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

Mechanisms Linking the Gut Microbiome and Glucose Metabolism

PubMed Central

Kratz, Mario; Damman, Chris J.; Hullarg, Meredith

2016-01-01

Context: Type 2 diabetes mellitus is associated with gastrointestinal dysbiosis involving both compositional and functional changes in the gut microbiome. Changes in diet and supplementation with probiotics and prebiotics (ie, fermentable fibers) can induce favorable changes in gut bacterial species and improve glucose homeostasis. Objective: This paper will review the data supporting several potential mechanisms whereby gut dysbiosis contributes to metabolic dysfunction, including microbiota driven increases in systemic lipopolysaccharide concentrations, changes in bile acid metabolism, alterations in short chain fatty acid production, alterations in gut hormone secretion, and changes in circulating branched-chain amino acids. Methods: Data for this review were identified by searching English language references from PubMed and relevant articles. Conclusions: Understanding the mechanisms linking the gut microbiome to glucose metabolism, and the relevant compositional and functional characteristics of the gut microbiome, will help direct future research to develop more targeted approaches or novel compounds aimed at restoring a more healthy gut microbiome as a new approach to prevent and treat type 2 diabetes mellitus and related metabolic conditions. PMID:26938201

Interpersonal mechanisms linking close relationships to health.

PubMed

Pietromonaco, Paula R; Collins, Nancy L

2017-09-01

Close relationships play a vital role in human health, but much remains to be learned about specific mechanisms of action and potential avenues for intervention. This article provides an evaluation of research on close relationships processes relevant to health, drawing on themes from major relationship science theories to present a broad conceptual framework for understanding the interpersonal processes and intrapersonal pathways linking relationships to health and disease outcomes. The analysis reveals that both social connection and social disconnection broadly shape biological responses and behaviors that are consequential for health. Furthermore, emerging work offers insights into the types of social dynamics that are most consequential for health, and the potential pathways through which they operate. Following from this analysis, the authors suggest several research priorities to facilitate the translation of discoveries from relationship science into relationship-based interventions and public health initiatives. These priorities include developing finer grained theoretical models to guide research, the systematic investigation of potential mediating pathways such as dyadic influences on health behavior and physiological coregulation, and taking into account individual differences and contextual factors such as attachment style, gender, socioeconomic status, and culture. In addition, a pressing need exists for laboratory and field research to determine which types of interventions are both practical and effective. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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...

Investigating the work-family conflict and health link: Repetitive thought as a mechanism.

PubMed

Davis, Kelly D; Gere, Judith; Sliwinski, Martin J

2017-10-01

Research is needed to investigate mechanisms linking work-family conflict to poor health in working adults. We took a novel approach to build on extant studies by testing a potential mechanism in these associations - repetitive thought. Data came from a sample of 203 partnered working adults. There were significant direct effects of work-family conflict with lower life satisfaction, positive affect, and perceived health as well as greater fatigue. As for total effects, work-family conflict was significantly associated with all health outcomes - life satisfaction, positive affect, negative affect, fatigue, perceived health, and chronic health conditions - in the expected directions through repetitive thought. This study provides support that repetitive thought is one potential mechanism of how work-family conflict can take a toll on psychological and physical health. Findings are discussed in relation to improving workplace policies to improve the health of working adults managing work-family conflict. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Linking traumatic brain injury to chronic traumatic encephalopathy: identification of potential mechanisms leading to neurofibrillary tangle development.

PubMed

Lucke-Wold, Brandon Peter; Turner, Ryan Coddington; Logsdon, Aric Flint; Bailes, Julian Edwin; Huber, Jason Delwyn; Rosen, Charles Lee

2014-07-01

Significant attention has recently been drawn to the potential link between head trauma and the development of neurodegenerative disease, namely chronic traumatic encephalopathy (CTE). The acute neurotrauma associated with sports-related concussions in athletes and blast-induced traumatic brain injury in soldiers elevates the risk for future development of chronic neurodegenerative diseases such as CTE. CTE is a progressive disease distinguished by characteristic tau neurofibrillary tangles (NFTs) and, occasionally, transactive response DNA binding protein 43 (TDP43) oligomers, both of which have a predilection for perivascular and subcortical areas near reactive astrocytes and microglia. The disease is currently only diagnosed postmortem by neuropathological identification of NFTs. A recent workshop sponsored by National Institute of Neurological Disorders and Stroke emphasized the need for premortem diagnosis, to better understand disease pathophysiology and to develop targeted treatments. In order to accomplish this objective, it is necessary to discover the mechanistic link between acute neurotrauma and the development of chronic neurodegenerative and neuropsychiatric disorders such as CTE. In this review, we briefly summarize what is currently known about CTE development and pathophysiology, and subsequently discuss injury-induced pathways that warrant further investigation. Understanding the mechanistic link between acute brain injury and chronic neurodegeneration will facilitate the development of appropriate diagnostic and therapeutic options for CTE and other related disorders.

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

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical, Physical, and Mechanical Characterization of Isocyanate Cross-linked Amine-Modified Silica Aerogels

NASA Technical Reports Server (NTRS)

Katti, Atul; Shimpi, Nilesh; Roy, Samit; Lu, Hongbing; Fabrizio, Eve F.; Dass, Amala; Capadona, Lynn A.; Leventis, Nicholas

2006-01-01

We describe a new mechanically strong lightweight porous composite material obtained by encapsulating the skeletal framework of amine-modified silica aerogels with polyurea. The conformal polymer coating preserves the mesoporous structure of the underlying silica framework and the thermal conductivity remains low at 0.041 plus or minus 0.001 W m(sup -1 K(sup -1). The potential of the new cross-linked silica aerogels for load-carrying applications was determined through characterization of their mechanical behavior under compression, three-point bending, and dynamic mechanical analysis (DMA). A primary glass transition temperature of 130 C was identified through DMA. At room temperature, results indicate a hyperfoam behavior where in compression cross-linked aerogels are linearly elastic under small strains (less than 4%) and then exhibit yield behavior (until 40% strain), followed by densification and inelastic hardening. At room temperature the compressive Young's modulus and the Poisson's ratio were determined to be 129 plus or minus 8 MPa and 0.18, respectively, while the strain at ultimate failure is 77% and the average specific compressive stress at ultimate failure is 3.89 x 10(exp 5) N m kg(sup -1). The specific flexural strength is 2.16 x 10(exp 4) N m kg(sup -1). Effects on the compressive behavior of strain rate and low temperature were also evaluated.

Linking Mechanisms of Work-Family Conflict and Segmentation

ERIC Educational Resources Information Center

Michel, Jesse S.; Hargis, Michael B.

2008-01-01

Despite the abundance of work and family research, few studies have compared the linking mechanisms specified in theoretical models of work-family conflict and segmentation. Accordingly, the current study provides a greater degree of empirical clarity concerning the interplay of work and family by directly examining the indirect effects of…

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

PubMed Central

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

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.

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%...

Cardiovascular reactivity as a mechanism linking child trauma to adolescent psychopathology

PubMed Central

Heleniak, Charlotte; McLaughlin, Katie A.; Ormel, Johan; Riese, Harriette

2016-01-01

Alterations in physiological reactivity to stress are argued to be central mechanisms linking adverse childhood environmental experiences to internalizing and externalizing psychopathology. Childhood trauma exposure may influence physiological reactivity to stress in distinct ways from other forms of childhood adversity. This study applied a novel theoretical model to investigate the impact of childhood trauma on cardiovascular stress reactivity – the biopsychosocial model of challenge and threat. This model suggests that inefficient cardiovascular responses to stress – a threat as opposed to challenge profile – are characterized by blunted cardiac output (CO) reactivity and increased vascular resistance. We examined whether childhood trauma exposure predicted an indicator of the threat profile of cardiovascular reactivity and whether such a pattern was associated with adolescent psychopathology in a population-representative sample of 488 adolescents (M = 16.17 years old, 49.2% boys) in the TRacking Adolescents’ Individual Lives Survey (TRAILS). Exposure to trauma was associated with both internalizing and externalizing symptoms and a pattern of cardiovascular reactivity consistent with the threat profile, including blunted CO reactivity during a social stress task. Blunted CO reactivity, in turn, was positively associated with externalizing, but not internalizing symptoms and mediated the link between trauma and externalizing psychopathology. None of these associations varied by gender. The biopsychosocial model of challenge and threat provides a novel theoretical framework for understanding disruptions in physiological reactivity to stress following childhood trauma exposure, revealing a potential pathway linking such exposure with externalizing problems in adolescents. PMID:27568327

The Link between Suicide and Insomnia: Theoretical Mechanisms

PubMed Central

Black, Carmen G.

2013-01-01

Insomnia has been established as a risk factor for depression and mental illness for decades, but a growing body of evidence has recently exposed insomnia to be an independent risk factor for suicide that encompasses all age ranges. This discovery has invigorated investigation to elucidate the relationship between insomnia and suicide, and over 20 studies reinforcing this association in adults have been published since 2010 alone. This article analyzes relevant research and emphasizes studies published within the last three years with the intent of proposing theoretical mechanisms explaining the link between suicide and insomnia. These mechanisms may then be used as targets for future investigation of treatment. PMID:23949486

Gaussian effective potential: Quantum mechanics

NASA Astrophysics Data System (ADS)

Stevenson, P. M.

1984-10-01

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

Mechanism linking T-wave alternans to the genesis of cardiac fibrillation.

PubMed

Pastore, J M; Girouard, S D; Laurita, K R; Akar, F G; Rosenbaum, D S

1999-03-16

Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear. -T-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209+/-46 bpm) that was significantly lower (by 57+/-36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular repolarization. Above a critical HR, membrane repolarization alternated with the opposite phase between neighboring cells (ie, discordant alternans), creating large spatial gradients of repolarization. In the presence of discordant alternans, a small acceleration of pacing cycle length produced a characteristic sequence of events: (1) unidirectional block of an impulse propagating against steep gradients of repolarization, (2) reentrant propagation, and (3) the initiation of ventricular fibrillation. Repolarization alternans at the level of the single cell accounts for T-wave alternans on the surface ECG. Discordant alternans produces spatial gradients of repolarization of sufficient magnitude to cause unidirectional block and reentrant ventricular fibrillation. These data establish a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death.

Cardiovascular reactivity as a mechanism linking child trauma to adolescent psychopathology.

PubMed

Heleniak, Charlotte; McLaughlin, Katie A; Ormel, Johan; Riese, Harriette

2016-10-01

Alterations in physiological reactivity to stress are argued to be central mechanisms linking adverse childhood environmental experiences to internalizing and externalizing psychopathology. Childhood trauma exposure may influence physiological reactivity to stress in distinct ways from other forms of childhood adversity. This study applied a novel theoretical model to investigate the impact of childhood trauma on cardiovascular stress reactivity - the biopsychosocial model of challenge and threat. This model suggests that inefficient cardiovascular responses to stress - a threat as opposed to challenge profile - are characterized by blunted cardiac output (CO) reactivity and increased vascular resistance. We examined whether childhood trauma exposure predicted an indicator of the threat profile of cardiovascular reactivity and whether such a pattern was associated with adolescent psychopathology in a population-representative sample of 488 adolescents (M=16.17years old, 49.2% boys) in the TRacking Adolescents' Individual Lives Survey (TRAILS). Exposure to trauma was associated with both internalizing and externalizing symptoms and a pattern of cardiovascular reactivity consistent with the threat profile, including blunted CO reactivity during a social stress task. Blunted CO reactivity, in turn, was positively associated with externalizing, but not internalizing symptoms and mediated the link between trauma and externalizing psychopathology. None of these associations varied by gender. The biopsychosocial model of challenge and threat provides a novel theoretical framework for understanding disruptions in physiological reactivity to stress following childhood trauma exposure, revealing a potential pathway linking such exposure with externalizing problems in adolescents. Copyright © 2016 Elsevier B.V. All rights reserved.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

Linking Mechanics and Statistics in Epidermal Tissues

NASA Astrophysics Data System (ADS)

Kim, Sangwoo; Hilgenfeldt, Sascha

2015-03-01

Disordered cellular structures, such as foams, polycrystals, or living tissues, can be characterized by quantitative measurements of domain size and topology. In recent work, we showed that correlations between size and topology in 2D systems are sensitive to the shape (eccentricity) of the individual domains: From a local model of neighbor relations, we derived an analytical justification for the famous empirical Lewis law, confirming the theory with experimental data from cucumber epidermal tissue. Here, we go beyond this purely geometrical model and identify mechanical properties of the tissue as the root cause for the domain eccentricity and thus the statistics of tissue structure. The simple model approach is based on the minimization of an interfacial energy functional. Simulations with Surface Evolver show that the domain statistics depend on a single mechanical parameter, while parameter fluctuations from cell to cell play an important role in simultaneously explaining the shape distribution of cells. The simulations are in excellent agreement with experiments and analytical theory, and establish a general link between the mechanical properties of a tissue and its structure. The model is relevant to diagnostic applications in a variety of animal and plant tissues.

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

PubMed

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

2017-11-01

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

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.

Potential of commercial microwave link network derived rainfall for river runoff simulations

NASA Astrophysics Data System (ADS)

Smiatek, Gerhard; Keis, Felix; Chwala, Christian; Fersch, Benjamin; Kunstmann, Harald

2017-03-01

Commercial microwave link networks allow for the quantification of path integrated precipitation because the attenuation by hydrometeors correlates with rainfall between transmitter and receiver stations. The networks, operated and maintained by cellphone companies, thereby provide completely new and country wide precipitation measurements. As the density of traditional precipitation station networks worldwide is significantly decreasing, microwave link derived precipitation estimates receive increasing attention not only by hydrologists but also by meteorological and hydrological services. We investigate the potential of microwave derived precipitation estimates for streamflow prediction and water balance analyses, exemplarily shown for an orographically complex region in the German Alps (River Ammer). We investigate the additional value of link derived rainfall estimations combined with station observations compared to station and weather radar derived values. Our river runoff simulation system employs a distributed hydrological model at 100 × 100 m grid resolution. We analyze the potential of microwave link derived precipitation estimates for two episodes of 30 days with typically moderate river flow and an episode of extreme flooding. The simulation results indicate the potential of this novel precipitation monitoring method: a significant improvement in hydrograph reproduction has been achieved in the extreme flooding period that was characterized by a large number of local strong precipitation events. The present rainfall monitoring gauges alone were not able to correctly capture these events.

Inflammatory Mechanisms Linking Periodontal Diseases to Cardiovascular Diseases

PubMed Central

Schenkein, Harvey A.; Loos, Bruno G.

2015-01-01

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

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.

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

PubMed

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

2015-03-01

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

Nonlinear optical collagen cross-linking and mechanical stiffening: a possible photodynamic therapeutic approach to treating corneal ectasia

PubMed Central

Chai, Dongyul; Juhasz, Tibor; Brown, Donald J.

2013-01-01

Abstract. In this study we test the hypothesis that nonlinear optical (NLO) multiphoton photoactivation of riboflavin using a focused femtosecond (FS) laser light can be used to induce cross-linking (CXL) and mechanically stiffen collagen as a potential clinical therapy for the treatment of keratoconus and corneal ectasia. Riboflavin-soaked, compressed collagen hydrogels are cross-linked using a FS laser tuned to 760 nm and set to either 100 mW (NLO CXL I) or 150 mW (NLO CXL II) of laser power. FS pulses are focused into the hydrogel using a 0.75 NA objective lens, and the hydrogel is three-dimensionally scanned. Measurement of hydrogel stiffness by indentation testing show that the calculated elastic modulus (E) values are significantly increased over twofold following NLO CXL I and II compared with baseline values (P<0.05). Additionally, no significant differences are detected between NLO CXL and single photon, UVA CXL (P>0.05). This data suggests that NLO CXL has a comparable effect to conventional UVA CXL in mechanically stiffening collagen and may provide a safe and effective approach to localize CXL at different regions and depths within the cornea. PMID:23515869

Children's Attentional Biases and "5-HTTLPR" Genotype: Potential Mechanisms Linking Mother and Child Depression

ERIC Educational Resources Information Center

Gibb, Brandon E.; Benas, Jessica S.; Grassia, Marie; McGeary, John

2009-01-01

In this study, we examined the roles of specific cognitive (attentional bias) and genetic ("5-HTTLPR") risk factors in the intergenerational transmission of depression. Focusing first on the link between maternal history of major depressive disorder (MDD) and children's attentional biases, we found that children of mothers with a history…

Potential fluid mechanic pathways of platelet activation.

PubMed

Shadden, Shawn C; Hendabadi, Sahar

2013-06-01

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

Potential fluid mechanic pathways of platelet activation

PubMed Central

Shadden, Shawn C.; Hendabadi, Sahar

2012-01-01

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

The Mechanisms Linking Health Literacy to Behavior and Health Status

PubMed Central

Osborn, Chandra Y.; Paasche-Orlow, Michael K.; Bailey, Stacy Cooper; Wolf, Michael S.

2011-01-01

Objective To examine the mechanisms linking health literacy to physical activity and self-reported health. Methods From 2005–2007, patients (N=330) with hypertension were recruited from safety net clinics. Path analytic models tested the pathways linking health literacy to physical activity and self-reported health. Results There were significant paths from health literacy to knowledge (r=0.22, P<0.001), knowledge to self-efficacy (r=0.13, P<0.01), self-efficacy to physical activity (r=0.17, P<0.01), and physical activity to health status (r=0.17, P<0.01). Conclusions Health education interventions should be literacy sensitive and aim to enhance patient health knowledge and self-efficacy to promote self-care behavior and desirable health outcomes. PMID:20950164

A General Bioinspired, Metals-Based Synergic Cross-Linking Strategy toward Mechanically Enhanced Materials.

PubMed

Chen, Ke; Ding, Jin; Zhang, Shuhao; Tang, Xuke; Yue, Yonghai; Guo, Lin

2017-03-28

Creating lightweight engineering materials combining high strength and great toughness remains a significant challenge. Despite possessing-enhanced strength and stiffness, bioinspired/polymeric materials usually suffer from clearly reduced extensibility and toughness when compared to corresponding bulk polymer materials. Herein, inspired by tiny amounts of various inorganic impurities for mechanical improvement in natural materials, we present a versatile and effective metal ion (M n+ )-based synergic cross-linking (MSC) strategy incorporating eight types of metal ions into material bulks that can drastically enhance the tensile strength (∼24.1-70.8%), toughness (∼18.6-110.1%), modulus (∼21.6-66.7%), and hardness (∼6.4-176.5%) of multiple types of pristine materials (from hydrophilic to hydrophobic and from unary to binary). More importantly, we also explore the primarily elastic-plastic deformation mechanism and brittle fracture behavior (indentation strain of >5%) of the synergic cross-linked graphene oxide (Syn-GO) paper by means of in situ nanoindentation SEM. The MSC strategy for mechanically enhanced integration can be readily attributed to the formation of the complicated metals-based cross-linking/complex networks in the interfaces and intermolecules between functional groups of materials and various metal ions that give rise to efficient energy dissipation. This work suggests a promising MSC strategy for designing advanced materials with outstanding mechanical properties by adding low amounts (<1.0 wt %) of synergic metal ions serving as synergic ion-bonding cross-linkers.

Time with friends and physical activity as mechanisms linking obesity and television viewing among youth.

PubMed

Vandewater, Elizabeth A; Park, Seoung Eun; Hébert, Emily T; Cummings, Hope M

2015-07-27

Though bivariate relationships between childhood obesity, physical activity, friendships and television viewing are well documented, empirical assessment of the extent to which links between obesity and television may be mediated by these factors is scarce. This study examines the possibility that time with friends and physical activity are potential mechanisms linking overweight/obesity to television viewing in youth. Data were drawn from children ages 10-18 years old (M = 13.81, SD = 2.55) participating in the 2002 wave of Child Development Supplement (CDS) to the Panel Study of Income Dynamics (PSID) (n = 1,545). Data were collected both directly and via self-report from children and their parents. Path analysis was employed to examine a model whereby the relationships between youth overweight/obesity and television viewing were mediated by time spent with friends and moderate-to-vigorous physical activity (MVPA). Overweight/obesity was directly related to less time spent with friends, but not to MVPA. Time spent with friends was directly and positively related to MVPA, and directly and negatively related to time spent watching television without friends. In turn, MVPA was directly and negatively related to watching television without friends. There were significant indirect effects of both overweight/obesity and time with friends on television viewing through MVPA, and of overweight/obesity on MVPA through time with friends. Net of any indirect effects, the direct effect of overweight/obesity on television viewing remained. The final model fit the data extremely well (χ2 = 5.77, df = 5, p<0.0001, RMSEA = 0.01, CFI = 0.99, TLI =0.99). We found good evidence that the positive relationships between time with friends and physical activity are important mediators of links between overweight/obesity and television viewing in youth. These findings highlight the importance of moving from examinations of bivariate relationships between weight status and television

Time with friends and physical activity as mechanisms linking obesity and television viewing among youth

PubMed Central

2015-01-01

Background Though bivariate relationships between childhood obesity, physical activity, friendships and television viewing are well documented, empirical assessment of the extent to which links between obesity and television may be mediated by these factors is scarce. This study examines the possibility that time with friends and physical activity are potential mechanisms linking overweight/obesity to television viewing in youth. Methods Data were drawn from children ages 10-18 years old (M = 13.81, SD = 2.55) participating in the 2002 wave of Child Development Supplement (CDS) to the Panel Study of Income Dynamics (PSID) (n = 1,545). Data were collected both directly and via self-report from children and their parents. Path analysis was employed to examine a model whereby the relationships between youth overweight/obesity and television viewing were mediated by time spent with friends and moderate-to-vigorous physical activity (MVPA). Results Overweight/obesity was directly related to less time spent with friends, but not to MVPA. Time spent with friends was directly and positively related to MVPA, and directly and negatively related to time spent watching television without friends. In turn, MVPA was directly and negatively related to watching television without friends. There were significant indirect effects of both overweight/obesity and time with friends on television viewing through MVPA, and of overweight/obesity on MVPA through time with friends. Net of any indirect effects, the direct effect of overweight/obesity on television viewing remained. The final model fit the data extremely well (χ2 = 5.77, df = 5, p<0.0001, RMSEA = 0.01, CFI = 0.99, TLI =0.99). Conclusions We found good evidence that the positive relationships between time with friends and physical activity are important mediators of links between overweight/obesity and television viewing in youth. These findings highlight the importance of moving from examinations of bivariate relationships

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.

Continuum mechanical model for cross-linked actin networks with contractile bundles

NASA Astrophysics Data System (ADS)

Ferreira, J. P. S.; Parente, M. P. L.; Natal Jorge, R. M.

2018-01-01

In the context of a mechanical approach to cell biology, there is a close relationship between cellular function and mechanical properties. In recent years, an increasing amount of attention has been given to the coupling between biochemical and mechanical signals by means of constitutive models. In particular, on the active contractility of the actin cytoskeleton. Given the importance of the actin contraction on the physiological functions, this study propose a constitutive model to describe how the filamentous network controls its mechanics actively. Embedded in a soft isotropic ground substance, the network behaves as a viscous mechanical continuum, comprised of isotropically distributed cross-linked actin filaments and actomyosin bundles. Trough virtual rheometry experiments, the present model relates the dynamics of the myosin motors with the network stiffness, which is to a large extent governed by the time-scale of the applied deformations/forces.

Mechanisms linking brain insulin resistance to Alzheimer's disease

PubMed Central

Matioli, Maria Niures P.S.; Nitrini, Ricardo

2015-01-01

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

Cell therapy for basement membrane-linked diseases.

PubMed

Nyström, Alexander; Bornert, Olivier; Kühl, Tobias

2017-01-01

For most disorders caused by mutations in genes encoding basement membrane (BM) proteins, there are at present only limited treatment options available. Genetic BM-linked disorders can be viewed as especially suited for treatment with cell-based therapy approaches because the proteins that need to be restored are located in the extracellular space. In consequence, complete and permanent engraftment of cells does not necessarily have to occur to achieve substantial causal therapeutic effects. For these disorders cells can be used as transient vehicles for protein replacement. In addition, it is becoming evident that BM-linked genetic disorders are modified by secondary diseases mechanisms. Cell-based therapies have also the ability to target such disease modifying mechanisms. Thus, cell therapies can simultaneously provide causal treatment and symptomatic relief, and accordingly hold great potential for treatment of BM-linked disorders. However, this potential has for most applications and diseases so far not been realized. Here, we will present the state of cell therapies for BM-linked diseases. We will discuss use of both pluripotent and differentiated cells, the limitation of the approaches, their challenges, and the way forward to potential wider implementation of cell therapies in the clinics. Copyright © 2016 Elsevier B.V. All rights reserved.

Barium-cross-linked alginate-gelatine microcapsule as a potential platform for stem cell production and modular tissue formation.

PubMed

Alizadeh Sardroud, Hamed; Nemati, Sorour; Baradar Khoshfetrat, Ali; Nabavinia, Mahbobeh; Beygi Khosrowshahi, Younes

2017-08-01

Influence of gelatine concentration and cross-linker ions of Ca 2+ and Ba 2+ was evaluated on characteristics of alginate hydrogels and proliferation behaviours of model adherent and suspendable stem cells of fibroblast and U937 embedded in alginate microcapsules. Increasing gelatine concentration to 2.5% increased extent of swelling to 15% and 25% for barium- and calcium-cross-linked hydrogels, respectively. Mechanical properties also decreased with increasing swelling of hydrogels. Both by increasing gelatine concentration and using barium ions increased considerably the proliferation of encapsulated model stem cells. Barium-cross-linked alginate-gelatine microcapsule tested for bone building block showed a 13.5 ± 1.5-fold expansion for osteoblast cells after 21 days with deposition of bone matrix. The haematopoietic stem cells cultured in the microcapsule after 7 days also showed up to 2-fold increase without adding any growth factor. The study demonstrates that barium-cross-linked alginate-gelatine microcapsule has potential for use as a simple and efficient 3D platform for stem cell production and modular tissue formation.

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

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

Dynamic Analysis and Control of Lightweight Manipulators with Flexible Parallel Link Mechanisms. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Lee, Jeh Won

1990-01-01

The objective 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. The resulting equation of motion have a structure which is useful to reduce the number of terms calculated, to check correctness, or to extend the model to higher order. 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. Elastic motion is expressed by the assumed mode method. Mode shape functions of each link are chosen using the load interfaced component mode synthesis. The discrepancies between the analytical model and the experiment are explained using a simplified and a detailed finite element model.

Psychosocial mechanisms linking the social environment to mental health in African Americans

USDA-ARS?s Scientific Manuscript database

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African Amer...

Tuning chemical and physical cross-links in silk electrogels for morphological analysis and mechanical reinforcement.

PubMed

Lin, Yinan; Xia, Xiaoxia; Shang, Ke; Elia, Roberto; Huang, Wenwen; Cebe, Peggy; Leisk, Gary; Omenetto, Fiorenzo; Kaplan, David L

2013-08-12

Electrochemically controlled, reversible assembly of biopolymers into hydrogel structures is a promising technique for on-demand cell or drug encapsulation and release systems. An electrochemically sol-gel transition has been demonstrated in regenerated Bombyx mori silk fibroin, offering a controllable way to generate biocompatible and reversible adhesives and other biomedical materials. Despite the involvement of an electrochemically triggered electrophoretic migration of the silk molecules, the mechanism of the reversible electrogelation remains unclear. It is, however, known that the freshly prepared silk electrogels (e-gels) adopt a predominantly random coil conformation, indicating a lack of cross-linking as well as thermal, mechanical, and morphological stabilities. In the present work, the tuning of covalent and physical β-sheet cross-links in silk hydrogels was studied for programming the structural properties. Scanning electron microscopy (SEM) revealed delicate morphology, including locally aligned fibrillar structures, in silk e-gels, preserved by combining glutaraldehyde-cross-linking and ethanol dehydration. Fourier transform infrared (FTIR) spectroscopic analysis of either electrogelled, vortex-induced or spontaneously formed silk hydrogels showed that the secondary structure of silk e-gels was tunable between non-β-sheet-dominated and β-sheet-dominated states. Dynamic oscillatory rheology confirmed the mechanical reinforcement of silk e-gels provided by controlled chemical and physical cross-links. The selective incorporation of either chemical or physical or both cross-links into the electrochemically responsive, originally unstructured silk e-gel should help in the design for electrochemically responsive protein polymers.

Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and Autism

PubMed Central

Hertz-Picciotto, Irva; Pessah, Isaac N.

2012-01-01

Background: Autism spectrum disorders (ASDs) have been increasing in many parts of the world and a portion of cases are attributable to environmental exposures. Conclusive replicated findings have yet to appear on any specific exposure; however, mounting evidence suggests gestational pesticides exposures are strong candidates. Because multiple developmental processes are implicated in ASDs during gestation and early life, biological plausibility is more likely if these agents can be shown to affect core pathophysiological features. Objectives: Our objectives were to examine shared mechanisms between autism pathophysiology and the effects of pesticide exposures, focusing on neuroexcitability, oxidative stress, and immune functions and to outline the biological correlates between pesticide exposure and autism risk. Methods: We review and discuss previous research related to autism risk, developmental effects of early pesticide exposure, and basic biological mechanisms by which pesticides may induce or exacerbate pathophysiological features of autism. Discussion: On the basis of experimental and observational research, certain pesticides may be capable of inducing core features of autism, but little is known about the timing or dose, or which of various mechanisms is sufficient to induce this condition. Conclusions: In animal studies, we encourage more research on gene × environment interactions, as well as experimental exposure to mixtures of compounds. Similarly, epidemiologic studies in humans with exceptionally high exposures can identify which pesticide classes are of greatest concern, and studies focused on gene × environment are needed to determine if there are susceptible subpopulations at greater risk from pesticide exposures. PMID:22534084

Linking Quantum Mechanics to Freshman Physics

NASA Astrophysics Data System (ADS)

Vandegrift, Guy

1998-10-01

First-year quantum mechanics can be linked to introductory physics. One example is the Mossbauer effect, which is explained using a simple solution to Schrodinger's equation involving the Dirac delta function. Generalization to N coupled harmonic oscillators shows that the equality of the forces exerted by winner and loser in the game of "tug-of-war" is only an approximation because Newton's third law of motion is not valid (unless phonon momentum is considered). Another example is a treatment of the Gaussian wavepacket which involves less algebra than found in standard textbooks, yet shows that the peak moves according to the familiar equation of motion x = vt + (1/2)at^2 when the applied force is uniform. Finally, a rendition of "Turkey in the Straw" on the viola illustrates Heisenberg's uncertainty principle, which can be written in the less mysterious form, f=(N+-.1)/T , where N cycles are counted in T seconds. Students experience this uncertainty as they try to measure the frequency of a stretched slinky.

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity.

PubMed

Chéreau, Ronan; Saraceno, G Ezequiel; Angibaud, Julie; Cattaert, Daniel; Nägerl, U Valentin

2017-02-07

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate.

PubMed

Geng, Guoqing; Myers, Rupert J; Li, Jiaqi; Maboudian, Roya; Carraro, Carlo; Shapiro, David A; Monteiro, Paulo J M

2017-03-10

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca 2+ of the interlayer. Dreierketten chain cross-links act as 'columns' to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a 'bottom-up' approach.

Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

PubMed Central

Gao, Yunfang; Arfat, Yasir; Wang, Huiping; Goswami, Nandu

2018-01-01

Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives. PMID:29615929

The mechanism of collagen cross-linking in diabetes: a puzzle nearing resolution.

PubMed

Monnier, V M; Glomb, M; Elgawish, A; Sell, D R

1996-07-01

Considerable interest has been focused in recent years on the mechanism of collagen cross-linking by high glucose in vitro and in vivo. Experiments in both diabetic humans and in animals have shown that over time collagen becomes less soluble, less digestible by collagenase, more stable to heat-induced denaturation, and more glycated. In addition, collagen becomes more modified by advanced products of the Maillard reaction, i.e., immunoreactive advanced glycation end products and the glycoxidation markers carboxymethyllysine and pentosidine. Mechanistic studies have shown that collagen cross-linking in vitro can be uncoupled from glycation by the use of antioxidants and chelating agents. Experiments in the authors' laboratory revealed that approximately 50% of carboxymethyllysine formed in vitro originates from pathways other than oxidation of Amadori products, i.e., most likely the oxidation of Schiff base-linked glucose. In addition, the increase in thermal stability of rat tail tendons exposed to high glucose in vitro or in vivo was found to strongly depend on H2O2 formation. The final missing piece of the puzzle is that of the structure of the major cross-link. We speculate that it is a nonfluorescent nonultraviolet active cross-link between two lysine residues, which includes a fragmentation product of glucose linked in a nonreducible bond labile to both strong acids and bases.

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.

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.

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.

Flight tests show potential benefits of data link as primary communication medium

NASA Technical Reports Server (NTRS)

Scanlon, Charles H.; Knox, Charles E.

1991-01-01

Message exchange for air traffic control (ATC) purposes via data link offers the potential benefits of increasing the airspace system safety and efficiency. This is accomplished by reducing communication errors and relieving the overloaded ATC radio frequencies, which hamper efficient message exchanges during peak traffic periods in many busy terminal areas. However, the many uses and advantages of data link create additional questions concerning the interface among the human-users and the cockpit and ground systems. A flight test was conducted in the NASA Langley B-737 airplane to contrast flight operations using current voice communications with the use of data link for transmitting both strategic and tactical ATC clearances during a typical commercial airline flight from takeoff to landing. Commercial airplane pilots were used as test subjects.

5-HTTLPR polymorphism is linked to neural mechanisms of selective attention in preschoolers from lower socioeconomic status backgrounds.

PubMed

Isbell, Elif; Stevens, Courtney; Hampton Wray, Amanda; Bell, Theodore; Neville, Helen J

2016-12-01

While a growing body of research has identified experiential factors associated with differences in selective attention, relatively little is known about the contribution of genetic factors to the skill of sustained selective attention, especially in early childhood. Here, we assessed the association between the serotonin transporter linked polymorphic region (5-HTTLPR) genotypes and the neural mechanisms of selective attention in young children from lower socioeconomic status (SES) backgrounds. Event-related potentials (ERPs) were recorded during a dichotic listening task from 121 children (76 females, aged 40-67 months), who were also genotyped for the short and long allele of 5-HTTLPR. The effect of selective attention was measured as the difference in ERP mean amplitudes elicited by identical probe stimuli embedded in stories when they were attended versus unattended. Compared to children homozygous for the long allele, children who carried at least one copy of the short allele showed larger effects of selective attention on neural processing. These findings link the short allele of the 5-HTTLPR to enhanced neural mechanisms of selective attention and lay the groundwork for future studies of gene-by-environment interactions in the context of key cognitive skills. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate

NASA Astrophysics Data System (ADS)

Geng, Guoqing; Myers, Rupert J.; Li, Jiaqi; Maboudian, Roya; Carraro, Carlo; Shapiro, David A.; Monteiro, Paulo J. M.

2017-03-01

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.

Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate

DOE PAGES

Geng, Guoqing; Myers, Rupert J.; Li, Jiaqi; ...

2017-03-10

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is moremore » deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca 2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.« less

Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate

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

Geng, Guoqing; Myers, Rupert J.; Li, Jiaqi

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is moremore » deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca 2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.« less

Cell mechanics and immune system link up to fight infections

NASA Astrophysics Data System (ADS)

Ekpenyong, Andrew; Man, Si Ming; Tourlomousis, Panagiotis; Achouri, Sarra; Cammarota, Eugenia; Hughes, Katherine; Rizzo, Alessandro; Ng, Gilbert; Guck, Jochen; Bryant, Clare

2015-03-01

Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection.

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.

Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

PubMed

Mama, Scherezade K; Li, Yisheng; Basen-Engquist, Karen; Lee, Rebecca E; Thompson, Deborah; Wetter, David W; Nguyen, Nga T; Reitzel, Lorraine R; McNeill, Lorna H

2016-01-01

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans

PubMed Central

Basen-Engquist, Karen; Lee, Rebecca E.; Thompson, Deborah; Wetter, David W.; Reitzel, Lorraine R.

2016-01-01

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans. PMID:27119366

Antenna Scan Mechanism for an Inter Satellite Link of a Constellation Program

NASA Astrophysics Data System (ADS)

Köker, Ingo; Härtel, Frank

2015-09-01

For a constellation program, RF Inter Satellite Links between single satellites can support ranging and communication for uploading mission data or telecommands. These data shall be uploaded from one single ground station to the next reachable satellite and transmitted by the Inter Satellite Link to further dedicated satellites. For this function each satellite has to be equipped with 2 Antenna Scan Mechanisms (ASM) for data transfer in the K-Band.The main challenges for the mechanisms are the high speed position change requirement, low mass requirement and the design to cost approach. Furthermore a small envelope to accommodate the 2- axes antenna scan mechanism was provided. The maximum position change of +/- 180° needs to be reached within 3 seconds. All requirements shall be achieved by relying on the heritage design of our downlink antenna pointing mechanism product.The ASM design approach was based on our 2-axes steerable downlink antenna; however during the definition phase it turned out that some major changes have to be implemented due to mission requirements (high operation speed and long lifetime). Following the design to cost approach most components could be procured from industrial standard but had to be qualified in terms of functionality, performance and life. The following industrial components have been selected: - Bearings procured from an industrial supplier and modified (cage) by a supporting supplier - The selected actuator is a standard stepper motor equipped with redundant windings - The slip ring design was used from a previous project in order to keep the heritage - Suitable rotary joints for the RF link were provided by a small and flexible company However at the very beginning of the project some difficulties with the bearings selection and procurementhave been identified. Since the most suitable standard catalog bearings were not available in time, we were forced to use alternatives. In parallel due to envelope constrains the re

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…

Translating Mechanism-Based Strategies to Break the Obesity-Cancer Link: A Narrative Review.

PubMed

Smith, Laura A; O'Flanagan, Ciara H; Bowers, Laura W; Allott, Emma H; Hursting, Stephen D

2018-04-01

Prevalence of obesity, an established risk factor for many cancers, has increased dramatically over the past 50 years in the United States and across the globe. Relative to normoweight cancer patients, obese cancer patients often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity-cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression and, thus, there are multiple opportunities for primary prevention and treatment of obesity-related cancers. Obesity-associated alterations, including systemic metabolism, adipose inflammation, growth factor signaling, and angiogenesis, are emerging as primary drivers of obesity-associated cancer development and progression. These obesity-associated host factors interact with the intrinsic molecular characteristics of cancer cells, facilitating several of the hallmarks of cancer. Each is considered in the context of potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers. In addition, this review focuses on emerging mechanisms behind the obesity-cancer link, as well as relevant dietary interventions, including calorie restriction, intermittent fasting, low-fat diet, and ketogenic diet, that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-related cancers. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Directed networks' different link formation mechanisms causing degree distribution distinction

NASA Astrophysics Data System (ADS)

Behfar, Stefan Kambiz; Turkina, Ekaterina; Cohendet, Patrick; Burger-Helmchen, Thierry

2016-11-01

Within undirected networks, scientists have shown much interest in presenting power-law features. For instance, Barabási and Albert (1999) claimed that a common property of many large networks is that vertex connectivity follows scale-free power-law distribution, and in another study Barabási et al. (2002) showed power law evolution in the social network of scientific collaboration. At the same time, Jiang et al. (2011) discussed deviation from power-law distribution; others indicated that size effect (Bagrow et al., 2008), information filtering mechanism (Mossa et al., 2002), and birth and death process (Shi et al., 2005) could account for this deviation. Within directed networks, many authors have considered that outlinks follow a similar mechanism of creation as inlinks' (Faloutsos et al., 1999; Krapivsky et al., 2001; Tanimoto, 2009) with link creation rate being the linear function of node degree, resulting in a power-law shape for both indegree and outdegree distribution. Some other authors have made an assumption that directed networks, such as scientific collaboration or citation, behave as undirected, resulting in a power-law degree distribution accordingly (Barabási et al., 2002). At the same time, we claim (1) Outlinks feature different degree distributions than inlinks; where different link formation mechanisms cause the distribution distinctions, (2) in/outdegree distribution distinction holds for different levels of system decomposition; therefore this distribution distinction is a property of directed networks. First, we emphasize in/outlink formation mechanisms as causal factors for distinction between indegree and outdegree distributions (where this distinction has already been noticed in Barker et al. (2010) and Baxter et al. (2006)) within a sample network of OSS projects as well as Java software corpus as a network. Second, we analyze whether this distribution distinction holds for different levels of system decomposition: open

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

PubMed

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

2018-01-01

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

Predicting missing links and identifying spurious links via likelihood analysis

NASA Astrophysics Data System (ADS)

Pan, Liming; Zhou, Tao; Lü, Linyuan; Hu, Chin-Kun

2016-03-01

Real network data is often incomplete and noisy, where link prediction algorithms and spurious link identification algorithms can be applied. Thus far, it lacks a general method to transform network organizing mechanisms to link prediction algorithms. Here we use an algorithmic framework where a network’s probability is calculated according to a predefined structural Hamiltonian that takes into account the network organizing principles, and a non-observed link is scored by the conditional probability of adding the link to the observed network. Extensive numerical simulations show that the proposed algorithm has remarkably higher accuracy than the state-of-the-art methods in uncovering missing links and identifying spurious links in many complex biological and social networks. Such method also finds applications in exploring the underlying network evolutionary mechanisms.

Predicting missing links and identifying spurious links via likelihood analysis

PubMed Central

Pan, Liming; Zhou, Tao; Lü, Linyuan; Hu, Chin-Kun

2016-01-01

Real network data is often incomplete and noisy, where link prediction algorithms and spurious link identification algorithms can be applied. Thus far, it lacks a general method to transform network organizing mechanisms to link prediction algorithms. Here we use an algorithmic framework where a network’s probability is calculated according to a predefined structural Hamiltonian that takes into account the network organizing principles, and a non-observed link is scored by the conditional probability of adding the link to the observed network. Extensive numerical simulations show that the proposed algorithm has remarkably higher accuracy than the state-of-the-art methods in uncovering missing links and identifying spurious links in many complex biological and social networks. Such method also finds applications in exploring the underlying network evolutionary mechanisms. PMID:26961965

Monogenic Mouse Models of Autism Spectrum Disorders: Common Mechanisms and Missing Links

PubMed Central

Hulbert, Samuel W.; Jiang, Yong-hui

2016-01-01

Autism Spectrum Disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral analysis with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

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

Interpersonal Stress Generation as a Mechanism Linking Rumination to Internalizing Symptoms in Early Adolescents

ERIC Educational Resources Information Center

McLaughlin, Katie A.; Nolen-Hoeksema, Susan

2012-01-01

Rumination is a risk factor for depressive and anxiety symptoms in adolescents. Previous investigations of the mechanisms linking rumination to internalizing problems have focused primarily on cognitive factors. We investigated whether interpersonal stress generation plays a role in the longitudinal relationship between rumination and…

Mutagenic Potential of Nitroguanidine in the Drosophila melanogaster Sex-Linked Recessive Lethal Test

DTIC Science & Technology

1988-07-01

Security Classification) Mtutagenic potential of nitroguan idine in the Drosophila melano- gaster sex-linked recessive lethal test 12. PERSONAL AUTHOR(S...Frederick, MD 21701-5012 Commander Commandant US Army Environmental Hygine Academy of Health Sciences. US Army Agency ATTN: AHS-CDM ATTN: Librarian, HSDH

Quantum mechanics without potential function

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

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

2015-07-15

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

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

PubMed

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

2017-03-15

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

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.

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

Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

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

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-inducedmore » mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.« less

Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

PubMed

Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

2014-09-01

An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration. Copyright © 2014 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.

Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction

PubMed Central

Stoeckel, Luke E.; Arvanitakis, Zoe; Gandy, Sam; Small, Dana; Kahn, C. Ronald; Pascual-Leone, Alvaro; Pawlyk, Aaron; Sherwin, Robert; Smith, Philip

2016-01-01

Scientific evidence has established several links between metabolic and neurocognitive dysfunction, and epidemiologic evidence has revealed an increased risk of Alzheimer’s disease and vascular dementia in patients with diabetes. In July 2015, the National Institute of Diabetes, Digestive, and Kidney Diseases gathered experts from multiple clinical and scientific disciplines, in a workshop entitled “The Intersection of Metabolic and Neurocognitive Dysfunction”, to clarify the state-of-the-science on the mechanisms linking metabolic dysfunction, and insulin resistance and diabetes in particular, to neurocognitive impairment and dementia. This perspective is intended to serve as a summary of the opinions expressed at this meeting, which focused on identifying gaps and opportunities to advance research in this emerging area with important public health relevance. PMID:27303627

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen.

PubMed

Uzel, Sebastien G M; Buehler, Markus J

2011-02-01

Collagen is a key constituent in structural materials found in biology, including bone, tendon, skin and blood vessels. Here we report a first molecular level model of an entire overlap region of a C-terminal cross-linked type I collagen assembly and carry out a nanomechanical characterization based on large-scale molecular dynamics simulation in explicit water solvent. Our results show that the deformation mechanism and strength of the structure are greatly affected by the presence of the cross-link, and by the specific loading condition of how the stretching is applied. We find that the presence of a cross-link results in greater strength during deformation as complete intermolecular slip is prevented, and thereby particularly affects larger deformation levels. Conversely, the lack of a cross-link results in the onset of intermolecular sliding during deformation and as a result an overall weaker structure is obtained. Through a detailed analysis of the distribution of deformation by calculating the molecular strain we show that the location of largest strains does not occur around the covalent bonding region, but is found in regions further away from this location. The insight developed from understanding collagenous materials from a fundamental molecular level upwards could play a role in advancing our understanding of physiological and disease states of connective tissues, and also enable the development of new scaffolding material for applications in regenerative medicine and biologically inspired materials. Copyright © 2011. Elsevier Ltd. All rights reserved.

Comparative investigation of thermal and mechanical properties of cross-linked epoxy polymers with different curing agents by molecular dynamics simulation.

PubMed

Jeyranpour, F; Alahyarizadeh, Gh; Arab, B

2015-11-01

Molecular dynamics (MD) simulations were carried out to predict the thermal and mechanical properties of the cross-linked epoxy system composed of DGEBA resin and the curing agent TETA. To investigate the effects of curing agents, a comprehensive and comparative study was also performed on the thermal and mechanical properties of DGEBA/TETA and DGEBA/DETDA epoxy systems such as density, glass transition temperature (Tg), coefficient of thermal expansion (CTE) and elastic properties of different cross-linking densities and different temperatures. The results indicated that the glass transition temperature of DGEBA/TETA system calculated through density-temperature data, ∼ 385-395 °K, for the epoxy system with the cross-linking density of 62.5% has a better agreement with the experimental value (Tg, ∼ 400 °K) in comparison to the value calculated through the variation of cell volume in terms of temperature, 430-440 °K. They also indicated that CTE related parameters and elastic properties including Young, Bulk, and shear's moduli, and Poisson's ratio have a relative agreement with the experimental results. Comparison between the thermal and mechanical properties of epoxy systems of DGEBA/TETA and DGEBA/DETDA showed that the DGEBA/DETDA has a higher Tg in all cross linking densities than that of DGEBA/TETA, while higher mechanical properties was observed in the case of DGEBA/TETA in almost all cross linking densities. Copyright © 2015 Elsevier Inc. All rights reserved.

A New Realistic Evaluation Analysis Method: Linked Coding of Context, Mechanism, and Outcome Relationships

ERIC Educational Resources Information Center

Jackson, Suzanne F.; Kolla, Gillian

2012-01-01

In attempting to use a realistic evaluation approach to explore the role of Community Parents in early parenting programs in Toronto, a novel technique was developed to analyze the links between contexts (C), mechanisms (M) and outcomes (O) directly from experienced practitioner interviews. Rather than coding the interviews into themes in terms of…

Linking admiration and adoration to self-expansion: different ways to enhance one's potential.

PubMed

Schindler, Ines; Paech, Juliane; Löwenbrück, Fabian

2015-01-01

How is admiration different from adoration? We provided one answer to this question by examining the pathways through which admiration and adoration linked to self-expansion in a questionnaire and an experimental (autobiographical recall of emotion episodes) study. Both emotions were associated with increased potential efficacy to accomplish goals (i.e., self-expansion), but different action tendencies accounted for these links. While our emotion inductions did not successfully distinguish between admiration and adoration, we could statistically disentangle their effects through mediator models. In both studies, self-reported admiration linked to self-expansion through the tendency to emulate admired others. Adoration related to self-expansion through the tendency to affiliate with adored others. These findings were obtained after controlling for other emotions in response to the target person (awe, love, hope, benign envy) and mutuality of the relationship. Our findings also suggest that considering specific emotions (rather than undifferentiated positive affect) helps uncover different pathways to self-expansion.

Fabrication of chemically cross-linked porous gelatin matrices.

PubMed

Bozzini, Sabrina; Petrini, Paola; Altomare, Lina; Tanzi, Maria Cristina

2009-01-01

The aim of this study was to chemically cross-link gelatin, by reacting its free amino groups with an aliphatic diisocyanate. To produce hydrogels with controllable properties, the number of reacting amino groups was carefully determined. Porosity was introduced into the gelatin-based hydrogels through the lyophilization process. Porous and non-porous matrices were characterized with respect to their chemical structure, morphology, water uptake and mechanical properties. The physical, chemical and mechanical properties of the porous matrices are related to the extent of their cross-linking, showing that they can be controlled by varying the reaction parameters. Water uptake values (24 hours) vary between 160% and 200% as the degree of cross-linking increases. The flexibility of the samples also decreases by changing the extent of cross-linking. Young's modulus shows values between 0.188 KPa, for the highest degree, and 0.142 KPa for the lowest degree. The matrices are potential candidates for use as tissue-engineering scaffolds by modulating their physical chemical properties according to the specific application.

How Does Consecutive Interpreting Training Influence Working Memory: A Longitudinal Study of Potential Links Between the Two

PubMed Central

Dong, Yanping; Liu, Yuhua; Cai, Rendong

2018-01-01

With an intention to contribute to the issue of how language experience may influence working memory (WM), we focused on consecutive interpreting (CI), analyzed its potential links with WM functions and tested these links in a longitudinal experiment, trying to answer the specific question of how CI training may influence WM. Two comparable groups of Chinese learners of English received either CI or general second language (L2) training for one semester, and were tested before and after the training with the tasks of n-back (non-verbal updating), L2 listening span, and letter running span (verbal spans). CI performance was tested in the posttest. The results showed that (1) updating efficiency in both the pretest and posttest predicted CI performance, and CI training enhanced updating efficiency while general L2 training did not; (2) the relationship between verbal spans and CI performance was weaker (i.e., only pretest L2 listening span correlated with CI performance and predicted CI performance with marginal significance), and CI training did not make a unique contribution to these spans (i.e., no group differences). The results indicated an “interpreter advantage” in updating, which was probably due to that updating was more central in the CI task than WM spans. Theoretically, we believe that updating and CI are closely related because they share the same underlying mechanism, or more specifically updating and the recalling process in the CI task share the same attentional control process, a unique link between updating and the CI task. Methodological implications are discussed. PMID:29922199

Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine

PubMed Central

Rapin, Jean Robert; Wiernsperger, Nicolas

2010-01-01

Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes. PMID:20613941

Formation mechanism of glyoxal-DNA adduct, a DNA cross-link precursor.

PubMed

Vilanova, B; Fernández, D; Casasnovas, R; Pomar, A M; Alvarez-Idaboy, J R; Hernández-Haro, N; Grand, A; Adrover, M; Donoso, J; Frau, J; Muñoz, F; Ortega-Castro, J

2017-05-01

DNA nucleobases undergo non-enzymatic glycation to nucleobase adducts which can play important roles in vivo. In this work, we conducted a comprehensive experimental and theoretical kinetic study of the mechanisms of formation of glyoxal-guanine adducts over a wide pH range in order to elucidate the molecular basis for the glycation process. Also, we performed molecular dynamics simulations to investigate how open or cyclic glyoxal-guanine adducts can cause structural changes in an oligonucleotide model. A thermodynamic study of other glycating agents including methylglyoxal, acrolein, crotonaldehyde, 4-hydroxynonenal and 3-deoxyglucosone revealed that, at neutral pH, cyclic adducts were more stable than open adducts; at basic pH, however, the open adducts of 3-deoxyglucosone, methylglyoxal and glyoxal were more stable than their cyclic counterparts. This result can be ascribed to the ability of the adducts to cross-link DNA. The new insights may contribute to improve our understanding of the connection between glycation and DNA cross-linking. Copyright © 2017 Elsevier B.V. All rights reserved.

Bio-Based Artificial Nacre with Excellent Mechanical and Barrier Properties Realized by a Facile In Situ Reduction and Cross-Linking Reaction.

PubMed

Shahzadi, Kiran; Mohsin, Imran; Wu, Lin; Ge, Xuesong; Jiang, Yijun; Li, Hui; Mu, Xindong

2017-01-24

Demands for high strength integrated materials have substantially increased across various kinds of industries. Inspired by the relationship of excellent integration of mechanical properties and hierarchical nano/microscale structure of the natural nacre, a simple and facile method to fabricate high strength integrated artificial nacre based on sodium carboxymethylcellulose (CMC) and borate cross-linked graphene oxide (GO) sheets has been developed. The tensile strength and toughness of cellulose-based hybrid material reached 480.5 ± 13.1 MPa and 11.8 ± 0.4 MJm -3 by a facile in situ reduction and cross-linking reaction between CMC and GO (0.7%), which are 3.55 and 6.55 times that of natural nacre. This hybrid film exhibits better thermal stability and flame retardancy. More interestingly, the hybrid material showed good water stability compared to that in the original water-soluble CMC. This type of hybrid has great potential applications in aerospace, artificial muscle, and tissue engineering.

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

PubMed Central

Folley, Bradley S.; Doop, Mikisha L.; Park, Sohee

2009-01-01

Recent evidence suggests that genetic and biochemical factors associated with psychoses may also provide an increased propensity to think creatively. The evolutionary theories linking brain growth and diet to the appearance of creative endeavors have been made recently, but they lack a direct link to research on the biological correlates of divergent and creative thought. Expanding upon Horrobin’s theory that changes in brain size and in neural microconnectivity came about as a result of changes in dietary fat and phospholipid incorporation of highly unsaturated fatty acids, we propose a theory relating phospholipase A2 (PLA2) activity to the neuromodulatory effects of the noradrenergic system. This theory offers probable links between attention, divergent thinking, and arousal through a mechanism that emphasizes optimal individual functioning of the PLA2 and NE systems as they interact with structural and biochemical states of the brain. We hope that this theory will stimulate new research in the neural basis of creativity and its connection to psychoses. PMID:14623501

Electro-Mechanical Actuator. DC Resonant Link Controller

NASA Technical Reports Server (NTRS)

Schreiner, Kenneth E.

1996-01-01

This report summarizes the work performed on the 68 HP electro-mechanical actuator (EMA) system developed on NASA contract for the Electrical Actuation (ELA) Technology Bridging Program. The system was designed to demonstrate the capability of large, high power linear ELAs for applications such as Thrust Vector Control (TVC) on rocket engines. It consists of a motor controller, drive electronics and a linear actuator capable of up to 32,00 lbs loading at 7.4 inches/second. The drive electronics are based on the Resonant DC link concept and operate at a nominal frequency of 55 kHz. The induction motor is a specially designed high speed, low inertia motor capable of a 68 peak HP. The actuator was originally designed by MOOG Aerospace under an internal R & D program to meet Space Shuttle Main Engine (SSME) TVC requirements. The design was modified to meet this programs linear rate specification of 7.4 inches/second. The motor and driver were tested on a dynamometer at the Martin Marietta Space Systems facility. System frequency response, step response and force-velocity tests were conducted at the MOOG Aerospace facility. A complete description of the system and all test results can be found in the body of the report.

Smoking and increased Alzheimer’s disease risk: A review of potential mechanisms

PubMed Central

Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.

2014-01-01

Background Cigarette smoking has been linked with both increased and decreased risk for Alzheimer’s disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians. Methods Systematic review of published studies on the association between smoking and increased risk for AD, and preclinical and human literature on the relationships between smoking, nicotine exposure and AD-related neuropathology. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented. Results Overall, the literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathophysiology and increased risk for AD. Conclusions A reduction in the incidence of smoking will likely reduce the future prevalence of AD. PMID:24924665

Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells

PubMed Central

Osawa, T; Davies, D; Hartley, J A

2011-01-01

DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced cell death is unclear. Here, we show a novel mechanism of p53-independent apoptotic cell death involving prolonged cell-cycle (G2) arrest, ICL repair involving HR, transient mitosis, incomplete cytokinesis, and gross chromosomal abnormalities resulting from ICLs in mammalian cells. This characteristic ‘giant' cell death, observed by using time-lapse video microscopy, was reduced in ICL repair ERCC1- and XRCC3-deficient cells. Collectively, the results illustrate the coordination of ICL-induced cellular responses, including cell-cycle arrest, DNA damage repair, and cell death. PMID:21814285

Potential mechanisms for chemotherapy-induced impairments in cognitive function.

PubMed

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

2005-11-03

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

Potential Mechanisms for Microbial Energy Acquisition in Oxic Deep-Sea Sediments

PubMed Central

Heidelberg, John F.

2016-01-01

ABSTRACT The South Pacific Gyre (SPG) possesses the lowest rates of sedimentation, surface chlorophyll concentration, and primary productivity in the global oceans. As a direct result, deep-sea sediments are thin and contain small amounts of labile organic carbon. It was recently shown that the entire SPG sediment column is oxygenated and may be representative of up to a third of the global marine environment. To understand the microbial processes that contribute to the removal of the labile organic matter at the water-sediment interface, a sediment sample was collected and subjected to metagenomic sequencing and analyses. Analysis of nine partially reconstructed environmental genomes, which represent approximately one-third of the microbial community, revealed that the members of the SPG surface sediment microbial community are phylogenetically distinct from surface/upper-ocean organisms. These genomes represent a wide distribution of novel organisms, including deep-branching Alphaproteobacteria, two novel organisms within the Proteobacteria, and new members of the Nitrospirae, Nitrospinae, and candidate phylum NC10. These genomes contain evidence for microbially mediated metal (iron/manganese) oxidation and carbon fixation linked to nitrification. Additionally, despite hypothesized energy limitation, members of the SPG microbial community had motility and chemotaxis genes and possessed mechanisms for the degradation of high-molecular-weight organic matter. This study contributes to our understanding of the metabolic potential of microorganisms in deep-sea oligotrophic sediments and their impact on local carbon geochemistry. IMPORTANCE This research provides insight into the microbial metabolic potential of organisms inhabiting oxygenated deep-sea marine sediments. Current estimates suggest that these environments account for up to a third of the global marine sediment habitat. Nine novel deep-sea microbial genomes were reconstructed from a metagenomic data set

Potential Mechanisms for Microbial Energy Acquisition in Oxic Deep-Sea Sediments.

PubMed

Tully, Benjamin J; Heidelberg, John F

2016-07-15

The South Pacific Gyre (SPG) possesses the lowest rates of sedimentation, surface chlorophyll concentration, and primary productivity in the global oceans. As a direct result, deep-sea sediments are thin and contain small amounts of labile organic carbon. It was recently shown that the entire SPG sediment column is oxygenated and may be representative of up to a third of the global marine environment. To understand the microbial processes that contribute to the removal of the labile organic matter at the water-sediment interface, a sediment sample was collected and subjected to metagenomic sequencing and analyses. Analysis of nine partially reconstructed environmental genomes, which represent approximately one-third of the microbial community, revealed that the members of the SPG surface sediment microbial community are phylogenetically distinct from surface/upper-ocean organisms. These genomes represent a wide distribution of novel organisms, including deep-branching Alphaproteobacteria, two novel organisms within the Proteobacteria, and new members of the Nitrospirae, Nitrospinae, and candidate phylum NC10. These genomes contain evidence for microbially mediated metal (iron/manganese) oxidation and carbon fixation linked to nitrification. Additionally, despite hypothesized energy limitation, members of the SPG microbial community had motility and chemotaxis genes and possessed mechanisms for the degradation of high-molecular-weight organic matter. This study contributes to our understanding of the metabolic potential of microorganisms in deep-sea oligotrophic sediments and their impact on local carbon geochemistry. This research provides insight into the microbial metabolic potential of organisms inhabiting oxygenated deep-sea marine sediments. Current estimates suggest that these environments account for up to a third of the global marine sediment habitat. Nine novel deep-sea microbial genomes were reconstructed from a metagenomic data set and expand the limited

Quantum mechanical streamlines. I - Square potential barrier

NASA Technical Reports Server (NTRS)

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

1974-01-01

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

Phylogenetic and functional potential links pH and N2O emissions in pasture soils.

PubMed

Samad, Md Sainur; Biswas, Ambarish; Bakken, Lars R; Clough, Timothy J; de Klein, Cecile A M; Richards, Karl G; Lanigan, Gary J; Morales, Sergio E

2016-10-26

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N 2 O and N 2 emissions. Soil pH regulates the reduction of N 2 O to N 2 , however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N 2 O emission ratio (N 2 O/(NO + N 2 O + N 2 )) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N 2 O emission ratio and community changes. Soil pH was negatively associated with N 2 O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir &nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N 2 O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N 2 O emission ratio through more efficient conversion of N 2 O to N 2 .

Phylogenetic and functional potential links pH and N2O emissions in pasture soils

NASA Astrophysics Data System (ADS)

Samad, M. D. Sainur; Biswas, Ambarish; Bakken, Lars R.; Clough, Timothy J.; de Klein, Cecile A. M.; Richards, Karl G.; Lanigan, Gary J.; Morales, Sergio E.

2016-10-01

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2.

Phylogenetic and functional potential links pH and N2O emissions in pasture soils

PubMed Central

Samad, M. d. Sainur; Biswas, Ambarish; Bakken, Lars R.; Clough, Timothy J.; de Klein, Cecile A. M.; Richards, Karl G.; Lanigan, Gary J.; Morales, Sergio E.

2016-01-01

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2. PMID:27782174

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.

Beyond Failure: Potentially Mitigating Failed Author Searches in the Online Library Catalog through the Use of Linked Data

ERIC Educational Resources Information Center

Moulaison, Heather Lea; Stanley, Susan Nicole

2013-01-01

Linked data stores house vetted content that can supplement the information available through online library catalogs, potentially mitigating failed author searches if information about the author exists in linked data formats. In this case study, a total of 689 failed author index queries from a large Midwestern academic library's online library…

The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms.

PubMed

Sahami, S; Kooij, I A; Meijer, S L; Van den Brink, G R; Buskens, C J; Te Velde, A A

2016-02-01

The human appendix has long been considered as a vestigial organ, an organ that has lost its function during evolution. In recent years, however, reports have emerged that link the appendix to numerous immunological functions in humans. Evidence has been presented for an important role of the appendix in maintaining intestinal health. This theory suggests that the appendix may be a reservoir or 'safe house' from which the commensal gut flora can rapidly be reestablished if it is eradicated from the colon. However, the appendix may also have a role in the development of inflammatory bowel disease (IBD). Several large epidemiological cohort studies have demonstrated the preventive effect of appendectomy on the development of ulcerative colitis, a finding that has been confirmed in murine colitis models. In addition, current studies are examining the possible therapeutic effect of an appendectomy to modulate disease course in patients with ulcerative colitis. This literature review assesses the current knowledge about the clinical and immunological aspects of the vermiform appendix in IBD and suggests that the idea of the appendix as a vestigial remnant should be discarded.

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

The link between otitis media with effusion and allergy: a potential role for intranasal corticosteroids.

PubMed

Lack, Gideon; Caulfield, Helen; Penagos, Martin

2011-05-01

We reviewed the evidence linking otitis media with effusion (OME) and atopy, with the goal of clarifying the possible role of intranasal corticosteroids (INSs) in OME treatment. In August 2009, the MEDLINE database was searched for primary studies on OME epidemiology, pathophysiology, and treatment. Relevant clinical guidelines were obtained. Interpreting OME research is complicated by variable disease definitions, patient populations, methodologies, and outcomes assessments, along with the possibility of spontaneous resolution. However, evidence links OME with atopic conditions including allergic rhinitis; observed prevalence of allergic rhinitis in patients with chronic or recurrent OME ranges from 24% to 89%. Such findings have prompted evaluations of common allergy medications for OME treatment. While short-term use of INSs alone or combined with antibiotics has shown benefit in some studies, more prolonged treatment protocols and long-term clinical outcomes will require critical assessment. Evidence suggesting epidemiologic and pathophysiologic links between allergy and OME has prompted investigation into a potential role for INSs in OME management, with promising initial results. Benefits of considering medical treatment in patients with OME prior to surgery include both the potential reductions in allergic inflammation and the naturally occurring spontaneous resolution of OME in these patients. © 2011 John Wiley & Sons A/S.

An epigenetic antimalarial resistance mechanism involving parasite genes linked to nutrient uptake.

PubMed

Sharma, Paresh; Wollenberg, Kurt; Sellers, Morgan; Zainabadi, Kayvan; Galinsky, Kevin; Moss, Eli; Nguitragool, Wang; Neafsey, Daniel; Desai, Sanjay A

2013-07-05

Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In Plasmodium falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag genes linked to channel activity, but had no genome-level changes. Silencing aborted production of the channel protein and was directly responsible for reduced uptake. Silencing affected clag paralogs on two chromosomes and was mediated by specific histone modifications, allowing a rapidly reversible drug resistance phenotype advantageous to the parasite. These findings implicate a novel epigenetic resistance mechanism that involves reduced host cell uptake and is a worrisome liability for water-soluble antimalarial drugs.

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

PubMed

Marini, Francesco; Chelazzi, Leonardo; Maravita, Angelo

2013-08-01

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

Mechanism-based Pharmacovigilance over the Life Sciences Linked Open Data Cloud.

PubMed

Kamdar, Maulik R; Musen, Mark A

2017-01-01

Adverse drug reactions (ADR) result in significant morbidity and mortality in patients, and a substantial proportion of these ADRs are caused by drug-drug interactions (DDIs). Pharmacovigilance methods are used to detect unanticipated DDIs and ADRs by mining Spontaneous Reporting Systems, such as the US FDA Adverse Event Reporting System (FAERS). However, these methods do not provide mechanistic explanations for the discovered drug-ADR associations in a systematic manner. In this paper, we present a systems pharmacology-based approach to perform mechanism-based pharmacovigilance. We integrate data and knowledge from four different sources using Semantic Web Technologies and Linked Data principles to generate a systems network. We present a network-based Apriori algorithm for association mining in FAERS reports. We evaluate our method against existing pharmacovigilance methods for three different validation sets. Our method has AUROC statistics of 0.7-0.8, similar to current methods, and event-specific thresholds generate AUROC statistics greater than 0.75 for certain ADRs. Finally, we discuss the benefits of using Semantic Web technologies to attain the objectives for mechanism-based pharmacovigilance.

Students' Conceptual Difficulties in Quantum Mechanics: Potential Well Problems

ERIC Educational Resources Information Center

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

2009-01-01

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

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

A novel mechanism of UV-A and riboflavin-mediated corneal cross-linking through induction of tissue transglutaminases.

PubMed

Kopsachilis, Nikolaos; Tsaousis, Konstantinos T; Tsinopoulos, Ioannis T; Kruse, Friedrich E; Welge-Luessen, Ulrich

2013-07-01

Collagen cross-linking using UV-A irradiation combined with the photosensitizer riboflavin is a new technique for treating progressive keratoconus. The purposes of this study were to examine whether primary human corneal keratocytes (HCKs) are capable of expressing and secreting fibronectin and tissue transglutaminase (tTgase), an enzyme cross-linking extracellular matrix protein, and to examine whether fibronectin and tTgase are increased after the treatment of HCK cells with UV-A irradiation combined with riboflavin (RFUV-A), thus providing another possible physiological mechanism of the cross-linking pathway. Cell cultures established from HCKs were treated with 0.025% riboflavin solution and UV-A (370 nm) irradiance 3 mW/cm2 for 30 minutes. Induction of fibronectin and tTgase was investigated by immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis. Cell viability was quantified by a microscopic live-dead assay. External tTgase activity was measured by the ability to form polymerized fibronectin and the incorporation of biotinylated cadaverine into fibronectin. Treatment of cultured HCK cells with RFUV-A increased the fibronectin and tTgase messenger RNA and protein levels. This effect was not observed in cells treated with riboflavin or UV-A radiation alone. Incorporation of biotinylated cadaverine was significantly increased when HCK cells were treated with RFUV-A. The enzymes tTgase and fibronectin are expressed by RFUV-A treatment in cultured HCK cells. This mechanism provides more information about the physiology of corneal cross-linking.

An Investigation of Siloxane Cross-linked Hydroxyapatite-Gelatin/Copolymer Composites for Potential Orthopedic Applications†

PubMed Central

Dyke, Jason Christopher; Knight, Kelly Jane; Zhou, Huaxing; Chiu, Chi-Kai; Ko, Ching-Chang; You, Wei

2012-01-01

Causes of bone deficiency are numerous, but biomimetic alloplastic grafts provide an alternative to repair tissue naturally. Previously, a hydroxyapatite-gelatin modified siloxane (HAp-Gemosil) composite was prepared by cross-linking (N, N′-bis[(3-trimethoxysilyl)propyl]ethylene diamine (enTMOS) around the HAp-Gel nanocomposite particles, to mimic the natural composition and properties of bone. However, the tensile strength remained too low for many orthopedic applications. It was hypothesized that incorporating a polymer chain into the composite could help improve long range interaction. Furthermore, designing this polymer to interact with the enTMOS siloxane cross-linked matrix would provide improved adhesion between the polymer and the ceramic composite, and improve mechanical properties. To this end, copolymers of L-Lactide (LLA), and a novel alkyne derivatized trimethylene carbonate, propargyl carbonate (PC), were synthesized. Incorporation of PC during copolymerization affects properties of copolymers such as molecular weight, Tg, and % PC incorporation. More importantly, PC monomers bear a synthetic handle, allowing copolymers to undergo post-polymerization functionalization with graft monomers to specifically tailor the properties of the final composite. For our investigation, P(LLA-co-PC) copolymers were functionalized by an azido-silane (AS) via copper catalyzed azide-alkyne cycloaddition (CuAAC) through terminal alkyne on PC monomers. The new functionalized polymer, P(LLA-co-PC)(AS) was blended with HAp-Gemosil, with the azido-silane linking the copolymer to the silsesquioxane matrix within the final composite. These HAp-Gemosil/P(LLA-co-PC)(AS) composites were subjected to mechanical and biological testing, and the results were compared with those from the HAp-Gemosil composites. This study revealed that incorporating a cross-linkable polymer served to increase the flexural strength of the composite by 50%, while maintaining the biocompatibility of

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.

Potential climatic mechanisms associated with the mega drought at 4200 cal yr BP: linking proxy data with modern climate analogues

NASA Astrophysics Data System (ADS)

Carter, V.; Shinker, J. J.

2017-12-01

Roughly 4200 years ago, a 150-year long mega drought occurred in the central Rocky Mountains, as indicated by pollen evidence from lake sediments from Long Lake, south-eastern Wyoming. However, pollen evidence does not record the climate mechanisms that caused the drought; they only provide evidence that the drought occurred. A modern climate analogue technique using North American Regional Reanalysis data was applied to the sedimentary data in order to identify possible synoptic and dynamic patterns that may have caused the mega drought at 4200 cal yr BP. Our results suggest warm and dry conditions were a result of anomalously higher-than-normal geopotential heights that were centred over the Great Plains beginning in the spring and persisting through the fall. Drought conditions during the growing seasons was the result of the anomalous high-pressure ridge, which suppressed moisture transport via the low level jet from the Gulf of Mexico, as well as brought in dry continental air from in the interior region of North America. The conditions associated with modern analogues offer a potential climate mechanism that caused the mega drought 4200 years ago, and likely led to the changes in vegetation composition as evidenced by the pollen record from Long Lake, Wyoming.

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

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

PubMed

Schiffmann, Christoph; Sebastiani, Daniel

2011-05-10

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

Synthesis and mechanical properties of double cross-linked gelatin-graphene oxide hydrogels.

PubMed

Piao, Yongzhe; Chen, Biqiong

2017-08-01

Gelatin is an interesting biological macromolecule for biomedical applications. Here, double cross-linked gelatin nanocomposite hydrogels with incorporation of graphene oxide (GO) were synthesized in one pot using glutaraldehyde (GTA) and GTA-grafted GO as double chemical cross-linkers. The nanocomposite hydrogels, in contrast to the neat gelatin hydrogel, exhibited significant increases in mechanical properties by up to 288% in compressive strength, 195% in compressive modulus, 267% in compressive fracture energy and 160% shear storage modulus with the optimal GO concentration. Fourier transform infrared spectroscopy, scanning electron microscopy and swelling tests were implemented to characterize the nanocomposite hydrogels. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

NASA Astrophysics Data System (ADS)

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

2006-02-01

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

Potential Mechanisms for Enhanced Zika Epidemic and Disease.

PubMed

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

2018-05-11

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

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

PubMed

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

2015-05-01

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

Immobilization of a phosphonated analog of matrix phosphoproteins within cross-linked collagen as a templating mechanism for biomimetic mineralization

PubMed Central

Gu, Li-sha; Kim, Young Kyung; Liu, Yan; Takahashi, Kei; Arun, Senthil; Wimmer, Courtney E.; Osorio, Raquel; Ling, Jun-qi; Looney, Stephen W.; Pashley, David H.; Tay, Franklin R.

2010-01-01

Immobilization of phosphoproteins on a collagen matrix is important for induction of intrafibrillar apatite mineralization. Unlike phosphate esters, polyphosphonic acid has no reactive sites for covalent binding to collagen amine groups. Binding of polyvinylphosphonic acid (PVPA), a biomimetic templating analog of matrix phosphoproteins, to collagen was found to be electrostatic in nature. Thus, an alternative retention mechanism was designed for immobilization of PVPA to collagen by cross-linking the latter with carbodiimide (EDC). This mechanism is based on the principle of size exclusion entrapment of PVPA molecules within the internal water compartments of collagen. By cross-linking collagen with EDC, a zero-length cross-linking agent, the sieving property of collagen is increased, enabling the PVPA to be immobilized within the collagen. Absence of covalent cross-linking between PVPA and collagen was confirmed by FT-IR spectroscopy. Based on these results, a concentration range for immobilized PVPA to template intrafibrillar apatite deposition was established and validated using a single-layer reconstituted type I collagen mineralization model. In the presence of a polyacrylic acid-containing mineralization medium, optimal intrafibrillar mineralization of the EDC-cross-linked collagen was achieved using 500 and 1,000 μg/mL PVPA. The mineralized fibrils exhibited a hierarchical order of intrafibrillar mineral infiltration, as manifested by the appearance of electron-dense periodicity within unstained fibrils. Understanding the basic processes in intrafibrillar mineralization of reconstituted collagen creates opportunities for the design of tissue engineering materials for hard tissue repair and regeneration. PMID:20688200

Imprinted and X-linked non-coding RNAs as potential regulators of human placental function

PubMed Central

Buckberry, Sam; Bianco-Miotto, Tina; Roberts, Claire T

2014-01-01

Pregnancy outcome is inextricably linked to placental development, which is strictly controlled temporally and spatially through mechanisms that are only partially understood. However, increasing evidence suggests non-coding RNAs (ncRNAs) direct and regulate a considerable number of biological processes and therefore may constitute a previously hidden layer of regulatory information in the placenta. Many ncRNAs, including both microRNAs and long non-coding transcripts, show almost exclusive or predominant expression in the placenta compared with other somatic tissues and display altered expression patterns in placentas from complicated pregnancies. In this review, we explore the results of recent genome-scale and single gene expression studies using human placental tissue, but include studies in the mouse where human data are lacking. Our review focuses on the ncRNAs epigenetically regulated through genomic imprinting or X-chromosome inactivation and includes recent evidence surrounding the H19 lincRNA, the imprinted C19MC cluster microRNAs, and X-linked miRNAs associated with pregnancy complications. PMID:24081302

Linking scales in sea ice mechanics.

PubMed

Weiss, Jérôme; Dansereau, Véronique

2017-02-13

Mechanics plays a key role in the evolution of the sea ice cover through its control on drift, on momentum and thermal energy exchanges between the polar oceans and the atmosphere along cracks and faults, and on ice thickness distribution through opening and ridging processes. At the local scale, a significant variability of the mechanical strength is associated with the microstructural heterogeneity of saline ice, however characterized by a small correlation length, below the ice thickness scale. Conversely, the sea ice mechanical fields (velocity, strain and stress) are characterized by long-ranged (more than 1000 km) and long-lasting (approx. few months) correlations. The associated space and time scaling laws are the signature of the brittle character of sea ice mechanics, with deformation resulting from a multi-scale accumulation of episodic fracturing and faulting events. To translate the short-range-correlated disorder on strength into long-range-correlated mechanical fields, several key ingredients are identified: long-ranged elastic interactions, slow driving conditions, a slow viscous-like relaxation of elastic stresses and a restoring/healing mechanism. These ingredients constrained the development of a new continuum mechanics modelling framework for the sea ice cover, called Maxwell-elasto-brittle. Idealized simulations without advection demonstrate that this rheological framework reproduces the main characteristics of sea ice mechanics, including anisotropy, spatial localization and intermittency, as well as the associated scaling laws.This article is part of the themed issue 'Microdynamics of ice'. © 2016 The Author(s).

Linking scales in sea ice mechanics

PubMed Central

Weiss, Jérôme; Dansereau, Véronique

2017-01-01

Mechanics plays a key role in the evolution of the sea ice cover through its control on drift, on momentum and thermal energy exchanges between the polar oceans and the atmosphere along cracks and faults, and on ice thickness distribution through opening and ridging processes. At the local scale, a significant variability of the mechanical strength is associated with the microstructural heterogeneity of saline ice, however characterized by a small correlation length, below the ice thickness scale. Conversely, the sea ice mechanical fields (velocity, strain and stress) are characterized by long-ranged (more than 1000 km) and long-lasting (approx. few months) correlations. The associated space and time scaling laws are the signature of the brittle character of sea ice mechanics, with deformation resulting from a multi-scale accumulation of episodic fracturing and faulting events. To translate the short-range-correlated disorder on strength into long-range-correlated mechanical fields, several key ingredients are identified: long-ranged elastic interactions, slow driving conditions, a slow viscous-like relaxation of elastic stresses and a restoring/healing mechanism. These ingredients constrained the development of a new continuum mechanics modelling framework for the sea ice cover, called Maxwell–elasto-brittle. Idealized simulations without advection demonstrate that this rheological framework reproduces the main characteristics of sea ice mechanics, including anisotropy, spatial localization and intermittency, as well as the associated scaling laws. This article is part of the themed issue ‘Microdynamics of ice’. PMID:28025300

Linking scales in sea ice mechanics

NASA Astrophysics Data System (ADS)

Weiss, Jérôme; Dansereau, Véronique

2017-02-01

Mechanics plays a key role in the evolution of the sea ice cover through its control on drift, on momentum and thermal energy exchanges between the polar oceans and the atmosphere along cracks and faults, and on ice thickness distribution through opening and ridging processes. At the local scale, a significant variability of the mechanical strength is associated with the microstructural heterogeneity of saline ice, however characterized by a small correlation length, below the ice thickness scale. Conversely, the sea ice mechanical fields (velocity, strain and stress) are characterized by long-ranged (more than 1000 km) and long-lasting (approx. few months) correlations. The associated space and time scaling laws are the signature of the brittle character of sea ice mechanics, with deformation resulting from a multi-scale accumulation of episodic fracturing and faulting events. To translate the short-range-correlated disorder on strength into long-range-correlated mechanical fields, several key ingredients are identified: long-ranged elastic interactions, slow driving conditions, a slow viscous-like relaxation of elastic stresses and a restoring/healing mechanism. These ingredients constrained the development of a new continuum mechanics modelling framework for the sea ice cover, called Maxwell-elasto-brittle. Idealized simulations without advection demonstrate that this rheological framework reproduces the main characteristics of sea ice mechanics, including anisotropy, spatial localization and intermittency, as well as the associated scaling laws. This article is part of the themed issue 'Microdynamics of ice'.

Linking conceptual mechanisms and transcriptomic evidence of plasticity-driven diversification.

PubMed

Young, Rebecca L

2013-09-01

The East African cichlid fishes provide text book examples of adaptive radiation. Diversification and speciation of cichlids associate with variation in diet and trophic morphologies among other ecological, behavioural and morphological phenotypes (Kocher 2004). Numerous case studies in cichlids reveal a role of developmental plasticity in generating jaw ecomorphs in response to variation in feeding ecology that can facilitate niche exploitation and subsequent diversification (e.g. Meyer 1987). Specifically, genetic divergence among such environmentally induced morphs can occur via reproductive isolation due to divergence in habitat and resource use in combination with genetic assimilation of environmentally induced phenotypes (West-Eberhard 2003; Pfennig et al. 2010). Expansion of this conceptual model has been hampered in part by the limited knowledge of the molecular mechanisms of plasticity in nonstandard model systems and the associated lack of evidence linking the molecular mechanisms of plasticity to those that generate phenotypic divergence among populations and taxa. In this issue of Molecular Ecology, Gunter et al. (2013) identify the transcriptional mechanisms of diet-induced lower pharyngeal jaw (LPJ) plasticity in the cichlid fish Astatoreochromis alluaudi. Natural populations of A. alluaudi exhibit variation in jaw morphology in relation to diet hardness. Among the plastic responses to diet are adjustments to the LPJ ranging from a robust molariform morph in response to a hard diet to a more gracile papilliform morph in response to a soft diet (Fig. 1). Gunter and colleagues induced developmental plasticity of the A. alluaudi jaw using diet manipulations and compared LPJ transcriptomic profiles of the resulting morphs. In this foundational work, the authors identify 187 differentially expressed genes that underlie the development and maintenance of diet-induced LPJ morphologies. This list includes a wide range of genes spanning from broad

The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life

PubMed Central

Molloy, John; Allen, Katrina; Collier, Fiona; Tang, Mimi L. K.; Ward, Alister C.; Vuillermin, Peter

2013-01-01

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field. PMID:24351744

High velocity impact on composite link of aircraft wing flap mechanism

NASA Astrophysics Data System (ADS)

Heimbs, Sebastian; Lang, Holger; Havar, Tamas

2012-12-01

This paper describes the numerical investigation of the mechanical behaviour of a structural component of an aircraft wing flap support impacted by a wheel rim fragment. The support link made of composite materials was modelled in the commercial finite element code Abaqus/Explicit, incorporating intralaminar and interlaminar failure modes by adequate material models and cohesive interfaces. Validation studies were performed step by step using quasi-static tensile test data and low velocity impact test data. Finally, high velocity impact simulations with a metallic rim fragment were performed for several load cases involving different impact angles, impactor rotation and pre-stress. The numerical rim release analysis turned out to be an efficient approach in the development process of such composite structures and for the identification of structural damage and worst case impact loading scenarios.

Impulsivity as a mechanism linking child abuse and neglect with substance use in adolescence and adulthood.

PubMed

Oshri, Assaf; Kogan, Steve M; Kwon, Josephine A; Wickrama, K A S; Vanderbroek, Lauren; Palmer, Abraham A; MacKillop, James

2018-05-01

Emerging developmental perspectives suggest that adverse rearing environments promote neurocognitive adaptations that heighten impulsivity and increase vulnerability to risky behavior. Although studies document links between harsh rearing environments and impulsive behavior on substance use, the developmental hypothesis that impulsivity acts as mechanism linking adverse rearing environments to downstream substance use remains to be investigated. The present study investigated the role of impulsivity in linking child abuse and neglect with adult substance use using data from (a) a longitudinal sample of youth (Study 1, N = 9,421) and (b) a cross-sectional sample of adults (Study 2, N = 1,011). In Study 1, the links between child abuse and neglect and young adult smoking and marijuana use were mediated by increases in adolescent impulsivity. In Study 2, indirect links between child abuse and neglect and substance use were evidenced via delayed reward discounting and impulsivity traits. Among impulsivity subcomponents, robust indirect effects connecting childhood experiences to cigarette use emerged for negative urgency. Negative urgency, positive urgency, and sensation seeking mediated the effect of child abuse and neglect on cannabis and alcohol use. Results suggest that child abuse and neglect increases risk for substance use in part, due to effects on impulsivity. Individuals with adverse childhood experiences may benefit from substance use preventive intervention programs that target impulsive behaviors.

Sleep Duration and Diabetes Risk: Population Trends and Potential Mechanisms.

PubMed

Grandner, Michael A; Seixas, Azizi; Shetty, Safal; Shenoy, Sundeep

2016-11-01

Sleep is important for regulating many physiologic functions that relate to metabolism. Because of this, there is substantial evidence to suggest that sleep habits and sleep disorders are related to diabetes risk. In specific, insufficient sleep duration and/or sleep restriction in the laboratory, poor sleep quality, and sleep disorders such as insomnia and sleep apnea have all been associated with diabetes risk. This research spans epidemiologic and laboratory studies. Both physiologic mechanisms such as insulin resistance, decreased leptin, and increased ghrelin and inflammation and behavioral mechanisms such as increased food intake, impaired decision-making, and increased likelihood of other behavioral risk factors such as smoking, sedentary behavior, and alcohol use predispose to both diabetes and obesity, which itself is an important diabetes risk factor. This review describes the evidence linking sleep and diabetes risk at the population and laboratory levels.

Sleep Duration and Diabetes Risk: Population Trends and Potential Mechanisms

PubMed Central

Grandner, Michael A.; Seixas, Azizi; Shetty, Safal; Shenoy, Sundeep

2016-01-01

Sleep is important for regulating many physiologic functions that relate to metabolism. Because of this, there is substantial evidence to suggest that sleep habits and sleep disorders are related to diabetes risk. In specific, insufficient sleep duration and/or sleep restriction in the laboratory, poor sleep quality, and sleep disorders such as insomnia and sleep apnea have all been associated with diabetes risk. This research spans epidemiologic and laboratory studies. Both physiologic mechanisms such as insulin resistance, decreased leptin, and increased ghrelin and inflammation and behavioral mechanisms such as increased food intake, impaired decision-making, and increased likelihood of other behavioral risk factors such as smoking, sedentary behavior, and alcohol use predispose to both diabetes and obesity, which itself is an important diabetes risk factor. This review describes the evidence linking sleep and diabetes risk at the population and laboratory levels. PMID:27664039

Possible molecular mechanisms linking air pollution and asthma in children.

PubMed

Esposito, Susanna; Tenconi, Rossana; Lelii, Mara; Preti, Valentina; Nazzari, Erica; Consolo, Silvia; Patria, Maria Francesca

2014-03-01

Air pollution has many effects on the health of both adults and children, but children's vulnerability is unique. The aim of this review is to discuss the possible molecular mechanisms linking air pollution and asthma in children, also taking into account their genetic and epigenetic characteristics. Air pollutants appear able to induce airway inflammation and increase asthma morbidity in children. A better definition of mechanisms related to pollution-induced airway inflammation in asthmatic children is needed in order to find new clinical and therapeutic strategies for preventing the exacerbation of asthma. Moreover, reducing pollution-induced oxidative stress and consequent lung injury could decrease children's susceptibility to air pollution. This would be extremely useful not only for the asthmatic children who seem to have a genetic susceptibility to oxidative stress, but also for the healthy population. In addition, epigenetics seems to have a role in the lung damage induced by air pollution. Finally, a number of epidemiological studies have demonstrated that exposure to common air pollutants plays a role in the susceptibility to, and severity of respiratory infections. Air pollution has many negative effects on pediatric health and it is recognised as a serious health hazard. There seems to be an association of air pollution with an increased risk of asthma exacerbations and acute respiratory infections. However, further studies are needed in order to clarify the specific mechanism of action of different air pollutants, identify genetic polymorphisms that modify airway responses to pollution, and investigate the effectiveness of new preventive and/or therapeutic approaches for subjects with low antioxidant enzyme levels. Moreover, as that epigenetic changes are inheritable during cell division and may be transmitted to subsequent generations, it is very important to clarify the role of epigenetics in the relationship between air pollution and lung disease

Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis.

PubMed

Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Avilés-Triqueros, Marcelino; Weber, Bernhard H F; Fernández, Eduardo; Gascón, Alicia R

2012-04-01

The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents

PubMed Central

Negriff, Sonya; Brensilver, Matthew; Trickett, Penelope K.

2015-01-01

Purpose To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: 1) peer influence links early pubertal timing to later sexual behavior and substance use, 2) early maturers engage in substance use on their own and then select substance-using friends, or 3) early maturers initiate sexual behaviors which leads them to substance-using peers. Methods The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age: 9–13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three timepoints including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Results Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. Conclusions The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects. PMID:26003577

POMC neurons in heat: A link between warm temperatures and appetite suppression.

PubMed

Vicent, Maria A; Mook, Conor L; Carter, Matthew E

2018-05-01

When core body temperature increases, appetite and food consumption decline. A higher core body temperature can occur during exercise, during exposure to warm environmental temperatures, or during a fever, yet the mechanisms that link relatively warm temperatures to appetite suppression are unknown. A recent study in PLOS Biology demonstrates that neurons in the mouse hypothalamus that express pro-opiomelanocortin (POMC), a neural population well known to suppress food intake, also express a temperature-sensitive ion channel, transient receptor potential vanilloid 1 (TRPV1). Slight increases in body temperature cause a TRPV1-dependent increase in activity in POMC neurons, which suppresses feeding in mice. Taken together, this study suggests a novel mechanism linking body temperature and food-seeking behavior.

Polychlorinated biphenyls and links to cardiovascular disease.

PubMed

Perkins, Jordan T; Petriello, Michael C; Newsome, Bradley J; Hennig, Bernhard

2016-02-01

The pathology of cardiovascular disease is multi-faceted, with links to many modifiable and non-modifiable risk factors. Epidemiological evidence now implicates exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), with an increased risk of developing diabetes, hypertension, and obesity; all of which are clinically relevant to the onset and progression of cardiovascular disease. PCBs exert their cardiovascular toxicity either directly or indirectly via multiple mechanisms, which are highly dependent on the type and concentration of PCBs present. However, many PCBs may modulate cellular signaling pathways leading to common detrimental outcomes including induction of chronic oxidative stress, inflammation, and endocrine disruption. With the abundance of potential toxic pollutants increasing globally, it is critical to identify sensible means of decreasing associated disease risks. Emerging evidence now implicates a protective role of lifestyle modifications such as increased exercise and/or nutritional modulation via anti-inflammatory foods, which may help to decrease the vascular toxicity of PCBs. This review will outline the current state of knowledge linking coplanar and non-coplanar PCBs to cardiovascular disease and describe the possible molecular mechanism of this association.

Explicating the Social Mechanisms Linking Alcohol Use Behaviors and Ecology to Child Maltreatment

PubMed Central

Freisthler, Bridget; Holmes, Megan R.

2013-01-01

This paper begins to describe and explicate the specific mechanisms by which alcohol use and the alcohol use environment contribute to specific types of child maltreatment. These mechanisms relating alcohol outlet densities to child maltreatment described here include effects on social disorganization, parent’s drinking behaviors, and parental supervision. By investigating potential mechanisms, new information could be obtained on the importance and role of alcohol and their availability in the etiology of child maltreatment. This knowledge can be used to further tailor interventions to those conditions most likely to prevent and reduce maltreatment. PMID:25284922

Haem-assisted dityrosine-cross-linking of fibrinogen under non-thermal plasma exposure: one important mechanism of facilitated blood coagulation

PubMed Central

Ke, Zhigang; Huang, Qing

2016-01-01

Although blood coagulation facilitated by non-thermal plasma has been reported several years ago, the insight to the involved mechanisms is still rather limited. In this work, we report our discovery of a new mechanism for the haem-promoted blood-coagulation caused by non-thermal plasma treatment. The reason for the haem role is due to that its oxidized form, namely, hematin, can promote the dityrosine cross-linking of fibrinogen, the most important coagulation protein, to form a membrane-like layer on the surface of the treated blood with plasma exposure. Both haem and non-thermal-plasma generated hydrogen peroxide are requisite for the cross-linking process. We confirmed that fibrinogen can coordinate with the haem iron to form a protein-haem complex which shows pseudo-peroxidase activity, and in the presence of hydrogen peroxide, the complex can induce the dityrosine formation between fibrinogen molecules, leading to the fibrin network necessary for the blood coagulation. Understanding of such an underlying mechanism can be useful to guide more efficient application of non-thermal plasma in the management of hemostasis, thrombosis and etc. PMID:27229173

Enzymatic cross-linking of human recombinant elastin (HELP) as biomimetic approach in vascular tissue engineering.

PubMed

Bozzini, Sabrina; Giuliano, Liliana; Altomare, Lina; Petrini, Paola; Bandiera, Antonella; Conconi, Maria Teresa; Farè, Silvia; Tanzi, Maria Cristina

2011-12-01

The use of polymers naturally occurring in the extracellular matrix (ECM) is a promising strategy in regenerative medicine. If compared to natural ECM proteins, proteins obtained by recombinant DNA technology have intrinsic advantages including reproducible macromolecular composition, sequence and molecular mass, and overcoming the potential pathogens transmission related to polymers of animal origin. Among ECM-mimicking materials, the family of recombinant elastin-like polymers is proposed for drug delivery applications and for the repair of damaged elastic tissues. This work aims to evaluate the potentiality of a recombinant human elastin-like polypeptide (HELP) as a base material of cross-linked matrices for regenerative medicine. The cross-linking of HELP was accomplished by the insertion of cross-linking sites, glutamine and lysine, in the recombinant polymer and generating ε-(γ-glutamyl) lysine links through the enzyme transglutaminase. The cross-linking efficacy was estimated by infrared spectroscopy. Freeze-dried cross-linked matrices showed swelling ratios in deionized water (≈2500%) with good structural stability up to 24 h. Mechanical compression tests, performed at 37°C in wet conditions, in a frequency sweep mode, indicated a storage modulus of 2/3 kPa, with no significant changes when increasing number of cycles or frequency. These results demonstrate the possibility to obtain mechanically resistant hydrogels via enzymatic crosslinking of HELP. Cytotoxicity tests of cross-linked HELP were performed with human umbilical vein endothelial cells, by use of transwell filter chambers for 1-7 days, or with its extracts in the opportune culture medium for 24 h. In both cases no cytotoxic effects were observed in comparison with the control cultures. On the whole, the results suggest the potentiality of this genetically engineered HELP for regenerative medicine applications, particularly for vascular tissue regeneration.

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

SASH1, a new potential link between smoking and atherosclerosis.

PubMed

Weidmann, Henri; Touat-Hamici, Zahia; Durand, Herve; Mueller, Christian; Chardonnet, Solenne; Pionneau, Cedric; Charlotte, Frédéric; Janssen, Klaus-Peter; Verdugo, Ricardo; Cambien, Francois; Blankenberg, Stefan; Tiret, Laurence; Zeller, Tanja; Ninio, Ewa

2015-10-01

We have previously reported that SASH1 expression is increased in circulating human monocytes from smokers and was positively correlated with the number of carotid atherosclerotic plaques. The aim of this study was to further validate the link between smoking, SASH1 and atherosclerosis within the vascular wall and to assess the impact of SASH1 expression on endothelial cell functions. Human carotids with atherosclerotic plaques were obtained from 58 patients (45 of them with known smoking status: smoker, non-smoker, ex-smokers), and were processed for gene expression analyses and immunostaining. To investigate its function, SASH1 was silenced in human aortic endothelial cells (HAECs) using two different siRNA and subcellular localization of SASH1 was determined by immunostaining and subcellular fractionation. Subsequently the transcriptomic analyses and functional experiments (wound healing, WST-1 proliferation or Matrigel assays) were performed to characterize SASH1 function. SASH1 was expressed in human vascular cells (HAECs, smooth muscle cells) and in monocytes/macrophages. Its tissue expression was significantly higher in the atherosclerotic carotids of smokers compared to non-smokers (p < 0.01). In HAECs, SASH1 was expressed mostly in the cytoplasm and SASH1 knockdown resulted in an increased cell migration, proliferation and angiogenesis. Transcriptomic and pathway analyses showed that SASH1 silencing results in a decreased CYP1A1 expression possibly through the inhibition of TP53 activity. We showed that SASH1 expression is increased in atherosclerotic carotids in smokers and its silencing affects endothelial angiogenic functions; therefore we provide a potential link between smoking and atherosclerosis through SASH1 expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Orozco Cortés, Luis Fernando; Fernández García, Nicolás

2014-05-01

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

Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents.

PubMed

Negriff, Sonya; Brensilver, Matthew; Trickett, Penelope K

2015-06-01

To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: (1) peer influence links early pubertal timing to later sexual behavior and substance use; (2) early maturers engage in substance use on their own and then select substance-using friends; or (3) early maturers initiate sexual behaviors which lead them to substance-using peers. The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age, 9-13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three time points including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Flour mill stream blending affects sugar snap cookie and Japanese sponge cake quality and oxidative cross-linking potential of soft white wheat.

PubMed

Ramseyer, Daniel D; Bettge, Arthur D; Morris, Craig F

2011-01-01

The purpose of this research was to study the functional differences between straight grade (75% extraction rate) and patent (60% extraction rate) flour blends from 28 genetically pure soft white and club wheat grain lots, as evidenced by variation in sugar snap cookie and Japanese sponge cake quality. Functional differences were examined relative to arabinoxylan content, protein content, and oxidative cross-linking potential of flour slurries. Oxidative cross-linking measurements were obtained on flour slurries with a low shear Bostwick consistometer and considered endogenous oxidative cross-linking potential (water alone) or enhanced oxidative cross-linking potential (with added hydrogen peroxide-peroxidase). A 2-way ANOVA indicated that flour blend was the greater source of variation compared to grain lot for all response variables except water-extractable arabinoxylan content. Patent flours produced larger sugar snap cookies and Japanese sponge cakes, and contained significantly less total and water-unextractable arabinoxylans, protein, and ash than did straight grade flours. Patent flours produced more viscous slurries for endogenous and enhanced cross-linking measurements compared to the straight grade flours. The functional differences between patent and straight grade flours appear to be related to the particular mill streams that were utilized in the formulation of the 2 flour blends and compositional differences among those streams. Journal of Food Science © 2011 Institute of Food Technologists® No claim to original US government works.

Family Socioeconomic Status and Academic Achievement among Korean Adolescents: Linking Mechanisms of Family Processes and Adolescents' Time Use

ERIC Educational Resources Information Center

Bae, Dayoung; Wickrama, K. A. S.

2015-01-01

This study examined pathways through which family socioeconomic status may influence adolescents' academic achievement. We focused on parental monitoring and adolescents' after-school time-use patterns as linking mechanisms. Participants were 441 twelve- to fourteen-year-old Korean adolescents who participated in the Korea Welfare Panel Study.…

Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.

PubMed

Zheng, Jifeng; Zhao, Wei; Xu, Kai; Chen, Qingmao; Chen, Yingying; Shen, Yueliang; Xiao, Liping; Jiang, Liqin; Chen, Yuan

2017-04-05

Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P<0.05; n=7). Caffeine was also found to be a hERG channel blocker with an IC 50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC 50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers. Published by Elsevier B.V.

The Potential Neural Mechanisms of Acute Indirect Vibration

PubMed Central

2011-01-01

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

Tank tread assemblies with track-linking mechanism

NASA Technical Reports Server (NTRS)

Collins, Earl R., Jr. (Inventor)

1986-01-01

The proposed tank tread assembly has adjacent tank tread segments joined by a link bearing tapered pins retained by clips inserted through the tread shells perpendicular to the axes of the pin. It also has highway pads attached by a release rod bearing tapered, grooved cams which interlockingly engage tabs inserted into the tread shells.

Relationship between sleep duration and childhood obesity: Systematic review including the potential underlying mechanisms.

PubMed

Felső, R; Lohner, S; Hollódy, K; Erhardt, É; Molnár, D

2017-09-01

The prevalence of obesity is continually increasing worldwide. Determining risk factors for obesity may facilitate effective preventive programs. The present review focuses on sleep duration as a potential risk factor for childhood obesity. The aim is to summarize the evidence on the association of sleep duration and obesity and to discuss the underlying potential physiological and/or pathophysiological mechanisms. The Ovid MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for papers using text words with appropriate truncation and relevant indexing terms. All studies objectively measuring sleep duration and investigating the association between sleep duration and obesity or factors (lifestyle and hormonal) possibly associated with obesity were included, without making restrictions based on study design or language. Data from eligible studies were extracted in tabular form and summarized narratively. After removing duplicates, 3540 articles were obtained. Finally, 33 studies (including 3 randomized controlled trials and 30 observational studies) were included in the review. Sleep duration seems to influence weight gain in children, however, the underlying explanatory mechanisms are still uncertain. In our review only the link between short sleep duration and the development of insulin resistance, sedentarism and unhealthy dietary patterns could be verified, while the role of other mediators, such as physical activity, screen time, change in ghrelin and leptin levels, remained uncertain. There are numerous evidence gaps. To answer the remaining questions, there is a need for studies meeting high methodological standards and including a large number of children. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. 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.

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.

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.

Recycling potential for low voltage and high voltage high rupturing capacity fuse links.

PubMed

Psomopoulos, Constantinos S; Barkas, Dimitrios A; Kaminaris, Stavros D; Ioannidis, George C; Karagiannopoulos, Panagiotis

2017-12-01

Low voltage and high voltage high-rupturing-capacity fuse links are used in LV and HV installations respectively, protecting mainly the LV and HV electricity distribution and transportation networks. The Waste Electrical and Electronic Equipment Directive (2002/96/EC) for "Waste of electrical and electronic equipment" is the main related legislation and as it concerns electrical and electronic equipment, it includes electric fuses. Although, the fuse links consist of recyclable materials, only small scale actions have been implemented for their recycling around Europe. This work presents the possibilities for material recovery from this specialized industrial waste for which there are only limited volume data. Furthermore, in order to present the huge possibilities and environmental benefits, it presents the potential for recycling of HRC fuses used by the Public Power Corporation of Greece, which is the major consumer for the country, but one of the smallest ones in Europe and globally, emphasizing in this way in the issue. According to the obtained results, fuse recycling could contribute to the effort for minimize the impacts on the environment through materials recovery and reduction of the wastes' volume disposed of in landfills. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of sex-linked genetic mechanisms on attention and impulsivity

PubMed Central

Trent, Simon; Davies, William

2012-01-01

It is now generally agreed that there are inherent sex differences in healthy individuals across a number of neurobiological domains (including brain structure, neurochemistry, and cognition). Moreover, there is a burgeoning body of evidence highlighting sex differences within neuropsychiatric populations (in terms of the rates of incidence, clinical features/progression, neurobiology and pathology). Here, we consider the extent to which attention and impulsivity are sexually dimorphic in healthy populations and the extent to which sex might modulate the expression of disorders characterised by abnormalities in attention and/or impulsivity such as attention deficit hyperactivity disorder (ADHD), autism and addiction. We then discuss general genetic mechanisms that might underlie sex differences in attention and impulsivity before focussing on specific positional and functional candidate sex-linked genes that are likely to influence these cognitive processes. Identifying novel sex-modulated molecular targets should ultimately enable us to develop more effective therapies in disorders associated with attentional/impulsive dysfunction. PMID:21983394

Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.

PubMed

Stanhope, K L; Goran, M I; Bosy-Westphal, A; King, J C; Schmidt, L A; Schwarz, J-M; Stice, E; Sylvetsky, A C; Turnbaugh, P J; Bray, G A; Gardner, C D; Havel, P J; Malik, V; Mason, A E; Ravussin, E; Rosenbaum, M; Welsh, J A; Allister-Price, C; Sigala, D M; Greenwood, M R C; Astrup, A; Krauss, R M

2018-05-14

Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis. © 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Light-induced cross-linking and post-cross-linking modification of polyglycidol.

PubMed

Marquardt, F; Bruns, M; Keul, H; Yagci, Y; Möller, M

2018-02-08

The photoinduced radical generation process has received renewed interest due to its economic and ecological appeal. Herein the light-induced cross-linking of functional polyglycidol and its post-cross-linking modification are presented. Linear polyglycidol was first functionalized with a tertiary amine in a two-step reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV-light mediated reaction with camphorquinone as a type II photoinitiator. The cross-linked polyglycidol was further functionalized by quaternization with various organoiodine compounds. Aqueous dispersions of the cross-linked polymers were investigated by means of DLS and zeta potential measurements. Polymer films were evaluated by DSC and XPS.

Age differences in search of web pages: the effects of link size, link number, and clutter.

PubMed

Grahame, Michael; Laberge, Jason; Scialfa, Charles T

2004-01-01

Reaction time, eye movements, and errors were measured during visual search of Web pages to determine age-related differences in performance as a function of link size, link number, link location, and clutter. Participants (15 young adults, M = 23 years; 14 older adults, M = 57 years) searched Web pages for target links that varied from trial to trial. During one half of the trials, links were enlarged from 10-point to 12-point font. Target location was distributed among the left, center, and bottom portions of the screen. Clutter was manipulated according to the percentage of used space, including graphics and text, and the number of potentially distracting nontarget links was varied. Increased link size improved performance, whereas increased clutter and links hampered search, especially for older adults. Results also showed that links located in the left region of the page were found most easily. Actual or potential applications of this research include Web site design to increase usability, particularly for older adults.

Linked shoulder replacement: current design problems and a new design proposal.

PubMed

Mohammed, Ali Abdullah; Frostick, Simon Peter

2016-04-01

Totally constrained shoulder replacement with linked components is one of the surgical options in post-tumor resection shoulder reconstruction or in complex shoulder revision operations. In this paper, we intend to shed light on such an implant design, which provides a linked constrained connection between the humeral head and the glenoid, and to show some immediate postoperative complications, implant progression to decrease the chances of implant mechanical postinsertion failure, and a new design proposal. In our center, we use the linked prosthesis in complex revision situations; however, there have been some complications, which could be attributed mainly to the engineering and the implant design, and hence potentially avoidable by making a different design to cover for those mechanical issues. Two such complications are described in this paper. Early revisions after linked shoulder replacement implantation were needed in two occasions due to implant disconnection: one of them was due to dislodgement from the native glenoid, and the second one was due to the disengagement of the ringlet which secures the linkage mechanism between the humeral head and the implanted glenoid shell. There is a need for a more stable design construct to avoid the reported complications that needed early revision surgeries. The new design proposed is an attempt to help providing a better and more stable implant to decrease the chances of revision in those complex situations where the patient already had many major operations, and working to increase the durability of the implant is crucial.

Link prediction based on local weighted paths for complex networks

NASA Astrophysics Data System (ADS)

Yao, Yabing; Zhang, Ruisheng; Yang, Fan; Yuan, Yongna; Hu, Rongjing; Zhao, Zhili

As a significant problem in complex networks, link prediction aims to find the missing and future links between two unconnected nodes by estimating the existence likelihood of potential links. It plays an important role in understanding the evolution mechanism of networks and has broad applications in practice. In order to improve prediction performance, a variety of structural similarity-based methods that rely on different topological features have been put forward. As one topological feature, the path information between node pairs is utilized to calculate the node similarity. However, many path-dependent methods neglect the different contributions of paths for a pair of nodes. In this paper, a local weighted path (LWP) index is proposed to differentiate the contributions between paths. The LWP index considers the effect of the link degrees of intermediate links and the connectivity influence of intermediate nodes on paths to quantify the path weight in the prediction procedure. The experimental results on 12 real-world networks show that the LWP index outperforms other seven prediction baselines.

Air pollution, inflammation and preterm birth: a potential mechanistic link.

PubMed

Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A; Sánchez, Brisa N; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G; O'Neill, Marie S

2014-02-01

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. Copyright © 2013 Elsevier Ltd. All rights reserved.

AIR POLLUTION, INFLAMMATION AND PRETERM BIRTH: A POTENTIAL MECHANISTIC LINK

PubMed Central

Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A.; Sánchez, Brisa N.; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G.; O´Neill, Marie S.

2014-01-01

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. PMID:24382337

Anti-inflammatory activities and potential mechanisms of phenolic acids isolated from Salvia miltiorrhiza f. alba roots in THP-1 macrophages.

PubMed

Liu, Haimei; Ma, Shuli; Xia, Hongrui; Lou, Hongxiang; Zhu, Faliang; Sun, Longru

2018-05-08

The roots of Salvia miltiorrhiza f. alba (Lamiaceae) (RSMA) are used as the Danshen, a traditional Chinese medicine, to treat the vascular diseases at local clinics, especially for the remedy of thromboangiitis obliterans (TAO) more than 100 years. Phenolic acids are one of the major effective constituents of RSMA, and some studies have linked phenolic acids with anti-inflammatory functions. The purpose of this research was to isolate phenolic acids from RSMA and investigate their anti-inflammatory effects and potential mechanisms. Nine already known compounds were obtained from RSMA. Their structures were elucidated through the spectroscopic analysis and comparing the reported data. The anti-inflammatory effects and potential mechanisms were investigated in LPS-stimulated THP-1 cells, using salvianolic acid B (SalB) as the positive control. The enzyme-linked immunosorbent assays (ELISA) were used to determine the secretory protein levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). And quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the mRNA levels of these inflammatory cytokines. The expression of TLR4, p65, p-p65, IκBα, and p-IκBα were measured using western blot. All these compounds, except for rosmarinic acid (5) and isosalvianolic acid (6) for IL-6 protein levels, rosmarinic acid-o-β-D-glucopyranoside (3) for IL-6 mRNA, and rosmarinic acid-o-β-D-glucopyranoside (3), rosmarinic acid (5) and isosalvianolic acid (6) for TNF-α mRNA levels, remarkably inhibited the production of TNF-α, IL-1β, and IL-6 at the concentration of 5 and 25μM in the mRNA and protein levels. Lithospermic acid (7) showed the strongest inhibitory effect among them and was similar to that of SalB. In particular, lithospermic acid (7) and SalB markedly downregulated the expressions of TLR4, p-p65, and p-IκBα induced by LPS in THP-1 macrophages. All the phenolic acids displayed anti-inflammatory properties

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

PubMed

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

2010-03-15

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

ROMP-based thermosetting polymers from modified castor oil with various cross-linking agents

NASA Astrophysics Data System (ADS)

Ding, Rui

Polymers derived from bio-renewable resources are finding an increase in global demand. In addition, polymers with distinctive functionalities are required in certain advanced fields, such as aerospace and civil engineering. In an attempt to meet both these needs, the goal of this work aims to develop a range of bio-based thermosetting matrix polymers for potential applications in multifunctional composites. Ring-opening metathesis polymerization (ROMP), which recently has been explored as a powerful method in polymer chemistry, was employed as a unique pathway to polymerize agricultural oil-based reactants. Specifically, a novel norbornyl-functionalized castor oil alcohol (NCA) was investigated to polymerize different cross-linking agents using ROMP. The effects of incorporating dicyclopentadiene (DCPD) and a norbornene-based crosslinker (CL) were systematically evaluated with respect to curing behavior and thermal mechanical properties of the polymers. Isothermal differential scanning calorimetry (DSC) was used to investigate the conversion during cure. Dynamic DSC scans at multiple heating rates revealed conversion-dependent activation energy by Ozawa-Flynn-Wall analysis. The glass transition temperature, storage modulus, and loss modulus for NCA/DCPD and NCA/CL copolymers with different cross-linking agent loading were compared using dynamic mechanical analysis. Cross-link density was examined to explain the very different dynamic mechanical behavior. Mechanical stress-strain curves were developed through tensile test, and thermal stability of the cross-linked polymers was evaluated by thermogravimetric analysis to further investigate the structure-property relationships in these systems.

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.

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.

Cow's Milk and Immune Function in the Respiratory Tract: Potential Mechanisms.

PubMed

Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F J; Brugman, Sylvia; van Neerven, R J Joost

2018-01-01

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow's milk. Indeed, recent studies show inverse associations between raw cow's milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow's milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow's milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow's milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow's milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow's milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw

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.

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

PubMed

Tikhonov, D B

2008-06-01

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

Antidiabetic Drugs in Alzheimer's Disease: Mechanisms of Action and Future Perspectives

PubMed Central

Femminella, Grazia Daniela; Bencivenga, Leonardo; Petraglia, Laura; Visaggi, Lucia; Gioia, Lucia; Grieco, Fabrizio Vincenzo; de Lucia, Claudio; Komici, Klara; Edison, Paul

2017-01-01

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results. Here, we review the evidence on the mechanisms of action of antidiabetic drugs and their potential use in AD. PMID:28656154

Potential Mechanisms of Action of Dietary Phytochemicals for Cancer Prevention by Targeting Cellular Signaling Transduction Pathways.

PubMed

Chen, Hongyu; Liu, Rui Hai

2018-04-04

Cancer is a severe health problem that significantly undermines life span and quality. Dietary approach helps provide preventive, nontoxic, and economical strategies against cancer. Increased intake of fruits, vegetables, and whole grains are linked to reduced risk of cancer and other chronic diseases. The anticancer activities of plant-based foods are related to the actions of phytochemicals. One potential mechanism of action of anticancer phytochemicals is that they regulate cellular signal transduction pathways and hence affects cancer cell behaviors such as proliferation, apoptosis, and invasion. Recent publications have reported phytochemicals to have anticancer activities through targeting a wide variety of cell signaling pathways at different levels, such as transcriptional or post-transcriptional regulation, protein activation and intercellular messaging. In this review, we discuss major groups of phytochemicals and their regulation on cell signaling transduction against carcinogenesis via key participators, such as Nrf2, CYP450, MAPK, Akt, JAK/STAT, Wnt/β-catenin, p53, NF-κB, and cancer-related miRNAs.

Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles.

PubMed

Yadav, Pinki; Lal, Kashmiri; Kumar, Ashwani; Guru, Santosh Kumar; Jaglan, Sundeep; Bhushan, Shashi

2017-01-27

A series of chalcone linked-1,2,3-triazoles was synthesized via cellulose supported copper nanoparticle catalyzed click reaction in water. The structures of all the compounds were analyzed by IR, NMR and Mass spectral techniques. All the synthesized products were subjected to 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay against a panel of four human cancer cell lines (MCF-7, MIA-Pa-Ca-2, A549, HepG2) to check their anticancer potential. Compound 6h was found to be most active against all the tested cancer cell lines with IC 50 values in the range of 4-11 μM and showed better or comparable activity to the reference drug against all the tested cell lines. Cell cycle analysis revealed that compound 6h induces apoptosis and G2/S arrest in MIA-Pa-Ca-2 cells. Compound 6h triggers mitochondrial potential loss in pancreatic cancer MIA-Pa-Ca-2 cells. Further, Compound 6h also triggers caspase-3 and PARP-1 cleavage, which increases in dose dependent manner. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Potential Mechanisms of Cancer Prevention by Weight Control

NASA Astrophysics Data System (ADS)

Jiang, Yu; Wang, Weiqun

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

Actin Cross-link Assembly and Disassembly Mechanics for α-Actinin and Fascin*

PubMed Central

Courson, David S.; Rock, Ronald S.

2010-01-01

Self-assembly of complex structures is commonplace in biology but often poorly understood. In the case of the actin cytoskeleton, a great deal is known about the components that include higher order structures, such as lamellar meshes, filopodial bundles, and stress fibers. Each of these cytoskeletal structures contains actin filaments and cross-linking proteins, but the role of cross-linking proteins in the initial steps of structure formation has not been clearly elucidated. We employ an optical trapping assay to investigate the behaviors of two actin cross-linking proteins, fascin and α-actinin, during the first steps of structure assembly. Here, we show that these proteins have distinct binding characteristics that cause them to recognize and cross-link filaments that are arranged with specific geometries. α-Actinin is a promiscuous cross-linker, linking filaments over all angles. It retains this flexibility after cross-links are formed, maintaining a connection even when the link is rotated. Conversely, fascin is extremely selective, only cross-linking filaments in a parallel orientation. Surprisingly, bundles formed by either protein are extremely stable, persisting for over 0.5 h in a continuous wash. However, using fluorescence recovery after photobleaching and fluorescence decay experiments, we find that the stable fascin population can be rapidly competed away by free fascin. We present a simple avidity model for this cross-link dissociation behavior. Together, these results place constraints on how cytoskeletal structures assemble, organize, and disassemble in vivo. PMID:20551315

Compulsive Eating: The Emotional Link of Its Use as a Coping Mechanism for Resident Freshman Female College Students.

ERIC Educational Resources Information Center

Beylerian, Nvair Kadian

An 18-year old's freshman year in college is not only a test of his or her intellect, but also a test in social skills, adaptability to new living situations, and other conditions. This study examined the link of emotions to compulsive eating and its use as a coping mechanism for female college students. It explores the stresses of the transition…

Analytic analysis of auxetic metamaterials through analogy with rigid link systems

NASA Astrophysics Data System (ADS)

Rayneau-Kirkhope, Daniel; Zhang, Chengzhao; Theran, Louis; Dias, Marcelo A.

2018-02-01

In recent years, many structural motifs have been designed with the aim of creating auxetic metamaterials. One area of particular interest in this subject is the creation of auxetic material properties through elastic instability. Such metamaterials switch from conventional behaviour to an auxetic response for loads greater than some threshold value. This paper develops a novel methodology in the analysis of auxetic metamaterials which exhibit elastic instability through analogy with rigid link lattice systems. The results of our analytic approach are confirmed by finite-element simulations for both the onset of elastic instability and post-buckling behaviour including Poisson's ratio. The method gives insight into the relationships between mechanisms within lattices and their mechanical behaviour; as such, it has the potential to allow existing knowledge of rigid link lattices with auxetic paths to be used in the design of future buckling-induced auxetic metamaterials.

Computerized symbolic manipulation in structural mechanics Progress and potential

NASA Technical Reports Server (NTRS)

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

1978-01-01

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

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.

Electron tomography provides a direct link between the Payne effect and the inter-particle spacing of rubber composites

PubMed Central

Staniewicz, Lech; Vaudey, Thomas; Degrandcourt, Christophe; Couty, Marc; Gaboriaud, Fabien; Midgley, Paul

2014-01-01

Rubber-filler composites are a key component in the manufacture of tyres. The filler provides mechanical reinforcement and additional wear resistance to the rubber, but it in turn introduces non-linear mechanical behaviour to the material which most likely arises from interactions between the filler particles, mediated by the rubber matrix. While various studies have been made on the bulk mechanical properties and of the filler network structure (both imaging and by simulations), there presently does not exist any work directly linking filler particle spacing and mechanical properties. Here we show that using STEM tomography, aided by a machine learning image analysis procedure, to measure silica particle spacings provides a direct link between the inter-particle spacing and the reduction in shear modulus as a function of strain (the Payne effect), measured using dynamic mechanical analysis. Simulations of filler network formation using attractive, repulsive and non-interacting potentials were processed using the same method and compared with the experimental data, with the net result being that an attractive inter-particle potential is the most accurate way of modelling styrene-butadiene rubber-silica composite formation. PMID:25487130

Designing cross-linked xylanase aggregates for bioconversion of agroindustrial waste biomass towards potential production of nutraceuticals.

PubMed

Hero, J S; Romero, C M; Pisa, J H; Perotti, N I; Olivaro, C; Martinez, M A

2018-05-01

Immobilized biocatalysts design has the potential to efficiently produce valuable bioproducts from lignocellulosic biomass. Among them, the carrier-free immobilization through the cross-linked enzyme aggregates technology is a simple and low-cost alternative. A two steps statistical approach was utilized to evaluate the synthesis of a cross-linked enzyme aggregate from a xylanolytic preparation, which was produced by Cohnella sp. AR92 grown in a peptone-based culture medium. The resulting immobilized biocatalyst, Xyl-CLEA, was significate more stable (25 to 45%) towards temperatures up to 50°C with respect to the free enzyme, and retained over 50% of its initial activity after 5 consecutive cycles of reuse. By means of infrared spectroscopy and electron microscopy, the Xyl-CLEA showed architectural features described as signature of type I and type II of protein aggregates. These, were the result of the simultaneous aggregation of a multiplicity of proteins from the crude enzymatic extract. The enzymatic activity was assessed using alkali pretreated sugar cane bagasse as substrate. Whereas the free enzymatic preparation released xylose as the main product, the immobilized xylanase produced xylooligosaccharides, thus showing that the immobilization procedure modified the potential application of the extracellular xylanase from Conhella sp. AR92. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Nuclear mRNA Surveillance Mechanisms: Function and Links to Human Disease.

PubMed

Singh, Pragyan; Saha, Upasana; Paira, Sunirmal; Das, Biswadip

2018-05-11

Production of export-competent mRNAs involves transcription and a series of dynamic processing and modification events of pre-messenger RNAs in the nucleus. Mutations in the genes encoding the transcription and mRNP processing machinery and the complexities involved in the biogenesis events lead to the formation of aberrant messages. These faulty transcripts are promptly eliminated by the nuclear RNA exosome and its cofactors to safeguard the cells and organisms from genetic catastrophe. Mutations in the components of the core nuclear exosome and its cofactors lead to the tissue-specific dysfunction of exosomal activities, which are linked to diverse human diseases and disorders. In this article, we examine the structure and function of both the yeast and human RNA exosome complex and its cofactors, discuss the nature of the various altered amino acid residues implicated in these diseases with the speculative mechanisms of the mutation-induced disorders and project the frontier and prospective avenues of the future research in this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

Shen, Lin; Yang, Weitao

2016-04-12

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

Tissue Vibration Induces Carotid Artery Endothelial Dysfunction: A Mechanism Linking Snoring and Carotid Atherosclerosis?

PubMed Central

Cho, Jin-Gun; Witting, Paul K.; Verma, Manisha; Wu, Ben J.; Shanu, Anu; Kairaitis, Kristina; Amis, Terence C.; Wheatley, John R.

2011-01-01

Study Objectives: We have previously identified heavy snoring as an independent risk factor for carotid atherosclerosis. In order to explore the hypothesis that snoring-associated vibration of the carotid artery induces endothelial dysfunction (an established atherogenic precursor), we utilized an animal model to examine direct effects of peri-carotid tissue vibration on carotid artery endothelial function and structure. Design: In supine anesthetized, ventilated rabbits, the right carotid artery (RCA) was directly exposed to vibrations for 6 h (peak frequency 60 Hz, energy matched to that of induced snoring in rabbits). Similarly instrumented unvibrated rabbits served as controls. Features of OSA such as hypoxemia, large intra-pleural swings and blood pressure volatility were prevented. Carotid endothelial function was then examined: (1) biochemically by measurement of tissue cyclic guanosine monophosphate (cGMP) to acetylcholine (ACh) and sodium nitroprusside (SNP); and (2) functionally by monitoring vessel relaxation with acetylcholine in a myobath. Measurement and Results: Vessel cGMP after stimulation with ACh was reduced in vibrated RCA compared with unvibrated (control) arteries in a vibration energy dose-dependent manner. Vibrated RCA also showed decreased vasorelaxation to ACh compared with control arteries. Notably, after addition of SNP (nitric oxide donor), cGMP levels did not differ between vibrated and control arteries, thereby isolating vibration-induced dysfunction to the endothelium alone. This dysfunction occurred in the presence of a morphologically intact endothelium without increased apoptosis. Conclusions: Carotid arteries subjected to 6 h of continuous peri-carotid tissue vibration displayed endothelial dysfunction, suggesting a direct plausible mechanism linking heavy snoring to the development of carotid atherosclerosis. Citation: Cho JG; Witting PK; Verma M; Wu BJ; Shanu A; Kairaitis K; Amis TC; Wheatley JR. Tissue vibration induces

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.

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

PubMed

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

2018-03-28

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

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

NASA Astrophysics Data System (ADS)

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

2013-04-01

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

EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

PubMed Central

Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

2017-01-01

Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

Linking Antimicrobial Potential of Natural Products Derived from Aquatic Organisms and Microbes Involved in Alzheimer's Disease - A Review.

PubMed

Stojkovic, Dejan; Kostic, Marina; Smiljkovic, Marija; Aleksic, Milena; Vasiljevic, Perica; Nikolic, Milos; Sokovic, Marina

2018-03-08

The following review is oriented towards microbes linked to Alzheimer's disease (AD) and antimicrobial effect of compounds and extracts derived from aquatic organisms against specific bacteria, fungi and viruses which were found previously in patients suffering from AD. Major group of microbes linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact, this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes. This literature review might serve as a starting platform to develop novel supportive therapy for patients suffering from AD and to possibly prevent escalation of the disease in patients already having high risk factors for AD occurrence. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The role of hexokinase in cardioprotection – mechanism and potential for translation

PubMed Central

Pereira, Gonçalo C; Pasdois, Philippe

2015-01-01

Mitochondrial permeability transition pore (mPTP) opening plays a critical role in cardiac reperfusion injury and its prevention is cardioprotective. Tumour cell mitochondria usually have high levels of hexokinase isoform 2 (HK2) bound to their outer mitochondrial membranes (OMM) and HK2 binding to heart mitochondria has also been implicated in resistance to reperfusion injury. HK2 dissociates from heart mitochondria during ischaemia, and the extent of this correlates with the infarct size on reperfusion. Here we review the mechanisms and regulations of HK2 binding to mitochondria and how this inhibits mPTP opening and consequent reperfusion injury. Major determinants of HK2 dissociation are the elevated glucose‐6‐phosphate concentrations and decreased pH in ischaemia. These are modulated by the myriad of signalling pathways implicated in preconditioning protocols as a result of a decrease in pre‐ischaemic glycogen content. Loss of mitochondrial HK2 during ischaemia is associated with permeabilization of the OMM to cytochrome c, which leads to greater reactive oxygen species production and mPTP opening during reperfusion. Potential interactions between HK2 and OMM proteins associated with mitochondrial fission (e.g. Drp1) and apoptosis (B‐cell lymphoma 2 family members) in these processes are examined. Also considered is the role of HK2 binding in stabilizing contact sites between the OMM and the inner membrane. Breakage of these during ischaemia is proposed to facilitate cytochrome c loss during ischaemia while increasing mPTP opening and compromising cellular bioenergetics during reperfusion. We end by highlighting the many unanswered questions and discussing the potential of modulating mitochondrial HK2 binding as a pharmacological target. Linked Articles This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8 PMID

Evidence for a Cyanine Link between Propargylamine Drugs and Monoamine Oxidase Clarifies the Inactivation Mechanism

NASA Astrophysics Data System (ADS)

Albreht, Alen; Vovk, Irena; Mavri, Janez; Marco-Contelles, Jose; Ramsay, Rona R.

2018-05-01

Successful propargylamine drugs such as deprenyl inactivate monoamine oxidase (MAO), a target in multi-faceted approaches to prevent neurodegeneration in the aging population, but the chemical structure and mechanism of the irreversible inhibition are still debated. We characterized the covalent cyanine structure linking the multi-target propargylamine inhibitor ASS234 and the flavin adenine dinucleotide in MAO-A using a combination of ultra-high performance liquid chromatography, spectroscopy, mass spectrometry, and computational methods. The partial double bond character of the cyanine chain gives rise to 4 interconverting geometric isomers of the adduct which were chromatographically separated at low temperatures. The configuration of the cyanine linker governs adduct stability with segments of much higher flexibility and rigidity than previously hypothesized. The findings indicate the importance of intramolecular electrostatic interactions in the MAO binding site and provide key information relevant to incorporation of the propargyl moiety into novel multi-target drugs. Based on the structure, we propose a mechanism of MAO inactivation applicable to all propargylamine inhibitors.

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

PubMed

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

2012-09-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Glacier surge mechanism based on linked cavity configuration of the basal water conduit system

NASA Astrophysics Data System (ADS)

Kamb, Barclay

1987-08-01

Based on observations of the 1982-1983 surge of Variegated Glacier, Alaska, a model of the surge mechanism is developed in terms of a transition from the normal tunnel configuration of the basal water conduit system to a linked cavity configuration that tends to restrict the flow of water, resulting in increased basal water pressures that cause rapid basal sliding. The linked cavity system consists of basal cavities formed by ice-bedrock separation (cavitation), ˜1 m high and ˜10 m in horizontal dimensions, widely scattered over the glacier bed, and hydraulically linked by narrow connections where separation is minimal (separation gap ≲ 0.1 m). The narrow connections, called orifices, control the water flow through the conduit system; by throttling the flow through the large cavities, the orifices keep the water flux transmitted by the basal water system at normal levels even though the total cavity cross-sectional area (˜200 m2) is much larger than that of a tunnel system (˜10 m2). A physical model of the linked cavity system is formulated in terms of the dimensions of the "typical" cavity and orifice and the numbers of these across the glacier width. The model concentrates on the detailed configuration of the typical orifice and its response to basal water pressure and basal sliding, which determines the water flux carried by the system under given conditions. Configurations are worked out for two idealized orifice types, step orifices that form in the lee of downglacier-facing bedrock steps, and wave orifices that form on the lee slopes of quasisinusoidal bedrock waves and are similar to transverse "N channels." The orifice configurations are obtained from the results of solutions of the basal-sliding-with-separation problem for an ice mass constituting of linear half-space of linear rheology, with nonlinearity introduced by making the viscosity stress-dependent on an intuitive basis. Modification of the orifice shapes by melting of the ice roof due to

Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy

PubMed Central

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

2018-01-01

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

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

PubMed

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-08-11

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

Potential Links between Hepadnavirus and Bornavirus Sequences in the Host Genome and Cancer.

PubMed

Honda, Tomoyuki

2017-01-01

Various viruses leave their sequences in the host genomes during infection. Such events occur mainly in retrovirus infection but also sometimes in DNA and non-retroviral RNA virus infections. If viral sequences are integrated into the genomes of germ line cells, the sequences can become inherited as endogenous viral elements (EVEs). The integration events of viral sequences may have oncogenic potential. Because proviral integrations of some retroviruses and/or reactivation of endogenous retroviruses are closely linked to cancers, viral insertions related to non-retroviral viruses also possibly contribute to cancer development. This article focuses on genomic viral sequences derived from two non-retroviral viruses, whose endogenization is already reported, and discusses their possible contributions to cancer. Viral insertions of hepatitis B virus play roles in the development of hepatocellular carcinoma. Endogenous bornavirus-like elements, the only non-retroviral RNA virus-related EVEs found in the human genome, may also be involved in cancer formation. In addition, the possible contribution of the interactions between viruses and retrotransposons, which seem to be a major driving force for generating EVEs related to non-retroviral RNA viruses, to cancers will be discussed. Future studies regarding the possible links described here may open a new avenue for the development of novel therapeutics for tumor virus-related cancers and/or provide novel insights into EVE functions.

Ventral striatal activity links adversity and reward processing in children.

PubMed

Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

2017-08-01

Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vegetation and erosion: comments on the linking mechanisms from the perspective of the Australian drylands.

NASA Astrophysics Data System (ADS)

Dunkerley, D.

2009-04-01

John Thorne's wide-ranging research included an emphasis on the diverse roles of vegetation in modifying erosion processes under Mediterranean conditions, with primary field studies in Spain. Different global drylands reflect some differences in the nature or strength of the mechanisms linking vegetation and erosion. In Australia, low topographic gradients and plants adapted to water scarcity have facilitated the widespread development of contour-aligned vegetation groves. In these landscapes, the role of individual plants in modifying raindrop impact energy or overland flow erosivity is secondary to the community-level effects of the grove structures. Erosion in common rain events is limited to quite local redistribution of soil materials on metre scales. This highlights one of the unresolved issues that warrants more attention in drylands globally: under what range of rain events does the protective role of individual plants (or of groves) operate, and what is the threshold event size beyond which their effect is swamped by integrated overland flow arriving from upslope? In contrast with, for example, the well-understood role of bankfull flows in river architecture, general principles underlying dryland hillslope and channel responses to events of various magnitudes remain obscure. Clearly, however, there is no single role for plant cover; rather, that role varies with event magnitude and related properties such as the time since the last rain event. An important conclusion is therefore that context is important when evaluating the links between vegetation and erosion. The developing view of overland flow generally, but particularly relevant in drylands where plant cover is sparse, is that the connectedness of runoff flowpaths is a key parameter. It partly determines the extent to which the downslope movement of resources (soil, water, organic matter) is free or constrained, and this conception has the potential to support the formulation of some general models

Obstructive Sleep Apnea is Linked to Depression and Cognitive Impairment: Evidence and Potential Mechanisms

PubMed Central

Kerner, Nancy A.; Roose, Steven P.

2017-01-01

Obstructive sleep apnea (OSA) is highly prevalent but very frequently undiagnosed. OSA is an independent risk factor for depression and cognitive impairment/dementia. Herein the authors review studies in the literature pertinent to the effects of OSA on the cerebral microvascular and neurovascular systems and present a model to describe the key pathophysiologic mechanisms that may underlie the associations, including hypoperfusion, endothelial dysfunction, and neuroinflammation. Intermittent hypoxia plays a critical role in initiating and amplifying these pathologic processes. Hypoperfusion and impaired cerebral vasomotor reactivity lead to the development or progression of cerebral small vessel disease (C-SVD). Hypoxemia exacerbates these processes, resulting in white matter lesions, white matter integrity abnormalities, and gray matter loss. Blood–brain barrier (BBB) hyperpermeability and neuroinflammation lead to altered synaptic plasticity, neuronal damage, and worsening C-SVD. Thus, OSA may initiate or amplify the pathologic processes of C-SVD and BBB dysfunction, resulting in the development or exacerbation of depressive symptoms and cognitive deficits. Given the evidence that adequate treatment of OSA with continuous positive airway pressure improves depression and neurocognitive functions, it is important to identify OSA when assessing patients with depression or cognitive impairment. Whether treatment of OSA changes the deteriorating trajectory of elderly patients with already-diagnosed vascular depression and cognitive impairment/dementia remains to be determined in randomized controlled trials. PMID:27139243

The counterbend dynamics of cross-linked filament bundles and flagella

PubMed Central

Coy, Rachel

2017-01-01

Cross-linked filament bundles, such as in cilia and flagella, are ubiquitous in biology. They are considered in textbooks as simple filaments with larger stiffness. Recent observations of flagellar counterbend, however, show that induction of curvature in one section of a passive flagellum instigates a compensatory counter-curvature elsewhere, exposing the intricate role of the diminutive cross-linking proteins at large scales. We show that this effect, a material property of the cross-linking mechanics, modifies the bundle dynamics and induces a bimodal L2 − L3 length-dependent material response that departs from the Euler–Bernoulli theory. Hence, the use of simpler theories to analyse experiments can result in paradoxical interpretations. Remarkably, the counterbend dynamics instigates counter-waves in opposition to driven oscillations in distant parts of the bundle, with potential impact on the regulation of flagellar bending waves. These results have a range of physical and biological applications, including the empirical disentanglement of material quantities via counterbend dynamics. PMID:28566516

Correlations between Community Structure and Link Formation in Complex Networks

PubMed Central

Liu, Zhen; He, Jia-Lin; Kapoor, Komal; Srivastava, Jaideep

2013-01-01

Background Links in complex networks commonly represent specific ties between pairs of nodes, such as protein-protein interactions in biological networks or friendships in social networks. However, understanding the mechanism of link formation in complex networks is a long standing challenge for network analysis and data mining. Methodology/Principal Findings Links in complex networks have a tendency to cluster locally and form so-called communities. This widely existed phenomenon reflects some underlying mechanism of link formation. To study the correlations between community structure and link formation, we present a general computational framework including a theory for network partitioning and link probability estimation. Our approach enables us to accurately identify missing links in partially observed networks in an efficient way. The links having high connection likelihoods in the communities reveal that links are formed preferentially to create cliques and accordingly promote the clustering level of the communities. The experimental results verify that such a mechanism can be well captured by our approach. Conclusions/Significance Our findings provide a new insight into understanding how links are created in the communities. The computational framework opens a wide range of possibilities to develop new approaches and applications, such as community detection and missing link prediction. PMID:24039818

Heterogeneity of link weight and the evolution of cooperation

NASA Astrophysics Data System (ADS)

Iwata, Manabu; Akiyama, Eizo

2016-04-01

In this paper, we investigate the effect of heterogeneity of link weight, heterogeneity of the frequency or amount of interactions among individuals, on the evolution of cooperation. Based on an analysis of the evolutionary prisoner's dilemma game on a weighted one-dimensional lattice network with intra-individual heterogeneity, we confirm that moderate level of link-weight heterogeneity can facilitate cooperation. Furthermore, we identify two key mechanisms by which link-weight heterogeneity promotes the evolution of cooperation: mechanisms for spread and maintenance of cooperation. We also derive the corresponding conditions under which the mechanisms can work through evolutionary dynamics.

Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity

PubMed Central

Jiang, Meiyan; Taghizadeh, Farshid; Steyger, Peter S.

2017-01-01

Aminoglycoside antibiotics remain widely used for urgent clinical treatment of life-threatening infections, despite the well-recognized risk of permanent hearing loss, i.e., cochleotoxicity. Recent studies show that aminoglycoside-induced cochleotoxicity is exacerbated by bacteriogenic-induced inflammation. This implies that those with severe bacterial infections (that induce systemic inflammation), and are treated with bactericidal aminoglycosides are at greater risk of drug-induced hearing loss than previously recognized. Incorporating this novel comorbid factor into cochleotoxicity risk prediction models will better predict which individuals are more predisposed to drug-induced hearing loss. Here, we review the cellular and/or signaling mechanisms by which host-mediated inflammatory responses to infection could enhance the trafficking of systemically administered aminoglycosides into the cochlea to enhance the degree of cochleotoxicity over that in healthy preclinical models. Once verified, these mechanisms will be potential targets for novel pharmacotherapeutics that reduce the risk of drug-induced hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of aminoglycosides. PMID:29209174

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

ERIC Educational Resources Information Center

Jelic, V.; Marsiglio, F.

2012-01-01

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

"Till Death Do Us Part": A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb.

PubMed

Omais, Saad; Jaafar, Carine; Ghanem, Noël

2018-01-01

Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival. Importantly, aberrant cell cycle re-entry (CCE) in post-mitotic neurons has been strongly linked to the abnormal pathophysiology in rodent models of neurodegenerative diseases with potential implications on the etiology and progression of such diseases in humans. Here, we present an overview of AN in the SVZ-OB and olfactory epithelium (OE) in mice and humans followed by a comprehensive update of the distinct roles played by cell cycle proteins including major tumors suppressor genes in various steps during neurogenesis. We also discuss accumulating evidence underlining a strong link between abnormal cell cycle control, olfactory dysfunction and neurodegeneration in the adult and aging brain. We emphasize that: (1) CCE in post-mitotic neurons due to loss of cell cycle suppression and/or age-related insults as well as DNA damage can anticipate the development of neurodegenerative lesions and protein aggregates, (2) the age-related decline in SVZ and OE neurogenesis is associated with compensatory pro-survival mechanisms in the aging OB which are interestingly similar to those detected in Alzheimer's disease and Parkinson's disease in humans, and (3) the OB represents a well suitable model to study the early manifestation of age-related defects that may eventually progress into the formation of neurodegenerative lesions and, possibly, spread to the rest of the brain. Such findings may provide a novel

Link Correlated Military Data for Better Decision Support

DTIC Science & Technology

2011-06-01

automatically translated into URI based links, thus can greatly reduce man power cost on software development. 3 Linked Data Technique Tim Berners - Lee ...Linked Data - while Linked Data is usually considered as part of Semantic Web, or “the Semantic Web done right” as described by Tim himself - has been...Required data of automatic link construction mechanism on more kinds of correlations. References [1] B. L. Tim , “The next Web of open, linked data

Neurocomputational mechanisms of prosocial learning and links to empathy

PubMed Central

Apps, Matthew A. J.; Valton, Vincent; Viding, Essi; Roiser, Jonathan P.

2016-01-01

Reinforcement learning theory powerfully characterizes how we learn to benefit ourselves. In this theory, prediction errors—the difference between a predicted and actual outcome of a choice—drive learning. However, we do not operate in a social vacuum. To behave prosocially we must learn the consequences of our actions for other people. Empathy, the ability to vicariously experience and understand the affect of others, is hypothesized to be a critical facilitator of prosocial behaviors, but the link between empathy and prosocial behavior is still unclear. During functional magnetic resonance imaging (fMRI) participants chose between different stimuli that were probabilistically associated with rewards for themselves (self), another person (prosocial), or no one (control). Using computational modeling, we show that people can learn to obtain rewards for others but do so more slowly than when learning to obtain rewards for themselves. fMRI revealed that activity in a posterior portion of the subgenual anterior cingulate cortex/basal forebrain (sgACC) drives learning only when we are acting in a prosocial context and signals a prosocial prediction error conforming to classical principles of reinforcement learning theory. However, there is also substantial variability in the neural and behavioral efficiency of prosocial learning, which is predicted by trait empathy. More empathic people learn more quickly when benefitting others, and their sgACC response is the most selective for prosocial learning. We thus reveal a computational mechanism driving prosocial learning in humans. This framework could provide insights into atypical prosocial behavior in those with disorders of social cognition. PMID:27528669

Neurocomputational mechanisms of prosocial learning and links to empathy.

PubMed

Lockwood, Patricia L; Apps, Matthew A J; Valton, Vincent; Viding, Essi; Roiser, Jonathan P

2016-08-30

Reinforcement learning theory powerfully characterizes how we learn to benefit ourselves. In this theory, prediction errors-the difference between a predicted and actual outcome of a choice-drive learning. However, we do not operate in a social vacuum. To behave prosocially we must learn the consequences of our actions for other people. Empathy, the ability to vicariously experience and understand the affect of others, is hypothesized to be a critical facilitator of prosocial behaviors, but the link between empathy and prosocial behavior is still unclear. During functional magnetic resonance imaging (fMRI) participants chose between different stimuli that were probabilistically associated with rewards for themselves (self), another person (prosocial), or no one (control). Using computational modeling, we show that people can learn to obtain rewards for others but do so more slowly than when learning to obtain rewards for themselves. fMRI revealed that activity in a posterior portion of the subgenual anterior cingulate cortex/basal forebrain (sgACC) drives learning only when we are acting in a prosocial context and signals a prosocial prediction error conforming to classical principles of reinforcement learning theory. However, there is also substantial variability in the neural and behavioral efficiency of prosocial learning, which is predicted by trait empathy. More empathic people learn more quickly when benefitting others, and their sgACC response is the most selective for prosocial learning. We thus reveal a computational mechanism driving prosocial learning in humans. This framework could provide insights into atypical prosocial behavior in those with disorders of social cognition.

Neural mechanisms of the link between giving social support and health.

PubMed

Inagaki, Tristen K

2018-05-11

Giving social support to others has emerged as an additional route by which social ties influence health. Thus, giving support to others not only influences the health of the individual receiving support, but also the health of the individual giving the support. However, the neural mechanisms by which giving support leads to health are only beginning to be explored. In hopes of consolidating and guiding future research on giving support and health, the current review considers why, how, and when giving support is health promoting. Special emphasis is placed on neural regions known to contribute to parental care in animals that both reinforce giving support behavior (ventral striatum and septal area) and reduce stress-related responding (e.g., amygdala) to facilitate care. Hypothesized links between neural regions involved in giving support and peripheral physiology (sympathetic nervous system, hypothalamic-pituitary-adrenal axis, and related inflammatory responding) are considered as well as the conditions under which giving support should be most beneficial for health. Finally, the implications of the current perspective for understanding how social relationships, more broadly, contribute to health and suggestions for future directions are offered. © 2018 New York Academy of Sciences.

New Potentials for Old: The Darboux Transformation in Quantum Mechanics

ERIC Educational Resources Information Center

Williams, Brian Wesley; Celius, Tevye C.

2008-01-01

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

Toward molecular mechanism of xenon anesthesia: a link to studies of xenon complexes with small aromatic molecules.

PubMed

Andrijchenko, Natalya N; Ermilov, Alexander Yu; Khriachtchev, Leonid; Räsänen, Markku; Nemukhin, Alexander V

2015-03-19

The present study illustrates the steps toward understanding molecular mechanism of xenon anesthesia by focusing on a link to the structures and spectra of intermolecular complexes of xenon with small aromatic molecules. A primary cause of xenon anesthesia is attributed to inhibition of N-methyl-D-aspartate (NMDA) receptors by an unknown mechanism. Following the results of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) calculations we report plausible xenon action sites in the ligand binding domain of the NMDA receptor, which are due to interaction of xenon atoms with aromatic amino-acid residues. We rely in these calculations on computational protocols adjusted in combined experimental and theoretical studies of intermolecular complexes of xenon with phenol. Successful reproduction of vibrational shifts in molecular species upon complexation with xenon measured in low-temperature matrices allowed us to select a proper functional form in density functional theory (DFT) approach for use in QM subsystems, as well as to calibrate force field parameters for MD simulations. The results of molecular modeling show that xenon atoms can compete with agonists for a place in the corresponding protein cavity, thus indicating their active role in anesthetic action.

The induction of reentry in cardiac tissue. The missing link: How electric fields alter transmembrane potential

NASA Astrophysics Data System (ADS)

Roth, Bradley J.; Krassowska, Wanda

1998-03-01

This review examines the initiation of reentry in cardiac muscle by strong electric shocks. Specifically, it concentrates on the mechanisms by which electric shocks change the transmembrane potential of the cardiac membrane and create the physiological substrate required by the critical point theory for the initiation of rotors. The mechanisms examined include (1) direct polarization of the tissue by the stimulating current, as described by the one-dimensional cable model and its two- and three-dimensional extensions, (2) the presence of virtual anodes and cathodes, as described by the bidomain model with unequal anisotropy ratios of the intra- and extracellular spaces, (3) polarization of the tissue due to changing orientation of cardiac fibers, and (4) polarization of individual cells or groups of cells by the electric field ("sawtooth potential"). The importance of these mechanisms in the initiation of reentry is examined in two case studies: the induction of rotors using successive stimulation with a unipolar electrode, and the induction of rotors using cross-field stimulation. These cases reveal that the mechanism by which a unipolar stimulation induces arrhythmias can be explained in the framework of the bidomain model with unequal anisotropy ratios. In contrast, none of the examined mechanisms provide an adequate explanation for the induction of rotors by cross-field stimulation. Hence, this study emphasizes the need for further experimental and theoretical work directed toward explaining the mechanism of field stimulation.

Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

PubMed

Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

2016-01-01

With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

Acupuncture for Visceral Pain: Neural Substrates and Potential Mechanisms

PubMed Central

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

2014-01-01

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

Linking abnormal mitosis to the acquisition of DNA damage

PubMed Central

Pellman, David

2012-01-01

Cellular defects that impair the fidelity of mitosis promote chromosome missegregation and aneuploidy. Increasing evidence reveals that errors in mitosis can also promote the direct and indirect acquisition of DNA damage and chromosome breaks. Consequently, deregulated cell division can devastate the integrity of the normal genome and unleash a variety of oncogenic stimuli that may promote transformation. Recent work has shed light on the mechanisms that link abnormal mitosis with the development of DNA damage, how cells respond to such affronts, and the potential impact on tumorigenesis. PMID:23229895

Mechanisms and therapeutic potential of microRNAs in hypertension

PubMed Central

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

2015-01-01

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

Plantar Fasciitis and the Windlass Mechanism: A Biomechanical Link to Clinical Practice

PubMed Central

Malone, Terry R.

2004-01-01

Objective: Plantar fasciitis is a prevalent problem, with limited consensus among clinicians regarding the most effective treatment. The purpose of this literature review is to provide a systematic approach to the treatment of plantar fasciitis based on the windlass mechanism model. Data Sources: We searched MEDLINE, SPORT Discus, and CINAHL from 1966 to 2003 using the key words plantar fasciitis, windlass mechanism, pronation, heel pain, and heel spur. Data Synthesis: We offer a biomechanical application for the evaluation and treatment of plantar fasciitis based on a review of the literature for the windlass mechanism model. This model provides a means for describing plantar fasciitis conditions such that clinicians can formulate a potential causal relationship between the conditions and their treatments. Conclusions/Recommendations: Clinicians' understanding of the biomechanical causes of plantar fasciitis should guide the decision-making process concerning the evaluation and treatment of heel pain. Use of this approach may improve clinical outcomes because intervention does not merely treat physical symptoms but actively addresses the influences that resulted in the condition. Principles from this approach might also provide a basis for future research investigating the efficacy of plantar fascia treatment. PMID:16558682

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

PubMed Central

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B.; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-01-01

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

Design and Development of a Linked Open Data-Based Health Information Representation and Visualization System: Potentials and Preliminary Evaluation

PubMed Central

Kauppinen, Tomi; Keßler, Carsten; Fritz, Fleur

2014-01-01

Background Healthcare organizations around the world are challenged by pressures to reduce cost, improve coordination and outcome, and provide more with less. This requires effective planning and evidence-based practice by generating important information from available data. Thus, flexible and user-friendly ways to represent, query, and visualize health data becomes increasingly important. International organizations such as the World Health Organization (WHO) regularly publish vital data on priority health topics that can be utilized for public health policy and health service development. However, the data in most portals is displayed in either Excel or PDF formats, which makes information discovery and reuse difficult. Linked Open Data (LOD)—a new Semantic Web set of best practice of standards to publish and link heterogeneous data—can be applied to the representation and management of public level health data to alleviate such challenges. However, the technologies behind building LOD systems and their effectiveness for health data are yet to be assessed. Objective The objective of this study is to evaluate whether Linked Data technologies are potential options for health information representation, visualization, and retrieval systems development and to identify the available tools and methodologies to build Linked Data-based health information systems. Methods We used the Resource Description Framework (RDF) for data representation, Fuseki triple store for data storage, and Sgvizler for information visualization. Additionally, we integrated SPARQL query interface for interacting with the data. We primarily use the WHO health observatory dataset to test the system. All the data were represented using RDF and interlinked with other related datasets on the Web of Data using Silk—a link discovery framework for Web of Data. A preliminary usability assessment was conducted following the System Usability Scale (SUS) method. Results We developed an LOD

Design and development of a linked open data-based health information representation and visualization system: potentials and preliminary evaluation.

PubMed

Tilahun, Binyam; Kauppinen, Tomi; Keßler, Carsten; Fritz, Fleur

2014-10-25

Healthcare organizations around the world are challenged by pressures to reduce cost, improve coordination and outcome, and provide more with less. This requires effective planning and evidence-based practice by generating important information from available data. Thus, flexible and user-friendly ways to represent, query, and visualize health data becomes increasingly important. International organizations such as the World Health Organization (WHO) regularly publish vital data on priority health topics that can be utilized for public health policy and health service development. However, the data in most portals is displayed in either Excel or PDF formats, which makes information discovery and reuse difficult. Linked Open Data (LOD)-a new Semantic Web set of best practice of standards to publish and link heterogeneous data-can be applied to the representation and management of public level health data to alleviate such challenges. However, the technologies behind building LOD systems and their effectiveness for health data are yet to be assessed. The objective of this study is to evaluate whether Linked Data technologies are potential options for health information representation, visualization, and retrieval systems development and to identify the available tools and methodologies to build Linked Data-based health information systems. We used the Resource Description Framework (RDF) for data representation, Fuseki triple store for data storage, and Sgvizler for information visualization. Additionally, we integrated SPARQL query interface for interacting with the data. We primarily use the WHO health observatory dataset to test the system. All the data were represented using RDF and interlinked with other related datasets on the Web of Data using Silk-a link discovery framework for Web of Data. A preliminary usability assessment was conducted following the System Usability Scale (SUS) method. We developed an LOD-based health information representation, querying

Effect of carbon nanotube functionalization on mechanical and thermal properties of cross-linked epoxy-carbon nanotube nanocomposites: role of strengthening the interfacial interactions.

PubMed

Khare, Ketan S; Khabaz, Fardin; Khare, Rajesh

2014-05-14

We have used amido-amine functionalized carbon nanotubes (CNTs) that form covalent bonds with cross-linked epoxy matrices to elucidate the role of the matrix-filler interphase in the enhancement of mechanical and thermal properties in these nanocomposites. For the base case of nanocomposites of cross-linked epoxy and pristine single-walled CNTs, our previous work (Khare, K. S.; Khare, R. J. Phys. Chem. B 2013, 117, 7444-7454) has shown that weak matrix-filler interactions cause the interphase region in the nanocomposite to be more compressible. Furthermore, because of the weak matrix-filler interactions, the nanocomposite containing dispersed pristine CNTs has a glass transition temperature (Tg) that is ∼66 K lower than the neat polymer. In this work, we demonstrate that in spite of the presence of stiff CNTs in the nanocomposite, the Young's modulus of the nanocomposite containing dispersed pristine CNTs is virtually unchanged compared to the neat cross-linked epoxy. This observation suggests that the compressibility of the matrix-filler interphase interferes with the ability of the CNTs to reinforce the matrix. Furthermore, when the compressibility of the interphase is reduced by the use of amido-amine functionalized CNTs, the mechanical reinforcement due to the filler is more effective, resulting in a ∼50% increase in the Young's modulus compared to the neat cross-linked epoxy. Correspondingly, the functionalization of the CNTs also led to a recovery in the Tg making it effectively the same as the neat polymer and also resulted in a ∼12% increase in the thermal conductivity of the nanocomposite containing functionalized CNTs compared to that containing pristine CNTs. These results demonstrate that the functionalization of the CNTs facilitates the transfer of both mechanical load and thermal energy across the matrix-filler interface.

X-linked cataract and Nance-Horan syndrome are allelic disorders.

PubMed

Coccia, Margherita; Brooks, Simon P; Webb, Tom R; Christodoulou, Katja; Wozniak, Izabella O; Murday, Victoria; Balicki, Martha; Yee, Harris A; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J; Maher, Eamonn R; Moore, Anthony T; Russell-Eggitt, Isabelle M; Hardcastle, Alison J

2009-07-15

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication-triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved.

X-linked cataract and Nance-Horan syndrome are allelic disorders

PubMed Central

Coccia, Margherita; Brooks, Simon P.; Webb, Tom R.; Christodoulou, Katja; Wozniak, Izabella O.; Murday, Victoria; Balicki, Martha; Yee, Harris A.; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K.; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J.; Maher, Eamonn R.; Moore, Anthony T.; Russell-Eggitt, Isabelle M.; Hardcastle, Alison J.

2009-01-01

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication–triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved. PMID:19414485

Electro-mechanical properties of hydrogel composites with micro- and nano-cellulose fillers

NASA Astrophysics Data System (ADS)

N, Mohamed Shahid U.; Deshpande, Abhijit P.; Lakshmana Rao, C.

2015-09-01

Stimuli responsive cross-linked hydrogels are of great interest for applications in diverse fields such as sensors and biomaterials. In this study, we investigate polymer composites filled with cellulose fillers. The celluloses used in making the composites were a microcrystalline cellulose of commercial grade and cellulose nano-whiskers obtained through acid hydrolysis of microcrystalline cellulose. The filler concentration was varied and corresponding physical, mechanical and electro-mechanical characterization was carried out. The electro-mechanical properties were determined using a quasi-static method. The fillers not only enhance the mechanical properties of the composite by providing better reinforcement but also provide a quantitative electric potential in the composite. The measurements reveal that the polymer composites prepared from two different cellulose fillers possess a quantitative electric potential which can be utilized in biomedical applications. It is argued that the mechanism behind the quantitative electric potential in the composites is due to streaming potentials arising due to electrical double layer formation.

A novel communication mechanism based on node potential multi-path routing

NASA Astrophysics Data System (ADS)

Bu, Youjun; Zhang, Chuanhao; Jiang, YiMing; Zhang, Zhen

2016-10-01

With the network scales rapidly and new network applications emerge frequently, bandwidth supply for today's Internet could not catch up with the rapid increasing requirements. Unfortunately, irrational using of network sources makes things worse. Actual network deploys single-next-hop optimization paths for data transmission, but such "best effort" model leads to the imbalance use of network resources and usually leads to local congestion. On the other hand Multi-path routing can use the aggregation bandwidth of multi paths efficiently and improve the robustness of network, security, load balancing and quality of service. As a result, multi-path has attracted much attention in the routing and switching research fields and many important ideas and solutions have been proposed. This paper focuses on implementing the parallel transmission of multi next-hop data, balancing the network traffic and reducing the congestion. It aimed at exploring the key technologies of the multi-path communication network, which could provide a feasible academic support for subsequent applications of multi-path communication networking. It proposed a novel multi-path algorithm based on node potential in the network. And the algorithm can fully use of the network link resource and effectively balance network link resource utilization.

From Fragmented Knowledge to a Knowledge Structure: Linking the Domains of Mechanics and Electromagnetism.

ERIC Educational Resources Information Center

Bagno, Esther; Eylon, Bat-Sheva; Ganiel, Uri

2000-01-01

Describes the MAOF physics education program which is designed to relate large parts of mechanics and electromagnetism to each other via the key concepts of field and potential, while at the same time treat students' conceptual difficulties. Finds that students who studied with the MAOF program significantly improved their physics knowledge…

ER-stress and apoptosis: molecular mechanisms and potential relevance in infection.

PubMed

Häcker, Georg

2014-10-01

During ER-stress, one of the responses a cell can choose is apoptosis. Apoptosis generally is a cell's preferred response when other control mechanisms are overwhelmed. We now have a reasonably clear molecular picture what is happening once the apoptotic apparatus has been started. Unclear however are the majority of the upstream pathways that connect other signalling to apoptosis. During ER-stress, confirmed apoptosis-regulating targets are pro- and anti-apoptotic proteins of the Bcl-2-family, whose concerted action induces apoptosis. I will here discuss how mitochondrial apoptosis is triggered, how this is linked to the ER-stress response and in what way this may be relevant during microbial infections. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

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.

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.

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

PubMed

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

2017-12-28

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

Amide Link Scission in the Polyamide Active Layers of Thin-Film Composite Membranes upon Exposure to Free Chlorine: Kinetics and Mechanisms.

PubMed

Powell, Joshua; Luh, Jeanne; Coronell, Orlando

2015-10-20

The volume-averaged amide link scission in the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine was quantified at a variety of free chlorine exposure times, concentrations, and pH and rinsing conditions. The results showed that (i) hydroxyl ions are needed for scission to occur, (ii) hydroxide-induced amide link scission is a strong function of exposure to hypochlorous acid, (iii) the ratio between amide links broken and chlorine atoms taken up increased with the chlorination pH and reached a maximum of ∼25%, (iv) polyamide disintegration occurs when high free chlorine concentrations, alkaline conditions, and high exposure times are combined, (v) amide link scission promotes further chlorine uptake, and (vi) scission at the membrane surface is unrepresentative of volume-averaged scission in the active layer. Our observations are consistent with previously proposed mechanisms describing amide link scission as a result of the hydrolysis of the N-chlorinated amidic N-C bond due to nucleophilic attack by hydroxyl ions. This study increases the understanding of the physicochemical changes that could occur for membranes in treatment plants using chlorine as an upstream disinfectant and the extent and rate at which those changes would occur.

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

PubMed

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

2018-03-11

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

Collagen cross-linking: insights on the evolution of metazoan extracellular matrix.

PubMed

Rodriguez-Pascual, Fernando; Slatter, David Anthony

2016-11-23

Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.

Endolysosomal Cation Channels and Cancer-A Link with Great Potential.

PubMed

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M; Biel, Martin

2018-01-05

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells.

Endolysosomal Cation Channels and Cancer—A Link with Great Potential

PubMed Central

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M.; Biel, Martin

2018-01-01

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells. PMID:29303993

“Till Death Do Us Part”: A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb

PubMed Central

Omais, Saad; Jaafar, Carine; Ghanem, Noël

2018-01-01

Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival. Importantly, aberrant cell cycle re-entry (CCE) in post-mitotic neurons has been strongly linked to the abnormal pathophysiology in rodent models of neurodegenerative diseases with potential implications on the etiology and progression of such diseases in humans. Here, we present an overview of AN in the SVZ-OB and olfactory epithelium (OE) in mice and humans followed by a comprehensive update of the distinct roles played by cell cycle proteins including major tumors suppressor genes in various steps during neurogenesis. We also discuss accumulating evidence underlining a strong link between abnormal cell cycle control, olfactory dysfunction and neurodegeneration in the adult and aging brain. We emphasize that: (1) CCE in post-mitotic neurons due to loss of cell cycle suppression and/or age-related insults as well as DNA damage can anticipate the development of neurodegenerative lesions and protein aggregates, (2) the age-related decline in SVZ and OE neurogenesis is associated with compensatory pro-survival mechanisms in the aging OB which are interestingly similar to those detected in Alzheimer's disease and Parkinson's disease in humans, and (3) the OB represents a well suitable model to study the early manifestation of age-related defects that may eventually progress into the formation of neurodegenerative lesions and, possibly, spread to the rest of the brain. Such findings may provide a novel

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

PubMed

Comanns, Philipp

2018-05-22

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

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

PubMed

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

2017-12-01

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

Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

PubMed Central

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

2016-01-01

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

Cow’s Milk and Immune Function in the Respiratory Tract: Potential Mechanisms

PubMed Central

Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F. J.; Brugman, Sylvia; van Neerven, R. J. Joost

2018-01-01

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we

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

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

PubMed Central

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

2015-01-01

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

A potential-of-mean-force approach for fracture mechanics of heterogeneous materials using the lattice element method

NASA Astrophysics Data System (ADS)

Laubie, Hadrien; Radjaï, Farhang; Pellenq, Roland; Ulm, Franz-Josef

2017-08-01

Fracture of heterogeneous materials has emerged as a critical issue in many engineering applications, ranging from subsurface energy to biomedical applications, and requires a rational framework that allows linking local fracture processes with global fracture descriptors such as the energy release rate, fracture energy and fracture toughness. This is achieved here by means of a local and a global potential-of-mean-force (PMF) inspired Lattice Element Method (LEM) approach. In the local approach, fracture-strength criteria derived from the effective interaction potentials between mass points are shown to exhibit a scaling commensurable with the energy dissipation of fracture processes. In the global PMF-approach, fracture is considered as a sequence of equilibrium states associated with minimum potential energy states analogous to Griffith's approach. It is found that this global approach has much in common with a Grand Canonical Monte Carlo (GCMC) approach, in which mass points are randomly removed following a maximum dissipation criterion until the energy release rate reaches the fracture energy. The duality of the two approaches is illustrated through the application of the PMF-inspired LEM for fracture propagation in a homogeneous linear elastic solid using different means of evaluating the energy release rate. Finally, by application of the method to a textbook example of fracture propagation in a heterogeneous material, it is shown that the proposed PMF-inspired LEM approach captures some well-known toughening mechanisms related to fracture energy contrast, elasticity contrast and crack deflection in the considered two-phase layered composite material.

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.

Do schema processes mediate links between parenting and eating pathology?

PubMed

Sheffield, Alex; Waller, Glenn; Emanuelli, Francesca; Murray, James; Meyer, Caroline

2009-07-01

Adverse parenting experiences are commonly linked to eating pathology. A schema-based model of the development and maintenance of eating pathology proposes that one of the potential mediators of the link between parenting and eating pathology might be the development of schema maintenance processes--mechanisms that operate to help the individual avoid intolerable emotions. To test this hypothesis, 353 female students and 124 female eating-disordered clients were recruited. They completed a measure of perceived parenting experiences as related to schema development (Young Parenting Inventory-Revised (YPI-R)), two measures of schema processes (Young Compensatory Inventory; Young-Rygh Avoidance Inventory (YRAI)) and a measure of eating pathology (Eating Disorders Inventory (EDI)). In support of the hypothesis, certain schema processes did mediate the relationship between specific perceptions of parenting and particular forms of eating pathology, although these were different for the clinical and non-clinical samples. In those patients where parenting is implicated in the development of eating pathology, treatment might need to target the cognitive processes that can explain this link. 2009 John Wiley & Sons, Ltd and Eating Disorders Association

Knowledge-Linking Perceptions of Late-Elementary Students

ERIC Educational Resources Information Center

Schuh, Kathy L.; Kuo, Yi-Lung; Knupp, Tawnya L.

2014-01-01

This study describes student perceptions of potential elaborative or generative learning strategies called student knowledge links. This construct was assessed using the Student Knowledge Linking Instrument-Perceptions (SKLIP), a new learning inventory to measure late-elementary student perceptions of the creation of student knowledge links. After…

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.

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

PubMed

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Precipitation links (PrecipLinks) - a prototype directory for precipitation information

NASA Technical Reports Server (NTRS)

Velanthapillia, Balendran; Stocker, Erich Franz

2006-01-01

This poster describes a web directory of research oriented precipitation links. In this era of sophisticated search engines and web agents, it might seem counterproductive to establish such a directory of links. However, entering precipitation into a search engine like google will yield over one million hits. To further exacerbate this situation many of the returned links are dead, duplicates of other links, incomplete, or only marginally related to research precipitation or even the broader precipitation area. Sometimes connecting the linked URL causes the browser to lose context and not be able to get back to the original page. Even using more sophisticated search engines query parameters or agents while reducing the overall return doesn't eliminate all of the other issues listed. As part of the development of the measurement-based Precipitation Processing System (PPS) that will support Tropical Rainfall Measuring Mission (TRMM) version 7 reprocessing and the Global Precipitation Measurement (GPM) mission a precipitation links (PrecipLinks) facility is being developed. PrecipLinks is intended to share locations of other sites that contain information or data pertaining to precipitation research. Potential contributors can log-on to the PrecipLinks website and register their site for inclusion in the directory. The price for inclusion is the requirement to place a link back to PrecipLinks on the webpage that is registered. This ensures that users will be able to easily get back to PrecipLinks regardless of any context issues that browsers might have. Perhaps more importantly users while visiting one site that they know can be referred to a location that has many others sites with which they might not be familiar. PrecipLinks is designed to have a very flat structure. This poster summarizes these categories (information, data, services) and the reasons for their selection. Providers may register multiple pages to which they wish to direct users. However, each page

Microtubule actin cross-linking factor 1, a novel potential target in cancer.

PubMed

Miao, Zhiping; Ali, Arshad; Hu, Lifang; Zhao, Fan; Yin, Chong; Chen, Chu; Yang, Tuanmin; Qian, Airong

2017-10-01

Cancer is a polygenic disease characterized by uncontrolled growth of normal body cells, deregulation of the cell cycle as well as resistance to apoptosis. The spectraplakin protein microtubule actin cross-linking factor 1 (MACF1) plays an essential function in various cellular processes, including cell proliferation, migration, signaling transduction and embryo development. MACF1 is also involved in processes such as metastatic invasion in which cytoskeleton organization is a critical element that contributes to tumor progression in various human cancers. Aberrant expression of MACF1 initiates the tumor cell proliferation, and migration and metastasis in numerous cancers, such as breast cancer, colon cancer, lung cancer and glioblastoma. In this review, we summarized the current knowledge of MACF1 and its critical role in different human cancers. This will be helpful for researchers to investigate the novel functional role of MACF1 in human cancers and as a potential target to enhance the efficacy of therapeutic treatment modalities. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Bound states of moving potential wells in discrete wave mechanics

NASA Astrophysics Data System (ADS)

Longhi, S.

2017-10-01

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

The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

PubMed Central

Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

2013-01-01

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

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.

The Potential of School-Linked Centers To Promote Adolescent Health and Development. Working Paper.

ERIC Educational Resources Information Center

Millstein, Susan G.

The future of school-linked adolescent health centers cannot be determined without further evaluation. The recent development of school-linked health centers stems from concerns about the special health needs of adolescents. Currently there are 125 school-based and school-linked centers in operation. Characteristics include the following: (1) most…

LinkMind: link optimization in swarming mobile sensor networks.

PubMed

Ngo, Trung Dung

2011-01-01

A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation.

LinkMind: Link Optimization in Swarming Mobile Sensor Networks

PubMed Central

Ngo, Trung Dung

2011-01-01

A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation. PMID:22164070

Puzzling Mechanisms

ERIC Educational Resources Information Center

van Deventer, M. Oskar

2009-01-01

The basis of a good mechanical puzzle is often a puzzling mechanism. This article will introduce some new puzzling mechanisms, like two knots that engage like gears, a chain whose links can be interchanged, and flat gears that do not come apart. It illustrates how puzzling mechanisms can be transformed into real mechanical puzzles, e.g., by…

HIV-1-Associated Atherosclerosis: Unraveling the Missing Link.

PubMed

Kearns, Alison; Gordon, Jennifer; Burdo, Tricia H; Qin, Xuebin

2017-06-27

Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation. There is a pressing need to experimentally unravel the missing link between HIV and atherosclerosis. Understanding these mechanisms will help to better develop and design novel therapeutic interventions for the treatment of HIV-associated cardiovascular disease. HIV mainly infects T cells and macrophages resulting in the induction of oxidative and endoplasmic reticulum stress, the formation of the inflammasome, and the dysregulation of autophagy. These mechanisms may contribute to HIV-associated atherogenesis. In this review, we will summarize our current understanding and propose potential mechanisms of HIV-associated atherosclerosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Tobacco nitrosamines as culprits in disease: mechanisms reviewed

PubMed Central

Yalcin, Emine

2016-01-01

The link between tobacco abuse and cancer is well-established. However, emerging data indicate that toxins in tobacco smoke cause cellular injury due to enhanced toxic/metabolic effects of metabolites, disruption of intracellular signaling mechanisms, and formation of DNA, protein, and lipid adducts that impair function and promote oxidative stress and inflammation. These effects of smoking, which are largely non-carcinogenic, can be produced by tobacco-specific nitrosamines and their metabolites. These factors could account for the increased rates of neurodegeneration and insulin resistance diseases among smokers. Herein, we review nicotine and tobacco-specific nitrosamine metabolism, mechanisms of adduct formation, DNA damage, mutagenesis, and potential mechanisms of disease. PMID:26767836

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

PubMed

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

2015-06-01

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

Maternal mind-mindedness as a linking mechanism between childbirth-related posttraumatic stress symptoms and parenting stress.

PubMed

Camisasca, Elena; Procaccia, Rossella; Miragoli, Sarah; Valtolina, Giovanni Giulio; Di Blasio, Paola

2017-06-01

The researchers of this study have two aims. The first aim is to verify whether posttraumatic stress (PTS) symptoms, evaluated at 87 hours and at 3 months postpartum, are associated with maternal mind-mindedness (MM) and parenting stress, measured at 17 months postpartum. The second aim is to investigate, at 17 months, the predictive effects of PTS symptoms on the dimensions of parenting stress and to explore whether MM mediates these associations. Forty-one mother-infant dyads participated in the study. The results show that at 17 months, hyper-arousal symptoms predicted both MM and parenting stress. MM was a linking mechanism between maternal PTS symptoms and parenting stress.

Linking governance mechanisms to health outcomes: a review of the literature in low- and middle-income countries.

PubMed

Ciccone, Dana Karen; Vian, Taryn; Maurer, Lydia; Bradley, Elizabeth H

2014-09-01

We conducted a synthesis of peer-reviewed literature to shed light on links between governance mechanisms and health outcomes in low- and middle-income countries. Our review yielded 30 studies, highlighting four key governance mechanisms by which governance may influence health outcomes in these settings: Health system decentralization that enables responsiveness to local needs and values; health policymaking that aligns and empowers diverse stakeholders; enhanced community engagement; and strengthened social capital. Most, but not all, studies found a positive association between governance and health. Additionally, the nature of the association between governance mechanisms and health differed across studies. In some studies (N = 9), the governance effect was direct and positive, while in others (N = 5), the effect was indirect or modified by contextual factors. In still other studies (N = 4), governance was found to have a moderating effect, indicating that governance mechanisms influenced other system processes or structures that improved health. The remaining studies reported mixed findings about the association between governance and health (N = 6), no association between governance and health (N = 4), or had inconclusive results (N = 2). Further exploration is needed to fully understand the relationship between governance and health and to inform the design and delivery of evidence-based, effective governance interventions around the world. Copyright © 2014 Elsevier Ltd. All rights reserved.

COPD and stroke: are systemic inflammation and oxidative stress the missing links?

PubMed

Austin, Victoria; Crack, Peter J; Bozinovski, Steven; Miller, Alyson A; Vlahos, Ross

2016-07-01

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. © 2016 The Author(s).

COPD and stroke: are systemic inflammation and oxidative stress the missing links?

PubMed Central

Austin, Victoria; Crack, Peter J.; Bozinovski, Steven; Miller, Alyson A.

2016-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. PMID:27215677

Hydrogels Prepared from Cross-Linked Nanofibrillated Cellulose

Treesearch

Sandeep S. Nair; J.Y. Zhu; Yulin Deng; Arthur J. Ragauskas

2014-01-01

Nanocomposite hydrogels were developed by cross-linking nanofibrillated cellulose with poly(methyl vinyl ether-co-maleic acid) and polyethylene glycol. The cross-linked hydrogels showed enhanced water absorption and gel content with the addition of nanocellulose. In addition, the thermal stability, mechanical strength, and modulus increased with an increase in the...

Metabolic endotoxaemia--a potential novel link between ovarian inflammation and impaired progesterone production.

PubMed

Tremellen, Kelton; Syedi, Naeema; Tan, Sze; Pearce, Karma

2015-04-01

Medical conditions such as obesity and inflammatory bowel disease are associated with impaired luteal function, menstrual disturbance and infertility. It is proposed that the disturbance in gut wall integrity ("leaky gut") seen in these conditions may result in the passage of bacterial endotoxin (LPS) from the colonic lumen into the circulation that may initiate inflammation in the ovary and subsequently impair hormone production. Quantify the association between systemic levels of LBP, a marker of endotoxin exposure, and levels of inflammation in the ovary (follicular fluid IL-6), plus steroid hormone production in 45 women undergoing IVF treatment. Endotoxaemia (LBP) were positively correlated with plasma CRP and inflammation within the ovary (follicular fluid IL-6). Furthermore, endotoxaemia was negatively correlated with progesterone production. The observed correlations, together with previously published animal studies linking endotoxin exposure to impaired luteal function, suggest that the translocation of bacterial endotoxin from the gut lumen into the circulation has the potential to interfere with progesterone production and result in luteal deficiency.

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

PubMed

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

2014-08-30

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

Tailoring chain length and cross-link density in dielectric elastomer toward enhanced actuation strain

NASA Astrophysics Data System (ADS)

Zhang, Quan-Ping; Liu, Jun-Hua; Liu, Hai-Dong; Jia, Fei; Zhou, Yuan-Lin; Zheng, Jian

2017-10-01

Adding ceramic or conductive fillers into polymers for increasing permittivity is a direct and effective approach to enhance the actuation strain of dielectric elastomer actuators (DEAs). Unfortunately, the major dielectric loss caused by weak interfaces potentially harms the electro-mechanical stability and lifetime of DEAs. Here, we construct a desired macromolecular network with a long chain length and low cross-link density to reduce the elastic modulus of silicone elastomers. Selecting a high molecular weight of polymethylvinylsiloxane and a low dose of the cross-linker leads the soft but tough networks with rich entanglements, poor cross-links, and a low amount of defects. Then, a ductile material with low elastic modulus but high elongation at break is obtained. It accounts for much more excellent actuation strain of Hl in comparison to that of the other silicone elastomers. Importantly, without other fillers, the ultralow dielectric loss, conductivity, and firm networks possibly promote the electro-mechanical stability and lifetime for the DEA application.

Magnetic Properties of Strongly Correlated Hubbard Model and Quantum Spin-One Ferromagnets with Arbitrary Crystal-Field Potential: Linked Cluster Series Expansion Approach

NASA Astrophysics Data System (ADS)

Pan, Kok-Kwei

We have generalized the linked cluster expansion method to solve more many-body quantum systems, such as quantum spin systems with crystal-field potentials and the Hubbard model. The technique sums up all connected diagrams to a certain order of the perturbative Hamiltonian. The modified multiple-site Wick reduction theorem and the simple tau dependence of the standard basis operators have been used to facilitate the evaluation of the integration procedures in the perturbation expansion. Computational methods are developed to calculate all terms in the series expansion. As a first example, the perturbation series expansion of thermodynamic quantities of the single-band Hubbard model has been obtained using a linked cluster series expansion technique. We have made corrections to all previous results of several papers (up to fourth order). The behaviors of the three dimensional simple cubic and body-centered cubic systems have been discussed from the qualitative analysis of the perturbation series up to fourth order. We have also calculated the sixth-order perturbation series of this model. As a second example, we present the magnetic properties of spin-one Heisenberg model with arbitrary crystal-field potential using a linked cluster series expansion. The calculation of the thermodynamic properties using this method covers the whole range of temperature, in both magnetically ordered and disordered phases. The series for the susceptibility and magnetization have been obtained up to fourth order for this model. The method sums up all perturbation terms to certain order and estimates the result using a well -developed and highly successful extrapolation method (the standard ratio method). The dependence of critical temperature on the crystal-field potential and the magnetization as a function of temperature and crystal-field potential are shown. The critical behaviors at zero temperature are also shown. The range of the crystal-field potential for Ni(2+) compounds is

Cross-linking of type I collagen with microbial transglutaminase: identification of cross-linking sites.

PubMed

Stachel, Ines; Schwarzenbolz, Uwe; Henle, Thomas; Meyer, Michael

2010-03-08

Collagen is a popular biomaterial. To deal with its lack of thermal stability and its weak resistance to proteolytic degradation, collagen-based materials are stabilized via different cross-linking procedures. Regarding the potential toxicity of residual cross-linking agents, enzyme-mediated cross-linking would provide an alternative and nontoxic method for collagen stabilization. The results of this study show that type I collagen is a substrate for mTG. However, epsilon-(gamma-glutamyl)lysine cross-links are only incorporated at elevated temperatures when the protein is partially or completely denatured. A maximum number of 5.4 cross-links per collagen monomer were found for heat-denatured collagen. Labeling with the primary amine monodansylcadaverine revealed that at least half of the cross-links are located within the triple helical region of the collagen molecule. Because the triple helix is highly ordered in its native state, this finding might explain why the glutamine residues are inaccessible for mTG under nondenaturing conditions.

Mechanical properties, biocompatibility, and biodegradation of cross-linked cellulose acetate-reinforced polyester composites.

PubMed

Wu, Chin-San

2014-05-25

Composites of treated (cross-linked) cellulose acetate (t-CA) and acrylic acid-grafted poly(hydroxyalkanoate) (PHA-g-AA/t-CA) exhibited noticeably superior mechanical properties compared with PHA/CA composites due to greater compatibility between the two components. The dispersion covering of t-CA in the PHA-g-AA matrix was highly homogeneous as a result of condensation reactions. Human lung fibroblasts (FBs) were seeded on these two series of composites to characterize the biocompatibility properties. In a time-dependent course, the FB proliferation results demonstrated higher performance from the PHA/CA series of composites than from the PHA-g-AA/t-CA composites. The water resistance of PHA-g-AA/t-CA was higher than that of PHA/CA, although the weight loss of both composites buried in Acetobacter pasteurianus (A. pasteurianus) indicated that they were both biodegradable, especially at higher levels of cellulose acetate substitution. The PHA/CA and PHA-g-AA/t-CA composites were more biodegradable than pure PHA, implying a strong connection between cellulose acetate content and biodegradability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advances in the mechanical modeling of filamentous actin and its cross-linked networks on multiple scales.

PubMed

Unterberger, Michael J; Holzapfel, Gerhard A

2014-11-01

The protein actin is a part of the cytoskeleton and, therefore, responsible for the mechanical properties of the cells. Starting with the single molecule up to the final structure, actin creates a hierarchical structure of several levels exhibiting a remarkable behavior. The hierarchy spans several length scales and limitations in computational power; therefore, there is a call for different mechanical modeling approaches for the different scales. On the molecular level, we may consider each atom in molecular dynamics simulations. Actin forms filaments by combining the molecules into a double helix. In a model, we replace molecular subdomains using coarse-graining methods, allowing the investigation of larger systems of several atoms. These models on the nanoscale inform continuum mechanical models of large filaments, which are based on worm-like chain models for polymers. Assemblies of actin filaments are connected with cross-linker proteins. Models with discrete filaments, so-called Mikado models, allow us to investigate the dependence of the properties of networks on the parameters of the constituents. Microstructurally motivated continuum models of the networks provide insights into larger systems containing cross-linked actin networks. Modeling of such systems helps to gain insight into the processes on such small scales. On the other hand, they call for verification and hence trigger the improvement of established experiments and the development of new methods.

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

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

Wang, Yongan

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposuremore » levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

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

Link between the potentially hazardous Asteroid (86039) 1999 NC43 and the Chelyabinsk meteoroid tenuous

NASA Astrophysics Data System (ADS)

Reddy, Vishnu; Vokrouhlický, David; Bottke, William F.; Pravec, Petr; Sanchez, Juan A.; Gary, Bruce L.; Klima, Rachel; Cloutis, Edward A.; Galád, Adrián; Guan, Tan Thiam; Hornoch, Kamil; Izawa, Matthew R. M.; Kušnirák, Peter; Le Corre, Lucille; Mann, Paul; Moskovitz, Nicholas; Skiff, Brian; Vraštil, Jan

2015-05-01

We explored the statistical and compositional link between Chelyabinsk meteoroid and potentially hazardous Asteroid (86039) 1999 NC43 to investigate their proposed relation proposed by Borovička et al. (Borovička, J., et al. [2013]. Nature 503, 235-237). First, using a slightly more detailed computation we confirm that the orbit of the Chelyabinsk impactor is anomalously close to the Asteroid 1999 NC43. We find ∼(1-3) × 10-4 likelihood of that to happen by chance. Taking the standpoint that the Chelyabinsk impactor indeed separated from 1999 NC43 by a cratering or rotational fission event, we run a forward probability calculation, which is an independent statistical test. However, we find this scenario is unlikely at the ∼(10-3-10-2) level. Secondly, we note that efforts to conclusively prove separation of the Chelyabinsk meteoroid from (86039) 1999 NC43 in the past needs to meet severe criteria: relative velocity ≃1-10 m/s or smaller, and ≃100 km distance (i.e. about the Hill sphere distance from the parent body). We conclude that, unless the separation event was an extremely recent event, these criteria present an insurmountable difficulty due to the combination of strong orbital chaoticity, orbit uncertainty and incompleteness of the dynamical model with respect to thermal accelerations. This situation leaves the link of the two bodies unresolved and calls for additional analyses. With that goal, we revisit the presumed compositional link between (86039) 1999 NC43 and the Chelyabinsk body. Borovička et al. (Borovička, J., et al. [2013]. Nature 503, 235-237) noted that given its Q-type taxonomic classification, 1999 NC43 may pass this test. However, here we find that while the Q-type classification of 1999 NC43 is accurate, assuming that all Q-types are LL chondrites is not. Our experiment shows that not all ordinary chondrites fall under Q-taxonomic type and not all LL chondrites are Q-types. Spectral curve matching between laboratory spectra of

Link-N: The missing link towards intervertebral disc repair is species-specific

PubMed Central

Bach, Frances C.; Laagland, Lisanne T.; Grant, Michael P.; Creemers, Laura B.; Ito, Keita; Meij, Björn P.; Mwale, Fackson

2017-01-01

Introduction Degeneration of the intervertebral disc (IVD) is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells. If Link-N appears to be effective in canines, this would facilitate translation of Link-N into the clinic using the dog as an in vivo large animal model for human IVD degeneration. Materials and methods This study’s objective was to determine the effect of the human and canine variant of Link-N and short (s) Link-N on canine chondrocyte-like cells (CLCs) and compare this to those on already studied species, i.e. human and bovine CLCs. Extracellular matrix (ECM) production was determined by measuring glycosaminoglycan (GAG) content and histological evaluation. Additionally, the micro-aggregates’ DNA content was measured. Phosphorylated (p) Smad1 and -2 levels were determined using ELISA. Results Human (s)Link-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (s)Link-N did not affect ECM production in human CLCs, while it mainly induced collagen type I and II deposition in bovine CLCs. In canine CLCs, both canine and human (s)Link-N induced negligible GAG deposition. Surprisingly, human and canine (s)Link-N did not induce Smad signaling in human and bovine CLCs. Human and canine (s)Link-N only mildly increased pSmad1 and Smad2 levels in canine CLCs. Conclusions Human and canine (s)Link-N exerted species-specific effects on CLCs from early degenerated IVDs. Both variants, however, lacked the potency as canine IVD regeneration agent. While these studies demonstrate the challenges of translational studies in large animal models, (s)Link

Link-N: The missing link towards intervertebral disc repair is species-specific.

PubMed

Bach, Frances C; Laagland, Lisanne T; Grant, Michael P; Creemers, Laura B; Ito, Keita; Meij, Björn P; Mwale, Fackson; Tryfonidou, Marianna A

2017-01-01

Degeneration of the intervertebral disc (IVD) is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells. If Link-N appears to be effective in canines, this would facilitate translation of Link-N into the clinic using the dog as an in vivo large animal model for human IVD degeneration. This study's objective was to determine the effect of the human and canine variant of Link-N and short (s) Link-N on canine chondrocyte-like cells (CLCs) and compare this to those on already studied species, i.e. human and bovine CLCs. Extracellular matrix (ECM) production was determined by measuring glycosaminoglycan (GAG) content and histological evaluation. Additionally, the micro-aggregates' DNA content was measured. Phosphorylated (p) Smad1 and -2 levels were determined using ELISA. Human (s)Link-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (s)Link-N did not affect ECM production in human CLCs, while it mainly induced collagen type I and II deposition in bovine CLCs. In canine CLCs, both canine and human (s)Link-N induced negligible GAG deposition. Surprisingly, human and canine (s)Link-N did not induce Smad signaling in human and bovine CLCs. Human and canine (s)Link-N only mildly increased pSmad1 and Smad2 levels in canine CLCs. Human and canine (s)Link-N exerted species-specific effects on CLCs from early degenerated IVDs. Both variants, however, lacked the potency as canine IVD regeneration agent. While these studies demonstrate the challenges of translational studies in large animal models, (s)Link-N still holds a regenerative potential for humans.

Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

PubMed Central

Monk, Catherine; Spicer, Julie; Champagne, Frances A.

2013-01-01

Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes.

PubMed

Pradat, Pierre-François; Kabashi, Edor; Desnuelle, Claude

2015-10-01

The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets.

Galectin-3 enhances angiogenic and migratory potential of microglial cells via modulation of integrin linked kinase signaling

PubMed Central

Wesley, Umadevi V.; Vemuganti, Raghu; Ayvaci, Rabia; Dempsey, Robert J.

2013-01-01

Focal cerebral ischemia initiates self-repair mechanisms that include the production of neurotrophic factors and cytokines. Galectin-3 is an important angiogenic cytokine. We have previously demonstrated that expression of galectin 3 (Gal-3), a carbohydrate binding protein is significantly upregulated in activated microglia in the brains of rats subjected to focal ischemia. Further blocking of Gal-3 function with Gal-3 neutralizing antibody decreased the microvessel density in ischemic brain. We currently show that Gal-3 significantly increases the viability of microglia BV2 cells subjected to oxygen glucose deprivation (OGD) and re-oxygenation. Exogenous Gal-3 promoted the formation of pro-angiogenic structures in an in vitro human umbilical vein endothelial (HUVEC) and BV2 cell co-culture model. Gal-3 induced angiogenesis was associated with increased expression of vascular endothelial growth factor. The conditioned medium of BV2 cells exposed to OGD contained increased Gal-3 levels, and promoted the formation of pro-angiogenic structures in an in vitro HUVEC culture model. Gal-3 also augmented the in vitro migratory potential of BV2 microglia. Gal-3 mediated functions were associated with increased levels of integrin-linked kinase (ILK) signaling as demonstrated by the impaired angiogenesis and migration of BV2 cells following targeted silencing of ILK expression by SiRNA. Furthermore, we show that ILK levels correlate with the levels of phos-AKT and ERK1/2 that are downstream effectors of ILK pathway. Taken together, our studies indicate that Gal-3 contributes to angiogenesis and microglia migration that may have implications in post stroke repair. PMID:23246924

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

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

PubMed Central

Williams, Stephen R; Stuart, Greg J

1999-01-01

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

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

PubMed Central

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

2014-01-01

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

Phospholipase C-ε links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of Langerhans

PubMed Central

Dzhura, Igor; Chepurny, Oleg G; Leech, Colin A; Roe, Michael W; Dzhura, Elvira; Xu, Xin; Lu, Youming; Schwede, Frank; Genieser, Hans-G; Smrcka, Alan V

2011-01-01

Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is potentiated by cAMP-elevating agents, such as the incretin hormone glucagon-like peptide-1 (GLP-1) and cAMP exerts its insulin secretagogue action by activating both protein kinase A (PKA) and the cAMP-regulated guanine nucleotide exchange factor designated as Epac2. Although prior studies of mouse islets demonstrated that Epac2 acts via Rap1 GTPase to potentiate GSIS, it is not understood which downstream targets of Rap1 promote the exocytosis of insulin. Here, we measured insulin secretion stimulated by a cAMP analog that is a selective activator of Epac proteins in order to demonstrate that a Rap1-regulated phospholipase C-epsilon (PLC-ε) links Epac2 activation to the potentiation of GSIS. Our analysis demonstrates that the Epac activator 8-pCPT-2′-O-Me-cAMP-AM potentiates GSIS from the islets of wild-type (WT) mice, whereas it has a greatly reduced insulin secretagogue action in the islets of Epac2 (−/−) and PLC-ε (−/−) knockout (KO) mice. Importantly, the insulin secretagogue action of 8-pCPT-2′-O-Me-cAMP-AM in WT mouse islets cannot be explained by an unexpected action of this cAMP analog to activate PKA, as verified through the use of a FRET-based A-kinase activity reporter (AKAR3) that reports PKA activation. Since the KO of PLC-ε disrupts the ability of 8-pCPT-2′-O-Me-cAMP-AM to potentiate GSIS, while also disrupting its ability to stimulate an increase of β-cell [Ca2+]i, the available evidence indicates that it is a Rap1-regulated PLC-ε that links Epac2 activation to Ca2+-dependent exocytosis of insulin. PMID:21478675

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

PubMed

Zwart, Ruud; Reed, Hannah; Sher, Emanuele

2018-01-01

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

Mechanical Design of High Lift Systems for High Aspect Ratio Swept Wings

NASA Technical Reports Server (NTRS)

Rudolph, Peter K. C.

1998-01-01

The NASA Ames Research Center is working to develop a methodology for the optimization and design of the high lift system for future subsonic airliners with the involvement of two partners. Aerodynamic analysis methods for two dimensional and three dimensional wing performance with flaps and slats deployed are being developed through a grant with the aeronautical department of the University of California Davis, and a flap and slat mechanism design procedure is being developed through a contract with PKCR, Inc., of Seattle, WA. This report documents the work that has been completed in the contract with PKCR on mechanism design. Flap mechanism designs have been completed for seven (7) different mechanisms with a total of twelve (12) different layouts all for a common single slotted flap configuration. The seven mechanisms are as follows: Simple Hinge, Upside Down/Upright Four Bar Linkage (two layouts), Upside Down Four Bar Linkages (three versions), Airbus A330/340 Link/Track Mechanism, Airbus A320 Link/Track Mechanism (two layouts), Boeing Link/Track Mechanism (two layouts), and Boeing 767 Hinged Beam Four Bar Linkage. In addition, a single layout has been made to investigate the growth potential from a single slotted flap to a vane/main double slotted flap using the Boeing Link/Track Mechanism. All layouts show Fowler motion and gap progression of the flap from stowed to a fully deployed position, and evaluations based on spanwise continuity, fairing size and number, complexity, reliability and maintainability and weight as well as Fowler motion and gap progression are presented. For slat design, the options have been limited to mechanisms for a shallow leading edge slat. Three (3) different layouts are presented for maximum slat angles of 20 deg, 15 deg and 1O deg all mechanized with a rack and pinion drive similar to that on the Boeing 757 airplane. Based on the work of Ljungstroem in Sweden, this type of slat design appears to shift the lift curve so that

Two-photon induced collagen cross-linking in bioartificial cardiac tissue

NASA Astrophysics Data System (ADS)

Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

2011-08-01

Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

Multi-level quantum mechanics theories and molecular mechanics study of the double-inversion mechanism of the F- + CH3I reaction in aqueous solution.

PubMed

Liu, Peng; Zhang, Jingxue; Wang, Dunyou

2017-06-07

A double-inversion mechanism of the F - + CH 3 I reaction was discovered in aqueous solution using combined multi-level quantum mechanics theories and molecular mechanics. The stationary points along the reaction path show very different structures to the ones in the gas phase due to the interactions between the solvent and solute, especially strong hydrogen bonds. An intermediate complex, a minimum on the potential of mean force, was found to serve as a connecting-link between the abstraction-induced inversion transition state and the Walden-inversion transition state. The potentials of mean force were calculated with both the DFT/MM and CCSD(T)/MM levels of theory. Our calculated free energy barrier of the abstraction-induced inversion is 69.5 kcal mol -1 at the CCSD(T)/MM level of theory, which agrees with the one at 72.9 kcal mol -1 calculated using the Born solvation model and gas-phase data; and our calculated free energy barrier of the Walden inversion is 24.2 kcal mol -1 , which agrees very well with the experimental value at 25.2 kcal mol -1 in aqueous solution. The calculations show that the aqueous solution makes significant contributions to the potentials of mean force and exerts a big impact on the molecular-level evolution along the reaction pathway.

Clarifying the link between von Neumann and thermodynamic entropies

NASA Astrophysics Data System (ADS)

Deville, Alain; Deville, Yannick

2013-01-01

The state of a quantum system being described by a density operator ρ, quantum statistical mechanics calls the quantity - kTr( ρln ρ), introduced by von Neumann, its von Neumann or statistical entropy. A 1999 Shenker's paper initiated a debate about its link with the entropy of phenomenological thermodynamics. Referring to Gibbs's and von Neumann's founding texts, we replace von Neumann's 1932 contribution in its historical context, after Gibbs's 1902 treatise and before the creation of the information entropy concept, which places boundaries into the debate. Reexamining von Neumann's reasoning, we stress that the part of his reasoning implied in the debate mainly uses thermodynamics, not quantum mechanics, and identify two implicit postulates. We thoroughly examine Shenker's and ensuing papers, insisting upon the presence of open thermodynamical subsystems, imposing us the use of the chemical potential concept. We briefly mention Landau's approach to the quantum entropy. On the whole, it is shown that von Neumann's viewpoint is right, and why Shenker's claim that von Neumann entropy "is not the quantum-mechanical correlate of thermodynamic entropy" can't be retained.

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

PubMed Central

ALLEN, LARRY A.; FELKER, G. MICHAEL; MEHRA, MANDEEP R.; CHIONG, JUN R.; DUNLAP, STEPHANIE H.; GHALI, JALAL K.; LENIHAN, DANIEL J.; OREN, RON M.; WAGONER, LYNNE E.; SCHWARTZ, TODD A.; ADAMS, KIRKWOOD F.

2014-01-01

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. PMID:20206898

Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure.

PubMed

Allen, Larry A; Felker, G Michael; Mehra, Mandeep R; Chiong, Jun R; Dunlap, Stephanie H; Ghali, Jalal K; Lenihan, Daniel J; Oren, Ron M; Wagoner, Lynne E; Schwartz, Todd A; Adams, Kirkwood F

2010-03-01

Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Potential mechanisms of resistance to venetoclax and strategies to circumvent it.

PubMed

Tahir, Stephen K; Smith, Morey L; Hessler, Paul; Rapp, Lisa Roberts; Idler, Kenneth B; Park, Chang H; Leverson, Joel D; Lam, Lloyd T

2017-06-02

Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges. In order to gain a more comprehensive insight into the nature of venetoclax resistance mechanisms, we evaluated the changes in the BCL-2 family members at the genetic and expression levels in seven different venetoclax-resistant derived leukemia and lymphoma cell lines. Gene and protein expression analyses identified a number of different alterations in the expression of pro- and anti-apoptotic BCL-2 family members. In the resistant derived cells, an increase in either or both the anti-apoptotic proteins BCL-X L or MCL-1, which are not targeted by venetoclax was observed, and either concomitant or exclusive with a decrease in one or more pro-apoptotic proteins. In addition, mutational analysis also revealed a mutation in the BH3 binding groove (F104L) that could potentially interfere with venetoclax-binding. Not all changes may be causally related to venetoclax resistance and may only be an epiphenomenon. For resistant cell lines showing elevations in BCL-X L or MCL-1, strong synergistic cell killing was observed when venetoclax was combined with either BCL-X L - or MCL-1-selective inhibitors, respectively. This highlights the importance of BCL-X L - and MCL-1 as causally contributing to venetoclax resistance. Overall our study identified numerous changes in multiple resistant lines; the changes were neither mutually exclusive nor universal across the cell lines tested, thus exemplifying the complexity

Linking plants, fungi and soil mechanics

NASA Astrophysics Data System (ADS)

Yildiz, Anil; Graf, Frank

2017-04-01

Plants provide important functions in respect soil strength and are increasingly considered for slope stabilisation within eco-engineering methods, particularly to prevent superficial soil failure. The protective functions include hydrological regulation through interception and evapo-transpiration as well as mechanical stabilisation through root reinforcement and, to a certain extent, chemical stabilisation through sticky metabolites. The ever-growing application of plants in slope stabilisation demanded more precise information of the vegetation effects and, concomitant, led the models for quantifying the reinforcement shoot up like mushrooms. However, so far, the framework and interrelationships for both the role of plants and the quantification concepts have not been thoroughly analysed and comprehensively considered, respectively, often resulting in unsatisfactory results. Although it seems obvious and is implicitly presupposed that the plant specific functions related to slope stability require growth and development, this is anything but given, particularly under the often hostile conditions dominating on bare and steep slopes. There, the superficial soil layer is often characterised by a lack of fines and missing medium-sized and fine pores due to an unstable soil matrix, predominantly formed by coarse grains. Low water retention capacity and substantial leaching of nutrients are the adverse consequences. Given this general set-up, sustainable plant growth and, particularly, root development is virtually unachievable. At exactly this point mycorrhizal fungi, the symbiotic partners of almost all plants used in eco-engineering, come into play. Though, they are probably well-known within the eco-engineering community, mycorrhizal fungi lead a humble existence. This is in spite of the fact that they supply their hosts with water and nutrients, improving the plant's ability to master otherwise unbridgeable environmental conditions. However, in order to support

Linking information and people in a social system for academic conferences

NASA Astrophysics Data System (ADS)

Brusilovsky, Peter; Oh, Jung Sun; López, Claudia; Parra, Denis; Jeng, Wei

2017-04-01

This paper investigates the feasibility of maintaining a social information system to support attendees at an academic conference. The main challenge of this work was to create an infrastructure where users' social activities, such as bookmarking, tagging, and social linking could be used to enhance user navigation and maximize the users' ability to locate two important types of information in conference settings: presentations to attend and attendees to meet. We developed Conference Navigator 3, a social conference support system that integrates a conference schedule planner with a social linking service. We examined its potential and functions in the context of a medium-scale academic conference. In this paper, we present the design of the system's socially enabled features and report the results of a conference-based study. Our study demonstrates the feasibility of social information systems for supporting academic conferences. Despite the low number of potential users and the short timeframe in which conferences took place, the usage of the system was high enough to provide sufficient data for social mechanisms. The study shows that most critical social features were highly appreciated and used, and provides direction for further research.

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

PubMed

Zhou, Lingyun; Zhao, Ye; Wang, Shuifeng

2015-11-01

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

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

PubMed Central

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

2015-01-01

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

Evidence for the Phospholipid Sponge Effect as the Biocidal Mechanism in Surface-Bound Polyquaternary Ammonium Coatings with Variable Cross-Linking Density.

PubMed

Gao, Jing; White, Evan M; Liu, Qiaohong; Locklin, Jason

2017-03-01

Poly quaternary "-oniums" derived from polyethylenimine (PEI), poly(vinyl-N-alkylpyridinium), or chitosan belong to a class of cationic polymers that are efficient antimicrobial agents. When dissolved in solution, the positively charged polycations are able to displace the divalent cations of the cellular phospholipid bilayer and disrupt the ionic cross-links and structural integrity of the membrane. However, when immobilized to a surface where confinement limits diffusion, poly -oniums still show excellent antimicrobial activity, which implies a different biocidal mode of action. Recently, a proposed mechanism, named phospholipid sponge effect, suggested that surface-bound polycationic networks are capable of recruiting negatively charged phospholipids out of the bacterial cell membrane and sequestering them within the polymer matrix.1 However, there has been insufficient evidence to support this hypothesis. In this study, a surface-bound N,N-dodecyl methyl-co-N,N-methylbenzophenone methyl quaternary PEI (DMBQPEI) was prepared to verify the phospholipid sponge effect. By tuning the irradiation time, the cross-linking densities of surface-bound DMBQPEI films were mediated. The modulus of films was measured by PeakForce Quantitative Nanomechanical Mapping (QNM) to indicate the cross-linking density variation with increasing irradiation time. A negative correlation between the film cross-linking density and the absorption of a negatively charged phospholipid (DPhPG) was observed, but no such correlations were observed with a neutral phospholipid (DPhPC), which strongly supported the action of anionic phospholipid suction proposed in the lipid sponge effect. Moreover, the killing efficiency toward S. aureus and E. coli was inversely affected by the cross-linking density of the films, providing evidence for the phospholipid sponge effect. The relationship between killing efficiency and film cross-linking density is discussed.

Sirtuins in neurodegenerative diseases: an update on potential mechanisms

PubMed Central

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

2013-01-01

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

Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

PubMed Central

Alexandre, Leo; Long, Elizabeth; Beales, Ian LP

2014-01-01

In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits. PMID:25400997

Genomic variation in the MMP-1 promoter influences estrogen receptor mediated activity in a mechanically activated environment: potential implications for microgravity risk assessment

NASA Astrophysics Data System (ADS)

Thaler, John; Myers, Ken; Lu, Ting; Hart, David

Background: Mechanotransduction, the conversion of mechanical forces (tensile, compression, shear etc.) into cellular signals is a significant response mechanism in bone that contributes to the balance between formation and resorption and helps maintain bone density. In microgravity the lack of mechanical signals can lead to a loss of bone density, however the signaling pathways responsible are not well understood. For women, sex-specific hormones are also important in maintaining bone density since estrogen deficiency is a major factor in the etiology of osteoporosis in postmenopausal women. Estrogen Receptors (ERs) are present in human connective tissue cells such as osteoblasts and may play a role in mechanotransduction responses. The two ER isoforms, alpha (ER-α) and beta (ER-β) differentially regulate expression of matrixmetalloproteinases (MMPs) which degrade extracellular matrix components found in connective tissues. Mechanical stimulation is known to affect the expression of MMP-1, a collagenase involved in the bone resorption process. The MMP-1 promoter region contains a single nucleotide polymorphism of an additional guanine (G) at position -1607 bp which creates a binding site for a member of the Ets family of mammalian transcription factors. The 2G allele is known to be present in 45-70% of healthy populations and has been associated with higher MMP-1 expression. The 2G allele has been linked to higher risk of several types of cancer but a link to osteoporosis or microgravity induced bone loss has not been explored. The purpose of the present study was to conduct a case-study to determine whether small genetic variations can influence cellular and tissue responses to mechanical loading. Specifically we examined the potential of the 1G/2G -1607 MMP-1 promoter SNP to alter the interplay between mechanical shear stress and estrogen receptors in controlling MMP-1 expression. Methods: Rabbit synovial cells (HIG-82) were used as an in vitro model system to

A link between LEAFY and B-gene homologues in Welwitschia mirabilis sheds light on ancestral mechanisms prefiguring floral development.

PubMed

Moyroud, Edwige; Monniaux, Marie; Thévenon, Emmanuel; Dumas, Renaud; Scutt, Charles P; Frohlich, Michael W; Parcy, François

2017-10-01

Flowering plants evolved from an unidentified gymnosperm ancestor. Comparison of the mechanisms controlling development in angiosperm flowers and gymnosperm cones may help to elucidate the mysterious origin of the flower. We combined gene expression studies with protein behaviour characterization in Welwitschia mirabilis to test whether the known regulatory links between LEAFY and its MADS-box gene targets, central to flower development, might also contribute to gymnosperm reproductive development. We found that WelLFY, one of two LEAFY-like genes in Welwitschia, could be an upstream regulator of the MADS-box genes APETALA3/PISTILLATA-like (B-genes). We demonstrated that, even though their DNA-binding domains are extremely similar, WelLFY and its paralogue WelNDLY exhibit distinct DNA-binding specificities, and that, unlike WelNDLY, WelLFY shares with its angiosperm orthologue the capacity to bind promoters of Welwitschia B-genes. Finally, we identified several cis-elements mediating these interactions in Welwitschia and obtained evidence that the link between LFY homologues and B-genes is also conserved in two other gymnosperms, Pinus and Picea. Although functional approaches to investigate cone development in gymnosperms are limited, our state-of-the-art biophysical techniques, coupled with expression studies, provide evidence that crucial links, central to the control of floral development, may already have existed before the appearance of flowers. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Permethrin potentiates adipogenesis via intracellular calcium and endoplasmic reticulum stress-mediated mechanisms in 3T3-L1 adipocytes.

PubMed

Xiao, Xiao; Qi, Weipeng; Clark, John M; Park, Yeonhwa

2017-11-01

Permethrin, a pyrethroid insecticide, was previously reported to promote adipogenesis in vitro and weight gain in vivo. The mechanism by which permethrin promotes adipogenesis/obesity, however, has not been fully explored. Intracellular calcium and endoplasmic reticulum (ER) stress have been reported to be linked with adipogenesis and obesity. Because pyrethroid insecticides have been determined to influence intracellular calcium and ER stress in vitro, the purpose of this current study was to investigate whether permethrin potentiates adipogenesis via a change in intracellular calcium, leading to endoplasmic reticulum (ER) stress in 3T3-L1 adipocytes. 3T3-L1 cells were exposed to four different concentrations of permethrin (0.01, 0.1, 1 & 10 μM) for 6 days during differentiation. Treatment of permethrin increased intracellular calcium level in a concentration-dependent manner. Similarly, permethrin treatment increased protein levels of ER stress markers in a concentration-dependent manner. These data suggest that intracellular calcium and ER stress may be involved in permethrin-induced adipogenesis of 3T3-L1 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2014-01-01

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

Drill drive mechanism

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

Dressel, M.O.

1979-10-30

A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfacesmore » of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the different gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft. 11 claims.« less

Drill drive mechanism

DOEpatents

Dressel, Michael O.

1979-01-01

A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfaces of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the differential gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft.

The potential role of neuropathic mechanisms in dry eye syndromes.

PubMed

Mcmonnies, Charles W

Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

A Single Molecular Diels-Alder Crosslinker for Achieving Recyclable Cross-Linked Polymers.

PubMed

Chen, Shengli; Wang, Fenfen; Peng, Yongjin; Chen, Tiehong; Wu, Qiang; Sun, Pingchuan

2015-09-01

A triol-functional crosslinker combining the thermoreversible properties of Diels-Alder (DA) adducts in one molecule is designed, synthesized, and used as an ideal substitute of a traditional crosslinker to prepare thermal recyclable cross-linked polyurethanes with excellent mechanical properties and recyclability in a very simple and efficient way. The recycle property of these materials achieved by the DA/retro-DA reaction at a suitable temperature is verified by differential scanning calorimetry and in situ variable temperature solid-state NMR experiments during the cyclic heating and cooling processes. The thermal recyclability and remending ability of the bulk polyurethanes is demonstrated by three polymer processing methods, including hot-press molding, injection molding, and solution casting. It is notable that all the recycled cross-linked polymers display nearly invariable elongation/stress at break compared to the as-synthesized samples. Further end-group functionalization of this single molecular DA crosslinker provides the potential in preparing a wide range of recyclable cross-linked polymers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2016-05-01

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

Forgiveness and relationship satisfaction: mediating mechanisms.

PubMed

Braithwaite, Scott R; Selby, Edward A; Fincham, Frank D

2011-08-01

Although the ability to forgive transgressions has been linked to overall relationship satisfaction, the mechanisms that mediate this association have not been established. We propose that the tendency to forgive a romantic partner increases relationship satisfaction via increased relational effort and decreased negative conflict. In two studies, we used structural equations modeling to examine these variables as potential mechanisms that drive this association. In Study 1 (N = 523) and Study 2 (N = 446) we found that these variables significantly mediated the association between forgiveness and relationship satisfaction. The findings were robust when examined concurrently and longitudinally, across multiple measures of forgiveness, and when accounting for baseline relationship satisfaction and interpersonal commitment. These two mechanisms parallel theorized positive and negative dimensions of forgiveness and the motivational transformation that is said to underlie forgiveness. Theoretical implications and implications for intervention are discussed.

Wireless optical transceiver design, link analisys and alignment control for mobile communication

NASA Astrophysics Data System (ADS)

Zhou, Dayong

Pointing, acquisition and tracking of a free-space optical node in a mobile network experiencing misalignment due to adverse factors including vibration, motion and atmospheric turbulence requires a different approach than traditional free-space optical transceivers. A recent fiber-bundle approach for beam steering at the transmitter was investigated to provide continuous beam coverage at the receiver without the application of mechanical devices. Utilizing multiple fibers-lenses sets at the receiver was also proposed to enhance the tolerance of optical link misalignment. In this work, both laboratory experiments and software simulation were implemented to evaluate the optical link performance for different fiber-bundle-based transceiver setups as the link parameters were varied. The performance was evaluated in terms of the coverage area at the receiver, which is a measure of misalignment tolerance and is dependent not only on wavelength but on other key parameters such as link length, transmitted power, the pattern of transmitters, beam divergence, and the receiver construction. The results showed that fiber-bindle-based transceivers reveal significant potential to maximize the up time of the link, and the results also provide guidance on the further development of the overall system. To incorporate the proposed transceiver designs, an alignment control system was developed and evaluated as well. The laboratory results show that the optical control system successfully recovered and maintained the link while the receiver was in motion and the signal coverage at the target area was enhanced significantly.

Attitude similarity and familiarity and their links to mental health: An examination of potential interpersonal mediators.

PubMed

Moore, Shannon M; Uchino, Bert N; Baucom, Brian R W; Behrends, Arwen A; Sanbonmatsu, David

2017-01-01

Similarity and familiarity with partner's attitudes are linked to positive relationship outcomes, while interpersonal variables have been linked to mental health. Using multilevel models (MLMs), we modeled the associations between these attitudinal variables and mental health outcomes in 74 married couples. We found that higher levels of attitude similarity in couples were linked to lower depression, while higher levels of attitude familiarity in couples were associated with greater satisfaction with life. Mediational analyses indicated marital satisfaction and interpersonal stress mediated the link between attitude similarity and depression. Marital satisfaction also mediated the link between familiarity and satisfaction with life. This study is the first linking attitude familiarity to mental health and provides evidence that familiarity and similarity have mental health effects partly due to their interpersonal consequences.

Chitosan supramolecularly cross linked with trimesic acid - Facile synthesis, characterization and evaluation of adsorption potential for chromium(VI).

PubMed

Bhatt, Ronak; Sreedhar, B; Padmaja, P

2017-11-01

A facile synthesis of Chitosan Supramolecularly cross-linked with Trimesic Acid (CTMA) is reported in this work. The adsorption potential of CTMA for removal of hexavalent chromium was evaluated and the influence of pH, temperature, contact time and adsorbent dose on the adsorption process was investigated. The experimental results showed that CTMA could efficiently adsorb Cr 6+ and partially reduce it to the less toxic Cr 3+ state. The maximum adsorption capacity of CTMA for Cr 6+ was found to be 129.53mg/g at pH 2.0. CTMA and chromium loaded CTMA were characterised by FT-IR, Raman, TGA-DSC, SEM-EDX, XRD, ESR and XPS spectroscopic techniques. Chitosan was observed to be cross- linked with TMA via ionic, hydrogen bonding and pi-pi supramolecular interactions while adsorption of chromium onto CTMA was by electrostatic forces and hydrogen bonding. From the observed results it was evident that CTMA was successfully applied for simultaneous removal of chromium, lead and iron from chrome plating effluent. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanical model testing of rebreathing potential in infant bedding materials

PubMed Central

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

1998-01-01

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

 PMID:9623394

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

PubMed

Särkämö, Teppo; Soto, David

2012-04-01

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

Supersymmetric quantum mechanics: Engineered hierarchies of integrable potentials and related orthogonal polynomials

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

Balondo Iyela, Daddy; Centre for Cosmology, Particle Physics and Phenomenology; Département de Physique, Université de Kinshasa

2013-09-15

Within the context of supersymmetric quantum mechanics and its related hierarchies of integrable quantum Hamiltonians and potentials, a general programme is outlined and applied to its first two simplest illustrations. Going beyond the usual restriction of shape invariance for intertwined potentials, it is suggested to require a similar relation for Hamiltonians in the hierarchy separated by an arbitrary number of levels, N. By requiring further that these two Hamiltonians be in fact identical up to an overall shift in energy, a periodic structure is installed in the hierarchy which should allow for its resolution. Specific classes of orthogonal polynomials characteristicmore » of such periodic hierarchies are thereby generated, while the methods of supersymmetric quantum mechanics then lead to generalised Rodrigues formulae and recursion relations for such polynomials. The approach also offers the practical prospect of quantum modelling through the engineering of quantum potentials from experimental energy spectra. In this paper, these ideas are presented and solved explicitly for the cases N= 1 and N= 2. The latter case is related to the generalised Laguerre polynomials, for which indeed new results are thereby obtained. In the context of dressing chains and deformed polynomial Heisenberg algebras, some partial results for N⩾ 3 also exist in the literature, which should be relevant to a complete study of the N⩾ 3 general periodic hierarchies.« less

Investigation of mechanisms linking media exposure to smoking in high school students.

PubMed

Carson, Nicholas J; Rodriguez, Daniel; Audrain-McGovern, Janet

2005-08-01

Media exposure has been found to impact adolescent smoking, although the mechanisms of this relationship have not been thoroughly investigated. Drive for thinness and tobacco advertising receptivity, both shown to be associated with smoking, are two potential mediators. 967 twelfth grade students completed a self-report survey as part of a longitudinal study of biobehavioral predictors of smoking. Exposure to magazines and television, drive for thinness, tobacco advertisement receptivity, and twelfth grade smoking level were the primary variables of interest. Effects of gender, race, BMI, smoking exposure, and perceived physical appearance were controlled for in the model. Exposure to fashion, entertainment, and gossip magazines had indirect effects on smoking via drive for thinness and tobacco advertisement receptivity. There was a direct effect of health, fitness, and sports magazine reading on smoking. Television watching had no significant effects on smoking. Adolescents who read fashion, entertainment, and gossip magazines may be more likely to smoke, in part, because of a higher drive for thinness and greater receptivity to cigarette advertisements. Conversely, adolescents reading Health and Fitness magazines may be less likely to smoke. Drive for thinness and tobacco advertising receptivity are thus potential targets for adolescent smoking intervention.

Evaluation of synthesized cross linked polyvinyl alcohol as potential disintegrant.

PubMed

Patel, Ashok R; Vavia, Pradeep R

2010-01-01

The present study deals with evaluation of crosslinked poly vinyl alcohol (PVA) as a potential disintegrant. Crosslinking of PVA was carried out using glutaraldehyde as a crosslinker, in presence of acidic conditions. The crosslinking reaction was optimized for a) polymer: crosslinker ratio; b) temperature requirement and c) reaction duration. Certain physical parameters of the disintegrant (including sedimentation volume, hydration capacity, specific surface area and bulk and tap density) were determined and compared to the known disintegrants. Characterization was carried out using FT-IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also studied for acute toxicity in rats and found to be safe for oral use. Disintegration property of formed product was compared to known disintegrant (Ac-Di-Sol) and it was found to give better results. The disintegration mechanism of developed disintegrant was postulated based on results obtained from various physical evaluations including: Study of effect of disintegrant concentration, fillers, and hardness, mode of incorporation and method of granulation on disintegration activity. By changing the condition parameters of well known crosslinking reaction of PVA, we obtained a crosslinked product which had excellent disintegration activity, good flow and optimal tableting properties.

Mechanotransduction mechanisms in growing spherically structured tissues

NASA Astrophysics Data System (ADS)

Littlejohns, Euan; Dunlop, Carina M.

2018-04-01

There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell–cell and cell–gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

Regulation of alternative splicing by local histone modifications: potential roles for RNA-guided mechanisms

PubMed Central

Zhou, Hua-Lin; Luo, Guangbin; Wise, Jo Ann; Lou, Hua

2014-01-01

The molecular mechanisms through which alternative splicing and histone modifications regulate gene expression are now understood in considerable detail. Here, we discuss recent studies that connect these two previously separate avenues of investigation, beginning with the unexpected discoveries that nucleosomes are preferentially positioned over exons and DNA methylation and certain histone modifications also show exonic enrichment. These findings have profound implications linking chromatin structure, histone modification and splicing regulation. Complementary single gene studies provided insight into the mechanisms through which DNA methylation and histones modifications modulate alternative splicing patterns. Here, we review an emerging theme resulting from these studies: RNA-guided mechanisms integrating chromatin modification and splicing. Several groundbreaking papers reported that small noncoding RNAs affect alternative exon usage by targeting histone methyltransferase complexes to form localized facultative heterochromatin. More recent studies provided evidence that pre-messenger RNA itself can serve as a guide to enable precise alternative splicing regulation via local recruitment of histone-modifying enzymes, and emerging evidence points to a similar role for long noncoding RNAs. An exciting challenge for the future is to understand the impact of local modulation of transcription elongation rates on the dynamic interplay between histone modifications, alternative splicing and other processes occurring on chromatin. PMID:24081581

Deciphering potential mechanisms of anaerobic soil disinfestation (ASD)-mediated control of Pratylenchus penetrans

USDA-ARS?s Scientific Manuscript database

Pratylenchus penetrans is a component of the apple replant disease (ARD) causal pathogen complex. The potential role for biological mechanisms contributing to ASD-mediated suppression of P. penetrans was examined in greenhouse study using orchard soil with a history of ARD. Populations of P. penetra...

Potential mechanisms for low uric acid in Parkinson disease

PubMed Central

Young, Sarah; Rosen, Ami; Bernhard, Douglas; Millington, David; Factor, Stewart

2018-01-01

Several epidemiologic studies have described an association between low serum uric acid (UA) and Parkinson disease (PD). Uric acid is a known antioxidant, and one proposed mechanism of neurodegeneration in PD is oxidative damage of dopamine neurons. However, other complex metabolic pathways may contribute. The purpose of this study is to elucidate potential mechanisms of low serum UA in PD. Subjects who met diagnostic criteria for definite or probable PD (n = 20) and controls (n = 20) aged 55–80 years were recruited. Twenty-four hour urine samples were collected from all participants, and both uric acid and allantoin were measured and corrected for body mass index (BMI). Urinary metabolites were compared using a twoway ANOVA with diagnosis and sex as the explanatory variables. There were no significant differences between PD and controls for total UA (p = 0.60), UA corrected for BMI (p = 0.37), or in the interaction of diagnosis and sex on UA (p = 0.24). Similarly, there were no significant differences between PD and controls for allantoin (p = 0.47), allantoin corrected for BMI (p = 0.57), or in the interaction of diagnosis and sex on allantoin (p = 0.78). Allantoin/UA ratios also did not significantly differ by diagnosis (p = 0.99). Our results imply that low serum UA in PD may be due to an intrinsic mechanism that alters the homeostatic set point for serum UA in PD, and may contribute to relatively lower protection against oxidative damage. These findings provide indirect support for neuroprotection trials aimed at raising serum UA. PMID:26747026

Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

PubMed

Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

2016-01-26

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

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.

Attitude Similarity and Familiarity and Their Links to Mental Health: An Examination of Potential Interpersonal Mediators

PubMed Central

Uchino, Bert; Baucom, Brian; Behrends, Arwen; Sanbonmatsu, David

2017-01-01

Similarity and familiarity with partner's attitudes (Byrne, Clore, & Smeaton, 1986; Sanbonmatsu, Uchino, & Birmingham, 2011) are linked to positive relationship outcomes, while interpersonal variables have been linked to mental health (e.g., Lakey & Cronin, 2008). Using multilevel models (MLMs), we modeled the associations between these attitudinal variables and mental health outcomes in 74 married couples. We found that higher levels of attitude similarity in couples were linked to lower depression, while higher levels of attitude familiarity in couples were associated with greater satisfaction with life. Mediational analyses indicated marital satisfaction and interpersonal stress mediated the link between attitude similarity and depression. Marital satisfaction also mediated the link between familiarity and satisfaction with life. This study is the first linking attitude familiarity to mental health and provides evidence that familiarity and similarity have mental health effects partly due to their interpersonal consequences. PMID:27065059

Opioid receptor desensitization: mechanisms and its link to tolerance

PubMed Central

Allouche, Stéphane; Noble, Florence; Marie, Nicolas

2014-01-01

Opioid receptors (OR) are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of the receptor. PMID:25566076

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.

PubMed

Forrester, Steven J; Kawai, Tatsuo; O'Brien, Shannon; Thomas, Walter; Harris, Raymond C; Eguchi, Satoru

2016-01-01

Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.

In Situ Cross-Linking of Stimuli-Responsive Hemicellulose Microgels during Spray Drying

PubMed Central

2015-01-01

Chemical cross-linking during spray drying offers the potential for green fabrication of microgels with a rapid stimuli response and good blood compatibility and provides a platform for stimuli-responsive hemicellulose microgels (SRHMGs). The cross-linking reaction occurs rapidly in situ at elevated temperature during spray drying, enabling the production of microgels in a large scale within a few minutes. The SRHMGs with an average size range of ∼1–4 μm contain O-acetyl-galactoglucomannan as a matrix and poly(acrylic acid), aniline pentamer (AP), and iron as functional additives, which are responsive to external changes in pH, electrochemical stimuli, magnetic field, or dual-stimuli. The surface morphologies, chemical compositions, charge, pH, and mechanical properties of these smart microgels were evaluated using scanning electron microscopy, IR, zeta potential measurements, pH evaluation, and quantitative nanomechanical mapping, respectively. Different oxidation states were observed when AP was introduced, as confirmed by UV spectroscopy and cyclic voltammetry. Systematic blood compatibility evaluations revealed that the SRHMGs have good blood compatibility. This bottom-up strategy to synthesize SRHMGs enables a new route to the production of smart microgels for biomedical applications. PMID:25630464

In situ cross-linking of stimuli-responsive hemicellulose microgels during spray drying.

PubMed

Zhao, Weifeng; Nugroho, Robertus Wahyu N; Odelius, Karin; Edlund, Ulrica; Zhao, Changsheng; Albertsson, Ann-Christine

2015-02-25

Chemical cross-linking during spray drying offers the potential for green fabrication of microgels with a rapid stimuli response and good blood compatibility and provides a platform for stimuli-responsive hemicellulose microgels (SRHMGs). The cross-linking reaction occurs rapidly in situ at elevated temperature during spray drying, enabling the production of microgels in a large scale within a few minutes. The SRHMGs with an average size range of ∼ 1-4 μm contain O-acetyl-galactoglucomannan as a matrix and poly(acrylic acid), aniline pentamer (AP), and iron as functional additives, which are responsive to external changes in pH, electrochemical stimuli, magnetic field, or dual-stimuli. The surface morphologies, chemical compositions, charge, pH, and mechanical properties of these smart microgels were evaluated using scanning electron microscopy, IR, zeta potential measurements, pH evaluation, and quantitative nanomechanical mapping, respectively. Different oxidation states were observed when AP was introduced, as confirmed by UV spectroscopy and cyclic voltammetry. Systematic blood compatibility evaluations revealed that the SRHMGs have good blood compatibility. This bottom-up strategy to synthesize SRHMGs enables a new route to the production of smart microgels for biomedical applications.

Adaptive nodes enrich nonlinear cooperative learning beyond traditional adaptation by links.

PubMed

Sardi, Shira; Vardi, Roni; Goldental, Amir; Sheinin, Anton; Uzan, Herut; Kanter, Ido

2018-03-23

Physical models typically assume time-independent interactions, whereas neural networks and machine learning incorporate interactions that function as adjustable parameters. Here we demonstrate a new type of abundant cooperative nonlinear dynamics where learning is attributed solely to the nodes, instead of the network links which their number is significantly larger. The nodal, neuronal, fast adaptation follows its relative anisotropic (dendritic) input timings, as indicated experimentally, similarly to the slow learning mechanism currently attributed to the links, synapses. It represents a non-local learning rule, where effectively many incoming links to a node concurrently undergo the same adaptation. The network dynamics is now counterintuitively governed by the weak links, which previously were assumed to be insignificant. This cooperative nonlinear dynamic adaptation presents a self-controlled mechanism to prevent divergence or vanishing of the learning parameters, as opposed to learning by links, and also supports self-oscillations of the effective learning parameters. It hints on a hierarchical computational complexity of nodes, following their number of anisotropic inputs and opens new horizons for advanced deep learning algorithms and artificial intelligence based applications, as well as a new mechanism for enhanced and fast learning by neural networks.

The origins of cognitive vulnerability in early childhood: mechanisms linking early attachment to later depression.

PubMed

Morley, Tara E; Moran, Greg

2011-11-01

This paper examines the theory and research linking attachment relationships to cognitive vulnerability to depression and assesses evidence that early attachment experiences contribute to the development of these cognitive processes. Most research in this area has involved adult participants using self-report measures of both attachment and depressive vulnerabilities and thus cannot convincingly speak to the existence of such a developmental pathway. Several studies, however, have followed individuals from infancy and examined the emergence of self-esteem and responses to failure throughout childhood and adolescence. These studies suggest that early experiences in non-secure attachment relationships place an individual at-risk for developing a cognitive framework that increases their vulnerability to depression following stressful life events. The paper concludes with a discussion of how future research might best explore specific mechanisms through which distinct attachment relationships may lead to divergent developmental pathways sharing the common outcome of cognitive processes that place individuals at risk for depression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mechanistic Target of Rapamycin Is a Novel Molecular Mechanism Linking Folate Availability and Cell Function.

PubMed

Silva, Elena; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

2017-07-01

Folate deficiency has been linked to a wide range of disorders, including cancer, neural tube defects, and fetal growth restriction. Folate regulates cellular function mediated by its involvement in the synthesis of nucleotides, which are needed for DNA synthesis, and its function as a methyl donor, which is critical for DNA methylation. Here we review current data showing that folate sensing by mechanistic target of rapamycin (mTOR) constitutes a novel and distinct pathway by which folate modulates cell functions such as nutrient transport, protein synthesis, and mitochondrial respiration. The mTOR signaling pathway responds to growth factors and changes in nutrient availability to control cell growth, proliferation, and metabolism. mTOR exists in 2 complexes, mTOR complex (mTORC) 1 and mTORC2, which have distinct upstream regulators and downstream targets. Folate deficiency in pregnant mice caused a marked inhibition of mTORC1 and mTORC2 signaling in multiple maternal and fetal tissues, downregulation of placental amino acid transporters, and fetal growth restriction. In addition, folate deficiency in primary human trophoblast (PHT) cells resulted in inhibition of mTORC1 and mTORC2 signaling and decreased the activity of key amino acid transporters. Folate sensing by mTOR in PHT cells is independent of the accumulation of homocysteine and requires the proton-coupled folate transporter (PCFT; solute carrier 46A1). Furthermore, mTORC1 and mTORC2 regulate trophoblast folate uptake by modulating the cell surface expression of folate receptor α and the reduced folate carrier. These findings, which provide a novel link between folate availability and cell function, growth, and proliferation, may have broad biological significance given the critical role of folate in normal cell function and the multiple diseases that have been associated with decreased or excessive folate availability. Low maternal folate concentrations are linked to restricted fetal growth, and we

Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits

PubMed Central

Beurel, E; Jope, R S

2014-01-01

Suicide is one of the leading causes of death in the United States, yet it remains difficult to understand the mechanistic provocations and to intervene therapeutically. Stress is recognized as a frequent precursor to suicide. Psychological stress is well established to cause activation of the inflammatory response, including causing neuroinflammation, an increase of inflammatory molecules in the central nervous system (CNS). Neuroinflammation is increasingly recognized as affecting many aspects of CNS functions and behaviors. In particular, much evidence demonstrates that inflammatory markers are elevated in traits that have been linked to suicidal behavior, including aggression, impulsivity and depression. Lithium is recognized as significantly reducing suicidal behavior, is anti-inflammatory and diminishes aggression, impulsivity and depression traits, each of which is associated with elevated inflammation. The anti-inflammatory effects of lithium result from its inhibition of glycogen synthase kinase-3 (GSK3). GSK3 has been demonstrated to strongly promote inflammation, aggressive behavior in rodents and depression-like behaviors in rodents, whereas regulation of impulsivity by GSK3 has not yet been investigated. Altogether, evidence is building supporting the hypothesis that stress activates GSK3, which in turn promotes inflammation, and that inflammation is linked to behaviors associated with suicide, including particularly aggression, impulsivity and depression. Further investigation of these links may provide a clearer understanding of the causes of suicidal behavior and provide leads for the development of effective preventative interventions, which may include inhibitors of GSK3. PMID:25514751

Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits.

PubMed

Beurel, E; Jope, R S

2014-12-16

Suicide is one of the leading causes of death in the United States, yet it remains difficult to understand the mechanistic provocations and to intervene therapeutically. Stress is recognized as a frequent precursor to suicide. Psychological stress is well established to cause activation of the inflammatory response, including causing neuroinflammation, an increase of inflammatory molecules in the central nervous system (CNS). Neuroinflammation is increasingly recognized as affecting many aspects of CNS functions and behaviors. In particular, much evidence demonstrates that inflammatory markers are elevated in traits that have been linked to suicidal behavior, including aggression, impulsivity and depression. Lithium is recognized as significantly reducing suicidal behavior, is anti-inflammatory and diminishes aggression, impulsivity and depression traits, each of which is associated with elevated inflammation. The anti-inflammatory effects of lithium result from its inhibition of glycogen synthase kinase-3 (GSK3). GSK3 has been demonstrated to strongly promote inflammation, aggressive behavior in rodents and depression-like behaviors in rodents, whereas regulation of impulsivity by GSK3 has not yet been investigated. Altogether, evidence is building supporting the hypothesis that stress activates GSK3, which in turn promotes inflammation, and that inflammation is linked to behaviors associated with suicide, including particularly aggression, impulsivity and depression. Further investigation of these links may provide a clearer understanding of the causes of suicidal behavior and provide leads for the development of effective preventative interventions, which may include inhibitors of GSK3.

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

PubMed Central

Ruiz de Garibay, Gorka; Herranz, Carmen; Llorente, Alicia; Boni, Jacopo; Serra-Musach, Jordi; Mateo, Francesca; Aguilar, Helena; Gómez-Baldó, Laia; Petit, Anna; Vidal, August; Climent, Fina; Hernández-Losa, Javier; Cordero, Álex; González-Suárez, Eva; Sánchez-Mut, José Vicente; Esteller, Manel; Llatjós, Roger; Varela, Mar; López, José Ignacio; García, Nadia; Extremera, Ana I.; Gumà, Anna; Ortega, Raúl; Plà, María Jesús; Fernández, Adela; Pernas, Sònia; Falo, Catalina; Morilla, Idoia; Campos, Miriam; Gil, Miguel; Román, Antonio; Molina-Molina, María; Ussetti, Piedad; Laporta, Rosalía; Valenzuela, Claudia; Ancochea, Julio; Xaubet, Antoni; Casanova, Álvaro; Pujana, Miguel Angel

2015-01-01

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM. PMID:26167915

Integral transforms of the quantum mechanical path integral: Hit function and path-averaged potential.

PubMed

Edwards, James P; Gerber, Urs; Schubert, Christian; Trejo, Maria Anabel; Weber, Axel

2018-04-01

We introduce two integral transforms of the quantum mechanical transition kernel that represent physical information about the path integral. These transforms can be interpreted as probability distributions on particle trajectories measuring respectively the relative contribution to the path integral from paths crossing a given spatial point (the hit function) and the likelihood of values of the line integral of the potential along a path in the ensemble (the path-averaged potential).

Integral transforms of the quantum mechanical path integral: Hit function and path-averaged potential

NASA Astrophysics Data System (ADS)

Edwards, James P.; Gerber, Urs; Schubert, Christian; Trejo, Maria Anabel; Weber, Axel

2018-04-01

We introduce two integral transforms of the quantum mechanical transition kernel that represent physical information about the path integral. These transforms can be interpreted as probability distributions on particle trajectories measuring respectively the relative contribution to the path integral from paths crossing a given spatial point (the hit function) and the likelihood of values of the line integral of the potential along a path in the ensemble (the path-averaged potential).

A realist evaluation of social prescribing: an exploration into the context and mechanisms underpinning a pathway linking primary care with the voluntary sector.

PubMed

Bertotti, Marcello; Frostick, Caroline; Hutt, Patrick; Sohanpal, Ratna; Carnes, Dawn

2018-05-01

This article adopts a realist approach to evaluate a social prescribing pilot in the areas of Hackney and City in London (United Kingdom). It unpacks the contextual factors and mechanisms that influenced the development of this pilot for the benefits of GPs, commissioners and practitioners, and reflects on the realist approach to evaluation as a tool for the evaluation of health interventions. Primary care faces considerable challenges including the increase in long-term conditions, GP consultation rates, and widening health inequalities. With its emphasis on linking primary care to non-clinical community services via a social prescribing coordinator (SPC), some models of social prescribing could contribute to reduce the burden on primary care, tackle health inequalities and encourage people to make greater use of non-clinical forms of support. This realist analysis was based on qualitative interviews with users, commissioners, a GP survey, focus groups and learning events to explore stakeholders' experience. To enable a detailed analysis, we adapted the realist approach by subdividing the social prescribing pathway into stages, each with contextual factors, mechanisms and outcomes. SPCs were pivotal to the effective functioning of the social prescribing service and responsible for the activation and initial beneficial impact on users. Although social prescribing shows significant potential for the benefit of patients and primary care, several challenges need to be considered and overcome, including 'buy in' from some GPs, branding, and funding for the third sector in a context where social care cuts are severely affecting the delivery of health care. With its emphasis on context and mechanisms, the realist evaluation approach is useful in understanding how to identify and improve health interventions, and analyse in greater detail the contribution of different stakeholders. As the SPC is central to social prescribing, more needs to be done to understand their role

Effects on DNA Damage and/or Repair Processes as Biological Mechanisms Linking Psychological Stress to Cancer Risk

PubMed Central

Jenkins, Frank J.; Van Houten, Bennett; Bovbjerg, Dana H.

2014-01-01

Considerable research effort in the past several decades has focused on the impact of psychological stress, and stress hormones, on cancer progression. Numerous studies have reported that stress hormone treatment or in vivo stress exposure can enhance the growth of tumor cell lines in vitro, as well as tumors in animal models, and have begun to explore molecular mechanisms. Comparatively little research has focused on the impact of psychological stress and stress hormones on cancer initiation, in part due to inherent methodological challenges, but also because potential underlying biological mechanisms have remained obscure. In this review, we present a testable theoretical model of pathways by which stress may result in cellular transformation and tumorigenesis. This model supports our overarching hypothesis that psychological stress, acting through increased levels of catecholamines and/or cortisol, can increase DNA damage and/or reduce repair mechanisms, resulting in increased risk of DNA mutations leading to carcinogenesis. A better understanding of molecular pathways by which psychological stress can increase the risk of cancer initiation would open new avenues of translational research, bringing together psychologists, neuroscientists, and molecular biologists, potentially resulting in the development of novel approaches for cancer risk reduction at the population level. PMID:24891812

Mechanisms linking metabolism of Helicobacter pylori to 18O and 13C-isotopes of human breath CO2

PubMed Central

Som, Suman; De, Anulekha; Banik, Gourab Dutta; Maity, Abhijit; Ghosh, Chiranjit; Pal, Mithun; Daschakraborty, Sunil B.; Chaudhuri, Sujit; Jana, Subhra; Pradhan, Manik

2015-01-01

The gastric pathogen Helicobacter pylori utilize glucose during metabolism, but the underlying mechanisms linking to oxygen-18 (18O) and carbon-13 (13C)-isotopic fractionations of breath CO2 during glucose metabolism are poorly understood. Using the excretion dynamics of 18O/16O and 13C/12C-isotope ratios of breath CO2, we found that individuals with Helicobacter pylori infections exhibited significantly higher isotopic enrichments of 18O in breath CO2 during the 2h-glucose metabolism regardless of the isotopic nature of the substrate, while no significant enrichments of 18O in breath CO2 were manifested in individuals without the infections. In contrast, the 13C-isotopic enrichments of breath CO2 were significantly higher in individuals with Helicobacter pylori compared to individuals without infections in response to 13C-enriched glucose uptake, whereas a distinguishable change of breath 13C/12C-isotope ratios was also evident when Helicobacter pylori utilize natural glucose. Moreover, monitoring the 18O and 13C-isotopic exchange in breath CO2 successfully diagnosed the eradications of Helicobacter pylori infections following a standard therapy. Our findings suggest that breath 12C18O16O and 13C16O16O can be used as potential molecular biomarkers to distinctively track the pathogenesis of Helicobacter pylori and also for eradication purposes and thus may open new perspectives into the pathogen’s physiology along with isotope-specific non-invasive diagnosis of the infection. PMID:26039789

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

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

PubMed

Gold, Brian T

2015-03-15

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

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine

PubMed Central

Andreou, Anna P.; Holland, Philip R.; Akerman, Simon; Summ, Oliver; Fredrick, Joe

2016-01-01

Abstract A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. PMID:27246325

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

NASA Astrophysics Data System (ADS)

Neate, Andrew; Truman, Aubrey

2016-05-01

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

Toward link predictability of complex networks

PubMed Central

Lü, Linyuan; Pan, Liming; Zhou, Tao; Zhang, Yi-Cheng; Stanley, H. Eugene

2015-01-01

The organization of real networks usually embodies both regularities and irregularities, and, in principle, the former can be modeled. The extent to which the formation of a network can be explained coincides with our ability to predict missing links. To understand network organization, we should be able to estimate link predictability. We assume that the regularity of a network is reflected in the consistency of structural features before and after a random removal of a small set of links. Based on the perturbation of the adjacency matrix, we propose a universal structural consistency index that is free of prior knowledge of network organization. Extensive experiments on disparate real-world networks demonstrate that (i) structural consistency is a good estimation of link predictability and (ii) a derivative algorithm outperforms state-of-the-art link prediction methods in both accuracy and robustness. This analysis has further applications in evaluating link prediction algorithms and monitoring sudden changes in evolving network mechanisms. It will provide unique fundamental insights into the above-mentioned academic research fields, and will foster the development of advanced information filtering technologies of interest to information technology practitioners. PMID:25659742

High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

NASA Astrophysics Data System (ADS)

Salzberg, Brian M.

2008-03-01

Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

tDCS potentiation provides no evidence for a link between right dorsal-lateral prefrontal cortical activity and empathic responding.

PubMed

Snowdon, Marion E; Cathcart, Stuart

2018-04-01

Previous studies suggest the dorsolateral prefrontal cortex (DLPFC) is involved in processing of empathic concern. This has not been experimentally tested to date. We tested the hypotheses that electrical potentiation in the right DLPFC would be associated with increased empathic concern and prosocial behavior. Participants were randomly allocated to one of three transcranial Direct Current Stimulation (tDCS) conditions: (a) relative right potentiation, (b) relative left potentiation, and (c) sham. Participants viewed images of African children in distressing circumstances, and completed measures of empathic concern pre- and post-tDCS manipulation. Contrary to our prediction, neither effects, nor interactions of heightened empathic concern were observed. These results conflict with previous studies using this bilateral tDCS montage. Explanations could be that stimulation used in this study had been simply too weak (1.5 mA). Alternatively, the area of the DLPFC involved in emotion regulation is closer to the cortex than the area involved in empathic concern, and more easily potentiated by tDCS. Therefore, the DLPFC potentiation in the present study may have linked empathic concern with adaptive emotion regulation strategies. Future research could examine this possibility using measures of emotion regulation and higher fidelity neurostimulation (e.g., repetitive Transcranial Magnetic Stimulation [rTMS]).

Molecular dynamics simulations for mechanical properties of borophene: parameterization of valence force field model and Stillinger-Weber potential

PubMed Central

Zhou, Yu-Ping; Jiang, Jin-Wu

2017-01-01

While most existing theoretical studies on the borophene are based on first-principles calculations, the present work presents molecular dynamics simulations for the lattice dynamical and mechanical properties in borophene. The obtained mechanical quantities are in good agreement with previous first-principles calculations. The key ingredients for these molecular dynamics simulations are the two efficient empirical potentials developed in the present work for the interaction of borophene with low-energy triangular structure. The first one is the valence force field model, which is developed with the assistance of the phonon dispersion of borophene. The valence force field model is a linear potential, so it is rather efficient for the calculation of linear quantities in borophene. The second one is the Stillinger-Weber potential, whose parameters are derived based on the valence force field model. The Stillinger-Weber potential is applicable in molecular dynamics simulations of nonlinear physical or mechanical quantities in borophene. PMID:28349983

Cauchy flights in confining potentials

NASA Astrophysics Data System (ADS)

Garbaczewski, Piotr

2010-03-01

We analyze confining mechanisms for Lévy flights evolving under an influence of external potentials. Given a stationary probability density function (pdf), we address the reverse engineering problem: design a jump-type stochastic process whose target pdf (eventually asymptotic) equals the preselected one. To this end, dynamically distinct jump-type processes can be employed. We demonstrate that one “targeted stochasticity” scenario involves Langevin systems with a symmetric stable noise. Another derives from the Lévy-Schrödinger semigroup dynamics (closely linked with topologically induced super-diffusions), which has no standard Langevin representation. For computational and visualization purposes, the Cauchy driver is employed to exemplify our considerations.

X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms

PubMed Central

Molday, Robert S.; Kellner, Ulrich; Weber, Bernhard H.F.

2012-01-01

X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long term retinoschisin expression and rescue of retinal structure and function providing a ‘proof of concept’ that gene therapy may be an effective treatment for XLRS. PMID:22245536

Simulation Of Wave Function And Probability Density Of Modified Poschl Teller Potential Derived Using Supersymmetric Quantum Mechanics

NASA Astrophysics Data System (ADS)

Angraini, Lily Maysari; Suparmi, Variani, Viska Inda

2010-12-01

SUSY quantum mechanics can be applied to solve Schrodinger equation for high dimensional system that can be reduced into one dimensional system and represented in lowering and raising operators. Lowering and raising operators can be obtained using relationship between original Hamiltonian equation and the (super) potential equation. In this paper SUSY quantum mechanics is used as a method to obtain the wave function and the energy level of the Modified Poschl Teller potential. The graph of wave function equation and probability density is simulated by using Delphi 7.0 programming language. Finally, the expectation value of quantum mechanics operator could be calculated analytically using integral form or probability density graph resulted by the programming.

VTST/MT studies of the catalytic mechanism of C-H activation by transition metal complexes with [Cu2(μ-O2)], [Fe2(μ-O2)] and Fe(IV)-O cores based on DFT potential energy surfaces.

PubMed

Kim, Yongho; Mai, Binh Khanh; Park, Sumin

2017-04-01

High-valent Cu and Fe species, which are generated from dioxygen activation in metalloenzymes, carry out the functionalization of strong C-H bonds. Understanding the atomic details of the catalytic mechanism has long been one of the main objectives of bioinorganic chemistry. Large H/D kinetic isotope effects (KIEs) were observed in the C-H activation by high-valent non-heme Cu or Fe complexes in enzymes and their synthetic models. The H/D KIE depends significantly on the transition state properties, such as structure, energies, frequencies, and shape of the potential energy surface, when the tunneling effect is large. Therefore, theoretical predictions of kinetic parameters such as rate constants and KIEs can provide a reliable link between atomic-level quantum mechanical mechanisms and experiments. The accurate prediction of the tunneling effect is essential to reproduce the kinetic parameters. The rate constants and HD/KIE have been calculated using the variational transition-state theory including multidimensional tunneling based on DFT potential energy surfaces along the reaction coordinate. Excellent agreement was observed between the predicted and experimental results, which assures the validity of the DFT potential energy surfaces and, therefore, the proposed atomic-level mechanisms. The [Cu 2 (μ-O) 2 ], [Fe 2 (μ-O) 2 ], and Fe(IV)-oxo species were employed for C-H activation, and their role as catalysts was discussed at an atomic level.

Linking extreme interannual changes in prey availability to foraging behaviour and breeding investment in a marine predator, the macaroni penguin.

PubMed

Horswill, Cat; Trathan, Philip N; Ratcliffe, Norman

2017-01-01

Understanding the mechanisms that link prey availability to predator behaviour and population change is central to projecting how a species may respond to future environmental pressures. We documented the behavioural responses and breeding investment of macaroni penguins Eudyptes chrysolophus across five breeding seasons where local prey density changed by five-fold; from very low to highly abundant. When prey availability was low, foraging trips were significantly longer and extended overnight. Birds also foraged farther from the colony, potentially in order to reach more distant foraging grounds and allow for increased search times. These extended foraging trips were also linked to a marked decrease in fledgling weights, most likely associated with reduced rates of provisioning. Furthermore, by comparing our results with previous work on this population, it appears that lowered first-year survival rates associated, at least partially, with fledging masses were also evident for this cohort. This study integrates a unique set of prey density, predator behaviour and predator breeding investment data to highlight a possible behavioural mechanism linking perturbations in prey availability to population demography.

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

PubMed

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

2017-12-01

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

J-integral fracture toughness and tearing modulus measurement of radiation cross-linked UHMWPE.

PubMed

Gomoll, A; Wanich, T; Bellare, A

2002-11-01

Radiation and chemical cross-linking of medical grade ultrahigh molecular weight polyethylene (UHMWPE) has recently been utilized in an effort to improve wear performance of total joint replacement components. However, reductions in mechanical properties with cross-linking are cause for concern regarding the use of cross-linked UHMWPE for high-stress applications such as in total knee replacement prostheses. In this study, the fracture behavior of radiation cross-linked UHMWPE was compared to that of uncross-linked UHMWPE. The Rice and Sorensen model that utilizes mechanical parameters obtained from uniaxial tensile and compact tension tests was used to calculate the steady state J-integral fracture toughness, Jss, for radiation cross-linked UHMWPE. Jss decreased monotonically with increase in radiation dose. UHMWPE exhibited tough, ductile tearing behavior with stable crack growth when it was cross-linked using a gamma radiation dose of 0-50 kGy. However, in cross-linked UHMWPE irradiated to a dose of 100 and 200 kGy, unstable fracture occurred spontaneously upon attaining the initial crack driving force, J1c. This indicates that a high degree of cross-linking is less desirable for high-stress applications in orthopaedic implants. However, a substantial increase in J1c, even at a low degree of cross-linking, suggests that a low degree of cross-linking may be beneficial for resistance to delamination and catastrophic failure, both of which require an initiation step for the fracture to propagate in the material. This mechanical test should, however, be considered along with fatigue tests and joint simulator testing before determination of an appropriate amount of cross-linking for total joint replacement prostheses that experience high stresses.

The links between hypertrophy, reproductive potential and longevity in the Saccharomyces cerevisiae yeast.

PubMed

Molon, Mateusz; Zadrag-Tecza, Renata

2016-01-01

The yeast Saccharomyces cerevisiae has long been used as a model organism for studying the basic mechanisms of aging. However, the main problem with the use of this unicellular fungus is the unit of "longevity". For all organisms, lifespan is expressed in units of time, while in the case of yeast it is defined by the number of daughter cells produced. Additionally, in yeast the phenotypic effects of mutations often show a clear dependence on the genetic background, suggesting the need for an analysis of strains representing different genetic backgrounds. Our results confirm the data presented in earlier papers that the reproductive potential is strongly associated with an increase in cell volume per generation. An excessive cell volume results in the loss of reproductive capacity. These data clearly support the hypertrophy hypothesis. The time of life of all analysed mutants, with the exception of sch9D, is the same as in the case of the wild-type strain. Interestingly, the 121% increase of the fob1D mutant's reproductive potential compared to the sfp1D mutant does not result in prolongation of the mutant's time of life (total lifespan).

Di-isodityrosine is the intermolecular cross-link of isodityrosine-rich extensin analogs cross-linked in vitro.

PubMed

Held, Michael A; Tan, Li; Kamyab, Abdolreza; Hare, Michael; Shpak, Elena; Kieliszewski, Marcia J

2004-12-31

Extensins are cell wall hydroxyproline-rich glycoproteins that form covalent networks putatively involving tyrosyl and lysyl residues in cross-links catalyzed by one or more extensin peroxidases. The precise cross-links remain to be chemically identified both as network components in muro and as enzymic products generated in vitro with native extensin monomers as substrates. However, some extensin monomers contain variations within their putative cross-linking motifs that complicate cross-link identification. Other simpler extensins are recalcitrant to isolation including the ubiquitous P3-type extensin whose major repetitive motif, Hyp)(4)-Ser-Hyp-Ser-(Hyp)(4)-Tyr-Tyr-Tyr-Lys, is of particular interest, not least because its Tyr-Tyr-Tyr intramolecular isodityrosine cross-link motifs are also putative candidates for further intermolecular cross-linking to form di-isodityrosine. Therefore, we designed a set of extensin analogs encoding tandem repeats of the P3 motif, including Tyr --> Phe and Lys --> Leu variations. Expression of these P3 analogs in Nicotiana tabacum cells yielded glycoproteins with virtually all Pro residues hydroxylated and subsequently arabinosylated and with likely galactosylated Ser residues. This was consistent with earlier analyses of P3 glycopeptides isolated from cell wall digests and the predictions of the Hyp contiguity hypothesis. The tyrosine-rich P3 analogs also contained isodityrosine, formed in vivo. Significantly, these isodityrosine-containing analogs were further cross-linked in vitro by an extensin peroxidase to form the tetra-tyrosine intermolecular cross-link amino acid di-isodityrosine. This is the first identification of an inter-molecular cross-link amino acid in an extensin module and corroborates earlier suggestions that di-isodityrosine represents one mechanism for cross-linking extensins in muro.

Bee venom therapy: Potential mechanisms and therapeutic applications.

PubMed

Zhang, Shuai; Liu, Yi; Ye, Yang; Wang, Xue-Rui; Lin, Li-Ting; Xiao, Ling-Yong; Zhou, Ping; Shi, Guang-Xia; Liu, Cun-Zhi

2018-06-15

Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

New potentials for conformal mechanics

NASA Astrophysics Data System (ADS)

Papadopoulos, G.

2013-04-01

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

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

PubMed Central

Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

2012-01-01

Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ9-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca2+) increase, etc.), on CBD behavioural effects. PMID:23108553

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

PubMed

Hasselmo, Michael E

2005-01-01

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

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

PubMed Central

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

2016-01-01

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

Do glucocorticoids mediate the link between environmental conditions and telomere dynamics in wild vertebrates? A review.

PubMed

Angelier, Frédéric; Costantini, David; Blévin, Pierre; Chastel, Olivier

2018-01-15

Following the discoveries of telomeres and of their implications in terms of health and ageing, there has been a growing interest into the study of telomere dynamics in wild vertebrates. Telomeres are repeated sequences of non-coding DNA located at the terminal ends of chromosomes and they play a major role in maintaining chromosome stability. Importantly, telomeres shorten over time and shorter telomeres seem to be related with lower survival in vertebrates. Because of this potential link with longevity, it is crucial to understand not only the ecological determinants of telomere dynamics but also the regulatory endocrine mechanisms that may mediate the effect of the environment on telomeres. In this paper, we review the relationships that link environmental conditions, glucocorticoids (GC, the main hormonal mediator of allostasis) and telomere length in vertebrates. First, we review current knowledge about the determinants of inter-individual variations in telomere length. We emphasize the potential strong impact of environmental stressors and predictable life-history events on telomere dynamics. Despite recent progress, we still lack crucial basic data to fully understand the costs of several life-history stages and biotic and abiotic factors on telomere length. Second, we review the link that exists between GCs, oxidative stress and telomere dynamics in vertebrates. Although circulating GC levels may be closely and functionally linked with telomere dynamics, data are still scarce and somewhat contradictory. Further laboratory and field studies are therefore needed not only to better assess the proximate link between GC levels and telomere dynamics, but also to ultimately understand to what extent GCs and telomere length could be informative to measure the fitness costs of specific life-history stages and environmental conditions. Finally, we highlight the importance of exploring the functional links that may exist between coping styles, the GC stress response

Preparation of Nanocellulose Reinforced Chitosan Films, Cross-Linked by Adipic Acid

PubMed Central

Falamarzpour, Pouria; Behzad, Tayebeh; Zamani, Akram

2017-01-01

Adipic acid, an abundant and nontoxic compound, was used to dissolve and cross-link chitosan. After the preparation of chitosan films through casting technique, the in situ amidation reaction was performed at 80–100 °C as verified by Fourier transform infrared (FT-IR). The reaction was accompanied by the release of water which was employed to investigate the reaction kinetics. Accordingly, the reaction rate followed the first-order model and Arrhenius equation, and the activation energy was calculated to be 18 kJ/mol. Furthermore, the mechanical properties of the chitosan films were comprehensively studied. First, optimal curing conditions (84 °C, 93 min) were introduced through a central composite design. In order to evaluate the effects of adipic acid, the mechanical properties of physically cross-linked (uncured), chemically cross-linked (cured), and uncross-linked (prepared by acetic acid) films were compared. The use of adipic acid improved the tensile strength of uncured and chemically cross-linked films more than 60% and 113%, respectively. Finally, the effect of cellulose nanofibrils (CNFs) on the mechanical performance of cured films, in the presence of glycerol as a plasticizer, was investigated. The plasticized chitosan films reinforced by 5 wt % CNFs showed superior properties as a promising material for the development of chitosan-based biomaterials. PMID:28208822

Preparation of Nanocellulose Reinforced Chitosan Films, Cross-Linked by Adipic Acid.

PubMed

Falamarzpour, Pouria; Behzad, Tayebeh; Zamani, Akram

2017-02-13

Adipic acid, an abundant and nontoxic compound, was used to dissolve and cross-link chitosan. After the preparation of chitosan films through casting technique, the in situ amidation reaction was performed at 80-100 °C as verified by Fourier transform infrared (FT-IR). The reaction was accompanied by the release of water which was employed to investigate the reaction kinetics. Accordingly, the reaction rate followed the first-order model and Arrhenius equation, and the activation energy was calculated to be 18 kJ/mol. Furthermore, the mechanical properties of the chitosan films were comprehensively studied. First, optimal curing conditions (84 °C, 93 min) were introduced through a central composite design. In order to evaluate the effects of adipic acid, the mechanical properties of physically cross-linked (uncured), chemically cross-linked (cured), and uncross-linked (prepared by acetic acid) films were compared. The use of adipic acid improved the tensile strength of uncured and chemically cross-linked films more than 60% and 113%, respectively. Finally, the effect of cellulose nanofibrils (CNFs) on the mechanical performance of cured films, in the presence of glycerol as a plasticizer, was investigated. The plasticized chitosan films reinforced by 5 wt % CNFs showed superior properties as a promising material for the development of chitosan-based biomaterials.

Aging Mechanisms and Nondestructive Aging Indicator of Filled Cross-linked Polyethylene (XLPE) Exposed to Simultaneous Thermal and Gamma Radiation

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

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

Aging mechanisms and a nondestructive aging indicator of filled cross-linked polyethylene (XLPE) cable insulation material used in nuclear power plants (NPPs) are studied. Using various material characterization techniques, likely candidates and functions for the main additives in a commercial filled-XLPE insulation material have been identified. These include decabromodiphenyl ether and Sb2O3 as flame retardants, ZnS as white pigment and polymerized 1,2-dihydro-2,2,4-trimethylquinoline as antioxidant. Gas chromatography-mass spectrometry, differential scanning calorimetry, oxidation induction time and measurements of dielectric loss tangent are utilized to monitor property changes as a function of thermal and radiation exposure of the cable material. Small-molecular-weight hydrocarbons are evolvemore » with gamma radiation aging at 90 °C. The level of antioxidant decreases with aging by volatilization and chemical reaction with free radicals. Thermal aging at 90 °C for 25 days or less causes no observable change to the cross-linked polymer structure. Gamma radiation causes damage to crystalline polymer regions and introduces defects. Dielectric loss tangent is shown to be an effective and reliable nondestructive indicator of the aging severity of the filled-XLPE insulation material.« less

Weak reversible cross links may decrease the strength of aligned fiber bundles.

PubMed

Nabavi, S Soran; Hartmann, Markus A

2016-02-21

Reversible cross-linking is an effective strategy to specifically tailor the mechanical properties of polymeric materials that can be found in a variety of biological as well as man-made materials. Using a simple model in this paper the influence of weak, reversible cross-links on the mechanical properties of aligned fiber bundles is investigated. Special emphasis in this analysis is put on the strength of the investigated structures. Using Monte Carlo methods two topologies of cross-links exceeding the strength of the covalent backbone are studied. Most surprisingly only two cross-links are sufficient to break the backbone of a multi chain system, resulting in a reduced strength of the material. The found effect crucially depends on the ratio of inter- to intra-chain cross-links and, thus, on the grafting density that determines this ratio.

Piezo1 links mechanical forces to red blood cell volume.

PubMed

Cahalan, Stuart M; Lukacs, Viktor; Ranade, Sanjeev S; Chien, Shu; Bandell, Michael; Patapoutian, Ardem

2015-05-22

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.

The Affective Core of Emotion: Linking Pleasure, Subjective Well-Being, and Optimal Metastability in the Brain

PubMed Central

Kringelbach, Morten L.; Berridge, Kent C.

2017-01-01

Arguably, emotion is always valenced—either pleasant or unpleasant—and dependent on the pleasure system. This system serves adaptive evolutionary functions; relying on separable wanting, liking, and learning neural mechanisms mediated by mesocorticolimbic networks driving pleasure cycles with appetitive, consummatory, and satiation phases. Liking is generated in a small set of discrete hedonic hotspots and coldspots, while wanting is linked to dopamine and to larger distributed brain networks. Breakdown of the pleasure system can lead to anhedonia and other features of affective disorders. Eudaimonia and well-being are difficult to study empirically, yet whole-brain computational models could offer novel insights (e.g., routes to eudaimonia such as caregiving of infants or music) potentially linking eudaimonia to optimal metastability in the pleasure system. PMID:28943891

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

X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms.

PubMed

Molday, Robert S; Kellner, Ulrich; Weber, Bernhard H F

2012-05-01

X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long-term retinoschisin expression and rescue of retinal structure and function providing a 'proof of concept' that gene therapy may be an effective treatment for XLRS. Copyright © 2012 Elsevier Ltd. All rights reserved.

POTENTIAL MECHANISMS RESPONSIBLE FOR CHLOROTRIAZINE-INDUCED ALTERATIONS IN CATECHOLAMINES IN PHEOCHROMOCYTOMA (PC12) CELLS

EPA Science Inventory

ABSTRACT

Potential Mechanisms Responsible for Chlorotriazine-induced Changes in Catecholamine Metabolism in Pheochromocytoma (PC12) Cells*
PARIKSHIT C. DAS1, WILLIAM K. McELROY2 , AND RALPH L. COOPER2+
1Curriculum in Toxicology, University of North Carolina, Chape...

Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance.

PubMed

Méndez-Balbuena, Ignacio; Huidobro, Nayeli; Silva, Mayte; Flores, Amira; Trenado, Carlos; Quintanar, Luis; Arias-Carrión, Oscar; Kristeva, Rumyana; Manjarrez, Elias

2015-10-01

The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP. Copyright © 2015 the American Physiological Society.

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.

Imaging Mitochondrial Redox Potential and Its Possible Link to Tumor Metastatic Potential

PubMed Central

Li, Lin Z.

2012-01-01

Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. Growing body of literature suggest importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinically-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research. PMID:22895837

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine.

PubMed

Andreou, Anna P; Holland, Philip R; Akerman, Simon; Summ, Oliver; Fredrick, Joe; Goadsby, Peter J

2016-07-01

A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Mechanical behavior of cells in microinjection: a minimum potential energy study.

PubMed

Liu, Fei; Wu, Dan; Chen, Ken

2013-08-01

Microinjection is a widely used technique to deliver foreign materials into biological cells. We propose a mathematical model to study the mechanical behavior of a cell in microinjection. Firstly, a cell is modeled by a hyperelastic membrane and interior cytoplasm. Then, based on the fact that the equilibrium configuration of a cell would minimize the potential energy, the energy function during microinjection is analyzed. With Lagrange multiplier and Rayleigh-Ritz technique, we successfully minimize the potential energy and obtain the equilibrium configuration. Upon this model, the injection force, the injection distance, the radius of the microinjector and the membrane stress are studied. The analysis demonstrates that the microinjector radius has a significant influence on the cell mechanical behavior: (1) the larger radius generates larger injection force and larger interior pressure at the same injection distance; (2) the radius determines the place where the membrane is most likely to rupture by governing the membrane stress distribution. For a fine microinjector with radius less than 20% of the cell radius, the most likely rupture point located at the edge of the contact area between the microinjector and the membrane; however, it may move to the middle of the equilibrium configuration as the radius increases. To verify our model, some experiments were conducted on zebrafish egg cells. The results show that the computational analysis agrees with the experimental data, which supports the findings from the theoretical model. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

The link between bond forfeiture and pretrial release mechanism: The case of Dallas County, Texas

PubMed Central

Morris, Robert G.; Russell-Kaplan, Amanda

2017-01-01

Purpose The goal of this study was to evaluate the efficacy of four pretrial jail release mechanisms (i.e., bond types) commonly used during the pretrial phase of the criminal justice process in terms of their ability to discriminate between defendants failing to appear in court (i.e., bond forfeiture). These include attorney bonds, cash bonds, commercial bail bonds, and release via a pretrial services agency. Methods A multi-treatment propensity score matching protocol was employed to assess between-release-mechanism differences in the conditional probability of failure to appear/bond forfeiture. Data were culled from archival state justice records comprising all defendants booked into the Dallas County, Texas jail during 2008 (n = 29,416). Results The results suggest that defendants released via commercial bail bonds were less likely to experience failure to appear leading to the bond forfeiture process compared to equivalent defendants released via cash, attorney, and pretrial services bonds. This finding held across different offense categories. The study frames these differences within a discussion encompassing procedural variation within and between each release mechanism, thereby setting the stage for further research and dialog regarding potential justice reform. PMID:28817579

Piezo1 links mechanical forces to red blood cell volume

PubMed Central

Cahalan, Stuart M; Lukacs, Viktor; Ranade, Sanjeev S; Chien, Shu; Bandell, Michael; Patapoutian, Ardem

2015-01-01

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis. DOI: http://dx.doi.org/10.7554/eLife.07370.001 PMID:26001274

Reliable and Persistent Identification of Linked Data Elements

NASA Astrophysics Data System (ADS)

Wood, David

Linked Data techniques rely upon common terminology in a manner similar to a relational database'vs reliance on a schema. Linked Data terminology anchors metadata descriptions and facilitates navigation of information. Common vocabularies ease the human, social tasks of understanding datasets sufficiently to construct queries and help to relate otherwise disparate datasets. Vocabulary terms must, when using the Resource Description Framework, be grounded in URIs. A current bestpractice on the World Wide Web is to serve vocabulary terms as Uniform Resource Locators (URLs) and present both human-readable and machine-readable representations to the public. Linked Data terminology published to theWorldWideWeb may be used by others without reference or notification to the publishing party. That presents a problem: Vocabulary publishers take on an implicit responsibility to maintain and publish their terms via the URLs originally assigned, regardless of the inconvenience such a responsibility may cause. Over the course of years, people change jobs, publishing organizations change Internet domain names, computers change IP addresses,systems administrators publish old material in new ways. Clearly, a mechanism is required to manageWeb-based vocabularies over a long term. This chapter places Linked Data vocabularies in context with the wider concepts of metadata in general and specifically metadata on the Web. Persistent identifier mechanisms are reviewed, with a particular emphasis on Persistent URLs, or PURLs. PURLs and PURL services are discussed in the context of Linked Data. Finally, historic weaknesses of PURLs are resolved by the introduction of a federation of PURL services to address needs specific to Linked Data.

Optical Phase Measurements of Disorder Strength Link Microstructure to Cell Stiffness.

PubMed

Eldridge, Will J; Steelman, Zachary A; Loomis, Brianna; Wax, Adam

2017-02-28

There have been sustained efforts on the part of cell biologists to understand the mechanisms by which cells respond to mechanical stimuli. To this end, many rheological tools have been developed to characterize cellular stiffness. However, measurement of cellular viscoelastic properties has been limited in scope by the nature of most microrheological methods, which require direct mechanical contact, applied at the single-cell level. In this article, we describe, to our knowledge, a new analysis approach for quantitative phase imaging that relates refractive index variance to disorder strength, a parameter that is linked to cell stiffness. Significantly, both disorder strength and cell stiffness are measured with the same phase imaging system, presenting a unique alternative for label-free, noncontact, single-shot imaging of cellular rheologic properties. To demonstrate the potential applicability of the technique, we measure phase disorder strength and shear stiffness across five cellular populations with varying mechanical properties and demonstrate an inverse relationship between these two parameters. The existence of this relationship suggests that predictions of cell mechanical properties can be obtained from examining the disorder strength of cell structure using this, to our knowledge, novel, noncontact technique. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.

PubMed

Marigorta, Urko M; Denson, Lee A; Hyams, Jeffrey S; Mondal, Kajari; Prince, Jarod; Walters, Thomas D; Griffiths, Anne; Noe, Joshua D; Crandall, Wallace V; Rosh, Joel R; Mack, David R; Kellermayer, Richard; Heyman, Melvin B; Baker, Susan S; Stephens, Michael C; Baldassano, Robert N; Markowitz, James F; Kim, Mi-Ok; Dubinsky, Marla C; Cho, Judy; Aronow, Bruce J; Kugathasan, Subra; Gibson, Greg

2017-10-01

Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus protection, thereby linking statistical association to biological mechanism. The TRS approach constitutes a potential strategy for personalized medicine that enhances inference from static genotypic risk assessment.

Classifying quantum entanglement through topological links

NASA Astrophysics Data System (ADS)

Quinta, Gonçalo M.; André, Rui

2018-04-01

We propose an alternative classification scheme for quantum entanglement based on topological links. This is done by identifying a nonrigid ring to a particle, attributing the act of cutting and removing a ring to the operation of tracing out the particle, and associating linked rings to entangled particles. This analogy naturally leads us to a classification of multipartite quantum entanglement based on all possible distinct links for a given number of rings. To determine all different possibilities, we develop a formalism that associates any link to a polynomial, with each polynomial thereby defining a distinct equivalence class. To demonstrate the use of this classification scheme, we choose qubit quantum states as our example of physical system. A possible procedure to obtain qubit states from the polynomials is also introduced, providing an example state for each link class. We apply the formalism for the quantum systems of three and four qubits and demonstrate the potential of these tools in a context of qubit networks.

Pathways from Religion to Health: Mediation by Psychosocial and Lifestyle Mechanisms

PubMed Central

Morton, Kelly R.; Lee, Jerry W.; Martin, Leslie R.

2016-01-01

Religiosity, often measured as attendance at religious services, is linked to better physical health and longevity though the mechanisms linking the two are debated. Potential explanations include: a healthier lifestyle, increased social support from congregational members, and/or more positive emotions. Thus far, these mechanisms have not been tested simultaneously in a single model though they likely operate synergistically. We test this model predicting all-cause mortality in Seventh-day Adventists, a denomination that explicitly promotes a healthy lifestyle. This allows the more explicit health behaviors linked to the religious doctrine (e.g., healthy diet) to be compared with other mechanisms not specific to religious doctrine (e.g., social support and positive emotions). Finally, this study examines both Church Activity (including worship attendance and church responsibilities) and Religious Engagement (coping, importance, and intrinsic beliefs). Religious Engagement is more is more inner-process focused (vs. activity-based) and less likely to be confounded with age and its associated functional status limitations, although it should be noted that age is controlled in the present study. The findings suggest that Religious Engagement and Church Activity operate through the mediators of health behavior, emotion, and social support to decrease mortality risk. All links between Religious Engagement and mortality are positive but indirect through positive Religious Support, Emotionality, and lifestyle mediators. However, Church Activity has a direct positive effect on mortality as well as indirect effects through, Religious Support, Emotionality, and lifestyle mediators (diet and exercise). The models were invariant by gender and for both Blacks and Whites. PMID:28435513

Pathways from Religion to Health: Mediation by Psychosocial and Lifestyle Mechanisms.

PubMed

Morton, Kelly R; Lee, Jerry W; Martin, Leslie R

2017-02-01

Religiosity, often measured as attendance at religious services, is linked to better physical health and longevity though the mechanisms linking the two are debated. Potential explanations include: a healthier lifestyle, increased social support from congregational members, and/or more positive emotions. Thus far, these mechanisms have not been tested simultaneously in a single model though they likely operate synergistically. We test this model predicting all-cause mortality in Seventh-day Adventists, a denomination that explicitly promotes a healthy lifestyle. This allows the more explicit health behaviors linked to the religious doctrine (e.g., healthy diet) to be compared with other mechanisms not specific to religious doctrine (e.g., social support and positive emotions). Finally, this study examines both Church Activity (including worship attendance and church responsibilities) and Religious Engagement (coping, importance, and intrinsic beliefs). Religious Engagement is more is more inner-process focused (vs. activity-based) and less likely to be confounded with age and its associated functional status limitations, although it should be noted that age is controlled in the present study. The findings suggest that Religious Engagement and Church Activity operate through the mediators of health behavior, emotion, and social support to decrease mortality risk. All links between Religious Engagement and mortality are positive but indirect through positive Religious Support, Emotionality, and lifestyle mediators. However, Church Activity has a direct positive effect on mortality as well as indirect effects through, Religious Support, Emotionality, and lifestyle mediators (diet and exercise). The models were invariant by gender and for both Blacks and Whites.

Cytotoxic T cells use mechanical force to potentiate target cell killing

PubMed Central

Basu, Roshni; Whitlock, Benjamin M.; Husson, Julien; Le Floc’h, Audrey; Jin, Weiyang; Oyler-Yaniv, Alon; Dotiwala, Farokh; Giannone, Gregory; Hivroz, Claire; Biais, Nicolas; Lieberman, Judy; Kam, Lance C.; Huse, Morgan

2016-01-01

SUMMARY The immunological synapse formed between a cytotoxic T lymphocyte (CTL) and an infected or transformed target cell is a physically active structure capable of exerting mechanical force. Here, we investigated whether synaptic forces promote the destruction of target cells. CTLs kill by secreting toxic proteases and the pore forming protein perforin into the synapse. Biophysical experiments revealed a striking correlation between the magnitude of force exertion across the synapse and the speed of perforin pore formation on the target cell, implying that force potentiates cytotoxicity by enhancing perforin activity. Consistent with this interpretation, we found that increasing target cell tension augmented pore formation by perforin and killing by CTLs. Our data also indicate that CTLs coordinate perforin release and force exertion in space and time. These results reveal an unappreciated physical dimension to lymphocyte function and demonstrate that cells use mechanical forces to control the activity of outgoing chemical signals. PMID:26924577

Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing.

PubMed

Basu, Roshni; Whitlock, Benjamin M; Husson, Julien; Le Floc'h, Audrey; Jin, Weiyang; Oyler-Yaniv, Alon; Dotiwala, Farokh; Giannone, Gregory; Hivroz, Claire; Biais, Nicolas; Lieberman, Judy; Kam, Lance C; Huse, Morgan

2016-03-24

The immunological synapse formed between a cytotoxic T lymphocyte (CTL) and an infected or transformed target cell is a physically active structure capable of exerting mechanical force. Here, we investigated whether synaptic forces promote the destruction of target cells. CTLs kill by secreting toxic proteases and the pore forming protein perforin into the synapse. Biophysical experiments revealed a striking correlation between the magnitude of force exertion across the synapse and the speed of perforin pore formation on the target cell, implying that force potentiates cytotoxicity by enhancing perforin activity. Consistent with this interpretation, we found that increasing target cell tension augmented pore formation by perforin and killing by CTLs. Our data also indicate that CTLs coordinate perforin release and force exertion in space and time. These results reveal an unappreciated physical dimension to lymphocyte function and demonstrate that cells use mechanical forces to control the activity of outgoing chemical signals. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits

PubMed Central

Machha, Ajay

2012-01-01

Purpose In the last decade, a growing scientific and medical interest has emerged toward cardiovascular effects of dietary nitrite and nitrate; however, many questions concerning their mode of action(s) remain unanswered. In this review, we focus on multiple mechanisms that might account for potential cardiovascular beneficial effects of dietary nitrite and nitrate. Results Beneficial changes to cardiovascular health from dietary nitrite and nitrate might result from several mechanism(s) including their reduction into nitric oxide, improvement in endothelial function, vascular relaxation, and/or inhibition of the platelet aggregation. From recently obtained evidence, it appears that the longstanding concerns about the toxicity of oral nitrite or nitrate are overstated. Conclusion Dietary nitrite and nitrate may have cardiovascular protective effects in both healthy individuals and also those with cardiovascular disease conditions. A role for nitrite and nitrate in nitric oxide biosynthesis and/or in improving nitric oxide bioavailability may eventually provide a rationale for using dietary nitrite and nitrate supplementation in the treatment and prevention of cardiovascular diseases. PMID:21626413

Probing cellular mechanics with Acoustic Force Spectroscopy.

PubMed

Sorkin, Raya; Bergamaschi, Giulia; Kamsma, Douwe; Brand, Guy; Dekel, Elya; Ofir-Birin, Yifat; Rudik, Ariel; Gironella, Marta; Ritort, Felix; Regev-Rudzki, Neta; Roos, Wouter; Wuite, Gijs J L

2018-06-21

A large number of studies demonstrate that cell mechanics and pathology are intimately linked. In particular, Red Blood Cell (RBC) deformability is key to their function, and is dramatically altered in the time course of diseases such as anemia and malaria. Due to the physiological importance of cell mechanics, many methods for cell mechanical probing have been developed. While single cell methods provide very valuable information, they are often technically challenging and lack high data throughput needed to distinguish differences in heterogeneous populations, while fluid flow high throughput methods miss the accuracy to detect subtle differences. Here, we present a new method for multiplexed single-cell mechanical probing using Acoustic Force Spectroscopy (AFS). We demonstrate that mechanical differences induced by chemical treatments of known effect can be measured and quantified. Furthermore, we explore the effect of extracellular-vesicles (EVs) uptake on RBC mechanics and demonstrate that EVs uptake increases RBC deformability. Our findings demonstrate the ability of AFS to manipulate cells with high stability and precision, and pave the way to further new insights into cellular mechanics and mechanobiology in health and disease, as well as potential biomedical applications.

Reprocessing and Recycling of Highly Cross-Linked Ion-Conducting Networks through Transalkylation Exchanges of C-N Bonds.

PubMed

Obadia, Mona M; Mudraboyina, Bhanu P; Serghei, Anatoli; Montarnal, Damien; Drockenmuller, Eric

2015-05-13

Exploiting exchangeable covalent bonds as dynamic cross-links recently afforded a new class of polymer materials coined as vitrimers. These permanent networks are insoluble and infusible, but the network topology can be reshuffled at high temperatures, thus enabling glasslike plastic deformation and reprocessing without depolymerization. We disclose herein the development of functional and high-value ion-conducting vitrimers that take inspiration from poly(ionic liquid)s. Tunable networks with high ionic content are obtained by the solvent- and catalyst-free polyaddition of an α-azide-ω-alkyne monomer and simultaneous alkylation of the resulting poly(1,2,3-triazole)s with a series of difunctional cross-linking agents. Temperature-induced transalkylation exchanges of C-N bonds between 1,2,3-triazolium cross-links and halide-functionalized dangling chains enable recycling and reprocessing of these highly cross-linked permanent networks. They can also be recycled by depolymerization with specific solvents able to displace the transalkylation equilibrium, and they display a great potential for applications that require solid electrolytes with excellent mechanical performances and facile processing such as supercapacitors, batteries, fuel cells, and separation membranes.

Classifying compound mechanism of action for linking whole cell phenotypes to molecular targets

PubMed Central

Bourne, Christina R.; Wakeham, Nancy; Bunce, Richard A.; Berlin, K. Darrell; Barrow, William W.

2013-01-01

Drug development programs have proven successful when performed at a whole cell level, thus incorporating solubility and permeability into the primary screen. However, linking those results to the target within the cell has been a major set-back. The Phenotype Microarray system, marketed and sold by Biolog, seeks to address this need by assessing the phenotype in combination with a variety of chemicals with known mechanism of action (MOA). We have evaluated this system for usefulness in deducing the MOA for three test compounds. To achieve this, we constructed a database with 21 known antimicrobials, which served as a comparison for grouping our unknown MOA compounds. Pearson correlation and Ward linkage calculations were used to generate a dendrogram that produced clustering largely by known MOA, although there were exceptions. Of the three unknown compounds, one was definitively placed as an anti-folate. The second and third compounds’ MOA were not clearly identified, likely due to unique MOA not represented within the commercial database. The availability of the database generated in this report for S. aureus ATCC 29213 will increase the accessibility of this technique to other investigators. From our analysis, the Phenotype Microarray system can group compounds with clear MOA, but distinction of unique or broadly acting MOA at this time is less clear. PMID:22434711

Cross-linking Chemistry of Squid Beak*

PubMed Central

Miserez, Ali; Rubin, Daniel; Waite, J. Herbert

2010-01-01

In stark contrast to most aggressive predators, Dosidicus gigas (jumbo squids) do not use minerals in their powerful mouthparts known as beaks. Their beaks instead consist of a highly sclerotized chitinous composite with incremental hydration from the tip to the base. We previously reported l-3,4-dihydroxyphenylalanine (dopa)-histidine (dopa-His) as an important covalent cross-link providing mechanical strengthening to the beak material. Here, we present a more complete characterization of the sclerotization chemistry and describe additional cross-links from D. gigas beak. All cross-links presented in this report share common building blocks, a family of di-, tri-, and tetra-histidine-catecholic adducts, that were separated by affinity chromatography and high performance liquid chromatography (HPLC) and identified by tandem mass spectroscopy and proton nuclear magnetic resonance (1H NMR). The data provide additional insights into the unusually high cross-link density found in mature beaks. Furthermore, we propose both a low molecular weight catechol, and peptidyl-dopa, to be sclerotization agents of squid beak. This appears to represent a new strategy for forming hard tissue in animals. The interplay between covalent cross-linking and dehydration on the graded properties of the beaks is discussed. PMID:20870720

Cross-linking chemistry of squid beak.

PubMed

Miserez, Ali; Rubin, Daniel; Waite, J Herbert

2010-12-03

In stark contrast to most aggressive predators, Dosidicus gigas (jumbo squids) do not use minerals in their powerful mouthparts known as beaks. Their beaks instead consist of a highly sclerotized chitinous composite with incremental hydration from the tip to the base. We previously reported l-3,4-dihydroxyphenylalanine (dopa)-histidine (dopa-His) as an important covalent cross-link providing mechanical strengthening to the beak material. Here, we present a more complete characterization of the sclerotization chemistry and describe additional cross-links from D. gigas beak. All cross-links presented in this report share common building blocks, a family of di-, tri-, and tetra-histidine-catecholic adducts, that were separated by affinity chromatography and high performance liquid chromatography (HPLC) and identified by tandem mass spectroscopy and proton nuclear magnetic resonance ((1)H NMR). The data provide additional insights into the unusually high cross-link density found in mature beaks. Furthermore, we propose both a low molecular weight catechol, and peptidyl-dopa, to be sclerotization agents of squid beak. This appears to represent a new strategy for forming hard tissue in animals. The interplay between covalent cross-linking and dehydration on the graded properties of the beaks is discussed.

Seismic link at plate boundary

NASA Astrophysics Data System (ADS)

Ramdani, Faical; Kettani, Omar; Tadili, Benaissa

2015-06-01

Seismic triggering at plate boundaries has a very complex nature that includes seismic events at varying distances. The spatial orientation of triggering cannot be reduced to sequences from the main shocks. Seismic waves propagate at all times in all directions, particularly in highly active zones. No direct evidence can be obtained regarding which earthquakes trigger the shocks. The first approach is to determine the potential linked zones where triggering may occur. The second step is to determine the causality between the events and their triggered shocks. The spatial orientation of the links between events is established from pre-ordered networks and the adapted dependence of the spatio-temporal occurrence of earthquakes. Based on a coefficient of synchronous seismic activity to grid couples, we derive a network link by each threshold. The links of high thresholds are tested using the coherence of time series to determine the causality and related orientation. The resulting link orientations at the plate boundary conditions indicate that causal triggering seems to be localized along a major fault, as a stress transfer between two major faults, and parallel to the geothermal area extension.

Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA).

PubMed

Roth, Christian L; Sathyanarayana, Sheela

2012-06-01

Signaling peptides produced in peripheral tissues such as gut, adipose tissue, and pancreas communicate with brain centers, such as hypothalamus and hindbrain to manage energy homeostasis. These regulatory mechanisms of energy intake and storage have evolved during long periods of hunger in the evolution of man to protect the species from extinction. It is now clear that these circuitries are influenced by prenatal and postnatal environmental factors including endocrine disruptive chemicals. Hypothalamic appetite regulatory systems develop and mature in utero and early infancy, and involve signaling pathways that are important also for the regulation of puberty onset. Recent studies in humans and animals have shown that metabolic pathways involved in regulation of growth, body weight gain and sexual maturation are largely affected by epigenetic programming that can impact both current and future generations. In particular, intrauterine and early infantile developmental phases of high plasticity are susceptible to factors that affect metabolic programming that therefore, affect metabolic function throughout life. In children born small for gestational age, poor nutritional conditions during gestation can modify metabolic systems to adapt to expectations of chronic undernutrition. These children are potentially poorly equipped to cope with energy-dense diets and are possibly programmed to store as much energy as possible, leading to later obesity, metabolic syndrome, disturbed regulation of normal puberty and early onset of cardiovascular disease. Most cases of disturbed energy balance are likely a result of a combination of genetics, epigenetics and environment. This review will discuss potential mechanisms linking intrauterine growth retardation with changes in growth, energy homeostasis and sexual maturation.

Development of safe mechanism for surgical robots using equilibrium point control method.

PubMed

Park, Shinsuk; Lim, Hokjin; Kim, Byeong-sang; Song, Jae-bok

2006-01-01

This paper introduces a novel mechanism for surgical robotic systems to generate human arm-like compliant motion. The mechanism is based on the idea of the equilibrium point control hypothesis which claims that multi-joint limb movements are achieved by shifting the limbs' equilibrium positions defined by neuromuscular activity. The equilibrium point control can be implemented on a robot manipulator by installing two actuators at each joint of the manipulator, one to control the joint position, and the other to control the joint stiffness. This double-actuator mechanism allows us to arbitrarily manipulate the stiffness (or impedance) of a robotic manipulator as well as its position. Also, the force at the end-effector can be estimated based on joint stiffness and joint angle changes without using force transducers. A two-link manipulator and a three-link manipulator with the double-actuator units have been developed, and experiments and simulation results show the potential of the proposed approach. By creating the human arm-like behavior, this mechanism can improve the performance of robot manipulators to execute stable and safe movement in surgical environments by using a simple control scheme.

Quantum mechanics on phase space and the Coulomb potential

NASA Astrophysics Data System (ADS)

Campos, P.; Martins, M. G. R.; Vianna, J. D. M.

2017-04-01

Symplectic quantum mechanics (SMQ) makes possible to derive the Wigner function without the use of the Liouville-von Neumann equation. In this formulation of the quantum theory the Galilei Lie algebra is constructed using the Weyl (or star) product with Q ˆ = q ⋆ = q +iħ/2∂p , P ˆ = p ⋆ = p -iħ/2∂q, and the Schrödinger equation is rewritten in phase space; in consequence physical applications involving the Coulomb potential present some specific difficulties. Within this context, in order to treat the Schrödinger equation in phase space, a procedure based on the Levi-Civita (or Bohlin) transformation is presented and applied to two-dimensional (2D) hydrogen atom. Amplitudes of probability in phase space and the correspondent Wigner quasi-distribution functions are derived and discussed.

Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.

PubMed

Richards, John R; Lapoint, Jeff M; Burillo-Putze, Guillermo

2018-01-01

Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits

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

PubMed Central

Gold, Brian T.

2014-01-01

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

Src-JNK Potentiation of Estrogen Receptor AF-1; Mechanism, and Role in Estrogen Action in Breast Cancer

DTIC Science & Technology

2002-08-01

an increase in estrogen receptor activity. A second objective is to understand the potential role of Src in estrogen induced mammary ductal development ...bPcis i on to The Ser-ilS-dependent link wt GR- t KaroBio AB, a Swedish pharmaceutical development company with CBP is in addition to the Ser-1l8...the ECL detection kit (Amersham Pharmacia Biotech ). phoresis, stained with Coomassic Blue to monitor expression, and sub- Fluorescence Microscopy

Eye coding mechanisms in early human face event-related potentials.

PubMed

Rousselet, Guillaume A; Ince, Robin A A; van Rijsbergen, Nicola J; Schyns, Philippe G

2014-11-10

In humans, the N170 event-related potential (ERP) is an integrated measure of cortical activity that varies in amplitude and latency across trials. Researchers often conjecture that N170 variations reflect cortical mechanisms of stimulus coding for recognition. Here, to settle the conjecture and understand cortical information processing mechanisms, we unraveled the coding function of N170 latency and amplitude variations in possibly the simplest socially important natural visual task: face detection. On each experimental trial, 16 observers saw face and noise pictures sparsely sampled with small Gaussian apertures. Reverse-correlation methods coupled with information theory revealed that the presence of the eye specifically covaries with behavioral and neural measurements: the left eye strongly modulates reaction times and lateral electrodes represent mainly the presence of the contralateral eye during the rising part of the N170, with maximum sensitivity before the N170 peak. Furthermore, single-trial N170 latencies code more about the presence of the contralateral eye than N170 amplitudes and early latencies are associated with faster reaction times. The absence of these effects in control images that did not contain a face refutes alternative accounts based on retinal biases or allocation of attention to the eye location on the face. We conclude that the rising part of the N170, roughly 120-170 ms post-stimulus, is a critical time-window in human face processing mechanisms, reflecting predominantly, in a face detection task, the encoding of a single feature: the contralateral eye. © 2014 ARVO.

Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

PubMed

Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

2018-01-01

Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Destabilization of the metal site as a hub for the pathogenic mechanism of five ALS-linked mutants of copper, zinc superoxide dismutase.

PubMed

Mera-Adasme, Raúl; Erdmann, Hannes; Bereźniak, Tomasz; Ochsenfeld, Christian

2016-10-01

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, with no effective pharmacological treatment. Its pathogenesis is unknown, although a subset of the cases is linked to genetic mutations. A significant fraction of the mutations occur in one protein, copper, zinc superoxide dismutase (SOD1). The toxic function of mutant SOD1 has not been elucidated, but damage to the metal site of the protein is believed to play a major role. In this work, we study the electrostatic loop of SOD1, which we had previously proposed to work as a "solvent seal" isolating the metal site from water molecules. Out of the five contact points identified between the electrostatic loop and its dock in the rest of the protein, three points were found to be affected by ALS-linked mutations, with a total of five mutations identified. The effect of the five mutations was studied using methods of computational chemistry. We found that four of the mutations destabilize the proposed solvent seal, while the fifth mutation directly affects the metal-site stability. In the two contact points unaffected by ALS-linked mutations, the side chains of the residues were not found to play a stabilizing role. Our results show that the docking of the electrostatic loop to the rest of SOD1 plays a role in ALS pathogenesis, in support of that structure acting as a solvent barrier for the metal site. The results provide a unified pathogenic mechanism for five different ALS-linked mutations of SOD1.

The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity

PubMed Central

2014-01-01

Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA's impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity. PMID:24804084

Anti-neuroinflammatory Potential of Natural Products in Attenuation of Alzheimer's Disease

PubMed Central

Shal, Bushra; Ding, Wei; Ali, Hussain; Kim, Yeong S.; Khan, Salman

2018-01-01

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder associated with dementia and cognitive impairment most common in elderly population. Various pathophysiological mechanisms have been proposed by numerous researcher, although, exact mechanism is not yet elucidated. Several studies have been indicated that neuroinflammation associated with deposition of amyloid- beta (Aβ) in brain is a major hallmark toward the pathology of neurodegenerative diseases. So, there is a need to unravel the link of inflammatory process in neurodegeneration. Increased microglial activation, expression of cytokines, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) participate in inflammatory process of AD. This review mainly concentrates on involvement of neuroinflammation and the molecular mechanisms adapted by various natural compounds, phytochemicals and herbal formulations in various signaling pathways involved in neuroprotection. Currently, pharmacologically active natural products, having anti-neuroinflammatory potential are being focused which makes them potential candidate to cure AD. A number of preclinical and clinical trials have been done on nutritional and botanical agents. Analysis of anti-inflammatory and neuroprotective phytochemicals such as terpenoids, phenolic derivatives, alkaloids, glycosides, and steroidal saponins displays therapeutic potential toward amelioration and prevention of devastating neurodegeneration observed in AD. PMID:29896105

Progress on Fault Mechanisms for Gear Transmissions in Coal Cutting Machines: From Macro to Nano Models.

PubMed

Jiang, Yu; Zhang, Xiaogang; Zhang, Chao; Li, Zhixiong; Sheng, Chenxing

2017-04-01

Numerical modeling has been recognized as the dispensable tools for mechanical fault mechanism analysis. Techniques, ranging from macro to nano levels, include the finite element modeling boundary element modeling, modular dynamic modeling, nano dynamic modeling and so forth. This work firstly reviewed the progress on the fault mechanism analysis for gear transmissions from the tribological and dynamic aspects. Literature review indicates that the tribological and dynamic properties were separately investigated to explore the fault mechanism in gear transmissions. However, very limited work has been done to address the links between the tribological and dynamic properties and scarce researches have been done for coal cutting machines. For this reason, the tribo-dynamic coupled model was introduced to bridge the gap between the tribological and dynamic models in fault mechanism analysis for gear transmissions in coal cutting machines. The modular dynamic modeling and nano dynamic modeling techniques are expected to establish the links between the tribological and dynamic models. Possible future research directions using the tribo dynamic coupled model were summarized to provide potential references for researchers in the field.

Discrimination of ethanol-nicotine drug mixtures in mice: dual interactive mechanisms of overshadowing and potentiation

PubMed Central

Ford, Matthew M.; McCracken, Aubrey D.; Davis, Natalie L.; Ryabinin, Andrey E.; Grant, Kathleen A.

2012-01-01

Rationale One possible basis for the proclivity of ethanol and nicotine co-abuse is an interaction between the discriminative stimulus (SD) effects of each drug. Objectives The current work sought to assess the discriminative control of ethanol and nicotine cues in mice trained with drug mixtures and to determine whether interactive mechanisms of overshadowing and potentiation occur. Methods Male C57BL/6J mice were trained to discriminate ethanol (1.5 g/kg) alone or ethanol plus nicotine (0.4, 0.8 or 1.2 mg/kg base) in experiment 1, and nicotine (0.8 mg/kg) alone or nicotine plus ethanol (0.5, 1.0 or 2.0 g/kg) in experiment 2. Stimulus generalization of the training mixtures to ethanol, nicotine and the drug combination were assessed. Results Ethanol (1.5 g/kg) retained discriminative control despite the inclusion of a progressively larger nicotine dose within the training mixtures in experiment 1. Although the nicotine SD was overshadowed by ethanol training doses > 0.5 g/kg in experiment 2, nicotine did potentiate the effects of low dose ethanol. Conclusions These findings are suggestive of dual mechanisms whereby ethanol (>0.5 g/kg) overshadows the SD effects of nicotine, and at lower doses (< 1 g/kg) the salience of ethanol’s SD effects is potentiated by nicotine. These mechanisms may contribute to the escalation of concurrent drinking and smoking in a binge-like fashion. PMID:22763667

Novel Magnetic Cross-Linked Cellulase Aggregates with a Potential Application in Lignocellulosic Biomass Bioconversion.

PubMed

Jia, Junqi; Zhang, Weiwei; Yang, Zengjie; Yang, Xianling; Wang, Na; Yu, Xiaoqi

2017-02-10

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has been developed and applied for biomass bioconversion. The crosslinked aggregates could purify and immobilize enzymes in a single operation, and could then be combined with magnetic nanoparticles (MNPs), which provides easy separation of the materials. The immobilized cellulase showed a better activity at a wider temperature range and pH values than that of the free cellulase. After six cycles of consecutive reuse, the immobilized cellulase performed successful magnetic separation and retained 74% of its initial activity when carboxylmethyl cellulose (CMC) was used as the model substrate. Furthermore, the structure and morphology of the immobilized cellulase were studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the immobilized cellulase was shown to hydrolyze bamboo biomass with a yield of 21%, and was re-used in biomass conversion up to four cycles with 38% activity retention, which indicated that the immobilized enzyme has good potential for biomass applications.

The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

PubMed Central

Li, Sha; Cheung, Fan

2018-01-01

Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases. It has been reported that many polyphenols from a wide range of foods and herbs exert therapeutic effects on liver injuries via complicated mechanisms. Therefore, it is necessary to have a systematical review to sort out current researches to help better understand the potentials of polyphenols in liver diseases. In this review, we aim to summarize and update the existing evidence of natural polyphenols in the treatment of various liver diseases by in vitro, in vivo, and clinical studies, while special attention is paid to the action mechanisms. PMID:29507653