Versatile functional roles of horizontal cells in the retinal circuit.

PubMed

Chaya, Taro; Matsumoto, Akihiro; Sugita, Yuko; Watanabe, Satoshi; Kuwahara, Ryusuke; Tachibana, Masao; Furukawa, Takahisa

2017-07-17

In the retinal circuit, environmental light signals are converted into electrical signals that can be decoded properly by the brain. At the first synapse of the visual system, information flow from photoreceptors to bipolar cells is modulated by horizontal cells (HCs), however, their functional contribution to retinal output and individual visual function is not fully understood. In the current study, we investigated functional roles for HCs in retinal ganglion cell (RGC) response properties and optokinetic responses by establishing a HC-depleted mouse line. We observed that HC depletion impairs the antagonistic center-surround receptive field formation of RGCs, supporting a previously reported HC function revealed by pharmacological approaches. In addition, we found that HC loss reduces both the ON and OFF response diversities of RGCs, impairs adjustment of the sensitivity to ambient light at the retinal output level, and alters spatial frequency tuning at an individual level. Taken together, our current study suggests multiple functional aspects of HCs crucial for visual processing.

Functionality Selection Principle for High Voltage Lithium-ion Battery Electrolyte Additives

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

Su, Chi-Cheung; He, Meinan; Peebles, Cameron

A new class of electrolyte additives based on cyclic fluorinated phosphate esters was rationally designed and identified as being able to stabilize the surface of a LiNi0.5Mn0.3Co0.2O2 (NMC532) cathode when cycled at potentials higher than 4.6 V vs Li+/Li. Cyclic fluorinated phosphates were designed to incorporate functionalities of various existing additives to maximize their utilization. The synthesis and characterization of these new additives are described and their electrochemical performance in a NMC532/graphite cell cycled between 4.6 and 3.0 V are investigated. With 1.0 wt % 2-(2,2,2-trifluoroethoxy)-1,3,2-dioxaphospholane 2-oxide (TFEOP) in the conventional electrolyte the NMC532/graphite cell exhibited much improved capacity retentionmore » compared to that without any additive. The additive is believed to form a passivation layer on the surface of the cathode via a sacrificial polymerization reaction as evidenced by X-ray photoelectron spectroscopy (XPS) and nuclear magnetic resonsance (NMR) analysis results. The rational pathway of a cathode-electrolyte-interface formation was proposed for this type of additive. Both experimental results and the mechanism hypothesis suggest the effectiveness of the additive stems from both the polymerizable cyclic ring and the electron-withdrawing fluorinated alkyl group in the phosphate molecular structure. The successful development of cyclic fluorinated phosphate additives demonstrated that this new functionality selection principle, by incorporating useful functionalities of various additives into one molecule, is an effective approach for the development of new additives.« less

Academic and social achievement goals: Their additive, interactive, and specialized effects on school functioning.

PubMed

Liem, Gregory Arief D

2016-03-01

Students' pursuit of academic and social goals has implications for school functioning. However, studies on academic and social achievement goals have been relatively independent and mainly conducted with students in culturally Western settings. Guided by multiple-goal perspectives, this study examined the role of academic and social achievement goals in outcome variables relevant to academic (achievement, effort/persistence), social (peer relationship satisfaction, loneliness), and socio-academic (cooperative learning, competitive learning, socially regulated, and self-regulated learning) functioning. A total of 356 Indonesian high-school students (mean age = 16 years; 36% girls) participated in the study. A self-report survey comprising items drawn from pre-existing instruments was administered to measure distinct dimensions of achievement goals and outcomes under focus. Regression analysis was performed to examine additive, interactive, and specialized effects of achievement goals on outcomes. Aligned with the hierarchical model of goal relationships (Wentzel, 2000, Contemp. Educ. Psychol., 25, 105), academic and social achievement goals bore additive effects on most outcomes. Findings also revealed a specialized effect on academic achievement and notable interactive effects on cooperative learning. In general, mastery-approach and performance-approach goals were more adaptive than their avoidance counterparts. The effects of social development goals were positive, whereas those of social demonstration-approach goals were mixed. Contrary to prior findings, social demonstration-avoidance goals did not appear to be inimical for school functioning. Findings underscore the importance of both academic and social achievement goals in day-to-day school functioning and the need to consider the meaning of goals and the coordination of multiple goals from cultural lenses. © 2015 The British Psychological Society.

Examining the Roles of Work Autonomous and Controlled Motivations on Satisfaction and Anxiety as a Function of Role Ambiguity.

PubMed

Gillet, Nicolas; Fouquereau, Evelyne; Lafrenière, Marc-André K; Huyghebaert, Tiphaine

2016-07-03

Past research in the self-determination theory has shown that autonomous motivation is associated with positive outcomes (e.g., work satisfaction), whereas controlled motivation is related to negative outcomes (e.g., anxiety). The purpose of the present research was to examine the moderating function of role ambiguity on the relationships between work autonomous and controlled motivations on the one hand, and work satisfaction and anxiety on the other. Six hundred and ninety-eight workers (449 men and 249 women) participated in this study. Results revealed that autonomous motivation was most strongly related to satisfaction when ambiguity was low. In addition, controlled motivation was most strongly related to anxiety when ambiguity was high. In other words, the present findings suggest that the outcomes associated with each form of motivation may vary as a function of role ambiguity. The present study thus offers meaningful insights for organizations, managers, and employees.

Spent yeast as natural source of functional food additives

PubMed

Rakowska, Rita; Sadowska, Anna; Dybkowska, Ewa; Świderski, Franciszek

Spent yeasts are by-products arising from beer and wine production which over many years have been chiefly used as feed additives for livestock. They contain many valuable and bioactive substances which has thereby generated much interest in their exploitation. Up till now, the main products obtained from beer-brewing yeasts are β-glucans and yeast extracts. Other like foodstuffs include dried brewer’s yeast, where this is dried and the bitterness removed to be fit for human consumption as well as mannan-oligosaccharides hitherto used in the feed industry. β-glucans constitute the building blocks of yeast cell walls and can thus be used in human nutrition as dietary supplements or serving as food additives in functional foods. β-glucans products obtained via post-fermentation of beer also exhibit a high and multi-faceted biological activity where they improve the blood’s lipid profile, enhance immunological status and have both prebiotic and anti-oxidant properties. Yeast extracts are currently being used more and more to enhance flavour in foodstuffs, particularly for meat and its products. Depending on how autolysis is carried out, it is possible to design extracts of various meat flavours characteristic of specific meats. Many different flavour profiles can be created which may be additionally increased in combination with vegetable extracts. Within the food market, yeast extracts can appear in various guises such as liquids, pastes or powders. They all contain significant amounts of glutamic acid, 5’-GMP and 5’-IMP nucleotides together with various amino acids and peptides that act synergistically for enhancing the flavour of foodstuff products. Recent studies have demonstrated additional benefits of yeast extracts as valuable sources of amino acids and peptides which can be used in functional foods and dietary supplements. These products possess GRAS status (Generally Recognised As Safe) which thereby also adds further as to why they should be used

[The role of vitamin D in the prevention and the additional therapy of cancers].

PubMed

Speer, Gábor

2010-12-01

The active metabolite of vitamin D apart from a crucial role in maintaining mineral homeostasis and skeletal functions, has antiproliferative, apoptosis and differentiation inducing as well as immunomodulatory effects in cancer. It is well known that with increasing sunshine exposure the incidence of breast, prostate and colorectal cancer is decreasing. A number of in vitro and in vivo experiments documented the effects of vitamin D in the inhibition of the tumorigenesis. In studying the role of vitamin D in cancer, it is imperative to examine the potential pathways that control local tissue levels of vitamin D. The enzyme 24-hydroxylase converts the active vitamin D to inactive metabolite. Extra-renal production of this enzyme is observed and has been increasingly recognized as present in cancer cells. This enzyme is rate limiting for the amount of local vitamin D in cancer tissues and elevated expression is associated with an adverse prognosis. 24-hydroxylase may be a predictive marker of vitamin D efficacy in patients with cancer as an adjunctive therapy. There are many vitamin D analogs with no pronounced hypercalcemizing effects. Some analogs are in phase 1 and 2 clinical test, and they might have a role in the therapy of several types of cancer. At present our main task is to make an effort to decrease the vitamin D deficiency in Hungary. Speer G. The D-day. The role of vitamin D in the prevention and the additional therapy of cancers.

Complementary Roles of Estrogen-Related Receptors in Brown Adipocyte Thermogenic Function

PubMed Central

Gantner, Marin L.; Hazen, Bethany C.; Eury, Elodie; Brown, Erin L.

2016-01-01

Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial Uncoupling Protein 1 (UCP1), which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor (ERR)α. Whole-body ERRα knockout mice show decreased BAT mitochondrial content and oxidative function but normal induction of Ucp1 in response to cold. In addition to ERRα, brown adipocytes express ERRβ and ERRγ, 2 nuclear receptors that are highly similar to ERRα and whose function in adipocytes is largely unknown. To gain insights into the roles of all 3 ERRs, we assessed mitochondrial function and adrenergic responses in primary brown adipocytes lacking combinations of ERRs. We show that adipocytes lacking just ERRα, the most abundant ERR, show only mild mitochondrial defects. Adipocytes lacking ERRβ and ERRγ also show just mild defects. In contrast, adipocytes lacking all 3 ERRs have severe reductions in mitochondrial content and oxidative capacity. Moreover, adipocytes lacking all 3 ERRs have defects in the transcriptional and metabolic response to adrenergic stimulation, suggesting a wider role of ERRs in BAT function than previously appreciated. Our study shows that ERRs have a great capacity to compensate for each other in protecting mitochondrial function and the metabolic response to adrenergic signaling, processes vital to BAT function. PMID:27763777

Roles of additives and surface control in slurry atomization

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

Tsai, S.C.

1992-01-01

This project studies the rheology and airblast atomization of micronized coal slurries. Its major objectives are (1) to promote further understanding of the mechanisms and the roles of additives in airblast atomization of coal water slurry (CWS), and (2) to investigate the impacts of coal particle surface properties and interparticle forces on CWS rheology. We have found that the flow behavior index (n) of a suspension (or slurry) is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The interparticle attraction, measured by the Hamaker constant scaled to the thermal energy atmore » 25[degrees]C (A/kT), causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior (n< 1). At a constant particle volume fraction and surface charge density (qualitatively measured by the zeta potential in deionized water), n decreases linearly as A/kT increases. The relative viscosity of the pseudoplastic suspension with respect to that of the suspending liquid is found to be independent of particle density and correlate well with the particle Peclet number which equals the particle diffusional relaxation time multiplied by shear rate. Specifically, the relative viscosities of the pseudoplastic glycerol/water coal slurry and the ethylene glycol/glycerol sand slurry, at same volume fractions as well as similar particle size distributions and liquid viscosities, as functions of the particle Peclet number fall along the same line.« less

Non-Structural Proteins of Arthropod-Borne Bunyaviruses: Roles and Functions

PubMed Central

Eifan, Saleh; Schnettler, Esther; Dietrich, Isabelle; Kohl, Alain; Blomström, Anne-Lie

2013-01-01

Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod. PMID:24100888

Kinetics of the addition of olefins to Si-centered radicals: the critical role of dispersion interactions revealed by theory and experiment.

PubMed

Johnson, Erin R; Clarkin, Owen J; Dale, Stephen G; DiLabio, Gino A

2015-06-04

Solution-phase rate constants for the addition of selected olefins to the triethylsilyl and tris(trimethylsilyl)silyl radicals are measured using laser-flash photolysis and competition kinetics. The results are compared with predictions from density functional theory (DFT) calculations, both with and without dispersion corrections obtained from the exchange-hole dipole moment (XDM) model. Without a dispersion correction, the rate constants are consistently underestimated; the errors increase with system size, up to 10(6) s(-1) for the largest system considered. Dispersion interactions preferentially stabilize the transition states relative to the separated reactants and bring the DFT-calculated rate constants into excellent agreement with experiment. Thus, dispersion interactions are found to play a key role in determining the kinetics for addition reactions, particularly those involving sterically bulky functional groups.

Addition of Rubber to soil damages the functional diversity of soil.

PubMed

Goswami, Madhurankhi; Bhattacharyya, Purnita; Tribedi, Prosun

2017-07-01

Rubber is a polymer of isoprene, consisting mainly of cis-1,4-polyisoprene units. The unmanageable production and its irresponsible disposal pose severe threats to environmental ecology. Therefore, the current study focuses extensively on the ill-effects of Rubber disposal on soil microbial functional diversity as it reflects the health of ecosystem by acting as a key component in ecosystem productivity. To investigate the effect of Rubber on soil microbial functional diversity, soil samples were collected from landfill sites and three different soil microcosms (Rubber treated, untreated, and sterile soil) were prepared. The soil enzymatic activity was determined by fluorescein diacetate hydrolysis followed by the determination of the microbial metabolic potential and functional diversity by average well color development and Shannon-Weaver index (H), respectively. BiOLOG ECO plates were used for determining the microbial functional diversity of the soil microcosms. Higher heterotrophic microbial count as well as higher soil microbial activity was observed in Rubber untreated soil than Rubber treated soil microcosm. The result indicated that the addition of Rubber to soil reduced soil heterotrophic microbial count and soil microbial activity considerably. Similarly, soil microbial metabolic potential as well as microbial functional diversity of soil had been decreased by the addition of Rubber gloves in it. Variation in soil microbial metabolic spectrum between Rubber treated and untreated microcosm was confirmed by multivariate analysis. Collectively, all the results demonstrated that the addition of Rubber to soil reduced the soil microbial functional diversity considerably. Therefore, it is necessary for the commission of serious steps regarding Rubber disposal and protection of the environment from serious environmental issues.

THE FUNCTIONAL ROLES OF MUSCLES DURING SLOPED WALKING

PubMed Central

Pickle, Nathaniel T.; Grabowski, Alena M.; Auyang, Arick G.; Silverman, Anne K.

2016-01-01

Sloped walking is biomechanically different from level-ground walking, as evidenced by changes in joint kinematics and kinetics. However, the changes in muscle functional roles underlying these altered movement patterns have not been established. In this study, we developed a total of 273 muscle-actuated simulations to assess muscle functional roles, quantified by induced body center-of-mass accelerations and trunk and leg power, during walking on slopes of 0°, ±3°, ±6°, and ±9° at 1.25 m/s. The soleus and gastrocnemius both provided greater forward acceleration of the body parallel to the slope at +9° compared to level ground (+126% and +66%, respectively). However, while the power delivered to the trunk by the soleus varied with slope, the magnitude of net power delivered to the trunk and ipsilateral leg by the biarticular gastrocnemius was similar across all slopes. At +9°, the hip extensors absorbed more power from the trunk (230% hamstrings, 140% gluteus maximus) and generated more power to both legs (200% hamstrings, 160% gluteus maximus) compared to level ground. At −9°, the knee extensors (rectus femoris and vasti) accelerated the body upward perpendicular to the slope at least 50% more and backward parallel to the slope twice as much as on level ground. In addition, the knee extensors absorbed greater amounts of power from the ipsilateral leg on greater declines to control descent. Future studies can use these results to develop targeted rehabilitation programs and assistive devices aimed at restoring sloped walking ability in impaired populations. PMID:27553849

21 CFR 14.142 - Functions of a color additive advisory committee.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Functions of a color additive advisory committee. 14.142 Section 14.142 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees § 14...

21 CFR 14.142 - Functions of a color additive advisory committee.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Functions of a color additive advisory committee. 14.142 Section 14.142 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees § 14...

21 CFR 14.142 - Functions of a color additive advisory committee.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Functions of a color additive advisory committee. 14.142 Section 14.142 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees § 14...

21 CFR 14.142 - Functions of a color additive advisory committee.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Functions of a color additive advisory committee. 14.142 Section 14.142 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees § 14...

Aquaporins in the eye: Expression, function, and roles in ocular disease☆

PubMed Central

Schey, Kevin L.; Wang, Zhen; Wenke, Jamie L.; Qi, Ying

2015-01-01

Background All thirteen known mammalian aquaporins have been detected in the eye. Moreover, aquaporins have been identified as playing essential roles in ocular functions ranging from maintenance of lens and corneal transparency to production of aqueous humor to maintenance of cellular homeostasis and regulation of signal transduction in the retina. Scope of review This review summarizes the expression and known functions of ocular aquaporins and discusses their known and potential roles in ocular diseases. Major conclusions Aquaporins play essential roles in all ocular tissues. Remarkably, not all aquaporin function as a water permeable channel and the functions of many aquaporins in ocular tissues remain unknown. Given their vital roles in maintaining ocular function and their roles in disease, aquaporins represent potential targets for future therapeutic development. General significance Since aquaporins play key roles in ocular physiology, an understanding of these functions is important to improving ocular health and treating diseases of the eye. It is likely that future therapies for ocular diseases will rely on modulation of aquaporin expression and/or function. This article is part of a Special Issue entitled Aquaporins. PMID:24184915

Low Molecular Weight Polymethacrylates as Multi-Functional Lubricant Additives

DOE PAGES

Cosimbescu, Lelia; Vellore, Azhar; Shantini Ramasamy, Uma; ...

2018-04-24

In this study, low molecular weight, moderately polar polymethacrylate polymers are explored as potential multi-functional lubricant additives. The performance of these novel additives in base oil is evaluated in terms of their viscosity index, shear stability, and friction-and-wear. The new compounds are compared to two benchmarks, a typical polymeric viscosity modifier and a fully-formulated oil. Results show that the best performing of the new polymers exhibit viscosity index and friction comparable to that of both benchmarks, far superior shear stability to either benchmark (as much as 15x lower shear loss), and wear reduction significantly better than a typical viscosity modifiermore » (lower wear volume by a factor of 2-3). The findings also suggest that the polarity and molecular weight of the polymers affect their performance which suggests future synthetic strategies may enable this new class of additives to replace multiple additives in typical lubricant formulations.« less

Low Molecular Weight Polymethacrylates as Multi-Functional Lubricant Additives

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

Cosimbescu, Lelia; Vellore, Azhar; Shantini Ramasamy, Uma

In this study, low molecular weight, moderately polar polymethacrylate polymers are explored as potential multi-functional lubricant additives. The performance of these novel additives in base oil is evaluated in terms of their viscosity index, shear stability, and friction-and-wear. The new compounds are compared to two benchmarks, a typical polymeric viscosity modifier and a fully-formulated oil. Results show that the best performing of the new polymers exhibit viscosity index and friction comparable to that of both benchmarks, far superior shear stability to either benchmark (as much as 15x lower shear loss), and wear reduction significantly better than a typical viscosity modifiermore » (lower wear volume by a factor of 2-3). The findings also suggest that the polarity and molecular weight of the polymers affect their performance which suggests future synthetic strategies may enable this new class of additives to replace multiple additives in typical lubricant formulations.« less

Bench to Bedside and Back Again: Molecular Mechanisms of α-Catenin Function and Roles in Tumorigenesis

PubMed Central

Benjamin, Jacqueline M.; Nelson, W. James

2009-01-01

The cadherin/catenin complex, comprised of E-cadherin, β-catenin and α-catenin, is essential for initiating cell-cell adhesion, establishing cellular polarity and maintaining tissue organization. Disruption or loss of the cadherin/catenin complex is common in cancer. As the primary cell-cell adhesion protein in epithelial cells, E-cadherin has long been studied in cancer progression. Similarly, additional roles for β-catenin in the Wnt signaling pathway has led to many studies of the role of β-catenin in cancer. Alpha-catenin, in contrast, has received less attention. However, recent data demonstrate novel functions for α-catenin in regulating the actin cytoskeleton and cell-cell adhesion, which when perturbed could contribute to cancer progression. In this review, we use cancer data to evaluate molecular models of α-catenin function, from the canonical role of α-catenin in cell-cell adhesion to non-canonical roles identified following conditional α-catenin deletion. This analysis identifies α-catenin as a prognostic factor in cancer progression. PMID:17945508

Review on Advances of Functional Material for Additive Manufacturing

NASA Astrophysics Data System (ADS)

Zulkifli, Nur Amalina Binti; Akmal Johar, Muhammad; Faizan Marwah, Omar Mohd; Irwan Ibrahim, Mohd Halim

2017-08-01

The attempt of finding and making new materials in improving products that are already in the market are widely done by researchers nowadays. This project is focusing on making new materials for functional material through additive manufacturing application. The idea of this project came from the ability limitation of capacitor in market nowadays in storing higher charges but smaller in size. Powder glass is the new material that could to be used as a dielectric material for capacitor with the help of palm kernel oil as the binder. This paper reviews on applications done through additive manufacturing method and also types of functional materials used in this method previously. Structure of a capacitor, dielectric properties and measurement techniques that are trying to be carried out are also explains in this paper. Last part of this paper brief on the material proposal and reasons those materials are chosen. New dielectric material for capacitor which are able to store more charges but still small in size are expected to be produced as the outcome of this research.

The structure and function of the dopamine transporter and its role in CNS diseases.

PubMed

McHugh, Patrick C; Buckley, David A

2015-01-01

In this chapter, we explore the basic science of the dopamine transporter (DAT), an integral component of a system that regulates dopamine homeostasis. Dopamine is a key neurotransmitter for several brain functions including locomotor control and reward systems. The transporter structure, function, mechanism of action, localization, and distribution, in addition to gene regulation, are discussed. Over many years, a wealth of information concerning the DAT has been accrued and has led to increased interest in the role of the DAT in a plethora of central nervous system diseases. These DAT characteristics are explored in relation to a range of neurological and neuropsychiatric diseases, with a particular focus on the genetics of the DAT. In addition, we discuss the pharmacology of the DAT and how this relates to disease and addiction. © 2015 Elsevier Inc. All rights reserved.

Generalized neurofuzzy network modeling algorithms using Bézier-Bernstein polynomial functions and additive decomposition.

PubMed

Hong, X; Harris, C J

2000-01-01

This paper introduces a new neurofuzzy model construction algorithm for nonlinear dynamic systems based upon basis functions that are Bézier-Bernstein polynomial functions. This paper is generalized in that it copes with n-dimensional inputs by utilising an additive decomposition construction to overcome the curse of dimensionality associated with high n. This new construction algorithm also introduces univariate Bézier-Bernstein polynomial functions for the completeness of the generalized procedure. Like the B-spline expansion based neurofuzzy systems, Bézier-Bernstein polynomial function based neurofuzzy networks hold desirable properties such as nonnegativity of the basis functions, unity of support, and interpretability of basis function as fuzzy membership functions, moreover with the additional advantages of structural parsimony and Delaunay input space partition, essentially overcoming the curse of dimensionality associated with conventional fuzzy and RBF networks. This new modeling network is based on additive decomposition approach together with two separate basis function formation approaches for both univariate and bivariate Bézier-Bernstein polynomial functions used in model construction. The overall network weights are then learnt using conventional least squares methods. Numerical examples are included to demonstrate the effectiveness of this new data based modeling approach.

Risk factors for psychosis: impaired social and role functioning.

PubMed

Cornblatt, Barbara A; Carrión, Ricardo E; Addington, Jean; Seidman, Larry; Walker, Elaine F; Cannon, Tyronne D; Cadenhead, Kristin S; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Woods, Scott W; Heinssen, Robert; Lencz, Todd

2012-11-01

Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.

Differing Roles of Functional Movement Variability as Experience Increases in Gymnastics

PubMed Central

Busquets, Albert; Marina, Michel; Davids, Keith; Angulo-Barroso, Rosa

2016-01-01

gymnasts). Longswing assessment allowed us to evaluate inter-trial variability in representative performance context. Coordination variability presented two different configurations across experience levels depending on the variable of interest: either a U-shaped or a L- or \\-shaped graph. Increased inter-trial variability of the functional phase events offered flexibility to adapt the longswing performance in the advanced gymnasts, while decreasing variability in arm-trunk coordination modes was critical to improve longswing and to achieve the most advanced level. In addition, the relationship between variability measures and the global performance outcome (i.e. the swing amplitude) revealed different functional roles of movement variability (exploratory or restrictive) as a function of changes in experience levels. PMID:27274664

The Role of Control Functions in Mentalizing: Dual-Task Studies of Theory of Mind and Executive Function

ERIC Educational Resources Information Center

Bull, Rebecca; Phillips, Louise H.; Conway, Claire A.

2008-01-01

Conflicting evidence has arisen from correlational studies regarding the role of executive control functions in Theory of Mind. The current study used dual-task manipulations of executive functions (inhibition, updating and switching) to investigate the role of these control functions in mental state and non-mental state tasks. The "Eyes"…

Unique roles of glucagon and glucagon-like peptides: Parallels in understanding the functions of adipokinetic hormones in stress responses in insects.

PubMed

Bednářová, Andrea; Kodrík, Dalibor; Krishnan, Natraj

2013-01-01

Glucagon is conventionally regarded as a hormone, counter regulatory in function to insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. Glucagon performs this function by increasing hepatic glucose output to the blood by stimulating glycogenolysis and gluconeogenesis in response to starvation. Additionally it plays a homeostatic role by decreasing glycogenesis and glycolysis in tandem to try and maintain optimal glucose levels. To perform this action, it also increases energy expenditure which is contrary to what one would expect and has actions which are unique and not entirely in agreement with its role in protection from hypoglycemia. Interestingly, glucagon-like peptides (GLP-1 and GLP-2) from the major fragment of proglucagon (in non-mammalian vertebrates, as well as in mammals) may also modulate response to stress in addition to their other physiological actions. These unique modes of action occur in response to psychological, metabolic and other stress situations and mirror the role of adipokinetic hormones (AKHs) in insects which perform a similar function. The findings on the anti-stress roles of glucagon and glucagon-like peptides in mammalian and non-mammalian vertebrates may throw light on the multiple stress responsive mechanisms which operate in a concerted manner under regulation by AKH in insects thus functioning as a stress responsive hormone while also maintaining organismal homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

PubMed

Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

2013-11-01

The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

A Novel Functional Role of Collagen Glycosylation

PubMed Central

Jürgensen, Henrik J.; Madsen, Daniel H.; Ingvarsen, Signe; Melander, Maria C.; Gårdsvoll, Henrik; Patthy, Laszlo; Engelholm, Lars H.; Behrendt, Niels

2011-01-01

Collagens make up the most abundant component of interstitial extracellular matrices and basement membranes. Collagen remodeling is a crucial process in many normal physiological events and in several pathological conditions. Some collagen subtypes contain specific carbohydrate side chains, the function of which is poorly known. The endocytic collagen receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 plays an important role in matrix remodeling through its ability to internalize collagen for lysosomal degradation. uPARAP/Endo180 is a member of the mannose receptor protein family. These proteins all include a fibronectin type II domain and a series of C-type lectin-like domains, of which only a minor part possess carbohydrate recognition activity. At least two of the family members, uPARAP/Endo180 and the mannose receptor, interact with collagens. The molecular basis for this interaction is known to involve the fibronectin type II domain but nothing is known about the function of the lectin domains in this respect. In this study, we have investigated a possible role of the single active lectin domain of uPARAP/Endo180 in the interaction with collagens. By expressing truncated recombinant uPARAP/Endo180 proteins and analyzing their interaction with collagens with high and low levels of glycosylation we demonstrated that this lectin domain interacts directly with glycosylated collagens. This interaction is functionally important because it was found to modulate the endocytic efficiency of the receptor toward highly glycosylated collagens such as basement membrane collagen IV. Surprisingly, this property was not shared by the mannose receptor, which internalized glycosylated collagens independently of its lectin function. This role of modulating its uptake efficiency by a specific receptor is a previously unrecognized function of collagen glycosylation. PMID:21768090

Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance.

PubMed

Mookerjee, Shona A; Lyon, Hiram D; Sia, Elaine A

2005-02-01

Mitochondrial DNA (mtDNA) repair occurs in all eukaryotic organisms and is essential for the maintenance of mitochondrial function. Evidence from both humans and yeast suggests that mismatch repair is one of the pathways that functions in overall mtDNA stability. In the mitochondria of the yeast Saccharomyces cerevisiae, the presence of a homologue to the bacterial MutS mismatch repair protein, MSH1, has long been known to be essential for mitochondrial function. The mechanisms for which it is essential are unclear, however. Here, we analyze the effects of two point mutations, msh1-F105A and msh1-G776D, both predicted to be defective in mismatch repair; and we show that they are both able to maintain partial mitochondrial function. Moreover, there are significant differences in the severity of mitochondrial disruption between the two mutants that suggest multiple roles for Msh1p in addition to mismatch repair. Our overall findings suggest that these additional predicted functions of Msh1p, including recombination surveillance and heteroduplex rejection, may be primarily responsible for its essential role in mtDNA stability.

Functional valve assessment: the emerging role of cardiovascular magnetic resonance.

PubMed

Shah, Dipan J

2010-01-01

The prevalence of valvular heart disease is increasing along with the life span of the population. In assessing individuals with valve disease, echocardiography is the primary imaging modality used by clinicians both for initial assessment and for longitudinal evaluation. Information regarding valve morphology and function, cardiac chamber size, wall thickness, ventricular function, and estimates of pulmonary artery pressures can be readily obtained and integrated to formulate an assessment of valve disease severity. In some instances, body habitus or the presence of coexisting lung disease may result in suboptimal acoustic windows on echocardiography, which may lead to technically difficult studies. Additionally, in some patients, information from clinical history and physical examination or other diagnostic tests may be discordant with echocardiographic findings. In these instances, there is a significant clinical role for cardiovascular magnetic resonance (CMR). The diagnostic capabilities of CMR have increased substantially over the past 20 years due to hardware and software advances. Today, CMR has a number of unique advantages over other imaging modalities - primarily, it provides a view of the entire heart without limitations from inadequate imaging windows or body habitus. Furthermore, CMR can obtain imaging data in any imaging plane prescribed by the scan operator, which makes it ideal for accurate investigation of all cardiac valves - aortic, mitral, pulmonic, and tricuspid. In addition, CMR for valve assessment is noninvasive, free of ionizing radiation, and in most instances does not require contrast administration. Since a comprehensive review of the role of CMR in all valve lesions is beyond the scope of this article, we will focus on the most common valvular indication for performance of clinical CMR techniques and an overview of selected validation and reproducibility studies. The objectives of a comprehensive CMR study for evaluating mitral

Impaired Social and Role Function in Ultra-High Risk for Psychosis and First-Episode Schizophrenia: Its Relations with Negative Symptoms.

PubMed

Lee, So Jung; Kim, Kyung Ran; Lee, Su Young; An, Suk Kyoon

2017-09-01

Psychosocial dysfunction was a nettlesome problem of schizophrenia even in their prodromal phase as well as in their first-episode. In addition, its relations with psychopathology were not determined. The aim of the present study was to examine whether the social and role function impairment was found in ultra-high risk for psychosis (UHR) individuals as well as first-episode schizophrenia patients and to explore its relations with psychopathology. Thirty-seven normal controls, 63 UHR participants and 28 young, first-episode schizophrenia patients were recruited. Psychosocial functioning was examined by using Global function: Social and Role scale. Psychopathologies of positive, negative and depressive symptom were also measured. Social and role functioning in UHR were compromised at the equivalent level of those of first-episode schizophrenia patients. Multiple linear regression analysis revealed that social and role dysfunction was associated with negative symptoms in each UHR and first-episode schizophrenia group. These findings suggest that the significant impairment of social and role function may be appeared before the active psychosis onset at the level of extent to those of first-episode schizophrenia patients. The psychosocial intervention strategy especially targeting the negative symptoms should be developed and provided to individuals from their prepsychotic stage of schizophrenia.

Family Functioning and Dysfunctional Eating Among Italian Adolescents: The Moderating Role of Gender.

PubMed

Laghi, Fiorenzo; McPhie, Meghan L; Baumgartner, Emma; Rawana, Jennine S; Pompili, Sara; Baiocco, Roberto

2016-02-01

The first aim of this study was to examine the association between different dimensions of family functioning and dysfunctional eating in a sample of Italian adolescent boys and girls. The second aim was to investigate whether gender moderates the relationship between family functioning and dysfunctional eating. Seven hundred and twenty seven adolescents (500 boys and 227 girls) with ages ranging from 15 to 18 years completed a survey of self-report measures. Findings from hierarchical multiple regression analysis suggested that aspects of family functioning such as flexibility, cohesion, disengagement, enmeshment, rigidity and chaotic were related to dysfunctional eating in adolescents. Additionally the results indicated differences between boys and girls, in particular dysfunctional eating in adolescent boys seemed to be more affected by dimensions of enmeshment and disengagement than dysfunctional eating in girls. This research highlights the important role of various aspects of family functioning in relation to dysfunctional eating in adolescents.

Functional studies on the role of Notch signaling in Hydractinia development.

PubMed

Gahan, James M; Schnitzler, Christine E; DuBuc, Timothy Q; Doonan, Liam B; Kanska, Justyna; Gornik, Sebastian G; Barreira, Sofia; Thompson, Kerry; Schiffer, Philipp; Baxevanis, Andreas D; Frank, Uri

2017-08-01

The function of Notch signaling was previously studied in two cnidarians, Hydra and Nematostella, representing the lineages Hydrozoa and Anthozoa, respectively. Using pharmacological inhibition in Hydra and a combination of pharmacological and genetic approaches in Nematostella, it was shown in both animals that Notch is required for tentacle morphogenesis and for late stages of stinging cell maturation. Surprisingly, a role for Notch in neural development, which is well documented in bilaterians, was evident in embryonic Nematostella but not in adult Hydra. Adult neurogenesis in the latter seemed to be unaffected by DAPT, a drug that inhibits Notch signaling. To address this apparent discrepancy, we studied the role of Notch in Hydractinia echinata, an additional hydrozoan, in all life stages. Using CRISPR-Cas9 mediated mutagenesis, transgenesis, and pharmacological interference we show that Notch is dispensable for Hydractinia normal neurogenesis in all life stages but is required for the maturation of stinging cells and for tentacle morphogenesis. Our results are consistent with a conserved role for Notch in morphogenesis and nematogenesis across Cnidaria, and a lineage-specific loss of Notch dependence in neurogenesis in hydrozoans. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-conscious emotions׳ role in functional outcomes within clinical populations.

PubMed

Macaulay, Rebecca; Cohen, Alex

2014-04-30

Patients with severe mental illnesses (SMI) often experience dysfunction in their ability to efficiently carry out everyday roles and/or skills. These deficits are seen across many domains of daily functioning. We suggest that the "self-conscious emotions" of pride and shame play a role in these functional outcomes. Pride and shame appear to facilitate individuals׳ ability to evaluate their group status, detect social threats, and to adjust their behaviors accordingly. This study utilized an objective performance measure of functional capacity and a self-report of quality of life (QoL) to examine the respective roles of pride and shame in functional outcomes within two SMI patient groups (schizophrenia and affective disorder) and a community control group. The influence of neurocognition, affect and symptomatology on functional outcomes was also assessed. The patient groups did not differ in cognitive functioning, QoL, or shame. The schizophrenia group reported significantly higher pride and displayed worse objective performance than the other groups. Within each of the groups, shame had an inverse relationship with QoL, while pride positively associated with QoL. Shame associated with worse functional capacity in the schizophrenia group. Shame associated with better functional capacity, while pride associated with worse functional capacity within the affective disorder group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Human BNST: Functional Role in Anxiety and Addiction.

PubMed

Avery, S N; Clauss, J A; Blackford, J U

2016-01-01

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region-the bed nucleus of the stria terminalis (BNST)-in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment.

The Human BNST: Functional Role in Anxiety and Addiction

PubMed Central

Avery, S N; Clauss, J A; Blackford, J U

2016-01-01

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region—the bed nucleus of the stria terminalis (BNST)—in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment. PMID:26105138

Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles.

PubMed

Singh, Sudhir Kumar; Pandey, Himanshu; Al-Bassam, Jawdat; Gheber, Larisa

2018-05-01

Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.

The role of neuropsychological performance in the relationship between chronic pain and functional physical impairment.

PubMed

Pulles, Wiesje L J A; Oosterman, Joukje M

2011-12-01

  In this study, the relationship between pain intensity, neuropsychological, and physical function in adult chronic pain patients was examined.   Thirty participants with chronic pain completed neuropsychological tests tapping mental processing speed, memory, and executive function. Pain intensity was measured with three visual analog scales and the Pain Rating Index of the McGill Pain Questionnaire. A grip strength test, the 6-minute walk test, the Unipedal Stance Test and the Lifting Low Test were administered in order to obtain a performance-based measure of physical capacity. Self-reported physical ability was assessed with the Disability Rating Index and the Short Form-36 Physical Functioning, and Role Physical scales. Psychosocial function was examined using the Mental Health and Role Emotional subscales of the Short Form-36.   The study was set in two outpatient physical therapy clinics in The Netherlands.   The analysis showed that a lower mental processing speed was related to a higher level of pain, as well as to a lower performance-based and self-reported physical functioning. In addition, both performance-based and self-reported physical function revealed an inverse correlation with pain intensity. Psychosocial function turned out to be an important mediator of the relationship between pain and self-reported, but not performance-based, physical function. Mental processing speed, on the other hand, was found to mediate the relationship between pain and performance-based physical functioning.   The results suggest that in chronic pain patients, mental processing speed mediates the relationship between pain and physical function. Wiley Periodicals, Inc.

The Functional Role of Neural Oscillations in Non-Verbal Emotional Communication

PubMed Central

Symons, Ashley E.; El-Deredy, Wael; Schwartze, Michael; Kotz, Sonja A.

2016-01-01

Effective interpersonal communication depends on the ability to perceive and interpret nonverbal emotional expressions from multiple sensory modalities. Current theoretical models propose that visual and auditory emotion perception involves a network of brain regions including the primary sensory cortices, the superior temporal sulcus (STS), and orbitofrontal cortex (OFC). However, relatively little is known about how the dynamic interplay between these regions gives rise to the perception of emotions. In recent years, there has been increasing recognition of the importance of neural oscillations in mediating neural communication within and between functional neural networks. Here we review studies investigating changes in oscillatory activity during the perception of visual, auditory, and audiovisual emotional expressions, and aim to characterize the functional role of neural oscillations in nonverbal emotion perception. Findings from the reviewed literature suggest that theta band oscillations most consistently differentiate between emotional and neutral expressions. While early theta synchronization appears to reflect the initial encoding of emotionally salient sensory information, later fronto-central theta synchronization may reflect the further integration of sensory information with internal representations. Additionally, gamma synchronization reflects facilitated sensory binding of emotional expressions within regions such as the OFC, STS, and, potentially, the amygdala. However, the evidence is more ambiguous when it comes to the role of oscillations within the alpha and beta frequencies, which vary as a function of modality (or modalities), presence or absence of predictive information, and attentional or task demands. Thus, the synchronization of neural oscillations within specific frequency bands mediates the rapid detection, integration, and evaluation of emotional expressions. Moreover, the functional coupling of oscillatory activity across multiples

The Functional Role of Neural Oscillations in Non-Verbal Emotional Communication.

PubMed

Symons, Ashley E; El-Deredy, Wael; Schwartze, Michael; Kotz, Sonja A

2016-01-01

Effective interpersonal communication depends on the ability to perceive and interpret nonverbal emotional expressions from multiple sensory modalities. Current theoretical models propose that visual and auditory emotion perception involves a network of brain regions including the primary sensory cortices, the superior temporal sulcus (STS), and orbitofrontal cortex (OFC). However, relatively little is known about how the dynamic interplay between these regions gives rise to the perception of emotions. In recent years, there has been increasing recognition of the importance of neural oscillations in mediating neural communication within and between functional neural networks. Here we review studies investigating changes in oscillatory activity during the perception of visual, auditory, and audiovisual emotional expressions, and aim to characterize the functional role of neural oscillations in nonverbal emotion perception. Findings from the reviewed literature suggest that theta band oscillations most consistently differentiate between emotional and neutral expressions. While early theta synchronization appears to reflect the initial encoding of emotionally salient sensory information, later fronto-central theta synchronization may reflect the further integration of sensory information with internal representations. Additionally, gamma synchronization reflects facilitated sensory binding of emotional expressions within regions such as the OFC, STS, and, potentially, the amygdala. However, the evidence is more ambiguous when it comes to the role of oscillations within the alpha and beta frequencies, which vary as a function of modality (or modalities), presence or absence of predictive information, and attentional or task demands. Thus, the synchronization of neural oscillations within specific frequency bands mediates the rapid detection, integration, and evaluation of emotional expressions. Moreover, the functional coupling of oscillatory activity across multiples

Nitric oxide and S-nitrosoglutathione function additively during plant immunity.

PubMed

Yun, Byung-Wook; Skelly, Michael J; Yin, Minghui; Yu, Manda; Mun, Bong-Gyu; Lee, Sang-Uk; Hussain, Adil; Spoel, Steven H; Loake, Gary J

2016-07-01

Nitric oxide (NO) is emerging as a key regulator of diverse plant cellular processes. A major route for the transfer of NO bioactivity is S-nitrosylation, the addition of an NO moiety to a protein cysteine thiol forming an S-nitrosothiol (SNO). Total cellular levels of protein S-nitrosylation are controlled predominantly by S-nitrosoglutathione reductase 1 (GSNOR1) which turns over the natural NO donor, S-nitrosoglutathione (GSNO). In the absence of GSNOR1 function, GSNO accumulates, leading to dysregulation of total cellular S-nitrosylation. Here we show that endogenous NO accumulation in Arabidopsis, resulting from loss-of-function mutations in NO Overexpression 1 (NOX1), led to disabled Resistance (R) gene-mediated protection, basal resistance and defence against nonadapted pathogens. In nox1 plants both salicylic acid (SA) synthesis and signalling were suppressed, reducing SA-dependent defence gene expression. Significantly, expression of a GSNOR1 transgene complemented the SNO-dependent phenotypes of paraquat resistant 2-1 (par2-1) plants but not the NO-related characters of the nox1-1 line. Furthermore, atgsnor1-3 nox1-1 double mutants supported greater bacterial titres than either of the corresponding single mutants. Our findings imply that GSNO and NO, two pivotal redox signalling molecules, exhibit additive functions and, by extension, may have distinct or overlapping molecular targets during both immunity and development. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

How Understanding the Role of an Additive Can Lead to an Improved Synthetic Protocol without an Additive: Organocatalytic Synthesis of Chiral Diarylmethyl Alkynes.

PubMed

Chen, Min; Sun, Jianwei

2017-09-18

The use of additives for organic synthesis has become a common tactic to improve the outcome of organic reactions. Herein, by using an organocatalytic process for the synthesis of chiral diarylmethyl alkynes as a platform, we describe how an additive is involved in the improvement of the process. The evolution of an excellent synthetic protocol has been achieved in three stages, from 1) initially no catalyst turnover, to 2) good conversion and enantioselectivity with a superior additive, and eventually 3) even better efficiency and selectivity without an additive. This study is an important and rare demonstration that understanding the role of additive can be so beneficial as to obviate the need for the additive. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alumina Matrix Composites with Non-Oxide Nanoparticle Addition and Enhanced Functionalities

PubMed Central

Galusek, Dušan; Galusková, Dagmar

2015-01-01

The addition of SiC or TiC nanoparticles to polycrystalline alumina matrix has long been known as an efficient way of improving the mechanical properties of alumina-based ceramics, especially strength, creep, and wear resistance. Recently, new types of nano-additives, such as carbon nanotubes (CNT), carbon nanofibers (CNF), and graphene sheets have been studied in order not only to improve the mechanical properties, but also to prepare materials with added functionalities, such as thermal and electrical conductivity. This paper provides a concise review of several types of alumina-based nanocomposites, evaluating the efficiency of various preparation methods and additives in terms of their influence on the properties of composites. PMID:28347002

ROLE OF TYROSINE-SULFATED PROTEINS IN RETINAL STRUCTURE AND FUNCTION

PubMed Central

Kanan, Y.; Al-Ubaidi, M.R.

2014-01-01

The extracellular matrix (ECM) plays a significant role in cellular and retinal health. The study of retinal tyrosine-sulfated proteins is an important first step toward understanding the role of ECM in retinal health and diseases. These secreted proteins are members of the retinal ECM. Tyrosine sulfation was shown to be necessary for the development of proper retinal structure and function. The importance of tyrosine sulfation is further demonstrated by the evolutionary presence of tyrosylprotein sulfotransferases, enzymes that catalyze proteins’ tyrosine sulfation, and the compensatory abilities of these enzymes. Research has identified four tyrosine-sulfated retinal proteins: fibulin 2, vitronectin, complement factor H (CFH), and opticin. Vitronectin and CFH regulate the activation of the complement system and are involved in the etiology of some cases of age-related macular degeneration. Analysis of the role of tyrosine sulfation in fibulin function showed that sulfation influences the protein's ability to regulate growth and migration. Although opticin was recently shown to exhibit anti-angiogenic properties, it is not yet determined what role sulfation plays in that function. Future studies focusing on identifying all of the tyrosine-sulfated retinal proteins would be instrumental in determining the impact of sulfation on retinal protein function in retinal homeostasis and diseases. PMID:25819460

A Genome-Wide Functional Investigation into the Roles of Receptor-Like Proteins in Arabidopsis1[W][OA

PubMed Central

Wang, Guodong; Ellendorff, Ursula; Kemp, Ben; Mansfield, John W.; Forsyth, Alec; Mitchell, Kathy; Bastas, Kubilay; Liu, Chun-Ming; Woods-Tör, Alison; Zipfel, Cyril; de Wit, Pierre J.G.M.; Jones, Jonathan D.G.; Tör, Mahmut; Thomma, Bart P.H.J.

2008-01-01

Receptor-like proteins (RLPs) are cell surface receptors that typically consist of an extracellular leucine-rich repeat domain, a transmembrane domain, and a short cytoplasmatic tail. In several plant species, RLPs have been found to play a role in disease resistance, such as the tomato (Solanum lycopersicum) Cf and Ve proteins and the apple (Malus domestica) HcrVf2 protein that mediate resistance against the fungal pathogens Cladosporium fulvum, Verticillium spp., and Venturia inaequalis, respectively. In addition, RLPs play a role in plant development; Arabidopsis (Arabidopsis thaliana) TOO MANY MOUTHS (TMM) regulates stomatal distribution, while Arabidopsis CLAVATA2 (CLV2) and its functional maize (Zea mays) ortholog FASCINATED EAR2 regulate meristem maintenance. In total, 57 RLP genes have been identified in the Arabidopsis genome and a genome-wide collection of T-DNA insertion lines was assembled. This collection was functionally analyzed with respect to plant growth and development and sensitivity to various stress responses, including susceptibility toward pathogens. A number of novel developmental phenotypes were revealed for our CLV2 and TMM insertion mutants. In addition, one AtRLP gene was found to mediate abscisic acid sensitivity and another AtRLP gene was found to influence nonhost resistance toward Pseudomonas syringae pv phaseolicola. This genome-wide collection of Arabidopsis RLP gene T-DNA insertion mutants provides a tool for future investigations into the biological roles of RLPs. PMID:18434605

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction.

PubMed

Podlasek, Carol A; Mulhall, John; Davies, Kelvin; Wingard, Christopher J; Hannan, Johanna L; Bivalacqua, Trinity J; Musicki, Biljana; Khera, Mohit; González-Cadavid, Nestor F; Burnett, Arthur L

2016-08-01

The biological importance of testosterone is generally accepted by the medical community; however, controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. To provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Testosterone plays an important role in sexual function through multiple processes: physiologic (stimulates activity of nitric oxide synthase), developmental (establishes and maintains the structural and functional integrity of the penis), neural (development, maintenance, function, and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes, and prostatectomy), and phosphodiesterase type 5 inhibition (testosterone supplement to counteract phosphodiesterase type 5 inhibitor resistance). Despite controversies concerning testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction. Published by Elsevier Inc.

The Role and Function of Presidential Libraries.

ERIC Educational Resources Information Center

Fischer, Linda

This paper identifies various elements of presidential libraries. The advantages and disadvantages of the libraries' centralization or decentralization are discussed, and some common misconceptions held by the public as to the role and function of presidential libraries are identified. Criticism and debate from the professional community about…

Syntactic Functions in Functional Discourse Grammar and Role and Reference Grammar: An Evaluative Comparison

ERIC Educational Resources Information Center

Butler, Christopher S.

2012-01-01

The aim of this paper is to compare the treatment of syntactic functions, and more particularly those traditionally labelled as Subject and Object, in Functional Discourse Grammar and Role and Reference Grammar. Relevant aspects of the overall structure of the two theories are briefly described. The concept of alignment between levels of the…

Morphology predicts species' functional roles and their degree of specialization in plant-frugivore interactions.

PubMed

Dehling, D Matthias; Jordano, Pedro; Schaefer, H Martin; Böhning-Gaese, Katrin; Schleuning, Matthias

2016-01-27

Species' functional roles in key ecosystem processes such as predation, pollination or seed dispersal are determined by the resource use of consumer species. An interaction between resource and consumer species usually requires trait matching (e.g. a congruence in the morphologies of interaction partners). Species' morphology should therefore determine species' functional roles in ecological processes mediated by mutualistic or antagonistic interactions. We tested this assumption for Neotropical plant-bird mutualisms. We used a new analytical framework that assesses a species's functional role based on the analysis of the traits of its interaction partners in a multidimensional trait space. We employed this framework to test (i) whether there is correspondence between the morphology of bird species and their functional roles and (ii) whether morphologically specialized birds fulfil specialized functional roles. We found that morphological differences between bird species reflected their functional differences: (i) bird species with different morphologies foraged on distinct sets of plant species and (ii) morphologically distinct bird species fulfilled specialized functional roles. These findings encourage further assessments of species' functional roles through the analysis of their interaction partners, and the proposed analytical framework facilitates a wide range of novel analyses for network and community ecology. © 2016 The Author(s).

Roles and Functions of the Psychologist in Special Education.

ERIC Educational Resources Information Center

Hestick, Henrietta

The paper, intended for a Chinese audience, examines roles and functions of the school psychologist in special education in the United States in the context of federal and state (Maryland) legislation and in correctional institutions. Some of the minimum roles of the school psychologist are to serve on the preplacement team, conduct student…

Roles and Functions of Community Health Workers in Primary Care.

PubMed

Hartzler, Andrea L; Tuzzio, Leah; Hsu, Clarissa; Wagner, Edward H

2018-05-01

Community health workers have potential to enhance primary care access and quality, but remain underutilized. To provide guidance on their integration, we characterized roles and functions of community health workers in primary care through a literature review and synthesis. Analysis of 30 studies identified 12 functions (ie, care coordination, health coaching, social support, health assessment, resource linking, case management, medication management, remote care, follow-up, administration, health education, and literacy support) and 3 prominent roles representing clusters of functions: clinical services, community resource connections, and health education and coaching. We discuss implications for community health worker training and clinical support in primary care. © 2018 Annals of Family Medicine, Inc.

The roles of sensory function and cognitive load in age differences in inhibition: Evidence from the Stroop task.

PubMed

Peng, Huamao; Gao, Yue; Mao, Xiaofei

2017-02-01

To explore the roles of visual function and cognitive load in aging of inhibition, the present study adopted a 2 (visual perceptual stress: noise, nonnoise) × 2 (cognitive load: low, high) × 2 (age: young, old) mixed design. The Stroop task was adopted to measure inhibition. The task presentation was masked with Gaussian noise according to the visual function of each individual in order to match visual perceptual stress between age groups. The results indicated that age differences in the Stroop effect were influenced by visual function and cognitive load. When the cognitive load was low, older adults exhibited a larger Stroop effect than did younger adults in the nonnoise condition, and this age difference disappeared when the visual noise of the 2 age groups was matched. Conversely, in the high cognitive load condition, we observed significant age differences in the Stroop effect in both the nonnoise and noise conditions. The additional cognitive load made the age differences in the Stroop task reappear even when visual perceptual stress was equivalent. These results demonstrate that visual function plays an important role in the aging of inhibition and its role is moderated by cognitive load. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome.

PubMed

Santana-Gálvez, Jesús; Cisneros-Zevallos, Luis; Jacobo-Velázquez, Daniel A

2017-02-26

Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from thehydroxycinnamic acid family. This polyphenol possesses many health-promoting properties, mostof them related to the treatment of metabolic syndrome, including anti-oxidant, anti-inflammatory,antilipidemic, antidiabetic, and antihypertensive activities. The first part of this review will discussthe role of chlorogenic acid as a nutraceutical for the prevention and treatment of metabolicsyndrome and associated disorders, including in vivo studies, clinical trials, and mechanisms ofaction. The second part of the review will be dealing with the role of chlorogenic acid as a foodadditive. Chlorogenic acid has shown antimicrobial activity against a wide range of organisms,including bacteria, yeasts, molds, viruses, and amoebas. These antimicrobial properties can beuseful for the food industry in its constant search for new and natural molecules for thepreservation of food products. In addition, chlorogenic acid has antioxidant activity, particularlyagainst lipid oxidation; protective properties against degradation of other bioactive compoundspresent in food, and prebiotic activity. The combination of these properties makes chlorogenic acidan excellent candidate for the formulation of dietary supplements and functional foods.

[Roles of additives and surface control in slurry atomization

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

Tsai, S.C.

1992-06-01

As reported in the quarterly report of March of 1992, the relative viscosity of a Newtonian Coal Water Slurry (CWS) in the presence of an anionic polymeric dispersant is an order of magnitude higher than the prediction of the well established Krieger-Dougherty Equation which describes the relative viscosity of a non-aggregated Newtonian suspension as a function of particle volume fraction. Note that the anionic dispersant is used in such a quantity that the resulting interparticle electrostatic repulsion counter-balances the interparticle van der Waals attraction. Investigation continues to determine the mechanisms of such excess energy dissipation under shear. New experimental resultsmore » are presented in this report to verify the role of the anionic polymeric dispersant in such excess energy dissipation of CWS.« less

The Role of Glia in Sleep Regulation and Function.

PubMed

Frank, Marcos G

2018-01-28

The cellular mechanisms governing the expression, regulation, and function of sleep are not entirely understood. The traditional view is that these mechanisms are neuronal. An alternative view is that glial brain cells may play important roles in these processes. Their ubiquity in the central nervous system makes them well positioned to modulate neuronal circuits that gate sleep and wake. Their ability to respond to chemical neuronal signals suggests that they form feedback loops with neurons that may globally regulate neuronal activity. Their potential role in detoxifying the brain, regulating neuronal metabolism, and promoting synaptic plasticity raises the intriguing possibility that glia mediate important functions ascribed to sleep.

THE ROLE OF SEROTONIN IN RESPIRATORY FUNCTION AND DYSFUNCTION

PubMed Central

Hilaire, Gérard; Voituron, Nicolas; Menuet, Clément; Ichiyama, Ronaldo M.; Subramanian, Hari H.; Dutschmann, Mathias

2010-01-01

Serotonin (5-HT) is a neuro-modulator–transmitter influencing global brain function. Past and present findings illustrate a prominent role for 5-HT in the modulation of ponto-medullary autonomic circuits. 5-HT is also involved in the control of neurotrophic processes during pre- and postnatal development of neural circuits. The functional implications of 5-HT is particularly illustrated in the alterations to the serotonergic system, as seen in a wide range of neurological disorders. This article reviews the role of 5-HT in the development and control of respiratory networks in the ponto-medullary brainstem. The review further examines the role of 5-HT in breathing disorders occurring at different stages of life, in particular, the neonatal neurodevelopmental diseases such as Rett, sudden infant death and Prader-Willi syndromes, adult diseases such as sleep apnoea and mental illness linked to neurodegeneration. PMID:20801236

The Use of Additive Manufacturing for Fabrication of Multi-Function Small Satellite Structures

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

Horais, Brian J; Love, Lonnie J; Dehoff, Ryan R

2013-01-01

The use of small satellites in constellations is limited only by the growing functionality of smallsats themselves. Additive manufacturing provides exciting new design opportunities for development of multifunction CubeSat structures that integrate such functions as propulsion and thermal control into the satellite structures themselves. Manufacturing of these complex multifunction structures is now possible in lightweight, high strength, materials such as titanium by using existing electron beam melting additive manufacturing processes. However, the use of today's additive manufacturing capabilities is often cost-prohibitive for small companies due to the large capital investments required. To alleviate this impediment the U.S. Department of Energymore » has established a Manufacturing Demonstration Facility (MDF) at their Oak Ridge National Laboratory (ORNL) in Tennessee that provides industry access to a broad range of energy-efficient additive manufacturing equipment for collaborative use by both small and large organizations. This paper presents a notional CubeSat multifunction design that integrates the propulsion system into a three-unit (3U) CubeSat structure. The full-scale structure has been designed and fabricated at the ORNL MDF. The use of additive manufacturing for spacecraft fabrication is opening up many new possibilities in design and fabrication capabilities for what had previously been impossible structures to fabricate.« less

The Effect of Small Molecule Additives on the Self-Assembly and Functionality of Protein-Polymer Diblock Copolymers

NASA Astrophysics Data System (ADS)

Thomas, Carla; Xu, Liza; Olsen, Bradley

2013-03-01

Self-assembly of globular protein-polymer block copolymers into well-defined nanostructures provides a route towards the manufacture of protein-based materials which maintains protein fold and function. The model material mCherry-b-poly(N-isopropyl acrylamide) forms self-assembled nanostructures from aqueous solutions via solvent evaporation. To improve retention of protein functionality when dehydrated, small molecules such as trehalose and glycerol are added in solution prior to solvent removal. With as little as 10 wt% additive, improvements in retained functionality of 20-60% are observed in the solid-state as compared to samples in which no additive is present. Higher additive levels (up to 50%) continue to show improvement until approximately 100% of the protein function is retained. These large gains are hypothesized to originate from the ability of the additives to replace hydrogen bonds normally fulfilled by water. The addition of trehalose in the bulk material also improves the thermal stability of the protein by 15-20 °C, while glycerol decreases the thermal stability. Materials containing up to 50% additives remain microphase separated, and, upon incorporation of additives, nanostructure domain spacing tends to increase, accompanied by order-order transitions.

Stability of a general mixed additive-cubic functional equation in non-Archimedean fuzzy normed spaces

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

Xu Tianzhou; Rassias, John Michael; Xu Wanxin

2010-09-15

We establish some stability results concerning the general mixed additive-cubic functional equation in non-Archimedean fuzzy normed spaces. In addition, we establish some results of approximately general mixed additive-cubic mappings in non-Archimedean fuzzy normed spaces. The results improve and extend some recent results.

On the role of block copolymer additives for calcium carbonate crystallization: small angle neutron scattering investigation by applying contrast variation.

PubMed

Endo, Hitoshi; Schwahn, Dietmar; Cölfen, Helmut

2004-05-15

The role of the double-hydrophilic block copolymer poly(ethylen glycol)-block-poly(methacrylic acid) (PEG-b-PMAA) on the morphogenesis of calcium carbonate (CaCO3) was studied by applying the contrast variation small angle neutron scattering technique. The morphology and size of CaCO3 crystals is strongly affected by the addition of PEG-b-PMAA. In order to determine the partial scattering functions of the polymer and CaCO3 mineral, we developed both an experimental and theoretical approach with a sophisticated method of their determination from the scattering intensity. Partial scattering functions give detailed information for each component. In particular, the partial scattering function of the polymer, Spp, shows a monotonic slope with Q(-2 to -3) where the scattering vector Q is low (Q < 0.01 Angstrom(-1)), which is a clear evidence that the polymer within the CaCO3 mineral has a mass fractal dimension. The other partial scattering functions reflected the geometry of the CaCO3 particles or the "interaction" of polymer and CaCO3 on a microscopic scale, which leads to a coherent view with Spp.

Prenatal alcohol exposure, adaptive function, and entry into adult roles in a prospective study of young adults.

PubMed

Lynch, Mary Ellen; Kable, Julie A; Coles, Claire D

2015-01-01

Although many studies have demonstrated effects of prenatal alcohol exposure (PAE) on physical, cognitive, and behavioral development in children, few have focused on the long term effects on adults. In this study, data are presented on adaptive function and entry into adult roles in a community sample of young adults with PAE. The expectation was that prenatally exposed adults would show lower adaptive functioning and more difficulty with entry into adult roles than the non-exposed control group and that these effects would be related to the severity of PAE effects. The predominantly African-American, low income sample included adults with a wide range of prenatal exposure (n = 123) as well as control groups for socioeconomic (SES) (n =5 9) and disability (n = 54) status. The mothers of the alcohol-exposed and SES-control group participants were recruited before birth and offspring have been followed up periodically. The disability control group was recruited in adolescence. The adults were interviewed about adaptive function in day-to-day life and adult role entry. Collateral adults who were well-acquainted with each participant were interviewed concerning adaptive function. Results showed that adults who were dysmorphic and/or cognitively affected by PAE had difficulty with adaptive function and entry into adult roles. Males showing cognitive effects with no physical effects were the most severely affected. Results for exposed adults not showing physical or cognitive effects were similar to or more positive than those of the control group for most outcomes. PAE has long-term effects on adaptive outcomes in early adulthood. Additional research should focus on possible interventions at this transition and on factors contributing to the adjustment of the exposed, but unaffected participants. Copyright © 2015 Elsevier Inc. All rights reserved.

Movement dynamics reflect a functional role for weak coupling and role structure in dyadic problem solving.

PubMed

Abney, Drew H; Paxton, Alexandra; Dale, Rick; Kello, Christopher T

2015-11-01

Successful interaction requires complex coordination of body movements. Previous research has suggested a functional role for coordination and especially synchronization (i.e., time-locked movement across individuals) in different types of human interaction contexts. Although such coordination has been shown to be nearly ubiquitous in human interaction, less is known about its function. One proposal is that synchrony supports and facilitates communication (Topics Cogn Sci 1:305-319, 2009). However, questions still remain about what the properties of coordination for optimizing communication might look like. In the present study, dyads worked together to construct towers from uncooked spaghetti and marshmallows. Using cross-recurrence quantification analysis, we found that dyads with loosely coupled gross body movements performed better, supporting recent work suggesting that simple synchrony may not be the key to effective performance (Riley et al. 2011). We also found evidence that leader-follower dynamics-when sensitive to the specific role structure of the interaction-impact task performance. We discuss our results with respect to the functional role of coordination in human interaction.

The Role of Inhibitory Control in Behavioral and Physiological Expressions of Toddler Executive Function

PubMed Central

Morasch, Katherine C.; Bell, Martha Ann

2010-01-01

Eighty-one toddlers (ranging from 24 to 27 months) participated in a biobehavioral investigation of inhibitory control. Maternal-report measures of inhibitory control were related to laboratory tasks assessing inhibitory abilities under conditions of conflict, delay, and compliance challenge as well as toddler verbal ability. Additionally, unique variance in inhibitory control was explained by task-related changes in brain electrical activity at lateral frontal scalp sites as well as concurrent inhibitory task performance. Implications regarding neural correlates of executive function in early development and a central, organizing role of inhibitory processing in toddlerhood are discussed. PMID:20719337

The role of dehydroepiandrosterone on functional innate immune responses to acute stress.

PubMed

Prall, Sean P; Larson, Emilee E; Muehlenbein, Michael P

2017-12-01

The androgen dehydroepiandrosterone (DHEA) responds to stress activation, exhibits anti-glucocorticoid properties, and modulates immunity in diverse ways, yet little is known of its role in acute stress responses. In this study, the effects of DHEA and its sulfate ester DHEA-S on human male immune function during exposure to an acute stressor is explored. Variation in DHEA, DHEA-S, testosterone, and cortisol, along with bacterial killing assays, was measured in response to a modified Trier Social Stress test in 27 young adult males. Cortisol was positively related to salivary innate immunity but only for participants who also exhibited high DHEA responses. Additionally, DHEA positively and DHEA-S negatively predicted salivary immunity, but the opposite was observed for serum-based innate immunity. The DHEA response to acute stress appears to be an important factor in stress-mediated immunological responses, with differential effects on immunity dependent upon the presence of other hormones, primarily cortisol and DHEA-S. These results suggest that DHEA plays an important role, alongside other hormones, in modulating immunological shifts during acute stress. Copyright © 2017 John Wiley & Sons, Ltd.

Functional role of adult hippocampal neurogenesis as a therapeutic strategy for mental disorders.

PubMed

Jun, Heechul; Mohammed Qasim Hussaini, Syed; Rigby, Michael J; Jang, Mi-Hyeon

2012-01-01

Adult neurogenesis, the process of generating new neurons from neural stem cells, plays significant roles in synaptic plasticity, memory, and mood regulation. In the mammalian brain, it continues to occur well into adulthood in discrete regions, namely, the hippocampus and olfactory bulb. During the past decade, significant progress has been made in understanding the mechanisms regulating adult hippocampal neurogenesis and its role in the etiology of mental disorders. In addition, adult hippocampal neurogenesis is highly correlated with the remission of the antidepressant effect. In this paper, we discuss three major psychiatric disorders, depression, schizophrenia, and drug addiction, in light of preclinical evidence used in establishing the neurobiological significance of adult neurogenesis. We interpret the significance of these results and pose questions that remain unanswered. Potential treatments which include electroconvulsive therapy, deep brain stimulation, chemical antidepressants, and exercise therapy are discussed. While consensus lacks on specific mechanisms, we highlight evidence which indicates that these treatments may function via an increase in neural progenitor proliferation and changes to the hippocampal circuitry. Establishing a significant role of adult neurogenesis in the pathogenicity of psychiatric disorders may hold the key to potential strategies toward effective treatment.

Left atrial size and function: role in prognosis.

PubMed

Hoit, Brian D

2014-02-18

The author examines the ability of left atrial size and function to predict cardiovascular outcomes. Data are sufficient to recommend evaluation of left atrial volume in certain populations, and although analysis of atrial reservoir, conduit, and booster pump function trails in that regard, the gap is rapidly closing. In this state-of-the-art paper, the author reviews the methods used to assess left atrial size and function and discusses their role in predicting cardiovascular events in general and referral populations and in patients with atrial fibrillation, cardiomyopathy, ischemic heart disease, and valvular heart disease. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nuclear speckles: molecular organization, biological function and role in disease

PubMed Central

Galganski, Lukasz; Urbanek, Martyna O.

2017-01-01

Abstract The nucleoplasm is not homogenous; it consists of many types of nuclear bodies, also known as nuclear domains or nuclear subcompartments. These self-organizing structures gather machinery involved in various nuclear activities. Nuclear speckles (NSs) or splicing speckles, also called interchromatin granule clusters, were discovered as sites for splicing factor storage and modification. Further studies on transcription and mRNA maturation and export revealed a more general role for splicing speckles in RNA metabolism. Here, we discuss the functional implications of the localization of numerous proteins crucial for epigenetic regulation, chromatin organization, DNA repair and RNA modification to nuclear speckles. We highlight recent advances suggesting that NSs facilitate integrated regulation of gene expression. In addition, we consider the influence of abundant regulatory and signaling proteins, i.e. protein kinases and proteins involved in protein ubiquitination, phosphoinositide signaling and nucleoskeletal organization, on pre-mRNA synthesis and maturation. While many of these regulatory proteins act within NSs, direct evidence for mRNA metabolism events occurring in NSs is still lacking. NSs contribute to numerous human diseases, including cancers and viral infections. In addition, recent data have demonstrated close relationships between these structures and the development of neurological disorders. PMID:28977640

Executive function moderates the role of muscular fitness in determining functional mobility in older adults.

PubMed

Forte, Roberta; Pesce, Caterina; Leite, Joao Costa; De Vito, Giuseppe; Gibney, Eileen R; Tomporowski, Phillip D; Boreham, Colin A G

2013-06-01

Both physical and cognitive factors are known to independently predict functional mobility in older people. However, the combined predictive value of both physical fitness and cognitive factors on functional mobility has been less investigated. The aim of the present study was to assess if cognitive executive functions moderate the role of physical fitness in determining functional mobility of older individuals. Fifty-seven 65- to 75-year-old healthy participants performed tests of functional mobility (habitual and maximal walking speed, maximal walking speed while picking up objects/stepping over obstacles), physical fitness (peak power, knee extensors torque, back/lower limb flexibility, aerobic fitness), and executive function (inhibition and cognitive flexibility). Maximal walking speeds were predicted by physical fitness parameters and their interaction with cognitive factors. Knee extensor torque emerged as the main predictor of all tested locomotor performances at maximal speed. The effect of peak power and back/lower limb flexibility was moderated by executive functions. In particular, inhibition and cognitive flexibility differed in the way in which they moderate the role of fitness. High levels of cognitive flexibility seem necessary to take advantage of leg power for walking at maximal speed. In contrast, high levels of inhibitory capacity seem to compensate for low levels of back/lower limb flexibility when picking up movements are added to a locomotor task. These findings may have important practical implications for the design and implementation of multi-component training programs aimed at optimizing functional abilities in older adults.

Roles of additives and surface control in slurry atomization. Final project report

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

Tsai, S.C.

1992-12-31

This project studies the rheology and airblast atomization of micronized coal slurries. Its major objectives are (1) to promote further understanding of the mechanisms and the roles of additives in airblast atomization of coal water slurry (CWS), and (2) to investigate the impacts of coal particle surface properties and interparticle forces on CWS rheology. We have found that the flow behavior index (n) of a suspension (or slurry) is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The interparticle attraction, measured by the Hamaker constant scaled to the thermal energy atmore » 25{degrees}C (A/kT), causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior (n< 1). At a constant particle volume fraction and surface charge density (qualitatively measured by the zeta potential in deionized water), n decreases linearly as A/kT increases. The relative viscosity of the pseudoplastic suspension with respect to that of the suspending liquid is found to be independent of particle density and correlate well with the particle Peclet number which equals the particle diffusional relaxation time multiplied by shear rate. Specifically, the relative viscosities of the pseudoplastic glycerol/water coal slurry and the ethylene glycol/glycerol sand slurry, at same volume fractions as well as similar particle size distributions and liquid viscosities, as functions of the particle Peclet number fall along the same line.« less

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Separable roles of UFO during floral development revealed by conditional restoration of gene function.

PubMed

Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

2003-02-01

The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

The role of natural color additives in food allergy.

PubMed

Lucas, C D; Hallagan, J B; Taylor, S L

2001-01-01

A critical evaluation of the available information demonstrates that reactions to natural color additives are rare. Studies of turmeric and carotenoid pigments administered in mixtures with other food colorings failed to definitely identify reactions to either color additive. For carotenoids, the one case report of an adverse reaction was not conclusive. An anaphylactic reaction to saffron does suggest an IgE-mediated reaction, but the high use of saffron as compared with this single report of an adverse reaction suggests that sensitivity to saffron is extremely rare. Numerous reports of reactions to grapes or grape products have been reported in the literature, but no reports of sensitivities to grape skin extract or grape color extract were found. In rare cases, annatto dye may provoke a severe, adverse reaction in individuals with an uncommon hypersensitivity, and may aggravate the symptoms of patients suffering from recurrent urticaria. In its long history of use, there has been only one reported case of anaphylaxis resulting from the ingestion of annatto. Studies designed to investigate the role of annatto in recurrent urticaria sufferers were limited due to the absence of double-blind challenge and placebo controls. A number of cases of adverse reactions to carmine following ingestion have been reported in the literature. These adverse reactions suggest an IgE-mediated hypersensitivity. In many of the reported cases, the cause of sensitization to carmine was topical exposure from the use of carmine-containing cosmetics or occupational exposure to carmine and not from ingestion of carmine-containing foods and beverages. Following sensitization, affected individuals would be sensitive to carmine and the amounts present in foods and beverages could elicit allergic reactions. It is not known whether all individuals with carmine sensitivity induced through topical use are sensitive to the ingestion of carmine in foods. However, reactions to carmine solely because

The Role of Noise in Brain Function

NASA Astrophysics Data System (ADS)

Roy, S.; Llinás, R.

2012-12-01

Noise plays a fundamental role in all living organisms from the earliest prokaryotes to advanced mammalian forms, such as ourselves. In the context of living organisms, the term 'noise' usually refers to the variance amongst measurements obtained from repeated identical experimental conditions, or from output signals from these systems. It is noteworthy that both these conditions are universally characterized by the presence of background fluctuations. In non-biological systems, such as electronics or in communications sciences, where the aim is to send error-free messages, noise was generally regarded as a problem. The discovery of Stochastic Resonances (SR) in non-linear dynamics brought a shift of perception where noise, rather than representing a problem, became fundamental to system function, especially so in biology. The question now is: to what extent is biological function dependent on random noise. Indeed, it seems feasible that noise also plays an important role in neuronal communication and oscillatory synchronization. Given this approach, it follows that determining Fisher information content could be relevant in neuronal communication. It also seems possible that the principle of least time, and that of the sum over histories, could be important basic principles in understanding the coherence dynamics responsible for action and perception. Ultimately, external noise cancellation combined with intrinsic noise signal embedding and, the use of the principle of least time may be considered an essential step in the organization of central nervous system (CNS) function.

Development of an item bank and computer adaptive test for role functioning.

PubMed

Anatchkova, Milena D; Rose, Matthias; Ware, John E; Bjorner, Jakob B

2012-11-01

Role functioning (RF) is a key component of health and well-being and an important outcome in health research. The aim of this study was to develop an item bank to measure impact of health on role functioning. A set of different instruments including 75 newly developed items asking about the impact of health on role functioning was completed by 2,500 participants. Established item response theory methods were used to develop an item bank based on the generalized partial credit model. Comparison of group mean bank scores of participants with different self-reported general health status and chronic conditions was used to test the external validity of the bank. After excluding items that did not meet established requirements, the final item bank consisted of a total of 64 items covering three areas of role functioning (family, social, and occupational). Slopes in the bank ranged between .93 and 4.37; the mean threshold range was -1.09 to -2.25. Item bank-based scores were significantly different for participants with and without chronic conditions and with different levels of self-reported general health. An item bank assessing health impact on RF across three content areas has been successfully developed. The bank can be used for development of short forms or computerized adaptive tests to be applied in the assessment of role functioning as one of the common denominators across applications of generic health assessment.

Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function

PubMed Central

Neve, Bernadette; Fernandez-Zapico, Martin E.; Ashkenazi-Katalan, Vered; Dina, Christian; Hamid, Yasmin H.; Joly, Erik; Vaillant, Emmanuel; Benmezroua, Yamina; Durand, Emmanuelle; Bakaher, Nicolas; Delannoy, Valerie; Vaxillaire, Martine; Cook, Tiffany; Dallinga-Thie, Geesje M.; Jansen, Hans; Charles, Marie-Aline; Clément, Karine; Galan, Pilar; Hercberg, Serge; Helbecque, Nicole; Charpentier, Guillaume; Prentki, Marc; Hansen, Torben; Pedersen, Oluf; Urrutia, Raul; Melloul, Danielle; Froguel, Philippe

2005-01-01

KLF11 (TIEG2) is a pancreas-enriched transcription factor that has elicited significant attention because of its role as negative regulator of exocrine cell growth in vitro and in vivo. However, its functional role in the endocrine pancreas remains to be established. Here, we report, for the first time, to our knowledge, the characterization of KLF11 as a glucose-inducible regulator of the insulin gene. A combination of random oligonucleotide binding, EMSA, luciferase reporter, and chromatin immunoprecipitation assays shows that KLF11 binds to the insulin promoter and regulates its activity in beta cells. Genetic analysis of the KLF11 gene revealed two rare variants (Ala347Ser and Thr220Met) that segregate with diabetes in families with early-onset type 2 diabetes, and significantly impair its transcriptional activity. In addition, analysis of 1,696 type 2 diabetes mellitus and 1,776 normoglycemic subjects show a frequent polymorphic Gln62Arg variant that significantly associates with type 2 diabetes mellitus in North European populations (OR = 1.29, P = 0.00033). Moreover, this variant alters the corepressor mSin3A-binding activity of KLF11, impairs the activation of the insulin promoter and shows lower levels of insulin expression in pancreatic beta cells. In addition, subjects carrying the Gln62Arg allele show decreased plasma insulin after an oral glucose challenge. Interestingly, all three nonsynonymous KLF11 variants show increased repression of the catalase 1 promoter, suggesting a role in free radical clearance that may render beta cells more sensitive to oxidative stress. Thus, both functional and genetic analyses reveal that KLF11 plays a role in the regulation of pancreatic beta cell physiology, and its variants may contribute to the development of diabetes. PMID:15774581

An essential role for IL-2 receptor in regulatory T cell function

PubMed Central

Levine, Andrew G; Fan, Xiying; Klein, Ulf; Zheng, Ye; Gasteiger, Georg; Feng, Yongqiang; Fontenot, Jason D.; Rudensky, Alexander Y.

2016-01-01

Regulatory T (Treg) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage specification factor Foxp3, confounding experimental efforts to understand the role of IL-2R expression and signaling in Treg suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4+ T cells, but is important for limiting CD8+ T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in Treg cell suppressor function separable from T cell receptor signaling. PMID:27595233

SCOP/PHLPP and its functional role in the brain.

PubMed

Shimizu, Kimiko; Mackenzie, Scott M; Storm, Daniel R

2010-01-01

SCOP (suprachiasmatic nucleus (SCN) circadian oscillatory protein) was originally identified in 1999 in a differential display screen of the rat SCN for genes whose expression were regulated in a circadian manner (K. Shimizu, M. Okada, A. Takano and K. Nagai, FEBS Lett., 1999, 458, 363-369). The SCN is the principle pacemaker of the circadian clock, and expression of SCOP protein in the SCN was found to oscillate, increasing during the subjective night, even when animals were housed in constant darkness. SCOP interacts with and inhibits multiple proteins important for intracellular signaling, either by directly binding to K-Ras or by dephosphorylating p-Akt and p-PKC. Since the functions of K-Ras, Akt, and PKC are considerably divergent, SCOP may have several roles. We recently discovered that SCOP participates in the formation of long-term hippocampus-dependent memories, and other investigators have examined its role in cell proliferation and survival. In this review, we introduce SCOP from its molecular structure to its physiological functions, focusing mainly on its role in ERK1/2 activation and memory consolidation.

SCOP/PHLPP and its functional role in the brain

PubMed Central

Shimizu, Kimiko; Mackenzie, Scott M.; Storm, Daniel R.

2012-01-01

SCOP (suprachiasmatic nucleus (SCN) circadian oscillatory protein) was originally identified in 1999 in a differential display screen of the rat SCN for genes whose expression were regulated in a circadian manner (K. Shimizu, M. Okada, A. Takano and K. Nagai, FEBS Lett., 1999, 458, 363–369). The SCN is the principle pacemaker of the circadian clock, and expression of SCOP protein in the SCN was found to oscillate, increasing during the subjective night, even when animals were housed in constant darkness. SCOP interacts with and inhibits multiple proteins important for intracellular signaling, either by directly binding to K-Ras or by dephosphorylating p-Akt and p-PKC. Since the functions of K-Ras, Akt, and PKC are considerably divergent, SCOP may have several roles. We recently discovered that SCOP participates in the formation of long-term hippocampus-dependent memories, and other investigators have examined its role in cell proliferation and survival. In this review, we introduce SCOP from its molecular structure to its physiological functions, focusing mainly on its role in ERK1/2 activation and memory consolidation. PMID:20024065

The Historical Role of the Production Function in Economics and Business

ERIC Educational Resources Information Center

Gordon, David; Vaughan, Richard

2011-01-01

The production function explains a basic technological relationship between scarce resources, or inputs, and output. This paper offers a brief overview of the historical significance and operational role of the production function in business and economics. The origin and development of this function over time is initially explored. Several…

Borderline intellectual functioning and sleep: the role of cyclic alternating pattern.

PubMed

Esposito, Maria; Carotenuto, Marco

2010-11-19

In the clinical literature there are few specific studies about the relationship between cognition processes and sleep during childhood. In addition, milder deficits in general intellectual capacity have received less attention relative to major cognitive dysfunctions (such as the genetic or environmental basis of mental retardation), especially concerning the low normal and borderline status. Sleep could play a key role in multiple intellectual abilities such as memory, executive functions, and school performances. Aim of our study is to assess the sleep macrostructure and NREM instability (cyclic alternating pattern) and their relationship with IQ in a sample of subjects with borderline intellectual functioning (BIF). The DSM-IV defines BIF as a total intelligence quotient (TIQ) ranging between 71 and 84. Intellective functioning was assessed using the Italian version of Wechsler Intelligence Scale for Children-Revised (WISC-R), a well validated test for the developmental age between 6 and 16. For this study, 12 BIF and 17 healthy children, matched for sex and age, underwent an overnight PSG recording. Macrostructural sleep and CAP analysis were also performed. To our knowledge, this study represents the first attempt to evaluate sleep architecture and NREM instability organization in children with BIF. Findings from this investigation evidence that BIF presents alterations in both macro- and microstructural sleep architecture, with an interesting statistical significant correlation with IQ. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Interactive effects between N addition and disturbance on boreal forest ecosystem structure and function

NASA Astrophysics Data System (ADS)

Nordin, Annika; Strengbom, Joachim; From, Fredrik

2014-05-01

In management of boreal forests, nitrogen (N) enrichment from atmospheric deposition or from forest fertilization can appear in combination with land-use related disturbances, i.e. tree harvesting by clear-felling. Long-term interactive effects between N enrichment and disturbance on boreal forest ecosystem structure and function are, however, poorly known. We investigated effects of N enrichment by forest fertilization done > 25 years ago on forest understory species composition in old-growth (undisturbed) forests, and in forests clear-felled 10 years ago (disturbed). In clear-felled forests we also investigated effects of the previous N addition on growth of tree saplings. The results show that the N enrichment effect on the understory species composition was strongly dependent on the disturbance caused by clear-felling. In undisturbed forests, there were small or no effects on understory species composition from N addition. In contrast, effects were large in forests first exposed to N addition and subsequently disturbed by clear-felling. Effects of N addition differed among functional groups of plants. Abundance of graminoids increased (+232%) and abundance of dwarf shrubs decreased (-44%) following disturbance in N fertilized forests. For vascular plants, the two perturbations had contrasting effects on α-(within forests) and β-diversity (among forests): in disturbed forests, N addition reduced, or had no effect on α-diversity, while β-diversity increased. For bryophytes, negative effects of disturbance on α-diversity were smaller in N fertilized forests than in forests not fertilized, while neither N addition nor disturbance had any effects on β-diversity. Moreover, sapling growth in forests clear-felled 10 years ago was significantly higher in previously N fertilized forests than in forests not fertilized. Our study show that effects of N addition on plant communities may appear small, short-lived, or even absent until exposed to a disturbance. This

Role and functions of beneficial microorganisms in sustainable aquaculture.

PubMed

Zhou, Qunlan; Li, Kangmin; Jun, Xie; Bo, Liu

2009-08-01

This paper aims to review the development of scientific concepts of microecology and ecology of microbes and the role and functions of beneficial microorganisms in aquaculture and mariculture. Beneficial microorganisms play a great role in natural and man-made aquatic ecosystems based on the co-evolution theory in living biosphere on earth. Their functions are to adjust algal population in water bodies so as to avoid unwanted algal bloom; to speed up decomposition of organic matter and to reduce CODmn, NH3-N and NO2-N in water and sediments so as to improve water quality; to suppress fish/shrimp diseases and water-borne pathogens; to enhance immune system of cultured aquatic animals and to produce bioactive compounds such as vitamins, hormones and enzymes that stimulate growth, thus to decrease the FCR of feed.

Gender differences in the roles and functions of inpatient psychiatric nurses.

PubMed

Torkelson, Diane J; Seed, Mary S

2011-03-01

This study explored the difference between male and female psychiatric nurses' job performance and job satisfaction levels on an acute care inpatient unit. The amount of time male (n = 28) and female (n = 45) nurses spent on 10 specific functions and roles during a shift were observed and recorded. The nurses also self-rated the amount of time they spent on these specific functions and roles. The observed and self-rated functions were then correlated with job satisfaction. Female nurses were observed and self-rated as spending significantly more time on patient care activities, and these activities were significantly correlated with higher job satisfaction levels. Male nurses who self-rated spending more time on patient care activities had significantly lower job satisfaction scores. Findings confirm the concepts from social role theory that gender identity and expectations influence job performance in psychiatric nursing. The results offer insight for increasing job satisfaction and recruitment/retention efforts. Copyright 2011, SLACK Incorporated.

Role of Gender, Sex Role Identity, and Type A Behavior in Anger Expression and Mental Health Functioning.

ERIC Educational Resources Information Center

Kopper, Beverly A.

1993-01-01

Investigated relationship of gender, sex role identity, Type A behavior to multiple dimensions of anger expression and mental health functioning among 407 female and 222 male college students. Found significant multivariate effects for sex role and behavior pattern type for anger expression. Significant gender differences were not observed.…

Role of selenium-containing proteins in T cell and macrophage function

PubMed Central

Carlson, Bradley A.; Yoo, Min-Hyuk; Shrimali, Rajeev K.; Irons, Robert; Gladyshev, Vadim N.; Hatfield, Dolph L.; Park, Jin Mo

2011-01-01

Synopsis Selenium has been known for many years to have a role in boosting immune function, but the manner in which this element acts at the molecular level in host defense and inflammatory diseases is poorly understood. To elucidate the role of selenium-containing proteins in immune function, we knocked out the expression of this protein class in T cells or macrophages of mice by targeting the removal of the selenocysteine tRNA gene using loxP-Cre technology. Mice with selenoprotein-less T cells manifested reduced pools of mature and functional T cells in lymphoid tissues and an impairment in T cell-dependent antibody responses. Furthermore, selenoprotein deficiency in T cells led to an inability of these cells to suppress reactive oxygen species (ROS) production, which in turn affected their ability to proliferate in response to T cell receptor stimulation. Selenoprotein-less macrophages, on the other hand, manifested mostly normal inflammatory responses, but this deficiency resulted in an altered regulation in extracellular matrix-related gene expression and a diminished migration of macrophages in a protein gel matrix. These observations provided novel insights into the role of selenoproteins in immune function and tissue homeostasis. PMID:20576203

Health and role functioning: the use of focus groups in the development of an item bank.

PubMed

Anatchkova, Milena D; Bjorner, Jakob B

2010-02-01

Role functioning is an important part of health-related quality of life. However, assessment of role functioning is complicated by the wide definition of roles and by fluctuations in role participation across the life-span. The aim of this study is to explore variations in role functioning across the lifespan using qualitative approaches, to inform the development of a role functioning item bank and to pilot test sample items from the bank. Eight focus groups were conducted with a convenience sample of 38 English-speaking adults recruited in Rhode Island. Participants were stratified by gender and four age groups. Focus groups were taped, transcribed, and analyzed for thematic content. Participants of all ages identified family roles as the most important. There was age variation in the importance of social life roles, with younger and older adults rating them as more important. Occupational roles were identified as important by younger and middle-aged participants. The potential of health problems to affect role participation was recognized. Participants found the sample items easy to understand, response options identical in meaning and preferred five response choices. Participants identified key aspects of role functioning and provided insights on their perception of the impact of health on their role participation. These results will inform item bank generation.

The role of the NG2 proteoglycan in OPC and CNS network function.

PubMed

Sakry, Dominik; Trotter, Jacqueline

2016-05-01

In the normal mammalian CNS, the NG2 proteoglycan is expressed by oligodendrocyte precursor cells (OPC) but not by any other neural cell-type. NG2 is a type-1 membrane protein, exerting multiple roles in the CNS including intracellular signaling within the OPC, with effects on migration, cytoskeleton interaction and target gene regulation. It has been recently shown that the extracellular region of NG2, in addition to an adhesive function, acts as a soluble ECM component with the capacity to alter defined neuronal network properties. This region of NG2 is thus endowed with neuromodulatory properties. In order to generate biologically active fragments yielding these properties, the sequential cleavage of the NG2 protein by α- and γ-secretases occurs. The basal level of constitutive cleavage is stimulated by neuronal network activity. This processing leads to 4 major NG2 fragments which all have been associated with distinct biological functions. Here we summarize these functions, focusing on recent discoveries and their implications for the CNS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). Copyright © 2015 Elsevier B.V. All rights reserved.

A Novel Role for the Immunoproteasome in Retinal Function

PubMed Central

Hussong, Stacy A.; Roehrich, Heidi; Kapphahn, Rebecca J.; Maldonado, Marcela; Pardue, Machelle T.

2011-01-01

Purpose. The immunoproteasome is a proteasome subtype with a well-characterized role in the immune system. The presence of high immunoproteasome concentrations in the photoreceptors and synaptic regions of the immune-privileged retina implies a role in visual transmission. In this study, immunoproteasome knockout (KO) mice lacking either one (lmp7−/−, L7) or two (lmp7−/−/mecl-1−/−, L7M1) catalytic subunits of the immunoproteasome were used to test the hypothesis that it is essential for the maintenance of normal retinal function. Methods. Wild-type (WT) and immunoproteasome KO mice lacking either one (L7) or two (L7M1) catalytic subunits of the immunoproteasome were studied to determine the importance of the immunoproteasome in maintaining normal retinal function and morphology. Changes in retinal morphology were assessed in mice 2 to 24 months of age. Retinal function was measured with electroretinography (ERG), and relative content of select retinal proteins was assessed by immunoblot analysis. Results. Retinal morphometry showed no major abnormalities in age-matched WT or KO mice. No significant difference was observed in the levels of proteins involved in vision transmission. ERGs from KO mice exhibited an approximate 25% decrease in amplitude of the dark- and light-adapted b-waves and faster dark-adapted b-wave implicit times. Conclusions. Immunoproteasome deficiency causes defects in bipolar cell response. These results support a previously unrecognized role for the immunoproteasome in vision transmission. PMID:20881299

Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles

NASA Astrophysics Data System (ADS)

Hsu, Justin Bo-Kai; Huang, Kai-Yao; Weng, Tzu-Ya; Huang, Chien-Hsun; Lee, Tzong-Yi

2014-01-01

Machinery of pre-mRNA splicing is carried out through the interaction of RNA sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g. spliceosome and splicing factors). Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated, partly because SRPs have not yet been exhaustively identified and the experimental identification is labor-intensive. Therefore, we are motivated to design a new method for identifying SRPs with their functional roles in the regulation of RNA splicing. The experimentally verified SRPs were manually curated from research articles. According to the functional annotation of Splicing Related Gene Database, the collected SRPs were further categorized into four functional groups including small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and Novel Spliceosome Protein. The composition of amino acid pairs indicates that there are remarkable differences among four functional groups of SRPs. Then, support vector machines (SVMs) were utilized to learn the predictive models for identifying SRPs as well as their functional roles. The cross-validation evaluation presents that the SVM models trained with significant amino acid pairs and functional domains could provide a better predictive performance. In addition, the independent testing demonstrates that the proposed method could accurately identify SRPs in mammals/plants as well as effectively distinguish between SRPs and RNA-binding proteins. This investigation provides a practical means to identifying potential SRPs and a perspective for exploring the regulation of RNA splicing.

Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles.

PubMed

Hsu, Justin Bo-Kai; Huang, Kai-Yao; Weng, Tzu-Ya; Huang, Chien-Hsun; Lee, Tzong-Yi

2014-01-01

Machinery of pre-mRNA splicing is carried out through the interaction of RNA sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g. spliceosome and splicing factors). Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated, partly because SRPs have not yet been exhaustively identified and the experimental identification is labor-intensive. Therefore, we are motivated to design a new method for identifying SRPs with their functional roles in the regulation of RNA splicing. The experimentally verified SRPs were manually curated from research articles. According to the functional annotation of Splicing Related Gene Database, the collected SRPs were further categorized into four functional groups including small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and Novel Spliceosome Protein. The composition of amino acid pairs indicates that there are remarkable differences among four functional groups of SRPs. Then, support vector machines (SVMs) were utilized to learn the predictive models for identifying SRPs as well as their functional roles. The cross-validation evaluation presents that the SVM models trained with significant amino acid pairs and functional domains could provide a better predictive performance. In addition, the independent testing demonstrates that the proposed method could accurately identify SRPs in mammals/plants as well as effectively distinguish between SRPs and RNA-binding proteins. This investigation provides a practical means to identifying potential SRPs and a perspective for exploring the regulation of RNA splicing.

Family Functioning and Adolescent Psychological Maladjustment: The Mediating Role of Coping Strategies.

PubMed

Francisco, Rita; Loios, Sara; Pedro, Marta

2016-10-01

This study aims to analyze the mediating role of coping strategies in the relationship between family functioning and youth maladjustment. A community sample of 341 adolescents (M = 15.11 years old; SD = 1.71) completed self-report measures about such variables. Results showed that a perception of an inadequate family functioning was associated with the use of maladaptive coping strategies, as well as with youth psychological maladjustment. The results also revealed that rumination and support-seeking mediated the relationship between family functioning and internalizing behavior, and hostile expression of feelings played a mediating role between family functioning and externalizing behavior. No gender differences were found in the relationship between variables. This study emphasizes the importance of coping strategies used by adolescents to understand the relationship between family functioning and youth psychological maladjustment.

The Role of Endogenous Neurogenesis in Functional Recovery and Motor Map Reorganization Induced by Rehabilitative Therapy after Stroke in Rats.

PubMed

Shiromoto, Takashi; Okabe, Naohiko; Lu, Feng; Maruyama-Nakamura, Emi; Himi, Naoyuki; Narita, Kazuhiko; Yagita, Yoshiki; Kimura, Kazumi; Miyamoto, Osamu

2017-02-01

Endogenous neurogenesis is associated with functional recovery after stroke, but the roles it plays in such recovery processes are unknown. This study aims to clarify the roles of endogenous neurogenesis in functional recovery and motor map reorganization induced by rehabilitative therapy after stroke by using a rat model of cerebral ischemia (CI). Ischemia was induced via photothrombosis in the caudal forelimb area of the rat cortex. First, we examined the effect of rehabilitative therapy on functional recovery and motor map reorganization, using the skilled forelimb reaching test and intracortical microstimulation. Next, using the same approaches, we examined how motor map reorganization changed when endogenous neurogenesis after stroke was inhibited by cytosine-β-d-arabinofuranoside (Ara-C). Rehabilitative therapy for 4 weeks after the induction of stroke significantly improved functional recovery and expanded the rostral forelimb area (RFA). Intraventricular Ara-C administration for 4-10 days after stroke significantly suppressed endogenous neurogenesis compared to vehicle, but did not appear to influence non-neural cells (e.g., microglia, astrocytes, and vascular endothelial cells). Suppressing endogenous neurogenesis via Ara-C administration significantly inhibited (~50% less than vehicle) functional recovery and RFA expansion (~33% of vehicle) induced by rehabilitative therapy after CI. After CI, inhibition of endogenous neurogenesis suppressed both the functional and anatomical markers of rehabilitative therapy. These results suggest that endogenous neurogenesis contributes to functional recovery after CI related to rehabilitative therapy, possibly through its promotion of motor map reorganization, although other additional roles cannot be ruled out. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Thai and Korean Students' Perceptions about the Roles and Functions of School Psychologists

ERIC Educational Resources Information Center

Tangdhanakanond, Kamonwan; Lee, Dong Hun

2014-01-01

The purpose of the present study was to compare Thai and Korean college students on their perceptions of the roles and functions of school psychologists. One hundred and ninety-three Thai college students and 238 Korean counterparts participated in this study. Students rated the importance of various roles/functions of a school psychologist and…

Academic and Social Achievement Goals: Their Additive, Interactive, and Specialized Effects on School Functioning

ERIC Educational Resources Information Center

Liem, Gregory Arief D.

2016-01-01

Background: Students' pursuit of academic and social goals has implications for school functioning. However, studies on academic and social achievement goals have been relatively independent and mainly conducted with students in culturally Western settings. Aims: Guided by multiple-goal perspectives, this study examined the role of academic and…

Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

PubMed

Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

2013-02-01

Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential. Copyright © 2013 Mosby, Inc. All rights reserved.

Additive Manufacturing: From Form to Function

DTIC Science & Technology

2016-01-01

embedded electronics in clothing that could allow additional protective benefits and health monitoring options.13 AM has also enabled proof-of-concept...the International Space Station (ISS) in September 2014 to test plastics . The second 3D printer was delivered to the ISS in April 2016. In addition...was developed by the Innovative Advanced Concepts program. The sensor is essentially a transparent sheet of plastic with printed elec- tronics that

Middle School Principals' Perceptions of Middle School Counselors' Roles and Functions

ERIC Educational Resources Information Center

Zalaquett, Carlos P.; Chatters, Seriashia J.

2012-01-01

The findings of this study expand current knowledge regarding principals' perceptions of school counselors. School principals play a key role in school counselors hiring or dismissal, and their perceptions of school counselors' roles and functions may influence their decisions. Reflecting on their views may also assist school principals in…

The Inexpressive Male: Functional-Conflict and Role Theory as Contrasting Explanations.

ERIC Educational Resources Information Center

Balswick, Jack

1979-01-01

Compares functional-conflict and role theory perspectives in their ability to explain male inexpressiveness. The role theory approach incorporates the individual and the social structure in explaining male inexpressiveness. Change in male expressiveness can be expected if males are encouraged to devote more time and energy to emotionally laden…

Additives

NASA Technical Reports Server (NTRS)

Smalheer, C. V.

1973-01-01

The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

On the role of second number-conserving functional derivatives

NASA Astrophysics Data System (ADS)

Gál, Tamás

2006-06-01

It is found that number-conserving second derivatives, of functional differentiation constrained to the domain of functional variables ρ(x) of a given norm ∫ρ(x)dx, are not obtained via two successive number-conserving differentiations, contrary to the case of unrestricted second derivatives. Investigating the role of second number-conserving derivatives, with the density-functional formulation of time-dependent quantum mechanics in focus, it is shown how number-conserving differentiation handles the dual nature of the Kohn Sham potential arising in the practical use of the theory. On the other hand, it is pointed out that number-conserving derivatives cannot resolve the causality paradox connected with the second derivative of the exchange-correlation part of the action density functional.

Role of Vitamin C in the Function of the Vascular Endothelium

PubMed Central

Harrison, Fiona E.

2013-01-01

Abstract Significance: Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. Recent Advances: Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. Critical Issues: The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. Future Directions: A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial

From Embryonic Development to Human Diseases: The Functional Role of Caveolae/Caveolin

PubMed Central

Sohn, Jihee; Brick, Rachel M.; Tuan, Rocky S.

2017-01-01

Caveolae, an almost ubiquitous, structural component of the plasma membrane, play a critical role in many functions essential for proper cell function, including membrane trafficking, signal transduction, extracellular matrix remodeling, and tissue regeneration. Three main types of caveolin proteins have been identified from caveolae since the discovery of caveolin-1 in the early 1990s. All three (Cav-1, Cav-2, and Cav-3) play crucial roles in mammalian physiology, and can effect pathogenesis in a wide range of human diseases. While many biological activities of caveolins have been uncovered since its discovery, their role and regulation in embryonic develop remain largely poorly understood, although there is increasing evidence that caveolins may be linked to lung and brain birth defects. Further investigations are clearly needed to decipher how caveolae/caveolins mediate cellular functions and activities of normal embryogenesis and how their perturbations contribute to developmental disorders. PMID:26991990

Drawing a dog: The role of working memory and executive function.

PubMed

Panesi, Sabrina; Morra, Sergio

2016-12-01

Previous research suggests that young children draw animals by adapting their scheme for the human figure. This can be considered an early form of drawing flexibility. This study investigated preschoolers' ability to draw a dog that is different from the human figure. The role of working memory capacity and executive function was examined. The participants were 123 children (36-73 months old) who were required to draw both a person and a dog. The dog figure was scored on a list of features that could render it different from the human figure. Regression analyses showed that both working memory capacity and executive function predicted development in the dog drawing; the dog drawing score correlated with working memory capacity and executive function, even partialling out age, motor coordination, and drawing ability (measured with Goodenough's Draw-a-Man test). These results suggest that both working memory capacity and executive function play an important role in the early development of drawing flexibility. The implications regarding executive functions and working memory are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Health benefits of air pollution abatement policy: Role of the shape of the concentration-response function.

PubMed

Pope, C Arden; Cropper, Maureen; Coggins, Jay; Cohen, Aaron

2015-05-01

There is strong evidence that fine particulate matter (aerodynamic diameter<2.5 μm; PM2.5) air pollution contributes to increased risk of disease and death. Estimates of the burden of disease attributable to PM2.5 pollution and benefits of reducing pollution are dependent upon the shape of the concentration response (C-R) functions. Recent evidence suggests that the C-R function between PM2.5 air pollution and mortality risk may be supralinear across wide ranges of exposure. Such results imply that incremental pollution abatement efforts may yield greater benefits in relatively clean areas than in highly polluted areas. The role of the shape of the C-R function in evaluating and understanding the costs and health benefits of air pollution abatement policy is explored. There remain uncertainties regarding the shape of the C-R function, and additional efforts to more fully understand the C-R relationships between PM2.5 and adverse health effects are needed to allow for more informed and effective air pollution abatement policies. Current evidence, however, suggests that there are benefits both from reducing air pollution in the more polluted areas and from continuing to reduce air pollution in cleaner areas. Estimates of the benefits of reducing PM2.5 air pollution are highly dependent upon the shape of the PM2.5-mortality concentration-response (C-R) function. Recent evidence indicates that this C-R function may be supralinear across wide ranges of exposure, suggesting that incremental pollution abatement efforts may yield greater benefits in relatively clean areas than in highly polluted areas. This paper explores the role of the shape of the C-R function in evaluating and understanding the costs and health benefits of PM2.5 air pollution abatement.

The Role of Executive Function in Children’s Competent Adjustment to Middle School

PubMed Central

Jacobson, Lisa A.; Williford, Amanda P.; Pianta, Robert C.

2012-01-01

Executive function (EF) skills play an important role in children’s cognitive and social functioning. These skills develop throughout childhood, concurrently with a number of developmental transitions and challenges. One of these challenges is the transition from elementary into middle-level schools, which has the potential to significantly disrupt children’s academic and social trajectories. However, little is known about the role of EF in children’s adjustment during this transition. This study investigated the relation between children’s EF skills, assessed both before and during elementary school, and sixth grade academic and social competence. In addition, the influences of the type of school setting attended in sixth grade on children’s academic and behavioral outcomes were examined. EF assessed prior to and during elementary school significantly predicted sixth grade competence, as rated by teachers and parents, in both academic and social domains, after controlling for background characteristics. The interactions between type of school setting and EF skills were significant: parents tended to report more behavioral problems and less regulatory control in children with weaker EF skills who were attending middle school. In contrast, teachers reported greater academic and behavioral difficulty in students with poorer EF attending elementary school settings. In conclusion, children’s performance-based EF skills significantly affect adjustment to the academic and behavioral demands of sixth grade, with parent report suggesting greater difficulty for children with poorer EF in settings where children are provided with less external supports (e.g., middle school). PMID:21246422

Phosphazene additives

DOEpatents

Harrup, Mason K; Rollins, Harry W

2013-11-26

An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

PubMed Central

Yi, Young-Su; Son, Young-Jin; Ryou, Chongsuk; Sung, Gi-Ho; Kim, Jong-Hoon; Cho, Jae Youl

2014-01-01

Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases. PMID:25045209

Variations in clinical nurse leaders' confidence with performing the core role functions.

PubMed

Gilmartin, Mattia J

2014-01-01

Clinical nurse leader (CNL) practice, by definition, requires individuals to make career transitions. CNLs must adjust to their new work role and responsibilities and doing so also entails individual adjustment. Prior work has not examined the role of individual-level factors in effective CNL role transition. This study contributes to CNL implementation efforts by developing understanding of personal and contextual factors that explain variation in individuals' levels of self-confidence with performing the key functions of the CNL role. Data were gathered using a cross-sectional survey from a national sample of registered nurses (RNs) certified as CNLs. Respondents' perceptions of their confidence in performing CNL role competencies were measured with the Clinical Nurse Leader Self-Efficacy Scale (CNLSES; Gilmartin MJ, Nokes, K. (in press). The Clinical Nurse Leader Self Efficacy Scale: Results of a pilot study. Nursing Economic$). The CNLSES is a 35-item state-specific self-efficacy scale with established measurement properties that assesses nurses' perceptions of their ability to function effectively as a CNL. Demographic data were also collected. Data were analyzed using a general linear regression model. One hundred forty-seven certified CNLs participated in the survey. Results indicate that respondents vary in their confidence with performing the nine role competencies associated with CNL practice. Results from regression analyses also show that respondents' confidence in their abilities to carry out the core functions associated with the CNL role varied significantly across geographic region, organizational type, and by CNL graduate program model. The results of this study show important differences in CNLs' levels of self-confidence with the core competencies of their role. As a result, it may be important to develop targeted career transition interventions to gain the full benefit of CNL practice. Copyright © 2014 Elsevier Inc. All rights reserved.

A Role for Transcription Factor GTF2IRD2 in Executive Function in Williams-Beuren Syndrome

PubMed Central

Porter, Melanie A.; Dobson-Stone, Carol; Kwok, John B. J.; Schofield, Peter R.; Beckett, William; Tassabehji, May

2012-01-01

Executive functions are amongst the most heritable cognitive traits with twin studies indicating a strong genetic origin. However genes associated with this domain are unknown. Our research into the neurodevelopmental disorder Williams-Beuren syndrome (WBS) has identified a gene within the causative recurrent 1.5/1.6 Mb heterozygous microdeletion on chromosome 7q11.23, which may be involved in executive functioning. Comparative genome array screening of 55 WBS patients revealed a larger ∼1.8 Mb microdeletion in 18% of cases, which results in the loss of an additional gene, the transcription factor GTF2IRD2. The GTF gene family of transcription factors (GTF2I, GTF2IRD1 and GTF2IRD2) are all highly expressed in the brain, and GTF2I and GTF2IRD1 are involved in the pathogenesis of the cognitive and behavioural phenotypes associated with WBS. A multi-level analysis of cognitive, behavioural and psychological functioning in WBS patients showed that those with slightly larger deletions encompassing GTF2IRD2 were significantly more cognitively impaired in the areas of spatial functioning, social reasoning, and cognitive flexibility (a form of executive functioning). They also displayed significantly more obsessions and externalizing behaviours, a likely manifestation of poor cognitive flexibility and executive dysfunction. We provide the first evidence for a role for GTF2IRD2 in higher-level (executive functioning) abilities and highlight the importance of integrating detailed molecular characterisation of patients with comprehensive neuropsychological profiling to uncover additional genotype-phenotype correlations. The identification of specific genes which contribute to executive function has important neuropsychological implications in the treatment of patients with conditions like WBS, and will allow further studies into their mechanism of action. PMID:23118870

Functional role of AMP-activated protein kinase in the heart during exercise.

PubMed

Musi, Nicolas; Hirshman, Michael F; Arad, Michael; Xing, Yanqiu; Fujii, Nobuharu; Pomerleau, Jason; Ahmad, Ferhaan; Berul, Charles I; Seidman, Jon G; Tian, Rong; Goodyear, Laurie J

2005-04-11

AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function during ischemia in the heart. However, the functional role of AMPK in the heart during exercise is unknown. We examined whether acute exercise increases AMPK activity in mouse hearts and determined the significance of these increases by studying transgenic (TG) mice expressing a cardiac-specific dominant-negative (inactivating) AMPKalpha2 subunit. Exercise increased cardiac AMPKalpha2 activity in the wild type mice but not in TG. We found that inactivation of AMPK did not result in abnormal ATP and glycogen consumption during exercise, cardiac function assessed by heart rhythm telemetry and stress echocardiography, or in maximal exercise capacity.

Switching roles: the functional plasticity of adult tissue stem cells

PubMed Central

Wabik, Agnieszka; Jones, Philip H

2015-01-01

Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

Tailoring magnetic properties in arrays of pulse-electrodeposited Co nanowires: The role of Cu additive

NASA Astrophysics Data System (ADS)

Esmaeili, A.; Almasi Kashi, M.; Ramazani, A.; Montazer, A. H.

2016-01-01

In this study, we aim to report the role of Cu additive in arrays of pulse-electrodeposited Co nanowires (NWs) with diameters from 30 to 75 nm, embedded in porous aluminum oxide templates. This features the role of Cu additive in composition and crystalline characteristics as well as in the magnetic properties of Co NWs. Increasing the duration of off-time between pulses during the electrodeposition of Co NWs made it possible to increase the amount of Cu content, so that Co-rich CoCu NWs were obtained. The parallel coercivity and squareness values increased up to 1500 Oe and 0.8 for 30 nm diameter Co94Cu6 NWs, starting from 500 Oe and 0.3 for pure Co NWs. On the other hand, although there was a substantial difference between the crystalline characteristics of 75 nm diameter pure Co and CoCu NWs, no considerable change in their magnetic properties was observed using hysteresis loop measurements. In this respect, the first-order reversal curve (FORC) analysis revealed strong inter-wire magnetostatic interactions for the CoCu NWs. Moreover, we studied the effect of thermal annealing, which resulted in an increase in the coercivity of CoCu NWs with different diameters up to 15%. As a result, the addition of small amount of Cu provides an alternative approach to tailoring the magnetic properties of Co NWs.

Role of AAA(+)-proteins in peroxisome biogenesis and function.

PubMed

Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

2016-05-01

Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

Increasing meat product functionality by the addition of milled flaxseed Linum usitatissimum.

PubMed

Zając, Marzena; Kulawik, Piotr; Tkaczewska, Joanna; Migdał, Władysław; Pustkowiak, Henryk

2017-07-01

Functional meat products are still rare on the market because it is difficult to incorporate new ingredients and obtain both a healthy and acceptable product. Flaxseed is known for its beneficial properties and, in the present study, it was used as an ingredient in the production of homogenised and liver sausages (0%, 5% and 10% flaxseed addition). Homogenised and liver sausages with the addition of 5% flaxseed were given the highest scores by the consumers, although the colour changed with the addition of flaxseed. The spreadability and hardness of the liver sausages increased with the addition of flaxseed, whereas the texture of homogenised sausages did not change. Addition of flaxseed improved the fatty acids profile from a health point of view for both products, as a result of increasing n-3 fatty acids and overall polyunsaturated fatty acids content. Values for thiobarbituric acid reactive substances were higher in products with flaxseed and were observed to increase during storage. The results of the present study indicate that it is possible to obtain products that are acceptable by consumers and, at the same time, are more healthy. A high level of α-linolenic acid in the sausages at a level of addition of 5% allows the product to be labelled with information regarding their high omega-3 fatty acid content. However, those products are more susceptible to oxidation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

[The roles and functions of volunteer counselors to the elderly].

PubMed

Chen, Chun-Yu

2004-06-01

In Taiwan's current counseling centers for the elderly, large numbers of volunteers are supervised by only a few social workers or nurses, so the roles and functions of these volunteers are very important. A neat summary of the services provided by the volunteers would include: (1) Direct services: telephone counseling, telephone interviewing, case handling, mail counseling, resource provision. (2) Indirect services: fundraising, supervision. (3) Administration: administrative assistance, management of institutional web sites. (4) Strategic consultancy: consultancy, provision of expertise. (5) Advocacy: service as educators and spokespersons; public relations and marketing. (6) MANAGEMENT: team leadership, plan implementation. To sum up, their functions are, by means of telephone and face-to-face contact, to provide information to the elderly about finances, medical services, housing, citizenship, the dignity of life and death, and related issues, as well as to serve as advocates for the provision of resources--such as educational courses--and to facilitate such provision. Indeed, the roles and functions of volunteer counselors become more diverse and more comprehensive by the day.

The role and functionality of Veterinary Services in food safety throughout the food chain.

PubMed

McKenzie, A I; Hathaway, S C

2006-08-01

Both national Veterinary Services and international standard-setting organisations have now embraced risk assessment as an essential tool for achieving their goals. Veterinarians have key roles in all aspects of the control of food-borne hazards of animal origin, but additional specialist skills are necessary for assessing, managing and communicating risk. Further, the deployment of Veterinary Services must reflect the multi-functional aspects of public and animal health activities. A generic risk management framework provides a systematic process whereby food safety standards and other measures are chosen and implemented on the basis of knowledge of risk and evaluation of other factors relevant to protecting human health and promoting non-discriminatory trade practices. In this context, a number of countries are exploring new administrative and structural arrangements for competent authorities. The traditional focus of veterinary involvement in food safety has been in meat hygiene at the level of the slaughterhouse. While this role continues, the emerging 'risk-based' approach to food control requires increased involvement in other segments of the meat food chain, as well as other areas such as production of milk and fish. This more extensive role requires a wider skill base and establishment of effective networks with a different range of stakeholders.

Species Pool Functional Diversity Plays a Hidden Role in Generating β-Diversity.

PubMed

Patrick, Christopher J; Brown, Bryan L

2018-05-01

Functional trait diversity is used as a way to infer mechanistic processes that drive community assembly. While functional diversity within communities is often viewed as a response variable, here we present and test a framework for how functional diversity among taxa in the regional species pool drives the assembly of communities among habitats. We predicted that species pool functional diversity should work with environmental heterogeneity to drive β-diversity. We tested these predictions by modeling empirical patterns in invertebrate communities from 570 streams in 52 watersheds. Our analysis of the field data provided strong support for the inclusion of both functional diversity and environmental heterogeneity in the models, and our predictions were supported when the community was analyzed all together. However, analyses within individual functional feeding guilds revealed strong context dependency in the relative importance of functional diversity, γ-richness, and environmental heterogeneity to β-diversity. We interpret the results to mean that functional diversity can play an important role in driving β-diversity; however, within guilds the nature of interspecific interactions and species pool size complicate the relationship. Future research should test this conceptual model across different ecosystems and in experimental settings using metacommunity mesocosms to enhance our understanding of the role that functional variation plays in generating spatial biodiversity patterns.

Effects of common mental disorders and physical conditions on role functioning in Spain.

PubMed

Barbaglia, Gabriela; Duran, Núria; Vilagut, Gemma; Forero, Carlos García; Haro, Josep Maria; Alonso, Jordi

2013-01-01

To examine the effects of common mental disorders and physical conditions on role functioning in Spain. Cross-sectional study of the general adult population of Spain (n = 2,121). Non-psychotic mental disorders were assessed with the Composite International Diagnostic Interview (CIDI 3.0) and physical conditions with a checklist. The role functioning dimension of the WHO-Disability Assessment Schedule (WHODAS) was used to asses the number of days in the past month in which respondents were fully or partially limited to perform daily activities. Generalized linear models were used to estimate individual-level associations of specific conditions and role functioning, controlling for co-morbidity. Societal level estimates were calculated using population attributable risk proportions (PARP). Mental disorders and physical conditions showed similar number of days with full role limitation (about 20 days per year); in contrast mental disorders were responsible for twice as many days with partial role limitation than physical conditions (42 vs 21 days, respectively). If the population were entirely unexposed to mental and physical conditions, days with full limitation would be reduced by 73% and days with partial limitation by 41%. Common health conditions in Spain are associated with considerably more days with role limitation than other Western countries. There is need of mainstreaming disability in the Spanish public health agenda in order to reduce role limitation among individuals with common conditions. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Role of ankle foot orthoses in functional stability of individuals with stroke.

PubMed

Rao, N; Aruin, A S

2016-10-01

Ankle foot orthoses (AFOs) are frequently prescribed to improve ambulation in individuals with stroke. However, the role of AFOs in balance control is not completely understood. The aim of the study was to evaluate the contribution of the AFOs in functional stability of individuals with stroke. Twenty three individuals with unilateral hemiparesis due to stroke were assessed using the Functional Reach Test. The subjects performed reaches forward, left and right while standing with or without an AFO. When provided with AFO, individuals with stroke improved the maximal reaching distance in all the directions (p < 0.05). The study found that individuals with unilateral stroke clearly demonstrated improvements in functional stability when they were provided with AFOs. This outcome could be used in the optimization of balance rehabilitation of individuals with stroke. Implications for Rehabilitation Functional stability is impaired in individuals with stroke. Functional Reach Test (FRT) was used to assess the role of ankle foot orthoses (AFOs) in balance control. Individuals with stroke improved their functional stability while they were provided with AFOs. Functional Reach Test could assist clinicians in the evaluation of postural stability associated with the use of AFOs.

miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

PubMed

Lim, Shok Ping; Ioannou, Nikolaos; Ramsay, Alan G; Darling, David; Gäken, Joop; Mufti, Ghulam J

2018-05-01

MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function. Stimulation of PBMC derived CD3 + T cells resulted in reduced miR-181c expression and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis is important in T cell activation. We further showed that overexpression of miR-181c or suppression of BRK1 resulted in inhibition of T cell activation and actin polymerization coupled with defective lamellipodia generation and immunological synapse formation. Additionally, we found that BRK1 silencing led to reduced expressions of other proteins in the WAVE2 complex, suggesting that the impairment of T cell actin dynamics was a result of the instability of the WAVE2 complex following BRK1 depletion. Collectively, we demonstrated that miR-181c reduces BRK1 protein expression level and highlighted the important role of miR-181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell functions. ©2018 Society for Leukocyte Biology.

The interactive effects of negative symptoms and social role functioning on suicide ideation in individuals with schizophrenia.

PubMed

Jahn, Danielle R; Bennett, Melanie E; Park, Stephanie G; Gur, Raquel E; Horan, William P; Kring, Ann M; Blanchard, Jack J

2016-02-01

Findings regarding the protective effect of social role functioning on suicide ideation in individuals with schizophrenia have been mixed. One reason for such inconsistencies in the literature may be that individuals with prominent negative symptoms of schizophrenia may not experience a desire for social closeness, and therefore social role functioning may not influence suicide risk in these individuals. The aim of this study was to examine the moderating effects of self-reported desire for social closeness and interviewer-rated negative symptoms on the relationship between social role functioning and suicide ideation. Our sample consisted of 162 individuals who had been diagnosed with schizophrenia-spectrum disorders; all participants completed self-report questionnaires and clinician-administered interviews, and moderation hypotheses were tested with a non-parametric procedure. The results indicated that motivation and pleasure-related negative symptoms moderated the relationship between social role functioning and suicide ideation; self-reported desire for social closeness and negative symptoms related to expression did not have such a moderating effect. Specifically, better social role functioning was associated with less suicide ideation only in those individuals who had low motivation and pleasure-related negative symptoms; no significant relationship was observed between social role functioning and suicide ideation among those with elevated motivation and pleasure-related negative symptoms. These findings suggest that assessing for negative symptoms and social role functioning may inform suicide risk assessments in individuals with schizophrenia, and improving social role functioning may reduce suicide ideation among those with few motivation and pleasure-related negative symptoms. Copyright © 2015 Elsevier B.V. All rights reserved.

The functional role of long non-coding RNA in digestive system carcinomas.

PubMed

Wang, Guang-Yu; Zhu, Yuan-Yuan; Zhang, Yan-Qiao

2014-09-01

In recent years, long non-coding RNAs (lncRNAs) are emerging as either oncogenes or tumor suppressor genes. Recent evidences suggest that lncRNAs play a very important role in digestive system carcinomas. However, the biological function of lncRNAs in the vast majority of digestive system carcinomas remains unclear. Recently, increasing studies has begun to explore their molecular mechanisms and regulatory networks that they are implicated in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in digestive system carcinomas. It is becoming clear that lncRNAs will be exciting and potentially useful for diagnosis and treatment of digestive system carcinomas, some of these lncRNAs might function as both diagnostic markers and the treatment targets of digestive system carcinomas.

Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

PubMed

Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

2012-09-01

Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

Chemical characteristic and functional properties of arenga starch-taro (Colocasia esculanta L.) flour noodle with turmeric extracts addition

NASA Astrophysics Data System (ADS)

Ervika Rahayu N., H.; Ariani, Dini; Miftakhussolikhah, E., Maharani P.; Yudi, P.

2017-01-01

Arenga starch-taro (Colocasia esculanta L.) flour noodle is an alternative carbohydrate source made from 75% arenga starch and 25% taro flour, but it has a different color with commercial noodle product. The addition of natural color from turmeric may change the consumer preference and affect chemical characteristic and functional properties of noodle. This research aims to identify chemical characteristic and functional properties of arenga starch-taro flour noodle with turmeric extract addition. Extraction was performed using 5 variances of turmeric rhizome (0.06; 0.12; 0.18; 0.24; and 0.30 g (fresh weight/ml water). Then, noodle was made and chemical characteristic (proximate analysis) as well as functional properties (amylose, resistant starch, dietary fiber, antioxidant activity) were then evaluated. The result showed that addition of turmeric extract did not change protein, fat, carbohydrate, amylose, and resistant starch content significantly, while antioxidant activity was increased (23,41%) with addition of turmeric extract.

[Roles of additives and surface control in slurry atomization]. Quarterly report

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

Tsai, S.C.

1992-06-01

As reported in the quarterly report of March of 1992, the relative viscosity of a Newtonian Coal Water Slurry (CWS) in the presence of an anionic polymeric dispersant is an order of magnitude higher than the prediction of the well established Krieger-Dougherty Equation which describes the relative viscosity of a non-aggregated Newtonian suspension as a function of particle volume fraction. Note that the anionic dispersant is used in such a quantity that the resulting interparticle electrostatic repulsion counter-balances the interparticle van der Waals attraction. Investigation continues to determine the mechanisms of such excess energy dissipation under shear. New experimental resultsmore » are presented in this report to verify the role of the anionic polymeric dispersant in such excess energy dissipation of CWS.« less

Functional roles affect diversity-succession relationships for boreal beetles.

PubMed

Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

2013-01-01

Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

Family Environments and Children's Executive Function: The Mediating Role of Children's Affective State and Stress.

PubMed

He, Zhong-Hua; Yin, Wen-Gang

2016-09-01

There is increasing evidence that inadequate family environments (family material environment and family psychosocial environment) are not only social problems but also factors contributing to adverse neurocognitive outcomes. In the present study, the authors investigated the relationship among family environments, children's naturalistic affective state, self-reported stress, and executive functions in a sample of 157 Chinese families. These findings revealed that in inadequate family material environments, reduced children's cognitive flexibility is associated with increased naturalistic negative affectivity and self-reported stress. In addition, naturalistic negative affectivity mediated the association between family expressiveness and children's cognitive flexibility. The authors used a structural equation model to examine the mediation model hypothesis, and the results confirmed the mediating roles of naturalistic negative affectivity and self-reported stress between family environments and the cognitive flexibility of Chinese children. These findings indicate the importance of reducing stress and negative emotional state for improving cognitive functions in children of low socioeconomic status.

Emerging roles for neurosteroids in sexual behavior and function.

PubMed

King, Steven R

2008-01-01

Although gonadal and adrenal steroids heavily impact sexual function at the level of the brain, the nervous system also produces its own steroids de novo that may regulate sexual behavior and reproduction. Current evidence points to important roles for neurosteroids in sexual and gender-typical behaviors, control of ovulation, and behaviors that strongly influence sexual interest and motivation like aggression, anxiety and depression. At the cellular level, neurosteroids act through stimulating rapid changes in excitability and direct activation of membrane receptors in neurons. Thus, unlike peripheral steroids, neurosteroids can have immediate and specific effects on select neuronal pathways to regulate sexual function.

MicroRNAs in prostate cancer: Functional role as biomarkers.

PubMed

Kanwal, Rajnee; Plaga, Alexis R; Liu, Xiaoqi; Shukla, Girish C; Gupta, Sanjay

2017-10-28

MicroRNAs (miRNAs) are small endogenous non-coding molecules that alters gene expression through post-transcriptional regulation of messenger RNA. Compelling evidence suggest the role of miRNA in cancer biology having potential as diagnostic, prognostic and predictive biomarkers. This review summarizes the current knowledge on miRNA deregulated in prostate cancer and their role as oncogene, tumor suppressor and metastasis regulators. The emerging information elucidating the biological function of miRNA is promising and may lead to their potential usefulness as diagnostic/prognostic markers and development as effective therapeutic tools for management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis

PubMed Central

Tonel, Giulia; Conrad, Curdin; Laggner, Ute; Di Meglio, Paola; Grys, Katarzyna; McClanahan, Terrill K.; Blumenschein, Wendy M.; Qin, Jian-Zhong; Xin, Hong; Oldham, Elizabeth; Kastelein, Robert; Nickoloff, Brian J.; Nestle, Frank O.

2013-01-01

Interleukin-23 is a key cytokine involved in the generation of Th17 effector cells. Clinical efficacy of an anti-p40 mAb blocking both IL-12 and IL-23 and disease association with single nucleotide polymorphisms in the IL23R gene raise the question of a functional role of IL-23 in psoriasis. In this study, we provide a comprehensive analysis of IL-23 and its receptor in psoriasis and demonstrate its functional importance in a disease-relevant model system. The expression of IL-23 and its receptor was increased in the tissues of patients with psoriasis. Injection of a mAb specifically neutralizing human IL-23 showed IL-23–dependent inhibition of psoriasis development comparable to the use of anti-TNF blockers in a clinically relevant xenotransplant mouse model of psoriasis. Together, our results identify a critical functional role for IL-23 in psoriasis and provide the rationale for new treatment strategies in chronic epithelial inflammatory disorders. PMID:20956338

Cutting edge: A critical functional role for IL-23 in psoriasis.

PubMed

Tonel, Giulia; Conrad, Curdin; Laggner, Ute; Di Meglio, Paola; Grys, Katarzyna; McClanahan, Terrill K; Blumenschein, Wendy M; Qin, Jian-Zhong; Xin, Hong; Oldham, Elizabeth; Kastelein, Robert; Nickoloff, Brian J; Nestle, Frank O

2010-11-15

Interleukin-23 is a key cytokine involved in the generation of Th17 effector cells. Clinical efficacy of an anti-p40 mAb blocking both IL-12 and IL-23 and disease association with single nucleotide polymorphisms in the IL23R gene raise the question of a functional role of IL-23 in psoriasis. In this study, we provide a comprehensive analysis of IL-23 and its receptor in psoriasis and demonstrate its functional importance in a disease-relevant model system. The expression of IL-23 and its receptor was increased in the tissues of patients with psoriasis. Injection of a mAb specifically neutralizing human IL-23 showed IL-23-dependent inhibition of psoriasis development comparable to the use of anti-TNF blockers in a clinically relevant xenotransplant mouse model of psoriasis. Together, our results identify a critical functional role for IL-23 in psoriasis and provide the rationale for new treatment strategies in chronic epithelial inflammatory disorders.

Structural Evolution of Electrochemically Lithiated MoS2 Nanosheets and the Role of Carbon Additive in Li-Ion Batteries

PubMed Central

2016-01-01

Understanding the structure and phase changes associated with conversion-type materials is key to optimizing their electrochemical performance in Li-ion batteries. For example, molybdenum disulfide (MoS2) offers a capacity up to 3-fold higher (∼1 Ah/g) than the currently used graphite anodes, but they suffer from limited Coulombic efficiency and capacity fading. The lack of insights into the structural dynamics induced by electrochemical conversion of MoS2 still hampers its implementation in high energy-density batteries. Here, by combining ab initio density-functional theory (DFT) simulation with electrochemical analysis, we found new sulfur-enriched intermediates that progressively insulate MoS2 electrodes and cause instability from the first discharge cycle. Because of this, the choice of conductive additives is critical for the battery performance. We investigate the mechanistic role of carbon additive by comparing equal loading of standard Super P carbon powder and carbon nanotubes (CNTs). The latter offer a nearly 2-fold increase in capacity and a 45% reduction in resistance along with Coulombic efficiency of over 90%. These insights into the phase changes during MoS2 conversion reactions and stabilization methods provide new solutions for implementing cost-effective metal sulfide electrodes, including Li–S systems in high energy-density batteries. PMID:27818575

Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function.

PubMed

Xing, Juan; Petranka, John G; Davis, Felicity M; Desai, Pooja N; Putney, James W; Bird, Gary S

2014-03-01

Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.

Asymmetric functional organozinc additions to aldehydes catalyzed by 1,1'-bi-2-naphthols (BINOLs).

PubMed

Pu, Lin

2014-05-20

Chiral alcohols are ubiquitous in organic structures. One efficient method to generate chiral alcohols is the catalytic asymmetric addition of a carbon nucleophile to a carbonyl compound since this process produces a C-C bond and a chiral center simultaneously. In comparison with the carbon nucleophiles such as an organolithium or a Grignard reagent, an organozinc reagent possesses the advantages of functional group tolerance and more mild reaction conditions. Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and alkynylzincs to generate functional chiral alcohols are discussed in this Account. Our laboratory has developed a series of 1,1'-bi-2-naphthol (BINOL)-based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is found that the 3,3'-dianisyl-substituted BINOLs are not only highly enantioselective for the alkylzinc addition to aldehydes, but also highly enantioselective for the diphenylzinc addition to aldehydes. A one-step synthesis has been achieved to incorporate Lewis basic amine groups into the 3,3'-positions of the partially hydrogenated H8BINOL. These H8BINOL-amine compounds have become more generally enantioselective and efficient catalysts for the diphenylzinc addition to aldehydes to produce various types of chiral benzylic alcohols. The application of the H8BINOL-amine catalysts is expanded by using in situ generated diarylzinc reagents from the reaction of aryl iodides with ZnEt2, which still gives high enantioselectivity and good catalytic activity. Such a H8BINOL-amine compound is further found to catalyze the highly enantioselective addition of vinylzincs, in situ generated from the treatment of vinyl iodides with ZnEt2, to aldehydes to give the synthetically very useful chiral allylic alcohols. We have discovered that the unfunctionalized BINOL in combination with ZnEt2 and Ti(O(i)Pr)4 can catalyze the terminal alkyne addition to aldehydes to produce chiral propargylic alcohols of high synthetic

The Role of Esophageal Hypersensitivity in Functional Heartburn.

PubMed

Kondo, Takashi; Miwa, Hiroto

2017-08-01

Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

Changes in enzyme activity and functional diversity in soil induced by Cd and glucose addition

NASA Astrophysics Data System (ADS)

Gilmullina, A. R.; Galitskaya, P. Yu; Selivanovskaya, S. Yu

2018-01-01

Toxic heavy metal (HM) contamination is a major global issue as it may have an indirect effect on the health of soil, plants, animals and, consequently, on human health. Agricultural soils’ fertilization is one of the reported sources of HM pollution in the world. In this case simultaneous input of stimulating and inhibiting agents into soil takes place, and effects of the combined influence of these agents is hardly predictable. In this study, a simultaneous inhibiting and stimulating effect of Cd and glucose on soil microbes was studied in a model experiment. Enzyme activities (phosphatase, β-glucosidase and cellobiohydrolase) and functional diversity (BIOLOG®EcoPlates ™) were assessed as a test functions. Cd (300 μg Cd g-1 ) amendment had a negative effect only on phosphatase activity. Glucose (3 mg C g-1) addition inhibited β-glucosidase activity and stimulated functional diversity. In joint addition of Cd and Glucose the leading effect belonged to that agent which had the greatest effect in case when it was added separately.

Regulation of Endothelial Barrier Function by Cyclic Nucleotides: The Role of Phosphodiesterases

PubMed Central

Surapisitchat, James

2014-01-01

The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction. PMID:21695641

Regulation of endothelial barrier function by cyclic nucleotides: the role of phosphodiesterases.

PubMed

Surapisitchat, James; Beavo, Joseph A

2011-01-01

The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction.

Functional Roles of Bestrophins in Ocular Epithelia

PubMed Central

Marmorstein, Alan D.; Cross, Harold E.; Peachey, Neal S.

2009-01-01

There are four members of the bestrophin family of proteins in the human genome, of which two are known to be expressed in the eye. The gene BEST1 (formerly VMD2) which encodes the protein bestrophin-1 (Best1) was first identified in 1998. Mutations in this gene have now been associated with four clinically distinguishable human eye diseases, collectively referred to as “bestrophinopathies”. Over the last decade, laboratories have sought to understand how Best1 mutations could result in eye diseases that range in presentation from macular degeneration to nanophthalmos. The majority of our knowledge comes from studies that have sought to understand how Best1 mutations or dysfunction could induce the classical symptoms of the most common of these diseases: Best vitelliform macular dystrophy (BVMD). BVMD is a dominant trait that is characterized electrophysiologically by a diminished electrooculogram light peak with a normal clinical electroretinogram. This together with the localization of Best1 to the retinal pigment epithelium (RPE) basolateral plasma membrane and data from heterologous expression studies, have led to the proposal that Best1 generates the light peak, and that bestrophins are a family of Ca2+ activated Cl- channels (CaCCs). However, data from Best1 knock-out and knock-in mice, coupled with the recent discovery of a recessive bestrophinopathy suggest that Best1 does not generate the light peak. Recently Best2 was found to be expressed in non-pigmented epithelia in the ciliary body. However, aqueous dynamics in Best2 knock-out mice do not support a role for Best2 as a Cl- channel. Thus, the purported CaCC function of the bestrophins and how loss of this function relates to clinical disease needs to be reassessed. In this article, we examine data obtained from tissue-type and animal models and discuss the current state of bestrophin research, what roles Best1 and Best2 may play in ocular epithelia and ocular electrophysiology, and how perturbation

Physical and role functioning among persons with HIV: results from a nationally representative survey.

PubMed

Crystal, S; Fleishman, J A; Hays, R D; Shapiro, M F; Bozzette, S A

2000-12-01

Functional limitations of persons living with HIV affect their care needs and ability to perform social roles such as employment. Earlier estimates are outdated, and nationally representative estimates of prevalence and distribution of these limitations have not previously been available. The objectives of this study were to characterize physical and role limitations experienced by adults in care for HIV disease in the United States and to analyze variations by demographic and health characteristics in a multivariate framework. Among 2,836 respondents in the HIV Cost and Services Utilization Survey, we assessed physical functioning with a 9-item scale designed to span a broad continuum of tasks and administered the 2-item ACTG SF-21 role functioning scale. Linearization methods were used to account for the multistage survey design. Limitation in complex roles-working at a job, working around the house, or going to school-was more prevalent than limitation in most specific physical tasks. Among physical tasks, limitation was more prevalent in energy-demanding activities such as climbing stairs (43%) or walking >1 block (26%) than in self-care tasks such as bathing and dressing (14%). Greater limitation was associated with older age, lower educational attainment, more advanced disease, and higher symptom burden. Protease inhibitor treatment was associated with somewhat less physical limitation but no difference in role limitation. Functional status varied widely, suggesting the need for flexible, individualized care system responses. Results identified subgroups whose needs warrant special attention. Symptom intensity, pain, and fatigue were strongly associated with limitation; improved management of these disease manifestations might improve physical and social functioning.

The Role of Cocoa as a Cigarette Additive: Opportunities for Product Regulation

PubMed Central

Kennedy, Ryan David; Connolly, Gregory N.

2014-01-01

Introduction: The 2009 Family Smoking Prevention and Tobacco Control Act prohibited the use of characterizing flavors in cigarettes; however, some of these flavors are still used in cigarettes at varying levels. We reviewed tobacco industry internal documents to investigate the role of one of these flavors, cocoa, with the objective of understanding its relationship to sensory and risk perception, promotion of dependence, and enhancement of attractiveness and acceptability. Methods: We used the Legacy Tobacco Documents Library to identify documents relevant to our research questions. Initial search terms were generated following an examination of published literature on cocoa, other cigarette additives, and sensory and risk perception. Further research questions and search terms were generated based on review of documents generated from the initial search terms. Results: Cocoa is widely applied to cigarettes and has been used by the tobacco industry as an additive since the early 20th century. Cocoa can alter the sensory properties of cigarette smoke, including by providing a more appealing taste and decreasing its harshness. The tobacco industry has experimented with manipulating cocoa levels as a means of achieving sensory properties that appeal to women and youth. Conclusions: Although cocoa is identified as a flavor on tobacco industry Web sites, it may serve other sensory purposes in cigarettes as well. Eliminating cocoa as an additive from tobacco products may affect tobacco product abuse liability by altering smokers’ perceptions of product risk, and decreasing product appeal, especially among vulnerable populations. PMID:24610479

The Role of Functional Foods in Cutaneous Anti-aging

PubMed Central

Cho, Soyun

2014-01-01

Oral supplementation of micronutrients, or functional foods, to prevent aging has gained much attention and popularity as society ages and becomes more affluent, and as science reveals the pathological mechanisms of aging. Aging of the skin combines biologic aging and extrinsic aging caused predominantly by sunlight and other environmental toxins. Anti-aging functional foods exert their influence mostly through their anti-oxidant and anti-inflammatory effects, thereby abrogating collagen degradation and/or increasing procollagen synthesis. Clinical evidence supporting a role in preventing cutaneous aging is available for oral supplements such as carotenoids, polyphenols, chlorophyll, aloe vera, vitamins C and E, red ginseng, squalene, and omega-3 fatty acids. Collagen peptides and proteoglycans are claimed to provide building blocks of the dermal matrix. This review summarizes the current study findings of these functional foods. PMID:26064850

The Profession, Functions, Roles, and Practices of the Rehabilitation Counselor.

ERIC Educational Resources Information Center

Muthard, John E., Ed.; And Others

Four investigations of the rehabilitation counselor were presented to and discussed by representatives of universities, professional associations, and public and private rehabilitation agencies. Four major aspects of the counselor's professional development and practice were covered in these studies: (1) his perceived role and function within…

Is there a role of food additives in recurrent aphthous stomatitis? A prospective study with patch testing.

PubMed

Gülseren, Duygu; Hapa, Asli; Ersoy-Evans, Sibel; Elçin, Gonca; Karaduman, Ayşen

2017-03-01

Recurrent aphthous stomatitis (RAS) is a common disease of the oral mucosa with an unknown etiology. This study aimed to determine if food additives play a role in the etiology of RAS as well as to determine if patch testing can be used to detect which allergens cause RAS. This prospective study included 24 patients with RAS and 22 healthy controls. All the participants underwent patch testing for 23 food additives. In total, 21 (87.5%) RAS patients and 3 (13.6%) controls had positive patch test reactions to ≥1 allergens; the difference in the patch test positivity rate between groups was significant (P < 0.05). The most common allergen that elicited positive patch test results in the patient group was cochineal red (n = 15 [62.5%]), followed by azorubine (n = 11 [45.8%]) and amaranth (n = 6 [25%]). The present findings show that food additives might play a role in the etiology of RAS and that patch testing could be a method for determining the etiology of RAS. © 2016 The International Society of Dermatology.

The mediating role of coping strategy in the association between family functioning and nonsuicidal self-injury among Taiwanese adolescents.

PubMed

Ren, Yaxuan; Lin, Min-Pei; Liu, Yin-Han; Zhang, Xu; Wu, Jo Yung-Wei; Hu, Wei-Hsuan; Xu, Sian; You, Jianing

2018-01-22

Nock's (2009) integrated theoretical model suggests that both intrapersonal and interpersonal factors contribute to the development of nonsuicidal self-injury (NSSI). Based on this model, the present study examined the roles of family functioning and coping strategy in predicting NSSI, as well as the mediating effect of coping strategy in the relationship between family functioning and NSSI. Gender differences on the associations of these variables were also examined. A sample of 1,989 secondary school students (52.0% females) in Taiwan was assessed by self-report measures of perceived family functioning, coping strategy, and NSSI. Results showed that both family functioning and avoidance/emotion-focused coping strategy predicted NSSI. Additionally, the association between family functioning and NSSI was mediated by avoidance/emotion-focused coping strategy. Gender differences were not found on the associations among these study variables. These data provided evidences that the Nock's (2009) integrated theoretical model may help to explain how coping strategy mediates the effect of family functioning on NSSI. The implications of the findings for future research and intervention were discussed. © 2018 Wiley Periodicals, Inc.

Incorporating Family Function into Chronic Pain Disability: The Role of Catastrophizing

PubMed Central

Akbari, Fatemeh; Dehghani, Mohsen; Khatibi, Ali; Vervoort, Tine

2016-01-01

Background. Observers' responses to pain are recently investigated to more comprehensively explain chronic pain (CP) and disability. However, the role of family context, defined as interference in roles, communication, and problem-solving, and how (i.e., through which mechanisms) these variables contribute to CP related disability have yet to be examined. Objectives. The aim of the present study is to examine family context in relationship to pain catastrophizing, fear of movement, and depression and its role in understanding CP disability. Three different models were examined. Methods. A total sample of 142 patients with musculoskeletal chronic pain was recruited to examine the role of fear of movement, pain intensity, pain catastrophizing, and depression in relationship to family functioning as predictors of disability. Results. Findings indicated that two models showed acceptable fit, but one of them revealed superior fit indices. Results of the model with superior fit indices indicated that family dysfunction may contribute to catastrophic thinking, which, in turn, contributes to patients' disability through increasing fear of movement and depression. Discussion. The current study provides further support for the notion that the impact of emotional and cognitive variables upon CP-related disability can be better understood when we consider the social context of pain patients and family function in particular. PMID:27445620

Incorporating Family Function into Chronic Pain Disability: The Role of Catastrophizing.

PubMed

Akbari, Fatemeh; Dehghani, Mohsen; Khatibi, Ali; Vervoort, Tine

2016-01-01

Background. Observers' responses to pain are recently investigated to more comprehensively explain chronic pain (CP) and disability. However, the role of family context, defined as interference in roles, communication, and problem-solving, and how (i.e., through which mechanisms) these variables contribute to CP related disability have yet to be examined. Objectives. The aim of the present study is to examine family context in relationship to pain catastrophizing, fear of movement, and depression and its role in understanding CP disability. Three different models were examined. Methods. A total sample of 142 patients with musculoskeletal chronic pain was recruited to examine the role of fear of movement, pain intensity, pain catastrophizing, and depression in relationship to family functioning as predictors of disability. Results. Findings indicated that two models showed acceptable fit, but one of them revealed superior fit indices. Results of the model with superior fit indices indicated that family dysfunction may contribute to catastrophic thinking, which, in turn, contributes to patients' disability through increasing fear of movement and depression. Discussion. The current study provides further support for the notion that the impact of emotional and cognitive variables upon CP-related disability can be better understood when we consider the social context of pain patients and family function in particular.

Role of the cysteine residues in Arabidopsis thaliana cyclophilin CYP20-3 in peptidyl-prolyl cis–trans isomerase and redox-related functions

PubMed Central

Laxa, Miriam; König, Janine; Dietz, Karl-Josef; Kandlbinder, Andrea

2006-01-01

Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. Conserved cysteine residues further suggest a role in redox regulation. In order to get insight into the conformational change mechanism and functional properties of the chloroplast-located CYP20-3, site-directed mutagenized cysteine→serine variants were generated and analysed for enzymatic and conformational properties under reducing and oxidizing conditions. Compared with the wild-type form, elimination of three out of the four cysteine residues decreased the catalytic efficiency of PPI (peptidyl-prolyl cis–trans isomerase) activity of the reduced CYP20-3, indicating a regulatory role of dithiol–disulfide transitions in protein function. Oxidation was accompanied by conformational changes with a predominant role in the structural rearrangement of the disulfide bridge formed between Cys54 and Cys171. The rather negative Em (midpoint redox potential) of −319 mV places CYP20-3 into the redox hierarchy of the chloroplast, suggesting the activation of CYP20-3 in the light under conditions of limited acceptor availability for photosynthesis as realized under environmental stress. Chloroplast Prx (peroxiredoxins) were identified as interacting partners of CYP20-3 in a DNA-protection assay. A catalytic role in the reduction of 2-Cys PrxA and 2-Cys PrxB was assigned to Cys129 and Cys171. In addition, it was shown that the isomerization and disulfide-reduction activities are two independent functions of CYP20-3 that both are regulated by the redox state of its active centre. PMID:16928193

The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats.

PubMed

Thongnak, Laongdao; Pongchaidecha, Anchalee; Jaikumkao, Krit; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

2017-10-19

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.

Additive manufacturing of materials: Opportunities and challenges

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

Babu, Sudarsanam Suresh; Love, Lonnie J.; Dehoff, Ryan R.

Additive manufacturing (also known as 3D printing) is considered a disruptive technology for producing components with topologically optimized complex geometries as well as functionalities that are not achievable by traditional methods. The realization of the full potential of 3D printing is stifled by a lack of computational design tools, generic material feedstocks, techniques for monitoring thermomechanical processes under in situ conditions, and especially methods for minimizing anisotropic static and dynamic properties brought about by microstructural heterogeneity. In this paper, we discuss the role of interdisciplinary research involving robotics and automation, process control, multiscale characterization of microstructure and properties, and high-performancemore » computational tools to address each of these challenges. In addition, emerging pathways to scale up additive manufacturing of structural materials to large sizes (>1 m) and higher productivities (5–20 kg/h) while maintaining mechanical performance and geometrical flexibility are also discussed.« less

Additive manufacturing of materials: Opportunities and challenges

DOE PAGES

Babu, Sudarsanam Suresh; Love, Lonnie J.; Dehoff, Ryan R.; ...

2015-11-01

Additive manufacturing (also known as 3D printing) is considered a disruptive technology for producing components with topologically optimized complex geometries as well as functionalities that are not achievable by traditional methods. The realization of the full potential of 3D printing is stifled by a lack of computational design tools, generic material feedstocks, techniques for monitoring thermomechanical processes under in situ conditions, and especially methods for minimizing anisotropic static and dynamic properties brought about by microstructural heterogeneity. In this paper, we discuss the role of interdisciplinary research involving robotics and automation, process control, multiscale characterization of microstructure and properties, and high-performancemore » computational tools to address each of these challenges. In addition, emerging pathways to scale up additive manufacturing of structural materials to large sizes (>1 m) and higher productivities (5–20 kg/h) while maintaining mechanical performance and geometrical flexibility are also discussed.« less

Accessing siloxane functionalized polynorbornenes via vinyl-addition polymerization for CO 2 separation membranes

DOE PAGES

Mahurin, Shannon Mark; Sokolov, Alexei P.; Saito, Tomonori; ...

2016-07-06

Here, the vinyl addition polymerization of norbornylbased monomers bearing polar functional groups is often problematic, leading to low molecular weight polymers in poor yield. Herein, we provide proof-of-principle evidence that addition-type homopolymers of siloxane substituted norbornyl-based monomers may be readily synthesized using the catalyst trans-[Ni(C 6F 5) 2(SbPh 3) 2]. Polymerizations using this catalyst reached moderate to high conversion in just 5 min of polymerization and produced siloxanesubstituted polymers with molecular weights exceeding 100 kg/mol. These polymers showed excellent thermal stability (T d ≥ 362 °C) and were cast into membranes that displayed high CO 2 permeability and enhanced COmore » 2/N 2 selectivity as compared to related materials.« less

Students' Ability to Connect Function Properties to Different Types of Elementary Functions: An Empirical Study on the Role of External Representations

ERIC Educational Resources Information Center

De Bock, Dirk; Neyens, Deborah; Van Dooren, Wim

2017-01-01

Recent research on the phenomenon of improper proportional reasoning focused on students' understanding of elementary functions and their external representations. So far, the role of basic function properties in students' concept images of functions remained unclear. We add to this research line by investigating how accurate students are in…

Hyaluronic acid: its role in voice.

PubMed

Ward, P Daniel; Thibeault, Susan L; Gray, Steven D

2002-09-01

The extracellular matrix (ECM), once regarded simply as a structural scaffold, is now recognized as an important modulator of cellular behavior and function. One component that plays a prominent role in this process is hyaluronic acid (HA)--a molecule found in many different tissues. Research into the roles of HA indicates that it plays a key role in tissue viscosity, shock absorption, and space filling. Specifically, research into the role of HA in laryngology indicates that it has profound effects on the structure and viscosity of vocal folds. This article provides an introduction to the structure and biological functions of HA and its importance in voice. In addition, an overview of the pharmaceutical applications of HA is discussed.

Important Functional Roles of Basigin in Thymocyte Development and T cell Activation

PubMed Central

Yao, Hui; Teng, Yan; Sun, Qian; Xu, Jing; Chen, Ya-Tong; Hou, Ning; Cheng, Xuan; Yang, Xiao; Chen, Zhi-Nan

2014-01-01

Basigin is a highly glycosylated transmembrane protein that is expressed in a broad range of tissues and is involved in a number of physiological and pathological processes. However, the in vivo role of basigin remains unknown. To better understand the physiological and pathological functions of basigin in vivo, we generated a conditional null allele by introducing two loxP sites flanking exons 2 and 7 of the basigin gene (Bsg). Bsgfl/fl mice were born at the expected Mendelian ratio and showed a similar growth rate compared with wildtype mice. After crossing these mice with Lck-Cre transgenic mice, basigin expression was specifically inactivated in T cells in the resulting Lck-Cre; Bsgfl/fl mice. Although the birth and growth rate of Lck-Cre; Bsgfl/fl mice were similar to control mice, thymus development was partially arrested in Lck-Cre; Bsgfl/fl mice, specifically at the CD4+CD8+ double-positive (DP) and CD4 single-positive (CD4+CD8-, CD4SP) stages. In addition, CD4+ T cell activation was enhanced upon Concanavalin A (Con A) or anti-CD3/anti-CD28 stimulation but not upon PMA/Ionomycin stimulation in the absence of basigin. Overall, this study provided the first in vivo evidence for the function of basigin in thymus development. Moreover, the successful generation of the conditional null basigin allele provides a useful tool for the study of distinct physiological or pathological functions of basigin in different tissues at different development stages. PMID:24391450

Elucidating the functional role of endoreduplication in tomato fruit development

PubMed Central

Chevalier, Christian; Nafati, Mehdi; Mathieu-Rivet, Elodie; Bourdon, Matthieu; Frangne, Nathalie; Cheniclet, Catherine; Renaudin, Jean-Pierre; Gévaudant, Frédéric; Hernould, Michel

2011-01-01

Background Endoreduplication is the major source of endopolyploidy in higher plants. The process of endoreduplication results from the ability of cells to modify their classical cell cycle into a partial cell cycle where DNA synthesis occurs independently from mitosis. Despite the ubiquitous occurrence of the phenomenon in eukaryotic cells, the physiological meaning of endoreduplication remains vague,although several roles during plant development have been proposed, mostly related to cell differentiation and cell size determination. Scope Here recent advances in the knowledge of endoreduplication and fruit organogenesis are reviewed, focusing on tomato (Solanum lycopersicum) as a model, and the functional analyses of endoreduplication-associated regulatory genes in tomato fruit are described. Conclusions The cyclin-dependent kinase inhibitory kinase WEE1 and the anaphase promoting complex activator CCS52A both participate in the control of cell size and the endoreduplication process driving cell expansion during early fruit development in tomato. Moreover the fruit-specific functional analysis of the tomato CDK inhibitor KRP1 reveals that cell size and fruit size determination can be uncoupled from DNA ploidy levels, indicating that endoreduplication acts rather as a limiting factor for cell growth. The overall functional data contribute to unravelling the physiological role of endoreduplication in growth induction of fleshy fruits. PMID:21199834

Use of Phenylboronic Acids to Investigate Boron Function in Plants. Possible Role of Boron in Transvacuolar Cytoplasmic Strands and Cell-to-Wall Adhesion

PubMed Central

Bassil, Elias; Hu, Hening; Brown, Patrick H.

2004-01-01

The only defined physiological role of boron in plants is as a cross-linking molecule involving reversible covalent bonds with cis-diols on either side of borate. Boronic acids, which form the same reversible bonds with cis-diols but cannot cross-link two molecules, were used to selectively disrupt boron function in plants. In cultured tobacco (Nicotiana tabacum cv BY-2) cells, addition of boronic acids caused the disruption of cytoplasmic strands and cell-to-cell wall detachment. The effect of the boronic acids could be relieved by the addition of boron-complexing sugars and was proportional to the boronic acid-binding strength of the sugar. Experiments with germinating petunia (Petunia hybrida) pollen and boronate-affinity chromatography showed that boronic acids and boron compete for the same binding sites. The boronic acids appear to specifically disrupt or prevent borate-dependent cross-links important for the structural integrity of the cell, including the organization of transvacuolar cytoplasmic strands. Boron likely plays a structural role in the plant cytoskeleton. We conclude that boronic acids can be used to rapidly and reversibly induce boron deficiency-like responses and therefore are useful tools for investigating boron function in plants. PMID:15466241

Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

PubMed Central

Keohane, John; Quigley, Eamonn M M

2006-01-01

Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD. PMID:16718751

Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

PubMed

Keohane, John; Quigley, Eamonn M M

2006-05-07

Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

PubMed

McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

2014-08-15

To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function

PubMed Central

Wu, Yipin; Baum, Michel; Huang, Chou-Long

2015-01-01

Inwardly rectifying potassium channels play essential roles in renal physiology across phyla. Barium-sensitive K+ conductances are found on the basolateral membrane of a variety of insect Malpighian (renal) tubules, including Drosophila melanogaster. We found that barium decreases the lumen-positive transepithelial potential difference in isolated perfused Drosophila tubules and decreases fluid secretion and transepithelial K+ flux. In those insect species in which it has been studied, transcripts from multiple genes encoding inwardly rectifying K+ channels are expressed in the renal (Malpighian) tubule. In Drosophila melanogaster, this includes transcripts of the Irk1, Irk2, and Irk3 genes. The role of each of these gene products in renal tubule function is unknown. We found that simultaneous knockdown of Irk1 and Irk2 in the principal cell of the fly tubule decreases transepithelial K+ flux, with no additive effect of Irk3 knockdown, and decreases barium sensitivity of transepithelial K+ flux by ∼50%. Knockdown of any of the three inwardly rectifying K+ channels individually has no effect, nor does knocking down Irk3 simultaneously with Irk1 or Irk2. Irk1/Irk2 principal cell double-knockdown tubules remain sensitive to the kaliuretic effect of cAMP. Inhibition of the Na+/K+-ATPase with ouabain and Irk1/Irk2 double knockdown have additive effects on K+ flux, and 75% of transepithelial K+ transport is due to Irk1/Irk2 or ouabain-sensitive pathways. In conclusion, Irk1 and Irk2 play redundant roles in transepithelial ion transport in the Drosophila melanogaster renal tubule and are additive to Na+/K+-ATPase-dependent pathways. PMID:26224687

Functional impairment in adults positively screened for attention-deficit hyperactivity disorder: the role of symptom presentation and executive functioning.

PubMed

Szuromi, Bálint; Bitter, István; Czobor, Pál

2013-10-01

While the number of symptoms of attention-deficit hyperactivity disorder (ADHD) decreases with age, a high proportion of adults with ADHD symptoms suffer from persistent functional impairment (Fi) linked to these symptoms. Our objective was to investigate the specific roles of two potentially important predictors of this Fi: the clinical symptom presentation and the deficit in executive functions (EFs). A total of 158 subjects from a community sample positively screened for ADHD were classified into two groups: those with and without Fi. Following a detailed diagnostic process, participants were administered a self-rating scale for ADHD symptoms as well as a neuropsychological test battery containing tests of EF and attention relevant as potential cognitive endophenotypes for ADHD. The overall number as well as the number of inattentive, hyperactive and impulsive symptoms, confirmed both by examiner and self-report, were significantly higher among Fi subjects. The highest odds ratio for Fi was associated with impulsive symptoms. Additionally, self-reported complaints of problems with self-concept were significantly higher among Fi subjects. No significant relationship between Fi and neuropsychological measures of EF and attention was detected. This study revealed that the number of symptoms, in particular that of impulsivity, had a significant impact on Fi in adults with symptoms of ADHD. Furthermore, our results underline the importance of assessing complaints and behaviors related to self-concept, which are not included in DSM-IV diagnostic criteria of ADHD but nonetheless may be associated with functional outcome of the disorder. Copyright © 2013 Elsevier Inc. All rights reserved.

The relationship between cognitive function and life space: the potential role of personal control beliefs.

PubMed

Sartori, Andrea C; Wadley, Virginia G; Clay, Olivio J; Parisi, Jeanine M; Rebok, George W; Crowe, Michael

2012-06-01

We examined the relationship of cognitive and functional measures with life space (a measure of spatial mobility examining extent of movement within a person's environment) in older adults, and investigated the potential moderating role of personal control beliefs. Internal control beliefs reflect feelings of competence and personal agency, while attributions of external control imply a more dependent or passive point of view. Participants were 2,737 adults from the ACTIVE study, with a mean age of 74 years. Females comprised 76% of the sample, with good minority representation (27% African American). In multiple regression models controlling for demographic factors, cognitive domains of memory, reasoning, and processing speed were significantly associated with life space (p < .001 for each), and reasoning ability appeared most predictive (B = .117). Measures of everyday function also showed significant associations with life space, independent from the traditional cognitive measures. Interactions between cognitive function and control beliefs were tested, and external control beliefs moderated the relationship between memory and life space, with the combination of high objective memory and low external control beliefs yielding the highest life space (t = -2.07; p = .039). In conclusion, older adults with better cognitive function have a larger overall life space. Performance-based measures of everyday function may also be useful in assessing the functional outcome of life space. Additionally, subjective external control beliefs may moderate the relationship between objective cognitive function and life space. Future studies examining the relationships between these factors longitudinally appear worthwhile to further elucidate the interrelationships of cognitive function, control beliefs, and life space. PsycINFO Database Record (c) 2012 APA, all rights reserved

Impact of Neurocognition on Social and Role Functioning in Individuals at Clinical High Risk for Psychosis

PubMed Central

Carrión, Ricardo E.; Goldberg, Terry E.; McLaughlin, Danielle; Auther, Andrea M.; Correll, Christoph U.; Cornblatt, Barbara A.

2011-01-01

Objective Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. Method A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Results Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. Conclusions These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning. PMID:21536691

Impact of neurocognition on social and role functioning in individuals at clinical high risk for psychosis.

PubMed

Carrión, Ricardo E; Goldberg, Terry E; McLaughlin, Danielle; Auther, Andrea M; Correll, Christoph U; Cornblatt, Barbara A

2011-08-01

Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning.

The role of executive functioning in children's attentional pain control: an experimental analysis.

PubMed

Verhoeven, Katrien; Dick, Bruce; Eccleston, Christopher; Goubert, Liesbet; Crombez, Geert

2014-02-01

Directing attention away from pain is often used in children's pain treatment programs to control pain. However, empirical evidence concerning its effectiveness is inconclusive. We therefore sought to understand other influencing factors, including executive function and its role in the pain experience. This study investigates the role of executive functioning in the effectiveness of distraction. School children (n=164) completed executive functioning tasks (inhibition, switching, and working memory) and performed a cold-pressor task. One half of the children simultaneously performed a distracting tone-detection task; the other half did not. Results showed that participants in the distraction group were engaged in the distraction task and were reported to pay significantly less attention to pain than controls. Executive functioning influenced distraction task engagement. More specifically, participants with good inhibition and working memory abilities performed the distraction task better; participants with good switching abilities reported having paid more attention to the distraction task. Furthermore, distraction was found to be ineffective in reducing pain intensity and affect. Executive functioning did not influence the effectiveness of distraction. However, a relationship was found between executive functioning and pain affect, indicating that participants with good inhibition and working memory abilities experienced the cold-pressor task as less stressful and unpleasant. Our findings suggest that distraction as a process for managing pain is complex. While it appears that executive function may play a role in adult distraction, in this study it did not direct attention away from pain. It may instead be involved in the overall pain experience. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Roles of proteolysis in regulation of GPCR function

PubMed Central

Cottrell, GS

2013-01-01

The enzymatic activity of peptidases must be tightly regulated to prevent uncontrolled hydrolysis of peptide bonds, which could have devastating effects on biological systems. Peptidases are often generated as inactive propeptidases, secreted with endogenous inhibitors, or they are compartmentalized. Propeptidases become active after proteolytic removal of N-terminal activation peptides by other peptidases. Some peptidases only become active towards substrates only at certain pHs, thus confining activity to specific compartments or conditions. This review discusses the different roles proteolysis plays in regulating GPCRs. At the cell-surface, certain GPCRs are regulated by the hydrolytic inactivation of bioactive peptides by membrane-anchored peptidases, which prevent signalling. Conversely, cell-surface peptidases can also generate bioactive peptides, which directly activate GPCRs. Alternatively, cell-surface peptidases activated by GPCRs, can generate bioactive peptides to cause transactivation of receptor tyrosine kinases, thereby promoting signalling. Certain peptidases can signal directly to cells, by cleaving GPCR to initiate intracellular signalling cascades. Intracellular peptidases also regulate GPCRs; lysosomal peptidases destroy GPCRs in lysosomes to permanently terminate signalling and mediate down-regulation; endosomal peptidases cleave internalized peptide agonists to regulate GPCR recycling, resensitization and signalling; and soluble intracellular peptidases also participate in GPCR function by regulating the ubiquitination state of GPCRs, thereby altering GPCR signalling and fate. Although the use of peptidase inhibitors has already brought success in the treatment of diseases such as hypertension, the discovery of new regulatory mechanisms involving proteolysis that control GPCRs may provide additional targets to modulate dysregulated GPCR signalling in disease. PMID:23043558

The role of food in the functional gastrointestinal disorders: introduction to a manuscript series.

PubMed

Chey, William D

2013-05-01

Functional gastrointestinal disorders (FGIDs) are characterized by the presence of chronic or recurrent symptoms that are felt to originate from the gastrointestinal (GI) tract, which cannot be attributed to an identifiable structural or biochemical cause. Food is associated with symptom onset or exacerbation in a significant proportion of FGID patients. Despite this, the role of food in the pathogenesis of the FGIDs has remained poorly understood. For this reason, diet has largely played an adjunctive rather than a primary role in the management of FGID patients. In recent years, there has been a rapid expansion in our understanding of the role of food in GI function and sensation and how food relates to GI symptoms in FGID patients. In a series of evidence-based manuscripts produced by the Rome Foundation Working Group on the role of food in FGIDs, comprehensive reviews of the physiological changes associated with nutrient intake, and the respective roles of carbohydrates, fiber, protein, and fats are provided. The series concludes with a manuscript that provides guidance on proper clinical trial design when considering the role of food in FGIDs.

Analagous Population Structures for Two Alphabaculoviruses Highlight a Functional Role for Deletion Mutants

PubMed Central

Serrano, Amaya; Williams, Trevor; Simón, Oihane; López-Ferber, Miguel; Caballero, Primitivo

2013-01-01

A natural Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) isolate from Florida shares a strikingly similar genotypic composition to that of a natural Spodoptera frugiperda MNPV (SfMNPV) isolate from Nicaragua. Both isolates comprise a high proportion of large-deletion genotypes that lack genes that are essential for viral replication or transmission. To determine the likely origins of such genotypically similar population structures, we performed genomic and functional analyses of these genotypes. The homology of nucleotides in the deleted regions was as high as 79%, similar to those of other colinear genomic regions, although some SfMNPV genes were not present in SeMNPV. In addition, no potential consensus sequences were shared between the deletion flanking sequences. These results indicate an evolutionary mechanism that independently generates and sustains deletion mutants within each virus population. Functional analyses using different proportions of complete and deletion genotypes were performed with the two viruses in mixtures of occlusion bodies (OBs) or co-occluded virions. Ratios greater than 3:1 of complete/deletion genotypes resulted in reduced pathogenicity (expressed as median lethal dose), but there were no significant changes in the speed of kill. In contrast, OB yields increased only in the 1:1 mixture. The three phenotypic traits analyzed provide a broader picture of the functional significance of the most extensively deleted SeMNPV genotype and contribute toward the elucidation of the role of such mutants in baculovirus populations. PMID:23204420

Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor*

PubMed Central

Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L.; Lee, Chow H.

2017-01-01

MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo, molecular beacons can also be employed to inhibit microRNAs in a specific manner. PMID:28100783

Thyroid function. Pathogenesis of Graves ophthalmopathy--a role for TSH-R?

PubMed

Wall, Jack R

2014-05-01

A new study highlights the complexities of anti-TSH-receptor antibody function and the differences between adult and paediatric patients with Graves disease, adding to the controversy regarding the possible role of these antibodies in the development of ophthalmopathy.

Protective role of Parkin in skeletal muscle contractile and mitochondrial function.

PubMed

Gouspillou, Gilles; Godin, Richard; Piquereau, Jérome; Picard, Martin; Mofarrahi, Mahroo; Mathew, Jasmin; Purves-Smith, Fennigje M; Sgarioto, Nicolas; Hepple, Russell T; Burelle, Yan; Hussain, Sabah N A

2018-04-22

Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are degraded. The exact physiological significance of Parkin in regulating mitochondrial function and contractility in skeletal muscle remains largely unexplored. Using Park2 -/- mice, we show that Parkin ablation causes a decrease in muscle specific force, a severe decrease in mitochondrial respiration, mitochondrial uncoupling and an increased susceptibility to opening of the permeability transition pore. These results demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in skeletal muscles. Parkin is an E3 ubiquitin ligase encoded by the Park2 gene. Parkin has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are sequestered in autophagosomes and delivered to lysosomes for degradation. Although Parkin has been mainly studied for its implication in neuronal degeneration in Parkinson disease, its role in other tissues remains largely unknown. In the present study, we investigated the skeletal muscles of Park2 knockout (Park2 -/- ) mice to test the hypothesis that Parkin plays a physiological role in mitochondrial quality control in normal skeletal muscle, a tissue highly reliant on mitochondrial content and function. We first show that the tibialis anterior (TA) of Park2 -/- mice display a slight but significant decrease in its specific force. Park2 -/ - muscles also show a trend for type IIB fibre hypertrophy without alteration in muscle fibre type proportion. Compared to Park2 +/+ muscles, the mitochondrial function of Park2 -/- skeletal muscles was significantly impaired, as indicated by the significant decrease in ADP-stimulated mitochondrial respiratory rates, uncoupling, reduced activities of respiratory chain complexes containing mitochondrial DNA (mtDNA)-encoded subunits

One-range addition theorems for derivatives of Slater-type orbitals.

PubMed

Guseinov, Israfil

2004-06-01

Using addition theorems for STOs introduced by the author with the help of complete orthonormal sets of psi(alpha)-ETOs (Guseinov II (2003) J Mol Model 9:190-194), where alpha=1, 0, -1, -2, ..., a large number of one-range addition theorems for first and second derivatives of STOs are established. These addition theorems are especially useful for computation of multicenter-multielectron integrals over STOs that arise in the Hartree-Fock-Roothaan approximation and also in the Hylleraas function method, which play a significant role for the study of electronic structure and electron-nuclei interaction properties of atoms, molecules, and solids. The relationships obtained are valid for arbitrary quantum numbers, screening constants and location of STOs.

When monoclonal antibodies are not monospecific: Hybridomas frequently express additional functional variable regions

PubMed Central

Bradbury, Andrew R. M.; Trinklein, Nathan D.; Wilkinson, Ian C.; Tandon, Atul K.; Anderson, Stephen; Bladen, Catherine L.; Jones, Brittany; Aldred, Shelley Force; Bestagno, Marco; Burrone, Oscar; Maynard, Jennifer; Ferrara, Fortunato; Görnemann, Janina; Glanville, Jacob; Wolf, Philipp; Frenzel, Andre; Wong, Julin; Koh, Xin Yu; Eng, Hui-Yan; Lane, David; Lefranc, Marie-Paule; Clark, Mike

2018-01-01

ABSTRACT Monoclonal antibodies are commonly assumed to be monospecific, but anecdotal studies have reported genetic diversity in antibody heavy chain and light chain genes found within individual hybridomas. As the prevalence of such diversity has never been explored, we analyzed 185 random hybridomas, in a large multicenter dataset. The hybridomas analyzed were not biased towards those with cloning difficulties or known to have additional chains. Of the hybridomas we evaluated, 126 (68.1%) contained no additional productive chains, while the remaining 59 (31.9%) contained one or more additional productive heavy or light chains. The expression of additional chains degraded properties of the antibodies, including specificity, binding signal and/or signal-to-noise ratio, as determined by enzyme-linked immunosorbent assay and immunohistochemistry. The most abundant mRNA transcripts found in a hybridoma cell line did not necessarily encode the antibody chains providing the correct specificity. Consequently, when cloning antibody genes, functional validation of all possible VH and VL combinations is required to identify those with the highest affinity and lowest cross-reactivity. These findings, reflecting the current state of hybridomas used in research, reiterate the importance of using sequence-defined recombinant antibodies for research or diagnostic use. PMID:29485921

Marine reserves lag behind wilderness in the conservation of key functional roles

PubMed Central

D'agata, Stéphanie; Mouillot, David; Wantiez, Laurent; Friedlander, Alan M.; Kulbicki, Michel; Vigliola, Laurent

2016-01-01

Although marine reserves represent one of the most effective management responses to human impacts, their capacity to sustain the same diversity of species, functional roles and biomass of reef fishes as wilderness areas remains questionable, in particular in regions with deep and long-lasting human footprints. Here we show that fish functional diversity and biomass of top predators are significantly higher on coral reefs located at more than 20 h travel time from the main market compared with even the oldest (38 years old), largest (17,500 ha) and most restrictive (no entry) marine reserve in New Caledonia (South-Western Pacific). We further demonstrate that wilderness areas support unique ecological values with no equivalency as one gets closer to humans, even in large and well-managed marine reserves. Wilderness areas may therefore serve as benchmarks for management effectiveness and act as the last refuges for the most vulnerable functional roles. PMID:27354026

Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

PubMed

Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

2015-11-26

Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

The role of cocoa as a cigarette additive: opportunities for product regulation.

PubMed

Sokol, Natasha A; Kennedy, Ryan David; Connolly, Gregory N

2014-07-01

The 2009 Family Smoking Prevention and Tobacco Control Act prohibited the use of characterizing flavors in cigarettes; however, some of these flavors are still used in cigarettes at varying levels. We reviewed tobacco industry internal documents to investigate the role of one of these flavors, cocoa, with the objective of understanding its relationship to sensory and risk perception, promotion of dependence, and enhancement of attractiveness and acceptability. We used the Legacy Tobacco Documents Library to identify documents relevant to our research questions. Initial search terms were generated following an examination of published literature on cocoa, other cigarette additives, and sensory and risk perception. Further research questions and search terms were generated based on review of documents generated from the initial search terms. Cocoa is widely applied to cigarettes and has been used by the tobacco industry as an additive since the early 20th century. Cocoa can alter the sensory properties of cigarette smoke, including by providing a more appealing taste and decreasing its harshness. The tobacco industry has experimented with manipulating cocoa levels as a means of achieving sensory properties that appeal to women and youth. Although cocoa is identified as a flavor on tobacco industry Web sites, it may serve other sensory purposes in cigarettes as well. Eliminating cocoa as an additive from tobacco products may affect tobacco product abuse liability by altering smokers' perceptions of product risk, and decreasing product appeal, especially among vulnerable populations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of alloy additions on strengthening in 17-4 PH stainless steel

NASA Astrophysics Data System (ADS)

Murthy, Arpana Sudershan

Alloy modifications by addition of niobium (Nb), vanadium (V), nitrogen (N) and cobalt (Co) to cast 17-4 PH steel were investigated to determine the effect on mechanical properties. Additions of Nb, V, and N increased the yield strength from 1120 MPa to 1310 MPa while decreased the room temperature charpy V notch (CVN) toughness from 20 J to four Joules. The addition of Co to cast 17-4 PH steel enhanced the yield strength and CVN toughness from 1140 MPa to 1290 MPa and from 3.7 J to 5.5 J, respectively. In the base 17-4 PH steel, an increase in block width from 2.27 ± 0.10 μm in the solution treated condition to 3.06 ± 0.17 μm upon aging at 755 K was measured using orientation image microscopy. Cobalt inhibited recrystallization and block boundary migration during aging resulting in a finer martensitic block structure. The influence of Co on copper (Cu) precipitation in steels was studied using atom probe tomography. A narrower precipitate size distribution was observed in the steels with Co addition. The concentration profile across the matrix / precipitate interface indicated rejection of Co atoms from the copper precipitates. This behavior was observed to be energetically favorable using first principle calculations. The activation energies for Cu precipitation increased from 205 kJ/ mol in the non-cobalt containing alloy, to 243 kJ/ mol, and 272 kJ/ mol in alloys with 3 wt. %Co, and 7 wt. % Co, respectively. The role of Co on Cu precipitation in cast 17-4 PH steel is proposed as follows: (i) Co is rejected out of the Cu precipitate and sets up a barrier to the growth of the Cu precipitate; (ii) results in Cu precipitates of smaller size and narrower distribution; (iii) the coarsening of Cu precipitates is inhibited; and (iv) the activation energy for Cu precipitation increases.

Children's Learning in Scientific Thinking: Instructional Approaches and Roles of Variable Identification and Executive Function

NASA Astrophysics Data System (ADS)

Blums, Angela

The present study examines instructional approaches and cognitive factors involved in elementary school children's thinking and learning the Control of Variables Strategy (CVS), a critical aspect of scientific reasoning. Previous research has identified several features related to effective instruction of CVS, including using a guided learning approach, the use of self-reflective questions, and learning in individual and group contexts. The current study examined the roles of procedural and conceptual instruction in learning CVS and investigated the role of executive function in the learning process. Additionally, this study examined how learning to identify variables is a part of the CVS process. In two studies (individual and classroom experiments), 139 third, fourth, and fifth grade students participated in hands-on and paper and pencil CVS learning activities and, in each study, were assigned to either a procedural instruction, conceptual instruction, or control (no instruction) group. Participants also completed a series of executive function tasks. The study was carried out with two parts--Study 1 used an individual context and Study 2 was carried out in a group setting. Results indicated that procedural and conceptual instruction were more effective than no instruction, and the ability to identify variables was identified as a key piece to the CVS process. Executive function predicted ability to identify variables and predicted success on CVS tasks. Developmental differences were present, in that older children outperformed younger children on CVS tasks, and that conceptual instruction was slightly more effective for older children. Some differences between individual and group instruction were found, with those in the individual context showing some advantage over the those in the group setting in learning CVS concepts. Conceptual implications about scientific thinking and practical implications in science education are discussed.

Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives - A Review.

PubMed

Melo, A D B; Silveira, H; Luciano, F B; Andrade, C; Costa, L B; Rostagno, M H

2016-01-01

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

A Functional Role for KLF6-SV1 in Lung Adenocarcinoma Prognosis and Chemotherapy Response

PubMed Central

DiFeo, Analisa; Feld, Lauren; Rodriguez, Estefania; Wang, Christine; Beer, David G.; Martignetti, John A.; Narla, Goutham

2009-01-01

Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer. PMID:18250346

The Role of Functional and Perceptual Attributes: Evidence from Picture Naming in Dementia

ERIC Educational Resources Information Center

Harley, Trevor A.; Grant, Fiona

2004-01-01

We examined the performance of a group of people with moderately severe Alzheimer's type dementia on a naming task. We found that functional information plays an important role in determining naming performance on both living and non-living things. Perceptual information may play some role in naming living things. We also found some evidence that…

Effects of the addition of functional electrical stimulation to ground level gait training with body weight support after chronic stroke.

PubMed

Prado-Medeiros, Christiane L; Sousa, Catarina O; Souza, Andréa S; Soares, Márcio R; Barela, Ana M F; Salvini, Tania F

2011-01-01

The addition of functional electrical stimulation (FES) to treadmill gait training with partial body weight support (BWS) has been proposed as a strategy to facilitate gait training in people with hemiparesis. However, there is a lack of studies that evaluate the effectiveness of FES addition on ground level gait training with BWS, which is the most common locomotion surface. To investigate the additional effects of commum peroneal nerve FES combined with gait training and BWS on ground level, on spatial-temporal gait parameters, segmental angles, and motor function. Twelve people with chronic hemiparesis participated in the study. An A1-B-A2 design was applied. A1 and A2 corresponded to ground level gait training using BWS, and B corresponded to the same training with the addition of FES. The assessments were performed using the Modified Ashworth Scale (MAS), Functional Ambulation Category (FAC), Rivermead Motor Assessment (RMA), and filming. The kinematics analyzed variables were mean walking speed of locomotion; step length; stride length, speed and duration; initial and final double support duration; single-limb support duration; swing period; range of motion (ROM), maximum and minimum angles of foot, leg, thigh, and trunk segments. There were not changes between phases for the functional assessment of RMA, for the spatial-temporal gait variables and segmental angles, no changes were observed after the addition of FES. The use of FES on ground level gait training with BWS did not provide additional benefits for all assessed parameters.

α,β-Unsaturated monoterpene acid glucose esters: structural diversity, bioactivities and functional roles.

PubMed

Goodger, Jason Q D; Woodrow, Ian E

2011-12-01

The glycosylation of lipophilic small molecules produces many important plant secondary metabolites. The majority of these are O-glycosides with relatively fewer occurring as glucose esters of aromatic or aliphatic acids. In particular, monoterpene acid glucose esters have much lower structural diversity and distribution compared to monoterpene glycosides. Nevertheless, there have been over 20 monoterpene acid glucose esters described from trees in the genus Eucalyptus (Myrtaceae) in recent years, all based on oleuropeic acid, menthiafolic acid or both. Here we review all of the glucose esters containing these monoterpenoids identified in plants to date. Many of the compounds contain phenolic aglycones and all contain at least one α,β-unsaturated carbonyl, affording a number of important potential therapeutic reactivities such as anti-tumor promotion, carcinogenesis suppression, and anti-oxidant and anti-inflammatory activities. Additional properties such as cytotoxicity, bitterness, and repellency are suggestive of a role in plant defence, but we also discuss their localization to the exterior of foliar secretory cavity lumina, and suggest they may also protect secretory cells from toxic terpenes housed within these structures. Finally we discuss how the use of a recently developed protocol to isolate secretory cavities in a functional state could be used in conjunction with systems biology approaches to help characterize their biosynthesis and roles in plants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fungal endophytes: diversity and functional roles

USGS Publications Warehouse

Rodriguez, R.J.; White, J.F.; Arnold, A.E.; Redman, R.S.

2009-01-01

All plants in natural ecosystems appear to be symbiotic with fungal endophytes. This highly diverse group of fungi can have profound impacts on plant communities through increasing fitness by conferring abiotic and biotic stress tolerance, increasing biomass and decreasing water consumption, or decreasing fitness by altering resource allocation. Despite more than 100 yr of research resulting in thousands of journal articles, the ecological significance of these fungi remains poorly characterized. Historically, two endophytic groups (clavicipitaceous (C) and nonclavicipitaceous (NC)) have been discriminated based on phylogeny and life history traits. Here, we show that NC-endophytes represent three distinct functional groups based on host colonization and transmission, in planta biodiversity and fitness benefits conferred to hosts. Using this framework, we contrast the life histories, interactions with hosts and potential roles in plant ecophysiology of C- and NC-endophytes, and highlight several key questions for future work in endophyte biology.

Brief Report: Additive and Subtractive Counterfactual Reasoning of Children with High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Begeer, Sander; Terwogt, Mark Meerum; Lunenburg, Patty; Stegge, Hedy

2009-01-01

The development of additive ("If only I had done...") and subtractive ("If only I had not done....") counterfactual reasoning was examined in children with High Functioning Autism Spectrum Disorders (HFASD) (n = 72) and typically developing controls (n = 71), aged 6-12 years. Children were presented four stories where they could generate…

Role of Corneal Stromal Cells on Epithelial Cell Function during Wound Healing

PubMed Central

Kowtharapu, Bhavani S.; Murín, Radovan; Jünemann, Anselm G. M.; Stachs, Oliver

2018-01-01

Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs) and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM) on corneal epithelial cell function along with substance P (SP). Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK), paxillin, vimentin, β-catenin and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT) regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits α4, α5, αV, β1 and β3 whereas SFCM increased α4, α5, αV, β1 and β5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained activation of ZEB1

The impact of premorbid adjustment, neurocognition, and depression on social and role functioning in patients in an early psychosis treatment program.

PubMed

Minor, Kyle S; Friedman-Yakoobian, Michelle; Leung, Y Jude; Meyer, Eric C; Zimmet, Suzanna V; Caplan, Brina; Monteleone, Thomas; Bryant, Caitlin; Guyer, Margaret; Keshavan, Matcheri S; Seidman, Larry J

2015-05-01

Functional impairments are debilitating concomitants of psychotic disorders and are present early in the illness course and, commonly, prior to psychosis onset. The factors affecting social and role functioning in early psychosis (EP) following treatment are unclear. We evaluated whether six months of participation in the PREP(R), Boston, EP treatment program, part of a public-academic community mental health center, was related to improvements in social and role functioning and whether premorbid adjustment in adolescence, baseline neurocognition, and depression symptoms predicted functional improvement. The Global Functioning Social and Role scales, MATRICS neurocognitive battery, and Calgary Depression Scale were assessed at baseline and six months during naturalistic treatment, while premorbid adjustment was measured at baseline. All participants were psychotic disorder patients in PREP(R) (n = 46 with social functioning and 47 with role functioning measures at both time points). Large improvements were observed in role functioning (d = 0.84) and medium to large improvements were observed in social functioning (d = 0.70). Models consisting of adolescent premorbid adjustment and change in depression symptoms predicted social and role functioning change, whereas neuropsychological functioning did not. Substantial improvements in social and role functioning were observed among this sample participating in a recovery-based EP program. The impact of clinical factors on social and role functioning was highlighted. Further studies of premorbid adjustment in adolescence and the treatment of depression in EP programs in controlled treatment trials are needed to confirm these findings. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Using NMR spectroscopy to elucidate the role of molecular motions in enzyme function

PubMed Central

Lisi, George P.; Loria, J. Patrick

2015-01-01

Conformational motions play an essential role in enzyme function, often facilitating the formation of enzyme-substrate complexes and/or product release. Although considerable debate remains regarding the role of molecular motions in the conversion of enzymatic substrates to products, numerous examples have found motions to be crucial for optimization of enzyme scaffolds, effective substrate binding, and product dissociation. Conformational fluctuations are often rate-limiting to enzyme catalysis, primarily through product release, with the chemical reaction occurring much more quickly. As a result, the direct involvement of motions at various stages along the enzyme reaction coordinate remains largely unknown and untested. In the following review, we describe the use of solution NMR techniques designed to probe various timescales of molecular motions and detail examples in which motions play a role in propagating catalytic effects from the active site and directly participate in essential aspects of enzyme function. PMID:26952190

Engineered silica nanoparticles as additives in lubricant oils

PubMed Central

López, Teresa Díaz-Faes; González, Alfonso Fernández; Del Reguero, Ángel; Matos, María; Díaz-García, Marta E; Badía-Laíño, Rosana

2015-01-01

Silica nanoparticles (SiO2 NPs) synthesized by the sol–gel approach were engineered for size and surface properties by grafting hydrophobic chains to prevent their aggregation and facilitate their contact with the phase boundary, thus improving their dispersibility in lubricant base oils. The surface modification was performed by covalent binding of long chain alkyl functionalities using lauric acid and decanoyl chloride to the SiO2 NP surface. The hybrid SiO2 NPs were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, simultaneous differential thermal analysis, nuclear magnetic resonance and dynamic light scattering, while their dispersion in two base oils was studied by static multiple light scattering at low (0.01% w/v) and high (0.50%w/v) concentrations. The nature of the functional layer and the functionalization degree seemed to be directly involved in the stability of the suspensions. The potential use of the functional SiO2 NPs as lubricant additives in base oils, specially designed for being used in hydraulic circuits, has been outlined by analyzing the tribological properties of the dispersions. The dendritic structure of the external layer played a key role in the tribological characteristics of the material by reducing the friction coefficient and wear. These nanoparticles reduce drastically the waste of energy in friction processes and are more environmentally friendly than other additives. PMID:27877840

Functional Gustatory Role of Chemoreceptors in Drosophila Wings.

PubMed

Raad, Hussein; Ferveur, Jean-François; Ledger, Neil; Capovilla, Maria; Robichon, Alain

2016-05-17

Neuroanatomical evidence argues for the presence of taste sensilla in Drosophila wings; however, the taste physiology of insect wings remains hypothetical, and a comprehensive link to mechanical functions, such as flight, wing flapping, and grooming, is lacking. Our data show that the sensilla of the Drosophila anterior wing margin respond to both sweet and bitter molecules through an increase in cytosolic Ca(2+) levels. Conversely, genetically modified flies presenting a wing-specific reduction in chemosensory cells show severe defects in both wing taste signaling and the exploratory guidance associated with chemodetection. In Drosophila, the chemodetection machinery includes mechanical grooming, which facilitates the contact between tastants and wing chemoreceptors, and the vibrations of flapping wings that nebulize volatile molecules as carboxylic acids. Together, these data demonstrate that the Drosophila wing chemosensory sensilla are a functional taste organ and that they may have a role in the exploration of ecological niches. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Teachers’ Beliefs and Practices Regarding the Role of Executive Functions in Reading and Arithmetic

PubMed Central

Rapoport, Shirley; Rubinsten, Orly; Katzir, Tami

2016-01-01

The current study investigated early elementary school teachers’ beliefs and practices regarding the role of Executive Functions (EFs) in reading and arithmetic. A new research questionnaire was developed and judged by professionals in the academia and the field. Reponses were obtained from 144 teachers from Israel. Factor analysis divided the questionnaire into three valid and reliable subscales, reflecting (1) beliefs regarding the contribution of EFs to reading and arithmetic, (2) pedagogical practices, and (3) a connection between the cognitive mechanisms of reading and arithmetic. Findings indicate that teachers believe EFs affect students’ performance in reading and arithmetic. These beliefs were also correlated with pedagogical practices. Additionally, special education teachers’ scored higher on the different subscales compared to general education teachers. These findings shed light on the way teachers perceive the cognitive foundations of reading and arithmetic and indicate to which extent these perceptions guide their teaching practices. PMID:27799917

Teachers' Beliefs and Practices Regarding the Role of Executive Functions in Reading and Arithmetic.

PubMed

Rapoport, Shirley; Rubinsten, Orly; Katzir, Tami

2016-01-01

The current study investigated early elementary school teachers' beliefs and practices regarding the role of Executive Functions (EFs) in reading and arithmetic. A new research questionnaire was developed and judged by professionals in the academia and the field. Reponses were obtained from 144 teachers from Israel. Factor analysis divided the questionnaire into three valid and reliable subscales, reflecting (1) beliefs regarding the contribution of EFs to reading and arithmetic, (2) pedagogical practices, and (3) a connection between the cognitive mechanisms of reading and arithmetic. Findings indicate that teachers believe EFs affect students' performance in reading and arithmetic. These beliefs were also correlated with pedagogical practices. Additionally, special education teachers' scored higher on the different subscales compared to general education teachers. These findings shed light on the way teachers perceive the cognitive foundations of reading and arithmetic and indicate to which extent these perceptions guide their teaching practices.

Role of strongly interacting additives in tuning the structure and properties of polymer systems

NASA Astrophysics Data System (ADS)

Daga, Vikram Kumar

Block copolymer (BCP) nanocomposites are an important class of hybrid materials in which the BCP guides the spatial location and the periodic assembly of the additives. High loadings of well-dispersed nanofillers are generally important for many applications including mechanical reinforcing of polymers. In particular the composites shown in this work might find use as etch masks in nanolithography, or for enabling various phase selective reactions for new materials development. This work explores the use of hydrogen bonding interactions between various additives (such as homopolymers and non-polymeric additives) and small, disordered BCPs to cause the formation of well-ordered morphologies with small domains. A detailed study of the organization of homopolymer chains and the evolution of structure during the process of ordering is performed. The results demonstrate that by tuning the selective interaction of the additive with the incorporating phase of the BCP, composites with significantly high loadings of additives can be formed while maintaining order in the BCP morphology. The possibility of high and selective loading of additives in one of the phases of the ordered BCP composite opens new avenues due to high degree of functionalization and the proximity of the additives within the incorporating phase. This aspect is utilized in one case for the formation of a network structure between adjoining additive cores to derive mesoporous inorganic materials with their structures templated by the BCP. The concept of additive-driven assembly is extended to formulate BCPadditive blends with an ability to undergo photo-induced ordering. Underlying this strategy is the ability to transition a weakly interacting additive to its strongly interacting form. This strategy provides an on-demand, non-intrusive route for formation of well-ordered nanostructures in arbitrarily defined regions of an otherwise disordered material. The second area explored in this dissertation deals

The roles and functions of safety professionals in Taiwan: Comparing the perceptions of safety professionals and safety educators.

PubMed

Wu, Tsung-Chih

2011-10-01

The perspectives of both internal and external members have to be considered when developing safety curricula. This study discusses perceptional differences between safety educators (SEs) and safety professionals (SPs) regarding the function of SPs. The findings will serve as a reference framework for the establishment of core safety competencies and the development of safety curricula for SPs. 248 respondents, including both SEs and SPs, completed self-administered questionnaires, which included the 45-item safety function scale (SFS). Nine factors were extracted from the scale using exploratory factor analysis (EFA), namely inspection and research, regulatory tasks, emergency procedures and settlement of damage, management and financial affairs, culture change, problem identification and analysis, developing and implementing solutions, knowledge management, and training and communications. Descriptive statistical results indicated that SPs and SEs hold differing views on the rank of the frequency of safety functions. MANOVA results indicated that SPs' perceptions of developing and implementing solutions, training and communications, inspection and research, and management and financial affairs were significantly higher than that of SEs. On the other hand, SE's perceptions regarding participation in regulatory tasks were significantly higher than those of SPs. Based on these results, the author suggests that a clear communication channel should be established between universities and industry to reduce the gap between the perceptions of SEs and SPs. The results of the study are statistically and practically significant. In addition to serving as a reference for the development of safety curricula, the results are also conducive to the establishment of SP roles and functions. Ultimately the development of more suitable safety curricula would open up employment competition for students who graduate from safety-related programs. SPs, on the other hand, can correctly

Exploring the role and function of trial steering committees: results of an expert panel meeting.

PubMed

Harman, Nicola L; Conroy, Elizabeth J; Lewis, Steff C; Murray, Gordon; Norrie, John; Sydes, Matt R; Lane, J Athene; Altman, Douglas G; Baigent, Colin; Bliss, Judith M; Campbell, Marion K; Elbourne, Diana; Evans, Stephen; Sandercock, Peter; Gamble, Carrol

2015-12-30

The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998. An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised. The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor. This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is

Role of p21-activated kinases in cardiovascular development and function.

PubMed

Kelly, Mollie L; Astsaturov, Artyom; Chernoff, Jonathan

2013-11-01

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.

Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor.

PubMed

Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L; Lee, Chow H

2017-03-03

MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo , molecular beacons can also be employed to inhibit microRNAs in a specific manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Benchmark calculations of excess electrons in water cluster cavities: balancing the addition of atom-centered diffuse functions versus floating diffuse functions.

PubMed

Zhang, Changzhe; Bu, Yuxiang

2016-09-14

Diffuse functions have been proved to be especially crucial for the accurate characterization of excess electrons which are usually bound weakly in intermolecular zones far away from the nuclei. To examine the effects of diffuse functions on the nature of the cavity-shaped excess electrons in water cluster surroundings, both the HOMO and LUMO distributions, vertical detachment energies (VDEs) and visible absorption spectra of two selected (H2O)24(-) isomers are investigated in the present work. Two main types of diffuse functions are considered in calculations including the Pople-style atom-centered diffuse functions and the ghost-atom-based floating diffuse functions. It is found that augmentation of atom-centered diffuse functions contributes to a better description of the HOMO (corresponding to the VDE convergence), in agreement with previous studies, but also leads to unreasonable diffuse characters of the LUMO with significant red-shifts in the visible spectra, which is against the conventional point of view that the more the diffuse functions, the better the results. The issue of designing extra floating functions for excess electrons has also been systematically discussed, which indicates that the floating diffuse functions are necessary not only for reducing the computational cost but also for improving both the HOMO and LUMO accuracy. Thus, the basis sets with a combination of partial atom-centered diffuse functions and floating diffuse functions are recommended for a reliable description of the weakly bound electrons. This work presents an efficient way for characterizing the electronic properties of weakly bound electrons accurately by balancing the addition of atom-centered diffuse functions and floating diffuse functions and also by balancing the computational cost and accuracy of the calculated results, and thus is very useful in the relevant calculations of various solvated electron systems and weakly bound anionic systems.

Embedding beyond electrostatics-The role of wave function confinement.

PubMed

Nåbo, Lina J; Olsen, Jógvan Magnus Haugaard; Holmgaard List, Nanna; Solanko, Lukasz M; Wüstner, Daniel; Kongsted, Jacob

2016-09-14

We study excited states of cholesterol in solution and show that, in this specific case, solute wave-function confinement is the main effect of the solvent. This is rationalized on the basis of the polarizable density embedding scheme, which in addition to polarizable embedding includes non-electrostatic repulsion that effectively confines the solute wave function to its cavity. We illustrate how the inclusion of non-electrostatic repulsion results in a successful identification of the intense π → π(∗) transition, which was not possible using an embedding method that only includes electrostatics. This underlines the importance of non-electrostatic repulsion in quantum-mechanical embedding-based methods.

Role of chronic exercise on pelvic floor support and function

PubMed Central

Shaw, Janet M.; Nygaard, Ingrid E.

2017-01-01

Purpose of review To summarize recent literature about the potential role of chronic exercise on pelvic floor support and function. Recent findings Stress urinary incontinence is common during physical activity. Scant evidence suggests a dose-response association between higher volumes of exercise and urinary incontinence. Athletes do not appear to have greater pelvic floor muscle strength or worse pelvic floor support compared to non-athletes. Pelvic floor muscle electromyographic activity increases substantially as running speeds increase. Summary Based on the current literature, no strong conclusions can be drawn about whether chronic exercise exerts a positive or negative influence on pelvic floor support and function. Adopting longitudinal research methodology that prospectively monitors exercise exposure and subsequent changes in pelvic floor support and function would help to reduce selection bias associated with cross sectional studies on groups of athletes. PMID:28212118

Functional Analogy in Human Metabolism: Enzymes with Different Biological Roles or Functional Redundancy?

PubMed Central

Piergiorge, Rafael Mina; de Miranda, Antonio Basílio; Catanho, Marcos

2017-01-01

Abstract Since enzymes catalyze almost all chemical reactions that occur in living organisms, it is crucial that genes encoding such activities are correctly identified and functionally characterized. Several studies suggest that the fraction of enzymatic activities in which multiple events of independent origin have taken place during evolution is substantial. However, this topic is still poorly explored, and a comprehensive investigation of the occurrence, distribution, and implications of these events has not been done so far. Fundamental questions, such as how analogous enzymes originate, why so many events of independent origin have apparently occurred during evolution, and what are the reasons for the coexistence in the same organism of distinct enzymatic forms catalyzing the same reaction, remain unanswered. Also, several isofunctional enzymes are still not recognized as nonhomologous, even with substantial evidence indicating different evolutionary histories. In this work, we begin to investigate the biological significance of the cooccurrence of nonhomologous isofunctional enzymes in human metabolism, characterizing functional analogous enzymes identified in metabolic pathways annotated in the human genome. Our hypothesis is that the coexistence of multiple enzymatic forms might not be interpreted as functional redundancy. Instead, these enzymatic forms may be implicated in distinct (and probably relevant) biological roles. PMID:28854631

Using NMR spectroscopy to elucidate the role of molecular motions in enzyme function.

PubMed

Lisi, George P; Loria, J Patrick

2016-02-01

Conformational motions play an essential role in enzyme function, often facilitating the formation of enzyme-substrate complexes and/or product release. Although considerable debate remains regarding the role of molecular motions in the conversion of enzymatic substrates to products, numerous examples have found motions to be crucial for optimization of enzyme scaffolds, effective substrate binding, and product dissociation. Conformational fluctuations are often rate-limiting to enzyme catalysis, primarily through product release, with the chemical reaction occurring much more quickly. As a result, the direct involvement of motions at various stages along the enzyme reaction coordinate remains largely unknown and untested. In the following review, we describe the use of solution NMR techniques designed to probe various timescales of molecular motions and detail examples in which motions play a role in propagating catalytic effects from the active site and directly participate in essential aspects of enzyme function. Copyright © 2015 Elsevier B.V. All rights reserved.

The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease.

PubMed

Townley-Tilson, W H Davin; Pi, Xinchun; Xie, Liang

2015-01-01

Ischemic heart disease is the leading cause of death worldwide. Oxygen-sensing proteins are critical components of the physiological response to hypoxia and reperfusion injury, but the role of oxygen and oxygen-mediated effects is complex in that they can be cardioprotective or deleterious to the cardiac tissue. Over 200 oxygen-sensing proteins mediate the effects of oxygen tension and use oxygen as a substrate for posttranslational modification of other proteins. Hydroxylases are an essential component of these oxygen-sensing proteins. While a major role of hydroxylases is regulating the transcription factor HIF, we investigate the increasing scope of hydroxylase substrates. This review discusses the importance of oxygen-mediated effects in the heart as well as how the field of oxygen-sensing proteins is expanding, providing a more complete picture into how these enzymes play a multifaceted role in cardiac function and disease. We also review how oxygen-sensing proteins and hydroxylase function could prove to be invaluable in drug design and therapeutic targets for heart disease.

Roles of water in protein structure and function studied by molecular liquid theory.

PubMed

Imai, Takashi

2009-01-01

The roles of water in the structure and function of proteins have not been completely elucidated. Although molecular simulation has been widely used for the investigation of protein structure and function, it is not always useful for elucidating the roles of water because the effect of water ranges from atomic to thermodynamic level. The three-dimensional reference interaction site model (3D-RISM) theory, which is a statistical-mechanical theory of molecular liquids, can yield the solvation structure at the atomic level and calculate the thermodynamic quantities from the intermolecular potentials. In the last few years, the author and coworkers have succeeded in applying the 3D-RISM theory to protein aqueous solution systems and demonstrated that the theory is useful for investigating the roles of water. This article reviews some of the recent applications and findings, which are concerned with molecular recognition by protein, protein folding, and the partial molar volume of protein which is related to the pressure effect on protein.

Spectral-domain Optical Coherence Tomography in Manifest Glaucoma: Its Additive Role in Structural Diagnosis.

PubMed

Kim, Ko Eun; Oh, Sohee; Jeoung, Jin Wook; Suh, Min Hee; Seo, Je Hyun; Kim, Martha; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2016-11-01

To investigate the additive role of spectral-domain optical coherence tomography (SDOCT) in the structural diagnosis in glaucoma. Reliability and validity analysis. Structural examinations from 109 eyes of 109 healthy individuals and 151 eyes of 151 glaucoma patients with different severities were included. Four structural-diagnostic examination sets were prepared using stereo-optic disc photography (SDP), red-free retinal nerve fiber layer photography (RNFLP), and SDOCT: (1) SDP (S), (2) SDP and SDOCT (SO), (3) SDP and RNFLP (SR), and (4) SDP, RNFLP, and SDOCT (SRO). Five glaucoma specialists were instructed to classify subjects as normal or glaucoma using each of the 4 diagnostic sets in the order S, SO, SR, and SRO, with a 1-month interval. The interobserver agreement was evaluated using kappa (κ) statistics. The additive effect of SDOCT on the diagnostic performance of the specialists was evaluated using the generalized estimating equation. Five glaucoma specialists showed an excellent level of interobserver agreement on the diagnostic assessments based on the 4 sets. In the comparison of the collective diagnostic performance of the specialists, addition of SDOCT to SDP showed an approximately 2-fold significant increase in the diagnostic accuracy. Adding SDOCT to SDP significantly enhanced the specialists' structural-diagnostic ability with respect to the moderate glaucoma, though not mild or advanced glaucoma. SDOCT significantly enhanced the diagnostic accuracy of the glaucoma specialists' performance, showing its additive diagnostic value in judging glaucomatous structural damage, especially in the moderate stage of glaucoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Microplastic moves pollutants and additives to worms, reducing functions linked to health and biodiversity.

PubMed

Browne, Mark Anthony; Niven, Stewart J; Galloway, Tamara S; Rowland, Steve J; Thompson, Richard C

2013-12-02

Inadequate products, waste management, and policy are struggling to prevent plastic waste from infiltrating ecosystems [1, 2]. Disintegration into smaller pieces means that the abundance of micrometer-sized plastic (microplastic) in habitats has increased [3] and outnumbers larger debris [2, 4]. When ingested by animals, plastic provides a feasible pathway to transfer attached pollutants and additive chemicals into their tissues [5-15]. Despite positive correlations between concentrations of ingested plastic and pollutants in tissues of animals, few, if any, controlled experiments have examined whether ingested plastic transfers pollutants and additives to animals. We exposed lugworms (Arenicola marina) to sand with 5% microplastic that was presorbed with pollutants (nonylphenol and phenanthrene) and additive chemicals (Triclosan and PBDE-47). Microplastic transferred pollutants and additive chemicals into gut tissues of lugworms, causing some biological effects, although clean sand transferred larger concentrations of pollutants into their tissues. Uptake of nonylphenol from PVC or sand reduced the ability of coelomocytes to remove pathogenic bacteria by >60%. Uptake of Triclosan from PVC diminished the ability of worms to engineer sediments and caused mortality, each by >55%, while PVC alone made worms >30% more susceptible to oxidative stress. As global microplastic contamination accelerates, our findings indicate that large concentrations of microplastic and additives can harm ecophysiological functions performed by organisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Benefits of Simulation and Role-Playing to Teach Performance of Functional Assessments.

PubMed

Trail Ross, Mary Ellen; Otto, Dorothy A; Stewart Helton, Anne

The use of simulation is an innovative teaching strategy that has proven to be valuable in nursing education. This article describes the benefits of a simulation lab involving faculty role-play to teach baccalaureate nursing students how to properly assess the functional status of older adults. Details about the simulation lab, which involved functional assessments of two elderly community-dwelling residents, are presented, along with student and faculty evaluations of this teaching modality.

From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease.

PubMed

Sun, Miao; Kraus, W Lee

2015-02-01

Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases.

The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

PubMed

Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

2018-03-21

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

PubMed Central

Entringer, Sonja; Buss, Claudia; Swanson, James M.; Cooper, Dan M.; Wing, Deborah A.; Waffarn, Feizal; Wadhwa, Pathik D.

2012-01-01

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice. PMID:22655178

Minnesota School Principals' Perceptions of Minnesota School Counselors' Role and Functions

ERIC Educational Resources Information Center

Karch, Lisa Irene Hanson

2010-01-01

The purpose of the concurrent mixed methods study was to explore Minnesota principals' perceptive responses regarding the role and functions of Minnesota school counselors. A convenience sample of K-12 school principals was used for this study. Participant criteria was that each individual be a school principal in the state of Minnesota. School…

Interactive Effects of Dopamine Baseline Levels and Cycle Phase on Executive Functions: The Role of Progesterone.

PubMed

Hidalgo-Lopez, Esmeralda; Pletzer, Belinda

2017-01-01

Estradiol and progesterone levels vary along the menstrual cycle and have multiple neuroactive effects, including on the dopaminergic system. Dopamine relates to executive functions in an "inverted U-shaped" manner and its levels are increased by estradiol. Accordingly, dopamine dependent changes in executive functions along the menstrual cycle have been previously studied in the pre-ovulatory phase, when estradiol levels peak. Specifically it has been demonstrated that working memory is enhanced during the pre-ovulatory phase in women with low dopamine baseline levels, but impaired in women with high dopamine baseline levels. However, the role of progesterone, which peaks in the luteal cycle phase, has not been taken into account previously. Therefore, the main goals of the present study were to extend these findings (i) to the luteal cycle phase and (ii) to other executive functions. Furthermore, the usefulness of the eye blink rate (EBR) as an indicator of dopamine baseline levels in menstrual cycle research was explored. 36 naturally cycling women were tested during three cycle phases (menses-low sex hormones; pre-ovulatory-high estradiol; luteal-high progesterone and estradiol). During each session, women performed a verbal N-back task, as measure of working memory, and a single trial version of the Stroop task, as measure of response inhibition and cognitive flexibility. Hormone levels were assessed from saliva samples and spontaneous eye blink rate was recorded during menses. In the N-back task, women were faster during the luteal phase the higher their progesterone levels, irrespective of their dopamine baseline levels. In the Stroop task, we found a dopamine-cycle interaction, which was also driven by the luteal phase and progesterone levels. For women with higher EBR performance decreased during the luteal phase, whereas for women with lower EBR performance improved during the luteal phase. These findings suggest an important role of progesterone in

Asymmetric Functional Organozinc Additions to Aldehydes Catalyzed by 1,1′-Bi-2-naphthols (BINOLs)†

PubMed Central

2015-01-01

Conspectus Chiral alcohols are ubiquitous in organic structures. One efficient method to generate chiral alcohols is the catalytic asymmetric addition of a carbon nucleophile to a carbonyl compound since this process produces a C–C bond and a chiral center simultaneously. In comparison with the carbon nucleophiles such as an organolithium or a Grignard reagent, an organozinc reagent possesses the advantages of functional group tolerance and more mild reaction conditions. Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and alkynylzincs to generate functional chiral alcohols are discussed in this Account. Our laboratory has developed a series of 1,1′-bi-2-naphthol (BINOL)-based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is found that the 3,3′-dianisyl-substituted BINOLs are not only highly enantioselective for the alkylzinc addition to aldehydes, but also highly enantioselective for the diphenylzinc addition to aldehydes. A one-step synthesis has been achieved to incorporate Lewis basic amine groups into the 3,3′-positions of the partially hydrogenated H8BINOL. These H8BINOL–amine compounds have become more generally enantioselective and efficient catalysts for the diphenylzinc addition to aldehydes to produce various types of chiral benzylic alcohols. The application of the H8BINOL–amine catalysts is expanded by using in situ generated diarylzinc reagents from the reaction of aryl iodides with ZnEt2, which still gives high enantioselectivity and good catalytic activity. Such a H8BINOL–amine compound is further found to catalyze the highly enantioselective addition of vinylzincs, in situ generated from the treatment of vinyl iodides with ZnEt2, to aldehydes to give the synthetically very useful chiral allylic alcohols. We have discovered that the unfunctionalized BINOL in combination with ZnEt2 and Ti(OiPr)4 can catalyze the terminal alkyne addition to aldehydes to produce chiral propargylic alcohols

The Crucial Role of Additive Manufacturing at NASA

NASA Technical Reports Server (NTRS)

Vickers, John

2016-01-01

At NASA, the first steps of the Journey to Mars are well underway with the development of NASA's next generation launch system and investments in research and technologies that should increase the affordability, capability, and safety of exploration activities. Additive Manufacturing presents a disruptive opportunity for NASA to design and manufacture hardware with new materials at dramatically reduced cost and schedule. Opportunities to incorporate additive manufacturing align very well with NASA missions and with most NASA programs related to space, science, and aeronautics. The Agency also relies on many partnerships with other government agencies, industry and academia.

Role of theory of mind and executive function in explaining social intelligence: a structural equation modeling approach.

PubMed

Yeh, Zai-Ting

2013-01-01

Social intelligence is the ability to understand others and the social context effectively and thus to interact with people successfully. Research has suggested that the theory of mind (ToM) and executive function may play important roles in explaining social intelligence. The specific aim of the present study was to test with structural equation modeling (SEM) the hypothesis that performance on ToM tasks is more associated with social intelligence in the elderly than is performance on executive functions. One hundred and seventy-seven participants (age 56-96) completed ToM, executive function, and other basic cognition tasks, and were rated with social intelligence scales. The SEM results showed that ToM and executive function were strongly correlated (0.54); however, only the path coefficient from ToM to social intelligence, and not from executive function, was significant (0.37). ToM performance, but not executive function, was strongly correlated with social intelligence among elderly individuals. ToM and executive function might play different roles in social behavior during normal aging; however, based on the present results, it is possible that ToM might play an important role in social intelligence.

Experiences of Habitual Physical Activity in Maintaining Roles and Functioning among Older Adults: A Qualitative Study

PubMed Central

Svantesson, Ulla; Willén, Carin

2016-01-01

Physically active older adults have reduced risk of functional restrictions and role limitations. Several aspects may interrelate and influence habitual physical activity (PA). However, older adults' own perspectives towards their PA need to be addressed. The aim of this study was to explore the experiences of habitual physical activity in maintaining roles and functioning among older adult Palestinians ≥60 years. Data were collected through in-depth interviews based on a narrative approach. Seventeen participants were recruited (aged 64–84 years). Data were analyzed using a narrative interpretative method. Findings. Three central narratives were identified, “keep moving, stay healthy,” “social connectedness, a motive to stay active,” and “adapting strategies to age-related changes.” Conclusion. Habitual physical activity was perceived as an important factor to maintain functioning and to preserve active roles in older adults. Walking was the most prominent pattern of physical activity and it was viewed as a vital tool to maintain functioning among the older adults. Social connectedness was considered as a contributing factor to the status of staying active. To adapt the process of age-related changes in a context to stay active, the participants have used different adapting strategies, including protective strategy, awareness of own capabilities, and modifying or adopting new roles. PMID:28078141

Overweight, obesity and work functioning: the role of working-time arrangements.

PubMed

Nigatu, Yeshambel T; van de Ven, Hardy A; van der Klink, Jac J L; Brouwer, Sandra; Reijneveld, Sijmen A; Bültmann, Ute

2016-01-01

Obesity is associated with productivity loss, but little is known about how obese workers function at work and also the role of working-time arrangements on this association is lacking. Therefore, the aim of this study was to examine the association of overweight and obesity with work functioning (WF), and to determine whether the associations differ between workers with different working-time arrangements. A cross-sectional study was conducted within the sampling frame of the 'Shift Your Work' study that examined the effect of irregular working-times in relation to health and functioning at work. We included N = 622 Dutch employees, of which N = 384 (62%) were shift-workers, N = 171 (27%) on-call workers and N = 67 (11%) day-workers. Overweight and obesity were defined as BMI 25-30 and ≥30, respectively. WF was assessed using the Work-Role Functioning Questionnaire. The prevalences of overweight and obesity were 48% and 10% in all workers, 49% and 11% in shift-workers, 45% and 10% in on-call workers, and 49% and 6% in day workers, respectively. In all workers, obesity was associated with lower WF scores for physical demands (adjusted estimate, aB = -5.5). In shift-workers, obesity was associated with lower WF scores for output and physical demands (aB = -8.8 and -6.8, respectively). In day and on-call workers, overweight and obesity were not associated with WF. Overweight and obesity are highly prevalent in the working population. Obesity might reduce the executive function performance beyond physical limitations, and limit the ability to accomplish tasks successfully, especially in shift workers. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Shyness and Vocabulary: The Roles of Executive Functioning and Home Environmental Stimulation

PubMed Central

Nayena Blankson, A.; O’Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

2010-01-01

Although shyness has often been found to be negatively related to vocabulary, few studies have examined the processes that produce or modify this relation. The present study examined executive functioning skills and home environmental stimulation as potential mediating and moderating mechanisms. A sample of 3.5-year-old children (N=254) were administered executive functioning tasks and a vocabulary test during a laboratory visit. Mothers completed questionnaires assessing child shyness and home environmental stimulation. Our primary hypothesis was that executive functioning mediates the association between shyness and vocabulary, and home environmental stimulation moderates the relation between executive functioning and vocabulary. Alternative hypotheses were also tested. Results indicated that children with better executive functioning skills developed stronger vocabularies when reared in more, versus less, stimulating environments. Implications of these results are discussed in terms of the role of shyness, executive functioning, and home environmental stimulation in early vocabulary development. PMID:22096267

Teachers' Understanding of the Role of Executive Functions in Mathematics Learning.

PubMed

Gilmore, Camilla; Cragg, Lucy

2014-09-01

Cognitive psychology research has suggested an important role for executive functions, the set of skills that monitor and control thought and action, in learning mathematics. However, there is currently little evidence about whether teachers are aware of the importance of these skills and, if so, how they come by this information. We conducted an online survey of teachers' views on the importance of a range of skills for mathematics learning. Teachers rated executive function skills, and in particular inhibition and shifting, to be important for mathematics. The value placed on executive function skills increased with increasing teaching experience. Most teachers reported that they were aware of these skills, although few knew the term "executive functions." This awareness had come about through their teaching experience rather than from formal instruction. Researchers and teacher educators could do more to highlight the importance of these skills to trainee or new teachers.

NUCLEAR FACTOR Y Transcription Factors Have Both Opposing and Additive Roles in ABA-Mediated Seed Germination

PubMed Central

Kumimoto, Roderick W.; Siriwardana, Chamindika L.; Gayler, Krystal K.; Risinger, Jan R.; Siefers, Nicholas; Holt, Ben F.

2013-01-01

In the model organism Arabidopsis thaliana the heterotrimeric transcription factor NUCLEAR FACTOR Y (NF-Y) has been shown to play multiple roles in facilitating plant growth and development. Although NF-Y itself represents a multi-protein transcriptional complex, recent studies have shown important interactions with other transcription factors, especially those in the bZIP family. Here we add to the growing evidence that NF-Y and bZIP form common complexes to affect many processes. We carried out transcriptional profiling on nf-yc mutants and through subsequent analyses found an enrichment of bZIP binding sites in the promoter elements of misregulated genes. Using NF-Y as bait, yeast two hybrid assays yielded interactions with bZIP proteins that are known to control ABA signaling. Accordingly, we find that plants mutant for several NF-Y subunits show characteristic phenotypes associated with the disruption of ABA signaling. While previous reports have shown additive roles for NF-YC family members in photoperiodic flowering, we found that they can have opposing roles in ABA signaling. Collectively, these results demonstrated the importance and complexity of NF-Y in the integration of environmental and hormone signals. PMID:23527203

Dosage and duration effects of nitrogen additions on ectomycorrhizal sporocarp production and functioning: an example from two N-limited boreal forests.

PubMed

Hasselquist, Niles J; Högberg, Peter

2014-08-01

Although it is well known that nitrogen (N) additions strongly affect ectomycorrhizal (EM) fungal community composition, less is known about how different N application rates and duration of N additions affect the functional role EM fungi play in the forest N cycle.We measured EM sporocarp abundance and species richness as well as determined the δ (15)N in EM sporocarps and tree foliage in two Pinus sylvestris forests characterized by short- and long-term N addition histories and multiple N addition treatments. After 20 and 39 years of N additions, two of the long-term N addition treatments were terminated, thereby providing a unique opportunity to examine the temporal recovery of EM sporocarps after cessation of high N loading.In general, increasing N availability significantly reduced EM sporocarp production, species richness, and the amount of N retained in EM sporocarps. However, these general responses were strongly dependent on the application rate and duration of N additions. The annual addition of 20 kg·N·ha(-1) for the past 6 years resulted in a slight increase in the production and retention of N in EM sporocarps, whereas the addition of 100 kg·N·ha(-1)·yr(-1) during the same period nearly eliminated EM sporocarps. In contrast, long-term additions of N at rates of ca. 35 or 70 kg·N·ha(-1)·yr(-1) for the past 40 years did not eliminate tree carbon allocation to EM sporocarps, although there was a decrease in the abundance and a shift in the dominant EM sporocarp taxa. Despite no immediate recovery, EM sporocarp abundance and species richness approached those of the control 20 years after terminating N additions in the most heavily fertilized treatment, suggesting a recovery of carbon allocation to EM sporocarps after cessation of high N loading.Our results provide evidence for a tight coupling between tree carbon allocation to and N retention in EM sporocarps and moreover highlight the potential use of δ (15)N in EM sporocarps as a

Pyruvate dehydrogenase has a major role in mast cell function, and its activity is regulated by mitochondrial microphthalmia transcription factor.

PubMed

Sharkia, Israa; Hadad Erlich, Tal; Landolina, Nadine; Assayag, Miri; Motzik, Alex; Rachmin, Inbal; Kay, Gillian; Porat, Ziv; Tshori, Sagi; Berkman, Neville; Levi-Schaffer, Francesca; Razin, Ehud

2017-07-01

We have recently observed that oxidative phosphorylation-mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream of the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number, and function of mast cells. Localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored. We sought to explore the role played by PDH in mast cell exocytosis and to determine whether MITF is localized in the mitochondria and involved in regulation of PDH activity. Experiments were performed in vitro by using human and mouse mast cells, as well as rat basophil leukemia cells, and in vivo in mice. The effect of PDH inhibition on mast cell function was examined. PDH interaction with MITF was measured before and after immunologic activation. Furthermore, mitochondrial localization of MITF and its effect on PDH activity were determined. PDH is essential for immunologically mediated degranulation of mast cells. After activation, PDH is serine dephosphorylated. In addition, for the first time, we show that MITF is partially located in the mitochondria and interacts with PDH. This interaction is dependent on the phosphorylation state of PDH. Furthermore, mitochondrial MITF regulates PDH activity. The association of mitochondrial MITF with PDH emerges as an important regulator of mast cell function. Our findings indicate that PDH could arise as a new target for the manipulation of allergic diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Lead facilitates foci formation in a Balb/c-3T3 two-step cell transformation model: role of Ape1 function.

PubMed

Hernández-Franco, Pablo; Silva, Martín; Franco, Rodrigo; Valverde, Mahara; Rojas, Emilio

2018-04-01

Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 μM induced APE1 mRNA and upregulation of protein expression. This increase in mRNA expression is consistent throughout the chronic exposure. Additionally, we also found an impaired function of Ape1 through molecular beacon-based assay. To evaluate the impact of lead on foci formation, a Balb/c-3T3 two-step transformation model was used. Balb/c-3T3 cells were pretreated 1 week with low concentrations of lead before induction of transformation with n-methyl-n-nitrosoguanidine (MNNG) (0.5 μg/mL) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 μg/mL) (a classical two-step protocol). Morphological cell transformation increased in response to lead pretreatment that was paralleled with an increase in Ape1 mRNA and protein overexpression and an impairment of Ape1 activity and correlating with foci number. In addition, we found that lead pretreatment and MNNG (transformation initiator) increased DNA damage, determined by comet assay. Our data suggest that low lead concentrations (5, 30 μM) could play a facilitating role in cellular transformation, probably through the impaired function of housekeeping genes such as Ape1, leading to DNA damage accumulation and chromosomal instability, one of the most important hallmarks of cancer induced by chronic exposures.

The Dean as Administrator: Roles, Functions and Attributes. A Compilation of Presentations from the Executive Development Series I: "Have You Ever Thought of Being a Dean?" (1980-1981). Volume I.

ERIC Educational Resources Information Center

American Association of Colleges of Nursing, Washington, DC.

The role and attributes of deans of nursing as administrators of baccalaureate or higher degree programs are considered by six deans who contributed to a continuing education workshop series. In addition to outlining skills and attributes needed by administrators, Elizabeth Grossman examines five basic administrative functions: planning,…

Amaranth addition to enzymatically modified wheat flour improves dough functionality, bread immunoreactivity and quality.

PubMed

Heredia-Sandoval, N G; Calderón de la Barca, A M; Carvajal-Millán, E; Islas-Rubio, A R

2018-01-24

Consumers with gluten-related disorders require gluten-free (GF) foods to avoid an immune response. Alternative to the use of non-gluten containing grains to prepare GF bread, the gluten reactivity has been greatly reduced using a proline specific cleavage enzyme, however, the gluten functionality was lost. The aim of this study was to evaluate the effect of adding an amaranth flour blend (AFB) to enzymatically modified wheat-flour proteins on dough functionality and to evaluate the immunoreactivity and acceptability of the prepared bread. First, wheat flour (20% w/v, substrate) was hydrolyzed using 8.4 U mg -1 protein Aspergillus niger prolyl-endopeptidase (AnPEP) for 8 h at 40 °C under constant agitation. Four types of breads were prepared with the same formulation except for the type of flour (14% w.b.): wheat flour (WF), WF-AFB unmodified not incubated, WF-AFB unmodified incubated and WF-AFB modified. The protein composition and free thiols were analyzed before and after amaranth addition, and the flour and bread proteins were run using SDS-PAGE and immune-detected in blots with IgA from celiac disease patients. The immunoreactive gluten content, specific volume and bread acceptability were evaluated. The polymeric proteins and free thiol groups of WF decreased after AnPEP treatment. The electrophoretic patterns of the modified flour and bread proteins were different and the IgA-immunodetection in blots was highly reduced, particularly for the higher molecular weight subunits. The addition of AFB to the modified wheat flour prepared using AnPEP improved the dough functionality by increasing the thiol groups and allowed the preparation of a sensorially acceptable bread with only 60 mg kg -1 immunoreactive gluten.

The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected?

PubMed

Naufahu, Jane; Cunliffe, Adam D; Murray, Joanne F

2013-01-01

Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis. Rodent studies have shown that the ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest among pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status affects reproductive physiology and behaviours, thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails the integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged, giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems that regulate energy balance and reproductive function. Hence, this review focuses on published evidence concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homoeostasis with the neuroendocrine reproductive axis and, if so, by what means has received limited coverage in the literature; evidence to date and current theories are summarised herein.

The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.

PubMed

Lee, Jinwoo; Choi, Sun Mi; Lee, Chang-Hoon; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

2017-06-01

Diagnosis of intrathoracic tuberculosis (TB) lymphadenitis remains a challenge because of difficulties in obtaining adequate tissue and the lack of a sensitive test. Recently, Xpert MTB/RIF assay is being used for rapid diagnosis of pulmonary TB, but it has not yet been widely validated in intrathoracic TB lymphadenitis. The aim of this study was to assess the additional role of Xpert MTB/RIF in diagnosing intrathoracic TB lymphadenitis using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen. Consecutive patients who underwent Xpert MTB/RIF assay using EBUS-TBNA specimen from January 2012 and November 2013 at a tertiary referral hospital were recruited. Among them, the cases with malignant lymph nodes were excluded. Among 73 patients, 13 (17.8%) cases were diagnosed with intrathoracic TB lymphadenitis. In detail, 10 patients were diagnosed using conventional methods only (histology or AFB culture) and 3 patients were additionally diagnosed when adding Xpert MTB/RIF assay. The median time to diagnosis using Xpert MTB/RIF (1 day) was shorter than conventional methods (3 days for histology, 14 days for AFB culture). Rifampin resistance was not detected in any patients. In patients with enlarged intrathoracic lymph nodes and low suspicion of malignancy, combination of conventional diagnostic methods with Xpert MTB/RIF could lead to additional and rapid diagnosis of intrathoracic TB lymphadenitis. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Developing a national role description for medical directors in long-term care

PubMed Central

Rahim-Jamal, Sherin; Quail, Patrick; Bhaloo, Tajudaullah

2010-01-01

OBJECTIVE To develop a national role description for medical directors in long-term care (LTC) based on role functions drawn from the literature and the LTC industry. DESIGN A questionnaire about the role functions identified from the literature was mailed or e-mailed to randomly selected medical directors, directors of care or nursing (DOCs), and administrators in LTC facilities. SETTING Long-term care facilities in Canada randomly selected from regional clusters. PARTICIPANTS Medical directors, DOCs, and administrators in LTC facilities; a national advisory group of medical directors from the Long Term Care Medical Directors Association of Canada; and a volunteer group of medical directors. MAIN OUTCOME MEASURES Respondents were asked to indicate, from the list of identified functions, 1) whether medical directors spent any time on each activity; 2) whether medical directors should spend time on each activity; and 3) if medical directors should spend time on an activity, whether the activity was “essential” or “desirable.” RESULTS An overall response rate of 37% was obtained. At least 80% of the respondents from all 3 groups (medical directors, DOCs, and administrators) highlighted 24 functions they deemed to be “essential” or “desirable,” which were then included in the role description. In addition, the advisory group expanded the role description to include 5 additional responsibilities from the remaining 18 functions originally identified. A volunteer group of medical directors confirmed the resulting role description. CONCLUSION The role description developed as a result of this study brings clarity to the medical director’s role in Canadian LTC facilities; the functions outlined are considered important for medical directors to undertake. The role description could be a useful tool in negotiations pertaining to time commitment and expectations of a medical director and fair compensation for services rendered. PMID:20090058

Dietary Additive Probiotics Modulation of the Intestinal Microbiota.

PubMed

Hu, Shenglan; Wang, Li; Jiang, Zongyong

2017-01-01

The importance of the intestinal microbiota of animals is widely acknowledged because of its vital role in the health of animals. There are complex communities of microbiota, which colonize the gastrointestinal tract. Intestinal microbiota are conductive to animal health and the development of the host immune system. Probiotics are commonly used dietary additives where they provide the host with many beneficial functions, such as modulating intestinal homeostasis and promoting gut health. These beneficial effects of probiotics may accrue from the inhibiting the growth of pathogenic bacteria and promoting the growth of beneficial flora in the gastrointestinal tract. Probiotics colonization and its impact on gut microbiota members are highly species specific. Different probiotics have been shown to have dramatically different capacities of modulation physiological function. This review summarizes existing studies of the influence of dietary additive probiotics on the gut microbiota in different animals, such as humans, mice, pigs and chickens, to clarify the contribution of different kinds of probiotics to the intestinal microbiota. Moreover, the probable mechanism for the benefits of dietary supplementation with probiotics will be discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Genetic contribution to the relationship between social role function and depressive symptoms in Japanese elderly twins: a twin study.

PubMed

Nishihara, Reiko; Inui, Fujio; Kato, Kenji; Tomizawa, Rie; Hayakawa, Kazuo

2011-03-01

Social role function is the capacity to maintain interpersonal relationships and is essential for being independent in the community. Limitations in social role function often coexist with depressive symptoms, suggesting a possible common mechanistic basis. We investigated whether the observed association between these traits is mainly a result of genetic or environmental influences. In 2008, a questionnaire was sent to 745 male twins aged 65 years and older. Our sample included 397 male twins. The number of monozygotic twins was 302, and dizygotic was 95. Among the twin pairs for whom data were available for both twins, 75 twin pairs (150 individuals) were monozygotic and 28 pairs (56 individuals) were dizygotic. Social role function was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Depressive symptoms were measured by the 15-item version of the Geriatric Depression Scale. Relative importance of genes and environments for the phenotypes was calculated using structural equation analyses. Our results show that genetic influence was the major contributor to the relationship between social role function and depressive symptoms, and non-shared environmental influence was important for overall variation in each trait. We concluded that focusing on a non-shared environment is an essential approach for maintaining social role function and psychological well-being. It is suggested that treatments specific to depressive symptoms are more effective than indirect intervention targeting social role function. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

The Role of the Replacement Behavior in Function-Based Intervention

ERIC Educational Resources Information Center

Reeves, Linda M.; Ferro, Jolenea B.; Umbreit, John; Liaupsin, Carl J.

2017-01-01

Three students with autism spectrum disorder (ASD) who displayed off-task behavior participated in a two-phase study. In Phase 1, a functional behavioral assessment (FBA) was conducted for each student. In addition, an assessment of each student's ability to perform the replacement behavior identified that none of the participants was able to do…

The role of the cerebellum in the regulation of language functions.

PubMed

Starowicz-Filip, Anna; Chrobak, Adrian Andrzej; Moskała, Marek; Krzyżewski, Roger M; Kwinta, Borys; Kwiatkowski, Stanisław; Milczarek, Olga; Rajtar-Zembaty, Anna; Przewoźnik, Dorota

2017-08-29

The present paper is a review of studies on the role of the cerebellum in the regulation of language functions. This brain structure until recently associated chiefly with motor skills, visual-motor coordination and balance, proves to be significant also for cognitive functioning. With regard to language functions, studies show that the cerebellum determines verbal fluency (both semantic and formal) expressive and receptive grammar processing, the ability to identify and correct language mistakes, and writing skills. Cerebellar damage is a possible cause of aphasia or the cerebellar mutism syndrome (CMS). Decreased cerebellocortical connectivity as well as anomalies in the structure of the cerebellum are emphasized in numerous developmental dyslexia theories. The cerebellum is characterized by linguistic lateralization. From the neuroanatomical perspective, its right hemisphere and dentate nucleus, having multiple cerebellocortical connections with the cerebral cortical language areas, are particularly important for language functions. Usually, language deficits developed as a result of a cerebellar damage have subclinical intensity and require applying sensitive neuropsychological diagnostic tools designed to assess higher verbal functions.

A continued role for signaling functions in the early evolution of feathers.

PubMed

Ruxton, Graeme D; Persons Iv, W Scott; Currie, Philip J

2017-03-01

Persons and Currie (2015) argued against either flight, thermoregulation, or signaling as a functional benefit driving the earliest evolution of feathers; rather, they favored simple feathers having an initial tactile sensory function, which changed to a thermoregulatory function as density increased. Here, we explore the relative merits of early simple feathers that may have originated as tactile sensors progressing instead toward a signaling, rather than (or in addition to) a thermoregulatory function. We suggest that signaling could act in concert with a sensory function more naturally than could thermoregulation. As such, the dismissal of a possible signaling function and the presumption that an initial sensory function led directly to a thermoregulatory function (implicit in the title "bristles before down") are premature. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Role of Escherichia coli dnaG function in coliphage M13 DNA synthesis

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

Dasgupta, S.; Mitra, S.

Examination of the role of Escherichia coli dnaG function in different stages of M13 phage DNA synthesis by ultracentrifugal analysis of intracellular phage DNA in a thermosensitive dnaG mutant shows that: (a) the formation of parental double-strand replicative-form DNA (rfDNA) from the infecting virus is independent of dnaG function; (b) the synthesis of progeny rfDNA requires dnaG product; (c) after a pool of rfDNA is made up, dnaG function is not required for the progeny single-strand DNA (ssDNA) synthesis. The ssDNAs produced under nonpermissive condition are mostly circular and biologically functional.

High work-function hole transport layers by self-assembly using a fluorinated additive

DOE PAGES

Mauger, Scott A.; Li, Jun; Özmen, Özge Tüzün; ...

2013-10-30

The hole transport polymer poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) derives many of its favorable properties from a PSS-rich interfacial layer that forms spontaneously during coating. Since PEDOT:PSS is only usable as a blend it is not possible to study PEDOT:PSS without this interfacial layer. Through the use of the self-doped polymer sulfonated poly(thiophene-3-[2-(2-methoxyethoxy) ethoxy]-2,5-diyl) (S-P3MEET) and a polyfluorinated ionomer (PFI) it is possible to compare transparent conducting organic films with and without interfacial layers and to understand their function. Using neutron reflectometry, we show that PFI preferentially segregates at the top surface of the film during coating and forms a thermally stable surfacemore » layer. Because of this distribution we find that even small amounts of PFI increase the electron work function of the HTL. We also find that annealing at 150°C and above reduces the work function compared to samples heated at lower temperatures. Using near edge x-ray absorption fine structure spectroscopy and gas chromatography we show that this reduction in work function is due to S-P3MEET being doped by PFI. Organic photovoltaic devices with S-P3MEET/PFI hole transport layers yield higher power conversion efficiency than devices with pure S-P3MEET or PEDOT:PSS hole transport layers. Additionally, devices with a doped interface layer of S-P3MEET/PFI show superior performance to those with un-doped S-P3MEET.« less

The role of cognitive impairment in psychosocial functioning in remitted depression.

PubMed

Knight, Mattew J; Air, Tracy; Baune, Bernhard T

2018-08-01

Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls. Data were obtained from 182 participants of the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood, and social cognition in mood disorders. Participants' (Remitted MDD n = 72, Healthy n = 110) cognition was assessed with a battery of cognitive tests including the Repeatable Battery for the Assessment of Neuropsychological Function (RBANS) and other standard measures of cognition (e.g., The Tower of London task). Psychosocial functioning was clinically evaluated with the Functioning Assessment Short Test (FAST). The results indicated that executive functioning was the strongest independent predictor of functioning in remitted MDD patients, whereas various cognitive domains predicted psychosocial functioning in healthy individuals. Psychosocial functioning was measured with a clinical interview, and was therefore reliant on clinicians' judgement of impairment, as opposed to more objective measures of functioning. These findings suggest that executive cognition plays an important role in functional recovery in remitted depression, and may be a crucial target in adjunctive treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Early Childcare, Executive Functioning, and the Moderating Role of Early Stress Physiology

ERIC Educational Resources Information Center

Berry, Daniel; Willoughby, Michael T.; Blair, Clancy; Ursache, Alexandra; Granger, Douglas A.

2014-01-01

Intervention studies indicate that children's childcare experiences can be leveraged to support the development of executive functioning (EF). The role of more normative childcare experiences is less clear. Increasingly, theory and empirical work suggest that individual differences in children's physiological stress systems may be associated with…

Teachers' Understanding of the Role of Executive Functions in Mathematics Learning

PubMed Central

Gilmore, Camilla; Cragg, Lucy

2014-01-01

Cognitive psychology research has suggested an important role for executive functions, the set of skills that monitor and control thought and action, in learning mathematics. However, there is currently little evidence about whether teachers are aware of the importance of these skills and, if so, how they come by this information. We conducted an online survey of teachers' views on the importance of a range of skills for mathematics learning. Teachers rated executive function skills, and in particular inhibition and shifting, to be important for mathematics. The value placed on executive function skills increased with increasing teaching experience. Most teachers reported that they were aware of these skills, although few knew the term “executive functions.” This awareness had come about through their teaching experience rather than from formal instruction. Researchers and teacher educators could do more to highlight the importance of these skills to trainee or new teachers. PMID:25674156

Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress Response in Vertebrates

PubMed Central

Deck, Courtney A.; Honeycutt, Jamie L.; Cheung, Eugene; Reynolds, Hannah M.; Borski, Russell J.

2017-01-01

Leptin is a pleiotropic hormone that plays a critical role in regulating appetite, energy metabolism, growth, stress, and immune function across vertebrate groups. In mammals, it has been classically described as an adipostat, relaying information regarding energy status to the brain. While retaining poor sequence conservation with mammalian leptins, teleostean leptins elicit a number of similar regulatory properties, although current evidence suggests that it does not function as an adipostat in this group of vertebrates. Teleostean leptin also exhibits functionally divergent properties, however, possibly playing a role in glucoregulation similar to what is observed in lizards. Further, leptin has been recently implicated as a mediator of immune function and the endocrine stress response in teleosts. Here, we provide a review of leptin physiology in vertebrates, with a particular focus on its actions and regulatory properties in the context of stress and the regulation of energy homeostasis. PMID:28439255

Role of Receptor Activity Modifying Protein 1 in Function of the Calcium Sensing Receptor in the Human TT Thyroid Carcinoma Cell Line

PubMed Central

Desai, Aditya J.; Roberts, David J.

2014-01-01

The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by sensing minute changes in serum Ca2+ and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively) and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has occurred. PMID

Role of receptor activity modifying protein 1 in function of the calcium sensing receptor in the human TT thyroid carcinoma cell line.

PubMed

Desai, Aditya J; Roberts, David J; Richards, Gareth O; Skerry, Timothy M

2014-01-01

The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by sensing minute changes in serum Ca(2+) and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively) and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has occurred.

Integrating products of Bessel functions with an additional exponential or rational factor

NASA Astrophysics Data System (ADS)

Van Deun, Joris; Cools, Ronald

2008-04-01

We provide two MATLAB programs to compute integrals of the form ex∏i=1kJν_i(ax)dxand 0∞xr+x∏i=1kJν_i(ax)dx with Jν_i(x) the Bessel function of the first kind and (real) order ν. The parameter m is a real number such that ∑ν+m>-1 (to assure integrability near zero), r is real and the numbers c and a are all strictly positive. The program can deliver accurate error estimates. Program summaryProgram title: BESSELINTR, BESSELINTC Catalogue identifier: AEAH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 1601 No. of bytes in distributed program, including test data, etc.: 13 161 Distribution format: tar.gz Programming language: Matlab (version ⩾6.5), Octave (version ⩾2.1.69) Computer: All supporting Matlab or Octave Operating system: All supporting Matlab or Octave RAM: For k Bessel functions our program needs approximately ( 500+140k) double precision variables Classification: 4.11 Nature of problem: The problem consists in integrating an arbitrary product of Bessel functions with an additional rational or exponential factor over a semi-infinite interval. Difficulties arise from the irregular oscillatory behaviour and the possible slow decay of the integrand, which prevents truncation at a finite point. Solution method: The interval of integration is split into a finite and infinite part. The integral over the finite part is computed using Gauss-Legendre quadrature. The integrand on the infinite part is approximated using asymptotic expansions and this approximation is integrated exactly with the aid of the upper incomplete gamma function. In the case where a rational factor is present, this factor is first expanded in a Taylor series around infinity. Restrictions: Some (and eventually all

Small heat shock proteins: Role in cellular functions and pathology.

PubMed

Bakthisaran, Raman; Tangirala, Ramakrishna; Rao, Ch Mohan

2015-04-01

Small heat shock proteins (sHsps) are conserved across species and are important in stress tolerance. Many sHsps exhibit chaperone-like activity in preventing aggregation of target proteins, keeping them in a folding-competent state and refolding them by themselves or in concert with other ATP-dependent chaperones. Mutations in human sHsps result in myopathies, neuropathies and cataract. Their expression is modulated in diseases such as Alzheimer's, Parkinson's and cancer. Their ability to bind Cu2+, and suppress generation of reactive oxygen species (ROS) may have implications in Cu2+-homeostasis and neurodegenerative diseases. Circulating αB-crystallin and Hsp27 in the plasma may exhibit immunomodulatory and anti-inflammatory functions. αB-crystallin and Hsp20 exhitbit anti-platelet aggregation: these beneficial effects indicate their use as potential therapeutic agents. sHsps have roles in differentiation, proteasomal degradation, autophagy and development. sHsps exhibit a robust anti-apoptotic property, involving several stages of mitochondrial-mediated, extrinsic apoptotic as well as pro-survival pathways. Dynamic N- and C-termini and oligomeric assemblies of αB-crystallin and Hsp27 are important factors for their functions. We propose a "dynamic partitioning hypothesis" for the promiscuous interactions and pleotropic functions exhibited by sHsps. Stress tolerance and anti-apoptotic properties of sHsps have both beneficial and deleterious consequences in human health and diseases. Conditional and targeted modulation of their expression and/or activity could be used as strategies in treating several human disorders. The review attempts to provide a critical overview of sHsps and their divergent roles in cellular processes particularly in the context of human health and disease. Copyright © 2015. Published by Elsevier B.V.

Functional metabolite assemblies—a review

NASA Astrophysics Data System (ADS)

Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

2018-05-01

Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

The physiological functions of central nervous system pericytes and a potential role in pain

PubMed Central

Beazley-Long, Nicholas; Durrant, Alexandra M; Swift, Matthew N; Donaldson, Lucy F

2018-01-01

Central nervous system (CNS) pericytes regulate critical functions of the neurovascular unit in health and disease. CNS pericytes are an attractive pharmacological target for their position within the neurovasculature and for their role in neuroinflammation. Whether the function of CNS pericytes also affects pain states and nociceptive mechanisms is currently not understood. Could it be that pericytes hold the key to pain associated with CNS blood vessel dysfunction? This article reviews recent findings on the important physiological functions of CNS pericytes and highlights how these neurovascular functions could be linked to pain states. PMID:29623199

Reviews of Interleukin-37: Functions, Receptors, and Roles in Diseases

PubMed Central

2018-01-01

Interleukin-37 (IL-37) is an IL-1 family cytokine discovered in recent years and has 5 different isoforms. As an immunosuppressive factor, IL-37 can suppress excessive immune response. IL-37 plays a role in protecting the body against endotoxin shock, ischemia-reperfusion injury, autoimmune diseases, and cardiovascular diseases. In addition, IL-37 has a potential antitumor effect. IL-37 and its receptors may serve as novel targets for the study, diagnosis, and treatment of immune-related diseases and tumors.

From Discovery to Function: The Expanding Roles of Long NonCoding RNAs in Physiology and Disease

PubMed Central

Sun, Miao

2015-01-01

Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases. PMID:25426780

Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

PubMed Central

Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

2014-01-01

Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

Long-term effects of early-life exposure to environmental oestrogens on ovarian function: role of epigenetics.

PubMed

Cruz, G; Foster, W; Paredes, A; Yi, K D; Uzumcu, M

2014-09-01

Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. © 2014 British Society for Neuroendocrinology.

The role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness.

PubMed

Zhao, Hua; Zhang, Bei-Lin; Yang, Shao-Jun; Rusak, Benjamin

2015-01-15

Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression. Copyright © 2014 Elsevier B.V. All rights reserved.

[Roles and functions of military flight nursing: aeromedical evacuation].

PubMed

Lee, Chun-Lan; Hsiao, Yun-Chien; Chen, Chao-Yen

2012-06-01

Evacuating the injured is an important part of disaster medicine. Aircraft provide timely access to distant and remote areas and, in an emergency, can evacuate sick or injured individuals in such areas quickly and safely for critical treatment elsewhere. Aeromedical evacuation (AE) comprises the two categories of fixed-wing ambulance service and helicopter emergency medical service (HEMS). Each aims to accomplish unique objectives. In Taiwan, the Second Taiwan Strait Crisis in 1958 established the unique role and functions of medical flight nursing. Significant knowledge and experience has been accumulated in the field since that time in such areas as the effects of high altitude environments on individuals and equipment; physiological, psychological, social and spiritual factors that affect the injured and / or response team members; and emergency care delivery techniques. All have been essential elements in the development and delivery of comprehensive medical flight nurse training. Medical flight nursing belongs in a special professional category, as nurses must master knowledge on general and special-case casualty evacuation procedures, relevant instruments and equipment, triage, in-flight medical care, and aircraft loading requirements related to transporting the sick and injured. The internationalization of medical care has opened the potential to expand medical flight nursing roles and functions into disaster nursing. Although military considerations continue to frame medical flight nursing training and preparation today, the authors feel that creating strategic alliances with disaster nursing specialists and organizations overseas is a future developmental direction for Taiwan's medical flight nursing sector worth formal consideration.

Supporting women with advanced breast cancer: the impact of altered functional status on their social roles.

PubMed

Chen, Bai Qi Peggy; Parmar, Monica P; Gartshore, Kimberley

2014-01-01

Despite early detection of breast cancer and the progress of treatment modalities, metastasis-specific symptoms continue to impact women's functional status and daily living. The aim of this study was to explore the experience of altered functional status and social roles of women with advanced breast cancer. Using qualitative descriptive methodology, semi-structured interviews were conducted with 10 women diagnosed with advanced breast cancer and altered functional status attending a tertiary care cancer centre. Results illustrated the adaptive experience of women living with their illness as they reshaped their social roles to fit with their altered functional status and advanced disease. These findings highlight the opportunity for supportive care nursing interventions to facilitate the behavioural and cognitive transitions that are experienced by women with advanced breast cancer and altered functional status. These results may have implications for women with other advanced chronic diseases, though more research is required.

Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement

PubMed Central

Khandaker, Morshed; Vaughan, Melville B; Morris, Tracy L; White, Jeremiah J; Meng, Zhaotong

2014-01-01

The most common bone cement material used clinically today for orthopedic surgery is poly(methyl methacrylate) (PMMA). Conventional PMMA bone cement has several mechanical, thermal, and biological disadvantages. To overcome these problems, researchers have investigated combinations of PMMA bone cement and several bioactive particles (micrometers to nanometers in size), such as magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica. A study comparing the effect of these individual additives on the mechanical, thermal, and cell functional properties of PMMA would be important to enable selection of suitable additives and design improved PMMA cement for orthopedic applications. Therefore, the goal of this study was to determine the effect of inclusion of magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica additives in PMMA on the mechanical, thermal, and cell functional performance of PMMA. American Society for Testing and Materials standard three-point bend flexural and fracture tests were conducted to determine the flexural strength, flexural modulus, and fracture toughness of the different PMMA samples. A custom-made temperature measurement system was used to determine maximum curing temperature and the time needed for each PMMA sample to reach its maximum curing temperature. Osteoblast adhesion and proliferation experiments were performed to determine cell viability using the different PMMA cements. We found that flexural strength and fracture toughness were significantly greater for PMMA specimens that incorporated silica than for the other specimens. All additives prolonged the time taken to reach maximum curing temperature and significantly improved cell adhesion of the PMMA samples. The results of this study could be useful for improving the union of implant-PMMA or bone-PMMA interfaces by incorporating nanoparticles into PMMA cement for orthopedic and orthodontic applications. PMID:24920906

Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement.

PubMed

Khandaker, Morshed; Vaughan, Melville B; Morris, Tracy L; White, Jeremiah J; Meng, Zhaotong

2014-01-01

The most common bone cement material used clinically today for orthopedic surgery is poly(methyl methacrylate) (PMMA). Conventional PMMA bone cement has several mechanical, thermal, and biological disadvantages. To overcome these problems, researchers have investigated combinations of PMMA bone cement and several bioactive particles (micrometers to nanometers in size), such as magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica. A study comparing the effect of these individual additives on the mechanical, thermal, and cell functional properties of PMMA would be important to enable selection of suitable additives and design improved PMMA cement for orthopedic applications. Therefore, the goal of this study was to determine the effect of inclusion of magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica additives in PMMA on the mechanical, thermal, and cell functional performance of PMMA. American Society for Testing and Materials standard three-point bend flexural and fracture tests were conducted to determine the flexural strength, flexural modulus, and fracture toughness of the different PMMA samples. A custom-made temperature measurement system was used to determine maximum curing temperature and the time needed for each PMMA sample to reach its maximum curing temperature. Osteoblast adhesion and proliferation experiments were performed to determine cell viability using the different PMMA cements. We found that flexural strength and fracture toughness were significantly greater for PMMA specimens that incorporated silica than for the other specimens. All additives prolonged the time taken to reach maximum curing temperature and significantly improved cell adhesion of the PMMA samples. The results of this study could be useful for improving the union of implant-PMMA or bone-PMMA interfaces by incorporating nanoparticles into PMMA cement for orthopedic and orthodontic applications.

Functional Role of Infective Viral Particles on Metal Reduction

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

Coates, John D.

2014-04-01

A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans andmore » the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.« less

Cytokines and macrophage function in humans - role of stress

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald (Principal Investigator)

1996-01-01

We have begun this study to commence the determination of the role of mild chronic stress in the effects of space flight on macrophage/monocyte function, a component of the immune response. Medical students undergoing regular periods of stress and relaxation have been shown to be an excellent model for determining the effects of stress on immune responses. We have begun using this model using the macrophage/monocyte as model leukocyte. The monocyte/macrophage plays a central role in immunoregulation. The studies to be included in this three year project are the effects of stress on: (1) interactions of monocytes with microbes, (2) monocyte production of cytokines, (3) monocyte phagocytosis and activity, and (4) monocyte expression of cell surface antigens important in immune responses. Stress hormone levels will also be carried out to determine if there is a correlation between stress effects on immune responses and hormonal levels. Psychological testing to insure subjects are actually stressed or relaxed at the time of testing will also be carried out. The results obtained from the proposed studies should be comparable with space flight studies with whole animals and isolated cell cultures. When complete this study should allow the commencement of the establishment of the role of stress as one compartment of the induction of immune alterations by space flight.

Common hydraulic fracturing fluid additives alter the structure and function of anaerobic microbial communities

USGS Publications Warehouse

Mumford, Adam C.; Akob, Denise M.; Klinges, J. Grace; Cozzarelli, Isabelle M.

2018-01-01

The development of unconventional oil and gas (UOG) resources results in the production of large volumes of wastewater containing a complex mixture of hydraulic fracturing chemical additives and components from the formation. The release of these wastewaters into the environment poses potential risks that are poorly understood. Microbial communities in stream sediments form the base of the food chain and may serve as sentinels for changes in stream health. Iron-reducing organisms have been shown to play a role in the biodegradation of a wide range of organic compounds, and so to evaluate their response to UOG wastewater, we enriched anaerobic microbial communities from sediments collected upstream (background) and downstream (impacted) of an UOG wastewater injection disposal facility in the presence of hydraulic fracturing fluid (HFF) additives: guar gum, ethylene glycol, and two biocides, 2,2-dibromo-3-nitrilopropionamide (DBNPA) and bronopol (C3H6BrNO4). Iron reduction was significantly inhibited early in the incubations with the addition of biocides, whereas amendment with guar gum and ethylene glycol stimulated iron reduction relative to levels in the unamended controls. Changes in the microbial community structure were observed across all treatments, indicating the potential for even small amounts of UOG wastewater components to influence natural microbial processes. The microbial community structure differed between enrichments with background and impacted sediments, suggesting that impacted sediments may have been preconditioned by exposure to wastewater. These experiments demonstrated the potential for biocides to significantly decrease iron reduction rates immediately following a spill and demonstrated how microbial communities previously exposed to UOG wastewater may be more resilient to additional spills.

The role of PTEN in regulation of hepatic macrophages activation and function in progression and reversal of liver fibrosis

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

Cheng, Yahui; Tian, Yuanyao; Xia, Jialu

Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl{sub 4}-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl{sub 4}-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantlymore » decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis. - Highlights: • CCl{sub 4} treatment triggered a mixed M1/M2 macrophage phenotype in fibrosis. • Lower expression of PTEN in murine M2 macrophages in vivo and vitro. • PTEN modulates M2 macrophages activation via PI3K/Akt/STAT6 signaling. • Provide a new cellular target modulate macrophage mediated hepatic fibrosis.« less

Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

PubMed

Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

2018-01-04

Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mitochondrial functionality in female reproduction.

PubMed

Gąsior, Łukasz; Daszkiewicz, Regina; Ogórek, Mateusz; Polański, Zbigniew

2017-01-04

In most animal species female germ cells are the source of mitochondrial genome for the whole body of individuals. As a source of mitochondrial DNA for future generations the mitochondria in the female germ line undergo dynamic quantitative and qualitative changes. In addition to maintaining the intact template of mitochondrial genome from one generation to another, mitochondrial role in oocytes is much more complex and pleiotropic. The quality of mitochondria determines the ability of meiotic divisions, fertilization ability, and activation after fertilization or sustaining development of a new embryo. The presence of normal number of functional mitochondria is also crucial for proper implantation and pregnancy maintaining. This article addresses issues of mitochondrial role and function in mammalian oocyte and presents new approaches in studies of mitochondrial function in female germ cells.

Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo.

PubMed

Klueh, Ulrike; Kaur, Manjot; Qiao, Yi; Kreutzer, Donald L

2010-06-01

Little is known about the specific cells, mediators and mechanisms involved in the loss of glucose sensor function (GSF) in vivo. Since mast cells (MC) are known to be key effector cells in inflammation and wound healing, we hypothesized that MC and their products are major contributors to the skin inflammation and wound healing that controls GSF at sites of sensor implantation. To test this hypothesis we utilized a murine model of continuous glucose monitoring (CGM) in vivo in both normal C57BL/6 mice (mast cell sufficient), as well as mast cell deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (Sash) mice over a 28 day CGM period. As expected, both strains of mice displayed excellent CGM for the first 7 days post sensor implantation (PSI). CGM in the mast cell sufficient C57BL/6 mice was erratic over the remaining 21 days PSI. CGM in the mast cell deficient Sash mice displayed excellent sensor function for the entire 28 day of CGM. Histopathologic evaluation of implantation sites demonstrated that tissue reactions in Sash mice were dramatically less compared to the reactions in normal C57BL/6 mice. Additionally, mast cells were also seen to be consistently associated with the margins of sensor tissue reactions in normal C57BL/6 mice. Finally, direct injection of bone marrow derived mast cells at sites of sensor implantation induced an acute and dramatic loss of sensor function in both C57BL/6 and Sash mice. These results demonstrate the key role of mast cells in controlling glucose sensor function in vivo. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Functional roles of CSPG4/NG2 in chondrosarcoma.

PubMed

Jamil, Nuor S M; Azfer, Asim; Worrell, Harrison; Salter, Donald M

2016-04-01

CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase). Chondrosarcoma cells in which CSPG4/NG2 was knocked down were more sensitive to doxorubicin than wild-type cells. The results indicate that CSPG4/NG2 has roles in regulating chondrosarcoma cell function in relation to growth, spread and resistance to chemotherapy and that anti-CSPG4/NG2 therapies may have potential in the treatment of surgically unresectable chondrosarcoma. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Reactive polymer multilayers fabricated by covalent layer-by-layer assembly: 1,4-conjugate addition-based approaches to the design of functional biointerfaces.

PubMed

Bechler, Shane L; Lynn, David M

2012-05-14

We report on conjugate addition-based approaches to the covalent layer-by-layer assembly of thin films and the post-fabrication functionalization of biointerfaces. Our approach is based on a recently reported approach to the "reactive" assembly of covalently cross-linked polymer multilayers driven by the 1,4-conjugate addition of amine functionality in poly(ethyleneimine) (PEI) to the acrylate groups in a small-molecule pentacrylate species (5-Ac). This process results in films containing degradable β-amino ester cross-links and residual acrylate and amine functionality that can be used as reactive handles for the subsequent immobilization of new functionality. Layer-by-layer growth of films fabricated on silicon substrates occurred in a supra-linear manner to yield films ≈ 750 nm thick after the deposition of 80 PEI/5-Ac layers. Characterization by atomic force microscopy (AFM) suggested a mechanism of growth that involves the reactive deposition of nanometer-scale aggregates of PEI and 5-Ac during assembly. Infrared (IR) spectroscopy studies revealed covalent assembly to occur by 1,4-conjugate addition without formation of amide functionality. Additional experiments demonstrated that acrylate-containing films could be postfunctionalized via conjugate addition reactions with small-molecule amines that influence important biointerfacial properties, including water contact angles and the ability of film-coated surfaces to prevent or promote the attachment of cells in vitro. For example, whereas conjugation of the hydrophobic molecule decylamine resulted in films that supported cell adhesion and growth, films treated with the carbohydrate-based motif D-glucamine resisted cell attachment and growth almost completely for up to 7 days in serum-containing media. We demonstrate that this conjugate addition-based approach also provides a means of immobilizing functionality through labile ester linkages that can be used to promote the long-term, surface-mediated release

Preventive and Therapeutic Role of Functional Ingredients of Barley Grass for Chronic Diseases in Human Beings

PubMed Central

Du, Juan; Yang, Xiaomeng; Li, Xia; Li, Ling; Zhou, Yan; Yang, Tao

2018-01-01

Barley grass powder is the best functional food that provides nutrition and eliminates toxins from cells in human beings; however, its functional ingredients have played an important role as health benefit. In order to better cognize the preventive and therapeutic role of barley grass for chronic diseases, we carried out the systematic strategies for functional ingredients of barley grass, based on the comprehensive databases, especially the PubMed, Baidu, ISI Web of Science, and CNKI, between 2008 and 2017. Barley grass is rich in functional ingredients, such as gamma-aminobutyric acid (GABA), flavonoids, saponarin, lutonarin, superoxide dismutase (SOD), K, Ca, Se, tryptophan, chlorophyll, vitamins (A, B1, C, and E), dietary fiber, polysaccharide, alkaloid, metallothioneins, and polyphenols. Barley grass promotes sleep; has antidiabetic effect; regulates blood pressure; enhances immunity; protects liver; has anti-acne/detoxifying and antidepressant effects; improves gastrointestinal function; has anticancer, anti-inflammatory, antioxidant, hypolipidemic, and antigout effects; reduces hyperuricemia; prevents hypoxia, cardiovascular diseases, fatigue, and constipation; alleviates atopic dermatitis; is a calcium supplement; improves cognition; and so on. These results support that barley grass may be one of the best functional foods for preventive chronic diseases and the best raw material of modern diet structure in promoting the development of large health industry and further reveal that GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan mechanism of barley grass have preventive and therapeutic role for chronic diseases. This paper can be used as a scientific evidence for developing functional foods and novel drugs for barley grass for preventive chronic diseases.

The addition of functional task-oriented mental practice to conventional physical therapy improves motor skills in daily functions after stroke.

PubMed

Santos-Couto-Paz, Clarissa C; Teixeira-Salmela, Luci F; Tierra-Criollo, Carlos J

2013-01-01

Mental practice (MP) is a cognitive strategy which may improve the acquisition of motor skills and functional performance of athletes and individuals with neurological injuries. To determine whether an individualized, specific functional task-oriented MP, when added to conventional physical therapy (PT), promoted better learning of motor skills in daily functions in individuals with chronic stroke (13 ± 6.5 months post-stroke). Nine individuals with stable mild and moderate upper limb impairments participated, by employing an A1-B-A2 single-case design. Phases A1 and A2 included one month of conventional PT, and phase B the addition of MP training to PT. The motor activity log (MAL-Brazil) was used to assess the amount of use (AOU) and quality of movement (QOM) of the paretic upper limb; the revised motor imagery questionnaire (MIQ-RS) to assess the abilities in kinesthetic and visual motor imagery; the Minnesota manual dexterity test to assess manual dexterity; and gait speed to assess mobility. After phase A1, no significant changes were observed for any of the outcome measures. However, after phase B, significant improvements were observed for the MAL, AOU and QOM scores (p<0.0001), and MIQ-RS kinesthetic and visual scores (p=0.003; p=0.007, respectively). The significant gains in manual dexterity (p=0.002) and gait speed (p=0.019) were maintained after phase A2. Specific functional task-oriented MP, when added to conventional PT, led to improvements in motor imagery abilities combined with increases in the AOU and QOM in daily functions, manual dexterity, and gait speed.

The role of the non-collagenous matrix in tendon function.

PubMed

Thorpe, Chavaunne T; Birch, Helen L; Clegg, Peter D; Screen, Hazel R C

2013-08-01

Tendon consists of highly ordered type I collagen molecules that are grouped together to form subunits of increasing diameter. At each hierarchical level, the type I collagen is interspersed with a predominantly non-collagenous matrix (NCM) (Connect. Tissue Res., 6, 1978, 11). Whilst many studies have investigated the structure, organization and function of the collagenous matrix within tendon, relatively few have studied the non-collagenous components. However, there is a growing body of research suggesting the NCM plays an important role within tendon; adaptations to this matrix may confer the specific properties required by tendons with different functions. Furthermore, age-related alterations to non-collagenous proteins have been identified, which may affect tendon resistance to injury. This review focuses on the NCM within the tensional region of developing and mature tendon, discussing the current knowledge and identifying areas that require further study to fully understand structure-function relationships within tendon. This information will aid in the development of appropriate techniques for tendon injury prevention and treatment. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

PubMed

Tranel, Daniel; Damasio, Hanna; Denburg, Natalie L; Bechara, Antoine

2005-12-01

We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

Pharmacological Tools to Study the Role of Astrocytes in Neural Network Functions.

PubMed

Peña-Ortega, Fernando; Rivera-Angulo, Ana Julia; Lorea-Hernández, Jonathan Julio

2016-01-01

Despite that astrocytes and microglia do not communicate by electrical impulses, they can efficiently communicate among them, with each other and with neurons, to participate in complex neural functions requiring broad cell-communication and long-lasting regulation of brain function. Glial cells express many receptors in common with neurons; secrete gliotransmitters as well as neurotrophic and neuroinflammatory factors, which allow them to modulate synaptic transmission and neural excitability. All these properties allow glial cells to influence the activity of neuronal networks. Thus, the incorporation of glial cell function into the understanding of nervous system dynamics will provide a more accurate view of brain function. Our current knowledge of glial cell biology is providing us with experimental tools to explore their participation in neural network modulation. In this chapter, we review some of the classical, as well as some recent, pharmacological tools developed for the study of astrocyte's influence in neural function. We also provide some examples of the use of these pharmacological agents to understand the role of astrocytes in neural network function and dysfunction.

Potentially important periods of change in the development of social and role functioning in youth at clinical high risk for psychosis.

PubMed

Velthorst, Eva; Zinberg, Jamie; Addington, Jean; Cadenhead, Kristin S; Cannon, Tyrone D; Carrión, Ricardo E; Auther, Andrea; Cornblatt, Barbara A; McGlashan, Thomas H; Mathalon, Daniel H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Reichenberg, Abraham; Bearden, Carrie E

2018-02-01

The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12-23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.

Role of the MAGUK protein family in synapse formation and function.

PubMed

Oliva, Carlos; Escobedo, Pía; Astorga, César; Molina, Claudia; Sierralta, Jimena

2012-01-01

Synaptic function is crucially dependent on the spatial organization of the presynaptic and postsynaptic apparatuses and the juxtaposition of both membrane compartments. This precise arrangement is achieved by a protein network at the submembrane region of each cell that is built around scaffold proteins. The membrane-associated guanylate kinase (MAGUK) family of proteins is a widely expressed and well-conserved group of proteins that plays an essential role in the formation and regulation of this scaffolding. Here, we review general features of this protein family, focusing on the discs large and calcium/calmodulin-dependent serine protein kinase subfamilies of MAGUKs in the formation, function, and plasticity of synapses. Copyright © 2011 Wiley Periodicals, Inc.

Clinical Evaluation of Functional Vision of +1.5 Diopters near Addition, Aspheric, Rotational Asymmetric Multifocal Intraocular Lens

PubMed Central

Khoramnia, Rahmin; Attia, Mary Safwat; Koss, Michael Janusz; Linz, Katharina; Auffarth, Gerd Uwe

2016-01-01

Purpose To evaluate postoperative outcomes and visual performance in intermediate distance after implantation of a +1.5 diopters (D) addition, aspheric, rotational asymmetric multifocal intraocular lens (MIOL). Methods Patients underwent bilateral cataract surgery with implantation of an aspheric, asymmetric MIOL with +1.5 D near addition. A complete ophthalmological examination was performed preoperatively and 3 months postoperatively. The main outcome measures were monocular and binocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), distance corrected intermediate visual acuity (DCIVA), uncorrected near visual acuity (UNVA) and distance corrected keratometry, and manifest refraction. The Salzburg Reading Desk was used to analyze unilateral and bilateral functional vision with uncorrected and corrected reading acuity, reading distance, reading speed, and the smallest log-scaled print size that could be read effectively at near and intermediate distances. Results The study comprised 60 eyes of 30 patients (mean age, 68.30 ± 9.26 years; range, 34 to 80 years). There was significant improvement in UDVA and CDVA. Mean UIVA was 0.01 ± 0.09 logarithm of the minimum angle of resolution (logMAR) and mean DCIVA was -0.02 ± 0.11 logMAR. In Salzburg Reading Desk analysis for UIVA, the mean subjective intermediate distance was 67.58 ± 8.59 cm with mean UIVA of -0.02 ± 0.09 logMAR and mean word count of 96.38 ± 28.32 words/min. Conclusions The new aspheric, asymmetric, +1.5 D near addition MIOL offers good results for distance visual function in combination with good performance for intermediate distances and functional results for near distance. PMID:27729759

Clinical Evaluation of Functional Vision of +1.5 Diopters near Addition, Aspheric, Rotational Asymmetric Multifocal Intraocular Lens.

PubMed

Kretz, Florian Tobias Alwin; Khoramnia, Rahmin; Attia, Mary Safwat; Koss, Michael Janusz; Linz, Katharina; Auffarth, Gerd Uwe

2016-10-01

To evaluate postoperative outcomes and visual performance in intermediate distance after implantation of a +1.5 diopters (D) addition, aspheric, rotational asymmetric multifocal intraocular lens (MIOL). Patients underwent bilateral cataract surgery with implantation of an aspheric, asymmetric MIOL with +1.5 D near addition. A complete ophthalmological examination was performed preoperatively and 3 months postoperatively. The main outcome measures were monocular and binocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), distance corrected intermediate visual acuity (DCIVA), uncorrected near visual acuity (UNVA) and distance corrected keratometry, and manifest refraction. The Salzburg Reading Desk was used to analyze unilateral and bilateral functional vision with uncorrected and corrected reading acuity, reading distance, reading speed, and the smallest log-scaled print size that could be read effectively at near and intermediate distances. The study comprised 60 eyes of 30 patients (mean age, 68.30 ± 9.26 years; range, 34 to 80 years). There was significant improvement in UDVA and CDVA. Mean UIVA was 0.01 ± 0.09 logarithm of the minimum angle of resolution (logMAR) and mean DCIVA was -0.02 ± 0.11 logMAR. In Salzburg Reading Desk analysis for UIVA, the mean subjective intermediate distance was 67.58 ± 8.59 cm with mean UIVA of -0.02 ± 0.09 logMAR and mean word count of 96.38 ± 28.32 words/min. The new aspheric, asymmetric, +1.5 D near addition MIOL offers good results for distance visual function in combination with good performance for intermediate distances and functional results for near distance.

PTEN: Multiple Functions in Human Malignant Tumors.

PubMed

Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M A; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

2015-01-01

PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors.

PTEN: Multiple Functions in Human Malignant Tumors

PubMed Central

Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M. A.; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

2015-01-01

PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors. PMID:25763354

Insulin: its Role in the Central Control of Reproduction

PubMed Central

Sliwowska, Joanna H.; Fergani, Chrysanthi; Gawałek, Monika; Skowronska, Bogda; Fichna, Piotr; Lehman, Michael N.

2014-01-01

Insulin has long been recognized as a key regulator of energy homeostasis via its actions at the level of the brain, but in addition, plays a role in regulating neural control of reproduction. In this review, we consider and compare evidence from animal models demonstrating a role for insulin for physiological control of reproduction by effects on GnRH/LH secretion. We also review the role that insulin plays in prenatal programming of adult reproduction, and consider specific candidate neurons in the adult hypothalamus by which insulin may act to regulate reproductive function. Finally, we review clinical evidence of the role that insulin may play in adult human fertility and reproductive disorders. Overall, while insulin appears to have a significant impact on reproductive neuroendocrine function, there are many unanswered questions regarding its precise sites and mechanisms of action, and their impact on developing and adult reproductive neuroendocrine function. PMID:24874777

An allelic series reveals essential roles for FY in plant development in addition to flowering-time control.

PubMed

Henderson, Ian R; Liu, Fuquan; Drea, Sinead; Simpson, Gordon G; Dean, Caroline

2005-08-01

The autonomous pathway functions to promote flowering in Arabidopsis by limiting the accumulation of the floral repressor FLOWERING LOCUS C (FLC). Within this pathway FCA is a plant-specific, nuclear RNA-binding protein, which interacts with FY, a highly conserved eukaryotic polyadenylation factor. FCA and FY function to control polyadenylation site choice during processing of the FCA transcript. Null mutations in the yeast FY homologue Pfs2p are lethal. This raises the question as to whether these essential RNA processing functions are conserved in plants. Characterisation of an allelic series of fy mutations reveals that null alleles are embryo lethal. Furthermore, silencing of FY, but not FCA, is deleterious to growth in Nicotiana. The late-flowering fy alleles are hypomorphic and indicate a requirement for both intact FY WD repeats and the C-terminal domain in repression of FLC. The FY C-terminal domain binds FCA and in vitro assays demonstrate a requirement for both C-terminal FY-PPLPP repeats during this interaction. The expression domain of FY supports its roles in essential and flowering-time functions. Hence, FY may mediate both regulated and constitutive RNA 3'-end processing.

The role of the Wnt signaling pathway in incretin hormone production and function

PubMed Central

Chiang, Yu-ting A.; Ip, Wilfred; Jin, Tianru

2012-01-01

Glucose metabolism is tightly controlled by multiple hormones and neurotransmitters in response to nutritional, environmental, and emotional changes. In addition to insulin and glucagon produced by pancreatic islets, two incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP, also known as glucose-dependent insulinotropic peptide), also play important roles in blood glucose homeostasis. The incretin hormones mainly exert their regulatory effects via their corresponding receptors, which are expressed in pancreatic islets as well as many other extra-pancreatic organs. Recent studies have shown that the genes which encode these two incretin hormones can be regulated by the effectors of the Wnt signaling pathway, including TCF7L2, a transcription factor identified recently by extensive genome wide association studies as an important type 2 diabetes risk gene. Interestingly, TCF7L2 and β-catenin (β-cat), another effector of Wnt signaling pathway, may also mediate the function of the incretin hormones as well as the expression of their receptors in pancreatic β-cells. In this review, we have introduced the incretin hormones and the Wnt signaling pathway, summarized recent findings in the field, and provided our perspectives. PMID:22934027

Impaired Social and Role Function in Ultra-High Risk for Psychosis and First-Episode Schizophrenia: Its Relations with Negative Symptoms.

PubMed

Lee, So Jung; Kim, Kyung Ran; Lee, Su Young; An, Suk Kyoon

2017-03-01

Psychosocial dysfunction was a nettlesome of schizophrenia even in their prodromal phase as well as first episode and its relations with psychopathology were not determined. The aim of the present study was to examine whether the social and role function impairment was found in ultra-high risk for psychosis (UHR) individuals as well as first-episode schizophrenia patients and to explore its relations with psychopathology. Thirty-seven normal controls, 63 UHR participants and 28 young, first-episode schizophrenia patients were recruited. Psychosocial functioning was examined by using Global function: Social and Role scale. Psychopathologies of positive, negative and depressive symptom were also measured. Social and role functioning in UHR were compromised at the equivalent level of those of first-episode schizophrenia patients. Multiple linear regression analysis revealed that social and role dysfunction was associated with negative symptoms in each UHR and first-episode schizophrenia group. These findings suggest that the significant impairment of social and role function may be appeared before the active psychosis onset at the level of extent to those of first-episode schizophrenia patients. The psychosocial intervention strategy especially targeting the negative symptoms should be developed and provided to individuals from their prepsychotic stage of schizophrenia.

Long-term functioning following whiplash injury: the role of social support and personality traits.

PubMed

Nijs, Jo; Inghelbrecht, Els; Daenen, Liesbeth; Hachimi-Idrissi, Said; Hens, Luc; Willems, Bert; Roussel, Nathalie; Cras, Patrick; Bernheim, Jan

2011-07-01

Transition from acute whiplash injury to either recovery or chronicity and the development of chronic whiplash-associated disorders (WAD) remains a challenging issue for researchers and clinicians. The roles of social support and personality traits in long-term functioning following whiplash have not been studied concomitantly. The present study aimed to examine whether social support and personality traits are related to long-term functioning following whiplash. One hundred forty-three subjects, who had experienced a whiplash injury in a traffic accident 10-26 months before the study took place, participated. The initial diagnoses were a 'sprain of the neck' (ICD-9 code 847.0); only the outcome of grades I-III acute WAD was studied. Long-term functioning was considered within the biopsychosocial model: it was expressed in terms of disability, functional status, quality of life and psychological well-being. Participants filled out a set of questionnaires to measure the long-term functioning parameters (i.e. the Neck Disability Index, Medical Outcome Study Short-Form General Health Survey, Anamnestic Comparative Self-Assessment measure of overall well-being and the Symptom Checklist-90) and potential determinants of long-term functioning (the Dutch Personality Questionnaire and the Social Support List). The results suggest that social support (especially the discrepancies dimension of social support) and personality traits (i.e. inadequacy, self-satisfaction and resentment) are related to long-term functioning following whiplash injury (Spearman rho varied between 0.32 and 0.57; p < 0.01). Within the discrepancy dimension, everyday emotional support, emotional support during problems, appreciative support and informative support were identified as important correlates of long-term functioning. Future prospective studies are required to confirm the role of social support and personality traits in relation to long-term functioning following whiplash. For such

Teachers' Understanding of the Role of Executive Functions in Mathematics Learning

ERIC Educational Resources Information Center

Gilmore, Camilla; Cragg, Lucy

2014-01-01

Cognitive psychology research has suggested an important role for executive functions, the set of skills that monitor and control thought and action, in learning mathematics. However, there is currently little evidence about whether teachers are aware of the importance of these skills and, if so, how they come by this information. We conducted an…

Functional roles of flavonoids in photoprotection: new evidence, lessons from the past.

PubMed

Agati, Giovanni; Brunetti, Cecilia; Di Ferdinando, Martina; Ferrini, Francesco; Pollastri, Susanna; Tattini, Massimiliano

2013-11-01

We discuss on the relative significance of different functional roles potentially served by flavonoids in photoprotection, with special emphasis to their ability to scavenge reactive oxygen species (ROS) and control the development of individual organs and whole plant. We propose a model in which chloroplast-located flavonoids scavenge H2O2 and singlet oxygen generated under excess light-stress, thus avoiding programmed cell death. We also draw a picture in which vacuolar flavonoids in conjunction with peroxidases and ascorbic acid constitute a secondary antioxidant system aimed at detoxifying H2O2, which may diffuse out of the chloroplast at considerable rates and enter the vacuole following excess light stress-induced depletion of ascorbate peroxidase. We hypothesize for flavonols key roles as developmental regulators in early and current-day land-plants, based on their ability to modulate auxin movement and auxin catabolism. We show that antioxidant flavonoids display the greatest capacity to regulate key steps of cell growth and differentiation in eukaryotes. These regulatory functions of flavonoids, which are shared by plants and animals, are fully accomplished in the nM concentration range, as likely occurred in early land plants. We therefore conclude that functions of flavonoids as antioxidants and/or developmental regulators flavonoids are of great value in photoprotection. We also suggest that UV-B screening was just one of the multiple functions served by flavonoids when early land-plants faced an abrupt increase in sunlight irradiance. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Catalytic functionalities of supported sulfides. I. Effect of support and additives on the CoMo catalyst

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

Muralidhar, G.; Massoth, F.E.; Shabtai, J.

1984-01-01

C-S hydrogenolysis (HDS) of thiophene, hydrogenation (HYD) of 1-hexene, and hydrocracking (HCG) of 2,4,4-trimethyl-1-pentene, were used as separate model test reactions to differentiate and assess the catalytic functionalities of sulfided CoMo catalysts, and their dependence on the nature of the support and incorporation of additives. Rate constants and relative catalyst activities for these three reaction types were determined. HDS and HYD activities of CoMo supported on different types of Al/sub 2/O/sub 3/ were higher, while the HCG activity was lower compared with CoMo supported on SiO/sub 2/-Al/sub 2/O/sub 3/, SiO/sub 2/-MgO, or TiO/sub 2/. For SiO/sub 2/-Al/sub 2/O/sub 3/ supportsmore » both HDS and HYD activities decreased with increase in SiO/sub 2/ content from 10 to 75%, while HCG activity showed the opposite trend. Additives to a finished CoMo catalyst at 0.5% level caused variations in HDS and HCG activities, while HYD was essentially unaffected. HDS was promoted by NH/sub 4/HF/sub 2/ and NH/sub 4/Cl, but depressed by NaNO/sub 3/, Ca(NO/sub 3/)/sub 2/, and H/sub 3/BO/sub 3/. HCG was promoted by NH/sub 4/HF/sub 2/, NH/sub 4/Cl, and H/sub 3/BO/sub 3/. Additives at 5% level, prior to or after CoMo impregnation, showed a strong depressing effect on HDS and a lesser effect on HYD, while HCG was strongly promoted by NH/sub 4/HF/sub 2/, Ti isopropoxide, and H/sub 3/BO/sub 3/. The changes in catalytic functionalities are rationalized in terms of different interactions between CoMo phase, support, and additives. 3 tables, 1 figure.« less

FEZ2 has acquired additional protein interaction partners relative to FEZ1: functional and evolutionary implications.

PubMed

Alborghetti, Marcos R; Furlan, Ariane S; Kobarg, Jörg

2011-03-08

The FEZ (fasciculation and elongation protein zeta) family designation was purposed by Bloom and Horvitz by genetic analysis of C. elegans unc-76. Similar human sequences were identified in the expressed sequence tag database as FEZ1 and FEZ2. The unc-76 function is necessary for normal axon fasciculation and is required for axon-axon interactions. Indeed, the loss of UNC-76 function results in defects in axonal transport. The human FEZ1 protein has been shown to rescue defects caused by unc-76 mutations in nematodes, indicating that both UNC-76 and FEZ1 are evolutionarily conserved in their function. Until today, little is known about FEZ2 protein function. Using the yeast two-hybrid system we demonstrate here conserved evolutionary features among orthologs and non-conserved features between paralogs of the FEZ family of proteins, by comparing the interactome profiles of the C-terminals of human FEZ1, FEZ2 and UNC-76 from C. elegans. Furthermore, we correlate our data with an analysis of the molecular evolution of the FEZ protein family in the animal kingdom. We found that FEZ2 interacted with 59 proteins and that of these only 40 interacted with FEZ1. Of the 40 FEZ1 interacting proteins, 36 (90%), also interacted with UNC-76 and none of the 19 FEZ2 specific proteins interacted with FEZ1 or UNC-76. This together with the duplication of unc-76 gene in the ancestral line of chordates suggests that FEZ2 is in the process of acquiring new additional functions. The results provide also an explanation for the dramatic difference between C. elegans and D. melanogaster unc-76 mutants on one hand, which cause serious defects in the nervous system, and the mouse FEZ1 -/- knockout mice on the other, which show no morphological and no strong behavioural phenotype. Likely, the ubiquitously expressed FEZ2 can completely compensate the lack of neuronal FEZ1, since it can interact with all FEZ1 interacting proteins and additional 19 proteins.

FEZ2 Has Acquired Additional Protein Interaction Partners Relative to FEZ1: Functional and Evolutionary Implications

PubMed Central

Alborghetti, Marcos R.; Furlan, Ariane S.; Kobarg, Jörg

2011-01-01

Background The FEZ (fasciculation and elongation protein zeta) family designation was purposed by Bloom and Horvitz by genetic analysis of C. elegans unc-76. Similar human sequences were identified in the expressed sequence tag database as FEZ1 and FEZ2. The unc-76 function is necessary for normal axon fasciculation and is required for axon-axon interactions. Indeed, the loss of UNC-76 function results in defects in axonal transport. The human FEZ1 protein has been shown to rescue defects caused by unc-76 mutations in nematodes, indicating that both UNC-76 and FEZ1 are evolutionarily conserved in their function. Until today, little is known about FEZ2 protein function. Methodology/Principal Findings Using the yeast two-hybrid system we demonstrate here conserved evolutionary features among orthologs and non-conserved features between paralogs of the FEZ family of proteins, by comparing the interactome profiles of the C-terminals of human FEZ1, FEZ2 and UNC-76 from C. elegans. Furthermore, we correlate our data with an analysis of the molecular evolution of the FEZ protein family in the animal kingdom. Conclusions/Significance We found that FEZ2 interacted with 59 proteins and that of these only 40 interacted with FEZ1. Of the 40 FEZ1 interacting proteins, 36 (90%), also interacted with UNC-76 and none of the 19 FEZ2 specific proteins interacted with FEZ1 or UNC-76. This together with the duplication of unc-76 gene in the ancestral line of chordates suggests that FEZ2 is in the process of acquiring new additional functions. The results provide also an explanation for the dramatic difference between C. elegans and D. melanogaster unc-76 mutants on one hand, which cause serious defects in the nervous system, and the mouse FEZ1 -/- knockout mice on the other, which show no morphological and no strong behavioural phenotype. Likely, the ubiquitously expressed FEZ2 can completely compensate the lack of neuronal FEZ1, since it can interact with all FEZ1 interacting

New role of flavin as a general acid-base catalyst with no redox function in type 2 isopentenyl-diphosphate isomerase.

PubMed

Unno, Hideaki; Yamashita, Satoshi; Ikeda, Yosuke; Sekiguchi, Shin-Ya; Yoshida, Norie; Yoshimura, Tohru; Kusunoki, Masami; Nakayama, Toru; Nishino, Tokuzo; Hemmi, Hisashi

2009-04-03

Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate isomerase catalyzes isomerization between isopentenyl diphosphate and dimethylallyl diphosphate, both of which are elemental units for the biosynthesis of highly diverse isoprenoid compounds. Although the flavin cofactor is expected to be integrally involved in catalysis, its exact role remains controversial. Here we report the crystal structures of the substrate-free and complex forms of type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon Sulfolobus shibatae, not only in the oxidized state but also in the reduced state. Based on the active-site structures of the reduced FMN-substrate-enzyme ternary complexes, which are in the active state, and on the data from site-directed mutagenesis at highly conserved charged or polar amino acid residues around the active site, we demonstrate that only reduced FMN, not amino acid residues, can catalyze proton addition/elimination required for the isomerase reaction. This discovery is the first evidence for this long suspected, but previously unobserved, role of flavins just as a general acid-base catalyst without playing any redox roles, and thereby expands the known functions of these versatile coenzymes.

Structure-Function Analysis of Rgs1 in Magnaporthe oryzae: Role of DEP Domains in Subcellular Targeting

PubMed Central

Ramanujam, Ravikrishna; Yishi, Xu; Liu, Hao; Naqvi, Naweed I.

2012-01-01

Background Rgs1, a prototypical Regulator of G protein Signaling, negatively modulates the cyclic AMP pathway thereby influencing various aspects of asexual development and pathogenesis in the rice-blast fungus Magnaporthe oryzae. Rgs1 possesses tandem DEP motifs (termed DEP-A and DEP-B; for Dishevelled, Egl-10, Pleckstrin) at the N-terminus, and a Gα-GTP interacting RGS catalytic core domain at the C-terminus. In this study, we focused on gaining further insights into the mechanisms of Rgs1 regulation and subcellular localization by characterizing the role(s) of the individual domains and the full-length protein during asexual development and pathogenesis in Magnaporthe. Methodology/Principal Findings Utilizing western blot analysis and specific antisera against the N- and C-terminal halves of Rgs1, we identify and report the in vivo endoproteolytic processing/cleavage of full-length Rgs1 that yields an N-terminal DEP and a RGS core domain. Independent expression of the resultant DEP-DEP half (N-Rgs1) or RGS core (C-Rgs1) fragments, failed to complement the rgs1Δ defects in colony morphology, aerial hyphal growth, surface hydrophobicity, conidiation, appressorium formation and infection. Interestingly, the full-length Rgs1-mCherry, as well as the tagged N-terminal DEP domains (individually or in conjunction) localized to distinct punctate vesicular structures in the cytosol, while the catalytic RGS core motif was predominantly vacuolar. Conclusions/Significance Based on our data from sequence alignments, immuno-blot and microscopic analysis, we propose that the post-translational proteolytic processing of Rgs1 and the vacuolar sequestration of the catalytic RGS domain represents an important means of down regulating Rgs1 function and thus forming an additional and alternative means of regulating G protein signaling in Magnaporthe. We further hypothesize the prevalence of analogous mechanisms functioning in other filamentous fungi. Furthermore, we conclusively

The Functional Role of the Periphery in Emotional Language Comprehension

PubMed Central

Havas, David A.; Matheson, James

2013-01-01

Language can impact emotion, even when it makes no reference to emotion states. For example, reading sentences with positive meanings (“The water park is refreshing on the hot summer day”) induces patterns of facial feedback congruent with the sentence emotionality (smiling), whereas sentences with negative meanings induce a frown. Moreover, blocking facial afference with botox selectively slows comprehension of emotional sentences. Therefore, theories of cognition should account for emotion-language interactions above the level of explicit emotion words, and the role of peripheral feedback in comprehension. For this special issue exploring frontiers in the role of the body and environment in cognition, we propose a theory in which facial feedback provides a context-sensitive constraint on the simulation of actions described in language. Paralleling the role of emotions in real-world behavior, our account proposes that (1) facial expressions accompany sudden shifts in wellbeing as described in language; (2) facial expressions modulate emotional action systems during reading; and (3) emotional action systems prepare the reader for an effective simulation of the ensuing language content. To inform the theory and guide future research, we outline a framework based on internal models for motor control. To support the theory, we assemble evidence from diverse areas of research. Taking a functional view of emotion, we tie the theory to behavioral and neural evidence for a role of facial feedback in cognition. Our theoretical framework provides a detailed account that can guide future research on the role of emotional feedback in language processing, and on interactions of language and emotion. It also highlights the bodily periphery as relevant to theories of embodied cognition. PMID:23750145

The Role of Functional Foods, Nutraceuticals, and Food Supplements in Intestinal Health

PubMed Central

Cencic, Avrelija; Chingwaru, Walter

2010-01-01

New eating habits, actual trends in production and consumption have a health, environmental and social impact. The European Union is fighting diseases characteristic of a modern age, such as obesity, osteoporosis, cancer, diabetes, allergies and dental problems. Developed countries are also faced with problems relating to aging populations, high energy foods, and unbalanced diets. The potential of nutraceuticals/functional foods/food supplements in mitigating health problems, especially in the gastrointestinal (GI) tract, is discussed. Certain members of gut microflora (e.g., probiotic/protective strains) play a role in the host health due to its involvement in nutritional, immunologic and physiological functions. The potential mechanisms by which nutraceuticals/functional foods/food supplements may alter a host’s health are also highlighted in this paper. The establishment of novel functional cell models of the GI and analytical tools that allow tests in controlled experiments are highly desired for gut research. PMID:22254045

Loss of tight junction barrier function and its role in cancer metastasis.

PubMed

Martin, Tracey A; Jiang, Wen G

2009-04-01

As the most apical structure between epithelial and endothelial cells, tight junctions (TJ) are well known as functioning as a control for the paracellular diffusion of ions and certain molecules. It has however, become increasingly apparent that the TJ has a vital role in maintaining cell to cell integrity and that the loss of cohesion of the structure can lead to invasion and thus metastasis of cancer cells. This article will present data showing how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the successful metastasis of a number of different cancer types.

Development of affective theory of mind across adolescence: disentangling the role of executive functions.

PubMed

Vetter, Nora C; Altgassen, Mareike; Phillips, Louise; Mahy, Caitlin E V; Kliegel, Matthias

2013-01-01

Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

Nursing Roles and Functions in the Acute and Subacute Rehabilitation of Patients With Stroke: Going All In for the Patient.

PubMed

Dreyer, Pia; Angel, Sanne; Langhorn, Leanne; Pedersen, Birgitte Blicher; Aadal, Lena

2016-04-01

The description of nursing roles and functions in rehabilitation of patients with stroke remains sparse. The aim of this study was to describe the experienced roles and functions of nurses during in-hospital rehabilitation of patients with stroke. Within a phenomenological hermeneutic approach, 19 nurses working with in-hospital rehabilitation of patients with stroke participated in three focus group interviews during 2013. The nurses' experiences were described in two themes: (a) the nurse's role and function in relation to the patient's needs 24/7 and (b) the nurse's role and function in the interdisciplinary team. Getting to know the patient as a person was essential to the nurses to care for the patient's basic needs; these must come first working with rehabilitation and always include the relatives. Recognition of the team members' individual skills with focus on the patient's needs must be the center of attention. An interdisciplinary rehabilitation program actively needs to include the patient by integrating the patient's perspective in the goals as well as in daily rehabilitation. In the team, nurses had the role of coordinator and the patient's voice.

Responses of Woody Plant Functional Traits to Nitrogen Addition: A Meta-Analysis of Leaf Economics, Gas Exchange, and Hydraulic Traits.

PubMed

Zhang, Hongxia; Li, Weibin; Adams, Henry D; Wang, Anzhi; Wu, Jiabing; Jin, Changjie; Guan, Dexin; Yuan, Fenghui

2018-01-01

Atmospheric nitrogen (N) deposition has been found to significantly affect plant growth and physiological performance in terrestrial ecosystems. Many individual studies have investigated how N addition influences plant functional traits, however these investigations have usually been limited to a single species, and thereby do not allow derivation of general patterns or underlying mechanisms. We synthesized data from 56 papers and conducted a meta-analysis to assess the general responses of 15 variables related to leaf economics, gas exchange, and hydraulic traits to N addition among 61 woody plant species, primarily from temperate and subtropical regions. Results showed that under N addition, leaf area index (+10.3%), foliar N content (+7.3%), intrinsic water-use efficiency (+3.1%) and net photosynthetic rate (+16.1%) significantly increased, while specific leaf area, stomatal conductance, and transpiration rate did not change. For plant hydraulics, N addition significantly increased vessel diameter (+7.0%), hydraulic conductance in stems/shoots (+6.7%), and water potential corresponding to 50% loss of hydraulic conductivity ( P 50 , +21.5%; i.e., P 50 became less negative), while water potential in leaves (-6.7%) decreased (became more negative). N addition had little effect on vessel density, hydraulic conductance in leaves and roots, or water potential in stems/shoots. N addition had greater effects on gymnosperms than angiosperms and ammonium nitrate fertilization had larger effects than fertilization with urea, and high levels of N addition affected more traits than low levels. Our results demonstrate that N addition has coupled effects on both carbon and water dynamics of woody plants. Increased leaf N, likely fixed in photosynthetic enzymes and pigments leads to higher photosynthesis and water use efficiency, which may increase leaf growth, as reflected in LAI results. These changes appear to have downstream effects on hydraulic function through increases

Is There a Role for Executive Functions in the Development of Mathematics Ability?

ERIC Educational Resources Information Center

Blair, Clancy; Knipe, Hilary; Gamson, David

2008-01-01

This article examines the role of working memory, attention shifting, and inhibitory control executive cognitive functions in the development of mathematics knowledge and ability in children. It suggests that an examination of the executive cognitive demand of mathematical thinking can complement procedural and conceptual knowledge-based…

VEGF and VEGFB Play Balancing Roles in Adipose Differentiation, Gene Expression, and Function.

PubMed

Jin, Honghong; Li, Dan; Wang, Xutong; Jia, Jia; Chen, Yang; Yao, Yapeng; Zhao, Chunlan; Lu, Xiaodan; Zhang, Shujie; Togo, Jacques; Ji, Yan; Zhang, Luqing; Feng, Xuechao; Zheng, Yaowu

2018-05-01

Obesity is the result of abnormal adipose development and energy metabolism. Using vascular endothelial growth factor (VEGF) B-knockout and inducible VEGF downregulation mouse models, we have shown that VEGFB inactivation caused expansion of white adipose, whitening of brown adipose, an increase in fat accumulation, and a reduction in energy consumption. At the same time, expression of the white adipose-associated genes was increased and brown adipose-associated genes decreased. VEGF repression, in contrast, induced brown adipose expansion and brown adipocyte development in white adipose, increased energy expenditure, upregulated brown adipose-associated genes, and downregulated white adipose-associated genes. When VEGFB-knockout and VEGF-repressed mice are crossed together, VEGF and VEGFB can counteractively regulate large numbers of genes and efficiently reverse each other's roles. These genes, under counteractive VEGF and VEGFB regulations, include transcription factors, adhesion molecules, and metabolic enzymes. This balancing role is confirmed by morphologic and functional changes. This study reports that VEGF and VEGFB counteractively regulate adipose development and function in energy metabolism.

Long noncoding RNAs in digestive system cancers: Functional roles, molecular mechanisms, and clinical implications (Review).

PubMed

Fu, Min; Zou, Chen; Pan, Lei; Liang, Wei; Qian, Hui; Xu, Wenrong; Jiang, Pengcheng; Zhang, Xu

2016-09-01

Long noncoding RNAs (lncRNAs) are emerging as new players in various diseases including cancer. LncRNAs have been shown to play multifaceted roles in the development, progression, and metastasis of cancer. In this review, we highlight the lncRNAs that are critically involved in the pathogenesis of digestive system cancers (DSCs). We summarize the roles of the lncRNAs in DSCs and the underlying mechanisms responsible for their functions. The DSC-associated lncRNAs interact with a wide spectrum of molecules to regulate gene expression at transcriptional, post-transcriptional, and translational levels. We also provide new insights into the clinical significance of these lncRNAs, which are found to be closely associated with the aggressiveness of DSCs and could predict the prognosis of DSC patients. Moreover, lncRNAs have been suggested as promising therapeutic targets in DSCs. Therefore, better understanding of the functional roles of lncRNAs will provide new biomarkers for DSC diagnosis, prognosis, and therapy.

On the role of resonantly stabilized radicals in polycyclic aromatic hydrocarbon (PAH) formation: pyrene and fluoranthene formation from benzyl-indenyl addition.

PubMed

Sinha, Sourab; Rahman, Ramees K; Raj, Abhijeet

2017-07-26

Resonantly stabilized radicals, such as propargyl, cyclopentadienyl, benzyl, and indenyl, play a vital role in the formation and growth of polycyclic aromatic hydrocarbons (PAHs) that are soot precursors in engines and flames. Pyrene is considered to be an important PAH, as it is thought to nucleate soot particles, but its formation pathways are not well known. This paper presents a reaction mechanism for the formation of four-ring aromatics, pyrene and fluoranthene, through the combination of benzyl and indenyl radicals. The intermediate species and transition structures involved in the elementary reactions of the mechanism were studied using density functional theory, and the reaction kinetics were evaluated using transition state theory. The barrierless addition of benzyl and indenyl to form the adduct, 1-benzyl-1H-indene, was found to be exothermic with a reaction energy of 204.2 kJ mol -1 . The decomposition of this adduct through H-abstraction and H 2 -loss was studied to determine the possible products. The rate-of-production analysis was conducted to determine the most favourable reactions for pyrene and fluoranthene formation. The premixed laminar flames of toluene, ethylbenzene, and benzene were simulated using a well-validated hydrocarbon fuel mechanism with detailed PAH chemistry after adding the proposed reactions to it. The computed and experimentally observed species profiles were compared to determine the effect of the new reactions for pyrene and fluoranthene formation on their concentration profiles. The role of benzyl and indenyl combination in PAH formation and growth is highlighted.

Enteric pathogens and gut function: Role of cytokines and STATs.

PubMed

Shea-Donohue, Terez; Fasano, Alessio; Smith, Allen; Zhao, Aiping

2010-09-01

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4(+) cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles.

Enteric pathogens and gut function: Role of cytokines and STATs

PubMed Central

Fasano, Alessio; Smith, Allen; Zhao, Aiping

2010-01-01

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4+ cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles. PMID:21327040

Insulin: its role in the central control of reproduction.

PubMed

Sliwowska, Joanna H; Fergani, Chrysanthi; Gawałek, Monika; Skowronska, Bogda; Fichna, Piotr; Lehman, Michael N

2014-06-22

Insulin has long been recognized as a key regulator of energy homeostasis via its actions at the level of the brain, but in addition, plays a role in regulating neural control of reproduction. In this review, we consider and compare evidence from animal models demonstrating a role for insulin for physiological control of reproduction by effects on GnRH/LH secretion. We also review the role that insulin plays in prenatal programming of adult reproduction, and consider specific candidate neurons in the adult hypothalamus by which insulin may act to regulate reproductive function. Finally, we review clinical evidence of the role that insulin may play in adult human fertility and reproductive disorders. Overall, while insulin appears to have a significant impact on reproductive neuroendocrine function, there are many unanswered questions regarding its precise sites and mechanisms of action, and their impact on developing and adult reproductive neuroendocrine function. Copyright © 2014 Elsevier Inc. All rights reserved.

More Than Cholesterol Transporters: Lipoprotein Receptors in CNS Function and Neurodegeneration

PubMed Central

Lane-Donovan, Courtney E.; Philips, Gary T.; Herz, Joachim

2014-01-01

Members of the low-density lipoprotein (LDL) receptor gene family have a diverse set of biological functions that transcend lipid metabolism. Lipoprotein receptors have broad effects in both the developing and adult brain and participate in synapse development, cargo trafficking, and signal transduction. In addition, several family members play key roles in Alzheimer's disease pathogenesis and neurodegeneration. This review summarizes our current understanding of the role lipoprotein receptors play in CNS function and AD pathology, with a special emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction. PMID:25144875

Children's Teaching Skills: The Role of Theory of Mind and Executive Function

ERIC Educational Resources Information Center

Davis-Unger, Angela C.; Carlson, Stephanie M.

2008-01-01

Teaching others effectively may rely on knowledge about the mind as well as self-control processes. The goal of this investigation was to explore the role of theory of mind (ToM) and executive function (EF) in children's developing teaching skills. Children 3.5-5.5 years of age (N = 82) were asked to teach a confederate learner how to play a board…

Additive diagnostic role of imaging in glaucoma: optical coherence tomography and retinal nerve fiber layer photography.

PubMed

Kim, Ko Eun; Kim, Seok Hwan; Oh, Sohee; Jeoung, Jin Wook; Suh, Min Hee; Seo, Je Hyun; Kim, Martha; Park, Ki Ho; Kim, Dong Myung

2014-11-20

To investigate the additive diagnostic role of spectral-domain optical coherence tomography (SD-OCT) and red-free retinal nerve fiber layer photography (RNFLP) in making clinical glaucoma diagnosis. Four diagnostic combination sets, including the most recent image from each measurement of 196 glaucoma eyes (including the 44 preperimetric glaucoma eyes) and 101 healthy eyes, were prepared: (1) stereo disc photography and Humphrey visual field (SH), (2) SH and SD-OCT (SHO), (3) SH and RNFLP (SHR), and (4) SHR and SD-OCT (SHRO). Each randomly sorted set was serially presented at 1-month intervals to five glaucoma specialists who were asked to evaluate them in a subjective and independent manner. The specialists' glaucoma-diagnostic performances based on the sets were then compared. For each specialist, adding SD-OCT to SH or SHR increased the glaucoma-diagnostic sensitivity but not to a level of statistical significance. For one specialist, adding RNFLP to SH significantly increased the sensitivity. Each specialist showed a high level of specificity regardless of the diagnostic set. The overall sensitivity of all specialists' assessments was significantly increased by adding RNFLP or the combination of SD-OCT and RNFLP to SH (P < 0.001); however, adding SD-OCT to SH or SHR did not significantly increase the sensitivity. A similar relationship was noted also for the preperimetric glaucoma subgroup. In contrast to RNFLP, SD-OCT did not significantly enhance the diagnostic accuracy of detecting glaucoma or even of preperimetric glaucoma. Our results suggest that, at least for glaucoma specialists, the additive diagnostic role of OCT is limited. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Clarifying functional roles: algal removal by the surgeonfishes Ctenochaetus striatus and Acanthurus nigrofuscus

NASA Astrophysics Data System (ADS)

Tebbett, Sterling B.; Goatley, Christopher H. R.; Bellwood, David R.

2017-09-01

The lined bristletooth, Ctenochaetus striatus, and the brown surgeonfish, Acanthurus nigrofuscus, are among the most abundant surgeonfishes on Indo-Pacific coral reefs. Yet, the functional role of these species has been the focus of an ongoing debate lasting at least six decades. Specifically, to what extent are C. striatus herbivorous like the visually similar A. nigrofuscus? To address this question, we used natural feeding surfaces, covered with late successional stage reef-grown algal turfs, to examine turf algal removal by the two species. Surfaces exposed to C. striatus in laboratory experiments exhibited no significant reductions in turf length or area covered by turfing algae. In marked contrast, A. nigrofuscus reduced turf length by 51% and area covered by turfing algae by 15% in 1 h. The gut contents of specimens from the reef revealed that A. nigrofuscus predominantly ingests algae (the dominant item in 79.6-94.7% of gut content quadrats), while C. striatus ingests detritus and sediments (dominant in 99.6-100% of quadrats). Therefore, C. striatus ingests detritus and sediment, leaving mature algal turfs relatively intact, while A. nigrofuscus directly removes and ingests turf algae. The function of C. striatus differs from cropping herbivorous surgeonfishes such as A. nigrofuscus. On coral reefs, C. striatus brush detrital aggregates from algal turfs, removing microorganisms, organic detritus and inorganic sediment. Confusion over the functional role of C. striatus may stem from an inability to fit it into a single functional category.

Hydrogen atom addition to the surface of graphene nanoflakes: A density functional theory study

NASA Astrophysics Data System (ADS)

Tachikawa, Hiroto

2017-02-01

Polycyclic aromatic hydrocarbons (PAHs) provide a 2-dimensional (2D) reaction surface in 3-dimensional (3D) interstellar space and have been utilized as a model of graphene surfaces. In the present study, the reaction of PAHs with atomic hydrogen was investigated by means of density functional theory (DFT) to systematically elucidate the binding nature of atomic hydrogen to graphene nanoflakes. PAHs with n = 4-37 were chosen, where n indicates the number of benzene rings. Activation energies of hydrogen addition to the graphene surface were calculated to be 5.2-7.0 kcal/mol at the CAM-B3LYP/6-311G(d,p) level, which is almost constant for all PAHs. The binding energies of hydrogen atom were slightly dependent on the size (n): 14.8-28.5 kcal/mol. The absorption spectra showed that a long tail is generated at the low-energy region after hydrogen addition to the graphene surface. The electronic states of hydrogenated graphenes were discussed on the basis of theoretical results.

Role of fatty-acid synthesis in dendritic cell generation and function.

PubMed

Rehman, Adeel; Hemmert, Keith C; Ochi, Atsuo; Jamal, Mohsin; Henning, Justin R; Barilla, Rocky; Quesada, Juan P; Zambirinis, Constantinos P; Tang, Kerry; Ego-Osuala, Melvin; Rao, Raghavendra S; Greco, Stephanie; Deutsch, Michael; Narayan, Suchithra; Pachter, H Leon; Graffeo, Christopher S; Acehan, Devrim; Miller, George

2013-05-01

Dendritic cells (DC) are professional APCs that regulate innate and adaptive immunity. The role of fatty-acid synthesis in DC development and function is uncertain. We found that blockade of fatty-acid synthesis markedly decreases dendropoiesis in the liver and in primary and secondary lymphoid organs in mice. Human DC development from PBMC precursors was also diminished by blockade of fatty-acid synthesis. This was associated with higher rates of apoptosis in precursor cells and increased expression of cleaved caspase-3 and BCL-xL and downregulation of cyclin B1. Further, blockade of fatty-acid synthesis decreased DC expression of MHC class II, ICAM-1, B7-1, and B7-2 but increased their production of selected proinflammatory cytokines including IL-12 and MCP-1. Accordingly, inhibition of fatty-acid synthesis enhanced DC capacity to activate allogeneic as well as Ag-restricted CD4(+) and CD8(+) T cells and induce CTL responses. Further, blockade of fatty-acid synthesis increased DC expression of Notch ligands and enhanced their ability to activate NK cell immune phenotype and IFN-γ production. Because endoplasmic reticulum (ER) stress can augment the immunogenic function of APC, we postulated that this may account for the higher DC immunogenicity. We found that inhibition of fatty-acid synthesis resulted in elevated expression of numerous markers of ER stress in humans and mice and was associated with increased MAPK and Akt signaling. Further, lowering ER stress by 4-phenylbutyrate mitigated the enhanced immune stimulation associated with fatty-acid synthesis blockade. Our findings elucidate the role of fatty-acid synthesis in DC development and function and have implications to the design of DC vaccines for immunotherapy.

Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.

PubMed

Tamaki, Mami; Konno, Yasunori; Kobayashi, Yoshiki; Takeda, Masahide; Itoga, Masamichi; Moritoki, Yuki; Oyamada, Hajime; Kayaba, Hiroyuki; Chihara, Junichi; Ueki, Shigeharu

2014-07-01

Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

New insights into the roles of megalin/LRP2 and the regulation of its functional expression.

PubMed

Marzolo, María-Paz; Farfán, Pamela

2011-01-01

Since the discovery of the low-density lipoprotein receptor (LDLR) and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been described. LRP2, or megalin, is a member of the LDLR family and was initially called gp330. Megalin is an endocytic receptor expressed on the apical surface of several epithelial cells that internalizes a variety of ligands including nutrients, hormones and their carrier proteins, signaling molecules, morphogens, and extracellular matrix proteins. Once internalized, these ligands are directed to the lysosomal degradation pathway or transported by transcytosis from one side of the cell to the opposite membrane. The availability of megalin at the cell surface is controlled by several regulatory mechanisms, including the phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the extracellular domain at the cell surface (shedding), the subsequent intramembrane proteolysis of the transmembrane domain by the gamma-secretase complex, and exosome secretion. Based on the important roles of its ligands and its tissue expression pattern, megalin has been recognized as an important component of many pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent disease, Alzheimer's disease (AD) and gallstone disease. In addition, the expression of megalin and some of its ligands in the central and peripheral nervous system suggests a role for this receptor in neural regeneration processes. Despite its obvious importance, the regulation of megalin expression is poorly understood. In this review, we describe the functions of megalin and its association with certain pathological conditions as well as the current understanding of the mechanisms that underlie the control of megalin expression.

Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity.

PubMed

Philpott, Stacy M; Pardee, Gabriella L; Gonthier, David J

2012-05-01

Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

In search for a common denominator for the diverse functions of arthropod corazonin: a role in the physiology of stress?

PubMed

Boerjan, Bart; Verleyen, Peter; Huybrechts, Jurgen; Schoofs, Liliane; De Loof, Arnold

2010-04-01

Corazonin (Crz) is an 11 amino acid C-terminally amidated neuropeptide that has been identified in most arthropods examined with the notable exception of beetles and an aphid. The Crz-receptor shares sequence similarity to the GnRH-AKH receptor family thus suggesting an ancestral function related to the control of reproduction and metabolism. In 1989, Crz was purified and identified as a potent cardioaccelerating agent in cockroaches (hence the Crz name based on "corazon", the Spanish word for "heart"). Since the initial assignment as a cardioacceleratory peptide, additional functions have been discovered, ranging from pigment migration in the integument of crustaceans and in the eye of locusts, melanization of the locust cuticle, ecdysis initiation and in various aspects of gregarization in locusts. The high degree of structural conservation of Crz, its well-conserved (immuno)-localization, mainly in specific neurosecretory cells in the pars lateralis, and its many functions, suggest that Crz is vital. Yet, Crz-deficient insects develop normally. Upon reexamining all known effects of Crz, a hypothesis was developed that the evolutionary ancient function of Crz may have been "to prepare animals for coping with the environmental stressors of the day". This function would then complement the role of pigment-dispersing factor (PDF), the prime hormonal effector of the clock, which is thought "to set a coping mechanism for the night". (c) 2009 Elsevier Inc. All rights reserved.

The Role of Bulk Additions in Solid Lubricant Compacts

DTIC Science & Technology

1987-04-01

compact Surface ............. 138 36. Wear Volume as a Function of Kohn Hardness.... 161 37. Melt Temperature of Oxides as Function of Kohs Hardness...PROPERTIES OF ANTIMONY AND ANTIMONY OXIDES ELEMENT OR FORMULA FORMULA CRYSTAL SP MELT BOILING COMPOUND WEIGHT FORM GRAY POINT POINT (C0 (00 Antimony...be rationalized as oxidation of smaller particle size Sb203(o) followed by melting and, 84 .40 00 0 o0 40 an M a CA 𔃺o 0u 1 "M OX3 ---- fýO’N Pý > 85

Identifying thematic roles from neural representations measured by functional magnetic resonance imaging.

PubMed

Wang, Jing; Cherkassky, Vladimir L; Yang, Ying; Chang, Kai-Min Kevin; Vargas, Robert; Diana, Nicholas; Just, Marcel Adam

2016-01-01

The generativity and complexity of human thought stem in large part from the ability to represent relations among concepts and form propositions. The current study reveals how a given object such as rabbit is neurally encoded differently and identifiably depending on whether it is an agent ("the rabbit punches the monkey") or a patient ("the monkey punches the rabbit"). Machine-learning classifiers were trained on functional magnetic resonance imaging (fMRI) data evoked by a set of short videos that conveyed agent-verb-patient propositions. When tested on a held-out video, the classifiers were able to reliably identify the thematic role of an object from its associated fMRI activation pattern. Moreover, when trained on one subset of the study participants, classifiers reliably identified the thematic roles in the data of a left-out participant (mean accuracy = .66), indicating that the neural representations of thematic roles were common across individuals.

New Role of Flavin as a General Acid-Base Catalyst with No Redox Function in Type 2 Isopentenyl-diphosphate Isomerase*S⃞

PubMed Central

Unno, Hideaki; Yamashita, Satoshi; Ikeda, Yosuke; Sekiguchi, Shin-ya; Yoshida, Norie; Yoshimura, Tohru; Kusunoki, Masami; Nakayama, Toru; Nishino, Tokuzo; Hemmi, Hisashi

2009-01-01

Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate isomerase catalyzes isomerization between isopentenyl diphosphate and dimethylallyl diphosphate, both of which are elemental units for the biosynthesis of highly diverse isoprenoid compounds. Although the flavin cofactor is expected to be integrally involved in catalysis, its exact role remains controversial. Here we report the crystal structures of the substrate-free and complex forms of type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon Sulfolobus shibatae, not only in the oxidized state but also in the reduced state. Based on the active-site structures of the reduced FMN-substrate-enzyme ternary complexes, which are in the active state, and on the data from site-directed mutagenesis at highly conserved charged or polar amino acid residues around the active site, we demonstrate that only reduced FMN, not amino acid residues, can catalyze proton addition/elimination required for the isomerase reaction. This discovery is the first evidence for this long suspected, but previously unobserved, role of flavins just as a general acid-base catalyst without playing any redox roles, and thereby expands the known functions of these versatile coenzymes. PMID:19158086

The Role and Functionality of Emotions in Feedback at University: A Qualitative Study

ERIC Educational Resources Information Center

Rowe, Anna D.; Fitness, Julie; Wood, Leigh N.

2014-01-01

This paper reports on a qualitative study exploring the role and functionality of emotions in feedback. In-depth interview data from students and lecturers at an Australian university are analysed using cognitive appraisal and prototype theory. Results suggest that students experience a range of positive and negative emotions in feedback contexts…

Masculine role adherence and outcomes among men with traumatic brain injury.

PubMed

Schopp, Laura H; Good, Glenn E; Barker, Katharine B; Mazurek, Micah O; Hathaway, Stefani L

2006-10-01

Traumatic brain injury (TBI) is a significant health problem disproportionately affecting men and is often associated with changes in masculine role functioning in life domains such as vocational functioning, sexual and inter-personal functioning and personal independence. These changes could have serious implications for men's adjustment following injury. The aim of this study was to examine the relations among traditional masculine role adherence, psychosocial adjustment and rehabilitation outcomes in men with TBI. A correlational design was chosen to examine the relations among variables. Spearman correlations and Wilcoxon Rank Sum tests were used to examine relationships between masculine role variables and outcome variables. The study included 33 men with TBI who had been discharged from inpatient rehabilitation within 5 years. Participants completed surveys on traditional masculine gender role adherence and gender role conflict and additional data, including measures of functional outcome, life satisfaction, psychosocial outcomes and earnings, were obtained through the TBI Model System longitudinal data collection system. The results revealed significant associations between masculine role adherence and satisfaction with life, follow-up earnings and FIM change from admission to discharge. In the current study, particular masculine role variables corresponded to different functional and psychological outcomes. Understanding these differences provides new directions for treatment and offers important information about aspects of traditional masculine roles that may enhance or hinder adjustment to injury.

Role tuning between caregiver and care receiver during discharge transition: an illustration of role function mode in Roy's adaptation theory.

PubMed

Shyu, Y I

2000-10-01

The purpose of this study was to develop a conceptual framework to explain the interaction between the caregiver and the care receiver during the discharge transition. Data from face-to-face interviews with 12 care receivers and 16 caregivers were subjected to constant comparative analysis. Findings revealed that role tuning was the process used by caregivers and care receivers to achieve a harmonious pattern of caregiving and care receiving during the transition from hospital to home. This empirical finding can illustrate the concept of role function mode in the Roy adaptation theory and sensitize healthcare providers to the needs of the families during the discharge transition.

Functional role of oppA encoding an oligopeptide-binding protein from Lactobacillus salivarius Ren in bile tolerance.

PubMed

Wang, Guohong; Li, Dan; Ma, Xiayin; An, Haoran; Zhai, Zhengyuan; Ren, Fazheng; Hao, Yanling

2015-08-01

Lactobacillus salivarius is a member of the indigenous microbiota of the human gastrointestinal tract (GIT), and some L. salivarius strains are considered as probiotics. Bile tolerance is a crucial property for probiotic bacteria to survive the transit through the GIT and exert their beneficial effects. In this work, the functional role of oppA encoding an oligopeptide transporter substrate-binding protein from L. salivarius Ren in bile salt tolerance was investigated. In silico analysis revealed that the oppA gene encodes a 61.7-kDa cell surface-anchored hydrophilic protein with a canonical lipoprotein signal peptide. Homologous overexpression of OppA was shown to confer 20-fold higher tolerance to 0.5 % oxgall in L. salivarius Ren. Furthermore, the recombinant strain exhibited 1.8-fold and 3.6-fold higher survival when exposed to the sublethal concentration of sodium taurocholate and sodium taurodeoxycholate, respectively, while no significant change was observed when exposed to sodium glycocholate and sodium glycodeoxycholate (GDCA). Our results indicate that OppA confers specific resistance to taurine-conjugated bile salts in L. salivarius Ren. In addition, the OppA overexpression strain also showed significant increased resistance to heat and salt stresses, suggesting the protective role of OppA against multiple stresses in L. salivarius Ren.

Developing a national role description for medical directors in long-term care: survey-based approach.

PubMed

Rahim-Jamal, Sherin; Quail, Patrick; Bhaloo, Tajudaullah

2010-01-01

To develop a national role description for medical directors in long-term care (LTC) based on role functions drawn from the literature and the LTC industry. A questionnaire about the role functions identified from the literature was mailed or e-mailed to randomly selected medical directors, directors of care or nursing (DOCs), and administrators in LTC facilities. Long-term care facilities in Canada randomly selected from regional clusters. Medical directors, DOCs, and administrators in LTC facilities; a national advisory group of medical directors from the Long Term Care Medical Directors Association of Canada; and a volunteer group of medical directors. Respondents were asked to indicate, from the list of identified functions, 1) whether medical directors spent any time on each activity; 2) whether medical directors should spend time on each activity; and 3) if medical directors should spend time on an activity, whether the activity was "essential" or "desirable." An overall response rate of 37% was obtained. At least 80% of the respondents from all 3 groups (medical directors, DOCs, and administrators) highlighted 24 functions they deemed to be "essential" or "desirable," which were then included in the role description. In addition, the advisory group expanded the role description to include 5 additional responsibilities from the remaining 18 functions originally identified. A volunteer group of medical directors confirmed the resulting role description. The role description developed as a result of this study brings clarity to the medical director's role in Canadian LTC facilities; the functions outlined are considered important for medical directors to undertake. The role description could be a useful tool in negotiations pertaining to time commitment and expectations of a medical director and fair compensation for services rendered.

Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors

PubMed Central

Zheng, Yingfeng; Murphy, Leigh C.

2016-01-01

Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M. PMID:26778927

The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors

PubMed Central

Root, David H.; Melendez, Roberto I.; Zaborszky, Laszlo; Napier, T. Celeste

2015-01-01

The ventral pallidum (VP) plays a critical role in the processing and execution of motivated behaviors. Yet this brain region is often overlooked in published discussions of the neurobiology of mental health (e.g., addiction, depression). This contributes to a gap in understanding the neurobiological mechanisms of psychiatric disorders. This review is presented to help bridge the gap by providing a resource for current knowledge of VP anatomy, projection patterns and subregional circuits, and how this organization relates to the function of VP neurons and ultimately behavior. For example, ventromedial (VPvm) and dorsolateral (VPdl) VP subregions receive projections from nucleus accumbens shell and core, respectively. Inhibitory GABAergic neurons of the VPvm project to mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area, and this VP subregion helps discriminate the appropriate conditions to acquire natural rewards or drugs of abuse, consume preferred foods, and perform working memory tasks. GABAergic neurons of the VPdl project to subthalamic nucleus and substantia nigra pars reticulata, and this VP subregion is modulated by, and is necessary for, drug-seeking behavior. Additional circuits arise from nonGABAergic neuronal phenotypes that are likely to excite rather than inhibit their targets. These subregional and neuronal phenotypic circuits place the VP in a unique position to process motivationally-relevant stimuli and coherent adaptive behaviors. PMID:25857550

Cholinergic modulation of the hippocampal region and memory function.

PubMed

Haam, Juhee; Yakel, Jerrel L

2017-08-01

Acetylcholine (ACh) plays an important role in memory function and has been implicated in aging-related dementia, in which the impairment of hippocampus-dependent learning strongly manifests. Cholinergic neurons densely innervate the hippocampus, mediating the formation of episodic as well as semantic memory. Here, we will review recent findings on acetylcholine's modulation of memory function, with a particular focus on hippocampus-dependent learning, and the circuits involved. In addition, we will discuss the complexity of ACh actions in memory function to better understand the physiological role of ACh in memory. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses.

PubMed

Nguyen, Quynh-Anh; Horn, Meryl E; Nicoll, Roger A

2016-11-02

Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses. These domains point to a gephyrin-dependent mechanism that is disrupted by an autism-associated mutation at R705 and a gephyrin-independent mechanism reliant on a putative phosphorylation site at S714. Our work highlights unique and separate roles for the extracellular and intracellular regions in specifying and carrying out NLGN function respectively.

Effect of Additives on Green Sand Molding Properties using Design of Experiments and Taguchi's Quality Loss Function - An Experimental Study

NASA Astrophysics Data System (ADS)

Desai, Bhagyashree; Mokashi, Pavani; Anand, R. L.; Burli, S. B.; Khandal, S. V.

2016-09-01

The experimental study aims to underseek the effect of various additives on the green sand molding properties as a particular combination of additives could yield desired sand properties. The input parameters (factors) selected were water and powder (Fly ash, Coconut shell and Tamarind) in three levels. Experiments were planned using design of experiments (DOE). On the basis of plans, experiments were conducted to understand the behavior of sand mould properties such as compression strength, shear strength, permeability number with various additives. From the experimental results it could be concluded that the factors have significant effect on the sand properties as P-value found to be less than 0.05 for all the cases studied. The optimization based on quality loss function was also performed. The study revealed that the quality loss associated with the tamarind powder was lesser compared to other additives selected for the study. The optimization based on quality loss function and the parametric analysis using ANOVA suggested that the tamarind powder of 8 gm per Kg of molding sand and moisture content of 7% yield better properties to obtain sound castings.

Role of the ectonucleotidase NTPDase2 in taste bud function

PubMed Central

Vandenbeuch, Aurelie; Anderson, Catherine B.; Parnes, Jason; Enjyoji, Keiichi; Robson, Simon C.; Finger, Thomas E.; Kinnamon, Sue C.

2013-01-01

Taste buds are unusual in requiring ATP as a transmitter to activate sensory nerve fibers. In response to taste stimuli, taste cells release ATP, activating purinergic receptors containing the P2X2 and P2X3 subunits on taste nerves. In turn, the released ATP is hydrolyzed to ADP by a plasma membrane nucleoside triphosphate previously identified as nucleoside triphosphate diphosphohydrolase-2 (NTPDase2). In this paper we investigate the role of this ectonucleotidase in the function of taste buds by examining gene-targeted Entpd2-null mice globally lacking NTPDase2. RT-PCR confirmed the absence of NTPDase2, and ATPase enzyme histochemistry reveals no reaction product in taste buds of knockout mice, suggesting that NTPDase2 is the dominant form in taste buds. RT-PCR and immunocytochemistry demonstrated that in knockout mice all cell types are present in taste buds, even those cells normally expressing NTPDase2. In addition, the overall number and size of taste buds are normal in Entpd2-null mice. Luciferin/luciferase assays of circumvallate tissue of knockout mice detected elevated levels of extracellular ATP. Electrophysiological recordings from two taste nerves, the chorda tympani and glossopharyngeal, revealed depressed responses to all taste stimuli in Entpd2-null mice. Responses were more depressed in the glossopharyngeal nerve than in the chorda tympani nerve and involved all taste qualities; responses in the chorda tympani were more depressed to sweet and umami stimuli than to other qualities. We suggest that the excessive levels of extracellular ATP in the Entpd2-knockout animals desensitize the P2X receptors associated with nerve fibers, thereby depressing taste responses. PMID:23959882

Role of the ectonucleotidase NTPDase2 in taste bud function.

PubMed

Vandenbeuch, Aurelie; Anderson, Catherine B; Parnes, Jason; Enjyoji, Keiichi; Robson, Simon C; Finger, Thomas E; Kinnamon, Sue C

2013-09-03

Taste buds are unusual in requiring ATP as a transmitter to activate sensory nerve fibers. In response to taste stimuli, taste cells release ATP, activating purinergic receptors containing the P2X2 and P2X3 subunits on taste nerves. In turn, the released ATP is hydrolyzed to ADP by a plasma membrane nucleoside triphosphate previously identified as nucleoside triphosphate diphosphohydrolase-2 (NTPDase2). In this paper we investigate the role of this ectonucleotidase in the function of taste buds by examining gene-targeted Entpd2-null mice globally lacking NTPDase2. RT-PCR confirmed the absence of NTPDase2, and ATPase enzyme histochemistry reveals no reaction product in taste buds of knockout mice, suggesting that NTPDase2 is the dominant form in taste buds. RT-PCR and immunocytochemistry demonstrated that in knockout mice all cell types are present in taste buds, even those cells normally expressing NTPDase2. In addition, the overall number and size of taste buds are normal in Entpd2-null mice. Luciferin/luciferase assays of circumvallate tissue of knockout mice detected elevated levels of extracellular ATP. Electrophysiological recordings from two taste nerves, the chorda tympani and glossopharyngeal, revealed depressed responses to all taste stimuli in Entpd2-null mice. Responses were more depressed in the glossopharyngeal nerve than in the chorda tympani nerve and involved all taste qualities; responses in the chorda tympani were more depressed to sweet and umami stimuli than to other qualities. We suggest that the excessive levels of extracellular ATP in the Entpd2-knockout animals desensitize the P2X receptors associated with nerve fibers, thereby depressing taste responses.

The roles of p53R2 in cancer progression based on the new function of mutant p53 and cytoplasmic p21.

PubMed

Yousefi, Bahman; Rahmati, Mohammad; Ahmadi, Yasin

2014-03-18

Although the deregulated expression of p53R2, a p53-inducible protein and homologue of the R2 subunit of ribonucleotide reductase, has been detected in several human cancers, p53R2 roles in cancer progression and malignancy still remains controversial. In this article, we present a viable hypothesis about the roles of p53R2 in cancer progression and therapy resistance based on the roles of cytoplasmic p21 and mutant p53. Since p53R2 can up-regulate p21 and p21, it in turn has a dual role in cell cycle. Hence, p53R2 can play a dual role in cell cycle progression. In addition, because p53 is the main regulator of p53R2, the mutant p53 may induce the expression of p53R2 in some cancer cells based on the "keep of function" phenomenon. Therefore, depending on the locations of p21 and the new abilities of mutant p53, p53R2 has dual role in cell cycle progression. Since the DNA damaging therapies induce p53R2 expression through the induction of p53, p53R2 can be the main therapy resistance mediator in cancers with cytoplasmic p21. Copyright © 2014 Elsevier Inc. All rights reserved.

The roles and functions of a lunar base Nuclear Technology Center

NASA Astrophysics Data System (ADS)

Buden, D.; Angelo, J. A., Jr.

This paper describes the roles and functions of a special Nuclear Technology Center which is developed as an integral part of a permanent lunar base. Numerous contemporary studies clearly point out that nuclear energy technology will play a major role in any successful lunar/Mars initiative program and in the overall establishment of humanity's solar system civilization. The key role of nuclear energy in the providing power has been recognized. A Nuclear Technology Center developed as part of a permanent lunar base can also help bring about many other nuclear technology applications, such as producing radioisotopes for self-illumination, food preservation, waste sterilization, and medical treatment; providing thermal energy for mining, materials processing and agricultural; and as a source of emergency habitat power. Designing such a center will involve the deployment, operation, servicing and waste product management and disposal of megawatt class reactor power plants. This challenge must be met with a minimum of direct human support at the facility. Furthermore, to support the timely, efficient integration of this Nuclear Technology Center in the evolving lunar base infrastructure, an analog of such a facility will be needed here on Earth.

Neurocognitive predictors of remission of symptoms and social and role functioning in the early course of first-episode schizophrenia.

PubMed

Torgalsbøen, Anne-Kari; Mohn, Christine; Rishovd Rund, Bjørn

2014-04-30

In a Norwegian ongoing longitudinal study, we investigate the neurocognitive development in first-episode schizophrenia patients, and the influence of neurocognition on remission and real life functioning. In the present study, results from the early course of illness are reported. The sample includes 28 schizophrenia spectrum patients and 28 pairwise matched healthy controls. The patients were recruited from mental health service institutions and data on psychosocial functioning, remission and neurocognition were obtained through a clinical interview, an inventory on social and role functioning, operational criteria of remission, and a standardized neurocognitive test battery, the MATRICS Consensus Cognitive Battery (MCCB). Large effect size differences between patients and controls were observed at baseline on every cognitive domain, as well as statistically significant improvements on overall cognitive function at follow-up for the patient group. A remission rate of 61% was found. The neurocognitive baseline measure of Attention significantly predicted remission status at follow-up, whereas Attention and Working Memory at baseline predicted levels of social and role functioning. In the early course of the illness, more than half of the group of first-episode patients were in remission, and neurocognitive functions are significantly associated with both remission of symptoms and social and role functioning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Distinct roles for Ste20-like kinase SLK in muscle function and regeneration

PubMed Central

2013-01-01

Background Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood. Methods To gain further insights into the role of SLK in differentiated muscles, we expressed a kinase-inactive SLK from the human skeletal muscle actin promoter. Transgenic muscles were surveyed for potential defects. Standard histological procedures and cardiotoxin-induced regeneration assays we used to investigate the role of SLK in myogenesis and muscle repair. Results High levels of kinase-inactive SLK in muscle tissue produced an overall decrease in SLK activity in muscle tissue, resulting in altered muscle organization, reduced litter sizes, and reduced breeding capacity. The transgenic mice did not show any differences in fiber-type distribution but displayed enhanced regeneration capacity in vivo and more robust differentiation in vitro. Conclusions Our results show that SLK activity is required for optimal muscle development in the embryo and muscle physiology in the adult. However, reduced kinase activity during muscle repair enhances regeneration and differentiation. Together, these results suggest complex and distinct roles for SLK in muscle development and function. PMID:23815977

Common Hydraulic Fracturing Fluid Additives Alter the Structure and Function of Anaerobic Microbial Communities.

PubMed

Mumford, Adam C; Akob, Denise M; Klinges, J Grace; Cozzarelli, Isabelle M

2018-04-15

The development of unconventional oil and gas (UOG) resources results in the production of large volumes of wastewater containing a complex mixture of hydraulic fracturing chemical additives and components from the formation. The release of these wastewaters into the environment poses potential risks that are poorly understood. Microbial communities in stream sediments form the base of the food chain and may serve as sentinels for changes in stream health. Iron-reducing organisms have been shown to play a role in the biodegradation of a wide range of organic compounds, and so to evaluate their response to UOG wastewater, we enriched anaerobic microbial communities from sediments collected upstream (background) and downstream (impacted) of an UOG wastewater injection disposal facility in the presence of hydraulic fracturing fluid (HFF) additives: guar gum, ethylene glycol, and two biocides, 2,2-dibromo-3-nitrilopropionamide (DBNPA) and bronopol (C 3 H 6 BrNO 4 ). Iron reduction was significantly inhibited early in the incubations with the addition of biocides, whereas amendment with guar gum and ethylene glycol stimulated iron reduction relative to levels in the unamended controls. Changes in the microbial community structure were observed across all treatments, indicating the potential for even small amounts of UOG wastewater components to influence natural microbial processes. The microbial community structure differed between enrichments with background and impacted sediments, suggesting that impacted sediments may have been preconditioned by exposure to wastewater. These experiments demonstrated the potential for biocides to significantly decrease iron reduction rates immediately following a spill and demonstrated how microbial communities previously exposed to UOG wastewater may be more resilient to additional spills. IMPORTANCE Organic components of UOG wastewater can alter microbial communities and biogeochemical processes, which could alter the rates of

Rule-Based Category Learning in Children: The Role of Age and Executive Functioning

PubMed Central

Rabi, Rahel; Minda, John Paul

2014-01-01

Rule-based category learning was examined in 4–11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working memory and inhibitory control were related to rule-based categorization and improved with age, working memory specifically was found to marginally mediate the age-related improvements in categorization. When analyses focused only on the sample of children, results showed that working memory ability and inhibitory control were associated with categorization performance and strategy use. The current findings track changes in categorization performance across childhood, demonstrating at which points performance begins to mature and resemble that of adults. Additionally, findings highlight the potential role that working memory and inhibitory control may play in rule-based category learning. PMID:24489658

The Role of Family Functioning in the Stress Process of Dementia Caregivers: A Structural Family Framework

ERIC Educational Resources Information Center

Mitrani, Victoria B.; Lewis, John E.; Feaster, Daniel J.; Czaja, Sara J.; Eisdorfer, Carl; Schulz, Richard; Szapocznik, Jose

2006-01-01

Purpose: The purpose of the study was to evaluate the role of family functioning in the stress process in a sample of caregivers of dementia patients by using a structural family framework. The stress-process model of caregiver distress included family functioning as an intervening variable in the relationship between objective burden and…

The Role of Species Traits in Mediating Functional Recovery during Matrix Restoration

PubMed Central

Barnes, Andrew D.; Emberson, Rowan M.; Krell, Frank-Thorsten; Didham, Raphael K.

2014-01-01

Reversing anthropogenic impacts on habitat structure is frequently successful through restoration, but the mechanisms linking habitat change, community reassembly and recovery of ecosystem functioning remain unknown. We test for the influence of edge effects and matrix habitat restoration on the reassembly of dung beetle communities and consequent recovery of dung removal rates across tropical forest edges. Using path modelling, we disentangle the relative importance of community-weighted trait means and functional trait dispersion from total biomass effects on rates of dung removal. Community trait composition and biomass of dung beetle communities responded divergently to edge effects and matrix habitat restoration, yielding opposing effects on dung removal. However, functional dispersion—used in this study as a measure of niche complementarity—did not explain a significant amount of variation in dung removal rates across habitat edges. Instead, we demonstrate that the path to functional recovery of these altered ecosystems depends on the trait-mean composition of reassembling communities, over and above purely biomass-dependent processes that would be expected under neutral theory. These results suggest that any ability to manage functional recovery of ecosystems during habitat restoration will demand knowledge of species' roles in ecosystem processes. PMID:25502448

The role of species traits in mediating functional recovery during matrix restoration.

PubMed

Barnes, Andrew D; Emberson, Rowan M; Krell, Frank-Thorsten; Didham, Raphael K

2014-01-01

Reversing anthropogenic impacts on habitat structure is frequently successful through restoration, but the mechanisms linking habitat change, community reassembly and recovery of ecosystem functioning remain unknown. We test for the influence of edge effects and matrix habitat restoration on the reassembly of dung beetle communities and consequent recovery of dung removal rates across tropical forest edges. Using path modelling, we disentangle the relative importance of community-weighted trait means and functional trait dispersion from total biomass effects on rates of dung removal. Community trait composition and biomass of dung beetle communities responded divergently to edge effects and matrix habitat restoration, yielding opposing effects on dung removal. However, functional dispersion--used in this study as a measure of niche complementarity--did not explain a significant amount of variation in dung removal rates across habitat edges. Instead, we demonstrate that the path to functional recovery of these altered ecosystems depends on the trait-mean composition of reassembling communities, over and above purely biomass-dependent processes that would be expected under neutral theory. These results suggest that any ability to manage functional recovery of ecosystems during habitat restoration will demand knowledge of species' roles in ecosystem processes.

The effects of increased testicular temperature on testis-specific isoform of Na+/K+ -ATPase in sperm and its role in spermatogenesis and sperm function.

PubMed

Thundathil, J C; Rajamanickam, G D; Kastelic, J P; Newton, L D

2012-08-01

Impaired testicular thermoregulation is commonly implicated in abnormal spermatogenesis and impaired sperm function in animals and humans, with outcomes ranging from subclinical infertility to sterility. Bovine testes must be maintained 4-5 °C below body-core temperature for normal spermatogenesis. The effects of elevated testicular temperature have been extensively studied in cattle using a scrotal insulation model, which results in abnormal spermatogenesis and impaired sperm morphology and function. Using this model and proteomic approaches, we compared normal and abnormal sperm (from the same bulls) to elucidate the molecular basis of impaired function. We identified a cohort of sperm functional proteins differentially expressed between normal vs abnormal sperm, including a testis-specific isoform of Na(+) /K(+) -ATPase. In addition to its role as a sodium pump regulating sperm motility, Na(+) /K(+) -ATPase is also involved as a signalling molecule during sperm capacitation. In conclusion, because of its involvement in regulation of sperm function, this protein has potential as a fertility marker. Furthermore, comparing normal vs abnormal sperm (induced by scrotal insulation) is a useful model for identifying proteins regulating sperm function. © 2012 Blackwell Verlag GmbH.

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

PubMed

Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

2017-03-20

As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

The role of early life nutrition in programming of reproductive function.

PubMed

Chadio, S; Kotsampasi, B

2014-02-01

Accumulating evidence suggest that the concept of programming can also be applied to reproductive development and function, representing an ever expanding research area. Recently issues such as peri- or even preconceptional nutrition, transgenerational effects and underlying mechanisms have received considerable attention. The present chapter presents the existed evidence and reviews the available data from numerous animal and human studies on the effects of early life nutritional environment on adult reproductive function. Specific outcomes depend on the severity, duration and stage of development when nutritional perturbations are imposed, while sex-specific effects are also manifested. Apart from undernutrition, effects of relative overnutrition as well as the complex interactions between pre- and postnatal nutrition is of high importance, especially in the context of our days obesity epidemic. Mechanisms underlying reproductive programming are yet unclear, but may include a role for epigenetic modifications. Epigenetic modulation of critical genes involved in the control of reproductive function and potential intergenerational effects represent an exciting area of interdisciplinary research toward the development of new nutritional approaches during pre- and postnatal periods to ensure reproductive health in later life.

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer.

PubMed

Fujisawa, Takao; Filippakopoulos, Panagis

2017-04-01

Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues - particularly in histones - and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves. Importantly, BRDs can be targeted by small-molecule inhibitors, which has stimulated many translational research projects that seek to attenuate the aberrant functions of BRD-containing proteins in disease.

The role of fear-avoidance and helplessness in explaining functional disability in chronic pain: a prospective study.

PubMed

Samwel, Han J A; Kraaimaat, Floris W; Crul, Ben J P; Evers, Andrea W M

2007-01-01

Based on the fear-avoidance and helplessness models, the relative contribution of fear of pain, avoidance behavior, worrying, and helplessness were examined in relation to fluctuations in functional disability in chronic-pain patients. A cohort of 181 chronic-pain patients first completed various questionnaires and kept a 7-day pain journal during a standard 3-month waiting-list period prior to their scheduled treatment at an Interdisciplinary Pain Centre and did so again immediately preceding the intervention. At baseline, fear of pain, avoidance behavior, and helplessness all predicted functional disability after 3 months. Stepwise regression analyses showed avoidance behavior to be the strongest predictor of change in functional disability followed by helplessness, thus both ahead of fear of pain. The current findings support the roles of both fear-avoidance factors and helplessness in the functional disability in chronic-pain patients awaiting treatment but revealed a central role for avoidance behavior.

Adult Roles & Functions. A Nonlaboratory Home Economics Course for Eleventh and Twelfth Graders.

ERIC Educational Resources Information Center

West Virginia State Vocational Curriculum Lab., Cedar Lakes.

This competency-based curriculum guide is designed for a non-laboratory course in home economics for eleventh and twelfth grades. It was developed and field tested by twenty-nine teachers in high schools in West Virginia. The Adult Roles and Functions curriculum is organized in two sections. The teacher's section contains information on teaching…

Role of Fatty-acid Synthesis in Dendritic Cell Generation and Function

PubMed Central

Rehman, Adeel; Hemmert, Keith C.; Ochi, Atsuo; Jamal, Mohsin; Henning, Justin R.; Barilla, Rocky; Quesada, Juan P.; Zambirinis, Constantinos P.; Tang, Kerry; Ego-Osuala, Melvin; Rao, Raghavendra S.; Greco, Stephanie; Deutsch, Michael; Narayan, Suchithra; Pachter, H. Leon; Graffeo, Christopher S.; Acehan, Devrim; Miller, George

2013-01-01

Dendritic cells (DC) are professional antigen presenting cells that regulate innate and adaptive immunity. The role of fatty-acid synthesis in DC development and function is uncertain. We found that blockade of fatty-acid synthesis markedly decreases dendropoiesis in the liver and in primary and secondary lymphoid organs in mice. Human DC development from PBMC precursors was also diminished by blockade of fatty-acid synthesis. This was associated with higher rates of apoptosis in precursor cells and increased expression of Cleaved Caspase 3 and BCL-xL, and down-regulation of Cyclin B1. Further, blockade of fatty-acid synthesis decreased DC expression of MHCII, ICAM-1, B7-1, B7-2 but increased their production of selected pro-inflammatory cytokines including IL-12 and MCP-1. Accordingly, inhibition of fatty-acid synthesis enhanced DC capacityto activate allogeneic as well as antigen-restricted CD4+ and CD8+ T cells and induce CTL responses. Further, blockade of fatty-acid synthesis increased DC expression of Notch ligands and enhanced their ability to activate NK cell immune-phenotype and IFN-γ production. Since endoplasmic reticular (ER)-stress can augment the immunogenic function of APC, we postulated that this may account for the higher DC immunogenicity. We found that inhibition of fatty-acid synthesis resulted in elevated expression of numerous markers of ER stress in humans and mice and was associated with increased MAP kinase and Akt signaling. Further, lowering ER-stress by 4-phenylbutyrate mitigated the enhanced immune-stimulation associated with fatty-acid synthesis blockade. Our findings elucidate the role of fatty-acid synthesis in DC development and function and have implications to the design of DC vaccines for immunotherapy. PMID:23536633

Social integration and age-related decline in lung function.

PubMed

Crittenden, Crista N; Murphy, Michael L M; Cohen, Sheldon

2018-05-01

We tested the hypothesis that social integration, measured as number of social roles, is associated with less age-related loss of lung function, an important marker of health and longevity. We also investigated possible psychological factors through which social integration might influence lung health. Data were analyzed from the Health and Retirement Study (ages 52-94, n = 4,224). Each additional social role reported at baseline was associated with less of a decline in lung function between baseline and the follow-up assessment four years later. The association withstood controls for demographics, weight, and height and was mediated by more positive and less negative affect and lower rates of cigarette smoking and more physical activity. Roles were mostly substitutable, with both high (spouse, parent, friends, relatives) and low (employee, religious service attendee, volunteer, members of other groups) intimacy roles independently contributing to less age-related decline in lung function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of change in physical activity on physical function limitations in older women: mediating roles of physical function performance and self-efficacy.

PubMed

McAuley, Edward; Morris, Katherine S; Doerksen, Shawna E; Motl, Robert W; Liang, Hu; White, Siobhan M; Wójcicki, Thomas R; Rosengren, Karl

2007-12-01

To examine the hypothesis that changes in self-efficacy and functional performance mediate, in part, the beneficial effect of physical activity on functional limitations over time. Prospective, observational study. Community-based. Two hundred forty-nine community-dwelling older women. Participants completed measures of self-reported physical activity, functional limitations, and self-efficacy. Four measures of physical function performance were also assessed. Measures were completed at baseline and 24 months. Data were analyzed using a panel model within a covariance modeling framework. Results indicated that increases in physical activity over time were associated with greater improvements in self-efficacy, which was associated in turn with improved physical function performance, both of which mediated the association between physical activity and functional limitations. Fewer functional limitations at baseline were also associated with higher levels of self-efficacy at 24 months. Age, race, and health status covariates did not significantly change these relationships. The findings support the mediating roles of self-efficacy and physical function performance in the relationship between longitudinal changes in physical activity and functional limitations in older women.

Another look at roles and functions: has hospital case management lost its way?

PubMed

Reynolds, John J

2013-01-01

The purpose of this study was to identify the roles, functions, and types of activities that hospital case managers engage in on a day-to-day basis and that leverage the most amounts of time. Previous studies superimpose a priori categories on research tools. Hospital case management. This study analyzes 4,064 spontaneous, unstructured list serve postings from the American Case Management Association Learning Link list serve from August 15, 2011, to August 18, 2012. The study group was a cross section of 415 case management professionals. The data suggest that hospital case managers' time is inordinately leveraged by issues related to observation status/leveling of patients and the Centers for Medicare and Medicaid Services compliance. The data also suggest that hospital case management has taken a conceptual trajectory that has deviated significantly from what was initially conceived (quality, advocacy, and care coordination) and what is publicly purported. Case management education and practical orientation will need to be commensurate with this emerging emphasis. Case management leadership will need to be adept at mitigating the stresses of role confusion, role conflict, and role ambiguity.

Role of Dietary Antioxidants in the Preservation of Vascular Function and the Modulation of Health and Disease

PubMed Central

Varadharaj, Saradhadevi; Kelly, Owen J.; Khayat, Rami N.; Kumar, Purnima S.; Ahmed, Naseer; Zweier, Jay L.

2017-01-01

In vascular diseases, including hypertension and atherosclerosis, vascular endothelial dysfunction (VED) occurs secondary to altered function of endothelial nitric oxide synthase (eNOS). A novel redox regulated pathway was identified through which eNOS is uncoupled due to S-glutathionylation of critical cysteine residues, resulting in superoxide free radical formation instead of the vasodilator molecule, nitric oxide. In addition, the redox sensitive cofactor tetrahydrobiopterin, BH4, is also essential for eNOS coupling. Antioxidants, either individually or combined, can modulate eNOS uncoupling by scavenging free radicals or impairing specific radical generating pathways, thus preventing oxidative stress and ameliorating VED. Epidemiological evidence and dietary guidelines suggest that diets high in antioxidants, or antioxidant supplementation, could preserve vascular health and prevent cardiovascular diseases (CVDs). Therefore, the purpose of this review is to highlight the possible role of dietary antioxidants in regulating eNOS function and uncoupling which is critical for maintenance of vascular health with normal blood flow/circulation and prevention of VED. We hypothesize that a conditioned dietary approach with suitable antioxidants may limit systemic oxidation, maintain a beneficial ratio of reduced to oxidized glutathione, and other redox markers, and minimize eNOS uncoupling serving to prevent CVD and possibly other chronic diseases. PMID:29164133

Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL6 in non-small cell lung cancer in vivo

PubMed Central

Vicent, Silvestre; Sayles, Leanne C.; Vaka, Dedeepya; Khatri, Purvesh; Gevaert, Olivier; Chen, Ron; Zheng, Yanyan; Gillespie, Anna K.; Clarke, Nicole; Xu, Yue; Shrager, Joseph; Hoang, Chuong D.; Plevritis, Sylvia; Butte, Atul J.; Sweet-Cordero, E. Alejandro

2013-01-01

Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in NSCLC patients. This secreted gene signature was upregulated in NFs after long-term exposure to tumor cells, demonstrating that NFs are “educated” by tumor cells to acquire a CAF-like phenotype. Functional studies identified important roles for CLCF1-CNTFR and IL6-IL6R signaling, in promoting growth of NSCLC cells. This study identifies novel soluble factors contributing to the CAF protumorigenic phenotype in NSCLC and suggests new avenues for the development of therapeutic strategies. PMID:22962265

Additive manufacturing of hybrid circuits

DOE PAGES

Bell, Nelson S.; Sarobol, Pylin; Cook, Adam; ...

2016-03-26

There is a rising interest in developing functional electronics using additively manufactured components. Considerations in materials selection and pathways to forming hybrid circuits and devices must demonstrate useful electronic function; must enable integration; and must complement the complex shape, low cost, high volume, and high functionality of structural but generally electronically passive additively manufactured components. This article reviews several emerging technologies being used in industry and research/development to provide integration advantages of fabricating multilayer hybrid circuits or devices. First, we review a maskless, noncontact, direct write (DW) technology that excels in the deposition of metallic colloid inks for electrical interconnects.more » Second, we review a complementary technology, aerosol deposition (AD), which excels in the deposition of metallic and ceramic powder as consolidated, thick conformal coatings and is additionally patternable through masking. As a result, we show examples of hybrid circuits/devices integrated beyond 2-D planes, using combinations of DW or AD processes and conventional, established processes.« less

Functional profiles reveal unique ecological roles of various biological soil crust organisms

USGS Publications Warehouse

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

The resilience and functional role of moss in boreal and arctic ecosystems.

PubMed

Turetsky, M R; Bond-Lamberty, B; Euskirchen, E; Talbot, J; Frolking, S; McGuire, A D; Tuittila, E-S

2012-10-01

Mosses in northern ecosystems are ubiquitous components of plant communities, and strongly influence nutrient, carbon and water cycling. We use literature review, synthesis and model simulations to explore the role of mosses in ecological stability and resilience. Moss community responses to disturbance showed all possible responses (increases, decreases, no change) within most disturbance categories. Simulations from two process-based models suggest that northern ecosystems would need to experience extreme perturbation before mosses were eliminated. But simulations with two other models suggest that loss of moss will reduce soil carbon accumulation primarily by influencing decomposition rates and soil nitrogen availability. It seems clear that mosses need to be incorporated into models as one or more plant functional types, but more empirical work is needed to determine how to best aggregate species. We highlight several issues that have not been adequately explored in moss communities, such as functional redundancy and singularity, relationships between response and effect traits, and parameter vs conceptual uncertainty in models. Mosses play an important role in several ecosystem processes that play out over centuries - permafrost formation and thaw, peat accumulation, development of microtopography - and there is a need for studies that increase our understanding of slow, long-term dynamical processes. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

[Roles, functions and myths in the family group of the psychotic patient].

PubMed

Gallego Lluesma, O; Pugliese, R

1986-12-01

With the study of two families in treatment we can see the roles that each one gets, and the functions that the psychotic assumes. Because the family has a particular story, a lot of myths appear and the interpretation is the hermeneutic method which serves to explain them. This fact is very important because some of those myths show the pathologic unconscious of the family. Through the myths, the family expresses the values, the credences, the familiar ideology and the ideals, which generally are neither possible, real nor concrete. To consider the clinic material, we start from the description of a pathological family and we continue with the theoretical approximation of Pichon Riviére: the antipsychiatry, the structuralism and the theories about the communication of Palo Alto. Then, we arrive at universal situations about the roles in the psychotic's family: fixation and immobility, stereotypy and aupplementarity, double vinculum situation, the family gives up modifying the structure and the patient who assumes the family pathology is almost permanently disqualified. There is a downfall in the identity of the psychotic mainly because the father's function is perverted (in both families, the father appears as "powerful" and considered in society, but disqualified in the family).

The resilience and functional role of moss in boreal and arctic ecosystems

USGS Publications Warehouse

Turetsky, M.; Bond-Lamberty, B.; Euskirchen, E.S.; Talbot, J. J.; Frolking, S.; McGuire, A.D.; Tuittila, E.S.

2012-01-01

Mosses in northern ecosystems are ubiquitous components of plant communities, and strongly influence nutrient, carbon and water cycling. We use literature review, synthesis and model simulations to explore the role of mosses in ecological stability and resilience. Moss community responses to disturbance showed all possible responses (increases, decreases, no change) within most disturbance categories. Simulations from two process-based models suggest that northern ecosystems would need to experience extreme perturbation before mosses were eliminated. But simulations with two other models suggest that loss of moss will reduce soil carbon accumulation primarily by influencing decomposition rates and soil nitrogen availability. It seems clear that mosses need to be incorporated into models as one or more plant functional types, but more empirical work is needed to determine how to best aggregate species. We highlight several issues that have not been adequately explored in moss communities, such as functional redundancy and singularity, relationships between response and effect traits, and parameter vs conceptual uncertainty in models. Mosses play an important role in several ecosystem processes that play out over centuries – permafrost formation and thaw, peat accumulation, development of microtopography – and there is a need for studies that increase our understanding of slow, long-term dynamical processes.

Social skills and sex-role functioning in borderline personality disorder: relationship to self-mutilating behavior.

PubMed

McKay, Dean; Gavigan, Carie A; Kulchycky, Sonia

2004-01-01

This study compared the social skills functioning and sex role affiliation of female inpatients diagnosed with borderline personality disorder who engaged in self-mutilating behavior (n = 30) with female patients with borderline personality disorder who did not engage in such behavior (n = 18). Patients with borderline personality disorder who engaged in self-mutilating behavior were found to have relatively poorer skills in communicating non-verbal emotional information to others and in receiving and interpreting such information from others. In terms of sex role orientation, patients who engaged in self-mutilating behavior were significantly more likely than non-mutilators to be typed as undifferentiated using the Bem Sex Role Inventory. These participants were less likely to identify with either masculine or feminine sex roles. Patients who did not self-mutilate were found to be significantly more likely than those who did self-mutilate to identify with the masculine sex role.

Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses

PubMed Central

Nguyen, Quynh-Anh; Horn, Meryl E; Nicoll, Roger A

2016-01-01

Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses. These domains point to a gephyrin-dependent mechanism that is disrupted by an autism-associated mutation at R705 and a gephyrin-independent mechanism reliant on a putative phosphorylation site at S714. Our work highlights unique and separate roles for the extracellular and intracellular regions in specifying and carrying out NLGN function respectively. DOI: http://dx.doi.org/10.7554/eLife.19236.001 PMID:27805570

The C. elegans Connectome Consists of Homogenous Circuits with Defined Functional Roles

PubMed Central

Azulay, Aharon; Zaslaver, Alon

2016-01-01

A major goal of systems neuroscience is to decipher the structure-function relationship in neural networks. Here we study network functionality in light of the common-neighbor-rule (CNR) in which a pair of neurons is more likely to be connected the more common neighbors it shares. Focusing on the fully-mapped neural network of C. elegans worms, we establish that the CNR is an emerging property in this connectome. Moreover, sets of common neighbors form homogenous structures that appear in defined layers of the network. Simulations of signal propagation reveal their potential functional roles: signal amplification and short-term memory at the sensory/inter-neuron layer, and synchronized activity at the motoneuron layer supporting coordinated movement. A coarse-grained view of the neural network based on homogenous connected sets alone reveals a simple modular network architecture that is intuitive to understand. These findings provide a novel framework for analyzing larger, more complex, connectomes once these become available. PMID:27606684

The diffuse chemosensory system: exploring the iceberg toward the definition of functional roles.

PubMed

Sbarbati, Andrea; Bramanti, Placido; Benati, Donatella; Merigo, Flavia

2010-05-01

The diffuse chemosensory system (DCS) is an anatomical structure composed of solitary chemosensory cells (SCCs, also called solitary chemoreceptor cells), which have analogies with taste cells but are not aggregated in buds. The concept of DCS has been advanced, after the discovery that cells similar to gustatory elements are present in several organs. The elements forming the DCS share common morphological and biochemical characteristics with the taste cells located in taste buds of the oro-pharyngeal cavity but they are localized in internal organs. In particular, they may express molecules of the chemoreceptorial cascade (e.g. trans-membrane taste receptors, the G-protein alpha-gustducin, PLCbeta2, TRPM5). This article will focus on the mammalian DCS in apparatuses of endodermic origin (i.e. digestive and respiratory systems), which is composed of an enormous number of sensory elements and presents a multiplicity of morphological aspects. Recent research has provided an adequate description of these elements, but the functional role for the DCS in these apparatuses is unknown. The initial findings led to the definition of a DCS structured like an iceberg, with a mysterious "submerged" portion localized in the distal part of endodermic apparatuses. Recent work has focussed on the discovery of this submerged portion, which now appears less puzzling. However, the functional roles of the different cytotypes belonging to the DCS are not well known. Recent studies linked chemosensation of the intraluminal content to local control of absorptive and secretory (exocrine and endocrine) processes. Control of the microbial population and detection of irritants seem to be other possible functions of the DCS. In the light of these new findings, the DCS might be thought to be involved in a wide range of diseases of both the respiratory (e.g. asthma, chronic obstructive pulmonary disease, cystic fibrosis) and digestive apparatuses (absorptive or secretive diseases, dysmicrobism

Modeling of digital mammograms using bicubic spline functions and additive noise

NASA Astrophysics Data System (ADS)

Graffigne, Christine; Maintournam, Aboubakar; Strauss, Anne

1998-09-01

The purpose of our work is the microcalcifications detection on digital mammograms. In order to do so, we model the grey levels of digital mammograms by the sum of a surface trend (bicubic spline function) and an additive noise or texture. We also introduce a robust estimation method in order to overcome the bias introduced by the microcalcifications. After the estimation we consider the subtraction image values as noise. If the noise is not correlated, we adjust its distribution probability by the Pearson's system of densities. It allows us to threshold accurately the images of subtraction and therefore to detect the microcalcifications. If the noise is correlated, a unilateral autoregressive process is used and its coefficients are again estimated by the least squares method. We then consider non overlapping windows on the residues image. In each window the texture residue is computed and compared with an a priori threshold. This provides correct localization of the microcalcifications clusters. However this technique is definitely more time consuming that then automatic threshold assuming uncorrelated noise and does not lead to significantly better results. As a conclusion, even if the assumption of uncorrelated noise is not correct, the automatic thresholding based on the Pearson's system performs quite well on most of our images.

The role of nanocrystalline binder metallic coating into WC after additive manufacturing

NASA Astrophysics Data System (ADS)

Cavaleiro, A. J.; Fernandes, C. M.; Farinha, A. R.; Gestel, C. V.; Jhabvala, J.; Boillat, E.; Senos, A. M. R.; Vieira, M. T.

2018-01-01

Tungsten carbide with microsized particle powders are commonly used embedded in a tough binder metal. The application of these composites is not limited to cutting tools, WC based material has been increasingly used in gaskets and other mechanical parts with complex geometries. Consequently, additive manufacturing processes as Selective Laser Sintering (SLS) might be the solution to overcome some of the manufacturing problems. However, the use of SLS leads to resolve the problems resulting from difference of physical properties between tungsten carbide and the metallic binder, such as laser absorbance and thermal conductivity. In this work, an original approach of powder surface modification was considered to prepare WC-metal composite powders and overcome these constraints, consisting on the sputter-coating of the WC particle surfaces with a nanocrystalline thin film of metallic binder material (stainless steel). The coating improves the thermal behavior and rheology of the WC particles and, at the same time, ensures a binder homogenous distribution. The feasibility of the SLS technology as manufacturing process for WC powder sputter-coated with 13 wt% stainless steel AISI 304L was explored with different laser power and scanning speed parameters. The SLS layers were characterized regarding elemental distribution, phase composition and morphology, and the results are discussed emphasizing the role of the coating on the consolidation process.

Listen to their answers! Response behaviour in the measurement of physical and role functioning.

PubMed

Westerman, Marjan J; Hak, Tony; Sprangers, Mirjam A G; Groen, Harry J M; van der Wal, Gerrit; The, Anne-Mei

2008-05-01

Quality of life (QoL) is considered to be an indispensable outcome measure of curative and palliative treatment. However, QoL research often yields findings that raise questions about what QoL measurement instruments actually assess and how the scores should be interpreted. To investigate how patients interpret and respond to questions on the EORTC-QLQ-C30 over time and to find explanations to account for counterintuitive findings in QoL measurement. Qualitative investigation was made of the response behaviour of small-cell lung cancer patients (n = 23) in the measurement of QoL with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Focus was on physical functioning (PF, items 1 to 5), role functioning (RF, items 6 and 7), global health and QoL rating (GH/QOL, items 29 and 30). Interviews were held at four points: at the start of the chemotherapy, 4 weeks later, at the end, and 6 weeks after the end of chemotherapy. Patients were asked to 'think aloud' when filling in the questionnaire. Patients used various response strategies when answering questions about problems and limitations in functioning, which impacted the accuracy of the scale. Patients had scores suggesting they were less limited than they actually were by taking the wording of questions literally, by guessing their functioning in activities that they did not perform, and by ignoring or excluding certain activities that they could not perform. Terminally ill patients evaluate their functioning in terms of what they perceive to be normal under the circumstances. Their answers can be interpreted in terms of change in the appraisal process (Rapkin and Schwartz 2004; Health and Quality of Life Outcomes, 2, 14). More care should be taken in assessing the quality of a set of questions about physical and role functioning.

Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

PubMed

Cox, Sophie C; Jamshidi, Parastoo; Eisenstein, Neil M; Webber, Mark A; Hassanin, Hany; Attallah, Moataz M; Shepherd, Duncan E T; Addison, Owen; Grover, Liam M

2016-07-01

Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of high level play as a predictor social functioning in autism.

PubMed

Manning, Margaret M; Wainwright, Laurel D

2010-05-01

Play and social abilities of a group of children diagnosed with high functioning autism were compared to a second group diagnosed with a variety of developmental language disorders (DLD). The children with autism engaged in fewer acts of high level play. The children with autism also had significantly lower social functioning than the DLD group early in the play session; however, these differences were no longer apparent by the end of the play session. In addition, a significant association existed between play and social functioning regardless of diagnosis. This suggests that play may act as a current indicator of social ability while providing an arena for social skills practice.

The Role of Functional Neuroimaging in Pre-Surgical Epilepsy Evaluation

PubMed Central

Pittau, Francesca; Grouiller, Frédéric; Spinelli, Laurent; Seeck, Margitta; Michel, Christoph M.; Vulliemoz, Serge

2014-01-01

The prevalence of epilepsy is about 1% and one-third of cases do not respond to medical treatment. In an eligible subset of patients with drug-resistant epilepsy, surgical resection of the epileptogenic zone is the only treatment that can possibly cure the disease. Non-invasive techniques provide information for the localization of the epileptic focus in the majority of cases, whereas in others invasive procedures are required. In the last years, non-invasive neuroimaging techniques, such as simultaneous recording of functional magnetic resonance imaging and electroencephalogram (EEG-fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), electric and magnetic source imaging (MSI, ESI), spectroscopy (MRS), have proved their usefulness in defining the epileptic focus. The combination of these functional techniques can yield complementary information and their concordance is crucial for guiding clinical decision, namely the planning of invasive EEG recordings or respective surgery. The aim of this review is to present these non-invasive neuroimaging techniques, their potential combination, and their role in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. PMID:24715886

Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits.

PubMed

Kennedy, David O

2014-09-01

Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways.

Crater function moments: Role of implanted noble gas atoms

NASA Astrophysics Data System (ADS)

Hobler, Gerhard; Maciążek, Dawid; Postawa, Zbigniew

2018-04-01

Spontaneous pattern formation by energetic ion beams is usually explained in terms of surface-curvature dependent sputtering and atom redistribution in the target. Recently, the effect of ion implantation on surface stability has been studied for nonvolatile ion species, but for the case of noble gas ion beams it has always been assumed that the implanted atoms can be neglected. In this work, we show by molecular dynamics (MD) and Monte Carlo (MC) simulations that this assumption is not valid in a wide range of implant conditions. Sequential-impact MD simulations are performed for 1-keV Ar, 2-keV Kr, and 2-keV Xe bombardments of Si, starting with a pure single-crystalline Si target and running impacts until sputtering equilibrium has been reached. The simulations demonstrate the importance of the implanted ions for crater-function estimates. The atomic volumes of Ar, Kr, and Xe in Si are found to be a factor of two larger than in the solid state. To extend the study to a wider range of energies, MC simulations are performed. We find that the role of the implanted ions increases with the ion energy although the increase is attenuated for the heavier ions. The analysis uses the crater function formalism specialized to the case of sputtering equilibrium.

Regulatory mechanisms of RNA function: emerging roles of DNA repair enzymes.

PubMed

Jobert, Laure; Nilsen, Hilde

2014-07-01

The acquisition of an appropriate set of chemical modifications is required in order to establish correct structure of RNA molecules, and essential for their function. Modification of RNA bases affects RNA maturation, RNA processing, RNA quality control, and protein translation. Some RNA modifications are directly involved in the regulation of these processes. RNA epigenetics is emerging as a mechanism to achieve dynamic regulation of RNA function. Other modifications may prevent or be a signal for degradation. All types of RNA species are subject to processing or degradation, and numerous cellular mechanisms are involved. Unexpectedly, several studies during the last decade have established a connection between DNA and RNA surveillance mechanisms in eukaryotes. Several proteins that respond to DNA damage, either to process or to signal the presence of damaged DNA, have been shown to participate in RNA quality control, turnover or processing. Some enzymes that repair DNA damage may also process modified RNA substrates. In this review, we give an overview of the DNA repair proteins that function in RNA metabolism. We also discuss the roles of two base excision repair enzymes, SMUG1 and APE1, in RNA quality control.

Microbial functional diversity plays an important role in the degradation of polyhydroxybutyrate (PHB) in soil.

PubMed

Dey, Samrat; Tribedi, Prosun

2018-03-01

Towards bioremediation of recalcitrant materials like synthetic polymer, soil has been recognized as a traditional site for disposal and subsequent degradation as some microorganisms in soil can degrade the polymer in a non-toxic, cost-effective, and environment friendly way. Microbial functional diversity is a constituent of biodiversity that includes wide range of metabolic activities that can influence numerous aspects of ecosystem functioning like ecosystem stability, nutrient availability, ecosystem dynamics, etc. Thus, in the current study, we assumed that microbial functional diversity could play an important role in polymer degradation in soil. To verify this hypothesis, we isolated soil from five different sites of landfill and examined several microbiological parameters wherein we observed a significant variation in heterotrophic microbial count as well as microbial activities among the soil microcosms tested. Multivariate analysis (principle component analysis) based on the carbon sources utilization pattern revealed that soil microcosms showed different metabolic patterns suggesting the variable distribution of microorganisms among the soil microcosms tested. Since microbial functional diversity depends on both microbial richness and evenness, Shannon diversity index was determined to measure microbial richness and Gini coefficient was determined to measure microbial evenness. The tested soil microcosms exhibited variation in both microbial richness and evenness suggesting the considerable difference in microbial functional diversity among the tested microcosms. We then measured polyhydroxybutyrate (PHB) degradation in soil microcosms after desired period of incubation of PHB in soil wherein we found that soil microcosms having higher functional diversity showed enhanced PHB degradation and soil microcosms having lower functional diversity showed reduced PHB degradation. We also noticed that all the tested soil microcosms showed similar pattern in both

Role of acetylcholinesterase in lung cancer

PubMed Central

Xi, Hui-Jun; Wu, Ren-Pei; Liu, Jing-Jing; Zhang, Ling-Juan; Li, Zhao-Shen

2015-01-01

Acetylcholinesterase (AChE) plays a key role in catalytic hydrolysis of cholinergic neurotransmitters. Intensive research has proven the involvement of this protein in novel functions, such as cell adhesion, differentiation, and proliferation. In addition, several recent studies have indicated that acetylcholinesterase is potentially a marker and regulator of apoptosis. Importantly, AChE is also a promising tumor suppressor. In this review, we briefly summarize the involvement of AChE in apoptosis and cancer, focusing on the role of AChE in lung cancer, as well as the therapeutic consideration of AChE for cancer therapy. PMID:26273392

Functions of Propolis as a natural feed additive in poultry

USDA-ARS?s Scientific Manuscript database

Propolis is a resinous hive product collected by honeybees from various sources of plants. Numerous scientific investigations have been focused on the biological activities of propolis and its functions as a health supplement in humans. It could have similar function in other animals, such as poultr...

Functional role of inorganic trace elements in angiogenesis-Part II: Cr, Si, Zn, Cu, and S.

PubMed

Saghiri, Mohammad Ali; Asatourian, Armen; Orangi, Jafar; Sorenson, Christine M; Sheibani, Nader

2015-10-01

Trace elements play critical roles in angiogenesis events. The effects of nitrogen, iron, selenium, phosphorus, gold, and calcium were discussed in part I. In part II, we evaluated the effect of chromium, silicon, zinc, copper, and sulfur on different aspects of angiogenesis, with critical roles in healing and regeneration processes, and undeniable roles in tumor growth and cancer therapy. This review is the second of series that serves as an overview of the role of inorganic elements in regulation of angiogenesis and vascular function. The methods of exposure, structure, mechanism, and potential activity of these trace elements are briefly discussed. An electronic search was performed on the role of these trace elements in angiogenesis from January 2005 to April 2014. The recent aspects of the relationship between five different trace elements and their role in regulation of angiogenesis, and homeostasis of pro- and anti-angiogenic factors were assessed. Many studies have investigated the effects and importance of these elements in angiogenesis events. Both stimulatory and inhibitory effects on angiogenesis are observed for the evaluated elements. Chromium can promote angiogenesis in pathological manners. Silicon as silica nanoparticles is anti-angiogenic, while in calcium silicate extracts and bioactive silicate glasses promote angiogenesis. Zinc is an anti-angiogenic agent acting on important genes and growth factors. Copper and sulfur compositions have pro-angiogenic functions by activating pro-angiogenic growth factors and promoting endothelial cells migration, growth, and tube formation. Thus, utilization of these elements may provide a unique opportunity to modulate angiogenesis under various setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The role of arthroscopy in the treatment of functional instability of the ankle.

PubMed

Kerr, Hui-Ling; Bayley, Edward; Jackson, Rosalyn; Kothari, Paresh

2013-12-01

Ankle sprains are common, the majority resolving with functional rehabilitation. Some patients are left with symptoms of functional instability (FI). Ankle arthroscopy in those with symptoms of FI is not well covered in the literature. Our aim was to assess its role in FI of the ankle. Retrospective case note analysis of patients with FI following an ankle sprain from 2005 to 2007. All underwent arthroscopy, provided mechanical instability was excluded (EUA and stress X-rays), and there were no signs of soft tissue impingement. These patients had exhausted all options of conservative therapy. Seventy-seven patients with a mean age of 38.1: five had true mechanical instability and were excluded. 72 underwent arthroscopy: 67 (93.1%) had significant amounts of scar tissue needing debridement, most commonly in the antero-lateral corner (58.3%). 52 patients improved (72.2%) at a minimum of 6 months follow-up. Our study supports the role of ankle arthroscopy in the treatment of FI following trauma. It should be considered when conservative measures have failed. Copyright © 2013 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

A family of triaxial modified Hubble mass models: Effects of the additional radial functions

NASA Astrophysics Data System (ADS)

Das, Mousumi; Thakur, Parijat; Ann, H. B.

2005-03-01

The projected properties of triaxial generalization of the modified Hubble mass models are studied. These models are constructed by adding the additional radial functions, each multiplied by a low-order spherical harmonic, to the models of [Chakraborty, D.K., Thakur, P., 2000. MNRAS 318, 1273]. The projected surface density of mass models can be calculated analytically which allows us to derive the analytic expressions of axial ratio and position angle of major axis of constant density elliptical contours at asymptotic radii. The models are more general than those studied earlier in the sense that the inclusions of additional terms in density distribution, allow one to produce varieties of the radial profile of axial ratio and position angle, in particular, their small scale variations at inner radii. Strong correlations are found to exist between the observed axial ratio evaluated at 0.25Re and at 4Re which occupy well-separated regions in the parameter space for different choices of the intrinsic axial ratios. These correlations can be exploited to predict the intrinsic shape of the mass model, independent of the viewing angles. Using Bayesian statistics, the result of a test case launched for an estimation of the shape of a model galaxy is found to be satisfactory.

Replacing and Additive Horizontal Gene Transfer in Streptococcus

PubMed Central

Choi, Sang Chul; Rasmussen, Matthew D.; Hubisz, Melissa J.; Gronau, Ilan; Stanhope, Michael J.; Siepel, Adam

2012-01-01

The prominent role of Horizontal Gene Transfer (HGT) in the evolution of bacteria is now well documented, but few studies have differentiated between evolutionary events that predominantly cause genes in one lineage to be replaced by homologs from another lineage (“replacing HGT”) and events that result in the addition of substantial new genomic material (“additive HGT”). Here in, we make use of the distinct phylogenetic signatures of replacing and additive HGTs in a genome-wide study of the important human pathogen Streptococcus pyogenes (SPY) and its close relatives S. dysgalactiae subspecies equisimilis (SDE) and S. dysgalactiae subspecies dysgalactiae (SDD). Using recently developed statistical models and computational methods, we find evidence for abundant gene flow of both kinds within each of the SPY and SDE clades and of reduced levels of exchange between SPY and SDD. In addition, our analysis strongly supports a pronounced asymmetry in SPY–SDE gene flow, favoring the SPY-to-SDE direction. This finding is of particular interest in light of the recent increase in virulence of pathogenic SDE. We find much stronger evidence for SPY–SDE gene flow among replacing than among additive transfers, suggesting a primary influence from homologous recombination between co-occurring SPY and SDE cells in human hosts. Putative virulence genes are correlated with transfer events, but this correlation is found to be driven by additive, not replacing, HGTs. The genes affected by additive HGTs are enriched for functions having to do with transposition, recombination, and DNA integration, consistent with previous findings, whereas replacing HGTs seen to influence a more diverse set of genes. Additive transfers are also found to be associated with evidence of positive selection. These findings shed new light on the manner in which HGT has shaped pathogenic bacterial genomes. PMID:22617954

Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy

PubMed Central

Roy, Sohini; Bag, Arup K.; Singh, Rakesh K.; Talmadge, James E.; Batra, Surinder K.; Datta, Kaustubh

2017-01-01

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, and bone diseases. However, little is known concerning the molecular pathways that govern these functions. In addition, NRP1 expression has been characterized in different immune cellular phenotypes including macrophages, dendritic cells, and T cell subsets, especially regulatory T cell populations. By contrast, the functions of NRP2 in immune cells are less well known. In this review, we briefly summarize the genomic organization, structure, and binding partners of the NRPs and extensively discuss the recent advances in their role and function in different immune cell subsets and their clinical implications. PMID:29067024

Ab-initio adsorption study of chitosan on functionalized graphene: critical role of van der Waals interactions.

PubMed

Rahman, R; Mazumdar, D

2012-03-01

We investigate the adsorption process of an organic biomolecule (chitosan) on epoxy-functionalized graphene using ab-initio density functional methods incorporating van-der-waals (vdW) interactions. The role of London dispersion force on the cohesive energy and conformal preference of the molecule is quantitatively elucidated. Functionalizing graphene with epoxy leads to weak hydrogen-bond interactions with chitosan. Binding energy values increase by over an order of magnitude after including vdW corrections, implying that dispersive interactions dominate the physisorption process. Conformal study show binding upto 30 kcal/mol when the molecule is oriented with the hydroxyl group approaching the functionalized graphene. Our study advances the promise of functionalized graphene for a variety of applications.

Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function

PubMed Central

Touat-Hamici, Zahia; Weidmann, Henri; Blum, Yuna; Proust, Carole; Durand, Hervé; Iannacci, Francesca; Codoni, Veronica; Gaignard, Pauline; Thérond, Patrice; Civelek, Mete; Karabina, Sonia A.; Lusis, Aldons J.; Cambien, François; Ninio, Ewa

2016-01-01

Aims Lipid phosphate phosphatase 3; type 2 phosphatidic acid phosphatase β (LPP3; PPAP2B) is a transmembrane protein dephosphorylating and thereby terminating signalling of lipid substrates including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Human LPP3 possesses a cell adhesion motif that allows interaction with integrins. A polymorphism (rs17114036) in PPAP2B is associated with coronary artery disease, which prompted us to investigate the possible role of LPP3 in human endothelial dysfunction, a condition promoting atherosclerosis. Methods and results To study the role of LPP3 in endothelial cells we used human primary aortic endothelial cells (HAECs) in which LPP3 was silenced or overexpressed using either wild type or mutated cDNA constructs. LPP3 silencing in HAECs enhanced secretion of inflammatory cytokines, leucocyte adhesion, cell survival, and migration and impaired angiogenesis, whereas wild-type LPP3 overexpression reversed these effects and induced apoptosis. We also demonstrated that LPP3 expression was negatively correlated with vascular endothelial growth factor expression. Mutations in either the catalytic or the arginine-glycine-aspartate (RGD) domains impaired endothelial cell function and pharmacological inhibition of S1P or LPA restored it. LPA was not secreted in HAECs under silencing or overexpressing LPP3. However, the intra- and extra-cellular levels of S1P tended to be correlated with LPP3 expression, indicating that S1P is probably degraded by LPP3. Conclusions We demonstrated that LPP3 is a negative regulator of inflammatory cytokines, leucocyte adhesion, cell survival, and migration in HAECs, suggesting a protective role of LPP3 against endothelial dysfunction in humans. Both the catalytic and the RGD functional domains were involved and S1P, but not LPA, might be the endogenous substrate of LPP3. PMID:27694435

Intermediate Filaments Play a Pivotal Role in Regulating Cell Architecture and Function*

PubMed Central

Lowery, Jason; Kuczmarski, Edward R.; Herrmann, Harald; Goldman, Robert D.

2015-01-01

Intermediate filaments (IFs) are composed of one or more members of a large family of cytoskeletal proteins, whose expression is cell- and tissue type-specific. Their importance in regulating the physiological properties of cells is becoming widely recognized in functions ranging from cell motility to signal transduction. IF proteins assemble into nanoscale biopolymers with unique strain-hardening properties that are related to their roles in regulating the mechanical integrity of cells. Furthermore, mutations in the genes encoding IF proteins cause a wide range of human diseases. Due to the number of different types of IF proteins, we have limited this short review to cover structure and function topics mainly related to the simpler homopolymeric IF networks composed of vimentin, and specifically for diseases, the related muscle-specific desmin IF networks. PMID:25957409

Functional roles of the sweet taste receptor in oral and extraoral tissues

PubMed Central

Laffitte, Anni; Neiers, Fabrice; Briand, Loïc

2014-01-01

Purpose of review This review summarizes and discusses the current knowledge about the physiological roles of the sweet taste receptor in oral and extraoral tissues. Recent findings The expression of a functional sweet taste receptor has been reported in numerous extragustatory tissues, including the gut, pancreas, bladder, brain and, more recently, bone and adipose tissues. In the gut, this receptor has been suggested to be involved in luminal glucose sensing, the release of some satiety hormones, the expression of glucose transporters, and the maintenance of glucose homeostasis. More recently, the sweet taste receptor was proposed to regulate adipogenesis and bone biology. Summary The perception of sweet taste is mediated by the T1R2/T1R3 receptor, which is expressed in the oral cavity, wherein it provides input on the caloric and macronutrient contents of ingested food. This receptor recognizes all the chemically diverse compounds perceived as sweet by human beings, including natural sugars and sweeteners. Importantly, the expression of a functional sweet taste receptor has been reported in numerous extragustatory tissues, wherein it has been proposed to regulate metabolic processes. This newly recognized role of the sweet taste receptor makes this receptor a potential novel therapeutic target for the treatment of obesity and related metabolic dysfunctions, such as diabetes and hyperlipidemia. PMID:24763065

Role of T Cells in Malnutrition and Obesity

PubMed Central

Gerriets, Valerie A.; MacIver, Nancie J.

2014-01-01

Nutritional status is critically important for immune cell function. While obesity is characterized by inflammation that promotes metabolic syndrome including cardiovascular disease and insulin resistance, malnutrition can result in immune cell defects and increased risk of mortality from infectious diseases. T cells play an important role in the immune adaptation to both obesity and malnutrition. T cells in obesity have been shown to have an early and critical role in inducing inflammation, accompanying the accumulation of inflammatory macrophages in obese adipose tissue, which are known to promote insulin resistance. How T cells are recruited to adipose tissue and activated in obesity is a topic of considerable interest. Conversely, T cell number is decreased in malnourished individuals, and T cells in the setting of malnutrition have decreased effector function and proliferative capacity. The adipokine leptin, which is secreted in proportion to adipocyte mass, may have a key role in mediating adipocyte-T cell interactions in both obesity and malnutrition, and has been shown to promote effector T cell function and metabolism while inhibiting regulatory T cell proliferation. Additionally, key molecular signals are involved in T cell metabolic adaptation during nutrient stress; among them, the metabolic regulator AMP kinase and the mammalian target of rapamycin have critical roles in regulating T cell number, function, and metabolism. In summary, understanding how T cell number and function are altered in obesity and malnutrition will lead to better understanding of and treatment for diseases where nutritional status determines clinical outcome. PMID:25157251

Functional role of frontal alpha oscillations in creativity.

PubMed

Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

2015-06-01

Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Functional Role of the T1R Family of Receptors in Sweet Taste and Feeding

PubMed Central

Treesukosol, Yada; Smith, Kimberly R.; Spector, Alan C.

2011-01-01

The discovery of the T1R family of Class C G protein-coupled receptors in the peripheral gustatory system a decade ago has been a tremendous advance for taste research, and its conceptual reach has extended to other organ systems. There are three proteins in the family, T1R1, T1R2, and T1R3, encoded by their respective genes, Tas1r1, Tas1r2, and Tas1r3. T1R2 combines with T1R3 to form a heterodimer that binds with sugars and other sweeteners. T1R3 also combines with T1R1 to form a heterodimer that binds with L-amino acids. These proteins are expressed not only in taste bud cells, but one or more of these T1Rs have also been identified in the nasal epithelium, gut, pancreas, liver, kidney, testes and brain in various mammalian species. Here we review current perspectives regarding the functional role of these receptors, concentrating on sweet taste and feeding. We also discuss behavioral findings suggesting that a glucose polymer mixture, Polycose, which rodents avidly prefer, appears to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In addition, although the T1Rs have been implicated as playing a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow and fluid intake as well as normal body weight compared with same-sex littermate wild type (WT) controls. Moreover, regardless of whether they are fasted or not, these KO mice do not differ from their WT counterparts in their Polycose intake across a broad range of concentrations in 30-min intake tests. The functional implications of these results and those in the literature are considered. PMID:21376068

Non-additivity of functional group contributions in protein-ligand binding: a comprehensive study by crystallography and isothermal titration calorimetry.

PubMed

Baum, Bernhard; Muley, Laveena; Smolinski, Michael; Heine, Andreas; Hangauer, David; Klebe, Gerhard

2010-04-09

Additivity of functional group contributions to protein-ligand binding is a very popular concept in medicinal chemistry as the basis of rational design and optimized lead structures. Most of the currently applied scoring functions for docking build on such additivity models. Even though the limitation of this concept is well known, case studies examining in detail why additivity fails at the molecular level are still very scarce. The present study shows, by use of crystal structure analysis and isothermal titration calorimetry for a congeneric series of thrombin inhibitors, that extensive cooperative effects between hydrophobic contacts and hydrogen bond formation are intimately coupled via dynamic properties of the formed complexes. The formation of optimal lipophilic contacts with the surface of the thrombin S3 pocket and the full desolvation of this pocket can conflict with the formation of an optimal hydrogen bond between ligand and protein. The mutual contributions of the competing interactions depend on the size of the ligand hydrophobic substituent and influence the residual mobility of ligand portions at the binding site. Analysis of the individual crystal structures and factorizing the free energy into enthalpy and entropy demonstrates that binding affinity of the ligands results from a mixture of enthalpic contributions from hydrogen bonding and hydrophobic contacts, and entropic considerations involving an increasing loss of residual mobility of the bound ligands. This complex picture of mutually competing and partially compensating enthalpic and entropic effects determines the non-additivity of free energy contributions to ligand binding at the molecular level. (c) 2010 Elsevier Ltd. All rights reserved.

The Role of Nutrition and Literacy on the Cognitive Functioning of Elderly Poor Individuals.

PubMed

Leist, Anja K; Novella, Rafael; Olivera, Javier

2018-06-08

Maintaining cognitive function is a prerequisite of living independently, which is a highly valued component in older individuals' wellbeing. In this paper we assess the role of early-life and later-life nutritional status, education and literacy on the cognitive functioning of older adults living in poverty in Peru. We exploit the baseline sample of the Peruvian non-contributory pension program Pension 65 and find that current nutritional status and literacy are strongly associated with cognitive functioning for poor older adults. In a context of rising popularity of non-contributory pension programs around the world, our study intends to contribute to the discussion of designing accompanying measures to the pension transfer, such as adult literacy programs and monitoring of adequate nutrition of older adults.

Platelet microparticles: detection and assessment of their paradoxical functional roles in disease and regenerative medicine.

PubMed

Burnouf, Thierry; Goubran, Hadi Alphonse; Chou, Ming-Li; Devos, David; Radosevic, Mirjana

2014-07-01

There is increasing research on and clinical interest in the physiological role played by platelet microparticles (PMPs). PMPs are 0.1-1-μm fragments shed from plasma membranes of platelets that are undergoing activation, stress, or apoptosis. They have a phospholipid-based structure and express functional receptors from platelet membranes. As they are the most abundant microparticles in the blood and they express the procoagulant phosphatidylserine, PMPs likely complement, if not amplify, the functions of platelets in hemostasis, thrombosis, cancer, and inflammation, but also act as promoters of tissue regeneration. Their size and structure make them instrumental in platelet-cell communications as a delivery tool of platelet-borne bioactive molecules including growth factors, other signaling molecules and micro (mi)RNA. PMPs can therefore be a pathophysiological threat or benefit to the cellular environment when interacting with the blood vasculature. There is also increasing evidence that PMP generation is triggered during blood collection, separation into components, and storage, a phenomenon potentially leading to thrombotic and inflammatory side effects in transfused patients. Evaluating PMPs requires strict pre-analytical and analytical procedures to avoid artifactual generation and ensure accurate assessment of the number, size repartitioning, and functional properties. This review describes the physical and functional methods developed for analyzing and quantifying PMPs. It then presents the functional roles of PMPs as markers or triggers of diseases like thrombosis, atherosclerosis, and cancer, and discusses the possible detrimental immunological impact of their generation in blood components. Finally we review the potential function of PMPs in tissue regeneration and the prospects for their use in therapeutic strategies for human health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Response of Functional Structure of Soil Microbial Community to Multi-level Nitrogen Additions on the Central Tibetan Plateau

NASA Astrophysics Data System (ADS)

Zhang, G.; Yuan, Y.

2015-12-01

The use of fossil fuels and fertilizers has increased the amount of biologically reactive nitrogen in the atmosphere over the past century. Tibet is the one of the most threatened regions by nitrogen deposition, thus understanding how its microbial communities function maybe of high importance to predicting microbial responses to nitrogen deposition. Here we describe a short-time nitrogen addition conducted in an alpine steppe ecosystem to investigate the response of functional structure of soil microbial community to multi-level nitrogen addition. Using a GeoChip 4.0, we showed that functional diversities and richness of functional genes were unchanged at low level of nitrogen fertilizer inputs (<20 kg N ha-1 yr-1), but significantly decreased at higher nitrogen fertilizer inputs (>=40 kg N ha-1 yr-1). Detrended correspondence analysis indicated that the functional structure of microbial communities was markedly different across the nitrogen gradients. Most C degradation genes whose abundances significantly increased under elevated N fertilizer were those involved in the degradation of relatively labile C (starch, hemicellulose, cellulose), whereas the abundance of certain genes involved in the degradation of recalcitrant C (i.e. lignin) was largely decreased (such as manganese peroxidase, mnp). The results suggest that the elevated N fertilization rates might significantly accelerate the labile C degradation, but might not spur recalcitrant C degradation. The combined effect of gdh and ureC genes involved in N cycling appeared to shift the balance between ammonia and organic N toward organic N ammonification and hence increased the N mineralization potential. Moreover, Urease directly involved in urea mineralization significantly increased. Lastly, Canonical correspondence analysis showed that soil (TOC+NH4++NO3-+NO2-+pH) and plant (Aboveground plant productivity + Shannon Diversity) variables could explain 38.9% of the variation of soil microbial community

Mesoporous Titania Powders: The Role of Precursors, Ligand Addition and Calcination Rate on Their Morphology, Crystalline Structure and Photocatalytic Activity

PubMed Central

Masolo, Elisabetta; Meloni, Manuela; Garroni, Sebastiano; Mulas, Gabriele; Enzo, Stefano; Baró, Maria Dolors; Rossinyol, Emma; Rzeszutek, Agnieszka; Herrmann-Geppert, Iris; Pilo, Maria

2014-01-01

We evaluate the influence of the use of different titania precursors, calcination rate, and ligand addition on the morphology, texture and phase content of synthesized mesoporous titania samples, parameters which, in turn, can play a key role in titania photocatalytic performances. The powders, obtained through the evaporation-induced self-assembly method, are characterized by means of ex situ X-Ray Powder Diffraction (XRPD) measurements, N2 physisorption isotherms and transmission electron microscopy. The precursors are selected basing on two different approaches: the acid-base pair, using TiCl4 and Ti(OBu)4, and a more classic route with Ti(OiPr)4 and HCl. For both precursors, different specimens were prepared by resorting to different calcination rates and with and without the addition of acetylacetone, that creates coordinated species with lower hydrolysis rates, and with different calcination rates. Each sample was employed as photoanode and tested in the water splitting reaction by recording I-V curves and comparing the results with commercial P25 powders. The complex data framework suggests that a narrow pore size distribution, due to the use of acetylacetone, plays a major role in the photoactivity, leading to a current density value higher than that of P25. PMID:28344237

The role of polymorphisms in the spliced leader addition domain in determining promoter activity in Brugia malayi.

PubMed

Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R

2011-03-01

Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.

Vav family exchange factors: an integrated regulatory and functional view

PubMed Central

Bustelo, Xosé R

2014-01-01

The Vav family is a group of tyrosine phosphorylation-regulated signal transduction molecules hierarchically located downstream of protein tyrosine kinases. The main function of these proteins is to work as guanosine nucleotide exchange factors (GEFs) for members of the Rho GTPase family. In addition, they can exhibit a variety of catalysis-independent roles in specific signaling contexts. Vav proteins play essential signaling roles for both the development and/or effector functions of a large variety of cell lineages, including those belonging to the immune, nervous, and cardiovascular systems. They also contribute to pathological states such as cancer, immune-related dysfunctions, and atherosclerosis. Here, I will provide an integrated view about the evolution, regulation, and effector properties of these signaling molecules. In addition, I will discuss the pros and cons for their potential consideration as therapeutic targets. PMID:25483299

Predicting organizational citizenship behavior from the functional analysis and role identity perspectives: further evidence in Spanish employees.

PubMed

Dávila, Ma Celeste; Finkelstein, Marcia A

2010-05-01

Organizational citizenship behavior (OCB) is a prosocial activity with similarities to volunteerism. The purpose of this work is to contribute new evidence about the relevance to OCB of two models of sustained volunteerism, functional analysis and role identity theory. A total of 983 Spanish employees at49 organizations completed surveys measuring amount of OCB, motives for engaging in citizenship behavior, and the degree to which respondents developed an organizational citizen role identity. The results showed that both motives and role identity were significant predictors of OCB, with motive partially mediating the role identity-OCB relationship. The findings suggest that similar mechanisms are involved in sustaining volunteerism and OCB.

Civil Society Organizations and the Functions of Global Health Governance: What Role within Intergovernmental Organizations?

PubMed Central

Lee, Kelley

2016-01-01

Amid discussion of how global health governance should and could be strengthened, the potential role of civil society organizations has been frequently raised. This paper considers the role of Civil Society Organizations (CSOs) in four health governance instruments under the auspices of the World Health Organization – the International Code on the Marketing of Breastmilk Substitutes, Framework Convention on Tobacco Control, International Health Regulations and Codex Alimentarius - and maps the functions they have contributed to. The paper draws conclusions about the opportunities and limitations CSOs represent for strengthening global health governance (GHG). PMID:27274776

Nickel superoxide dismutase: structural and functional roles of His1 and its H-bonding network

DOE PAGES

Maroney, Michael J.; Cabelli, Diane E.; Ryan, Kelly C.; ...

2015-01-21

Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the presence of a H-bonding network formed between the NH group of the apical imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit in the hexameric enzyme. This interaction is supported by another intrasubunit H-bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were produced to experimentally evaluate the roles of this H-bonding network and compare the results with prior predictions from density functional theory calculations. The X-ray crystal structure of H1A-NiSOD, which lacks the apical ligand entirely, reveals that in the absence of the Glu17-His1more » H-bond, the active site is disordered. Characterization of this variant using X-ray absorption spectroscopy (XAS) shows that Ni(II) is bound in the expected N₂S₂ planar coordination site. Despite these structural perturbations, the H1A-NiSOD variant retains 4% of wild-type (WT) NiSOD activity. Three other mutations were designed to preserve the apical imidazole ligand but perturb the H-bonding network: R47A-NiSOD, which lacks the intramolecular H-bonding interaction; E17R/R47A-NiSOD, which retains the intramolecular H-bond but lacks the intermolecular Glu17-His1 H-bond; and E17A/R47ANiSOD, which lacks both H-bonding interactions. These variants were characterized by a combination of techniques, including XAS to probe the nickel site structure, kinetic studies employing pulse-radiolytic production of superoxide, and electron paramagnetic resonance to assess the Ni redox activity. The results indicate that in addition to the roles in redox tuning suggested on the basis of previous computational studies, the Glu17-His1 H-bond plays an important structural role in the proper folding of the “Ni-hook” motif that is a critical feature of the active site.« less

Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo.

PubMed

Dodson, Mark W; Leung, Lok K; Lone, Mohiddin; Lizzio, Michael A; Guo, Ming

2014-12-01

Mutations in LRRK2 cause a dominantly inherited form of Parkinson's disease (PD) and are the most common known genetic determinant of PD. Inhibitor-based therapies targeting LRRK2 have emerged as a key therapeutic strategy in PD; thus, understanding the consequences of inhibiting the normal cellular functions of this protein is vital. Despite much interest, the physiological functions of LRRK2 remain unclear. Several recent studies have linked the toxicity caused by overexpression of pathogenic mutant forms of LRRK2 to defects in the endolysosomal and autophagy pathways, raising the question of whether endogenous LRRK2 might play a role in these processes. Here, we report the characterization of multiple novel ethyl methanesulfonate (EMS)-induced nonsense alleles in the Drosophila LRRK2 homolog, lrrk. Using these alleles, we show that lrrk loss-of-function causes striking defects in the endolysosomal and autophagy pathways, including the accumulation of markedly enlarged lysosomes that are laden with undigested contents, consistent with a defect in lysosomal degradation. lrrk loss-of-function also results in the accumulation of autophagosomes, as well as the presence of enlarged early endosomes laden with mono-ubiquitylated cargo proteins, suggesting an additional defect in lysosomal substrate delivery. Interestingly, the lysosomal abnormalities in these lrrk mutants can be suppressed by a constitutively active form of the small GTPase rab9, which promotes retromer-dependent recycling from late endosomes to the Golgi. Collectively, our data provides compelling evidence of a vital role for lrrk in lysosomal function and endolysosomal membrane transport in vivo, and suggests a link between lrrk and retromer-mediated endosomal recycling. © 2014. Published by The Company of Biologists Ltd.

The potential role of melatonin on sleep deprivation-induced cognitive impairments: implication of FMRP on cognitive function.

PubMed

Kwon, K J; Lee, E J; Kim, M K; Jeon, S J; Choi, Y Y; Shin, C Y; Han, S-H

2015-08-20

While prolonged sleep deprivation (SD) could lead to profound negative health consequences, such as impairments in vital biological functions of immunity and cognition, melatonin possesses powerful ameliorating effects against those harmful insults. Melatonin has strong antioxidant and anti-inflammatory effects that help to restore body's immune and cognitive functions. In this study, we investigated the possible role of melatonin in reversing cognitive dysfunction induced by SD in rats. Our experimental results revealed that sleep-deprived animals exhibited spatial memory impairment in the Morris water maze tasks compared with the control groups. Furthermore, there was an increased glial activation most prominent in the hippocampal region of the SD group compared to the normal control (NC) group. Additionally, markers of oxidative stress such as 4-hydroxynonenal (4-HNE) and 7,8-dihydro-8-oxo-deoxyguanine (8-oxo-dG) were significantly increased, while fragile X-mental retardation protein (FMRP) expression was decreased in the SD group. Interestingly, melatonin treatment normalized these events to control levels following SD. Our data demonstrate that SD induces oxidative stress through glial activation and decreases FMRP expression in the neurons. Furthermore, our results suggest the efficacy of melatonin for the treatment of sleep-related neuronal dysfunction, which occurs in neurological disorders such as Alzheimer's disease and autism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Role of oxygen functional groups in reduced graphene oxide for lubrication

PubMed Central

Gupta, Bhavana; Kumar, Niranjan; Panda, Kalpataru; Kanan, Vigneshwaran; Joshi, Shailesh; Visoly-Fisher, Iris

2017-01-01

Functionalized and fully characterized graphene-based lubricant additives are potential 2D materials for energy-efficient tribological applications in machine elements, especially at macroscopic contacts. Two different reduced graphene oxide (rGO) derivatives, terminated by hydroxyl and epoxy-hydroxyl groups, were prepared and blended with two different molecular weights of polyethylene glycol (PEG) for tribological investigation. Epoxy-hydroxyl-terminated rGO dispersed in PEG showed significantly smaller values of the friction coefficient. In this condition, PEG chains intercalate between the functionalized graphene sheets, and shear can take place between the PEG and rGO sheets. However, the friction coefficient was unaffected when hydroxyl-terminated rGO was coupled with PEG. This can be explained by the strong coupling between graphene sheets through hydroxyl units, causing the interaction of PEG with the rGO to be non- effective for lubrication. On the other hand, antiwear properties of hydroxyl-terminated rGO were significantly enhanced compared to epoxy-hydroxyl functionalized rGO due to the integrity of graphene sheet clusters. PMID:28344337

The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

PubMed

Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

2004-11-01

To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

Management by Trajectory Trade Study of Roles and Responsibilities Between Participants and Automation Report

NASA Technical Reports Server (NTRS)

Fernandes, Alicia D.; Kaler, Curt; Leiden, Kenneth; Atkins, Stephen; Bell, Alan; Kilbourne, Todd; Evans, Mark

2017-01-01

This report describes a trade study of roles and responsibilities associated with the Management by Trajectory (MBT) concept. The MBT concept describes roles, responsibilities, and information and automation requirements for providing air traffic controllers and managers the ability to quickly generate, evaluate and implement changes to an aircraft's trajectory. In addition, the MBT concept describes mechanisms for imposing constraints on flight operator preferred trajectories only to the extent necessary to maintain safe and efficient traffic flows, and the concept provides a method for the exchange of trajectory information between ground automation systems and the aircraft that allows for trajectory synchronization and trajectory negotiation. The participant roles considered in this trade study include: airline dispatcher, flight crew, radar controller, traffic manager, and Air Traffic Control System Command Center (ATCSCC) traffic management specialists. The proposed allocation of roles and responsibilities was based on analysis of several use cases that were developed for this purpose as well as for walking through concept elements. The resulting allocation of roles and responsibilities reflects both increased automation capability to support many aviation functions, as well as increased flexibility to assign responsibilities to different participants - in many cases afforded by the increased automation capabilities. Note that the selection of participants to consider for allocation of each function is necessarily rooted in the current environment, in that MBT is envisioned as an evolution of the National Airspace System (NAS), and not a revolution. A key feature of the MBT allocations is a vision for the traffic management specialist to take on a greater role. This is facilitated by the vision that separation management functions, in addition to traffic management functions, will be carried out as trajectory management functions. This creates an opportunity

Role of motor unit structure in defining function

NASA Technical Reports Server (NTRS)

Monti, R. J.; Roy, R. R.; Edgerton, V. R.

2001-01-01

Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.

Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

PubMed

Battini, R; Chieffo, D; Bulgheroni, S; Piccini, G; Pecini, C; Lucibello, S; Lenzi, S; Moriconi, F; Pane, M; Astrea, G; Baranello, G; Alfieri, P; Vicari, S; Riva, D; Cioni, G; Mercuri, E

2018-02-01

The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy. Copyright © 2017 Elsevier B.V. All rights reserved.

Listen to their answers! Response behaviour in the measurement of physical and role functioning

PubMed Central

Hak, Tony; Sprangers, Mirjam A. G.; Groen, Harry J. M.; van der Wal, Gerrit; The, Anne-Mei

2008-01-01

Background Quality of life (QoL) is considered to be an indispensable outcome measure of curative and palliative treatment. However, QoL research often yields findings that raise questions about what QoL measurement instruments actually assess and how the scores should be interpreted. Objective To investigate how patients interpret and respond to questions on the EORTC-QLQ-C30 over time and to find explanations to account for counterintuitive findings in QoL measurement. Methods Qualitative investigation was made of the response behaviour of small-cell lung cancer patients (n = 23) in the measurement of QoL with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Focus was on physical functioning (PF, items 1 to 5), role functioning (RF, items 6 and 7), global health and QoL rating (GH/QOL, items 29 and 30). Interviews were held at four points: at the start of the chemotherapy, 4 weeks later, at the end, and 6 weeks after the end of chemotherapy. Patients were asked to ‘think aloud’ when filling in the questionnaire. Results Patients used various response strategies when answering questions about problems and limitations in functioning, which impacted the accuracy of the scale. Patients had scores suggesting they were less limited than they actually were by taking the wording of questions literally, by guessing their functioning in activities that they did not perform, and by ignoring or excluding certain activities that they could not perform. Conclusion Terminally ill patients evaluate their functioning in terms of what they perceive to be normal under the circumstances. Their answers can be interpreted in terms of change in the appraisal process (Rapkin and Schwartz 2004; Health and Quality of Life Outcomes, 2, 14). More care should be taken in assessing the quality of a set of questions about physical and role functioning. PMID:18389384

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism.

PubMed

Shi, Yuguang; Cheng, Dong

2009-07-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications.

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism

PubMed Central

Shi, Yuguang; Cheng, Dong

2009-01-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications. PMID:19116371

The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens.

PubMed

Salerni, Sara; Di Francescomarino, Samanta; Cadeddu, Christian; Acquistapace, Flavio; Maffei, Silvia; Gallina, Sabina

2015-06-01

Human response to different physiologic stimuli and cardiovascular (CV) adaptation to various pathologies seem to be gender specific. Sex-steroid hormones have been postulated as the major contributors towards these sex-related differences. This review will discuss current evidence on gender differences in CV function and remodelling, and will present the different role of the principal sex-steroid hormones on female heart. Starting from a review of sex hormones synthesis, receptors and CV signalling, we will summarize the current knowledge concerning the role of sex hormones on the regulation of our daily activities throughout the life, via the modulation of autonomic nervous system, excitation-contraction coupling pathway and ion channels activity. Many unresolved questions remain even if oestrogen effects on myocardial remodelling and function have been extensively studied. So this work will focus attention also on the controversial and complex relationship existing between androgens, progesterone and female heart. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.