIG-I activation. However the molecular mechanism underlying RIG-I activation by Riplet remains unclear, and the functional differences between Riplet and TRIM25 are also unknown. A genetic study and a pull-down assay indicated that Riplet was dispensable for RIG-I RNA binding activity but required for TRIM25 to activate RIG-I. Mutational analysis demonstrated that Lys-788 within the RIG-I repressor domain was critical for Riplet-mediated K63-linked polyubiquitination and that Riplet was required for the release of RIG-I autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling. We investigated the biological importance of this mechanism in human cells and found that hepatitis C virus (HCV) abrogated this mechanism. Interestingly, HCV NS3-4A proteases targeted the Riplet protein and abrogated endogenous RIG-I polyubiquitination and association with TRIM25 and TBK1, emphasizing the biological importance of this mechanism in human antiviral innate immunity. In conclusion, our results establish that Riplet-mediated K63-linked polyubiquitination released RIG-I RD autorepression, which allowed the access of positive factors to the RIG-I protein. PMID:23950712

A Neurobehavioral Mechanism Linking Behaviorally Inhibited Temperament and Later Adolescent Social Anxiety.

PubMed

Buzzell, George A; Troller-Renfree, Sonya V; Barker, Tyson V; Bowman, Lindsay C; Chronis-Tuscano, Andrea; Henderson, Heather A; Kagan, Jerome; Pine, Daniel S; Fox, Nathan A

2017-12-01

Behavioral inhibition (BI) is a temperament identified in early childhood that is a risk factor for later social anxiety. However, mechanisms underlying the development of social anxiety remain unclear. To better understand the emergence of social anxiety, longitudinal studies investigating changes at behavioral neural levels are needed. BI was assessed in the laboratory at 2 and 3 years of age (N = 268). Children returned at 12 years, and an electroencephalogram was recorded while children performed a flanker task under 2 conditions: once while believing they were being observed by peers and once while not being observed. This methodology isolated changes in error monitoring (error-related negativity) and behavior (post-error reaction time slowing) as a function of social context. At 12 years, current social anxiety symptoms and lifetime diagnoses of social anxiety were obtained. Childhood BI prospectively predicted social-specific error-related negativity increases and social anxiety symptoms in adolescence; these symptoms directly related to clinical diagnoses. Serial mediation analysis showed that social error-related negativity changes explained relations between BI and social anxiety symptoms (n = 107) and diagnosis (n = 92), but only insofar as social context also led to increased post-error reaction time slowing (a measure of error preoccupation); this model was not significantly related to generalized anxiety. Results extend prior work on socially induced changes in error monitoring and error preoccupation. These measures could index a neurobehavioral mechanism linking BI to adolescent social anxiety symptoms and diagnosis. This mechanism could relate more strongly to social than to generalized anxiety in the peri-adolescent period. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta.

PubMed

Dobrowolny, Gabriella; Martini, Martina; Scicchitano, Bianca Maria; Romanello, Vanina; Boncompagni, Simona; Nicoletti, Carmine; Pietrangelo, Laura; De Panfilis, Simone; Catizone, Angela; Bouchè, Marina; Sandri, Marco; Rudolf, Rüdiger; Protasi, Feliciano; Musarò, Antonio

2018-04-20

Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1 G93A in transgenic MLC/SOD1 G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1 G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration. The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1 G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity. Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 28, 1105-1119.

The Hv1 proton channel responds to mechanical stimuli.

PubMed

Pathak, Medha M; Tran, Truc; Hong, Liang; Joós, Béla; Morris, Catherine E; Tombola, Francesco

2016-11-01

The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain. Here, we report that these VSDs directly respond to mechanical stimuli. We find that membrane stretch facilitates Hv1 channel opening by increasing the rate of activation and shifting the steady-state activation curve to less depolarized potentials. In the presence of a transmembrane pH gradient, membrane stretch alone opens the channel without the need for strong depolarizations. The effect of membrane stretch persists for several minutes after the mechanical stimulus is turned off, suggesting that the channel switches to a "facilitated" mode in which opening occurs more readily and then slowly reverts to the normal mode observed in the absence of membrane stretch. Conductance simulations with a six-state model recapitulate all the features of the channel's response to mechanical stimulation. Hv1 mechanosensitivity thus provides a mechanistic link between channel activation in microglia and brain damage after stroke. © 2016 Pathak et al.

Lipids, adiposity and tendinopathy: is there a mechanistic link? Critical review

PubMed Central

Scott, Alex; Zwerver, Johannes; Grewal, Navi; de Sa, Agnetha; Alktebi, Thuraya; Granville, David J; Hart, David A

2015-01-01

Being overweight or obese is associated with an elevated risk of tendon pathology. However, for sportspeople the epidemiological data linking weight or adiposity on one hand, and risk of tendon pathology on the other, are less consistent. Indeed, the mechanistic links between diet, adiposity and tendon pathology remain largely unexamined. Recent studies have begun to examine the effects of dietary interventions on outcomes such as tendon biomechanics or pain. Oxidised low-density lipoprotein has been shown to (A) accumulate in the tendon tissues of mice that eat a fatty diet and (B) induce a pathological phenotype in human tendon cells. This paper addresses the current debate: is excessive body mass index (causing increased load and strain on tendon tissue) per se the underlying mechanism? Or do local or systemic influences of fat on tendons predispose to tendon pathology? This narrative review argues that excessive blood lipids may be an important avenue for clinical investigations. PMID:25488953

Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex Determination

PubMed Central

Burridge, Christopher P; Ezaz, Tariq; Wapstra, Erik

2018-01-01

Abstract Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here, we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whereas in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater differentiation of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems can be facilitated by subtle genetic differences. PMID:29659810

The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper

PubMed Central

Gillberg, Christopher; Fernell, Elisabeth; Kočovská, Eva; Minnis, Helen; Bourgeron, Thomas; Thompson, Lucy

2017-01-01

Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the “autisms” [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as “steroid metabolism” and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. Autism Res 2017, 10: 1022–1044. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. PMID:28401679

Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic.

PubMed

Carroll, Joseph; Rossi, Ethan A; Porter, Jason; Neitz, Jay; Roorda, Austin; Williams, David R; Neitz, Maureen

2010-09-15

Blue cone monochromacy (BCM) is an X-linked condition in which long- (L) and middle- (M) wavelength-sensitive cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal cone electroretinograms. Here we imaged the cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M opsin gene expression (effectively acting as a cone opsin knockout). On average, they had cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of opsin in a subset of cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers. Copyright 2010 Elsevier Ltd. All rights reserved.

Toggle mechanism for pinching metal tubes

NASA Technical Reports Server (NTRS)

Stengard, E. O. (Inventor)

1979-01-01

A toggle mechanism pinches a metal tube and maintains the tube in a pinched condition, without fracturing. The toggle mechanism includes a plunger translatable along a longitudinal axis, as well as a pair of links pivoted about a common axis extending through an end of the plunger. One of the links also pivots about a fixed axis. A free end of the other link carries a push link which the other link translates at right angles to the plunger longitudinal axis. First and second sides of the tube bear against a first stop block and are engaged by the push link when a compression spring, attached to the plunger, is suddenly released to irreversibly drive the plunger along its longitudinal axis so the pivot point of the two links is driven to an over travel position.

Neuronal mechanisms underlying differences in spatial resolution between darks and lights in human vision.

PubMed

Pons, Carmen; Mazade, Reece; Jin, Jianzhong; Dul, Mitchell W; Zaidi, Qasim; Alonso, Jose-Manuel

2017-12-01

Artists and astronomers noticed centuries ago that humans perceive dark features in an image differently from light ones; however, the neuronal mechanisms underlying these dark/light asymmetries remained unknown. Based on computational modeling of neuronal responses, we have previously proposed that such perceptual dark/light asymmetries originate from a luminance/response saturation within the ON retinal pathway. Consistent with this prediction, here we show that stimulus conditions that increase ON luminance/response saturation (e.g., dark backgrounds) or its effect on light stimuli (e.g., optical blur) impair the perceptual discrimination and salience of light targets more than dark targets in human vision. We also show that, in cat visual cortex, the magnitude of the ON luminance/response saturation remains relatively constant under a wide range of luminance conditions that are common indoors, and only shifts away from the lowest luminance contrasts under low mesopic light. Finally, we show that the ON luminance/response saturation affects visual salience mostly when the high spatial frequencies of the image are reduced by poor illumination or optical blur. Because both low luminance and optical blur are risk factors in myopia, our results suggest a possible neuronal mechanism linking myopia progression with the function of the ON visual pathway.

Neuronal mechanisms underlying differences in spatial resolution between darks and lights in human vision

PubMed Central

Pons, Carmen; Mazade, Reece; Jin, Jianzhong; Dul, Mitchell W.; Zaidi, Qasim; Alonso, Jose-Manuel

2017-01-01

Artists and astronomers noticed centuries ago that humans perceive dark features in an image differently from light ones; however, the neuronal mechanisms underlying these dark/light asymmetries remained unknown. Based on computational modeling of neuronal responses, we have previously proposed that such perceptual dark/light asymmetries originate from a luminance/response saturation within the ON retinal pathway. Consistent with this prediction, here we show that stimulus conditions that increase ON luminance/response saturation (e.g., dark backgrounds) or its effect on light stimuli (e.g., optical blur) impair the perceptual discrimination and salience of light targets more than dark targets in human vision. We also show that, in cat visual cortex, the magnitude of the ON luminance/response saturation remains relatively constant under a wide range of luminance conditions that are common indoors, and only shifts away from the lowest luminance contrasts under low mesopic light. Finally, we show that the ON luminance/response saturation affects visual salience mostly when the high spatial frequencies of the image are reduced by poor illumination or optical blur. Because both low luminance and optical blur are risk factors in myopia, our results suggest a possible neuronal mechanism linking myopia progression with the function of the ON visual pathway. PMID:29196762

Progressing neurobiological strategies against proteostasis failure: Challenges in neurodegeneration.

PubMed

Amanullah, Ayeman; Upadhyay, Arun; Joshi, Vibhuti; Mishra, Ribhav; Jana, Nihar Ranjan; Mishra, Amit

2017-12-01

Proteins are ordered useful cellular entities, required for normal health and organism's survival. The proteome is the absolute set of cellular expressed proteins, which regulates a wide range of physiological functions linked with all domains of life. In aging cells or under unfavorable cellular conditions, misfolding of proteins generates common pathological events linked with neurodegenerative diseases and aging. Current advances of proteome studies systematically generates some progress in our knowledge that how misfolding of proteins or their accumulation can contribute to the impairment or depletion of proteome functions. Still, the underlying causes of this unrecoverable loss are not clear that how such unsolved transitions give rise to multifactorial challengeable degenerative pathological conditions in neurodegeneration. In this review, we specifically focus and systematically summarize various molecular mechanisms of proteostasis maintenance, as well as discuss progressing neurobiological strategies, promising natural and pharmacological candidates, which can be useful to counteract the problem of proteopathies. Our article emphasizes an urgent need that now it is important for us to recognize the fundamentals of proteostasis to design a new molecular framework and fruitful strategies to uncover how the proteome defects are associated with aging and neurodegenerative diseases. A enhance understanding of progress link with proteome and neurobiological challenges may provide new basic concepts in the near future, based on pharmacological agents, linked with impaired proteostasis and neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Initial dislocation structure and dynamic dislocation multiplication in Mo single crystals

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

Hsiung, L M; Lassila, D H

Initial dislocation structure in annealed high-purity Mo single crystals and deformation substructure in a crystal subjected to 1% compression have been examined and studied in order to investigate dislocation multiplication mechanisms in the early stages of plastic deformation. The initial dislocation density is in a range of 10{sup 6} {approx} 10{sup 7} cm{sup -2}, and the dislocation structure is found to contain many grown-in superjogs along dislocation lines. The dislocation density increases to a range of 10{sup 8} {approx} 10{sup 9} cm{sup -2}, and the average jog height is also found to increase after compressing for a total strain ofmore » 1%. It is proposed that the preexisting jogged screw dislocations can act as (multiple) dislocation multiplication sources when deformed under quasi-static conditions. Both the jog height and length of link segment (between jogs) can increase by stress-induced jog coalescence, which takes place via the lateral migration (drift) of superjogs driven by unbalanced line-tension partials acting on link segments of unequal lengths. Applied shear stress begins to push each link segment to precede dislocation multiplication when link length and jog height are greater than critical lengths. This dynamic dislocation multiplication source is subsequently verified by direct simulations of dislocation dynamics under stress to be crucial in the early stages of plastic deformation in Mo single crystals.« less

Controllable synthesis of mesoporous carbon nanospheres and Fe-N/carbon nanospheres as efficient oxygen reduction electrocatalysts

NASA Astrophysics Data System (ADS)

Wei, Jing; Liang, Yan; Zhang, Xinyi; Simon, George P.; Zhao, Dongyuan; Zhang, Jin; Jiang, Sanping; Wang, Huanting

2015-03-01

The synthesis of mesoporous carbon nanospheres (MCNs), especially with diameters below 200 nm remains a great challenge due to weak interactions between the carbon precursors and soft templates, as well as the uncontrollable cross-linking rate of carbon precursors. Herein, we demonstrate a simple acid-assisted, hydrothermal synthesis approach to synthesizing such uniform MCNs with well controlled diameters ranging from 20 to 150 nm under highly acidic conditions (2 M HCl). Both the carbon precursor and the template are partly protonated under such conditions and show additional Coulombic interactions with chloride ions (acts as mediators). This kind of enhanced interaction is similar to that of the ``I+X-S+'' mechanism in the synthesis of mesoporous metal oxide, which can effectively retard the cross-linking rate of resol molecules and avoid macroscopic phase separation during the hydrothermal synthesis. Due to their uniform spherical morphology, small diameter, and high surface areas, MCNs can be modified with Fe and N species via impregnation of cheap precursors (ferric nitrate and dicyandiamide), which are further converted into nonprecious electrocatalysts for oxygen reduction reactions. The resulting Fe-N/MCNs exhibit high catalytic activities, long-term stability and improved methanol tolerance under alkaline conditions, which can be potentially used in direct methanol fuel cells and metal-air batteries.The synthesis of mesoporous carbon nanospheres (MCNs), especially with diameters below 200 nm remains a great challenge due to weak interactions between the carbon precursors and soft templates, as well as the uncontrollable cross-linking rate of carbon precursors. Herein, we demonstrate a simple acid-assisted, hydrothermal synthesis approach to synthesizing such uniform MCNs with well controlled diameters ranging from 20 to 150 nm under highly acidic conditions (2 M HCl). Both the carbon precursor and the template are partly protonated under such conditions and show additional Coulombic interactions with chloride ions (acts as mediators). This kind of enhanced interaction is similar to that of the ``I+X-S+'' mechanism in the synthesis of mesoporous metal oxide, which can effectively retard the cross-linking rate of resol molecules and avoid macroscopic phase separation during the hydrothermal synthesis. Due to their uniform spherical morphology, small diameter, and high surface areas, MCNs can be modified with Fe and N species via impregnation of cheap precursors (ferric nitrate and dicyandiamide), which are further converted into nonprecious electrocatalysts for oxygen reduction reactions. The resulting Fe-N/MCNs exhibit high catalytic activities, long-term stability and improved methanol tolerance under alkaline conditions, which can be potentially used in direct methanol fuel cells and metal-air batteries. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00331h

On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth

PubMed Central

Wang, Wei-Chun; Brashier, Nadia M.; Wing, Erik A.; Marsh, Elizabeth J.; Cabeza, Roberto

2016-01-01

The “illusory truth” effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency or the subjective ease experienced while processing a statement underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency. PMID:26765947

Structure–property study of cross-linked hydrocarbon/poly(ethylene oxide) electrolytes with superior conductivity and dendrite resistance† †Electronic supplementary information (ESI) available: Synthetic procedures, characterization data, electrochemical impedance spectra and additional SEM images. See DOI: 10.1039/c6sc01813k Click here for additional data file.

PubMed Central

Zheng, Qi; Ma, Lin; Khurana, Rachna

2016-01-01

Lithium dendrite growth is a fundamental problem that precludes the practical use of lithium metal batteries. Solid polymer electrolytes (SPEs) have been widely studied to resist the growth of lithium dendrites but the underlying mechanisms are still unclear. Most SPEs sacrifice high ionic conductivities for increased dendrite suppression performance by using components with high mechanical stiffness. We report a class of cross-linked hydrocarbon/poly(ethylene oxide) SPEs with both high ionic conductivities (approaching 1 × 10–3 S cm–1 at 25 °C) and superior dendrite suppression characteristics. A systematic structure–property study shows that the crystallinity of the hydrocarbon backbones plays a key role in regulating size and morphology of lithium dendrites, as well as the ability to suppress their growth. PMID:28451125

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

PubMed

Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

2015-11-01

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

PubMed Central

Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

2015-01-01

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

Does the Concept of “Sensitization” Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?

PubMed Central

Collip, Dina; Myin-Germeys, Inez; Van Os, Jim

2008-01-01

Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as “sensitization,” facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder. PMID:18203757

Inferring multi-scale neural mechanisms with brain network modelling

PubMed Central

Schirner, Michael; McIntosh, Anthony Randal; Jirsa, Viktor; Deco, Gustavo

2018-01-01

The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood. Here, we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects' individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) resting-state fMRI oscillations, (2) functional connectivity networks, (3) excitation-inhibition balance, (4, 5) inverse relationships between α-rhythms, spike-firing and fMRI on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies. PMID:29308767

The mediating role of social support in the relationship between psychological well-being and health-risk behaviors among Chinese university students

PubMed Central

Lai, Catie CW; Ma, Cecilia MS

2016-01-01

While literature has displayed a link between psychological well-being (i.e. depression, hopelessness, and life satisfaction) and health-risk behaviors (i.e. smoking, drinking, suicide, and physical inactivity), the mechanisms underlying this relationship have received little empirical attention. This study examines the mediation effects of social support (from family, friends, and significant others) that accounted for the link. Participants were 2023 university students (47.7% male). Structural equation modeling showed partial mediation effect of social support between psychological well-being and health-risk behaviors. In particular, social support from family and friends jointly mediated about 80 percent of the effect of life satisfaction and hopelessness on drinking. These results offered novel evidence that helps improve theorizing the mechanisms of the relationship between psychological well-being and health-risk behaviors. They also highlighted the potential benefits of social support for university students to help them stay healthy. The implications of these results are discussed. PMID:28070409

A water-responsive shape memory ionomer with permanent shape reconfiguration ability

NASA Astrophysics Data System (ADS)

Bai, Yongkang; Zhang, Jiwen; Tian, Ran; Chen, Xin

2018-04-01

In this work, a water-responsive shape memory ionomer with high toughness was fabricated by cross-linking hyaluronic acid sodium (HAS) and polyvinyl alcohol (PVA) through coordination interactions. The strong Fe3+-carboxyl (from HAS) coordination interactions served as main physical cross-linking points for the performance of water-responsive shape memory, which associated with the flexibility of PVA chain producing excellent mechanical properties of this ionomer. The optimized ionomer was not only able to recover to its original shape within just 22 s by exposing to water, but exhibited high tensile strength up to 35.4 MPa and 4 times higher tractility than the ionomer without PVA. Moreover, the ionomers can be repeatedly programed to various new permanent shapes on demand due to the reversible physical interactions, which still performed complete and fast geometric recovery under stimuli even after 4 cycles of reprograming with 3 different shapes. The excellent shape memory and strong mechanical behaviors make our ionomers significant and promising smart materials for variety of applications.

Recovery of lactic acid from the pretreated fermentation broth based on a novel hyper-cross-linked meso-micropore resin: Modeling.

PubMed

Song, Mingkai; Jiao, Pengfei; Qin, Taotao; Jiang, Kangkang; Zhou, Jingwei; Zhuang, Wei; Chen, Yong; Liu, Dong; Zhu, Chenjie; Chen, Xiaochun; Ying, Hanjie; Wu, Jinglan

2017-10-01

An innovative benign process for recovery lactic acid from its fermentation broth is proposed using a novel hyper-cross-linked meso-micropore resin and water as eluent. This work focuses on modeling the competitive adsorption behaviors of glucose, lactic acid and acetic acid ternary mixture and explosion of the adsorption mechanism. The characterization results showed the resin had a large BET surface area and specific pore structure with hydrophobic properties. By analysis of the physicochemical properties of the solutes and the resin, the mechanism of the separation is proposed as hydrophobic effect and size-exclusion. Subsequently three chromatographic models were applied to predict the competitive breakthrough curves of the ternary mixture under different operating conditions. The pore diffusion was the major limiting factor for the adsorption process, which was consistent with the BET results. The novel HD-06 resin can be a good potential adsorbent for the future SMB continuous separation process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans.

PubMed

Gifford, Robert M; Reynolds, Rebecca M

2017-11-01

Increasing evidence supports fetal glucocorticoid exposure with associated altered offspring hypothalamic-pituitary-adrenal (HPA) axis activity as a key mechanism linking early life events with later life disease. Alterations in HPA axis activity are linked to a range of cardiometabolic and psychiatric diseases. As many of these diseases manifest sex differences in presentation we review the evidence for programmed sex-differences in the HPA axis. Available literature suggests vulnerability of the female HPA axis to prenatal stressors with female offspring demonstrating increased HPA axis reactivity. This may be due to changes in placental glucocorticoid metabolism leading to increased fetal glucocorticoid exposure. We discuss the potential consequences of increased vulnerability of the female HPA axis for later life health and consider the underlying mechanisms. Further studies are needed to determine whether sex-differences in early-life programming of the HPA axis represent a pathway underpinning the sex-differences in common cardiometabolic and psychiatric diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

A new look at cardiac defense: attention or emotion?

PubMed

Vila, Jaime; Fernández, María Carmen; Pegalajar, Joaquín; Nieves Vera, María; Robles, Humbelina; Pérez, Nieves; Sánchez, María B; Ramírez, Isabel; Ruiz-Padial, Elisabeth

2003-05-01

The study of cardiac defense has a long tradition in psychological research both within the cognitive approach--linked to Pavlov, Sokolov, and Graham's work on sensory reflexes--and within the motivational one--linked to the work of Cannon and subsequent researchers on the concepts of activation and stress. These two approaches have been difficult to reconcile in the past. We summarize a series of studies on cardiac defense from a different perspective, which allows integration of the traditional approaches. This new perspective emphasizes a sequential process interpretation of the cardiac defense response. Results of descriptive and parametric studies, as well as those of studies examining the physiological and psychological mechanisms underlying the response, show a complex response pattern with both accelerative and decelerative components, with both sympathetic and parasympathetic influences, and with both attentional and emotional significance. The implications of this new look at cardiac defense are discussed in relation to defensive reactions in natural settings, the brain mechanisms controlling such reactions, and their effects on health and illness.

Cellular Auxin Homeostasis under High Temperature Is Regulated through a SORTING NEXIN1–Dependent Endosomal Trafficking Pathway[C][W

PubMed Central

Hanzawa, Taiki; Shibasaki, Kyohei; Numata, Takahiro; Kawamura, Yukio; Gaude, Thierry; Rahman, Abidur

2013-01-01

High-temperature-mediated adaptation in plant architecture is linked to the increased synthesis of the phytohormone auxin, which alters cellular auxin homeostasis. The auxin gradient, modulated by cellular auxin homeostasis, plays an important role in regulating the developmental fate of plant organs. Although the signaling mechanism that integrates auxin and high temperature is relatively well understood, the cellular auxin homeostasis mechanism under high temperature is largely unknown. Using the Arabidopsis thaliana root as a model, we demonstrate that under high temperature, roots counterbalance the elevated level of intracellular auxin by promoting shootward auxin efflux in a PIN-FORMED2 (PIN2)-dependent manner. Further analyses revealed that high temperature selectively promotes the retrieval of PIN2 from late endosomes and sorts them to the plasma membrane through an endosomal trafficking pathway dependent on SORTING NEXIN1. Our results demonstrate that recycling endosomal pathway plays an important role in facilitating plants adaptation to increased temperature. PMID:24003052

Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.

PubMed

Strahler, Jana; Skoluda, Nadine; Rohleder, Nicolas; Nater, Urs M

2016-09-01

Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic Nonreciprocity in Loss-Compensated Piezophononic Media

NASA Astrophysics Data System (ADS)

Merkel, Aurélien; Willatzen, Morten; Christensen, Johan

2018-03-01

Violating time-reversal symmetry enables one to engineer nonreciprocal structures for isolating and rectifying sound and mechanical vibrations. Rectifying sound is commonly achieved in nonlinear media, but the operation is inherently linked to weak and distorted signals. Here, we show how a pronounced electron-phonon coupling in linear piezophononic media under electrical bias can generate full mechanical rectification of broad spectral width, which permits the isolation of pulsed vibrations while keeping the wave-front shape fully intact. In this context, we deliberately show how the acoustoelectric effect can provide active loss compensation against lattice anharmonicity and thermoelastic damping. Further, our predictions confirm tunable nonreciprocity at an ultralarge contrast ratio, which should open the doors for future mechanical diodes and compact ultrasonic transducers for sensing and imaging.

NSR&D FY15 Final Report. Modeling Mechanical, Thermal, and Chemical Effects of Impact

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

Long, Christopher Curtis; Ma, Xia; Zhang, Duan Zhong

2015-11-02

The main goal of this project is to develop a computer model that explains and predicts coupled mechanical, thermal and chemical responses of HE under impact and friction insults. The modeling effort is based on the LANL-developed CartaBlanca code, which is implemented with the dual domain material point (DDMP) method to calculate complex and coupled thermal, chemical and mechanical effects among fluids, solids and the transitions between the states. In FY 15, we have implemented the TEPLA material model for metal and performed preliminary can penetration simulation and begun to link with experiment. Currently, we are working on implementing amore » shock to detonation transition (SDT) model (SURF) and JWL equation of state.« less

Multiscale mechanical effects of native collagen cross-linking in tendon.

PubMed

Eekhoff, Jeremy D; Fang, Fei; Lake, Spencer P

2018-06-06

The hierarchical structure of tendon allows for attenuation of mechanical strain down decreasing length scales. While reorganization of collagen fibers accounts for microscale strain attenuation, cross-linking between collagen molecules contributes to deformation mechanisms at the fibrillar and molecular scales. Divalent and trivalent enzymatic cross-links form during the development of collagen fibrils through the enzymatic activity of lysyl oxidase (LOX). By establishing connections between telopeptidyl and triple-helical domains of adjacent molecules within collagen fibrils, these cross-links stiffen the fibrils by resisting intermolecular sliding. Ultimately, greater enzymatic cross-linking leads to less compliant and stronger tendon as a result of stiffer fibrils. In contrast, nonenzymatic cross-links such as glucosepane and pentosidine are not produced during development but slowly accumulate through glycation of collagen. Therefore, these cross-links are only expected to be present in significant quantities in advanced age, where there has been sufficient time for glycation to occur, and in diabetes, where the presence of more free sugar in the extracellular matrix increases the rate of glycation. Unlike enzymatic cross-links, current evidence suggests that nonenzymatic cross-links are at least partially isolated to the surface of collagen fibers. As a result, glycation has been proposed to primarily impact tendon mechanics by altering molecular interactions at the fiber interface, thereby diminishing sliding between fibers. Thus, increased nonenzymatic cross-linking decreases microscale strain attenuation and the viscous response of tendon. In conclusion, enzymatic and nonenzymatic collagen cross-links have demonstrable and distinct effects on the mechanical properties of tendon across different length scales.

Links between fluid mechanics and quantum mechanics: a model for information in economics?

PubMed

Haven, Emmanuel

2016-05-28

This paper tallies the links between fluid mechanics and quantum mechanics, and attempts to show whether those links can aid in beginning to build a formal template which is usable in economics models where time is (a)symmetric and memory is absent or present. An objective of this paper is to contemplate whether those formalisms can allow us to model information in economics in a novel way. © 2016 The Author(s).

A comprehensive combined experimental and computational framework for pre-clinical wear simulation of total knee replacements.

PubMed

Abdelgaied, A; Fisher, J; Jennings, L M

2018-02-01

A more robust pre-clinical wear simulation framework is required in order to simulate wider and higher ranges of activities, observed in different patient populations such as younger more active patients. Such a framework will help to understand and address the reported higher failure rates for younger and more active patients (National_Joint_Registry, 2016). The current study has developed and validated a comprehensive combined experimental and computational framework for pre-clinical wear simulation of total knee replacements (TKR). The input mechanical (elastic modulus and Poisson's ratio) and wear parameters of the moderately cross-linked ultra-high molecular weight polyethylene (UHMWPE) bearing material were independently measured from experimental studies under realistic test conditions, similar to the loading conditions found in the total knee replacements. The wear predictions from the computational wear simulation were validated against the direct experimental wear measurements for size 3 Sigma curved total knee replacements (DePuy, UK) in an independent experimental wear simulation study under three different daily activities; walking, deep squat, and stairs ascending kinematic conditions. The measured compressive mechanical properties of the moderately cross-linked UHMWPE material were more than 20% lower than that reported in the literature under tensile test conditions. The pin-on-plate wear coefficient of moderately cross-linked UHMWPE was significantly dependant of the contact stress and the degree of cross-shear at the articulating surfaces. The computational wear predictions for the TKR from the current framework were consistent and in a good agreement with the independent full TKR experimental wear simulation measurements, with 0.94 coefficient of determination of the framework. In addition, the comprehensive combined experimental and computational framework was able to explain the complex experimental wear trends from the three different daily activities investigated. Therefore, such a framework can be adopted as a pre-clinical simulation approach to optimise different designs, materials, as well as patient's specific total knee replacements for a range of activities. Copyright © 2017. Published by Elsevier Ltd.

Blind Predictions of DNA and RNA Tweezers Experiments with Force and Torque

PubMed Central

Chou, Fang-Chieh; Lipfert, Jan; Das, Rhiju

2014-01-01

Single-molecule tweezers measurements of double-stranded nucleic acids (dsDNA and dsRNA) provide unprecedented opportunities to dissect how these fundamental molecules respond to forces and torques analogous to those applied by topoisomerases, viral capsids, and other biological partners. However, tweezers data are still most commonly interpreted post facto in the framework of simple analytical models. Testing falsifiable predictions of state-of-the-art nucleic acid models would be more illuminating but has not been performed. Here we describe a blind challenge in which numerical predictions of nucleic acid mechanical properties were compared to experimental data obtained recently for dsRNA under applied force and torque. The predictions were enabled by the HelixMC package, first presented in this paper. HelixMC advances crystallography-derived base-pair level models (BPLMs) to simulate kilobase-length dsDNAs and dsRNAs under external forces and torques, including their global linking numbers. These calculations recovered the experimental bending persistence length of dsRNA within the error of the simulations and accurately predicted that dsRNA's “spring-like” conformation would give a two-fold decrease of stretch modulus relative to dsDNA. Further blind predictions of helix torsional properties, however, exposed inaccuracies in current BPLM theory, including three-fold discrepancies in torsional persistence length at the high force limit and the incorrect sign of dsRNA link-extension (twist-stretch) coupling. Beyond these experiments, HelixMC predicted that ‘nucleosome-excluding’ poly(A)/poly(T) is at least two-fold stiffer than random-sequence dsDNA in bending, stretching, and torsional behaviors; Z-DNA to be at least three-fold stiffer than random-sequence dsDNA, with a near-zero link-extension coupling; and non-negligible effects from base pair step correlations. We propose that experimentally testing these predictions should be powerful next steps for understanding the flexibility of dsDNA and dsRNA in sequence contexts and under mechanical stresses relevant to their biology. PMID:25102226

Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms.

PubMed

Wu, Xin-Ping; Gagliardi, Laura; Truhlar, Donald G

2018-05-30

Combined quantum mechanical and molecular mechanical (QM/MM) methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM-MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM-MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM-MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme.

Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation

PubMed Central

Jaiswal, Deepika; Jezek, Meagan; Quijote, Jeremiah; Lum, Joanna; Choi, Grace; Kulkarni, Rushmie; Park, DoHwan; Green, Erin M.

2017-01-01

The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1. Our results also show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression, and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation. PMID:29066473

Systems genetics: a paradigm to improve discovery of candidate genes and mechanisms underlying complex traits.

PubMed

Feltus, F Alex

2014-06-01

Understanding the control of any trait optimally requires the detection of causal genes, gene interaction, and mechanism of action to discover and model the biochemical pathways underlying the expressed phenotype. Functional genomics techniques, including RNA expression profiling via microarray and high-throughput DNA sequencing, allow for the precise genome localization of biological information. Powerful genetic approaches, including quantitative trait locus (QTL) and genome-wide association study mapping, link phenotype with genome positions, yet genetics is less precise in localizing the relevant mechanistic information encoded in DNA. The coupling of salient functional genomic signals with genetically mapped positions is an appealing approach to discover meaningful gene-phenotype relationships. Techniques used to define this genetic-genomic convergence comprise the field of systems genetics. This short review will address an application of systems genetics where RNA profiles are associated with genetically mapped genome positions of individual genes (eQTL mapping) or as gene sets (co-expression network modules). Both approaches can be applied for knowledge independent selection of candidate genes (and possible control mechanisms) underlying complex traits where multiple, likely unlinked, genomic regions might control specific complex traits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Zinc as a Gatekeeper of Immune Function

PubMed Central

Wessels, Inga; Maywald, Martina; Rink, Lothar

2017-01-01

After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function. PMID:29186856

Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus.

PubMed

Stephens, Andrew D; Banigan, Edward J; Adam, Stephen A; Goldman, Robert D; Marko, John F

2017-07-07

The cell nucleus must continually resist and respond to intercellular and intracellular mechanical forces to transduce mechanical signals and maintain proper genome organization and expression. Altered nuclear mechanics is associated with many human diseases, including heart disease, progeria, and cancer. Chromatin and nuclear envelope A-type lamin proteins are known to be key nuclear mechanical components perturbed in these diseases, but their distinct mechanical contributions are not known. Here we directly establish the separate roles of chromatin and lamin A/C and show that they determine two distinct mechanical regimes via micromanipulation of single isolated nuclei. Chromatin governs response to small extensions (<3 μm), and euchromatin/heterochromatin levels modulate the stiffness. In contrast, lamin A/C levels control nuclear strain stiffening at large extensions. These results can be understood through simulations of a polymeric shell and cross-linked polymer interior. Our results provide a framework for understanding the differential effects of chromatin and lamin A/C in cell nuclear mechanics and their alterations in disease. © 2017 Stephens et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Cellular Mechanosensing: Getting to the nucleus of it all

PubMed Central

Fedorchak, Gregory R.; Kaminski, Ashley; Lammerding, Jan

2014-01-01

Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins. PMID:25008017

Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure.

PubMed

Koyani, Chintan N; Kolesnik, Ewald; Wölkart, Gerald; Shrestha, Niroj; Scheruebel, Susanne; Trummer, Christopher; Zorn-Pauly, Klaus; Hammer, Astrid; Lang, Petra; Reicher, Helga; Maechler, Heinrich; Groschner, Klaus; Mayer, Bernd; Rainer, Peter P; Sourij, Harald; Sattler, Wolfgang; Malle, Ernst; Pelzmann, Brigitte; von Lewinski, Dirk

2017-12-01

Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca 2+ /calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca 2+ -ATPase 2a axis and Na + -Ca 2+ exchanger function in Ca 2+ extrusion. This resulted in reduced sarcoplasmic reticulum Ca 2+ content, diastolic Ca 2+ overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K + current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Supertoughened Biobased Poly(lactic acid)-Epoxidized Natural Rubber Thermoplastic Vulcanizates: Fabrication, Co-continuous Phase Structure, Interfacial in Situ Compatibilization, and Toughening Mechanism.

PubMed

Wang, Youhong; Chen, Kunling; Xu, Chuanhui; Chen, Yukun

2015-09-10

In the presence of dicumyl peroxide (DCP), biobased thermoplastic vulcanizates (TPVs) composed of poly(lactic acid) (PLA) and epoxidized natural rubber (ENR) were prepared through dynamic vulcanization. Interfacial in situ compatibilization between PLA and ENR phases was confirmed by Fourier transform infrared spectroscopy (FT-IR). A novel "sea-sea" co-continuous phase in the PLA/ENR TPVs was observed through scanning electron microscopy (SEM) and differed from the typical "sea-island" morphology that cross-linked rubber particles dispersed in plastic matrix. A sharp, brittle-ductile transition occurred with 40 wt % of ENR, showing a significantly improved impact strength of 47 kJ/m(2), nearly 15 times that of the neat PLA and 2.6 times that of the simple blend with the same PLA/ENR ratio. Gel permeation chromatography (GPC) and dynamic mechanical analysis (DMA) results suggested that a certain amount of DCP was consumed in the PLA phase, causing a slight cross-linking or branching of PLA molecules. the effects of various DCP contents on the impact property were investigated. The toughening mechanism under impact testing was researched, and the influence factors for toughening were discussed.

Molecular mechanisms of mechanotransduction in integrin-mediated cell-matrix adhesion

PubMed Central

Li, Zhenhai; Lee, Hyunjung; Zhu, Cheng

2016-01-01

Cell-matrix adhesion complexes are multi-protein structures linking the extracellular matrix (ECM) to the cytoskeleton. They are essential to both cell motility and function by bidirectionally sensing and transmitting mechanical and biochemical stimulations. Several types of cell-matrix adhesions have been identified and they share many key molecular components, such as integrins and actin-integrin linkers. Mechanochemical coupling between ECM molecules and the actin cytoskeleton has been observed from the single cell to the single molecule level and from immune cells to neuronal cells. However, the mechanisms underlying force regulation of integrin-mediated mechanotransduction still need to be elucidated. In this review article, we focus on integrin-mediated adhesions and discuss force regulation of cell-matrix adhesions and key adaptor molecules, three different force-dependent behaviors, and molecular mechanisms for mechanochemical coupling in force regulation. PMID:27720950

Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

PubMed

Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

2014-02-01

Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimization of biomass composition explains microbial growth-stoichiometry relationships

USGS Publications Warehouse

Franklin, O.; Hall, E.K.; Kaiser, C.; Battin, T.J.; Richter, A.

2011-01-01

Integrating microbial physiology and biomass stoichiometry opens far-reaching possibilities for linking microbial dynamics to ecosystem processes. For example, the growth-rate hypothesis (GRH) predicts positive correlations among growth rate, RNA content, and biomass phosphorus (P) content. Such relationships have been used to infer patterns of microbial activity, resource availability, and nutrient recycling in ecosystems. However, for microorganisms it is unclear under which resource conditions the GRH applies. We developed a model to test whether the response of microbial biomass stoichiometry to variable resource stoichiometry can be explained by a trade-off among cellular components that maximizes growth. The results show mechanistically why the GRH is valid under P limitation but not under N limitation. We also show why variability of growth rate-biomass stoichiometry relationships is lower under P limitation than under N or C limitation. These theoretical results are supported by experimental data on macromolecular composition (RNA, DNA, and protein) and biomass stoichiometry from two different bacteria. In addition, compared to a model with strictly homeostatic biomass, the optimization mechanism we suggest results in increased microbial N and P mineralization during organic-matter decomposition. Therefore, this mechanism may also have important implications for our understanding of nutrient cycling in ecosystems.

Prevalence and proposed mechanisms of chronic low back pain in baseball: part i

PubMed Central

Wasser, Joseph G.; Zaremski, Jason L.; Herman, Daniel C.; Vincent, Heather K.

2017-01-01

The prevalence of low back pain (LBP) among active baseball players ranges between 3 and 15%. The execution of baseball-specific manoeuvres, such as pitching or batting, may be related to the onset of LBP. These baseball motions are complex and require appropriate activation of the core musculature to produce a well-timed motion with forces minimized at the extremities. The spine, core and back musculature are involved with acceleration and deceleration of rotational motions. This narrative review synopsizes the available evidence of the prevalence of and mechanical factors underlying LBP in the baseball population. Possible mechanical mechanisms linking baseball play to LBP include aberrant motion, improper timing, high lumbar stress due to mechanical loading and lumbopelvic strength deficits. Potential clinical implications relating to these possible mechanical mechanisms will also be highlighted. The state of the evidence suggests that there are deficits in understanding the role of baseball motion and playing history in the development of spine conditions. PMID:28128007

Prevalence and proposed mechanisms of chronic low back pain in baseball: part i.

PubMed

Wasser, Joseph G; Zaremski, Jason L; Herman, Daniel C; Vincent, Heather K

2017-01-01

The prevalence of low back pain (LBP) among active baseball players ranges between 3 and 15%. The execution of baseball-specific manoeuvres, such as pitching or batting, may be related to the onset of LBP. These baseball motions are complex and require appropriate activation of the core musculature to produce a well-timed motion with forces minimized at the extremities. The spine, core and back musculature are involved with acceleration and deceleration of rotational motions. This narrative review synopsizes the available evidence of the prevalence of and mechanical factors underlying LBP in the baseball population. Possible mechanical mechanisms linking baseball play to LBP include aberrant motion, improper timing, high lumbar stress due to mechanical loading and lumbopelvic strength deficits. Potential clinical implications relating to these possible mechanical mechanisms will also be highlighted. The state of the evidence suggests that there are deficits in understanding the role of baseball motion and playing history in the development of spine conditions.

New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes

DTIC Science & Technology

2006-11-01

NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is cleaved from podocytes by metalloproteinases. J Am Soc Nephrol 2005 16...localization of nephrin , podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation. Am J Pathol 2002 161:1459... markers linked to these phenotypes will improve understanding of the molecular mechanisms underlying these diseases and enable the development of

Environmental epigenetics in metal exposure

PubMed Central

Martinez-Zamudio, Ricardo

2011-01-01

Although it is widely accepted that chronic exposure to arsenite, nickel, chromium and cadmium increases cancer incidence in individuals, the molecular mechanisms underlying their ability to transform cells remain largely unknown. Carcinogenic metals are typically weak mutagens, suggesting that genetic-based mechanisms may not be primarily responsible for metal-induced carcinogenesis. Growing evidence shows that environmental metal exposure involves changes in epigenetic marks, which may lead to a possible link between heritable changes in gene expression and disease susceptibility and development. Here, we review recent advances in the understanding of metal exposure affecting epigenetic marks and discuss establishment of heritable gene expression in metal-induced carcinogenesis. PMID:21610324

Emotions in action through the looking glass.

PubMed

Sinigaglia, Corrado; Sparaci, Laura

2010-02-01

The paper aims at highlighting how our primary understanding of others' actions is rooted in the mirror mechanism. To this end, the anatomical architecture of the mirror neuron system for action will be outlined as well as its role in grasping goals and intentions in others' motor behaviour. One further step through the looking glass of social cognition will be referring to the ubiquitous emotional colouring of actions and considering its links with the motor domain. This will allow a clearer perspective on the mechanism underlying our abilities for emotional understanding and on cases in which these abilities are amiss, as in autistic spectrum disorders.

In Search of 'Birth Month Genes': Using Existing Data Repositories to Locate Genes Underlying Birth Month-Disease Relationships.

PubMed

Boland, Mary Regina; Tatonetti, Nicholas P

2016-01-01

Prenatal and perinatal exposures vary seasonally (e.g., sunlight, allergens) and many diseases are linked with variance in exposure. Epidemiologists often measure these changes using birth month as a proxy for seasonal variance. Likewise, Genome-Wide Association Studies have associated or implicated these same diseases with many genes. Both disparate data types (epidemiological and genetic) can provide key insights into the underlying disease biology. We developed an algorithm that links 1) epidemiological data from birth month studies with 2) genetic data from published gene-disease association studies. Our framework uses existing data repositories - PubMed, DisGeNET and Gene Ontology - to produce a bipartite network that connects enriched seasonally varying biofactorss with birth month dependent diseases (BMDDs) through their overlapping developmental gene sets. As a proof-of-concept, we investigate 7 known BMDDs and highlight three important biological networks revealed by our algorithm and explore some interesting genetic mechanisms potentially responsible for the seasonal contribution to BMDDs.

Lamin B1 mediated demyelination: Linking Lamins, Lipids and Leukodystrophies

PubMed Central

Padiath, Quasar S.

2016-01-01

ABSTRACT Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating disorder, is the only human disease that has been linked to mutations of the nuclear lamina protein, lamin B1, and is primarily caused by duplications of the LMNB1 gene. Why CNS myelin is specifically targeted and the mechanisms underlying ADLD are unclear. Recent work from our group has demonstrated that over expression of lamin B1 in oligodendrocytes, the myelin producing cells in the CNS, resulted in age dependent epigenetic modifications, transcriptional down-regulation of lipogenic gene expression and significant reductions of myelin-enriched lipids. Given the high lipid content of meylin, we hypothesize that lipid loss is one of the primary drivers of the demyelination phenotype. These results can, at least partially, explain the age dependence and cell type specificity in ADLD and are discussed in the context of the existing literature, in an attempt to delineate potential pathways underlying the disease phenotype. PMID:27854160

Motivations for Providing a Secure Base: Links with Attachment Orientation and Secure Base Support Behavior

PubMed Central

Feeney, Brooke C.; Collins, Nancy L.; Van Vleet, Meredith; Tomlinson, Jennifer

2015-01-01

This investigation examined the importance of underlying motivations in predicting secure base support behavior, as well as the extent to which support motivations are predicted by individual differences in attachment orientation. Participants were 189 married couples who participated in two laboratory sessions: During a questionnaire session, couples completed assessments of their underlying motivations for providing, and for not providing, support for their partner's exploration (i.e., goal-strivings), as well as assessments of their typical secure base support behavior. In an observational session, couples engaged in a discussion of one member's personal goals, during which the partner's secure base support was assessed. Results revealed a variety of distinct motivations for providing, and for not providing, secure base support to one's partner, as well as theoretically expected links between these motivations and both secure base behavior and attachment orientation. This work establishes motivations as important mechanisms that underlie the effective or ineffective provision of relational support. PMID:23581972

Biology of diesel exhaust effects on respiratory function.

PubMed

Riedl, Marc; Diaz-Sanchez, David

2005-02-01

In recent decades, clinicians and scientists have witnessed a significant increase in the prevalence of allergic rhinitis and asthma. The factors underlying this phenomenon are clearly complex; however, this rapid increase in the burden of atopic disease has undeniably occurred in parallel with rapid industrialization and urbanization in many parts of the world. Consequently, more people are exposed to air pollutants than at any point in human history. Worldwide, increases in allergic respiratory disease have mainly been observed in urban communities. Epidemiologic and clinical investigations have suggested a strong link between particulate air pollution and detrimental health effects, including cardiopulmonary morbidity and mortality. The purpose of this review is to provide an evidence-based summary of the health effects of air pollutants on asthma, focusing on diesel exhaust particles (DEPs) as a model particulate air pollutant. An overview of observational and experimental studies linking DEPs and asthma will be provided, followed by consideration of the mechanisms underlying DEP-induced inflammation and a brief discussion of future research and clinical directions.

Using stamping punch force variation for the identification of changes in lubrication and wear mechanism

NASA Astrophysics Data System (ADS)

Voss, B. M.; Pereira, M. P.; Rolfe, B. F.; Doolan, M. C.

2017-09-01

The growth in use of Advanced High Strength Steels in the automotive industry for light-weighting and safety has increased the rates of tool wear in sheet metal stamping. This is an issue that adds significant costs to production in terms of manual inspection and part refinishing. To reduce these costs, a tool condition monitoring system is required and a firm understanding of process signal variation must form the foundation for any such monitoring system. Punch force is a stamping process signal that is widely collected by industrial presses and has been linked closely to part quality and tool condition, making it an ideal candidate as a tool condition monitoring signal. In this preliminary investigation, the variation of punch force due to different lubrication conditions and progressive wear are examined. Linking specific punch force signature changes to developing lubrication and wear events is valuable for die wear and stamping condition monitoring. A series of semi-industrial channel forming trials were conducted under different lubrication regimes and progressive die wear. Punch force signatures were captured for each part and Principal Component Analysis (PCA) was applied to determine the key Principal Components of the signature data sets. These Principal Components were linked to the evolution of friction conditions over the course of the stroke for the different lubrication regimes and mechanism of galling wear. As a result, variation in punch force signatures were correlated to the current mechanism of wear dominant on the formed part; either abrasion or adhesion, and to changes in lubrication mechanism. The outcomes of this study provide important insights into punch force signature variation, that will provide a foundation for future work into the development of die wear and lubrication monitoring systems for sheet metal stamping.

Neural Correlates of Opposing Effects of Emotional Distraction on Perception and Episodic Memory: An Event-Related fMRI Investigation

PubMed Central

Shafer, Andrea T.; Dolcos, Florin

2012-01-01

A main question in emotion and memory literature concerns the relationship between the immediate impact of emotional distraction on perception and the long-term impact of emotion on memory. While previous research shows both automatic and resource-mediated mechanisms to be involved in initial emotion processing and memory, it remains unclear what the exact relationship between the immediate and long-term effects is, and how this relationship may change as a function of manipulations at perception favoring the engagement of either more automatic or mediated mechanisms. Using event-related functional magnetic resonance imaging, we varied the degree of resource availability for processing task-irrelevant emotional information, to determine how the initial (impairing) impact of emotional distraction related to the long-term (enhancing) impact of emotion on memory. Results showed that a direct relationship between emotional distraction and memory was dependent on automatic mechanisms, as this was found only under conditions of limited resource availability and engagement of amygdala (AMY)-hippocampal (HC) mechanisms to both impairing and enhancing effects. A hemispheric disassociation was also identified in AMY-HC, where while both sides were associated with emotional distraction and left AMY and anterior HC were linked to emotional memory, functional asymmetry was only identified in the posterior HC, with only the left side contributing to emotional memory. Finally, areas dissociating between the two opposing effects included the medial frontal, precentral, superior temporal, and middle occipital gyri (linked to emotional distraction), and the superior parietal cortex (linked to emotional memory). These findings demonstrate the relationship between emotional distraction and memory is context dependent and that specific brain regions may be more or less susceptible to the direction of emotional modulation (increased or decreased), depending on the task manipulation, and processes investigated. PMID:23049502

The heuristic value of redundancy models of aging.

PubMed

Boonekamp, Jelle J; Briga, Michael; Verhulst, Simon

2015-11-01

Molecular studies of aging aim to unravel the cause(s) of aging bottom-up, but linking these mechanisms to organismal level processes remains a challenge. We propose that complementary top-down data-directed modelling of organismal level empirical findings may contribute to developing these links. To this end, we explore the heuristic value of redundancy models of aging to develop a deeper insight into the mechanisms causing variation in senescence and lifespan. We start by showing (i) how different redundancy model parameters affect projected aging and mortality, and (ii) how variation in redundancy model parameters relates to variation in parameters of the Gompertz equation. Lifestyle changes or medical interventions during life can modify mortality rate, and we investigate (iii) how interventions that change specific redundancy parameters within the model affect subsequent mortality and actuarial senescence. Lastly, as an example of data-directed modelling and the insights that can be gained from this, (iv) we fit a redundancy model to mortality patterns observed by Mair et al. (2003; Science 301: 1731-1733) in Drosophila that were subjected to dietary restriction and temperature manipulations. Mair et al. found that dietary restriction instantaneously reduced mortality rate without affecting aging, while temperature manipulations had more transient effects on mortality rate and did affect aging. We show that after adjusting model parameters the redundancy model describes both effects well, and a comparison of the parameter values yields a deeper insight in the mechanisms causing these contrasting effects. We see replacement of the redundancy model parameters by more detailed sub-models of these parameters as a next step in linking demographic patterns to underlying molecular mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

The Kinematic Analysis of Flat Leverage Mechanism of the Third Class

NASA Astrophysics Data System (ADS)

Zhauyt, A.; Mamatova, G.; Abdugaliyeva, G.; Alipov, K.; Sakenova, A.; Alimbetov, A.

2017-10-01

It is necessary to make link mechanisms calculation to the strength at designing of flat link mechanisms of high class after definition of block diagrams and link linear sizes i.e. it is rationally to choose their forms and to determine the section sizes. The algorithm of the definition of dimension of link mechanism lengths of high classes (MHC) and their metric parameters at successive approach is offered in this work. It this paper educational and research software named GIM is presented. This software has been developed with the aim of approaching the difficulties students usually encounter when facing up to kinematic analysis of mechanisms. A deep understanding of the kinematic analysis is necessary to go a step further into design and synthesis of mechanisms. In order to support and complement the theoretical lectures, GIM software is used during the practical exercises, serving as an educational complementary tool reinforcing the knowledge acquired by the students.

Controlling Hydrogel Mechanics via Bio-Inspired Polymer-Nanoparticle Bond Dynamics.

PubMed

Li, Qiaochu; Barrett, Devin G; Messersmith, Phillip B; Holten-Andersen, Niels

2016-01-26

Interactions between polymer molecules and inorganic nanoparticles can play a dominant role in nanocomposite material mechanics, yet control of such interfacial interaction dynamics remains a significant challenge particularly in water. This study presents insights on how to engineer hydrogel material mechanics via nanoparticle interface-controlled cross-link dynamics. Inspired by the adhesive chemistry in mussel threads, we have incorporated iron oxide nanoparticles (Fe3O4 NPs) into a catechol-modified polymer network to obtain hydrogels cross-linked via reversible metal-coordination bonds at Fe3O4 NP surfaces. Unique material mechanics result from the supra-molecular cross-link structure dynamics in the gels; in contrast to the previously reported fluid-like dynamics of transient catechol-Fe(3+) cross-links, the catechol-Fe3O4 NP structures provide solid-like yet reversible hydrogel mechanics. The structurally controlled hierarchical mechanics presented here suggest how to develop hydrogels with remote-controlled self-healing dynamics.

Coating gigaporous polystyrene microspheres with cross-linked poly(vinyl alcohol) hydrogel as a rapid protein chromatography matrix.

PubMed

Qu, Jian-Bo; Huan, Guan-Sheng; Chen, Yan-Li; Zhou, Wei-Qing; Liu, Jian-Guo; Huang, Fang

2014-08-13

Gigaporous polystyrene (PS) microspheres were hydrophilized by in situ polymerization to give a stable cross-linked poly(vinyl alcohol) (PVA) hydrogel coating, which can shield proteins from the hydrophobic PS surface underneath. The amination of microspheres (PS-NH2) was first carried out through acetylization, oximation and reduction, and then 4,4'-azobis (4-cyanovaleric acid) (ACV), a polymerization initiator, was covalently immobilized on PS-NH2 through amide bond formation, and the cross-linked poly(vinyl acetate) (PVAc) was prepared by radical polymerization at the surfaces of ACV-immobilized PS microspheres (PS-ACV). Finally, the cross-linked PVA hydrogel coated gigaporous PS microspheres (PS-PVA) was easily achieved through alcoholysis of PVAc. Results suggested that the PS microspheres were effectively coated with cross-linked PVA hydrogel, where the gigaporrous structure remained under optimal conditions. After hydrophilic modification (PS-PVA), the protein-resistant ability of microspheres was greatly improved. The hydroxyl-rich PS-PVA surface can be easily derivatized by classical chemical methods. Performance advantages of the PS-PVA column in flow experiment include good permeability, low backpressure, and mechanical stability. These results indicated that PS-PVA should be promising in rapid protein chromatography.

Revisiting the Link between Job Satisfaction and Life Satisfaction: The Role of Basic Psychological Needs

PubMed Central

Unanue, Wenceslao; Gómez, Marcos E.; Cortez, Diego; Oyanedel, Juan C.; Mendiburo-Seguel, Andrés

2017-01-01

The link between job satisfaction and life satisfaction has been extensively explored in the relevant literature. However, the great majority of past research has been carried out using cross-sectional analyses, and almost exclusively in the Western world. Moreover, the underlying psychological mechanisms explaining the link are not yet completely understood. Thus, we report the first research to date which uses both cross-sectional and longitudinal data among workers in Chile—a fast-developing Latin American economy—and which aims to tackle previous limitations. Three studies consistently support a positive link between the constructs. Study 1 (N = 636) found that higher job satisfaction predicted higher life satisfaction both contemporaneously and longitudinally, and vice versa, above and beyond several key control variables. Study 2 (N = 725) and Study 3 (N = 703) replicated Study 1 results, but tested for the first time the role of satisfaction of basic psychological needs (as stated by self-determination theory) in the job–life satisfaction link. This is the most novel contribution of our paper. Key implications not only for individual quality of life, but also for companies' human resource practices emerge from our findings. PMID:28536541

Motor and sensory neuropathy due to myelin infolding and paranodal damage in a transgenic mouse model of Charcot–Marie–Tooth disease type 1C

PubMed Central

Lee, Samuel M.; Sha, Di; Mohammed, Anum A.; Asress, Seneshaw; Glass, Jonathan D.; Chin, Lih-Shen; Li, Lian

2013-01-01

Charcot–Marie–Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt–Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients. PMID:23359569

Shy birds play it safe: personality in captivity predicts risk responsiveness during reproduction in the wild

PubMed Central

Cole, Ella F.; Quinn, John L.

2014-01-01

Despite a growing body of evidence linking personality to life-history variation and fitness, the behavioural mechanisms underlying these relationships remain poorly understood. One mechanism thought to play a key role is how individuals respond to risk. Relatively reactive and proactive (or shy and bold) personality types are expected to differ in how they manage the inherent trade-off between productivity and survival, with bold individuals being more risk-prone with lower survival probability, and shy individuals adopting a more risk-averse strategy. In the great tit (Parus major), the shy–bold personality axis has been well characterized in captivity and linked to fitness. Here, we tested whether ‘exploration behaviour’, a captive assay of the shy–bold axis, can predict risk responsiveness during reproduction in wild great tits. Relatively slow-exploring (shy) females took longer than fast-exploring (bold) birds to resume incubation after a novel object, representing an unknown threat, was attached to their nest-box, with some shy individuals not returning within the 40 min trial period. Risk responsiveness was consistent within individuals over days. These findings provide rare, field-based experimental evidence that shy individuals prioritize survival over reproductive investment, supporting the hypothesis that personality reflects life-history variation through links with risk responsiveness. PMID:24829251

Label-free Quantitative Protein Profiling of vastus lateralis Muscle During Human Aging*

PubMed Central

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe

2014-01-01

Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers. PMID:24217021

Label-free quantitative protein profiling of vastus lateralis muscle during human aging.

PubMed

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe

2014-01-01

Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers.

Responses to olfactory signals reflect network structure of flower-visitor interactions.

PubMed

Junker, Robert R; Höcherl, Nicole; Blüthgen, Nico

2010-07-01

1. Network analyses provide insights into the diversity and complexity of ecological interactions and have motivated conclusions about community stability and co-evolution. However, biological traits and mechanisms such as chemical signals regulating the interactions between individual species--the microstructure of a network--are poorly understood. 2. We linked the responses of receivers (flower visitors) towards signals (flower scent) to the structure of a highly diverse natural flower-insect network. For each interaction, we define link temperature--a newly developed metric--as the deviation of the observed interaction strength from neutrality, assuming that animals randomly interact with flowers. 3. Link temperature was positively correlated to the specific visitors' responses to floral scents, experimentally examined in a mobile olfactometer. Thus, communication between plants and consumers via phytochemical signals reflects a significant part of the microstructure in a complex network. Negative as well as positive responses towards floral scents contributed to these results, where individual experience was important apart from innate behaviour. 4. Our results indicate that: (1) biological mechanisms have a profound impact on the microstructure of complex networks that underlies the outcome of aggregate statistics, and (2) floral scents act as a filter, promoting the visitation of some flower visitors, but also inhibiting the visitation of others.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes.

PubMed

Nomura, Yoko; John, Rosalind M; Janssen, Anna Bugge; Davey, Charles; Finik, Jackie; Buthmann, Jessica; Glover, Vivette; Lambertini, Luca

2017-06-01

Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3-8% of all pregnancies in the US are complicated by preeclampsia and another 5-7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. Pub Med and Web of Science databases were searched using the terms "preeclampsia," "gestational hypertension," "imprinting genes," "imprinting dysregulation," and "epigenetic modification," in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

Population health management guiding principles to stimulate collaboration and improve pharmaceutical care.

PubMed

Steenkamer, Betty; Baan, Caroline; Putters, Kim; van Oers, Hans; Drewes, Hanneke

2018-04-09

Purpose A range of strategies to improve pharmaceutical care has been implemented by population health management (PHM) initiatives. However, which strategies generate the desired outcomes is largely unknown. The purpose of this paper is to identify guiding principles underlying collaborative strategies to improve pharmaceutical care and the contextual factors and mechanisms through which these principles operate. Design/methodology/approach The evaluation was informed by a realist methodology examining the links between PHM strategies, their outcomes and the contexts and mechanisms by which these strategies operate. Guiding principles were identified by grouping context-specific strategies with specific outcomes. Findings In total, ten guiding principles were identified: create agreement and commitment based on a long-term vision; foster cooperation and representation at the board level; use layered governance structures; create awareness at all levels; enable interpersonal links at all levels; create learning environments; organize shared responsibility; adjust financial strategies to market contexts; organize mutual gains; and align regional agreements with national policies and regulations. Contextual factors such as shared savings influenced the effectiveness of the guiding principles. Mechanisms by which these guiding principles operate were, for instance, fostering trust and creating a shared sense of the problem. Practical implications The guiding principles highlight how collaboration can be stimulated to improve pharmaceutical care while taking into account local constraints and possibilities. The interdependency of these principles necessitates effectuating them together in order to realize the best possible improvements and outcomes. Originality/value This is the first study using a realist approach to understand the guiding principles underlying collaboration to improve pharmaceutical care.

Ghrelin and cachexia in chronic kidney disease.

PubMed

Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

2013-04-01

Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

Crossed wires: 3D genome misfolding in human disease.

PubMed

Norton, Heidi K; Phillips-Cremins, Jennifer E

2017-11-06

Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

Collective helping and bystander effects in coevolving helping networks.

PubMed

Jo, Hang-Hyun; Lee, Hyun Keun; Park, Hyunggyu

2010-06-01

We study collective helping behavior and bystander effects in a coevolving helping network model. A node and a link of the network represents an agent who renders or receives help and a friendly relation between agents, respectively. A helping trial of an agent depends on relations with other involved agents and its result (success or failure) updates the relation between the helper and the recipient. We study the network link dynamics and its steady states analytically and numerically. The full phase diagram is presented with various kinds of active and inactive phases and the nature of phase transitions are explored. We find various interesting bystander effects, consistent with the field study results, of which the underlying mechanism is proposed.

The effect of cross linking density on the mechanical properties and structure of the epoxy polymers: molecular dynamics simulation.

PubMed

Shokuhfar, Ali; Arab, Behrouz

2013-09-01

Recently, great attention has been focused on using epoxy polymers in different fields such as aerospace, automotive, biotechnology, and electronics, owing to their superior properties. In this study, the classical molecular dynamics (MD) was used to simulate the cross linking of diglycidyl ether of bisphenol-A (DGEBA) with diethylenetriamine (DETA) curing agent, and to study the behavior of resulted epoxy polymer with different conversion rates. The constant-strain (static) approach was then applied to calculate the mechanical properties (Bulk, shear and Young's moduli, elastic stiffness constants, and Poisson's ratio) of the uncured and cross-linked systems. Estimated material properties were found to be in good agreement with experimental observations. Moreover, the dependency of mechanical properties on the cross linking density was investigated and revealed improvements in the mechanical properties with increasing the cross linking density. The radial distribution function (RDF) was also used to study the evolution of local structures of the simulated systems as a function of cross linking density.

Autoimmunity-Basics and link with periodontal disease.

PubMed

Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali

2017-01-01

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Gender development and the human brain.

PubMed

Hines, Melissa

2011-01-01

Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

Autophagy dictates metabolism and differentiation of inflammatory immune cells

PubMed Central

Riffelmacher, Thomas; Richter, Felix Clemens; Simon, Anna Katharina

2018-01-01

ABSTRACT The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. In particular, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation. This concept is strengthened through novel molecular insights into how AMPK and MTOR signaling cascades affect both autophagy and metabolism. In this review, we discuss direct and indirect evidence linking autophagy, metabolic pathways and immune cell differentiation including T, B, and innate lymphocytes as well as in myeloid cells that are direct mediators of inflammation. Herein, we propose a model for autophagy-driven immunometabolism controlling immune cell differentiation. PMID:28806133

Neural and Computational Mechanisms of Action Processing: Interaction between Visual and Motor Representations.

PubMed

Giese, Martin A; Rizzolatti, Giacomo

2015-10-07

Action recognition has received enormous interest in the field of neuroscience over the last two decades. In spite of this interest, the knowledge in terms of fundamental neural mechanisms that provide constraints for underlying computations remains rather limited. This fact stands in contrast with a wide variety of speculative theories about how action recognition might work. This review focuses on new fundamental electrophysiological results in monkeys, which provide constraints for the detailed underlying computations. In addition, we review models for action recognition and processing that have concrete mathematical implementations, as opposed to conceptual models. We think that only such implemented models can be meaningfully linked quantitatively to physiological data and have a potential to narrow down the many possible computational explanations for action recognition. In addition, only concrete implementations allow judging whether postulated computational concepts have a feasible implementation in terms of realistic neural circuits. Copyright © 2015 Elsevier Inc. All rights reserved.

Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells.

PubMed

Chen, Xing-Shu; Huang, Nanxin; Michael, Namaka; Xiao, Lan

2015-01-01

Schizophrenia (SZ) is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells.

Relationship Quality and Alcohol-Related Social Reinforcement during Couples Interaction.

PubMed

Fairbairn, Catharine E; Testa, Maria

2016-01-01

Individuals who are unhappy in their intimate partnerships are at risk for developing alcohol problems. But little is known about the mechanisms underlying this link. One possibility is that couples with poor relationship quality gain more reinforcement from alcohol in certain contexts-a possibility that has never previously been empirically examined. In the current study, 304 individuals (152 couples) were assigned to receive alcohol (target BAC .08%) or a non-alcoholic beverage. They then engaged in a conflict-resolution interaction with their partners. Videotaped interactions were coded by trained observers. Results revealed a significant interaction between alcohol and relationship quality across multiple measures. Alcohol decreased negative behaviors, decreased negative reciprocity, and enhanced self-reported experience to a greater extent during interactions involving individuals reporting low relationship quality and had comparatively little effect among those reporting high relationship quality. Findings point to a potential mechanism underlying problem drinking among couples with poor relationship quality.

Signaling mechanisms underlying the robustness and tunability of the plant immune network

PubMed Central

Kim, Yungil; Tsuda, Kenichi; Igarashi, Daisuke; Hillmer, Rachel A.; Sakakibara, Hitoshi; Myers, Chad L.; Katagiri, Fumiaki

2014-01-01

Summary How does robust and tunable behavior emerge in a complex biological network? We sought to understand this for the signaling network controlling pattern-triggered immunity (PTI) in Arabidopsis. A dynamic network model containing four major signaling sectors, the jasmonate, ethylene, PAD4, and salicylate sectors, which together explain up to 80% of the PTI level, was built using data for dynamic sector activities and PTI levels under exhaustive combinatorial sector perturbations. Our regularized multiple regression model had a high level of predictive power and captured known and unexpected signal flows in the network. The sole inhibitory sector in the model, the ethylene sector, was central to the network robustness via its inhibition of the jasmonate sector. The model's multiple input sites linked specific signal input patterns varying in strength and timing to different network response patterns, indicating a mechanism enabling tunability. PMID:24439900

Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits.

PubMed

Wu, Yang; Zeng, Jian; Zhang, Futao; Zhu, Zhihong; Qi, Ting; Zheng, Zhili; Lloyd-Jones, Luke R; Marioni, Riccardo E; Martin, Nicholas G; Montgomery, Grant W; Deary, Ian J; Wray, Naomi R; Visscher, Peter M; McRae, Allan F; Yang, Jian

2018-03-02

The identification of genes and regulatory elements underlying the associations discovered by GWAS is essential to understanding the aetiology of complex traits (including diseases). Here, we demonstrate an analytical paradigm of prioritizing genes and regulatory elements at GWAS loci for follow-up functional studies. We perform an integrative analysis that uses summary-level SNP data from multi-omics studies to detect DNA methylation (DNAm) sites associated with gene expression and phenotype through shared genetic effects (i.e., pleiotropy). We identify pleiotropic associations between 7858 DNAm sites and 2733 genes. These DNAm sites are enriched in enhancers and promoters, and >40% of them are mapped to distal genes. Further pleiotropic association analyses, which link both the methylome and transcriptome to 12 complex traits, identify 149 DNAm sites and 66 genes, indicating a plausible mechanism whereby the effect of a genetic variant on phenotype is mediated by genetic regulation of transcription through DNAm.

Flexibility and rigidity of cross-linked Straight Fibrils under axial motion constraints.

PubMed

Nagy Kem, Gyula

2016-09-01

The Straight Fibrils are stiff rod-like filaments and play a significant role in cellular processes as structural stability and intracellular transport. Introducing a 3D mechanical model for the motion of braced cylindrical fibrils under axial motion constraint; we provide some mechanism and a graph theoretical model for fibril structures and give the characterization of the flexibility and the rigidity of this bar-and-joint spatial framework. The connectedness and the circuit of the bracing graph characterize the flexibility of these structures. In this paper, we focus on the kinematical properties of hierarchical levels of fibrils and evaluate the number of the bracing elements for the rigidity and its computational complexity. The presented model is a good characterization of the frameworks of bio-fibrils such as microtubules, cellulose, which inspired this work. Copyright © 2016 Elsevier Ltd. All rights reserved.

Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations

PubMed Central

Papke, Christina L.; Tsunezumi, Jun; Ringuette, Léa-Jeanne; Nagaoka, Hideaki; Terajima, Masahiko; Yamashiro, Yoshito; Urquhart, Greg; Yamauchi, Mitsuo; Davis, Elaine C.; Yanagisawa, Hiromi

2015-01-01

Homozygous recessive mutations in either EFEMP2 (encoding fibulin-4) or FBLN5 (encoding fibulin-5), critical genes for elastogenesis, lead to autosomal recessive cutis laxa types 1B and 1A, respectively. Previously, fibulin-4 was shown to bind lysyl oxidase (LOX), an elastin/collagen cross-linking enzyme, in vitro. Consistently, reported defects in humans with EFEMP2 mutations are more severe and broad in range than those due to FBLN5 mutations and encompass both elastin-rich and collagen-rich tissues. However, the underlying disease mechanism in EFEMP2 mutations has not been fully addressed. Here, we show that fibulin-4 is important for the integrity of aortic collagen in addition to elastin. Smooth muscle-specific Efemp2 loss in mouse (termed SMKO) resulted in altered fibrillar collagen localization with larger, poorly organized fibrils. LOX activity was decreased in Efemp2-null cells, and collagen cross-linking was diminished in SMKO aortas; however, elastin cross-linking was unaffected and the level of mature LOX was maintained to that of wild-type aortas. Proteomic screening identified multiple proteins involved in procollagen processing and maturation as potential fibulin-4-binding partners. We showed that fibulin-4 binds procollagen C-endopeptidase enhancer 1 (Pcolce), which enhances proteolytic cleavage of the procollagen C-terminal propeptide during procollagen processing. Interestingly, however, procollagen cleavage was not affected by the presence or absence of fibulin-4 in vitro. Thus, our data indicate that fibulin-4 serves as a potential scaffolding protein during collagen maturation in the extracellular space. Analysis of collagen in other tissues affected by fibulin-4 loss should further increase our understanding of underlying pathologic mechanisms in patients with EFEMP2 mutations. PMID:26220971

A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes.

PubMed

Ren, Rui; Chen, Zhufeng; Zhao, Xia; Sun, Tao; Zhang, Yuchao; Chen, Jie; Lu, Sumei; Ma, Wanshan

2016-11-08

Peroxisome proliferator-activated receptor γ (PPARγ) is a critical gene that regulates the function of adipocytes. Therefore, studies on the molecular regulation mechanism of PPARγ are important to understand the function of adipose tissue. Twist 1 is another important functional gene in adipose tissue, and hundreds of genes are regulated by Twist 1. The aim of this study was to investigate the regulation of Twist 1 and PPARγ expression in 3T3-L1 mature adipocytes. We induced differentiation in 3T3-L1 preadipocytes and examined alterations in Twist 1 and PPARγ expression. We used the PPARγ agonist pioglitazone and the PPARγ antagonist T0070907 to investigate the effect of PPARγ on Twist 1 expression. In addition, we utilized retroviral interference and overexpression of Twist 1 to determine the effects of Twist 1 on PPARγ expression. The expression levels of Twist 1 and PPARγ were induced during differentiation in 3T3-L1 adipocytes. Application of either a PPARγ agonist (pioglitazone) or antagonist (T0070907) influenced Twist 1 expression, with up-regulation of Twist 1 under pioglitazone (1 μM, 24 h) and down-regulation of Twist 1 under T0070907 (100 μM, 24 h) exposure. Furthermore, the retroviral interference of Twist 1 decreased the protein and mRNA expression of PPARγ, while Twist 1 overexpression had the opposite effect. There was a possible regulatory link between Twist 1 and PPARγ in 3T3-L1 mature adipocytes. This regulatory link enhanced the regulation of PPARγ and may be a functional mechanism of Twist 1 regulation of adipocyte physiology and pathology.

Synthesis and characterization of photo-crosslinkable 4-styryl-pyridine modified alginate.

PubMed

Elsayed, Nadia H; Monier, M; Alatawi, Raedah A S

2016-07-10

In this article photo-crosslinkablestyryl-pyridine modified alginate (ASP-Alg) was prepared and entirely investigated utilizing different instrumental techniques such as Elemental analysis, Fourier transform infrared (FTIR),(13)C and (1)H nuclear magnetic resonance (NMR), ultraviolet-visible light (UV-vis), X-ray diffraction (XRD) spectra and scanning electron microscope (SEM). Upon irradiation in the UV region, the casted ASP-Alg membranes were cross-linked through the [2π+2π] cycloaddition reaction of the inserted photo-active styryl pyridine moieties. Both cross-linking density and kinetics were monitored by examining the UV-vis light spectra of the irradiated membrane at predetermined time intervals and the obtained results were found to fit with the second order mathematical kinetic model, revealing the performance of the cross-linking via bimolecular [2π+2π] cycloaddition reaction. Also, the swelling behaviors along with biodegradability were also studied, and the results indicated the decrease of the swelling ratio and degradation rate by increasing the cross-linking density. Moreover, the mechanical properties were also examined under both wet and dry conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study of a Car Body Tilting System Using a Variable Link Mechanism: Fundamental Characteristics of Pendulum Motion and Strategy for Perfect Tilting

NASA Astrophysics Data System (ADS)

Yoshida, Hidehisa; Nagai, Masao

This paper analyzes the fundamental dynamic characteristics of a tilting railway vehicle using a variable link mechanism for compensating both the lateral acceleration experienced by passengers and the wheel load imbalance between the inner and outer rails. The geometric relations between the center of rotation, the center of gravity, and the positions of all four links of the tilting system are analyzed. Then, equations of the pendulum motions of the railway vehicle body with a four-link mechanism are derived. A theoretically discussion is given on the geometrical shapes employed in the link mechanism that can simultaneously provide zero lateral acceleration and zero wheel load fluctuation. Then, the perfect tilting condition, which is the control target of the feedforward tilting control, is derived from the linear equation of tilting motion.

Hierarchical Structure Controls Nanomechanical Properties of Vimentin Intermediate Filaments

PubMed Central

Qin, Zhao; Kreplak, Laurent; Buehler, Markus J.

2009-01-01

Intermediate filaments (IFs), in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, playing a vital role in mechanotransduction and in providing mechanical stability to cells. Despite the importance of IF mechanics for cell biology and cell mechanics, the structural basis for their mechanical properties remains unknown. Specifically, our understanding of fundamental filament properties, such as the basis for their great extensibility, stiffening properties, and their exceptional mechanical resilience remains limited. This has prevented us from answering fundamental structure-function relationship questions related to the biomechanical role of intermediate filaments, which is crucial to link structure and function in the protein material's biological context. Here we utilize an atomistic-level model of the human vimentin dimer and tetramer to study their response to mechanical tensile stress, and describe a detailed analysis of the mechanical properties and associated deformation mechanisms. We observe a transition from alpha-helices to beta-sheets with subsequent interdimer sliding under mechanical deformation, which has been inferred previously from experimental results. By upscaling our results we report, for the first time, a quantitative comparison to experimental results of IF nanomechanics, showing good agreement. Through the identification of links between structures and deformation mechanisms at distinct hierarchical levels, we show that the multi-scale structure of IFs is crucial for their characteristic mechanical properties, in particular their ability to undergo severe deformation of ≈300% strain without breaking, facilitated by a cascaded activation of a distinct deformation mechanisms operating at different levels. This process enables IFs to combine disparate properties such as mechanosensitivity, strength and deformability. Our results enable a new paradigm in studying biological and mechanical properties of IFs from an atomistic perspective, and lay the foundation to understanding how properties of individual protein molecules can have profound effects at larger length-scales. PMID:19806221

Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments.

PubMed

Qin, Zhao; Kreplak, Laurent; Buehler, Markus J

2009-10-06

Intermediate filaments (IFs), in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, playing a vital role in mechanotransduction and in providing mechanical stability to cells. Despite the importance of IF mechanics for cell biology and cell mechanics, the structural basis for their mechanical properties remains unknown. Specifically, our understanding of fundamental filament properties, such as the basis for their great extensibility, stiffening properties, and their exceptional mechanical resilience remains limited. This has prevented us from answering fundamental structure-function relationship questions related to the biomechanical role of intermediate filaments, which is crucial to link structure and function in the protein material's biological context. Here we utilize an atomistic-level model of the human vimentin dimer and tetramer to study their response to mechanical tensile stress, and describe a detailed analysis of the mechanical properties and associated deformation mechanisms. We observe a transition from alpha-helices to beta-sheets with subsequent interdimer sliding under mechanical deformation, which has been inferred previously from experimental results. By upscaling our results we report, for the first time, a quantitative comparison to experimental results of IF nanomechanics, showing good agreement. Through the identification of links between structures and deformation mechanisms at distinct hierarchical levels, we show that the multi-scale structure of IFs is crucial for their characteristic mechanical properties, in particular their ability to undergo severe deformation of approximately 300% strain without breaking, facilitated by a cascaded activation of a distinct deformation mechanisms operating at different levels. This process enables IFs to combine disparate properties such as mechanosensitivity, strength and deformability. Our results enable a new paradigm in studying biological and mechanical properties of IFs from an atomistic perspective, and lay the foundation to understanding how properties of individual protein molecules can have profound effects at larger length-scales.

Mechanisms of gender-linked ischemic brain injury

PubMed Central

Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

2010-01-01

Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

Three-dimensional optical coherence micro-elastography of skeletal muscle tissue

PubMed Central

Chin, Lixin; Kennedy, Brendan F.; Kennedy, Kelsey M.; Wijesinghe, Philip; Pinniger, Gavin J.; Terrill, Jessica R.; McLaughlin, Robert A.; Sampson, David D.

2014-01-01

In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue. We show that this technique can resolve features of muscle tissue including fibers, fascicles and tendon, and can also detect necrotic lesions in skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy. In many instances, OCME provides better or additional contrast complementary to that provided by OCT. These results suggest that OCME could provide new understanding and opportunity for assessment of skeletal muscle pathologies. PMID:25401023

Issues in development, evaluation, and use of the NASA Preflight Adaptation Trainer (PAT)

NASA Technical Reports Server (NTRS)

Lane, Norman E.; Kennedy, Robert S.

1988-01-01

The Preflight Adaptation Trainer (PAT) is intended to reduce or alleviate space adaptation syndrome by providing opportunities for portions of that adaptation to occur under normal gravity conditions prior to space flight. Since the adaptation aspects of the PAT objectives involve modification not only of the behavior of the trainee, but also of sensiomotor skills which underly the behavioral generation, the defining of training objectives of the PAT utilizes four mechanisms: familiarization, demonstration, training and adaptation. These mechanisms serve as structural reference points for evaluation, drive the content and organization of the training procedures, and help to define the roles of the PAT instructors and operators. It was determined that three psychomotor properties are most critical for PAT evaluation: reliability; sensitivity; and relevance. It is cause for concern that the number of measures available to examine PAT effects exceed those that can be properly studied with the available sample sizes; special attention will be required in selection of the candidate measure set. The issues in PAT use and application within a training system context are addressed through linking the three training related mechanisms of familiarization, demonstration and training to the fourth mechanism, adaptation.

Predicting links based on knowledge dissemination in complex network

NASA Astrophysics Data System (ADS)

Zhou, Wen; Jia, Yifan

2017-04-01

Link prediction is the task of mining the missing links in networks or predicting the next vertex pair to be connected by a link. A lot of link prediction methods were inspired by evolutionary processes of networks. In this paper, a new mechanism for the formation of complex networks called knowledge dissemination (KD) is proposed with the assumption of knowledge disseminating through the paths of a network. Accordingly, a new link prediction method-knowledge dissemination based link prediction (KDLP)-is proposed to test KD. KDLP characterizes vertex similarity based on knowledge quantity (KQ) which measures the importance of a vertex through H-index. Extensive numerical simulations on six real-world networks demonstrate that KDLP is a strong link prediction method which performs at a higher prediction accuracy than four well-known similarity measures including common neighbors, local path index, average commute time and matrix forest index. Furthermore, based on the common conclusion that an excellent link prediction method reveals a good evolving mechanism, the experiment results suggest that KD is a considerable network evolving mechanism for the formation of complex networks.

Inflammation and hypoxia in the kidney: friends or foes?

PubMed

Haase, Volker H

2015-08-01

Hypoxic injury is commonly associated with inflammatory-cell infiltration, and inflammation frequently leads to the activation of cellular hypoxia response pathways. The molecular mechanisms underlying this cross-talk during kidney injury are incompletely understood. Yamaguchi and colleagues identify CCAAT/enhancer-binding protein δ as a cytokine- and hypoxia-regulated transcription factor that fine-tunes hypoxia-inducible factor-1 signaling in renal epithelial cells and thus provide a novel molecular link between hypoxia and inflammation in kidney injury.

Biological life-support systems

NASA Technical Reports Server (NTRS)

Shepelev, Y. Y.

1975-01-01

The establishment of human living environments by biologic methods, utilizing the appropriate functions of autotrophic and heterotrophic organisms is examined. Natural biologic systems discussed in terms of modeling biologic life support systems (BLSS), the structure of biologic life support systems, and the development of individual functional links in biologic life support systems are among the factors considered. Experimental modeling of BLSS in order to determine functional characteristics, mechanisms by which stability is maintained, and principles underlying control and regulation is also discussed.

Proceedings of the 1998 Space Control Conference,

DTIC Science & Technology

1998-04-16

later in this paper. The second radar under development was the HAVE STARE radar. This was also an X -band radar but was a mechanically steered, dish... spacecraft . The commands are sent via electronic link to Johns Hopkins Applied Physics Laboratory for inclusion in the MSX upload and are uplinked...with all the other sensors on the MSX along the + X axis of the spacecraft and is not sepa- rately gimbaled. Thus, to point the SBV, the entire

Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations.

PubMed

Gardner, J C; Michaelides, M; Hardcastle, A J

2016-05-25

X-linked cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) cone opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of cone opsin disorders.

Helicobacter pylori infection and inflammatory bowel disease: Is there a link?

PubMed Central

Papamichael, Konstantinos; Konstantopoulos, Panagiotis; Mantzaris, Gerassimos J

2014-01-01

Helicobacter pylori (H. pylori) infection is one of the most widely spread infectious diseases in humans. It can cause chronic gastritis, peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders. H. pylori elicit a chronic systemic inflammatory response which, under certain conditions, may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases. Although the pathogenesis of inflammatory bowel disease (IBD) is unknown, it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible. Several bacterial and viral agents have been implicated in the aetiology of IBD. In theory, H. pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways. Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations. However, the epidemiological data fail to support this association. In fact, various studies indicate that the prevalence of H. pylori infection is low in patients with IBD, suggesting a protective role for this infection in the development of IBD. In this report, we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H. pylori infection and IBD. PMID:24914359

Genome Wide Association Mapping in Arabidopsis thaliana Identifies Novel Genes Involved in Linking Allyl Glucosinolate to Altered Biomass and Defense.

PubMed

Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A; Lin, Catherine; Kerwin, Rachel E; Burow, Meike; Kliebenstein, Daniel J

2016-01-01

A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis.

Active transfer fault zone linking a segmented extensional system (Betics, southern Spain): Insight into heterogeneous extension driven by edge delamination

NASA Astrophysics Data System (ADS)

Martínez-Martínez, José Miguel; Booth-Rea, Guillermo; Azañón, José Miguel; Torcal, Federico

2006-08-01

Pliocene and Quaternary tectonic structures mainly consisting of segmented northwest-southeast normal faults, and associated seismicity in the central Betics do not agree with the transpressive tectonic nature of the Africa-Eurasia plate boundary in the Ibero-Maghrebian region. Active extensional deformation here is heterogeneous, individual segmented normal faults being linked by relay ramps and transfer faults, including oblique-slip and both dextral and sinistral strike-slip faults. Normal faults extend the hanging wall of an extensional detachment that is the active segment of a complex system of successive WSW-directed extensional detachments which have thinned the Betic upper crust since middle Miocene. Two areas, which are connected by an active 40-km long dextral strike-slip transfer fault zone, concentrate present-day extension. Both the seismicity distribution and focal mechanisms agree with the position and regime of the observed faults. The activity of the transfer zone during middle Miocene to present implies a mode of extension which must have remained substantially the same over the entire period. Thus, the mechanisms driving extension should still be operating. Both the westward migration of the extensional loci and the high asymmetry of the extensional systems can be related to edge delamination below the south Iberian margin coupled with roll-back under the Alborán Sea; involving the asymmetric westward inflow of asthenospheric material under the margins.

Leisure activities are linked to mental health benefits by providing time structure: comparing employed, unemployed and homemakers.

PubMed

Goodman, William K; Geiger, Ashley M; Wolf, Jutta M

2017-01-01

Unemployment has consistently been linked to negative mental health outcomes, emphasising the need to characterise the underlying mechanisms. The current study aimed at testing whether compared with other employment groups, fewer leisure activities observed in unemployment may contribute to elevated risk for negative mental health via loss of time structure. Depressive symptoms (Center for Epidemiologic Studies Depression), leisure activities (exercise, self-focused, social), and time structure (Time Structure Questionnaire (TSQ)) were assessed cross-sectionally in 406 participants (unemployed=155, employed=140, homemakers=111) recruited through Amazon Mechanical Turk. Controlling for gender and age, structural equation modelling revealed time structure partially (employed, homemakers) and fully (unemployed) mediated the relationship between leisure activities and depressive symptoms. With the exception of differential effects for structured routines, all other TSQ factors (sense of purpose, present orientation, effective organisation and persistence) contributed significantly to all models. These findings support the idea that especially for the unemployed, leisure activities impose their mental health benefits through increasing individuals' perception of spending their time effectively. Social leisure activities that provide a sense of daily structure may thereby be a particularly promising low-cost intervention to improve mental health in this population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Helicobacter pylori infection and inflammatory bowel disease: is there a link?

PubMed

Papamichael, Konstantinos; Konstantopoulos, Panagiotis; Mantzaris, Gerassimos J

2014-06-07

Helicobacter pylori (H. pylori) infection is one of the most widely spread infectious diseases in humans. It can cause chronic gastritis, peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders. H. pylori elicit a chronic systemic inflammatory response which, under certain conditions, may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases. Although the pathogenesis of inflammatory bowel disease (IBD) is unknown, it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible. Several bacterial and viral agents have been implicated in the aetiology of IBD. In theory, H. pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways. Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations. However, the epidemiological data fail to support this association. In fact, various studies indicate that the prevalence of H. pylori infection is low in patients with IBD, suggesting a protective role for this infection in the development of IBD. In this report, we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H. pylori infection and IBD.

Transparent Ethenylene-Bridged Polymethylsiloxane Aerogels: Mechanical Flexibility and Strength and Availability for Addition Reaction.

PubMed

Shimizu, Taiyo; Kanamori, Kazuyoshi; Maeno, Ayaka; Kaji, Hironori; Doherty, Cara M; Nakanishi, Kazuki

2017-05-09

Transparent, low-density ethenylene-bridged polymethylsiloxane [Ethe-BPMS, O 2/2 (CH 3 )Si-CH═CH-Si(CH 3 )O 2/2 ] aerogels from 1,2-bis(methyldiethoxysilyl)ethene have successfully been synthesized via a sol-gel process. A two-step sol-gel process composed of hydrolysis under acidic conditions and polycondensation under basic conditions in a liquid surfactant produces a homogeneous pore structure based on cross-linked nanosized colloidal particles. Visible-light transmittance of the aerogels varies with the concentration of the base catalyst and reaches as high as 87% (at a wavelength of 550 nm for a 10 mm thick sample). Gelation and aging temperature strongly affect the deformation behavior of the resultant aerogels against uniaxial compression, and the obtained aerogels prepared at 80 °C show high elasticity after being unloaded. This highly resilient behavior is primarily derived from the rigidity of ethenylene groups, which is confirmed by a comparison with other aerogels with similar molecular structures, ethylene-bridged polymethylsiloxane and polymethylsilsesquioxane. Applicability of the addition reaction using a Diels-Alder reaction of benzocyclobutene has also been investigated, revealing that a successful addition takes place on the ethenylene linkings, which is verified using Raman and solid-state NMR spectroscopies. Insights into the effect of molecular structure on mechanical properties and the availability of surface functionalization provided in this study are important for realizing transparent aerogels with the desired functionality.

α -Actinin TvACTN3 of Trichomonas vaginalis is an RNA-binding protein that could participate in its posttranscriptional iron regulatory mechanism.

PubMed

Calla-Choque, Jaeson Santos; Figueroa-Angulo, Elisa Elvira; Ávila-González, Leticia; Arroyo, Rossana

2014-01-01

Trichomonas vaginalis is a sexually transmitted flagellated protist parasite responsible for trichomoniasis. This parasite is dependent on high levels of iron, favoring its growth and multiplication. Iron also differentially regulates some trichomonad virulence properties by unknown mechanisms. However, there is evidence to support the existence of gene regulatory mechanisms at the transcriptional and posttranscriptional levels that are mediated by iron concentration in T. vaginalis. Thus, the goal of this study was to identify an RNA-binding protein in T. vaginalis that interacts with the tvcp4 RNA stem-loop structure, which may participate in a posttranscriptional iron regulatory mechanism mediated by RNA-protein interactions. We performed RNA electrophoretic mobility shift assay (REMSA) and supershift, UV cross-linking, Northwestern blot, and western blot (WB) assays using cytoplasmic protein extracts from T. vaginalis with the tvcp4 RNA hairpin structure as a probe. We identified a 135-kDa protein isolated by the UV cross-linking assays as α-actinin 3 (TvACTN3) by MALDI-TOF-MS that was confirmed by LS-MS/MS and de novo sequencing. TvACTN3 is a cytoplasmic protein that specifically binds to hairpin RNA structures from trichomonads and humans when the parasites are grown under iron-depleted conditions. Thus, TvACTN3 could participate in the regulation of gene expression by iron in T. vaginalis through a parallel posttranscriptional mechanism similar to that of the IRE/IRP system.

α-Actinin TvACTN3 of Trichomonas vaginalis Is an RNA-Binding Protein That Could Participate in Its Posttranscriptional Iron Regulatory Mechanism

PubMed Central

Calla-Choque, Jaeson Santos; Figueroa-Angulo, Elisa Elvira; Ávila-González, Leticia; Arroyo, Rossana

2014-01-01

Trichomonas vaginalis is a sexually transmitted flagellated protist parasite responsible for trichomoniasis. This parasite is dependent on high levels of iron, favoring its growth and multiplication. Iron also differentially regulates some trichomonad virulence properties by unknown mechanisms. However, there is evidence to support the existence of gene regulatory mechanisms at the transcriptional and posttranscriptional levels that are mediated by iron concentration in T. vaginalis. Thus, the goal of this study was to identify an RNA-binding protein in T. vaginalis that interacts with the tvcp4 RNA stem-loop structure, which may participate in a posttranscriptional iron regulatory mechanism mediated by RNA-protein interactions. We performed RNA electrophoretic mobility shift assay (REMSA) and supershift, UV cross-linking, Northwestern blot, and western blot (WB) assays using cytoplasmic protein extracts from T. vaginalis with the tvcp4 RNA hairpin structure as a probe. We identified a 135-kDa protein isolated by the UV cross-linking assays as α-actinin 3 (TvACTN3) by MALDI-TOF-MS that was confirmed by LS-MS/MS and de novo sequencing. TvACTN3 is a cytoplasmic protein that specifically binds to hairpin RNA structures from trichomonads and humans when the parasites are grown under iron-depleted conditions. Thus, TvACTN3 could participate in the regulation of gene expression by iron in T. vaginalis through a parallel posttranscriptional mechanism similar to that of the IRE/IRP system. PMID:24719864

Formation mechanism of monodispersed spherical core-shell ceria/polymer hybrid nanoparticles

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

Izu, Noriya, E-mail: n-izu@aist.go.jp; Uchida, Toshio; Matsubara, Ichiro

2011-08-15

Graphical abstract: The formation mechanism for core-shell nanoparticles is considered to be as follows: nucleation and particle growth occur simultaneously (left square); very slow particle growth occurs (middle square). Highlights: {yields} The size of the resultant nanoparticles was strongly and complicatedly dependent on the set temperature used during reflux heating and the PVP molecular weight. {yields} The size of the nanoparticles increased by a 2-step process as the reflux heating time increased. {yields} The IR spectral changes with increasing reflux time indicated the increase in the number of cross-linked polymers in the shell. -- Abstract: Very unique core-shell ceria (ceriummore » oxide)/polymer hybrid nanoparticles that have monodispersed spherical structures and are easily dispersed in water or alcohol without the need for a dispersant were reported recently. The formation mechanism of the unique nanoparticles, however, was not clear. In order to clarify the formation mechanism, these nanoparticles were prepared using a polyol method (reflux heating) under varied conditions of temperature, time, and concentration and molecular weight of added polymer (poly(vinylpyrrolidone)). The size of the resultant nanoparticles was strongly and complicatedly dependent on the set temperature used during reflux heating and the poly(vinylpyrrolidone) molecular weight. Furthermore, the size of the nanoparticles increased by a 2-step process as the reflux heating time increased. The IR spectral changes with increasing reflux time indicated the increase in the number of cross-linked polymers in the shell. From these results, the formation mechanism was discussed and proposed.« less

Evolutionary conservation of regulated longevity assurance mechanisms

PubMed Central

McElwee, Joshua J; Schuster, Eugene; Blanc, Eric; Piper, Matthew D; Thomas, James H; Patel, Dhaval S; Selman, Colin; Withers, Dominic J; Thornton, Janet M; Partridge, Linda; Gems, David

2007-01-01

Background To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator of longevity; yet it remains unclear whether the genes and biochemical processes through which IIS acts on aging are public or private (that is, lineage specific). To address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased longevity in mutant nematodes, fruitflies and mice with reduced IIS. Results Surprisingly, there is little evolutionary conservation at the level of individual, orthologous genes or paralogous genes under IIS regulation. However, a number of gene categories are significantly enriched for genes whose expression changes in long-lived animals of all three species. Down-regulated categories include protein biosynthesis-associated genes. Up-regulated categories include sugar catabolism, energy generation, glutathione-S-transferases (GSTs) and several other categories linked to cellular detoxification (that is, phase 1 and phase 2 metabolism of xenobiotic and endobiotic toxins). Protein biosynthesis and GST activity have recently been linked to aging and longevity assurance, respectively. Conclusion These processes represent candidate, regulated mechanisms of longevity-control that are conserved across animal species. The longevity assurance mechanisms via which IIS acts appear to be lineage-specific at the gene level (private), but conserved at the process level (or semi-public). In the case of GSTs, and cellular detoxification generally, this suggests that the mechanisms of aging against which longevity assurance mechanisms act are, to some extent, lineage specific. PMID:17612391

Linking Major Depression and The Neural Substrates of Associative Processing

PubMed Central

Harel, Eiran Vadim; Tennyson, Robert Langley; Fava, Maurizio; Bar, Moshe

2016-01-01

It has been proposed that mood correlates with the breadth of associative thinking. Here we set to test this hypothesis in healthy and depressed individuals. Generating contextual associations engages a network of cortical regions including the parahippocampal cortex (PHC), retrosplenial complex, and medial prefrontal cortex. The link between mood, associative processing, and its underlying cortical infrastructure provides a promising avenue for elucidating the mechanisms underlying cognitive impairments in Major Depressive Disorder (MDD). Participants included fifteen non-medicated individuals with acute Major Depressive Episode and fifteen healthy matched controls. In an fMRI experiment, participants viewed images of objects that are either strongly or weakly associated with a specific context (e.g., a beach chair vs. a water bottle), while rating the commonality of each object. Analyses were performed to examine brain activation and structural differences between groups. Consistent with our hypothesis, controls showed greater activation of the contextual associations network compared with depressed participants. In addition, PHC structural volume was correlated with ruminative tendency and, volumes of the hippocampal subfields were significantly smaller in depressed participants. Surprisingly, depressed participants showed increased activity in the entorhinal cortex (ERC) compared with controls. We integrate these findings within a mechanistic account linking mood and associative thinking, and suggest directions for the future. PMID:27553369

Ecological Interventionist Causal Models in Psychosis: Targeting Psychological Mechanisms in Daily Life

PubMed Central

Reininghaus, Ulrich; Depp, Colin A.; Myin-Germeys, Inez

2016-01-01

Integrated models of psychotic disorders have posited a number of putative psychological mechanisms that may contribute to the development of psychotic symptoms, but it is only recently that a modest amount of experience sampling research has provided evidence on their role in daily life, outside the research laboratory. A number of methodological challenges remain in evaluating specificity of potential causal links between a given psychological mechanism and psychosis outcomes in a systematic fashion, capitalizing on longitudinal data to investigate temporal ordering. In this article, we argue for testing ecological interventionist causal models that draw on real world and real-time delivered, ecological momentary interventions for generating evidence on several causal criteria (association, time order, and direction/sole plausibility) under real-world conditions, while maximizing generalizability to social contexts and experiences in heterogeneous populations. Specifically, this approach tests whether ecological momentary interventions can (1) modify a putative mechanism and (2) produce changes in the mechanism that lead to sustainable changes in intended psychosis outcomes in individuals’ daily lives. Future research using this approach will provide translational evidence on the active ingredients of mobile health and in-person interventions that promote sustained effectiveness of ecological momentary interventions and, thereby, contribute to ongoing efforts that seek to enhance effectiveness of psychological interventions under real-world conditions. PMID:26707864

Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease

PubMed Central

2012-01-01

Particulate matter (PM) pollution is responsible for hundreds of thousands of deaths worldwide, the majority due to cardiovascular disease (CVD). While many potential pathophysiological mechanisms have been proposed, there is not yet a consensus as to which are most important in causing pollution-related morbidity/mortality. Nor is there consensus regarding which specific types of PM are most likely to affect public health in this regard. One toxicological mechanism linking exposure to airborne PM with CVD outcomes is oxidative stress, a contributor to the development of CVD risk factors including atherosclerosis. Recent work suggests that accelerated shortening of telomeres and, thus, early senescence of cells may be an important pathway by which oxidative stress may accelerate biological aging and the resultant development of age-related morbidity. This pathway may explain a significant proportion of PM-related adverse health outcomes, since shortened telomeres accelerate the progression of many diseases. There is limited but consistent evidence that vehicular emissions produce oxidative stress in humans. Given that oxidative stress is associated with accelerated erosion of telomeres, and that shortened telomeres are linked with acceleration of biological ageing and greater incidence of various age-related pathology, including CVD, it is hypothesized that associations noted between certain pollution types and sources and oxidative stress may reflect a mechanism by which these pollutants result in CVD-related morbidity and mortality, namely accelerated aging via enhanced erosion of telomeres. This paper reviews the literature providing links among oxidative stress, accelerated erosion of telomeres, CVD, and specific sources and types of air pollutants. If certain PM species/sources might be responsible for adverse health outcomes via the proposed mechanism, perhaps the pathway to reducing mortality/morbidity from PM would become clearer. Not only would pollution reduction imperatives be more focused, but interventions which could reduce oxidative stress would become all the more important. PMID:22713210

Mechanisms of transgenerational inheritance of addictive-like behaviors.

PubMed

Vassoler, F M; Sadri-Vakili, G

2014-04-04

Genetic factors are implicated in the heritability of drug abuse. However, even with advances in current technology no specific genes have been identified that are critical for the transmission of drug-induced phenotypes to subsequent generations. It is now evident that epigenetic factors contribute to disease heritability and represent a link between genes and the environment. Recently, epigenetic mechanisms have been shown to underlie drug-induced structural, synaptic, and behavioral plasticity by coordinating the expression of gene networks within the brain. Therefore, the epigenome provides a direct mechanism for drugs of abuse to influence the genetic events involved in the development of addiction as well as its heritability to subsequent generations. In this review we discuss the mechanisms underlying intergenerational epigenetic transmission, highlight studies that demonstrate this phenomenon with particular attention to the field of addiction, and identify gaps for future studies. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Neurite, a Finite Difference Large Scale Parallel Program for the Simulation of Electrical Signal Propagation in Neurites under Mechanical Loading

PubMed Central

García-Grajales, Julián A.; Rucabado, Gabriel; García-Dopico, Antonio; Peña, José-María; Jérusalem, Antoine

2015-01-01

With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite—explicit and implicit—were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented dendritic tree, and a damaged axon. The capabilities of the program to deal with large scale scenarios, segmented neuronal structures, and functional deficits under mechanical loading are specifically highlighted. PMID:25680098

Effects of cross-linking on mechanical, biological properties and biodegradation behavior of Nile tilapia skin collagen sponge as a biomedical material.

PubMed

Sun, Leilei; Li, Bafang; Yao, Di; Song, Wenkui; Hou, Hu

2018-04-01

The objective of this study was to explore the effects of dehydrothermal treatment (DHT) and glutaraldehyde (GTA) cross-linking on mechanical, biological properties and biodegradation behavior of Nile tilapia skin collagen sponge fabricated by freeze-drying technology. It was found that the GTA cross-linked collagen sponge exhibited a higher degree of cross-linking in comparison with DHT. The extent of increased tensile strength as well as hygroscopicity indicated that GTA cross-linking was superior to DHT in mechanical properties and liquid absorption, which was attributed to different cross-linking mechanisms. Hygroscopicity assay indicated that cross-linking could improve stability of collagen in solutions. No obvious changes in porosity and blood coagulation time were observed whether cross-linking or not. Results from collagenase biodegradation assay in vitro illustrated that GTA-treated collagen sponge was more resistant to collagenase biodegradation, while DHT exhibited negligible resistance. In addition, photochemical stability of collagen sponge was studied by Fourier transforms infrared spectroscopy (FTIR), which indicated that both cross-linking treatments could not change the backbone structure of collagen. Furthermore, the microstructure of collagen sponge was stable after cross-linking. The highly porous and interconnected structure of collagen sponge was helpful to the absorption of wound exudates, supplement of oxygen and cell proliferation, accompanied with good blood compatibility, which indicated that our fabricated collagen sponge could be applied in biomedical materials field as wound dressings. Copyright © 2018. Published by Elsevier Ltd.

Efficient Pb(II) removal using sodium alginate-carboxymethyl cellulose gel beads: Preparation, characterization, and adsorption mechanism.

PubMed

Ren, Huixue; Gao, Zhimin; Wu, Daoji; Jiang, Jiahui; Sun, Youmin; Luo, Congwei

2016-02-10

Alginate-carboxymethyl cellulose (CMC) gel beads were prepared in this study using sodium alginate (SA) and sodium CMC through blending and cross-linking. The specific surface area and aperture of the prepared SA-CMC gel beads were tested. The SA-CMC structure was characterized and analyzed via infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Static adsorption experiment demonstrated that Pb(II) adsorption of SA-CMC exceeded 99% under the optimized conditions. In addition, experiments conducted under the same experimental conditions showed that the lead ion removal efficiency of SA-CMC was significantly higher than that of conventional adsorbents. The Pb(II) adsorption process of SA-CMC followed the Langmuir adsorption isotherm, and the dynamic adsorption model could be described through a pseudo-second-order rate equation. Pb(II) removal mechanisms of SA-CMC, including physical, chemical, and electrostatic adsorptions, were discussed based on microstructure analysis and adsorption kinetics. Chemical adsorption was the main adsorption method among these mechanisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Traits One Can Trust: Dissecting Reciprocity and Kindness as Determinants of Trustworthy Behavior.

PubMed

Thielmann, Isabel; Hilbig, Benjamin E

2015-11-01

Trustworthiness is a vital pillar of various social interactions hinging upon trust. However, the underlying determinants of trustworthiness-especially in terms of (basic) personality traits-are insufficiently understood. Specifically, three mechanisms underlying trustworthiness have been proposed: unconditional kindness, positive reciprocity, and negative reciprocity. The present research aims to disentangle these mechanisms using a trait-based approach, relying on the HEXACO (Honesty-Humility, Emotionality, eXtraversion, Agreeableness, Conscientiousness, and Openness to Experience) model of personality. In three studies, participants acted as the trustee in the trust game. All studies revealed consistent support for the unconditional kindness mechanism, showing an exclusive link between Honesty-Humility and trustworthiness, irrespective of the level of prior trust. In turn, positive and negative reciprocity could not account for the pattern of results. In addition, our results reconcile the inconsistent evidence on the relation between Big Five-Agreeableness and trustworthiness: Unconditional kindness only refers to one component of the broad Big Five-Agreeableness factor (which subsumes various cooperative tendencies). © 2015 by the Society for Personality and Social Psychology, Inc.

Metabolic dysfunction in obstructive sleep apnea: A critical examination of underlying mechanisms

PubMed Central

MESARWI, Omar A.; SHARMA, Ellora V.; JUN, Jonathan C.; POLOTSKY, Vsevolod Y.

2015-01-01

It has recently become clear that obstructive sleep apnea (OSA) is an independent risk factor for the development of metabolic syndrome, a disorder of defective energy storage and use. Several mechanisms have been proposed to explain this finding, drawing upon the characteristics that define OSA. In particular, intermittent hypoxia, sleep fragmentation, elevated sympathetic tone, and oxidative stress – all consequences of OSA – have been implicated in the progression of poor metabolic outcomes in OSA. In this review we examine the evidence to support each of these disease manifestations of OSA as a unique risk for metabolic dysfunction. Tissue hypoxia and sleep fragmentation are each directly connected to insulin resistance and hypertension, and each of these also may increase sympathetic tone, resulting in defective glucose homeostasis, excessive lipolysis, and elevated blood pressure. Oxidative stress further worsens insulin resistance and in turn, metabolic dysfunction also increases oxidative stress. However, despite many studies linking each of these individual components of OSA to the development of metabolic syndrome, there are very few reports that actually provide a coherent narrative about the mechanism underlying metabolic dysfunction in OSA. PMID:26412981

The kinetics and mechanism of nanoconfined molten salt reactions: trimerization of potassium and rubidium dicyanamide.

PubMed

Yancey, Benjamin; Vyazovkin, Sergey

2015-04-21

This study highlights the effect of the aggregate state of a reactant on the reaction kinetics under the conditions of nanoconfinement. Our previous work (Phys. Chem. Chem. Phys., 2014, 16, 11409) has demonstrated considerable deceleration of the solid state trimerization of sodium dicyanamide in organically modified silica nanopores. In the present study we use FTIR, NMR, pXRD, TGA and DSC to analyze the kinetics and mechanism of the liquid state trimerization of potassium and rubidium dicyanamide under similar conditions of nanoconfinement. It is found that nanoconfinement accelerates dramatically the kinetics of the liquid state trimerization, whereas it does not appear to affect the reaction mechanism. Kinetic analysis indicates that the acceleration is associated with an increase in the preexponential factor. Although nanoconfinement has the opposite effects on the respective kinetics of solid and liquid state trimerization, both effects are linked to a change in the preexponential factor. The results obtained are consistent with our hypothesis that the effects differ because nanoconfinement may promote disordering of the solid and ordering of the liquid reaction media.

Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms

PubMed Central

Jing, Liang; Duan, Ting-Ting; Tian, Meng; Yuan, Qiang; Tan, Ji-Wei; Zhu, Yong-Yong; Ding, Ze-Yang; Cao, Jun; Yang, Yue-Xiong; Zhang, Xia; Mao, Rong-Rong; Richter-levin, Gal; Zhou, Qi-Xin; Xu, Lin

2015-01-01

The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair. PMID:26449319

Posttraumatic Stress Symptom Severity and Cognitive-Based Smoking Processes Among Trauma-Exposed Treatment-Seeking Smokers: The Role of Perceived Stress

PubMed Central

Garey, Lorra; Bakhshaie, Jafar; Vujanovic, Anka A.; Reitzel, Lorraine R.; Schmidt, Norman B.; Zvolensky, Michael J.

2016-01-01

Trauma exposure and smoking co-occur at an alarmingly high rate. However, there is little understanding of the mechanisms underlying this clinically significant relation. The present study examined perceived stress as an explanatory mechanism linking posttraumatic stress symptom severity and smoking-specific avoidance/inflexibility, perceived barriers to smoking cessation, and negative affect reduction/negative reinforcement expectancies from smoking among trauma-exposed smokers. Participants were trauma-exposed, treatment-seeking daily cigarette smokers (n = 179; 48.0% female; Mage = 41.17; SD = 12.55). Results indicated that posttraumatic stress symptom severity had an indirect significant effect on each of the dependent variables via perceived stress. The present results provide empirical support that perceived stress may be an underlying mechanism that indirectly explains posttraumatic symptoms relation to smoking-specific avoidance/inflexibility, perceived barriers to smoking cessation, and negative affect reduction/negative reinforcement expectancies among trauma-exposed smokers. These findings suggest that there may be clinical utility in targeting perceived stress among trauma-exposed smokers via stress management psychoeducation and skills training. PMID:27100473

Dynamic analysis and control of lightweight manipulators with flexible parallel link mechanisms

NASA Technical Reports Server (NTRS)

Lee, Jeh Won

1991-01-01

The flexible parallel link mechanism is designed for increased rigidity to sustain the buckling when it carries a heavy payload. Compared to a one link flexible manipulator, a two link flexible manipulator, especially the flexible parallel mechanism, has more complicated characteristics in dynamics and control. The objective of this research is the theoretical analysis and the experimental verification of dynamics and control of a two link flexible manipulator with a flexible parallel link mechanism. Nonlinear equations of motion of the lightweight manipulator are derived by the Lagrangian method in symbolic form to better understand the structure of the dynamic model. A manipulator with a flexible parallel link mechanism is a constrained dynamic system whose equations are sensitive to numerical integration error. This constrained system is solved using singular value decomposition of the constraint Jacobian matrix. The discrepancies between the analytical model and the experiment are explained using a simplified and a detailed finite element model. The step response of the analytical model and the TREETOPS model match each other well. The nonlinear dynamics is studied using a sinusoidal excitation. The actuator dynamic effect on a flexible robot was investigated. The effects are explained by the root loci and the Bode plot theoretically and experimentally. For the base performance for the advanced control scheme, a simple decoupled feedback scheme is applied.

Molecular Mechanism of Photoactivation and Structural Location of the Cyanobacterial Orange Carotenoid Protein

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

Zhang, Hao; Liu, Haijun; Niedzwiedzki, Dariusz M.

The orange carotenoid protein (OCP) plays a photoprotective role in cyanobacterial photosynthesis similar to that of nonphotochemical quenching in higher plants. Under high-light conditions, the OCP binds to the phycobilisome (PBS) and reduces the extent of transfer of energy to the photosystems. The protective cycle starts from a light-induced activation of the OCP. Detailed information about the molecular mechanism of this process as well as the subsequent recruitment of the active OCP to the phycobilisome are not known. We report here our investigation on the OCP photoactivation from the cyanobacterium Synechocystis sp. PCC 6803 by using a combination of nativemore » electrospray mass spectrometry (MS) and protein cross-linking. We demonstrate that native MS can capture the OCP with its intact pigment and further reveal that the OCP undergoes a dimer-to-monomer transition upon light illumination. The reversion of the activated form of the OCP to the inactive, dark form was also observed by using native MS. Furthermore, in vitro reconstitution of the OCP and PBS allowed us to perform protein chemical cross-linking experiments. Liquid chromatography–MS/MS analysis identified cross-linking species between the OCP and the PBS core components. Our result indicates that the N-terminal domain of the OCP is closely involved in the association with a site formed by two allophycocyanin trimers in the basal cylinders of the phycobilisome core. This report improves our understanding of the activation mechanism of the OCP and the structural binding site of the OCP during the cyanobacterial nonphotochemical quenching process.« less

Pregnancy-induced remodeling of heart valves.

PubMed

Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

2015-11-01

Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. Copyright © 2015 the American Physiological Society.

Elucidating the Role of Compression Waves and Impact Duration for Generating mild Traumatic Brain Injury in Rats

PubMed Central

Lucke-Wold, Brandon P.; Phillips, Michael; Turner, Ryan C.; Logsdon, Aric F.; Smith, Kelly E.; Huber, Jason D.; Rosen, Charles L.; Regele, Jonathan D.

2016-01-01

3 million concussions occur each year in the United States. The mechanisms linking acute injury to chronic deficits are poorly understood. Mild traumatic brain injury has been described clinically in terms of acute functional deficits, but the underlying histopathologic changes that occur are relatively unknown due to limited high-function imaging modalities. In order to improve our understanding of acute injury mechanisms, appropriately designed preclinical models must be utilized. The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Repetitive mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers, and increases in amyloid precursor protein in both humans and rodents. Humans however infrequently succumb to mild traumatic brain injuries and therefore the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following repetitive concussions. Advances in mathematical and computer modeling can help characterize the wave properties generated by the compression wave model. While this concept of linking duration and intensity of impact to subsequent histopathologic deficits makes sense, numerical modeling of compression waves has not been performed in this context. In this collaborative interdisciplinary work, numerical simulations were performed to study the creation of compression waves in our experimental model. This work was conducted in conjunction with a repetitive compression wave injury paradigm in rats in order to better understand how the wave generation correlates with validated histopathologic deficits. PMID:27880054

Extracurricular Activity Participation in High School: Mechanisms Linking Participation to Math Achievement and 4-Year College Attendance

ERIC Educational Resources Information Center

Morris, David S.

2016-01-01

Extracurricular activity participation (EAP) has been positively linked with increased academic achievement and college attendance. However, the mechanisms linking EAP to educational outcomes are poorly understood. Using the Education Longitudinal Study of 2002 (ELS), this study contributes to our understanding of the relationship between EAP and…

Coding for Parallel Links to Maximize the Expected Value of Decodable Messages

NASA Technical Reports Server (NTRS)

Klimesh, Matthew A.; Chang, Christopher S.

2011-01-01

When multiple parallel communication links are available, it is useful to consider link-utilization strategies that provide tradeoffs between reliability and throughput. Interesting cases arise when there are three or more available links. Under the model considered, the links have known probabilities of being in working order, and each link has a known capacity. The sender has a number of messages to send to the receiver. Each message has a size and a value (i.e., a worth or priority). Messages may be divided into pieces arbitrarily, and the value of each piece is proportional to its size. The goal is to choose combinations of messages to send on the links so that the expected value of the messages decodable by the receiver is maximized. There are three parts to the innovation: (1) Applying coding to parallel links under the model; (2) Linear programming formulation for finding the optimal combinations of messages to send on the links; and (3) Algorithms for assisting in finding feasible combinations of messages, as support for the linear programming formulation. There are similarities between this innovation and methods developed in the field of network coding. However, network coding has generally been concerned with either maximizing throughput in a fixed network, or robust communication of a fixed volume of data. In contrast, under this model, the throughput is expected to vary depending on the state of the network. Examples of error-correcting codes that are useful under this model but which are not needed under previous models have been found. This model can represent either a one-shot communication attempt, or a stream of communications. Under the one-shot model, message sizes and link capacities are quantities of information (e.g., measured in bits), while under the communications stream model, message sizes and link capacities are information rates (e.g., measured in bits/second). This work has the potential to increase the value of data returned from spacecraft under certain conditions.

Diffusion Barriers, Mechanical Forces, and the Biophysics of Phagocytosis.

PubMed

Ostrowski, Philip P; Grinstein, Sergio; Freeman, Spencer A

2016-07-25

Phagocytes recognize and eliminate pathogens, alert other tissues of impending threats, and provide a link between innate and adaptive immunity. They also maintain tissue homeostasis, consuming dead cells without causing alarm. The receptor engagement, signal transduction, and cytoskeletal rearrangements underlying phagocytosis are paradigmatic of other immune responses and bear similarities to macropinocytosis and cell migration. We discuss how the glycocalyx restricts access to phagocytic receptors, the processes that enable receptor engagement and clustering, and the remodeling of the actin cytoskeleton that controls the mobility of membrane proteins and lipids and provides the mechanical force propelling the phagocyte membrane toward and around the phagocytic prey. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2008-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2009-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Mitochondria: the next (neurode)generation

PubMed Central

Schon, Eric A.; Przedborski, Serge

2012-01-01

SUMMARY Adult-onset neurodegenerative disorders are disabling and often fatal diseases of the nervous system whose underlying mechanisms of cell death remain, in most instances, unknown. Defects in mitochondrial respiration had previously been proposed to contribute to the occurrence of many, if not all of the most common neurodegenerative disorders. However, the discovery of genes mutated in hereditary forms of these enigmatic diseases has additionally suggested defects in mitochondrial dynamics. Such disturbances can lead to changes in mitochondrial trafficking, in interorganellar communication, and in mitochondrial quality control. These new mechanisms by which mitochondria may also be linked to neurodegeneration will likely have far-reaching implications for our understanding of the pathophysiology and treatment of adult-onset neurodegenerative disorders. PMID:21689593

Diet-induced obesity, gut microbiota and bone, including alveolar bone loss.

PubMed

Eaimworawuthikul, Sathima; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-06-01

Obesity is a major risk factor for several pathologies, including jaw bone resorption. The underlying mechanisms involved in pathological conditions resulting from obesity include chronic systemic inflammation and the development of insulin resistance. Although numerous studies have indicated the importance of the role of gut microbiota in the pathogenesis of inflammation and insulin resistance in obesity, only a few studies have established a relationship between obesity, gut microbiota and status of the jaw bone. This review aims to summarize current findings relating to these issues, focusing on the role of obesity and gut microbiota on jaw bone health, including possible mechanisms which can explain this link. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity.

PubMed

Novosyadlyy, Ruslan; Leroith, Derek

2012-06-01

Numerous lines of evidence indicate that insulin-like growth factor signaling plays an important role in the regulation of life span and tumor development. In the present paper, the role of individual components of insulin-like growth factor signaling in aging and tumor development has been extensively analyzed. The molecular mechanisms underlying aging and tumor development are frequently overlapping. Although the link between reduced insulin-like growth factor signaling and suppressed tumor growth and development is well established, it remains unclear whether extended life span results from direct suppression of insulin-like growth factor signaling or this effect is caused by indirect mechanisms such as improved insulin sensitivity.

Media exposure and smoking intention in adolescents: a moderated mediation analysis from a cultivation perspective.

PubMed

Yang, Fang; Salmon, Charles T; Pang, Joyce S; Cheng, Wendy J Y

2015-02-01

The study tested a moderated mediation model to examine the mechanisms underlying the link between media exposure and adolescent smoking intention by utilizing a modification of cultivation theory. A total of 12,586 non-current smoker adolescents in California were included in the analysis. Results showed that media exposure was positively related to smoking intention via perceived prevalence of peer smoking when friend disapproval of cigarette use was low. This study contributes to a better understanding of the mechanisms regarding the media effects on smoking intention, but the findings should be interpreted with caution due to the small effect size. © The Author(s) 2013.

Design and modelling of a link monitoring mechanism for the Common Data Link (CDL)

NASA Astrophysics Data System (ADS)

Eichelberger, John W., III

1994-09-01

The Common Data Link (CDL) is a full duplex, point-to-point microwave communications system used in imagery and signals intelligence collection systems. It provides a link between two remote Local Area Networks (LAN's) aboard collection and surface platforms. In a hostile environment, there is an overwhelming need to dynamically monitor the link and thus, limit the impact of jamming. This work describes steps taken to design, model, and evaluate a link monitoring system suitable for the CDL. The monitoring system is based on features and monitoring constructs of the Link Control Protocol (LCP) in the Point-to-Point Protocol (PPP) suite. The CDL model is based on a system of two remote Fiber Distributed Data Interface (FDDI) LAN's. In particular, the policies and mechanisms associated with monitoring are described in detail. An implementation of the required mechanisms using the OPNET network engineering tool is described. Performance data related to monitoring parameters is reported. Finally, integration of the FDDI-CDL model with the OPNET Internet model is described.

Different types of interactions of links in artificial and natural ecosystems under anthropogenic pressure

NASA Astrophysics Data System (ADS)

Somova, Lydia; Pisman, Tamara; Mikheeva, Galina; Pechurkin, Nickolay

The life of organisms in an ecosystem depends not only on abiotic factors, but also on the interaction of organisms in which they come with each other. The study of mechanisms of the bioregulation based on ecological - biochemical interactions of ecosystem links is necessary to know the ecosystem development, its stability, survival of ecosystem organisms. It is of high importance as for the creation of artificial ecosystems, and also for the study of natural ecosystems under anthropogenic pressure on them. To create well-functioning ecosystems is necessary to study and consider the basic types of relationships between organisms. The basic types of interactions between organisms have been studied with simple terrestrial and water ecosystems. 1. The interaction of microbiocenoses and plants were studied in experiments with agrocenoses. Microbiocenosis proposed for increase of productivity of plants and for obtaining ecologically pure production of plants has been created taking into account mutual relationships between species of microorganisms. 2. The experimental model of the atmosphere closed «autotroph - heterotroph» system in which heterotrophic link was the mixed population of yeasts (Candida utilis and Candida guilliermondii) was studied. The algae Chlorella vulgaris was used as an autotroph link. It was shown, that the competition result for heterotrophic link depended on strategy of populations of yeast in relation to a substrate and oxygen utilization. 3. As a result of experimental and theoretical modelling of a competition of algae Chlorella vulgaris and Scenedesmus quadricauda at continuous cultivation, the impossibility of their coexistence in the conditions of limitation on nitrogen was shown. 4. Pray-predator interactions between algae (Chlorella vulgaris, Scenedesmus quadricauda) and invertebrates (Paramecium caudatum, Brachionus plicatilis) were studied in experimental closed ecosystem. This work was partly supported by the Russian Foundation for Basic Research, project No.13-06-00060

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.

Characteristics of Crushing Energy and Fractal of Magnetite Ore under Uniaxial Compression

NASA Astrophysics Data System (ADS)

Gao, F.; Gan, D. Q.; Zhang, Y. B.

2018-03-01

The crushing mechanism of magnetite ore is a critical theoretical problem on the controlling of energy dissipation and machine crushing quality in ore material processing. Uniaxial crushing tests were carried out to research the deformation mechanism and the laws of the energy evolution, based on which the crushing mechanism of magnetite ore was explored. The compaction stage and plasticity and damage stage are two main compression deformation stages, the main transitional forms from inner damage to fracture are plastic deformation and stick-slip. In the process of crushing, plasticity and damage stage is the key link on energy absorption for that the specimen tends to saturate energy state approaching to the peak stress. The characteristics of specimen deformation and energy dissipation can synthetically reply the state of existed defects inner raw magnetite ore and the damage process during loading period. The fast releasing of elastic energy and the work done by the press machine commonly make raw magnetite ore thoroughly broken after peak stress. Magnetite ore fragments have statistical self-similarity and size threshold of fractal characteristics under uniaxial squeezing crushing. The larger ratio of releasable elastic energy and dissipation energy and the faster energy change rate is the better fractal properties and crushing quality magnetite ore has under uniaxial crushing.

LRP8-Reelin-regulated Neuronal (LRN) Enhancer Signature Underlying Learning and Memory Formation

PubMed Central

Telese, Francesca; Ma, Qi; Perez, Patricia Montilla; Notani, Dimple; Oh, Soohwan; Li, Wenbo; Comoletti, Davide; Ohgi, Kenneth A.; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signature of the neuronal enhancers required for transcriptional regulation of synaptic plasticity genes during memory formation, linking this to Reelin signaling. The binding of Reelin to its receptor, LRP8, triggers activation of this cohort of LRP8-Reelin-regulated-Neuronal (LRN) enhancers that serve as the ultimate convergence point of a novel synapse-to-nucleus pathway. Reelin simultaneously regulates NMDA-receptor transmission, which reciprocally permits the required, γ-secretase-dependent cleavage of LRP8, revealing an unprecedented role for its intracellular domain in the regulation of synaptically generated signals. These results uncover an in vivo enhancer code serving as a critical molecular component of cognition and relevant to psychiatric disorders linked to defects in Reelin signaling. PMID:25892301

Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

PubMed

Seibt, Julie; Richard, Clément J; Sigl-Glöckner, Johanna; Takahashi, Naoya; Kaplan, David I; Doron, Guy; de Limoges, Denis; Bocklisch, Christina; Larkum, Matthew E

2017-09-25

How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.

X-linked Alport syndrome caused by splicing mutations in COL4A5.

PubMed

Nozu, Kandai; Vorechovsky, Igor; Kaito, Hiroshi; Fu, Xue Jun; Nakanishi, Koichi; Hashimura, Yuya; Hashimoto, Fusako; Kamei, Koichi; Ito, Shuichi; Kaku, Yoshitsugu; Imasawa, Toshiyuki; Ushijima, Katsumi; Shimizu, Junya; Makita, Yoshio; Konomoto, Takao; Yoshikawa, Norishige; Iijima, Kazumoto

2014-11-07

X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism. In total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) mRNA analysis using RT-PCR to detect RNA processing abnormalities. Six splicing consensus site mutations resulting in aberrant splicing patterns, one exonic mutation leading to exon skipping, and four deep intronic mutations producing cryptic splice site activation were identified. Interestingly, one case produced a cryptic splice site with a single nucleotide substitution in the deep intron that led to intronic exonization containing a stop codon; however, the patient showed a clearly milder phenotype for X-linked Alport syndrome in men with a truncating mutation. mRNA extracted from the kidney showed both normal and abnormal transcripts, with the normal transcript resulting in the milder phenotype. This novel mechanism leads to mild clinical characteristics. This report highlights the importance of analyzing transcripts to enhance the mutation detection rate and provides insight into genotype-phenotype correlations. This approach can clarify the cause of atypically mild phenotypes in X-linked Alport syndrome. Copyright © 2014 by the American Society of Nephrology.

Dysregulated LRRK2 Signaling in Response to Endoplasmic Reticulum Stress Leads to Dopaminergic Neuron Degeneration in C. elegans

PubMed Central

Yuan, Yiyuan; Cao, Pengxiu; Smith, Mark A.; Kramp, Kristopher; Huang, Ying; Hisamoto, Naoki; Matsumoto, Kunihiro; Hatzoglou, Maria; Jin, Hui; Feng, Zhaoyang

2011-01-01

Mutation of leucine-rich repeat kinase 2 (LRRK2) is the leading genetic cause of Parkinson's Disease (PD), manifested as age-dependent dopaminergic neurodegeneration, but the underlying molecular mechanisms remain unclear. Multiple roles of LRRK2 may contribute to dopaminergic neurodegeneration. Endoplasmic reticulum (ER) stress has also been linked to PD pathogenesis, but its interactive mechanism with PD genetic factors is largely unknown. Here, we used C. elegans, human neuroblastoma cells and murine cortical neurons to determine the role of LRRK2 in maintaining dopaminergic neuron viability. We found that LRRK2 acts to protect neuroblastoma cells and C. elegans dopaminergic neurons from the toxicity of 6-hydroxydopamine and/or human α-synuclein, possibly through the p38 pathway, by supporting upregulation of GRP78, a key cell survival molecule during ER stress. A pathogenic LRRK2 mutant (G2019S), however, caused chronic p38 activation that led to death of murine neurons and age-related dopaminergic-specific neurodegeneration in nematodes. These observations establish a critical functional link between LRRK2 and ER stress. PMID:21857923

Mechanisms of age-related cognitive change and targets for intervention: social interactions and stress.

PubMed

Kremen, William S; Lachman, Margie E; Pruessner, Jens C; Sliwinski, Martin; Wilson, Robert S

2012-06-01

The effects of biological and physical factors on cognitive aging are widely studied. Less is known about the role of psychosocial factors such as stress and social relationships for cognitive functioning. Speakers in Session IV of the Summit focused on possible mechanisms linking social interactions and stressful experiences to cognitive changes with aging. Elevated cortisol, repetitive thinking, negative emotions, neuroticism, chronic stress, and early life adversity were negatively associated with memory and other cognitive dimensions in later life. In contrast, supportive social relationships were found to be positively related to cognitive functioning. Some evidence was provided for multidirectional, causal relationships involving stress and negative affect as both antecedents and consequences of cognitive decline. The findings contribute to understanding the potential underlying causal processes linking psychosocial factors and cognitive aging with a developmental focus on the etiology of declines and onset of cognitive impairments. This work provides an important foundation for future research to identify modifiable factors and to design interventions to minimize cognitive declines and optimize cognitive health in adulthood.

3D Progressive Damage Modeling for Laminated Composite Based on Crack Band Theory and Continuum Damage Mechanics

NASA Technical Reports Server (NTRS)

Wang, John T.; Pineda, Evan J.; Ranatunga, Vipul; Smeltzer, Stanley S.

2015-01-01

A simple continuum damage mechanics (CDM) based 3D progressive damage analysis (PDA) tool for laminated composites was developed and implemented as a user defined material subroutine to link with a commercially available explicit finite element code. This PDA tool uses linear lamina properties from standard tests, predicts damage initiation with an easy-to-implement Hashin-Rotem failure criteria, and in the damage evolution phase, evaluates the degradation of material properties based on the crack band theory and traction-separation cohesive laws. It follows Matzenmiller et al.'s formulation to incorporate the degrading material properties into the damaged stiffness matrix. Since nonlinear shear and matrix stress-strain relations are not implemented, correction factors are used for slowing the reduction of the damaged shear stiffness terms to reflect the effect of these nonlinearities on the laminate strength predictions. This CDM based PDA tool is implemented as a user defined material (VUMAT) to link with the Abaqus/Explicit code. Strength predictions obtained, using this VUMAT, are correlated with test data for a set of notched specimens under tension and compression loads.

An Overview of the Protective Effects of Chitosan and Acetylated Chitosan Oligosaccharides against Neuronal Disorders.

PubMed

Hao, Cui; Wang, Wei; Wang, Shuyao; Zhang, Lijuan; Guo, Yunliang

2017-03-23

Chitin is the second most abundant biopolymer on Earth and is mainly comprised of a marine invertebrate, consisting of repeating β-1,4 linked N-acetylated glucosamine units, whereas its N-deacetylated product, chitosan, has broad medical applications. Interestingly, chitosan oligosaccharides have therapeutic effects on different types of neuronal disorders, including, but not limited to, Alzheimer's disease, Parkinson's disease, and nerve crush injury. A common link among neuronal disorders is observed at a sub-cellular level, such as atypical protein assemblies and induced neuronal death. Chronic activation of innate immune responses that lead to neuronal injury is also common in these diseases. Thus, the common mechanisms of neuronal disorders might explain the general therapeutic effects of chitosan oligosaccharides and their derivatives in these diseases. This review provides an update on the pathogenesis and therapy for neuronal disorders and will be mainly focused on the recent progress made towards the neuroprotective properties of chitosan and acetylated chitosan oligosaccharides. Their structural features and the underlying molecular mechanisms will also be discussed.

Nonlinear deformations of microcapsules in elongation flow

NASA Astrophysics Data System (ADS)

Deschamps, Julien; de Loubens, Clément; Boedec, Gwenn; Georgelin, Marc; Leonetti, Marc; Soft Matter; Biophysics Group Team

2014-11-01

Soft microcapsules are drops bounded by a thin elastic shell made of cross-linked proteins. They have numerous applications for drug delivery in bioengineering, pharmaceutics and medicine, where their mechanical stability and their dynamics under flow are crucial. They can also be used as red blood cells models. Here, we investigate the mechanical behaviour of microcapsules made of albumine in strong elongational flow, up to a stretching of 180% just before breaking. The set-up allows us to visualize the deformed shape in the two perpendicular main fields of view, to manage high capillary number and to manipulate soft microcapsules. The steady-state shape of a capsule in the planar elongational flow is non-axisymmetric. In each cross section, the shape is an ellipse but with different small axis which vary in opposite sense with the stretching. Whatever the degree of cross-linking and the size of the capsules, the deformations followed the same master-curve. Comparisons between numerical predictions and experimental results permit to conclude unambiguously that the more properly strain-energy model of membrane is the generalized Hooke model.

SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

PubMed Central

Tulino, Raffaella; Benjamin, Agnesska C.; Jolinon, Nelly; Smith, Donna L.; Chini, Eduardo N.; Carnemolla, Alisia; Bates, Gillian P.

2016-01-01

Huntington’s disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies. PMID:26815359

A mechanistic link between gene regulation and genome architecture in mammalian development.

PubMed

Bonora, Giancarlo; Plath, Kathrin; Denholtz, Matthew

2014-08-01

The organization of chromatin within the nucleus and the regulation of transcription are tightly linked. Recently, mechanisms underlying this relationship have been uncovered. By defining the organizational hierarchy of the genome, determining changes in chromatin organization associated with changes in cell identity, and describing chromatin organization within the context of linear genomic features (such as chromatin modifications and transcription factor binding) and architectural proteins (including Cohesin, CTCF, and Mediator), a new paradigm in genome biology was established wherein genomes are organized around gene regulatory factors that govern cell identity. As such, chromatin organization plays a central role in establishing and maintaining cell state during development, with gene regulation and genome organization being mutually dependent effectors of cell identity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Does the Incredible Years reduce child externalizing problems through improved parenting? The role of child negative affectivity and serotonin transporter linked polymorphic region (5-HTTLPR) genotype.

PubMed

Weeland, Joyce; Chhangur, Rabia R; Jaffee, Sara R; Van Der Giessen, Danielle; Matthys, Walter; Orobio De Castro, Bram; Overbeek, Geertjan

2018-02-01

In a randomized controlled trial, the Observational Randomized Controlled Trial of Childhood Differential Susceptibility (ORCHIDS study), we tested whether observed parental affect and observed and reported parenting behavior are mechanisms of change underlying the effects of the behavioral parent training program the Incredible Years (IY). Furthermore, we tested whether some children are more susceptible to these change mechanisms because of their temperamental negative affectivity and/or serotonin transporter linked polymorphic region (5-HTTLPR) genotype. Participants were 387 Dutch children between 4 and 8 years of age (M age = 6.31, SD = 1.33; 55.3% boys) and their parents. Results showed that although IY was successful in improving parenting behavior and increasing parental positive affect, these effects did not explain the significant decreases in child externalizing problems. We therefore found no evidence for changes in parenting behavior or parental affect being the putative mechanisms of IY effectiveness. Furthermore, intervention effects on child externalizing behavior were not moderated by child negative affectivity or 5-HTTLPR genotype. However, child 5-HTTLPR genotype did moderate intervention effects on negative parenting behavior. This suggests that in research on behavioral parent training programs, "what works for which parents" might also be an important question.

Oligosilylarylnitrile: The Thermoresistant Thermosetting Resin with High Comprehensive Properties.

PubMed

Wang, Mingcun; Ning, Yi

2018-04-11

One of the highest thermoresistant thermosetting resins ever studied so far, oligosilylarylnitrile resin, was investigated first in this study. Oligosilylarylnitrile was synthesized by lithium-reduced Wurtz-Fittig condensation reaction, and the prepared viscous resin exhibited moderate rheological behaviors while heated purely or together with 20% polysilazane as a cross-linking agent. The thermal curing temperatures were found by differential scanning calorimetry at 268 °C (pure) and 158 °C (with the polysilazane cross-linking agent), which is comparably close to that of polysilylarylacetylene resin (normally at 220-250 °C) but much lower than those of polyimide and phthalonitrile resins (normally >300 °C), indicating the admirable material processability of oligosilylnitrile. The cured oligosilylarylnitrile resins have extremely high thermal resistance, indicated by the results of thermogravimetric analysis (the mass residue at 800 °C is >90% under N 2 ) and dynamic mechanical analysis (the glass-transition temperature is >420 °C). The mechanical property of the oligosilylarylnitrile-matrixed silica-cloth reinforced laminate is comparably close to those of polyimide and phthalonitrile but much higher than that of polysilylarylacetylene, indicating the enviable thermal and mechanical properties of oligosilylnitrile. Thus, among the high-temperature resins ever studied so far, the oligosilylarylnitrile resin was found to have the almost best comprehensive characteristics of processability and properties.

Motion sickness susceptibility in parabolic flight and velocity storage activity

NASA Technical Reports Server (NTRS)

Dizio, Paul; Lackner, James R.

1991-01-01

In parabolic flight experiments, postrotary nystagmus is as found to be differentially suppressed in free fall (G) and in a high gravitoinertial force (1.8 G) background relative to 1 G. In addition, the influence of postrotary head movements on nystagmus suppression was found to be contingent on G-dependency of the velocity storage and dumping mechanisms. Here, susceptibility to motion sickness during head movements in 0 G and 1.8 G was rank-correlated with the following: (1) the decay time constant of the slow phase velocity of postrotary nystagmus under 1 G, no head movement, baseline conditions, (2) the extent of time constant reduction elicited in 0 G and 1.8 G; (3) the extent of time constant reduction elicited by head tilts in 1 G; and (4) changes in the extent of time constants reduction in 0 G and 1.8 G over repeated tests. Susceptibility was significantly correlated with the extent to which a head movement reduced the time constant in 1 G, was weakly correlated with the baseline time constant, but was not correlated with the extent of reduction in 0 G or 1.8 G. This pattern suggests a link between mechanisms evoking symptoms of space motion sickness and the mechanisms of velocity storage and dumping. Experimental means of evaluating this link are described.

Protein O-GlcNAcylation: A critical regulator of the cellular response to stress.

PubMed

Chatham, John C; Marchase, Richard B

2010-01-01

The post-translational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ß-N-acetyl-glucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O-GlcNAc on cellular function has been in the context of chronic disease processes. However, there is increasing evidence that O-GlcNAc levels are increased in response to stress and that acute augmentation of this response is cytoprotective, at least in the short term. Conversely, a reduction in O-GlcNAc levels appears to be associated with decreased cell survival in response to an acute stress. Here we summarize our current understanding of protein O-GlcNAcylation on the cellular response to stress and in mediating cellular protective mechanisms focusing primarily on the cardiovascular system as an example. We consider the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis and explore the parallels between O-GlcNAc signaling and redox signaling. We also discuss the apparent paradox between the reported adverse effects of increased O-GlcNAcylation with its recently reported role in mediating cell survival mechanisms.

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

PubMed Central

McLaughlin, Katie A.; Hatzenbuehler, Mark L.

2012-01-01

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

On the water lapping of felines and the water running of lizards

PubMed Central

Aristoff, Jeffrey M; Stocker, Roman; Reis, Pedro M

2011-01-01

We consider two biological phenomena taking place at the air-water interface: the water lapping of felines and the water running of lizards. Although seemingly disparate motions, we show that they are intimately linked by their underlying hydrodynamics and belong to a broader class of processes called Froude mechanisms. We describe how both felines and lizards exploit inertia to defeat gravity, and discuss water lapping and water running in the broader context of water exit and water entry, respectively. PMID:21655444

The Changing Face of Hypophosphatemic Disorders in the FGF-23 Era

PubMed Central

Lee, Janet Y.; Imel, Erik A.

2014-01-01

In the past decade, research in genetic disorders of hypophosphatemia has significantly expanded our understanding of phosphate metabolism. X-linked hypophosphatemia (XLH) is the most common inherited form of rickets due to renal phosphate wasting. Recent understanding of the mechanisms of disease and role of fibroblast growth factor 23 (FGF-23) in XLH and other hypophosphatemic disorders have opened new potential therapeutic avenues. We will discuss the current standard of treatment for XLH as well as promising future directions under study. PMID:23858620

A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.

PubMed

Stephenson, Jason R; Wang, Xiaohan; Perfitt, Tyler L; Parrish, Walker P; Shonesy, Brian C; Marks, Christian R; Mortlock, Douglas P; Nakagawa, Terunaga; Sutcliffe, James S; Colbran, Roger J

2017-02-22

Characterizing the functional impact of novel mutations linked to autism spectrum disorder (ASD) provides a deeper mechanistic understanding of the underlying pathophysiological mechanisms. Here we show that a de novo Glu183 to Val (E183V) mutation in the CaMKIIα catalytic domain, identified in a proband diagnosed with ASD, decreases both CaMKIIα substrate phosphorylation and regulatory autophosphorylation, and that the mutated kinase acts in a dominant-negative manner to reduce CaMKIIα-WT autophosphorylation. The E183V mutation also reduces CaMKIIα binding to established ASD-linked proteins, such as Shank3 and subunits of l-type calcium channels and NMDA receptors, and increases CaMKIIα turnover in intact cells. In cultured neurons, the E183V mutation reduces CaMKIIα targeting to dendritic spines. Moreover, neuronal expression of CaMKIIα-E183V increases dendritic arborization and decreases both dendritic spine density and excitatory synaptic transmission. Mice with a knock-in CaMKIIα-E183V mutation have lower total forebrain CaMKIIα levels, with reduced targeting to synaptic subcellular fractions. The CaMKIIα-E183V mice also display aberrant behavioral phenotypes, including hyperactivity, social interaction deficits, and increased repetitive behaviors. Together, these data suggest that CaMKIIα plays a previously unappreciated role in ASD-related synaptic and behavioral phenotypes. SIGNIFICANCE STATEMENT Many autism spectrum disorder (ASD)-linked mutations disrupt the function of synaptic proteins, but no single gene accounts for >1% of total ASD cases. The molecular networks and mechanisms that couple the primary deficits caused by these individual mutations to core behavioral symptoms of ASD remain poorly understood. Here, we provide the first characterization of a mutation in the gene encoding CaMKIIα linked to a specific neuropsychiatric disorder. Our findings demonstrate that this ASD-linked de novo CAMK2A mutation disrupts multiple CaMKII functions, induces synaptic deficits, and causes ASD-related behavioral alterations, providing novel insights into the synaptic mechanisms contributing to ASD. Copyright © 2017 the authors 0270-6474/17/372217-18$15.00/0.

Words, rules, and mechanisms of language acquisition.

PubMed

Endress, Ansgar D; Bonatti, Luca L

2016-01-01

We review recent artificial language learning studies, especially those following Endress and Bonatti (Endress AD, Bonatti LL. Rapid learning of syllable classes from a perceptually continuous speech stream. Cognition 2007, 105:247-299), suggesting that humans can deploy a variety of learning mechanisms to acquire artificial languages. Several experiments provide evidence for multiple learning mechanisms that can be deployed in fluent speech: one mechanism encodes the positions of syllables within words and can be used to extract generalization, while the other registers co-occurrence statistics of syllables and can be used to break a continuum into its components. We review dissociations between these mechanisms and their potential role in language acquisition. We then turn to recent criticisms of the multiple mechanisms hypothesis and show that they are inconsistent with the available data. Our results suggest that artificial and natural language learning is best understood by dissecting the underlying specialized learning abilities, and that these data provide a rare opportunity to link important language phenomena to basic psychological mechanisms. For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

Spectroscopic characterization of collagen cross-links in bone

NASA Technical Reports Server (NTRS)

Paschalis, E. P.; Verdelis, K.; Doty, S. B.; Boskey, A. L.; Mendelsohn, R.; Yamauchi, M.

2001-01-01

Collagen is the most abundant protein of the organic matrix in mineralizing tissues. One of its most critical properties is its cross-linking pattern. The intermolecular cross-linking provides the fibrillar matrices with mechanical properties such as tensile strength and viscoelasticity. In this study, Fourier transform infrared (FTIR) spectroscopy and FTIR imaging (FTIRI) analyses were performed in a series of biochemically characterized samples including purified collagen cross-linked peptides, demineralized bovine bone collagen from animals of different ages, collagen from vitamin B6-deficient chick homogenized bone and their age- and sex-matched controls, and histologically stained thin sections from normal human iliac crest biopsy specimens. One region of the FTIR spectrum of particular interest (the amide I spectral region) was resolved into its underlying components. Of these components, the relative percent area ratio of two subbands at approximately 1660 cm(-1) and approximately 1690 cm(-1) was related to collagen cross-links that are abundant in mineralized tissues (i.e., pyridinoline [Pyr] and dehydrodihydroxylysinonorleucine [deH-DHLNL]). This study shows that it is feasible to monitor Pyr and DHLNL collagen cross-links spatial distribution in mineralized tissues. The spectroscopic parameter established in this study may be used in FTIRI analyses, thus enabling the calculation of relative Pyr/DHLNL amounts in thin (approximately 5 microm) calcified tissue sections with a spatial resolution of approximately 7 microm.

Dependence of nanomechanical modification of polymers on plasma-induced cross-linking

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

Tajima, S.; Komvopoulos, K.

2007-01-01

The nanomechanical properties of low-density polyethylene (LDPE) modified by inductively coupled, radio-frequency Ar plasma were investigated by surface force microscopy. The polymer surface was modified under plasma conditions of different ion energy fluences and radiation intensities obtained by varying the sample distance from the plasma power source. Nanoindentation results of the surface stiffness versus maximum penetration depth did not reveal discernible differences between untreated and plasma-treated LDPE, presumably due to the small thickness of the modified surface layer that resulted in a substrate effect. On the contrary, nanoscratching experiments demonstrated a significant increase in the surface shear resistance of plasma-modifiedmore » LDPE due to chain cross-linking. These experiments revealed an enhancement of cross-linking with increasing ion energy fluence and radiation intensity, and a tip size effect on the friction force and dominant friction mechanisms (adhesion, plowing, and microcutting). In addition, LDPE samples with a LiF crystal shield were exposed to identical plasma conditions to determine the role of vacuum ultraviolet (VUV) and ultraviolet (UV) radiation in the cross-linking process. The cross-linked layer of plasma-treated LDPE exhibited much higher shear strength than that of VUV/UV-treated LDPE. Plasma-induced surface modification of the nanomechanical properties of LDPE is interpreted in the context of molecular models of the untreated and cross-linked polymer surfaces derived from experimental findings.« less

Coating of Carbon Fiber with Polyhedral Oligomeric Silsesquioxane (POSS) to Enhance Mechanical Properties and Durability of Carbon/Vinyl Ester Composites

PubMed Central

Mahfuz, Hassan; Powell, Felicia; Granata, Richard; Hosur, Mahesh; Khan, Mujib

2011-01-01

Our continuing quest to improve the performance of polymer composites under moist and saltwater environments has gained momentum in recent years with the reinforcement of inorganic nanoparticles into the polymer. The key to mitigate degradation of composites under such environments is to maintain the integrity of the fiber/matrix (F/M) interface. In this study, the F/M interface of carbon/vinyl ester composites has been modified by coating the carbon fiber with polyhedral oligomeric silsesquioxane (POSS). POSS is a nanostructured inorganic-organic hybrid particle with a cubic structure having silicon atoms at the core and linked to oxygen atoms. The advantage of using POSS is that the silicon atoms can be linked to a substituent that can be almost any chemical group known in organic chemistry. Cubic silica cores are ‘hard particles’ and are about 0.53 nm in diameter. The peripheral organic unit is a sphere of about 1–3 nm in diameter. Further, cubic structure of POSS remains intact during the polymerization process and therefore with appropriate functional groups, if installed on the fiber surface, would provide a stable and strong F/M interface. Two POSS systems with two different functional groups; namely, octaisobutyl and trisilanolphenyl have been investigated. A set of chemical and mechanical procedures has been developed to coat carbon fibers with POSS, and to fabricate layered composites with vinyl ester resin. Interlaminar shear and low velocity impact tests have indicated around 17–38% improvement in mechanical properties with respect to control samples made without the POSS coating. Saltwater and hygrothermal tests at various environmental conditions have revealed that coating with POSS reduces water absorption by 20–30% and retains the composite properties. PMID:28824160

The Mechanism of Isotonic Water Transport

PubMed Central

Diamond, Jared M.

1964-01-01

The mechanism by which active solute transport causes water transport in isotonic proportions across epithelial membranes has been investigated. The principle of the experiments was to measure the osmolarity of the transported fluid when the osmolarity of the bathing solution was varied over an eightfold range by varying the NaCl concentration or by adding impermeant non-electrolytes. An in vitro preparation of rabbit gall bladder was suspended in moist oxygen without an outer bathing solution, and the pure transported fluid was collected as it dripped off the serosal surface. Under all conditions the transported fluid was found to approximate an NaCl solution isotonic to whatever bathing solution used. This finding means that the mechanism of isotonic water transport in the gall bladder is neither the double membrane effect nor co-diffusion but rather local osmosis. In other words, active NaCl transport maintains a locally high concentration of solute in some restricted space in the vicinity of the cell membrane, and water follows NaCl in response to this local osmotic gradient. An equation has been derived enabling one to calculate whether the passive water permeability of an organ is high enough to account for complete osmotic equilibration of actively transported solute. By application of this equation, water transport associated with active NaCl transport in the gall bladder cannot go through the channels for water flow under passive conditions, since these channels are grossly too impermeable. Furthermore, solute-linked water transport fails to produce the streaming potentials expected for water flow through these passive channels. Hence solute-linked water transport does not occur in the passive channels but instead involves special structures in the cell membrane, which remain to be identified. PMID:14212146

3D Bi2S3/TiO2 cross-linked heterostructure: An efficient strategy to improve charge transport and separation for high photoelectrochemical performance

NASA Astrophysics Data System (ADS)

Han, Minmin; Jia, Junhong

2016-10-01

A novel 3D cross-linked heterostructure of TiO2 nanorods connecting with each other via ultrathin Bi2S3 nanosheets is constructed by a facile and effective strategy. The growth mechanism has been investigated and proposed based on the evolution of microstructure by changing the reaction parameters. Benefiting from the unique cross-linked heterostructure, the as-prepared Bi2S3 nanosheets modified TiO2 nanorods arrays could achieve a high energy conversion efficiency of 3.29% which is the highest value to date for Bi2S3-only sensitized solar cells as the reported highest value is 2.23% and other reported values are less than 1%. Furthermore, the photoelectrochemical studies clearly reveal that the novel cross-linked heterostructure exhibits much better activity than 0D nanoparticles decorated TiO2 nanorods under visible light irradiation, which may be primarily ascribed to the efficient electron transfer from 2D ultrathin Bi2S3 nanosheets to 1D TiO2 nanorod arrays. The promising results in this work confirm the advantages of cross-linked heterostructure and also undoubtedly offer an attractive synthesis strategy to fabricate other nanorod-based hierarchical architecture as well as nano-devices for solar energy conversion.

To Cross-Link or Not to Cross-Link? Cross-Linking Associated Foreign Body Response of Collagen-Based Devices

PubMed Central

Delgado, Luis M.; Bayon, Yves; Pandit, Abhay

2015-01-01

Collagen-based devices, in various physical conformations, are extensively used for tissue engineering and regenerative medicine applications. Given that the natural cross-linking pathway of collagen does not occur in vitro, chemical, physical, and biological cross-linking methods have been assessed over the years to control mechanical stability, degradation rate, and immunogenicity of the device upon implantation. Although in vitro data demonstrate that mechanical properties and degradation rate can be accurately controlled as a function of the cross-linking method utilized, preclinical and clinical data indicate that cross-linking methods employed may have adverse effects on host response, especially when potent cross-linking methods are employed. Experimental data suggest that more suitable cross-linking methods should be developed to achieve a balance between stability and functional remodeling. PMID:25517923

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links.

PubMed

De Rosa, Salvatore; Arcidiacono, Biagio; Chiefari, Eusebio; Brunetti, Antonio; Indolfi, Ciro; Foti, Daniela P

2018-01-01

Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

1D and 2D oxidized carbon nanomaterials on epoxy matrix: performance of composites over the same processing conditions

NASA Astrophysics Data System (ADS)

Ramos-Galicia, Lourdes; Martinez-Hernandez, Ana Laura; Fuentes-Ramirez, Rosalba; Velasco-Santos, Carlos

2017-11-01

Oxidized multi-walled carbon nanotubes and graphene oxide were evaluated as reinforcements of an epoxy resin. The composites were synthesized at concentrations of 0.1, 0.5, and 1.0 wt% under the same processing conditions. Nanocomposites with graphene oxide at 0.5 wt% present the highest mechanical properties, reaching up to ~180%, and ~760% of improvement in tensile strength and tensile toughness with respect to neat epoxy. Nevertheless, composites with oxidized nanotubes exhibit a tendency to improve mechanical properties as load increases. Storage moduli diminish due to cross-linking density reduction in all nanocomposites. Difference in thermal degradation are not observed in composites in comparison with matrix. Dimension play an important role in mechanical properties, because each nanoreinforcement has different performance with the concentration.

The mechanism of sound production in túngara frogs and its role in sexual selection and speciation.

PubMed

Ryan, Michael J; Guerra, Mónica A

2014-10-01

Sexual communication can evolve in response to sexual selection, and it can also cause behavioral reproductive isolation between populations and thus drive speciation. Anurans are an excellent system to investigate these links between behavior and evolution because we have detailed knowledge of how neural mechanisms generate behavioral preferences for calls and how these preferences then generate selection on call variation. But we know far less about the physical mechanisms of call production, especially how different laryngeal morphologies generate call variation. Here we review studies of a group of species that differ in the presence of a secondary call component that evolved under sexual selection. We discuss how the larynx produces this call component, and how laryngeal morphology generates sexual selection and can contribute to speciation. Copyright © 2014. Published by Elsevier Ltd.

Virus/allergen interactions in asthma.

PubMed

Gavala, Monica L; Bashir, Hiba; Gern, James E

2013-06-01

Understanding the underlying mechanisms that cause and exacerbate allergic asthmatic disease is of great clinical interest. Clinical studies have revealed that allergies and viral respiratory illnesses are strongly linked to the inception and exacerbation of asthma, and suggest the possibility that there are interactive inflammatory mechanisms. Recent work has revealed a number of mechanisms of virus and allergen cross-talk that may play a role in the pathophysiology of allergic asthma, including (1) deficiency in virus-induced interferon responses, (2) defective epithelial barrier function, (3) increased release of epithelium-derived cytokines (e.g., thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, IL-33), (4) dysregulation of lymphocytes [e.g., innate lymphoid cells (ILCs), regulatory T cells (Tregs)], and (5) altered activation of purinergic receptors. One or more of these processes may provide targets for new therapeutics to treat allergic asthma and prevent disease exacerbation.

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

PubMed Central

Kim, Hyo Jung; Cha, Jiyoung Y.; Seok, Jo Woon; Choi, Yoonjeong; Yoon, Bo Kyung; Choi, Hyeonjin; Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Lee, Hyemin; Kim, Daeun; Han, Ji Yoon; Kim, Jae-woo

2016-01-01

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223–276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis. PMID:27345868

Defining the cause of skewed X-chromosome inactivation in X-linked mental retardation by use of a mouse model.

PubMed

Muers, Mary R; Sharpe, Jacqueline A; Garrick, David; Sloane-Stanley, Jacqueline; Nolan, Patrick M; Hacker, Terry; Wood, William G; Higgs, Douglas R; Gibbons, Richard J

2007-06-01

Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female population but is observed frequently in carriers of some X-linked mutations. Recently, it has been shown that various forms of X-linked mental retardation (XLMR) have a strong association with skewed XCI in female carriers, but the mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by mutations in a ubiquitously expressed, chromatin-associated protein, provides a clear example of XLMR in which phenotypically normal female carriers virtually all have highly skewed XCI biased against the X chromosome that harbors the mutant allele. Here, we have used a mouse model to understand the processes causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found that XCI is balanced early in embryogenesis but becomes skewed over the course of development, because of selection favoring cells expressing the wild-type Atrx allele. Unexpectedly, selection does not appear to be the result of general cellular-viability defects in Atrx-deficient cells, since it is restricted to specific stages of development and is not ongoing throughout the life of the animal. Instead, there is evidence that selection results from independent tissue-specific effects. This illustrates an important mechanism by which skewed XCI may occur in carriers of XLMR and provides insight into the normal role of ATRX in regulating cell fate.

Metabolome of human gut microbiome is predictive of host dysbiosis.

PubMed

Larsen, Peter E; Dai, Yang

2015-01-01

Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome's interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome-host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

Metabolome of human gut microbiome is predictive of host dysbiosis

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

Larsen, Peter E.; Dai, Yang

Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent onmore » its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

Metabolome of human gut microbiome is predictive of host dysbiosis

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

Larsen, Peter E.; Dai, Yang

Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependentmore » on its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

Metabolome of human gut microbiome is predictive of host dysbiosis

DOE PAGES

Larsen, Peter E.; Dai, Yang

2015-09-14

Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent onmore » its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

Simulation of Delamination Propagation in Composites Under High-Cycle Fatigue by Means of Cohesive-Zone Models

NASA Technical Reports Server (NTRS)

Turon, Albert; Costa, Josep; Camanho, Pedro P.; Davila, Carlos G.

2006-01-01

A damage model for the simulation of delamination propagation under high-cycle fatigue loading is proposed. The basis for the formulation is a cohesive law that links fracture and damage mechanics to establish the evolution of the damage variable in terms of the crack growth rate dA/dN. The damage state is obtained as a function of the loading conditions as well as the experimentally-determined coefficients of the Paris Law crack propagation rates for the material. It is shown that by using the constitutive fatigue damage model in a structural analysis, experimental results can be reproduced without the need of additional model-specific curve-fitting parameters.

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

PubMed

Henrickson, Sarah E; Manne, Sasikanth; Dolfi, Douglas V; Mansfield, Kathleen D; Parkhouse, Kaela; Mistry, Rakesh D; Alpern, Elizabeth R; Hensley, Scott E; Sullivan, Kathleen E; Coffin, Susan E; Wherry, E John

2018-01-09

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Effect of microwave-enhanced superconductivity in YBa2Cu3O7 Bi-crystalline grain bounda ry weak-links

NASA Technical Reports Server (NTRS)

Fu, C. M.; Chen, C. M.; Lin, H. C.; Wu, K. H.; Juang, J. Y.; Uen, T. M.; Gou, Y. S.

1995-01-01

We have studied systematically the effect of microwave irradiation on the temperature dependent resistivity (R(I) and the current-voltage (I-V) characteristics of YBa2Gu3O(7 - x) (YBCO) bicrystalline grain boundary weak-links (GBWL's), with grain boundary of three different tilt angles. The superconducting transition temperature, T(sub c), has significant enhancement upon microwave irradiation. The microwave enhanced T(sub c) is increased as a function of incident microwave power, but limited to an optimum power level. The GBWL's of 45 deg tilt boundary has shown to be most sensitive to the microwave irradiation power, and the GBWL's of 36.8 deg tilt boundary has displayed a moderate response. In contrast, no enhancement of T(sub c) was observed in the GBWL's of 24 deg tilt boundary, as well as in the uniform films. Under the microwave irradiation, the R(T) dependent is hystertic as the transition taken from superconducting state to normal state and vice versa. Mechanisms associated with the redistribution of nonequilibrium quasiparticles under microwave irradiation are discussed.

Cell protein cross-linking by erbstatin and related compounds | Center for Cancer Research

Cancer.gov

The scheme depicts a possible mechanism of cross-linking by erbstatin and related analogues. A mechanism of action is proposed which involves initial oxidation to reactive quinone intermediates that subsequently cross-link protein nucleophiles via multiple 1,4-Michael-type additions. Similar alkylation of protein by protein-tyrosine kinase inhibitors, such as herbimycin A, has

Durability and mechanical properties of silane cross-linked wood thermoplastic composites

Treesearch

Magnus Bengtsson; Nicole M. Stark; Kristiina Oksman

2007-01-01

In this study, silane cross-linked wood–polyethylene composite profiles were manufactured by reactive extrusion. These composites were evaluated regarding their durability and mechanical properties in comparison with two non-cross-linked wood– polyethylene composites. An addition of only 2% w/w of silane solution during manufacturing was enough to achieve almost 60%...

Bulk chlorine uptake by polyamide active layers of thin-film composite membranes upon exposure to free chlorine-kinetics, mechanisms, and modeling.

PubMed

Powell, Joshua; Luh, Jeanne; Coronell, Orlando

2014-01-01

We studied the volume-averaged chlorine (Cl) uptake into the bulk region of the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine. Volume-averaged measurements were obtained using Rutherford backscattering spectrometry with samples prepared at a range of free chlorine concentrations, exposure times, and mixing, rinsing, and pH conditions. Our volume-averaged measurements complement previous studies that have quantified Cl uptake at the active layer surface (top ≈ 7 nm) and advance the mechanistic understanding of Cl uptake by aromatic polyamide active layers. Our results show that surface Cl uptake is representative of and underestimates volume-averaged Cl uptake under acidic conditions and alkaline conditions, respectively. Our results also support that (i) under acidic conditions, N-chlorination followed by Orton rearrangement is the dominant Cl uptake mechanism with N-chlorination as the rate-limiting step; (ii) under alkaline conditions, N-chlorination and dechlorination of N-chlorinated amide links by hydroxyl ion are the two dominant processes; and (iii) under neutral pH conditions, the rates of N-chlorination and Orton rearrangement are comparable. We propose a kinetic model that satisfactorily describes Cl uptake under acidic and alkaline conditions, with the largest discrepancies between model and experiment occurring under alkaline conditions at relatively high chlorine exposures.

Study of thermal aging effects on the conduction and trapping of charges in XLPE cable insulations under electron beam irradiation

NASA Astrophysics Data System (ADS)

Boukezzi, L.; Rondot, S.; Jbara, O.; Boubakeur, A.

2018-08-01

The effect of thermal aging on the charging phenomena in cross-linked polyethylene (XLPE) has been studied under electron beam irradiation in scanning electron microscope (SEM). The dynamic variation of trapped charge represents the trapping process of XLPE under electron beam irradiation. We have found that the trapped charge variation can be approximated by a first order exponential function. The amount of trapped charge presents enhanced values at the beginning of aging at lower temperatures (80 °C and 100 °C). This suggests the diffusion of cross-linking by-products to the surface of sample that acts as traps for injected electrons. The oxidation which is a very important form of XLPE degradation has an effect at the advanced stage of the aging process. For higher temperatures (120 °C and 140 °C), the taken part process in the evolution of the trapped charge is the crystallinity increase at the beginning of aging leading to the trapped charge decreasing, and the polar groups generated by thermo-oxidation process at the end of aging leading to the trapped charge increase. Variations of leakage current according to the aging time have quite similar trends with the dielectric losses factor and consequently some correlations must be made between charging mechanisms and the electrical behaviour of XLPE under thermal aging.

Ultralow stress, thermally stable cross-linked polymer films of polydivinylbenzene (PDVB)

DOE PAGES

Lepro, Xavier; Ehrmann, Paul; Menapace, Joseph; ...

2017-05-10

Although closely related to polystyrene, poly(divinylbenzene) (PDVB) has found limited utility due to the difficulties associated with its synthesis. As a highly cross-linked polymer, PDVB is infusible and insoluble and thus nearly impossible to shape into films by either melt or solvent-based processes. Here, we report the initiated chemical vapor deposition (iCVD) of nearly stress-free, highly transparent, free-standing films of PDVB up to 25 μm thick. Films initially grow under tensile intrinsic stress but become more compressive with thickness and eventually converge to zero-stress values once they reach ≥10 μm in thickness. Upon initial heating, the evaporative loss of unreactedmore » monomer left in the polymer matrix induces between 35 and 45 MPa of tensile stress in the films. Afterward, subsequent heating cycles induce reversible stress and film expansion behaviors. We estimate the degree of cross-linking to be 44%, resulting in high thermal stability (up to 300 °C) and mechanical stiffness (Young’s modulus of 5.2 GPa). As a result, the low stress combined with high cross-linking makes iCVD PDVB an excellent candidate for protective coatings in harsh environments.« less

Ultralow stress, thermally stable cross-linked polymer films of polydivinylbenzene (PDVB)

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

Lepro, Xavier; Ehrmann, Paul; Menapace, Joseph

Although closely related to polystyrene, poly(divinylbenzene) (PDVB) has found limited utility due to the difficulties associated with its synthesis. As a highly cross-linked polymer, PDVB is infusible and insoluble and thus nearly impossible to shape into films by either melt or solvent-based processes. Here, we report the initiated chemical vapor deposition (iCVD) of nearly stress-free, highly transparent, free-standing films of PDVB up to 25 μm thick. Films initially grow under tensile intrinsic stress but become more compressive with thickness and eventually converge to zero-stress values once they reach ≥10 μm in thickness. Upon initial heating, the evaporative loss of unreactedmore » monomer left in the polymer matrix induces between 35 and 45 MPa of tensile stress in the films. Afterward, subsequent heating cycles induce reversible stress and film expansion behaviors. We estimate the degree of cross-linking to be 44%, resulting in high thermal stability (up to 300 °C) and mechanical stiffness (Young’s modulus of 5.2 GPa). As a result, the low stress combined with high cross-linking makes iCVD PDVB an excellent candidate for protective coatings in harsh environments.« less

Mechanical Strength Improvements of Carbon Nanotube Threads through Epoxy Cross-Linking

PubMed Central

Yu, Qingyue; Alvarez, Noe T.; Miller, Peter; Malik, Rachit; Haase, Mark R.; Schulz, Mark; Shanov, Vesselin; Zhu, Xinbao

2016-01-01

Individual Carbon Nanotubes (CNTs) have a great mechanical strength that needs to be transferred into macroscopic fiber assemblies. One approach to improve the mechanical strength of the CNT assemblies is by creating covalent bonding among their individual CNT building blocks. Chemical cross-linking of multiwall CNTs (MWCNTs) within the fiber has significantly improved the strength of MWCNT thread. Results reported in this work show that the cross-linked thread had a tensile strength six times greater than the strength of its control counterpart, a pristine MWCNT thread (1192 MPa and 194 MPa, respectively). Additionally, electrical conductivity changes were observed, revealing 2123.40 S·cm−1 for cross-linked thread, and 3984.26 S·cm−1 for pristine CNT thread. Characterization suggests that the obtained high tensile strength is due to the cross-linking reaction of amine groups from ethylenediamine plasma-functionalized CNT with the epoxy groups of the cross-linking agent, 4,4-methylenebis(N,N-diglycidylaniline). PMID:28787868

Worry processes in patients with persecutory delusions.

PubMed

Startup, Helen; Pugh, Katherine; Dunn, Graham; Cordwell, Jacinta; Mander, Helen; Černis, Emma; Wingham, Gail; Shirvell, Katherine; Kingdon, David; Freeman, Daniel

2016-11-01

Worry may be common in patients with paranoia and a contributory causal factor in the occurrence of the delusions. A number of psychological mechanisms have been linked to the occurrence of worry in emotional disorders but these are yet to be investigated in psychosis. The primary aim of the study was to test the links between five main worry mechanisms - perseverative thinking, catastrophizing, stop rules, metacognitive beliefs, and intolerance of uncertainty - and the cognitive style of worry in patients with persecutory delusions. One hundred and fifty patients with persecutory delusions completed assessments of paranoia, worry, and worry mechanisms. Worry in patients with psychosis was associated with the following: a perseverative thinking style, an 'as many as can' stop rule, a range of metacognitive beliefs (cognitive confidence, worry as uncontrollable and the need to control thoughts), and intolerance of uncertainty. Higher levels of worry were associated with higher levels of paranoia. There was also evidence that intolerance of uncertainty and the metacognitive belief concerning the need to control thoughts were independently associated with paranoia. Worry in patients with persecutory delusions may well be understood by similar underlying mechanisms as worry in emotional disorders. This supports the use of interventions targeting worry, suitably modified, for patients with psychosis. Worry is a significant concern for patients with paranoia Worry in paranoia is likely to be caused by similar mechanisms as worry in emotional disorders The results support the recent trial findings that standard techniques for treating worry in anxiety, suitably modified, are applicable for patients with paranoia LIMITATIONS: The findings are limited by the self-report nature of measures and by the study design which precludes any assumptions about the direction of causality between the psychological mechanisms and worry. © 2016 The British Psychological Society.

Multiscale characteristics of mechanical and mineralogical heterogeneity using nanoindentation and Maps Mineralogy in Mancos Shale

NASA Astrophysics Data System (ADS)

Yoon, H.; Mook, W. M.; Dewers, T. A.

2017-12-01

Multiscale characteristics of textural and compositional (e.g., clay, cement, organics, etc.) heterogeneity profoundly influence the mechanical properties of shale. In particular, strongly anisotropic (i.e., laminated) heterogeneities are often observed to have a significant influence on hydrological and mechanical properties. In this work, we investigate a sample of the Cretaceous Mancos Shale to explore the importance of lamination, cements, organic content, and the spatial distribution of these characteristics. For compositional and structural characterization, the mineralogical distribution of thin core sample polished by ion-milling is analyzed using QEMSCAN® with MAPS MineralogyTM (developed by FEI Corporoation). Based on mineralogy and organic matter distribution, multi-scale nanoindentation testing was performed to directly link compositional heterogeneity to mechanical properties. With FIB-SEM (3D) and high-magnitude SEM (2D) images, key nanoindentation patterns are analyzed to evaluate elastic and plastic responses. Combined with MAPs Mineralogy data and fine-resolution BSE images, nanoindentation results are explained as a function of compositional and structural heterogeneity. Finite element modeling is used to quantitatively evaluate the link between the heterogeneity and mechanical behavior during nanoindentation. In addition, the spatial distribution of compositional heterogeneity, anisotropic bedding patterns, and mechanical anisotropy are employed as inputs for multiscale brittle fracture simulations using a phase field model. Comparison of experimental and numerical simulations reveal that proper incorporation of additional material information, such as bedding layer thickness and other geometrical attributes of the microstructures, may yield improvements on the numerical predictions of the mesoscale fracture patterns and hence the macroscopic effective toughness. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525.

Mechanistic Insights into the Efficacy of Sodium Bicarbonate Supplementation to Improve Athletic Performance.

PubMed

Siegler, Jason C; Marshall, Paul W M; Bishop, David; Shaw, Greg; Green, Simon

2016-12-01

A large proportion of empirical research and reviews investigating the ergogenic potential of sodium bicarbonate (NaHCO 3 ) supplementation have focused predominately on performance outcomes and only speculate about underlying mechanisms responsible for any benefit. The aim of this review was to critically evaluate the influence of NaHCO 3 supplementation on mechanisms associated with skeletal muscle fatigue as it translates directly to exercise performance. Mechanistic links between skeletal muscle fatigue, proton accumulation (or metabolic acidosis) and NaHCO 3 supplementation have been identified to provide a more targeted, evidence-based approach to direct future research, as well as provide practitioners with a contemporary perspective on the potential applications and limitations of this supplement. The mechanisms identified have been broadly categorised under the sections 'Whole-body Metabolism', 'Muscle Physiology' and 'Motor Pathways', and when possible, the performance outcomes of these studies contextualized within an integrative framework of whole-body exercise where other factors such as task demand (e.g. large vs. small muscle groups), cardio-pulmonary and neural control mechanisms may outweigh any localised influence of NaHCO 3 . Finally, the 'Performance Applications' section provides further interpretation for the practitioner founded on the mechanistic evidence provided in this review and other relevant, applied NaHCO 3 performance-related studies.

Internet Addiction and Psychosocial Maladjustment: Avoidant Coping and Coping Inflexibility as Psychological Mechanisms.

PubMed

Cheng, Cecilia; Sun, Peizhen; Mak, Kwok-Kei

2015-09-01

This 6 month prospective study systematically tested some multivariate models that advanced the understanding of the psychological mechanisms underlying Internet addiction and psychosocial maladjustment. On the basis of previous theories, avoidant coping and coping inflexibility were proposed as underlying mechanisms. Participants were 271 Chinese undergraduates (75% women, Mage=20.49) who took part in both phases of this study. Structural equation modeling was performed to obtain the best fit models for both the cross-sectional and the prospective data. The cross-sectional model testing revealed statistically significant mediating effects for both avoidant coping (β=0.149 [95% CI 0.071-0.226], p=0.002) and coping flexibility (β=0.048 [95% CI 0.013-0.081], p=0.032). The prospective model testing further showed that avoidant coping mediated the relationship between Internet addiction and Time 2 psychosocial maladjustment (β=0.141 [95% CI 0.065-0.216], p=0.005), as well as that between coping flexibility and Time 2 psychosocial maladjustment (β=-0.096 [95% CI -0.161 to -0.031], p=0.015). This study was the first to establish theory-driven models, which unveiled an inflexible, avoidant coping style as psychological mechanisms that explained the link between Internet addiction and psychosocial maladjustment.

Mechanism of deoxynivalenol effects on the reproductive system and fetus malformation: Current status and future challenges.

PubMed

Yu, Miao; Chen, Liangkai; Peng, Zhao; Nüssler, Andreas K; Wu, Qinghua; Liu, Liegang; Yang, Wei

2017-06-01

Deoxynivalenol (DON) is a toxic fungal secondary metabolite produced by molds of the Fusarium genus, and it is known to cause a spectrum of diseases both in humans and animals, such as emesis, diarrhea, anorexia, immunotoxicity, hematological disorders, impairment of maternal reproduction, and fetal development. The recently revealed teratogenic potential of DON has received much attention. In various animal models, it has been shown that DON led to skeletal deformities of the fetus. However, the underlying mechanisms are not yet fully understood, and toxicological data are also scarce. Several animal research studies highlight the potential link between morphological abnormalities and changes of autophagy in the reproductive system. Because autophagy is involved in fetal development, maintenance of placental function, and bone remodeling, this mechanism has become a high priority for future research. The general aim of the present review is to deliver a comprehensive overview of the current state of knowledge of DON-induced reproductive toxicity in different animal models and to provide some prospective ideas for further research. The focus of the current review is to summarize toxic and negative effects of DON exposure on the reproductive system and the potential underlying molecular mechanisms in various animal models. Copyright © 2017 Elsevier B.V. All rights reserved.

Gut microbiota alterations and dietary modulation in childhood malnutrition - The role of short chain fatty acids.

PubMed

Pekmez, Ceyda Tugba; Dragsted, Lars Ove; Brahe, Lena Kirchner

2018-02-17

The gut microbiome affects the health status of the host through different mechanisms and is associated with a wide variety of diseases. Both childhood undernutrition and obesity are linked to alterations in composition and functionality of the gut microbiome. One of the possible mechanisms underlying the interplay between microbiota and host metabolism is through appetite-regulating hormones (including leptin, ghrelin, glucagon-like peptide-1). Short chain fatty acids, the end product of bacterial fermentation of non-digestible carbohydrates, might be able to alter energy harvest and metabolism through enteroendocrine cell signaling, adipogenesis and insulin-like growth factor-1 production. Elucidating these mechanisms may lead to development of new modulation practices of the gut microbiota as a potential prevention and treatment strategy for childhood malnutrition. The present overview will briefly outline the gut microbiota development in the early life, gut microbiota alterations in childhood undernutrition and obesity, and whether this relationship is causal. Further we will discuss possible underlying mechanisms in relation to the gut-brain axis and short chain fatty acids, and the potential of probiotics, prebiotics and synbiotics for modulating the gut microbiota during childhood as a prevention and treatment strategy against undernutrition and obesity. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Epigenetic Effects of Cadmium in Cancer: Focus on Melanoma

PubMed Central

Venza, Mario; Visalli, Maria; Biondo, Carmelo; Oteri, Rosaria; Agliano, Federica; Morabito, Silvia; Caruso, Gerardo; Caffo, Maria; Teti, Diana; Venza, Isabella

2014-01-01

Cadmium is a highly toxic heavy metal, which has a destroying impact on organs. Exposure to cadmium causes severe health problems to human beings due to its ubiquitous environmental presence and features of the pathologies associated with pro-longed exposure. Cadmium is a well-established carcinogen, although the underlying mechanisms have not been fully under-stood yet. Recently, there has been considerable interest in the impact of this environmental pollutant on the epigenome. Be-cause of the role of epigenetic alterations in regulating gene expression, there is a potential for the integration of cadmium-induced epigenetic alterations as critical elements in the cancer risk assessment process. Here, after a brief review of the ma-jor diseases related to cadmium exposure, we focus our interest on the carcinogenic potential of this heavy metal. Among the several proposed pathogenetic mechanisms, particular attention is given to epigenetic alterations, including changes in DNA methylation, histone modifications and non-coding RNA expression. We review evidence for a link between cadmium-induced epigenetic changes and cell transformation, with special emphasis on melanoma. DNA methylation, with reduced expression of key genes that regulate cell proliferation and apoptosis, has emerged as a possible cadmium-induced epigenetic mechanism in melanoma. A wider comprehension of mechanisms related to this common environmental contaminant would allow a better cancer risk evaluation. PMID:25646071

Dietary protein intake and quality in early life: impact on growth and obesity.

PubMed

Lind, Mads V; Larnkjær, Anni; Mølgaard, Christian; Michaelsen, Kim F

2017-01-01

Obesity is an increasing problem and high-protein intake early in life seems to increase later risk of obesity. This review summarizes recent publications in the area including observational and intervention studies and publications on underlying mechanisms. Recent observational and randomized controlled trials confirmed that high-protein intake in early life seems to increase early weight gain and the risk of later overweight and obesity. Recent studies have looked at the effect of different sources of protein, and especially high-animal protein intake seems to have an effect on obesity. Specific amino acids, such as leucine, have also been implicated in increasing later obesity risk maybe via specific actions on insulin-like growth factor I. Furthermore, additional underlying mechanisms including epigenetics have been linked to long-term obesogenic programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved and the role of different dietary protein sources and amino acids has increased, but intervention studies are needed to confirm the mechanisms. Avoiding high-protein intake in early life holds promise as a preventive strategy for childhood obesity.

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

(Finite) statistical size effects on compressive strength.

PubMed

Weiss, Jérôme; Girard, Lucas; Gimbert, Florent; Amitrano, David; Vandembroucq, Damien

2014-04-29

The larger structures are, the lower their mechanical strength. Already discussed by Leonardo da Vinci and Edmé Mariotte several centuries ago, size effects on strength remain of crucial importance in modern engineering for the elaboration of safety regulations in structural design or the extrapolation of laboratory results to geophysical field scales. Under tensile loading, statistical size effects are traditionally modeled with a weakest-link approach. One of its prominent results is a prediction of vanishing strength at large scales that can be quantified in the framework of extreme value statistics. Despite a frequent use outside its range of validity, this approach remains the dominant tool in the field of statistical size effects. Here we focus on compressive failure, which concerns a wide range of geophysical and geotechnical situations. We show on historical and recent experimental data that weakest-link predictions are not obeyed. In particular, the mechanical strength saturates at a nonzero value toward large scales. Accounting explicitly for the elastic interactions between defects during the damage process, we build a formal analogy of compressive failure with the depinning transition of an elastic manifold. This critical transition interpretation naturally entails finite-size scaling laws for the mean strength and its associated variability. Theoretical predictions are in remarkable agreement with measurements reported for various materials such as rocks, ice, coal, or concrete. This formalism, which can also be extended to the flowing instability of granular media under multiaxial compression, has important practical consequences for future design rules.

The localization of nuclear exporters of the importin-beta family is regulated by Snf1 kinase, nutrient supply and stress.

PubMed

Quan, XinXin; Yu, Jennifer; Bussey, Howard; Stochaj, Ursula

2007-07-01

In the budding yeast Saccharomyces cerevisiae, four members of the importin-beta family of nuclear carriers, Xpo1p/Crm1p, Cse1p, Msn5p and Los1p, function as exporters of protein and tRNA. Under normal growth conditions GFP-tagged exporters are predominantly associated with nuclei. The presence of Snf1 kinase, a key regulator of cell growth and a metabolic sensor, controls the localization of GFP-exporters. Additional glucose-dependent, but Snf1-independent, mechanisms regulate carrier distribution and a switch from fermentable to non-fermentable carbon sources relocates all of the carriers, suggesting a link to the nutritional status of the cell. Moreover, stress controls the proper localization of GFP-exporters, which mislocalize upon exposure to heat, ethanol and starvation. Stress may activate the MAPK cell integrity cascade, and we tested the role of this pathway in exporter localization. Under non-stress conditions, the proper distribution of GFP-Cse1p and Xpo1p/Crm1p-GFP requires kinases of the cell integrity cascade. By contrast, Msn5p-GFP and Los1p-GFP rely on the MAPK module to relocate to the cytoplasm when cells are stressed with ethanol. Our results indicate that the association of nuclear exporters with nuclei is controlled by multiple mechanisms that are organized in a hierarchical fashion and linked to the physiological state of the cell.

Incidence of pancreatic cancer is dramatically increased by a high fat, high calorie diet in KrasG12D mice.

PubMed

Chang, Hui-Hua; Moro, Aune; Takakura, Kazuki; Su, Hsin-Yuan; Mo, Allen; Nakanishi, Masako; Waldron, Richard T; French, Samuel W; Dawson, David W; Hines, O Joe; Li, Gang; Go, Vay Liang W; Sinnett-Smith, James; Pandol, Stephen J; Lugea, Aurelia; Gukovskaya, Anna S; Duff, Michael O; Rosenberg, Daniel W; Rozengurt, Enrique; Eibl, Guido

2017-01-01

Epidemiologic data has linked obesity to a higher risk of pancreatic cancer, but the underlying mechanisms are poorly understood. To allow for detailed mechanistic studies in a relevant model mimicking diet-induced obesity and pancreatic cancer, a high-fat, high-calorie diet (HFCD) was given to P48+/Cre;LSL-KRASG12D (KC) mice carrying a pancreas-specific oncogenic Kras mutation. The mice were randomly allocated to a HFCD or control diet (CD). Cohorts were sacrificed at 3, 6, and 9 months and tissues were harvested for further analysis. Compared to CD-fed mice, HFCD-fed animals gained significantly more weight. Importantly, the cancer incidence was remarkably increased in HFCD-fed KC mice, particularly in male KC mice. In addition, KC mice fed the HFCD showed more extensive inflammation and fibrosis, and more advanced PanIN lesions in the pancreas, compared to age-matched CD-fed animals. Interestingly, we found that the HFCD reduced autophagic flux in PanIN lesions in KC mice. Further, exome sequencing of isolated murine PanIN lesions identified numerous genetic variants unique to the HFCD. These data underscore the role of sustained inflammation and dysregulated autophagy in diet-induced pancreatic cancer development and suggest that diet-induced genetic alterations may contribute to this process. Our findings provide a better understanding of the mechanisms underlying the obesity-cancer link in males and females, and will facilitate the development of interventions targeting obesity-associated pancreatic cancer.

Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

PubMed Central

Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

2016-01-01

The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

Glycosylation Is a Major Regulator of Phenylpropanoid Availability and Biological Activity in Plants

PubMed Central

Le Roy, Julien; Huss, Brigitte; Creach, Anne; Hawkins, Simon; Neutelings, Godfrey

2016-01-01

The phenylpropanoid pathway in plants is responsible for the biosynthesis of a huge amount of secondary metabolites derived from phenylalanine and tyrosine. Both flavonoids and lignins are synthesized at the end of this very diverse metabolic pathway, as well as many intermediate molecules whose precise biological functions remain largely unknown. The diversity of these molecules can be further increased under the action of UDP-glycosyltransferases (UGTs) leading to the production of glycosylated hydroxycinnamates and related aldehydes, alcohols and esters. Glycosylation can change phenylpropanoid solubility, stability and toxic potential, as well as influencing compartmentalization and biological activity. (De)-glycosylation therefore represents an extremely important regulation point in phenylpropanoid homeostasis. In this article we review recent knowledge on the enzymes involved in regulating phenylpropanoid glycosylation status and availability in different subcellular compartments. We also examine the potential link between monolignol glycosylation and lignification by exploring co-expression of lignin biosynthesis genes and phenolic (de)glycosylation genes. Of the different biological roles linked with their particular chemical properties, phenylpropanoids are often correlated with the plant's stress management strategies that are also regulated by glycosylation. UGTs can for instance influence the resistance of plants during infection by microorganisms and be involved in the mechanisms related to environmental changes. The impact of flavonoid glycosylation on the color of flowers, leaves, seeds and fruits will also be discussed. Altogether this paper underlies the fact that glycosylation and deglycosylation are powerful mechanisms allowing plants to regulate phenylpropanoid localisation, availability and biological activity. PMID:27303427

Modeling dynamic interactions and coherence between marine zooplankton and fishes linked to environmental variability

NASA Astrophysics Data System (ADS)

Liu, Hui; Fogarty, Michael J.; Hare, Jonathan A.; Hsieh, Chih-hao; Glaser, Sarah M.; Ye, Hao; Deyle, Ethan; Sugihara, George

2014-03-01

The dynamics of marine fishes are closely related to lower trophic levels and the environment. Quantitatively understanding ecosystem dynamics linking environmental variability and prey resources to exploited fishes is crucial for ecosystem-based management of marine living resources. However, standard statistical models typically grounded in the concept of linear system may fail to capture the complexity of ecological processes. We have attempted to model ecosystem dynamics using a flexible, nonparametric class of nonlinear forecasting models. We analyzed annual time series of four environmental indices, 22 marine copepod taxa, and four ecologically and commercially important fish species during 1977 to 2009 on Georges Bank, a highly productive and intensively studied area of the northeast U.S. continental shelf ecosystem. We examined the underlying dynamic features of environmental indices and copepods, quantified the dynamic interactions and coherence with fishes, and explored the potential control mechanisms of ecosystem dynamics from a nonlinear perspective. We found: (1) the dynamics of marine copepods and environmental indices exhibiting clear nonlinearity; (2) little evidence of complex dynamics across taxonomic levels of copepods; (3) strong dynamic interactions and coherence between copepods and fishes; and (4) the bottom-up forcing of fishes and top-down control of copepods coexisting as target trophic levels vary. These findings highlight the nonlinear interactions among ecosystem components and the importance of marine zooplankton to fish populations which point to two forcing mechanisms likely interactively regulating the ecosystem dynamics on Georges Bank under a changing environment.

Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity.

PubMed

Gu, Yuxin; Yang, Yu; Wan, Bin; Li, Minjie; Guo, Liang-Hong

2018-06-01

Organophosphate flame retardants (OPFRs), as alternatives of brominated flame retardants, can cause neurodevelopmental effects similar to organophosphate pesticides. However, the molecular mechanisms underlying the toxicity remain elusive. O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates numerous neural processes through the O-GlcNAcylation modification of nuclear and cytoplasmic proteins. In this study, we aimed to investigate the molecular mechanisms accounting for the developmental neurotoxicity of OPFRs by identifying potential targets of OPFRs and the attendant effects. Twelve OPFRs were evaluated for inhibition of OGT activity using an electrochemical biosensor. Their potency differed with substituent groups. The alkyl group substituted OPFRs had no inhibitory effect. Instead, the six OPFRs substituted with aromatic or chlorinated alkyl groups inhibited OGT activity significantly, with tri-m-cresyl phosphate (TCrP) being the strongest. The six OPFRs (0-100 μM exposure) also inhibited OGT activity in PC12 cells and decreased protein O-GlcNAcylation level. Inhibition of OGT by OPFRs might be involved in the subsequent toxic effects, including intracellular reactive oxygen species (ROS), calcium level, as well as cell proliferation and autophagy. Molecular docking of the OGT/OPFR complexes provided rationales for the difference in their structure-dependent inhibition potency. Our findings may provide a new biological target of OPFRs in their neurotoxicological actions, which might be a major molecular mechanism of OPFRs developmental neurotoxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulation of Food Intake, Energy Balance, and Body Fat Mass: Implications for the Pathogenesis and Treatment of Obesity

PubMed Central

Guyenet, Stephan J.

2012-01-01

Context: Obesity has emerged as one of the leading medical challenges of the 21st century. The resistance of this disorder to effective, long-term treatment can be traced to the fact that body fat stores are subject to homeostatic regulation in obese individuals, just as in lean individuals. Because the growing obesity epidemic is linked to a substantial increase in daily energy intake, a key priority is to delineate how mechanisms governing food intake and body fat content are altered in an obesogenic environment. Evidence Acquisition: We considered all relevant published research and cited references that represented the highest quality evidence available. Where space permitted, primary references were cited. Evidence Synthesis: The increase of energy intake that has fueled the U.S. obesity epidemic is linked to greater availability of highly rewarding/palatable and energy-dense food. Obesity occurs in genetically susceptible individuals and involves the biological defense of an elevated body fat mass, which may result in part from interactions between brain reward and homeostatic circuits. Inflammatory signaling, accumulation of lipid metabolites, or other mechanisms that impair hypothalamic neurons may also contribute to the development of obesity and offer a plausible mechanism to explain the biological defense of elevated body fat mass. Conclusions: Despite steady research progress, mechanisms underlying the resistance to fat loss once obesity is established remain incompletely understood. Breakthroughs in this area may be required for the development of effective new obesity prevention and treatment strategies. PMID:22238401

Hormone-mediated maternal effects in birds: mechanisms matter but what do we know of them?

PubMed

Groothuis, Ton G G; Schwabl, Hubert

2008-05-12

Over the past decade, birds have proven to be excellent models to study hormone-mediated maternal effects in an evolutionary framework. Almost all these studies focus on the function of maternal steroid hormones for offspring development, but lack of knowledge about the underlying mechanisms hampers further progress. We discuss several hypotheses concerning these mechanisms, point out their relevance for ecological and evolutionary interpretations, and review the relevant data. We first examine whether maternal hormones can accumulate in the egg independently of changes in hormone concentrations in the maternal circulation. This is important for Darwinian selection and female physiological trade-offs, and possible mechanisms for hormone accumulation in the egg, which may differ among hormones, are reviewed. Although independent regulation of plasma and yolk concentrations of hormones is conceivable, the data are as yet inconclusive for ovarian hormones. Next, we discuss embryonic utilization of maternal steroids, since enzyme and receptor systems in the embryo may have coevolved with maternal effect mechanisms in the mother. We consider dose-response relationships and action pathways of androgens and argue that these considerations may help to explain the apparent lack of interference of maternal steroids with sexual differentiation. Finally, we discuss mechanisms underlying the pleiotropic actions of maternal steroids, since linked effects may influence the coevolution of parent and offspring traits, owing to their role in the mediation of physiological trade-offs. Possible mechanisms here are interactions with other hormonal systems in the embryo. We urge endocrinologists to embark on suggested mechanistic studies and behavioural ecologists to adjust their interpretations to accommodate the current knowledge of mechanisms.

Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system.

PubMed

Gomes, Clarissa P C; de Gonzalo-Calvo, David; Toro, Rocio; Fernandes, Tiago; Theisen, Daniel; Wang, Da-Zhi; Devaux, Yvan

2018-05-23

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Single-Dose Testosterone Administration Impairs Cognitive Reflection in Men.

PubMed

Nave, Gideon; Nadler, Amos; Zava, David; Camerer, Colin

2017-10-01

In nonhumans, the sex steroid testosterone regulates reproductive behaviors such as fighting between males and mating. In humans, correlational studies have linked testosterone with aggression and disorders associated with poor impulse control, but the neuropsychological processes at work are poorly understood. Building on a dual-process framework, we propose a mechanism underlying testosterone's behavioral effects in humans: reduction in cognitive reflection. In the largest study of behavioral effects of testosterone administration to date, 243 men received either testosterone or placebo and took the Cognitive Reflection Test (CRT), which estimates the capacity to override incorrect intuitive judgments with deliberate correct responses. Testosterone administration reduced CRT scores. The effect remained after we controlled for age, mood, math skills, whether participants believed they had received the placebo or testosterone, and the effects of 14 additional hormones, and it held for each of the CRT questions in isolation. Our findings suggest a mechanism underlying testosterone's diverse effects on humans' judgments and decision making and provide novel, clear, and testable predictions.

Dyslipidemia in Dermatological Disorders

PubMed Central

Shenoy, Chetana; Shenoy, Manjunath Mala; Rao, Gururaja K.

2015-01-01

Dyslipidemias are one of the common metabolic disorders. A link between dermatological disorders like psoriasis and dyslipidemia has been established in the recent past. Many dermatological disorders could have a systemic inflammatory component which explains such association. Chronic inflammatory dermatological disorders could also have other metabolic imbalances that may contribute to dyslipidemia. Presence of such abnormal metabolism may justify routine screening of these disorders for associated dyslipidemia and other metabolic abnormalities and early treatment of such comorbidities to improve quality of life. Some of the drugs used by dermatologists such as retinoids are also likely to be a cause of dyslipidemia. Hence, it is imperative that the dermatologists obtain scientific knowledge on the underlying mechanisms involved in dyslipidemia and understand when to intervene with therapies. A systematic review of the English language literature was done by using Google Scholar and PubMed. In this review, attempts are made to list the dermatological disorders associated with dyslipidemia; to simplify the understanding of underlying mechanisms; and to give a brief idea about the interventions. PMID:26713286

Strain response of thermal barrier coatings captured under extreme engine environments through synchrotron X-ray diffraction

NASA Astrophysics Data System (ADS)

Knipe, Kevin; Manero, Albert; Siddiqui, Sanna F.; Meid, Carla; Wischek, Janine; Okasinski, John; Almer, Jonathan; Karlsson, Anette M.; Bartsch, Marion; Raghavan, Seetha

2014-07-01

The mechanical behaviour of thermal barrier coatings in operation holds the key to understanding durability of jet engine turbine blades. Here we report the results from experiments that monitor strains in the layers of a coating subjected to thermal gradients and mechanical loads representing extreme engine environments. Hollow cylindrical specimens, with electron beam physical vapour deposited coatings, were tested with internal cooling and external heating under various controlled conditions. High-energy synchrotron X-ray measurements captured the in situ strain response through the depth of each layer, revealing the link between these conditions and the evolution of local strains. Results of this study demonstrate that variations in these conditions create corresponding trends in depth-resolved strains with the largest effects displayed at or near the interface with the bond coat. With larger temperature drops across the coating, significant strain gradients are seen, which can contribute to failure modes occurring within the layer adjacent to the interface.

Neural and computational processes underlying dynamic changes in self-esteem

PubMed Central

Rutledge, Robb B; Moutoussis, Michael; Dolan, Raymond J

2017-01-01

Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an ‘interpersonal vulnerability’ dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability. PMID:29061228

Neural and computational processes underlying dynamic changes in self-esteem.

PubMed

Will, Geert-Jan; Rutledge, Robb B; Moutoussis, Michael; Dolan, Raymond J

2017-10-24

Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an 'interpersonal vulnerability' dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability.

An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity.

PubMed

Lovelace, Jonathan W; Corches, Alex; Vieira, Philip A; Hiroto, Alex S; Mackie, Ken; Korzus, Edward

2015-12-01

Cannabis continues to be the most accessible and popular illicit recreational drug. Whereas current data link adolescence cannabinoid exposure to increased risk for dependence on other drugs, depression, anxiety disorders and psychosis, the mechanism(s) underlying these adverse effects remains controversial. Here we show in a mouse model of female adolescent cannabinoid exposure deficient endocannabinoid (eCB)-mediated signaling and presynaptic forms of long-term depression at adult central glutamatergic synapses in the prefrontal cortex. Increasing endocannabinoid levels by blockade of monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG), with the specific inhibitor JZL 184 ameliorates eCB-LTD deficits. The observed deficit in cortical presynaptic signaling may represent a neural maladaptation underlying network instability and abnormal cognitive functioning. Our study suggests that adolescent cannabinoid exposure may permanently impair brain functions, including the brain's intrinsic ability to appropriately adapt to external influences. Published by Elsevier Ltd.

Chaotic home environment is associated with reduced infant processing speed under high task demands.

PubMed

Tomalski, Przemysław; Marczuk, Karolina; Pisula, Ewa; Malinowska, Anna; Kawa, Rafał; Niedźwiecka, Alicja

2017-08-01

Early adversity has profound long-term consequences for child development across domains. The effects of early adversity on structural and functional brain development were shown for infants under 12 months of life. However, the causal mechanisms of these effects remain relatively unexplored. Using a visual habituation task we investigated whether chaotic home environment may affect processing speed in 5.5 month-old infants (n=71). We found detrimental effects of chaos on processing speed for complex but not for simple visual stimuli. No effects of socio-economic status on infant processing speed were found although the sample was predominantly middle class. Our results indicate that chaotic early environment may adversely affect processing speed in early infancy, but only when greater cognitive resources need to be deployed. The study highlights an attractive avenue for research on the mechanisms linking home environment with the development of attention control. Copyright © 2017 Elsevier Inc. All rights reserved.

An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity

PubMed Central

Lovelace, Jonathan W.; Corches, Alex; Vieira, Philip A.; Mackie, Ken; Korzus, Edward

2015-01-01

Cannabis continues to be the most accessible and popular illicit recreational drug. Whereas current data link adolescence cannabinoid exposure to increased risk for dependence on other drugs, depression, anxiety disorders and psychosis, the mechanism(s) underlying these adverse effects remains controversial. Here we show in a mouse model of female adolescent cannabinoid exposure a deficient endocannabinoid (eCB)-mediated signaling and presynaptic forms of long-term depression at adult central glutamatergic synapses in the prefrontal cortex. Increasing endocannabinoid levels by blockade of monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG), with the specific inhibitor JZL184 ameliorates these deficits. The observed deficit in cortical eCB-dependent signaling may represent a neural maladaptation underlying network instability and abnormal cognitive functioning. Our study suggests that adolescent cannabinoid exposure may permanently impair brain functions, including the brain’s intrinsic ability to appropriately adapt to external influences. PMID:25979486

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.

Longitudinal links between childhood peer acceptance and the neural correlates of sharing.

PubMed

Will, Geert-Jan; Crone, Eveline A; van Lier, Pol A C; Güroğlu, Berna

2018-01-01

Childhood peer acceptance is associated with high levels of prosocial behavior and advanced perspective taking skills. Yet, the neurobiological mechanisms underlying these associations have not been studied. This functional magnetic resonance imaging study examined the neural correlates of sharing decisions in a group of adolescents who had a stable accepted status (n = 27) and a group who had a chronic rejected status (n = 19) across six elementary school grades. Both groups of adolescents played three allocation games in which they could share money with strangers with varying costs and profits to them and the other person. Stably accepted adolescents were more likely to share their money with unknown others than chronically rejected adolescents when sharing was not costly. Neuroimaging analyses showed that stably accepted adolescents, compared to chronically rejected adolescents, exhibited higher levels of activation in the temporo-parietal junction, posterior superior temporal sulcus, temporal pole, pre-supplementary motor area, and anterior insula during costly sharing decisions. These findings demonstrate that stable peer acceptance across childhood is associated with heightened activity in brain regions previously linked to perspective taking and the detection of social norm violations during adolescence, and thereby provide insight into processes underlying the widely established links between peer acceptance and prosocial behavior. © 2016 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Ploidally antagonistic selection maintains stable genetic polymorphism.

PubMed

Immler, Simone; Arnqvist, Göran; Otto, Sarah Perin

2012-01-01

Understanding the maintenance of genetic variation in the face of selection remains a key issue in evolutionary biology. One potential mechanism for the maintenance of genetic variation is opposing selection during the diploid and haploid stages of biphasic life cycles universal among eukaryotic sexual organisms. If haploid and diploid gene expression both occur, selection can act in each phase, potentially in opposing directions. In addition, sex-specific selection during haploid phases is likely simply because male and female gametophytes/gametes tend to have contrasting life histories. We explored the potential for the maintenance of a stable polymorphism under ploidally antagonistic as well as sex-specific selection. Furthermore, we examined the role of the chromosomal location of alleles (autosomal or sex-linked). Our analyses show that the most permissible conditions for the maintenance of polymorphism occur under negative ploidy-by-sex interactions, where stronger selection for an allele in female than male diploids is coupled with weaker selection against the allele in female than male haploids. Such ploidy-by-sex interactions also promote allele frequency differences between the sexes. With constant fitness, ploidally antagonistic selection can maintain stable polymorphisms for autosomal and X-linked genes but not for Y-linked genes. We discuss the implications of our results and outline a number of biological settings where the scenarios modeled may apply. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution.

Controllable synthesis of mesoporous carbon nanospheres and Fe-N/carbon nanospheres as efficient oxygen reduction electrocatalysts.

PubMed

Wei, Jing; Liang, Yan; Zhang, Xinyi; Simon, George P; Zhao, Dongyuan; Zhang, Jin; Jiang, Sanping; Wang, Huanting

2015-04-14

The synthesis of mesoporous carbon nanospheres (MCNs), especially with diameters below 200 nm remains a great challenge due to weak interactions between the carbon precursors and soft templates, as well as the uncontrollable cross-linking rate of carbon precursors. Herein, we demonstrate a simple acid-assisted, hydrothermal synthesis approach to synthesizing such uniform MCNs with well controlled diameters ranging from 20 to 150 nm under highly acidic conditions (2 M HCl). Both the carbon precursor and the template are partly protonated under such conditions and show additional Coulombic interactions with chloride ions (acts as mediators). This kind of enhanced interaction is similar to that of the "I(+)X(-)S(+)" mechanism in the synthesis of mesoporous metal oxide, which can effectively retard the cross-linking rate of resol molecules and avoid macroscopic phase separation during the hydrothermal synthesis. Due to their uniform spherical morphology, small diameter, and high surface areas, MCNs can be modified with Fe and N species via impregnation of cheap precursors (ferric nitrate and dicyandiamide), which are further converted into nonprecious electrocatalysts for oxygen reduction reactions. The resulting Fe-N/MCNs exhibit high catalytic activities, long-term stability and improved methanol tolerance under alkaline conditions, which can be potentially used in direct methanol fuel cells and metal-air batteries.

Microbiology and potential applications of aerobic methane oxidation coupled to denitrification (AME-D) process: A review.

PubMed

Zhu, Jing; Wang, Qian; Yuan, Mengdong; Tan, Giin-Yu Amy; Sun, Faqian; Wang, Cheng; Wu, Weixiang; Lee, Po-Heng

2016-03-01

Aerobic methane oxidation coupled to denitrification (AME-D) is an important link between the global methane and nitrogen cycles. This mini-review updates discoveries regarding aerobic methanotrophs and denitrifiers, as a prelude to spotlight the microbial mechanism and the potential applications of AME-D. Until recently, AME-D was thought to be accomplished by a microbial consortium where denitrifying bacteria utilize carbon intermediates, which are excreted by aerobic methanotrophs, as energy and carbon sources. Potential carbon intermediates include methanol, citrate and acetate. This mini-review presents microbial thermodynamic estimations and postulates that methanol is the ideal electron donor for denitrification, and may serve as a trophic link between methanotrophic bacteria and denitrifiers. More excitingly, new discoveries have revealed that AME-D is not only confined to the conventional synergism between methanotrophic bacteria and denitrifiers. Specifically, an obligate aerobic methanotrophic bacterium, Methylomonas denitrificans FJG1, has been demonstrated to couple partial denitrification with methane oxidation, under hypoxia conditions, releasing nitrous oxide as a terminal product. This finding not only substantially advances the understanding of AME-D mechanism, but also implies an important but unknown role of aerobic methanotrophs in global climate change through their influence on both the methane and nitrogen cycles in ecosystems. Hence, further investigation on AME-D microbiology and mechanism is essential to better understand global climate issues and to develop niche biotechnological solutions. This mini-review also presents traditional microbial techniques, such as pure cultivation and stable isotope probing, and powerful microbial techniques, such as (meta-) genomics and (meta-) transcriptomics, for deciphering linked methane oxidation and denitrification. Although AME-D has immense potential for nitrogen removal from wastewater, drinking water and groundwater, bottlenecks and potential issues are also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early Life Stress and the Anxious Brain: Evidence for A Neural Mechanism Linking Childhood Emotional Maltreatment to Anxiety in Adulthood

PubMed Central

Fonzo, Gregory A.; Ramsawh, Holly J.; Flagan, Taru M.; Simmons, Alan N.; Sullivan, Sarah G.; Allard, Carolyn B.; Paulus, Martin P.; Stein, Murray B.

2016-01-01

Background Childhood emotional maltreatment (CEM) increases likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. Methods One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. Results During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray matter volumes also partially mediated the CEM-anxiety relationship. Conclusions Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes. PMID:26670947

Multiple biological pathways link cognitive lifestyle to protection from dementia.

PubMed

Valenzuela, Michael J; Matthews, Fiona E; Brayne, Carol; Ince, Paul; Halliday, Glenda; Kril, Jillian J; Dalton, Marshall A; Richardson, Kathryn; Forster, Gill; Sachdev, Perminder S

2012-05-01

An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population-based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans. Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 individuals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinically matched individuals with high and low CLS. CLS groups did not differ on several Alzheimer disease neuropathologic measures; however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness. An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Killing mechanism of stable N-halamine cross-linked polymethacrylamide nanoparticles that selectively target bacteria.

PubMed

Natan, Michal; Gutman, Ori; Lavi, Ronit; Margel, Shlomo; Banin, Ehud

2015-02-24

Increased resistance of bacteria to disinfection and antimicrobial treatment poses a serious public health threat worldwide. This has prompted the search for agents that can inhibit both bacterial growth and withstand harsh conditions (e.g., high organic loads). In the current study, N-halamine-derivatized cross-linked polymethacrylamide nanoparticles (NPs) were synthesized by copolymerization of the monomer methacrylamide (MAA) and the cross-linker monomer N,N-methylenebis(acrylamide) (MBAA) and were subsequently loaded with oxidative chlorine using sodium hypochlorite (NaOCl). The chlorinated NPs demonstrated remarkable stability and durability to organic reagents and to repetitive bacterial loading cycles as compared with the common disinfectant NaOCl (bleach), which was extremely labile under these conditions. The antibacterial mechanism of the cross-linked P(MAA-MBAA)-Cl NPs was found to involve generation of reactive oxygen species (ROS) only upon exposure to organic media. Importantly, ROS were not generated upon suspension in water, revealing that the mode of action is target-specific. Further, a unique and specific interaction of the chlorinated NPs with Staphylococcus aureus was discovered, whereby these microorganisms were all specifically targeted and marked for destruction. This bacterial encircling was achieved without using a targeting module (e.g., an antibody or a ligand) and represents a highly beneficial, natural property of the P(MAA-MBAA)-Cl nanostructures. Our findings provide insights into the mechanism of action of P(MAA-MBAA)-Cl NPs and demonstrate the superior efficacy of the NPs over bleach (i.e., stability, specificity, and targeting). This work underscores the potential of developing sustainable P(MAA-MBAA)-Cl NP-based devices for inhibiting bacterial colonization and growth.

Mechanism of self-sterility in a hermaphroditic chordate.

PubMed

Harada, Yoshito; Takagaki, Yuhei; Sunagawa, Masahiko; Saito, Takako; Yamada, Lixy; Taniguchi, Hisaaki; Shoguchi, Eiichi; Sawada, Hitoshi

2008-04-25

Hermaphroditic organisms avoid inbreeding by a system of self-incompatibility (SI). A primitive chordate (ascidian) Ciona intestinalis is an example of such an organism, but the molecular mechanism underlying its SI system is not known. Here, we show that the SI system is governed by two gene loci that act cooperatively. Each locus contains a tightly linked pair of polycystin 1-related receptor (s-Themis) and fibrinogen-like ligand (v-Themis) genes, the latter of which is located in the first intron of s-Themis but transcribed in the opposite direction. These genes may encode male- and female-side self-recognition molecules. The SI system of C. intestinalis has a similar framework to that of flowering plants but utilizing different molecules.

The role of discharge variation in scaling of drainage area and food chain length in rivers

USGS Publications Warehouse

Sabo, John L.; Finlay, Jacques C.; Kennedy, Theodore A.; Post, David M.

2010-01-01

Food chain length (FCL) is a fundamental component of food web structure. Studies in a variety of ecosystems suggest that FCL is determined by energy supply, environmental stability, and/or ecosystem size, but the nature of the relationship between environmental stability and FCL, and the mechanism linking ecosystem size to FCL, remain unclear. Here we show that FCL increases with drainage area and decreases with hydrologic variability and intermittency across 36 North American rivers. Our analysis further suggests that hydrologic variability is the mechanism underlying the correlation between ecosystem size and FCL in rivers. Ecosystem size lengthens river food chains by integrating and attenuating discharge variation through stream networks, thereby enhancing environmental stability in larger river systems.

How Attention Affects Spatial Resolution

PubMed Central

Carrasco, Marisa; Barbot, Antoine

2015-01-01

We summarize and discuss a series of psychophysical studies on the effects of spatial covert attention on spatial resolution, our ability to discriminate fine patterns. Heightened resolution is beneficial in most, but not all, visual tasks. We show how endogenous attention (voluntary, goal driven) and exogenous attention (involuntary, stimulus driven) affect performance on a variety of tasks mediated by spatial resolution, such as visual search, crowding, acuity, and texture segmentation. Exogenous attention is an automatic mechanism that increases resolution regardless of whether it helps or hinders performance. In contrast, endogenous attention flexibly adjusts resolution to optimize performance according to task demands. We illustrate how psychophysical studies can reveal the underlying mechanisms of these effects and allow us to draw linking hypotheses with known neurophysiological effects of attention. PMID:25948640

Carbon in oxides and silicates - Dissolution versus exsolution

NASA Technical Reports Server (NTRS)

Freund, F.

1986-01-01

A theory of CO2 dissolution in the solid state is developed, using the idea proposed by Freund (1983) concerning dissolution of CO/CO2 in MgO on the basis of their experimental results obtained with an MgO-containing carbon impurity. It is shown that the dissolution mechanism may be linked to an internal redox reaction by which a certain number of lattice oxygens change their formal oxidation state from -2 to -1, while the carbon becomes reduced. The similarities between the mechanisms of CO and/or CO2 dissolution and that of H2O dissolution are pointed out. A hypothesis is proposed concerning the exsolution of reduced carbon from supersaturated solid solutions under conditions which permit C-C bond formation.

The role of discharge variation in scaling of drainage area and food chain length in rivers.

PubMed

Sabo, John L; Finlay, Jacques C; Kennedy, Theodore; Post, David M

2010-11-12

Food chain length (FCL) is a fundamental component of food web structure. Studies in a variety of ecosystems suggest that FCL is determined by energy supply, environmental stability, and/or ecosystem size, but the nature of the relationship between environmental stability and FCL, and the mechanism linking ecosystem size to FCL, remain unclear. Here we show that FCL increases with drainage area and decreases with hydrologic variability and intermittency across 36 North American rivers. Our analysis further suggests that hydrologic variability is the mechanism underlying the correlation between ecosystem size and FCL in rivers. Ecosystem size lengthens river food chains by integrating and attenuating discharge variation through stream networks, thereby enhancing environmental stability in larger river systems.

Neurotrophin signaling endosomes; biogenesis, regulation, and functions

PubMed Central

Yamashita, Naoya; Kuruvilla, Rejji

2016-01-01

In the nervous system, communication between neurons and their post-synaptic target cells is critical for the formation, refinement and maintenance of functional neuronal connections. Diffusible signals secreted by target tissues, exemplified by the family of neurotrophins, impinge on nerve terminals to influence diverse developmental events including neuronal survival and axonal growth. Key mechanisms of action of target-derived neurotrophins include the cell biological processes of endocytosis and retrograde trafficking of their Trk receptors from growth cones to cell bodies. In this review, we summarize the molecular mechanisms underlying this endosome-mediated signaling, focusing on the instructive role of neurotrophin signaling itself in directing its own trafficking. Recent studies have linked impaired neurotrophin trafficking to neurodevelopmental disorders, highlighting the relevance of neurotrophin endosomes in human health. PMID:27327126

Overlapping memory trace indispensable for linking, but not recalling, individual memories.

PubMed

Yokose, Jun; Okubo-Suzuki, Reiko; Nomoto, Masanori; Ohkawa, Noriaki; Nishizono, Hirofumi; Suzuki, Akinobu; Matsuo, Mina; Tsujimura, Shuhei; Takahashi, Yukari; Nagase, Masashi; Watabe, Ayako M; Sasahara, Masakiyo; Kato, Fusao; Inokuchi, Kaoru

2017-01-27

Memories are not stored in isolation from other memories but are integrated into associative networks. However, the mechanisms underlying memory association remain elusive. Using two amygdala-dependent behavioral paradigms-conditioned taste aversion (CTA) and auditory-cued fear conditioning (AFC)-in mice, we found that presenting the conditioned stimulus used for the CTA task triggered the conditioned response of the AFC task after natural coreactivation of the memories. This was accompanied through an increase in the overlapping neuronal ensemble in the basolateral amygdala. Silencing of the overlapping ensemble suppressed CTA retrieval-induced freezing. However, retrieval of the original CTA or AFC memory was not affected. A small population of coshared neurons thus mediates the link between memories. They are not necessary for recalling individual memories. Copyright © 2017, American Association for the Advancement of Science.

Cognitive control, cognitive reserve, and memory in the aging bilingual brain

PubMed Central

Grant, Angela; Dennis, Nancy A.; Li, Ping

2014-01-01

In recent years bilingualism has been linked to both advantages in executive control and positive impacts on aging. Such positive cognitive effects of bilingualism have been attributed to the increased need for language control during bilingual processing and increased cognitive reserve, respectively. However, a mechanistic explanation of how bilingual experience contributes to cognitive reserve is still lacking. The current paper proposes a new focus on bilingual memory as an avenue to explore the relationship between executive control and cognitive reserve. We argue that this focus will enhance our understanding of the functional and structural neural mechanisms underlying bilingualism-induced cognitive effects. With this perspective we discuss and integrate recent cognitive and neuroimaging work on bilingual advantage, and suggest an account that links cognitive control, cognitive reserve, and brain reserve in bilingual aging and memory. PMID:25520695

Experiment definition phase shuttle laboratory LDRL-10.6 experiment

NASA Technical Reports Server (NTRS)

1975-01-01

This report for the Experiment Definition Phase of the Shuttle Laboratory LDRL 10.6 Micrometer Experiment covers period 27 June through 26 September 1975. Activities during the fifth quarter included: (1) reevaluation of system obscuration ratio with a subsequent reduction of this ratio from 0.417 to 0.362, (2) completion of detail drawings for the 6X pre-expander, (3) completion of detail drawings for the nine mirrors that comprise pointing and tracking optomechanical subsystem, (4) continuation of detailing of mechanical portions of CMSS and modifications to accommodate new obscuration ratio, (5) qualitative operation of the optomechanical subsystem of the 10.6 um receiver achieved under experiment measurement task; receiver fully integrated and operation demonstrated over a 10 km experimental link, and (6) data collection task initiated to begin preparation of link analysis volumes.

Maternal emotional feeding practices and adolescent daughters' emotional eating: Mediating roles of avoidant and preoccupied coping.

PubMed

Goldstein, Miriam; Tan, Cin Cin; Chow, Chong Man

2017-09-01

The current study examined the link between early childhood emotional feeding and adolescent girls' emotional eating, using maladaptive coping styles as the underlying mechanisms mediating these associations. We examined adolescent girls' and mothers' retrospective reports of emotional feeding during childhood, as well as adolescent girls' current reports of their coping behaviors (i.e., preoccupied and avoidant) and emotional eating. Findings showed that adolescent girls' and mothers' retrospective reports of early emotional feeding were positively associated with adolescent girls' emotional eating. Preoccupied coping, but not avoidant coping, mediated the associations between early emotional feeding (reported by adolescents and mothers) and adolescents' current emotional eating. In conclusion, findings suggest that early childhood feeding experiences are linked to the development of maladaptive coping and emotional eating among adolescent girls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.