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.

Functional sub-division of the Drosophila genome via chromatin looping

PubMed Central

Ahanger, Sajad H.; Shouche, Yogesh S.; Mishra, Rakesh K.

2013-01-01

Insulators help in organizing the eukaryotic genomes into physically and functionally autonomous regions through the formation of chromatin loops. Recent findings in Drosophila and vertebrates suggest that insulators anchor multiple loci through long-distance interactions which may be mechanistically linked to insulator function. Important to such processes in Drosophila is CP190, a common co-factor of insulator complexes. CP190 is also known to associate with the nuclear matrix, components of the RNAi machinery, active promoters and borders of the repressive chromatin domains. Although CP190 plays a pivotal role in insulator function in Drosophila, vertebrates lack a probable functional equivalent of CP190 and employ CTCF as the major factor to carry out insulator function/chromatin looping. In this review, we discuss the emerging role of CP190 in tethering genome, specifically in the perspective of insulator function in Drosophila. Future studies aiming genome-wide role of CP190 in chromatin looping is likely to give important insights into the mechanism of genome organization. PMID:23333867

The Role of Intelligence and Education in the Division of Labor. Report No. 355.

ERIC Educational Resources Information Center

Gottfredson, Linda S.

This paper suggests that the occupational hierarchy is based on functionally important differences among workers and their jobs and proposes a modified functional theory of occupational stratification. Section I examines the role of education in social stratification. Sections II, III, and IV review (1) functions of schooling, (2) evidence about…

When does diversity matter? Species functional diversity and ecosystem functioning across habitats and seasons in a field experiment.

PubMed

Frainer, André; McKie, Brendan G; Malmqvist, Björn

2014-03-01

Despite ample experimental evidence indicating that biodiversity might be an important driver of ecosystem processes, its role in the functioning of real ecosystems remains unclear. In particular, the understanding of which aspects of biodiversity are most important for ecosystem functioning, their importance relative to other biotic and abiotic drivers, and the circumstances under which biodiversity is most likely to influence functioning in nature, is limited. We conducted a field study that focussed on a guild of insect detritivores in streams, in which we quantified variation in the process of leaf decomposition across two habitats (riffles and pools) and two seasons (autumn and spring). The study was conducted in six streams, and the same locations were sampled in the two seasons. With the aid of structural equations modelling, we assessed spatiotemporal variation in the roles of three key biotic drivers in this process: functional diversity, quantified based on a species trait matrix, consumer density and biomass. Our models also accounted for variability related to different litter resources, and other sources of biotic and abiotic variability among streams. All three of our focal biotic drivers influenced leaf decomposition, but none was important in all habitats and seasons. Functional diversity had contrasting effects on decomposition between habitats and seasons. A positive relationship was observed in pool habitats in spring, associated with high trait dispersion, whereas a negative relationship was observed in riffle habitats during autumn. Our results demonstrate that functional biodiversity can be as significant for functioning in natural ecosystems as other important biotic drivers. In particular, variation in the role of functional diversity between seasons highlights the importance of fluctuations in the relative abundances of traits for ecosystem process rates in real ecosystems. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

The Ecological Role of Sharks on Coral Reefs.

PubMed

Roff, George; Doropoulos, Christopher; Rogers, Alice; Bozec, Yves-Marie; Krueck, Nils C; Aurellado, Eleanor; Priest, Mark; Birrell, Chico; Mumby, Peter J

2016-05-01

Sharks are considered the apex predator of coral reefs, but the consequences of their global depletion are uncertain. Here we explore the ecological roles of sharks on coral reefs and, conversely, the importance of reefs for sharks. We find that most reef-associated shark species do not act as apex predators but instead function as mesopredators along with a diverse group of reef fish. While sharks perform important direct and indirect ecological roles, the evidence to support hypothesised shark-driven trophic cascades that benefit corals is weak and equivocal. Coral reefs provide some functional benefits to sharks, but sharks do not appear to favour healthier reef environments. Restoring populations of sharks is important and can yet deliver ecological surprise. Copyright © 2016 Elsevier Ltd. All rights reserved.

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…

Examining the association between social cognition and functioning in individuals at ultra-high risk for psychosis.

PubMed

Cotter, Jack; Bartholomeusz, Cali; Papas, Alicia; Allott, Kelly; Nelson, Barnaby; Yung, Alison R; Thompson, Andrew

2017-01-01

Social and role functioning are compromised for the majority of individuals at ultra-high risk of psychosis, and it is important to identify factors that contribute to this functional decline. This study aimed to investigate social cognitive abilities, which have previously been linked to functioning in schizophrenia, as potential factors that impact social, role and global functioning in ultra-high risk patients. A total of 30 ultra-high risk patients were recruited from an established at-risk clinical service in Melbourne, Australia, and completed a battery of social cognitive, neurocognitive, clinical and functioning measures. We examined the relationships between all four core domains of social cognition (emotion recognition, theory of mind, social perception and attributional style), neurocognitive, clinical and demographic variables with three measures of functioning (the Global Functioning Social and Role scales and the Social and Occupational Functioning Assessment Scale) using correlational and multiple regression analyses. Performance on a visual theory of mind task (visual jokes task) was significantly correlated with both concurrent role ( r = 0.425, p = 0.019) and global functioning ( r = 0.540, p = 0.002). In multivariate analyses, it also accounted for unique variance in global, but not role functioning after adjusting for negative symptoms and stress. Social functioning was not associated with performance on any of the social cognition tasks. Among specific social cognitive abilities, only a test of theory of mind was associated with functioning in our ultra-high risk sample. Further longitudinal research is needed to examine the impact of social cognitive deficits on long-term functional outcome in the ultra-high risk group. Identifying social cognitive abilities that significantly impact functioning is important to inform the development of targeted intervention programmes for ultra-high risk individuals.

Phosphatidic acid and neurotransmission

PubMed Central

Raben, Daniel M.; Barber, Casey N.

2016-01-01

Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system. PMID:27671966

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

Left atrial function: evaluation by strain analysis

PubMed Central

Gan, Gary C. H.; Ferkh, Aaisha; Boyd, Anita

2018-01-01

The left atrium has an important role in modulating left ventricular filling and is an important biomarker of cardiovascular disease and adverse cardiovascular outcomes. While previously left atrial (LA) size was utilised, the role of LA function as a biomarker is increasingly being evaluated, both independently and also in combination with LA size. Strain analysis has been utilised for evaluation of LA function and can be measured throughout the cardiac cycle, thereby enabling the evaluation of LA reservoir, conduit and contractile function. Strain evaluates myocardial deformation while strain rate examines the rate of change in strain. This review will focus on the various types of strain analysis for evaluation of LA function, alterations in LA strain in physiological and pathologic states that alter LA function and finally evaluate its utility as a prognostic marker. PMID:29541609

Contributions of physical function and satisfaction with social roles to emotional distress in chronic pain: a Collaborative Health Outcomes Information Registry (CHOIR) study.

PubMed

Sturgeon, John A; Dixon, Eric A; Darnall, Beth D; Mackey, Sean C

2015-12-01

Individuals with chronic pain show greater vulnerability to depression or anger than those without chronic pain, and also show greater interpersonal difficulties and physical disability. The present study examined data from 675 individuals with chronic pain during their initial visits to a tertiary care pain clinic using assessments from Stanford University's Collaborative Health Outcomes Information Registry (CHOIR). Using a path modeling analysis, the mediating roles of Patient-Reported Outcomes Measurement Information Systems (PROMIS) Physical Function and PROMIS Satisfaction with Social Roles and Activities were tested between pain intensity and PROMIS Depression and Anger. Pain intensity significantly predicted both depression and anger, and both physical function and satisfaction with social roles mediated these relationships when modeled in separate 1-mediator models. Notably, however, when modeled together, ratings of satisfaction with social roles mediated the relationship between physical function and both anger and depression. Our results suggest that the process by which chronic pain disrupts emotional well-being involves both physical function and disrupted social functioning. However, the more salient factor in determining pain-related emotional distress seems to be disruption of social relationships, than global physical impairment. These results highlight the particular importance of social factors to pain-related distress, and highlight social functioning as an important target for clinical intervention in chronic pain.

The Kölliker-Fuse nucleus: a review of animal studies and the implications for cranial nerve function in humans.

PubMed

Browaldh, Nanna; Bautista, Tara G; Dutschmann, Mathias; Berkowitz, Robert G

2016-11-01

To review the scientific literature on the relationship between Kölliker-Fuse nucleus (KF) and cranial nerve function in animal models, with view to evaluating the potential role of KF maturation in explaining age-related normal physiologic parameters and developmental and acquired impairment of cranial nerve function in humans. Medical databases (Medline and PubMed). Studies investigating evidence of KF activity responsible for a specific cranial nerve function that were based on manipulation of KF activity or the use of neural markers were included. Twenty studies were identified that involved the trigeminal (6 studies), vagus (9), and hypoglossal nerves (5). These pertained specifically to a role of the KF in mediating the dive reflex, laryngeal adductor control, swallowing function and upper airway tone. The KF acts as a mediator of a number of important functions that relate primarily to laryngeal closure, upper airway tone and swallowing. These areas are characterized by a variety of disorders that may present to the otolaryngologist, and hence the importance of understanding the role played by the KF in maintaining normal function.

Intra-articular pressures and joint mechanics: should we pay attention to effusion in knee osteoarthritis?

PubMed

Rutherford, Derek James

2014-09-01

What factors play a role to ensure a knee joint does what it should given the demands of moving through the physical environment? This paper aims to probe the hypothesis that intra-articular joint pressures, once a topic of interest, have been left aside in contemporary frameworks in which we now view knee joint function. The focus on ligamentous deficiencies and the chondrocentric view of osteoarthritis, while important, have left little attention to the consideration of other factors that can impair joint function across the lifespan. Dynamic knee stability is required during every step we take. While there is much known about the role that passive structures and muscular activation play in maintaining a healthy knee joint, this framework does not account for the role that intra-articular joint pressures may have in providing joint stability during motion and how these factors interact. Joint injuries invariably result in some form of intra-articular fluid accumulation. Ultimately, it may be how the knee mechanically responds to this fluid, of which pressure plays a significant role that provides the mechanisms for continued function. Do joint pressures provide an important foundation for maintaining knee function? This hypothesis is unique and argues that we are missing an important piece of the puzzle when attempting to understand implications that joint injury and disease have for joint function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology.

PubMed

Turan, Belma; Tuncay, Erkan

2017-11-12

Zinc plays an important role in biological systems as bound and histochemically reactive labile Zn 2+ . Although Zn 2+ concentration is in the nM range in cardiomyocytes at rest and increases dramatically under stimulation, very little is known about precise mechanisms controlling the intracellular distribution of Zn 2+ and its variations during cardiac function. Recent studies are focused on molecular and cellular aspects of labile Zn 2+ and its homeostasis in mammalian cells and growing evidence clarified the molecular mechanisms underlying Zn 2+ -diverse functions in the heart, leading to the discovery of novel physiological functions of labile Zn 2+ in parallel to the discovery of subcellular localization of Zn 2+ -transporters in cardiomyocytes. Additionally, important experimental data suggest a central role of intracellular labile Zn 2+ in excitation-contraction coupling in cardiomyocytes by shaping Ca 2+ dynamics. Cellular labile Zn 2+ is tightly regulated against its adverse effects through either Zn 2+ -transporters, Zn 2+ -binding molecules or Zn 2+ -sensors, and, therefore plays a critical role in cellular signaling pathways. The present review summarizes the current understanding of the physiological role of cellular labile Zn 2+ distribution in cardiomyocytes and how a remodeling of cellular Zn 2+ -homeostasis can be important in proper cell function with Zn 2+ -transporters under hyperglycemia. We also emphasize the recent investigations on Zn 2+ -transporter functions from the standpoint of human heart health to diseases together with their clinical interest as target proteins in the heart under pathological condition, such as diabetes.

Mechanisms and function of autophagy in intestinal disease.

PubMed

Lassen, Kara G; Xavier, Ramnik J

2018-01-01

The discovery of numerous genetic variants in the human genome that are associated with inflammatory bowel disease (IBD) has revealed critical pathways that play important roles in intestinal homeostasis. These genetic studies have identified a critical role for macroautophagy/autophagy and more recently, lysosomal function, in maintaining the intestinal barrier and mucosal homeostasis. This review highlights recent work on the functional characterization of IBD-associated human genetic variants in cell type-specific functions for autophagy.

Role of PPARγ in the Differentiation and Function of Neurons

PubMed Central

Quintanilla, Rodrigo A.; Utreras, Elias; Cabezas-Opazo, Fabián A.

2014-01-01

Neuronal processes (neurites and axons) have an important role in brain cells communication and, generally, they are damaged in neurodegenerative diseases. Recent evidence has showed that the activation of PPARγ pathway promoted neuronal differentiation and axon polarity. In addition, activation of PPARγ using thiazolidinediones (TZDs) prevented neurodegeneration by reducing neuronal death, improving mitochondrial function, and decreasing neuroinflammation in neuropathic pain. In this review, we will discuss important evidence that supports a possible role of PPARγ in neuronal development, improvement of neuronal health, and pain signaling. Therefore, activation of PPARγ is a potential target with therapeutic applications against neurodegenerative disorders, brain injury, and pain regulation. PMID:25246934

Functional Analysis of the Hsp93/ClpC Chaperone at the Chloroplast Envelope1[OPEN

PubMed Central

Tanabe, Noriaki; Clarke, Adrian K.

2016-01-01

The Hsp100-type chaperone Hsp93/ClpC has crucial roles in chloroplast biogenesis. In addition to its role in proteolysis in the stroma, biochemical and genetic evidence led to the hypothesis that this chaperone collaborates with the inner envelope TIC complex to power preprotein import. Recently, it was suggested that Hsp93, working together with the Clp proteolytic core, can confer a protein quality control mechanism at the envelope. Thus, the role of envelope-localized Hsp93, and the mechanism by which it participates in protein import, remain unclear. To analyze the function of Hsp93 in protein import independently of its ClpP association, we created a mutant of Hsp93 affecting its ClpP-binding motif (PBM) (Hsp93[P-]), which is essential for the chaperone’s interaction with the Clp proteolytic core. The Hsp93[P-] construct was ineffective at complementing the pale-yellow phenotype of hsp93 Arabidopsis (Arabidopsis thaliana) mutants, indicating that the PBM is essential for Hsp93 function. As expected, the PBM mutation negatively affected the degradation activity of the stromal Clp protease. The mutation also disrupted association of Hsp93 with the Clp proteolytic core at the envelope, without affecting the envelope localization of Hsp93 itself or its association with the TIC machinery, which we demonstrate to be mediated by a direct interaction with Tic110. Nonetheless, Hsp93[P-] expression did not detectably improve the protein import efficiency of hsp93 mutant chloroplasts. Thus, our results do not support the proposed function of Hsp93 in protein import propulsion, but are more consistent with the notion of Hsp93 performing a quality control role at the point of import. PMID:26586836

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

Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis

PubMed Central

Anand, Sudarshan; Wang, Pu; Yoshimura, Kiyoshi; Choi, In-Hak; Hilliard, Anja; Chen, Youhai H.; Wang, Chyung-Ru; Schulick, Richard; Flies, Andrew S.; Flies, Dallas B.; Zhu, Gefeng; Xu, Yanhui; Pardoll, Drew M.; Chen, Lieping; Tamada, Koji

2006-01-01

LIGHT is an important costimulatory molecule for T cell immunity. Recent studies have further implicated its role in innate immunity and inflammatory diseases, but its cellular and molecular mechanisms remain elusive. We report here that LIGHT is upregulated and functions as a proinflammatory cytokine in 2 independent experimental hepatitis models, induced by concanavalin A and Listeria monocytogenes. Molecular mutagenesis studies suggest that soluble LIGHT protein produced by cleavage from the cell membrane plays an important role in this effect through the interaction with the lymphotoxin-β receptor (LTβR) but not herpes virus entry mediator. NK1.1+ T cells contribute to the production, but not the cleavage or effector functions, of soluble LIGHT. Importantly, treatment with a mAb that specifically interferes with the LIGHT-LTβR interaction protects mice from lethal hepatitis. Our studies thus identify a what we believe to be a novel function of soluble LIGHT in vivo and offer a potential target for therapeutic interventions in hepatic inflammatory diseases. PMID:16557300

Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291).

PubMed

Sabui, Subrata; Subramanian, Veedamali S; Kapadia, Rubina; Said, Hamid M

2016-08-01

Thiamin plays a critical role in cellular energy metabolism. Mammalian cells obtain the vitamin from their surroundings, converted it to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria via a carrier-mediated process that involves the MTPPT (product of the SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the human MTPPT (hMTPPT), but less is known about structural features that are important for its function. Here, we used a protein-docking model ("Phyre2" and "DockingServer") to predict residues that may be important for function (substrate recognition) of the hMTPPT; we also examined the role of conserved positively-charged residues predicted ("PRALINE") to be in the trans-membrane domains (TMDs) in uptake of the negatively-charged TPP. Among the six residues predicted by the docking model (i.e., Thr(29), Arg(30), Ile(33), Ser(34), Asp(37) and Phe(298)), only Ile(33), Ser(34) and Asp(37) were found to be critical for function. While no change in translational efficiency/protein stability of the Ser(34) mutant was observed, both the Ile(33) and Asp(37) mutants showed a decrease in this parameter(s); there was also a decrease in the expression of the latter two mutants in mitochondria. A need for a polar residue at position 34 of the hMTPPT was evident. Our findings with the positively-charged residues (i.e., His(82), His(137), Lys(231) and Lys(291)) predicted in the TMD showed that His(137) and Lys(291) are important for function (via a role in proper delivery of the protein to mitochondria). These investigations provide important information about the structure-function relationship of the hMTPPT. Copyright © 2016 Elsevier B.V. All rights reserved.

Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

PubMed

Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

2012-12-01

IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

From Vesicles to Protocells: The Roles of Amphiphilic Molecules

PubMed Central

Sakuma, Yuka; Imai, Masayuki

2015-01-01

It is very challenging to construct protocells from molecular assemblies. An important step in this challenge is the achievement of vesicle dynamics that are relevant to cellular functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. Soft matter physics will play an important role in the development of vesicles that have these functions. Here, we show that simple binary phospholipid vesicles have the potential to reproduce the relevant functions of adhesion, pore formation and self-reproduction of vesicles, by coupling the lipid geometries (spontaneous curvatures) and the phase separation. This achievement will elucidate the pathway from molecular assembly to cellular life. PMID:25738256

Brain aromatase: roles in reproduction and neuroprotection.

PubMed

Roselli, Charles F

2007-01-01

It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

Transitioning between Work and Family Roles as a Function of Boundary Flexibility and Role Salience

ERIC Educational Resources Information Center

Winkel, Doan E.; Clayton, Russell W.

2010-01-01

This study investigates the manner in which people separate their work and family roles and how they manage the boundaries of these two important roles. Specifically, we focus on how role flexibility and salience influence transitions between roles. Results indicate that the ability and willingness to flex a role boundary and role salience are…

The Role of Communication in Library Management. Occasional Paper No. 34.

ERIC Educational Resources Information Center

Mwenegoha, Hamza A.

This paper defines and discusses the nature of management; outlines the primary management functions and activities, emphasizing the importance of communication and coordination to successful management; and examines the place of communication as a management function in the library setting. After a discussion of the key role of coordination in…

Phosphatidic acid and neurotransmission.

PubMed

Raben, Daniel M; Barber, Casey N

2017-01-01

Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Leaf bacterial diversity mediates plant diversity and ecosystem function relationships.

PubMed

Laforest-Lapointe, Isabelle; Paquette, Alain; Messier, Christian; Kembel, Steven W

2017-06-01

Research on biodiversity and ecosystem functioning has demonstrated links between plant diversity and ecosystem functions such as productivity. At other trophic levels, the plant microbiome has been shown to influence host plant fitness and function, and host-associated microbes have been proposed to influence ecosystem function through their role in defining the extended phenotype of host organisms However, the importance of the plant microbiome for ecosystem function has not been quantified in the context of the known importance of plant diversity and traits. Here, using a tree biodiversity-ecosystem functioning experiment, we provide strong support for the hypothesis that leaf bacterial diversity is positively linked to ecosystem productivity, even after accounting for the role of plant diversity. Our results also show that host species identity, functional identity and functional diversity are the main determinants of leaf bacterial community structure and diversity. Our study provides evidence of a positive correlation between plant-associated microbial diversity and terrestrial ecosystem productivity, and a new mechanism by which models of biodiversity-ecosystem functioning relationships can be improved.

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.

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.

Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology

PubMed Central

Turan, Belma; Tuncay, Erkan

2017-01-01

Zinc plays an important role in biological systems as bound and histochemically reactive labile Zn2+. Although Zn2+ concentration is in the nM range in cardiomyocytes at rest and increases dramatically under stimulation, very little is known about precise mechanisms controlling the intracellular distribution of Zn2+ and its variations during cardiac function. Recent studies are focused on molecular and cellular aspects of labile Zn2+ and its homeostasis in mammalian cells and growing evidence clarified the molecular mechanisms underlying Zn2+-diverse functions in the heart, leading to the discovery of novel physiological functions of labile Zn2+ in parallel to the discovery of subcellular localization of Zn2+-transporters in cardiomyocytes. Additionally, important experimental data suggest a central role of intracellular labile Zn2+ in excitation-contraction coupling in cardiomyocytes by shaping Ca2+ dynamics. Cellular labile Zn2+ is tightly regulated against its adverse effects through either Zn2+-transporters, Zn2+-binding molecules or Zn2+-sensors, and, therefore plays a critical role in cellular signaling pathways. The present review summarizes the current understanding of the physiological role of cellular labile Zn2+ distribution in cardiomyocytes and how a remodeling of cellular Zn2+-homeostasis can be important in proper cell function with Zn2+-transporters under hyperglycemia. We also emphasize the recent investigations on Zn2+-transporter functions from the standpoint of human heart health to diseases together with their clinical interest as target proteins in the heart under pathological condition, such as diabetes. PMID:29137144

Role of sleep quality in the metabolic syndrome

PubMed Central

Koren, Dorit; Dumin, Magdalena; Gozal, David

2016-01-01

Emerging evidence has assigned an important role to sleep as a modulator of metabolic homeostasis. The impact of variations in sleep duration, sleep-disordered breathing, and chronotype to cardiometabolic function encompasses a wide array of perturbations spanning from obesity, insulin resistance, type 2 diabetes, the metabolic syndrome, and cardiovascular disease risk and mortality in both adults and children. Here, we critically and extensively review the published literature on such important issues and provide a comprehensive overview of the most salient pathophysiologic pathways underlying the links between sleep, sleep disorders, and cardiometabolic functioning. PMID:27601926

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.

Possible roles of platelet-derived microparticles in atherosclerosis.

PubMed

Wang, Zhi-Ting; Wang, Zi; Hu, Yan-Wei

2016-05-01

Platelets and platelet-derived microparticles (PMPs) play important roles in cardiovascular diseases, especially atherosclerosis. Continued research has revealed that PMPs have numerous functions in atherosclerosis, not only in thrombosis formation, but also by induction of inflammation. PMPs also induce formation of foam cells. Recent evidence strongly indicates a significant role of PMPs in atherosclerosis. Here, current research on the function of PMPs in atherosclerosis is reviewed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Measuring Work Functioning: Validity of a Weighted Composite Work Functioning Approach.

PubMed

Boezeman, Edwin J; Sluiter, Judith K; Nieuwenhuijsen, Karen

2015-09-01

To examine the construct validity of a weighted composite work functioning measurement approach. Workers (health-impaired/healthy) (n = 117) completed a composite measure survey that recorded four central work functioning aspects with existing scales: capacity to work, quality of work performance, quantity of work, and recovery from work. Previous derived weights reflecting the relative importance of these aspects of work functioning were used to calculate the composite weighted work functioning score of the workers. Work role functioning, productivity, and quality of life were used for validation. Correlations were calculated and norms applied to examine convergent and divergent construct validity. A t test was conducted and a norm applied to examine discriminative construct validity. Overall the weighted composite work functioning measure demonstrated construct validity. As predicted, the weighted composite score correlated (p < .001) strongly (r > .60) with work role functioning and productivity (convergent construct validity), and moderately (.30 < r < .60) with physical quality of life and less strongly than work role functioning and productivity with mental quality of life (divergent validity). Further, the weighted composite measure detected that health-impaired workers show with a large effect size (Cohen's d > .80) significantly worse work functioning than healthy workers (discriminative validity). The weighted composite work functioning measurement approach takes into account the relative importance of the different work functioning aspects and demonstrated good convergent, fair divergent, and good discriminative construct validity.

Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

PubMed Central

Sun, Xiaolin; Rikkerink, Erik H.A.; Jones, William T.; Uversky, Vladimir N.

2013-01-01

Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes. Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs. Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein–protein interactions. Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners. In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs. Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development. Based on the roles of disorder in the protein–protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways. PMID:23362206

Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles

PubMed Central

Ang, Swee Kim; Zhang, Mengqi; Lodi, Tiziana; Lu, Hui

2014-01-01

Erv1 (essential for respiration and viability 1), is an essential component of the MIA (mitochondrial import and assembly) pathway, playing an important role in the oxidative folding of mitochondrial intermembrane space proteins. In the MIA pathway, Mia40, a thiol oxidoreductase with a CPC motif at its active site, oxidizes newly imported substrate proteins. Erv1 a FAD-dependent thiol oxidase, in turn reoxidizes Mia40 via its N-terminal Cys30–Cys33 shuttle disulfide. However, it is unclear how the two shuttle cysteine residues of Erv1 relay electrons from the Mia40 CPC motif to the Erv1 active-site Cys130–Cys133 disulfide. In the present study, using yeast genetic approaches we showed that both shuttle cysteine residues of Erv1 are required for cell growth. In organelle and in vitro studies confirmed that both shuttle cysteine residues were indeed required for import of MIA pathway substrates and Erv1 enzyme function to oxidize Mia40. Furthermore, our results revealed that the two shuttle cysteine residues of Erv1 are functionally distinct. Although Cys33 is essential for forming the intermediate disulfide Cys33–Cys130′ and transferring electrons to the redox active-site directly, Cys30 plays two important roles: (i) dominantly interacts and receives electrons from the Mia40 CPC motif; and (ii) resolves the Erv1 Cys33–Cys130 intermediate disulfide. Taken together, we conclude that both shuttle cysteine residues are required for Erv1 function, and play complementary, but distinct, roles to ensure rapid turnover of active Erv1. PMID:24625320

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing.

PubMed

Gökirmak, Tufan; Campanale, Joseph P; Reitzel, Adam M; Shipp, Lauren E; Moy, Gary W; Hamdoun, Amro

2016-06-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. Copyright © 2016 the American Physiological Society.

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing

PubMed Central

Gökirmak, Tufan; Campanale, Joseph P.; Reitzel, Adam M.; Shipp, Lauren E.; Moy, Gary W.

2016-01-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. PMID:27053522

Context-Specific Trophic and Functional Ecology of Fishes of Small Stream Ecosystems in the Ouachita National Forest

Treesearch

William J. Matthews; A. Maria Miller-Lemke; Melvin L. Warren; Donna Cobb; Jeffery G. Stewart; Betty Crump; Frances P. Gelwick

2004-01-01

Abstract - Fish play diverse and important roles in stream ecosystems, but details about ecosystem effects are poorly known for many freshwater fish species. A requisite first step to understanding functional roles of individual species is information on their trophic ecology in the context of particular environmental settings. Stomach contents were...

Dynamic Processes in Network Goods: Modeling, Analysis and Applications

ERIC Educational Resources Information Center

Paothong, Arnut

2013-01-01

The network externality function plays a very important role in the study of economic network industries. Moreover, the consumer group dynamic interactions coupled with network externality concept is going to play a dominant role in the network goods in the 21st century. The existing literature is stemmed on a choice of externality function with…

Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation

PubMed Central

Celi, Pietro; Gabai, Gianfranco

2015-01-01

This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions, such as respiratory diseases and parasitic infection; however, some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions, such as reproduction, nutrition, metabolism, lactation, gut health, and neonatal physiology. As the characterization of the mechanisms by which OS may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins. PMID:26664975

MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination.

PubMed

Bhattacharjee, Sonali; Osman, Fekret; Feeney, Laura; Lorenz, Alexander; Bryer, Claire; Whitby, Matthew C

2013-09-11

The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important functions in vertebrate cells. First, they are components of the constitutive centromere-associated network, aiding kinetochore assembly and function. Second, they work with the FANCM DNA translocase to promote DNA repair. However, it has been unclear whether there is crosstalk between these roles. We show that Mhf1 and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA repair/recombination and localizing to centromeres to promote chromosome segregation. Importantly, these functions are distinct, with the former being dependent on their interaction with the FANCM orthologue Fml1 and the latter not. Together with Fml1, they play a second role in aiding chromosome segregation by processing sister chromatid junctions. However, a failure of this activity does not manifest dramatically increased levels of chromosome missegregation due to the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions before the end of mitosis.

Two roles of the context in Pavlovian fear conditioning.

PubMed

Urcelay, Gonzalo P; Miller, Ralph R

2010-04-01

At both empirical and theoretical levels, multiple functional roles of contextual information upon memory performance have been proposed without a clear dissociation of these roles. Some theories have assumed that contexts are functionally similar to cues, whereas other views emphasize the retrieval facilitating properties of contextual information. In Experiment 1, we observed that one critical parameter, the spacing of trials, could determine whether the context would function as a conditioned stimulus or as a retrieval cue for memories trained in different phases. Experiments 2 and 3 doubly dissociated these functions by selectively disrupting one role but not the other, and vice versa. Overall, these observations identify one determinant of different functions of contextual information and pose a major challenge to theories of learning that assume exclusively one or the other function of the context. Moreover, these data emphasize the importance of parametric variations on behavioral control, which has critical implications for studies designed to understand the role of the hippocampus in processing of contextual attributes.

THE REGULATION ROLE OF CAROTID BODY PERIPHERAL CHEMORECEPTORS IN PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS.

PubMed

Lazovic, Biljana; Zlatkovic Svenda, Mirjana; Durmic, Tijana; Stajic, Zoran; Duric, Vesna; Zugic, Vladimir

2016-11-01

The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

Influence of physical exercise on microRNAs in skeletal muscle regeneration, aging and diseases

PubMed Central

Ultimo, Simona; Zauli, Giorgio; Martelli, Alberto M.; Vitale, Marco; McCubrey, James A.; Capitani, Silvano; Neri, Luca M.

2018-01-01

Skeletal muscle is a dynamic tissue with remarkable plasticity and its growth and regeneration are highly organized, with the activation of specific transcription factors, proliferative pathways and cytokines. The decline of skeletal muscle tissue with age, is one of the most important causes of functional loss of independence in older adults. Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living. Physical activity represents one of the most effective preventive agents for muscle decay in aging. Several studies have underlined the importance of microRNAs (miRNAs) in the control of myogenesis and of skeletal muscle regeneration and function. In this review, we reported an overview and recent advances about the role of miRNAs expressed in the skeletal muscle, miRNAs regulation by exercise in skeletal muscle, the consequences of different physical exercise training modalities in the skeletal muscle miRNA profile, their regulation under pathological conditions and the role of miRNAs in age-related muscle wasting. Specific miRNAs appear to be involved in response to different types of exercise and therefore to play an important role in muscle fiber identity and myofiber gene expression in adults and elder population. Understanding the roles and regulation of skeletal muscle miRNAs during muscle regeneration may result in new therapeutic approaches in aging or diseases with impaired muscle function or re-growth. PMID:29682218

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 essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity.

PubMed

Wang, Dashan

2018-06-01

The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and β-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. GPCR signaling plays an important role in T cell activation, homeostasis and function. GPCR signaling is critical in regulating T cell immunity.

The left heart can only be as good as the right heart: determinants of function and dysfunction of the right ventricle.

PubMed

Magder, Sheldon

2007-12-01

Discussions of cardiac physiology and pathophysiology most often emphasise the function of the left heart. However, right heart dysfunction plays an important role in critically ill patients and is often not recognised. This is probably because the role of the right ventricle is for generating flow more than pressure, and flow is not easy to evaluate. Of importance, when right ventricular function limits cardiac output, assessing left ventricular function gives little indication of overall cardiac performance. It has recently become evident that the right ventricle also has different genetic origins and characteristics from the left ventricle. The right and left ventricles interact through series effects, diastolic interactions and systolic interactions. The mechanisms of these, and their physiological and pathological significance are discussed.

Consensus Paper: The Cerebellum's Role in Movement and Cognition

PubMed Central

Koziol, Leonard F.; Budding, Deborah; Andreasen, Nancy; D'Arrigo, Stefano; Bulgheroni, Sara; Imamizu, Hiroshi; Ito, Masao; Manto, Mario; Marvel, Cherie; Parker, Krystal; Pezzulo, Giovanni; Ramnani, Narender; Riva, Daria; Schmahmann, Jeremy; Vandervert, Larry; Yamazaki, Tadashi

2014-01-01

While the cerebellum's role in motor function is well recognized, the nature of its concurrent role in cognitive function remains considerably less clear. The current consensus paper gathers diverse views on a variety of important roles played by the cerebellum across a range of cognitive and emotional functions. This paper considers the cerebellum in relation to neurocognitive development, language function, working memory, executive function, and the development of cerebellar internal control models and reflects upon some of the ways in which better understanding the cerebellum's status as a “supervised learning machine” can enrich our ability to understand human function and adaptation. As all contributors agree that the cerebellum plays a role in cognition, there is also an agreement that this conclusion remains highly inferential. Many conclusions about the role of the cerebellum in cognition originate from applying known information about cerebellar contributions to the coordination and quality of movement. These inferences are based on the uniformity of the cerebellum's compositional infrastructure and its apparent modular organization. There is considerable support for this view, based upon observations of patients with pathology within the cerebellum. PMID:23996631

The angiosperm phloem sieve tube system: a role in mediating traits important to modern agriculture.

PubMed

Ham, Byung-Kook; Lucas, William J

2014-04-01

The plant vascular system serves a vital function by distributing water, nutrients and hormones essential for growth and development to the various organs of the plant. In this review, attention is focused on the role played by the phloem as the conduit for delivery of both photosynthate and information macromolecules, especially from the context of its mediation in traits that are important to modern agriculture. Resource allocation of sugars and amino acids, by the phloem, to specific sink tissues is of importance to crop yield and global food security. Current findings are discussed in the context of a hierarchical control network that operates to integrate resource allocation to competing sinks. The role of plasmodesmata that connect companion cells to neighbouring sieve elements and phloem parenchyma cells is evaluated in terms of their function as valves, connecting the sieve tube pressure manifold system to the various plant tissues. Recent studies have also revealed that plasmodesmata and the phloem sieve tube system function cooperatively to mediate the long-distance delivery of proteins and a diverse array of RNA species. Delivery of these information macromolecules is discussed in terms of their roles in control over the vegetative-to-floral transition, tuberization in potato, stress-related signalling involving miRNAs, and genetic reprogramming through the delivery of 24-nucleotide small RNAs that function in transcriptional gene silencing in recipient sink organs. Finally, we discuss important future research areas that could contribute to developing agricultural crops with engineered performance characteristics for enhance yield potential.

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior.

PubMed

Hutchison, M A; Gu, X; Adrover, M F; Lee, M R; Hnasko, T S; Alvarez, V A; Lu, W

2018-05-01

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.

How cancer cells dictate their microenvironment: present roles of extracellular vesicles.

PubMed

Naito, Yutaka; Yoshioka, Yusuke; Yamamoto, Yusuke; Ochiya, Takahiro

2017-02-01

Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells. Cancer cells utilize EVs to dictate the unique phenotype of surrounding cells, thereby promoting cancer progression. Against such "education" by cancer cells, non-tumoral cells suppress cancer initiation and progression via EVs. Therefore, researchers consider EVs to be important cues to clarify the molecular mechanisms of cancer biology. Understanding the functions of EVs in cancer progression is an important aspect of cancer biology that has not been previously elucidated. In this review, we summarize experimental data that indicate the pivotal roles of EVs in cancer progression.

The importance of surface functional groups in the adsorption of copper onto walnut shell derived activated carbon.

PubMed

Xie, Ruzhen; Jin, Yan; Chen, Yao; Jiang, Wenju

2017-12-01

In this study, activated carbon (AC) was prepared from walnut shell using chemical activation. The surface chemistry of the prepared AC was modified by introducing or blocking certain functional groups, and the role of the different functional groups involved in the copper uptake was investigated. The structural and chemical heterogeneity of the produced carbons are characterized by Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, Boehm titration method and N 2 /77 K adsorption isotherm analysis. The equilibrium and the kinetics of copper adsorption onto AC were studied. The results demonstrated that the functional groups on AC played an important role in copper uptake. Among various surface functional groups, the oxygen-containing group was found to play a critical role in the copper uptake, and oxidation is the most effective way to improve Cu (II) adsorption onto AC. Ion-exchange was identified to be the dominant mechanism in the copper uptake by AC. Some other types of interactions, like complexation, were also proven to be involved in the adsorption process, while physical force was found to play a small role in the copper uptake. The regeneration of copper-loaded AC and the recovery of copper were also studied to evaluate the reusability of the oxidized AC.

A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development.

PubMed

Betson, Martha; Settleman, Jeffrey

2007-08-01

The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

Reclaiming "Old" Literacies in the New Literacy Information Age: The Functional Literacies of the Mediated Workstation

ERIC Educational Resources Information Center

Shepherd, Ryan; Goggin, Peter

2012-01-01

For many writing faculty, electronic or digital literacies may not play an overtly significant role in their course designs and teaching practices, but these literacies still play a significant role in how students write. Whether or not writing teachers want to accept it, functional computer literacies are an important aspect of teaching writing.…

The roles of Microphthalmia Transcription Factor and pigmentation in melanoma

PubMed Central

Hsiao, Jennifer J; Fisher, David E

2014-01-01

MITF and pigmentation play important roles in both normal melanocyte and transformed melanoma cell biology. MITF is regulated by many pathways and it also regulates many targets, some of which are still being discovered and functionally validated. MITF is involved in a wide range of processes in melanocytes, including pigment synthesis and lineage survival. Pigmentation itself plays an important role as the interface between genetic and environmental factors that contribute to melanoma. PMID:25111671

The role of acculturation and family functioning in predicting HIV risk behaviors among Hispanic delinquent youth.

PubMed

Farrelly, Colleen; Cordova, David; Huang, Shi; Estrada, Yannine; Prado, Guillermo

2013-06-01

The present study examined the relationship between Berry's acculturation typology and HIV risk behaviors and whether family functioning mediated any such effects. A total of 235 high risk Hispanic adolescents were categorized into one of Berry's four acculturation typologies through the use of cut-off scores on measures of Hispanicism and Americanism. Structural equation modeling was used to examine the effects of acculturation typology on HIV risk behaviors and the indirect effects of acculturation typology on HIV risk behaviors through family functioning. Acculturation typology was related to HIV risk behaviors. Family functioning partially mediated the effects of acculturation typology on the HIV risk behavior outcomes. These findings suggest that both Americanism and Hispanicism play an important role in the etiology of HIV risk behaviors among Hispanic youth and that both, along with family functioning, are important to consider when designing preventive interventions for this population.

The Popeye Domain Containing Genes and Their Function as cAMP Effector Proteins in Striated Muscle.

PubMed

Brand, Thomas

2018-03-13

The Popeye domain containing (POPDC) genes encode transmembrane proteins, which are abundantly expressed in striated muscle cells. Hallmarks of the POPDC proteins are the presence of three transmembrane domains and the Popeye domain, which makes up a large part of the cytoplasmic portion of the protein and functions as a cAMP-binding domain. Interestingly, despite the prediction of structural similarity between the Popeye domain and other cAMP binding domains, at the protein sequence level they strongly differ from each other suggesting an independent evolutionary origin of POPDC proteins. Loss-of-function experiments in zebrafish and mouse established an important role of POPDC proteins for cardiac conduction and heart rate adaptation after stress. Loss-of function mutations in patients have been associated with limb-girdle muscular dystrophy and AV-block. These data suggest an important role of these proteins in the maintenance of structure and function of striated muscle cells.

The Role of Acculturation and Family Functioning in Predicting HIV Risk Behaviors Among Hispanic Delinquent Youth

PubMed Central

Farrelly, Colleen; Cordova, David; Huang, Shi; Estrada, Yannine

2012-01-01

The present study examined the relationship between Berry’s acculturation typology and HIV risk behaviors and whether family functioning mediated any such effects. A total of 235 high risk Hispanic adolescents were categorized into one of Berry’s four acculturation typologies through the use of cut-off scores on measures of Hispanicism and Americanism. Structural equation modeling was used to examine the effects of acculturation typology on HIV risk behaviors and the indirect effects of acculturation typology on HIV risk behaviors through family functioning. Acculturation typology was related to HIV risk behaviors. Family functioning partially mediated the effects of acculturation typology on the HIV risk behavior outcomes. These findings suggest that both Americanism and Hispanicism play an important role in the etiology of HIV risk behaviors among Hispanic youth and that both, along with family functioning, are important to consider when designing preventive interventions for this population. PMID:22532299

Autophagy in the eye: Development, degeneration, and aging.

PubMed

Boya, Patricia; Esteban-Martínez, Lorena; Serrano-Puebla, Ana; Gómez-Sintes, Raquel; Villarejo-Zori, Beatriz

2016-11-01

Autophagy is a catabolic pathway that promotes the degradation and recycling of cellular components. Proteins, lipids, and even whole organelles are engulfed in autophagosomes and delivered to the lysosome for elimination. In response to stress, autophagy mediates the degradation of cell components, which are recycled to generate the nutrients and building blocks required to sustain cellular homeostasis. Moreover, it plays an important role in cellular quality control, particularly in neurons, in which the total burden of altered proteins and damaged organelles cannot be reduced by redistribution to daughter cells through cell division. Research has only begun to examine the role of autophagy in the visual system. The retina, a light-sensitive tissue, detects and transmits electrical impulses through the optic nerve to the visual cortex in the brain. Both the retina and the eye are exposed to a variety of environmental insults and stressors, including genetic mutations and age-associated alterations that impair their function. Here, we review the main studies that have sought to explain autophagy's importance in visual function. We describe the role of autophagy in retinal development and cell differentiation, and discuss the implications of autophagy dysregulation both in physiological aging and in important diseases such as age-associated macular degeneration and glaucoma. We also address the putative role of autophagy in promoting photoreceptor survival and discuss how selective autophagy could provide alternative means of protecting retinal cells. The findings reviewed here underscore the important role of autophagy in maintaining proper retinal function and highlight novel therapeutic approaches for blindness and other diseases of the eye. Copyright © 2016 Elsevier Ltd. All rights reserved.

Roles and responsibilities: theoretical issues in the definition of consultation liaison psychiatry.

PubMed

Agich, G J

1985-05-01

Central to much medical ethical analysis is the concept of the role of the physician. While this concept plays an important role in medical ethics, its function is largely tacit. The present paper attempts to bring the concept of a social role to prominence by focusing on an historically recent and rather richly contextured role, namely, that of consultation liaison psychiatry. Since my intention is primarily theoretical, I largely ignore the empirical studies which purport to develop the detailed functioning of the role. My limited intent is to draw attention to the theoretical complexity of the consultation liaison role as an example of the general relevance of role concepts to medical ethics. For this reason, consultation liaison psychiatry will function as an illustration of fundamental concepts of medical ethics rather than as a subject of analysis in its own right. Similarly, the concept of the social role will be developed only as is necessary to explore the general relationship between the consultation liaison role and ethical analysis.

Cognitive Functions Buffer Age Differences in Technology Ownership.

PubMed

Kamin, Stefan T; Lang, Frieder R

2016-01-01

Technology plays a major role in enhancing quality of life and everyday competence in old age. Mechanic and pragmatic cognitive functions are known to serve as resources when using technology in everyday life. Not much is known about the differential role of mechanic and pragmatic cognitive functions when moderating reduced technology ownership in old age. In this research, we explored whether perceptual speed or verbal fluency is more important for buffering age differences in technology ownership. We investigate possible moderation effects of cognitive functions relative to demographic characteristics, socioeconomic status, and household composition variables. We report findings based on a nationally representative German sample of 3,357 younger and older adults between 18 and 94 years of age (mean = 51.2, SD = 17.3). Interaction and relative importance analyses were conducted to examine the relative importance of perceptual speed and verbal fluency for the moderation of age differences in technology ownership across adulthood. Findings suggest that perceptual speed (B = 0.0008, t = 6.23, p < 0.001) and verbal fluency (B = 0.0003, t = 2.70, p < 0.01) buffered age differences in technology ownership. The moderating role of perceptual speed remained robust (B = 0.0007, t = 5.48, p < 0.001) when including interactions of age with demographic, socioeconomic, and household composition variables; however, the interaction between age and verbal fluency was no longer significant (B = 0.0002, t = 1.82, p = 0.069). Relative importance analysis indicates that perceptual speed was the most important moderator of age differences (DW = 0.0121), whereas verbal fluency was less important for moderating the relation between age and technology ownership (DW = 0.0039). Mechanic and pragmatic cognitive functions may serve differently as moderators of the relation between age and technology ownership. Our findings suggest that perceptual speed was more important for buffering age differences in technology ownership than verbal fluency. Such findings underscore the relevance of information processing for the ownership of technological devices in late life. © 2015 S. Karger AG, Basel.

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

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

The Impact of Functional Reading Instruction on Individual and Social Life

ERIC Educational Resources Information Center

Bulut, Mesut

2015-01-01

The functional importance of reading instruction with regard to society and individual is an undeniable fact. One of the essential goals of education is to actualize reading instruction which has a very important role in adopting the values of the contemporary civilization. Considering teaching, these educational goals which are based on a solid…

UnPAKing RUNX3 functions-Both sides of the coin.

PubMed

Kumar, Arun; Sundaram, Sandhya; Rayala, Suresh K; Venkatraman, Ganesh

2017-06-19

Post translational modifications of RUNX3 have been shown to play an important role in directing RUNX3 functions. In this review we highlight the phosphorylation dependent functions of RUNX3 as regulated by PAK1 and its implications on tumorigenesis.

Symbiodinium—Invertebrate Symbioses and the Role of Metabolomics

PubMed Central

Gordon, Benjamin R.; Leggat, William

2010-01-01

Symbioses play an important role within the marine environment. Among the most well known of these symbioses is that between coral and the photosynthetic dinoflagellate, Symbiodinium spp. Understanding the metabolic relationships between the host and the symbiont is of the utmost importance in order to gain insight into how this symbiosis may be disrupted due to environmental stressors. Here we summarize the metabolites related to nutritional roles, diel cycles and the common metabolites associated with the invertebrate-Symbiodinium relationship. We also review the more obscure metabolites and toxins that have been identified through natural products and biomarker research. Finally, we discuss the key role that metabolomics and functional genomics will play in understanding these important symbioses. PMID:21116405

Is testosterone important in LUT function in men and women? ICI-RS 2015.

PubMed

Badawi, Jasmin Katrin; Bosch, Ruud; Djurhuus, Jens Christian; Hanna-Mitchell, Ann T

2017-04-01

This review article is a collaborative report based upon the Authors' presentations and Group discussion on the role of testosterone (T) in the male and female lower urinary tract (LUT) which took place at the 6th International Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in Bristol, UK (September 8-10, 2015). It comprises overviews and opinions on both the current state of knowledge of the role of T in LUT function and dysfunction in both sexes. Results from animal studies suggest that T treatment may be beneficial for disorders of the LUT in women including urinary incontinence and pelvic organ prolapse. The need for clinical studies to evaluate the effect of T treatment in peri- and post-menopausal women, taking into account the type of applied androgen, the application form, timing and dosage, is especially emphasized. In males, findings on the impact of T on the male external urethral sphincter underscores that there is still much to learn about its role in male LUT physiology. The important topic of the use of T therapy in the treatment of enuresis in the young, both sexes, is also discussed. The importance of understanding the steroidogenic pathways linking T with estradiol is discussed as being of paramount importance in researching the unique actions of T in the LUT. The overall conclusion is that further research into the role of T in LUT function and dysfunction across genders and age groups (young to old) is extremely important. Neurourol. Urodynam. 36:859-862, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Managerial Roles and Functions at the Corporate Level of Television Group Ownerships.

ERIC Educational Resources Information Center

Phillips, Dennis D.

A study was undertaken to provide a base of knowledge concerning managerial roles at the corporate level in the television industry. Specifically, the study sought to determine (1) the amount of time consumed by corporate television executives in different managerial roles, (2) the importance of different managerial roles as perceived by the…

Quark fragmentation functions in NJL-jet model

NASA Astrophysics Data System (ADS)

Bentz, Wolfgang; Matevosyan, Hrayr; Thomas, Anthony

2014-09-01

We report on our studies of quark fragmentation functions in the Nambu-Jona-Lasinio (NJL) - jet model. The results of Monte-Carlo simulations for the fragmentation functions to mesons and nucleons, as well as to pion and kaon pairs (dihadron fragmentation functions) are presented. The important role of intermediate vector meson resonances for those semi-inclusive deep inelastic production processes is emphasized. Our studies are very relevant for the extraction of transverse momentum dependent quark distribution functions from measured scattering cross sections. We report on our studies of quark fragmentation functions in the Nambu-Jona-Lasinio (NJL) - jet model. The results of Monte-Carlo simulations for the fragmentation functions to mesons and nucleons, as well as to pion and kaon pairs (dihadron fragmentation functions) are presented. The important role of intermediate vector meson resonances for those semi-inclusive deep inelastic production processes is emphasized. Our studies are very relevant for the extraction of transverse momentum dependent quark distribution functions from measured scattering cross sections. Supported by Grant in Aid for Scientific Research, Japanese Ministry of Education, Culture, Sports, Science and Technology, Project No. 20168769.

Androgens and Female Sexual Function and Dysfunction--Findings From the Fourth International Consultation of Sexual Medicine.

PubMed

Davis, Susan R; Worsley, Roisin; Miller, Karen K; Parish, Sharon J; Santoro, Nanette

2016-02-01

Androgens have been implicated as important for female sexual function and dysfunction. To review the role of androgens in the physiology and pathophysiology of female sexual functioning and the evidence for efficacy of androgen therapy for female sexual dysfunction (FSD). We searched the literature using online databases for studies pertaining to androgens and female sexual function. Major reviews were included and their findings were summarized to avoid replicating their content. Quality of data published in the literature and recommendations were based on the GRADES system. The literature supports an important role for androgens in female sexual function. There is no blood androgen level below which women can be classified as having androgen deficiency. Clinical trials have consistently demonstrated that transdermal testosterone (T) therapy improves sexual function and sexual satisfaction in women who have been assessed as having hypoactive sexual desire disorder. The use of T therapy is limited by the lack of approved formulations for women and long-term safety data. Most studies do not support the use of systemic dehydroepiandrosterone therapy for the treatment of FSD in women with normally functioning adrenals or adrenal insufficiency. Studies evaluating the efficacy and safety of vaginal testosterone and dehydroepiandrosterone for the treatment of vulvovaginal atrophy are ongoing. Available data support an important role of androgens in female sexual function and dysfunction and efficacy of transdermal T therapy for the treatment of some women with FSD. Approved T formulations for women are generally unavailable. In consequence, the prescribing of T mostly involves off-label use of T products formulated for men and individually compounded T formulations. Long-term studies to determine the safety of T therapy for women and possible benefits beyond that of sexual function are greatly needed. Copyright © 2016. Published by Elsevier Inc.

Analyzing Online Behaviors, Roles, and Learning Communities via Online Discussions

ERIC Educational Resources Information Center

Yeh, Yu-Chu

2010-01-01

Online learning communities are an important means of sharing and creating knowledge. Online behaviors and online roles can reveal how online learning communities function. However, no study has elucidated the relationships among online behaviors, online roles, and online learning communities. In this study, 32 preservice teachers participated in…

Cholinergic modulation of cognitive processing: insights drawn from computational models

PubMed Central

Newman, Ehren L.; Gupta, Kishan; Climer, Jason R.; Monaghan, Caitlin K.; Hasselmo, Michael E.

2012-01-01

Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory, and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory, and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm plays a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers. PMID:22707936

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

Pan, Ronghui; Satkovich, John; Hu, Jianping

Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite of metabolic processes and often act coordinately with other organelles, such as chloroplasts and mitochondria. Peroxisomes import proteins to the peroxisome matrix by peroxins (PEX proteins), but how the function of the PEX proteins is regulated is poorly understood. In this study, we identified the Arabidopsis RING (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane protein with a regulatory role in peroxisome protein import. SP1 interacts physically with the two components of the peroxisomemore » protein docking complex PEX13–PEX14 and the (RING)-finger peroxin PEX2. Loss of SP1 function suppresses defects of the pex14-2 and pex13-1 mutants, and SP1 is involved in the degradation of PEX13 and possibly PEX14 and all three RING peroxins. An in vivo ubiquitination assay showed that SP1 has the ability to promote PEX13 ubiquitination. Our study has revealed that, in addition to its previously reported function in chloroplast biogenesis, SP1 plays a role in peroxisome biogenesis. The same E3 ubiquitin ligase promotes the destabilization of components of two distinct protein-import machineries, indicating that degradation of organelle biogenesis factors by the ubiquitin–proteasome system may constitute an important regulatory mechanism in coordinating the biogenesis of metabolically linked organelles in eukaryotes.« less

Peroxisome biogenesis, protein targeting mechanisms and PEX gene functions in plants.

PubMed

Cross, Laura L; Ebeed, Heba Talat; Baker, Alison

2016-05-01

Peroxisomes play diverse and important roles in plants. The functions of peroxisomes are dependent upon their steady state protein composition which in turn reflects the balance of formation and turnover of the organelle. Protein import and turnover of constituent peroxisomal proteins are controlled by the state of cell growth and environment. The evolutionary origin of the peroxisome and the role of the endoplasmic reticulum in peroxisome biogenesis are discussed, as informed by studies of the trafficking of peroxisome membrane proteins. The process of matrix protein import in plants and its similarities and differences with peroxisomes in other organisms is presented and discussed in the context of peroxin distribution across the green plants. Copyright © 2015 Elsevier B.V. All rights reserved.

Interferon regulatory factors: A key to tumour immunity.

PubMed

Chen, Yan-Jie; Li, Jing; Lu, Nan; Shen, Xi-Zhong

2017-08-01

Interferon regulatory factors (IRFs), which have 10 members, belong to the transcription factor family and were named because of the regulation of interferon expression. They play important roles in the immune regulation, cell differentiation, cell apoptosis, and cell cycle regulation. This article will review the functional characteristics and immune activity of the family members, especially in the role of cell differentiation and autoimmune diseases. Intensive studies will help uncover the pathogenesis of the disease in a more comprehensive view, and provide novel targets for disease treatment. But the most important problems yet to solve is IRFs function in the development processes of tumour, and whether IRFs can be an important regulator in tumour immune treatment. Copyright © 2017. Published by Elsevier B.V.

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.

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

DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis, rice, and budding yeast.

PubMed

Liu, Yun-Hua; Zhang, Meiping; Wu, Chengcang; Huang, James J; Zhang, Hong-Bin

2014-01-01

Knowledge of how a genome is structured and organized from its constituent elements is crucial to understanding its biology and evolution. Here, we report the genome structuring and organization pattern as revealed by systems analysis of the sequences of three model species, Arabidopsis, rice and yeast, at the whole-genome and chromosome levels. We found that all fundamental function elements (FFE) constituting the genomes, including genes (GEN), DNA transposable elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR), and (or) low complexity repeats (LCR), are structured in a nonrandom and correlative manner, thus leading to a hypothesis that the DNA of the species is structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE differ in their importance in the formation and evolution of the DNA jigsaw puzzle structure between species. DTE and RTE play more important roles than GEN, LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than LCR, SSR, and DTE in rice. The genes having multiple recognized functions play more important roles than those having single functions. These results provide useful knowledge necessary for better understanding genome biology and evolution of the species and for effective molecular breeding of rice.

Motoring through: the role of kinesin superfamily proteins in female meiosis.

PubMed

Camlin, Nicole J; McLaughlin, Eileen A; Holt, Janet E

2017-07-01

The kinesin motor protein family consists of 14 distinct subclasses and 45 kinesin proteins in humans. A large number of these proteins, or their orthologues, have been shown to possess essential function(s) in both the mitotic and the meiotic cell cycle. Kinesins have important roles in chromosome separation, microtubule dynamics, spindle formation, cytokinesis and cell cycle progression. This article contains a review of the literature with respect to the role of kinesin motor proteins in female meiosis in model species. Throughout, we discuss the function of each class of kinesin proteins during oocyte meiosis, and where such data are not available their role in mitosis is considered. Finally, the review highlights the potential clinical importance of this family of proteins for human oocyte quality. To examine the role of kinesin motor proteins in oocyte meiosis. A search was performed on the Pubmed database for journal articles published between January 1970 and February 2017. Search terms included 'oocyte kinesin' and 'meiosis kinesin' in addition to individual kinesin names with the terms oocyte or meiosis. Within human cells 45 kinesin motor proteins have been discovered, with the role of only 13 of these proteins, or their orthologues, investigated in female meiosis. Furthermore, of these kinesins only half have been examined in mammalian oocytes, despite alterations occurring in gene transcripts or protein expression with maternal ageing, cryopreservation or behavioral conditions, such as binge drinking, for many of them. Kinesin motor proteins have distinct and important roles throughout oocyte meiosis in many non-mammalian model species. However, the functions these proteins have in mammalian meiosis, particularly in humans, are less clear owing to lack of research. This review brings to light the need for more experimental investigation of kinesin motor proteins, particularly those associated with maternal ageing, cryopreservation or exposure to environmental toxicants. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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.

Contribution of Insula in Parkinson’s Disease: A Quantitative Meta-Analysis Study

PubMed Central

Criaud, Marion; Christopher, Leigh; Boulinguez, Philippe; Ballanger, Benedicte; Lang, Anthony E.; Cho, Sang S.; Houle, Sylvain; Strafella, Antonio P.

2016-01-01

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson’s disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. PMID:26800238

Contribution of insula in Parkinson's disease: A quantitative meta-analysis study.

PubMed

Criaud, Marion; Christopher, Leigh; Boulinguez, Philippe; Ballanger, Benedicte; Lang, Anthony E; Cho, Sang S; Houle, Sylvain; Strafella, Antonio P

2016-04-01

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson's disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. © 2016 Wiley Periodicals, Inc.

Stress and sodium intake in neural control of renal function in hypertension.

PubMed

DiBona, G F

1991-04-01

The interaction between genetic and environmental factors is important in the pathophysiology of hypertension. By examining the effects of two environmental factors--acute psychoemotional stress and dietary sodium intake--in rats with genetic hypertension, an important influence on central neural mechanisms governing the renal sympathetic neural control of renal function has been demonstrated. Additional studies of the central opioid systems have demonstrated an important role of opioid peptides in modulating the renal functional responses to acute psychoemotional stress. The observed renal functional alterations--antidiuresis, antinatriuresis, and renal vasoconstriction--are known to be capable of contributing to the initiation, development, and maintenance of the hypertensive process.

The Indispensable Roles of Microglia and Astrocytes during Brain Development

PubMed Central

Reemst, Kitty; Noctor, Stephen C.; Lucassen, Paul J.; Hol, Elly M.

2016-01-01

Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease. PMID:27877121

Concise review: genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells.

PubMed

Gezer, Deniz; Vukovic, Milica; Soga, Tomoyoshi; Pollard, Patrick J; Kranc, Kamil R

2014-06-01

Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that self-renew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1α. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-of-function studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions. © 2014 AlphaMed Press.

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.

Asymptote Misconception on Graphing Functions: Does Graphing Software Resolve It?

ERIC Educational Resources Information Center

Öçal, Mehmet Fatih

2017-01-01

Graphing function is an important issue in mathematics education due to its use in various areas of mathematics and its potential roles for students to enhance learning mathematics. The use of some graphing software assists students' learning during graphing functions. However, the display of graphs of functions that students sketched by hand may…

Speech and Language Functions that Require a Functioning Broca's Area

ERIC Educational Resources Information Center

Davis, Cameron; Kleinman, Jonathan T.; Newhart, Melissa; Gingis, Leila; Pawlak, Mikolaj; Hillis, Argye E.

2008-01-01

A number of previous studies have indicated that Broca's area has an important role in understanding and producing syntactically complex sentences and other language functions. If Broca's area is critical for these functions, then either infarction of Broca's area or temporary hypoperfusion within this region should cause impairment of these…

PPAR-γ in innate and adaptive lung immunity.

PubMed

Nobs, Samuel Philip; Kopf, Manfred

2018-05-16

The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells. Due to this plethora of functions and its involvement in multiple pulmonary diseases including asthma and pulmonary alveolar proteinosis, understanding the role of PPAR-γ in lung immunity is an important subject of ongoing research. ©2018 Society for Leukocyte Biology.

The important and diverse roles of antibodies in the host response to Borrelia infections.

PubMed

LaRocca, T J; Benach, J L

2008-01-01

Antibodies are of critical importance in the host response to tick-borne Borrelia species that cause relapsing fever and Lyme disease. Recent studies on the role of various B cell subsets in the host response to Borrelia, complement-independent, bactericidal antibodies, and diagnostics led to this review that focuses on the array of functions that antibodies to Borrelia can perform.

[Physical rehabilitation in multiple sclerosis: general principles and high-tech approaches].

PubMed

Peresedova, A V; Chernikova, L A; Zavalishin, I A

2013-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation programs are of major importance for the preservation of physical, physiological, social and professional functioning and improvement of quality of life. Currently, it is generally assumed that physical activity is an important component of non-pharmacological rehabilitation in multiple sclerosis. Properly organized exercise is a safe and efficient way to induce improvements in a number of physiological functions. A multidisciplinary rehabilitative approach should be recommended. The main recommendations for the use of exercise for patients with multiple sclerosis have been listed. An important aspect of the modern physical rehabilitation in multiple sclerosis is the usage of high-tech methods. The published results of robot-assisted training to improve the hand function and walking impairment have been represented. An important trend in the rehabilitation of patients with multiple sclerosis is the reduction of postural disorders through training balance coordination. The role of transcranial magnetic stimulation in spasticity reducing is being investigated. The use of telemedicine capabilities is quite promising. Due to the fact that the decline in physical activity can lead to the deterioration of many aspects of physiological functions and, ultimately, to mobility decrease, further research of the role of physical rehabilitation as an important therapeutic approach in preventing the progression of disability in multiple sclerosis is required.

Short communication: molecular characterization of dog and cat p65 subunits of NF-kappaB.

PubMed

Ishikawa, Shingo; Takemitsu, Hiroshi; Li, Gebin; Mori, Nobuko; Yamamoto, Ichiro; Arai, Toshiro

2015-04-01

Nuclear factor kappa B (NF-κB) plays an important role in the immune system. The p65 subunit is an important part of NF-κB unit, and studies of dog and cat p65 subunits of NF-κB (dp65 and cp65) are important in understanding their immune function. In this study, we described the molecular characterization of dp65 and cp65. The dp65 and cp65 complementary DNA encoded 542 and 555 amino acids, respectively, showing a high sequence homology with the mammalian p65 subunit (>87.5%). Quantitative polymerase chain reaction revealed that the p65 messenger RNA is highly expressed in the dog stomach and cat heart and adipose tissue. Functional NF-κB promoter-luciferase reporter vectors revealed that our isolated dp65 and cp65 cDNA encodes a functionally active protein. Transiently expressed dp65 and cp65 up-regulated pro-inflammatory cytokine expression levels in dog and cat, respectively. These findings suggest that dp65 and cp65 play important roles in regulating immune function. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of JAM-A in inflammatory bowel disease: unrevealing the ties that bind.

PubMed

Vetrano, Stefania; Danese, Silvio

2009-05-01

Tight junctions (TJ) are junctional proteins whose function is to maintain an intact intestinal epithelial barrier and regulate the paracellular movement of water and solutes. Altered TJ structure and epithelial permeability are observed in inflammatory bowel disease and seem to have an important role in the pathogenesis of these diseases. Junctional adhesion molecule-A (JAM-A) is a protein expressed at tight junctions of epithelial and endothelial cells, as well as on circulating leukocytes. Its function at tight junctions appears to be crucial as an extracellular adhesive molecule in the direct regulation of intestinal barrier function. This review focuses on the role of JAM-A in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function.

Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase.

PubMed

Takahata, Tatsuro; Takeda, Eri; Tobiume, Minoru; Tokunaga, Kenzo; Yokoyama, Masaru; Huang, Yu-Lun; Hasegawa, Atsuhiko; Shioda, Tatsuo; Sato, Hironori; Kannagi, Mari; Masuda, Takao

2017-01-01

Nonenzymatic roles for HIV-1 integrase (IN) at steps prior to the enzymatic integration step have been reported. To obtain structural and functional insights into the nonenzymatic roles of IN, we performed genetic analyses of HIV-1 IN, focusing on a highly conserved Tyr15 in the N-terminal domain (NTD), which has previously been shown to regulate an equilibrium state between two NTD dimer conformations. Replacement of Tyr15 with alanine, histidine, or tryptophan prevented HIV-1 infection and caused severe impairment of reverse transcription without apparent defects in reverse transcriptase (RT) or in capsid disassembly kinetics after entry into cells. Cross-link analyses of recombinant IN proteins demonstrated that lethal mutations of Tyr15 severely impaired IN structure for assembly. Notably, replacement of Tyr15 with phenylalanine was tolerated for all IN functions, demonstrating that a benzene ring of the aromatic side chain is a key moiety for IN assembly and functions. Additional mutagenic analyses based on previously proposed tetramer models for IN assembly suggested a key role of Tyr15 in facilitating the hydrophobic interaction among IN subunits, together with other proximal residues within the subunit interface. A rescue experiment with a mutated HIV-1 with RT and IN deleted (ΔRT ΔIN) and IN and RT supplied in trans revealed that the nonenzymatic IN function might be exerted through the IN precursor conjugated with RT (RT-IN). Importantly, the lethal mutations of Tyr15 significantly reduced the RT-IN function and assembly. Taken together, Tyr15 seems to play a key role in facilitating the proper assembly of IN and RT on viral RNA through the RT-IN precursor form. Inhibitors of the IN enzymatic strand transfer function (INSTI) have been applied in combination antiretroviral therapies to treat HIV-1-infected patients. Recently, allosteric IN inhibitors (ALLINIs) that interact with HIV-1 IN residues, the locations of which are distinct from the catalytic sites targeted by INSTI, have been discovered. Importantly, ALLINIs affect the nonenzymatic role(s) of HIV-1 IN, providing a rationale for the development of next-generation IN inhibitors with a mechanism that is distinct from that of INSTI. Here, we demonstrate that Tyr15 in the HIV-1 IN NTD plays a critical role during IN assembly by facilitating the hydrophobic interaction of the NTD with the other domains of IN. Importantly, we found that the functional assembly of IN through its fusion form with RT is critical for IN to exert its nonenzymatic function. Our results provide a novel mechanistic insight into the nonenzymatic function of HIV-1 IN and its prevention. Copyright © 2016 American Society for Microbiology.

Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import

PubMed Central

Paila, Yamuna D; Richardson, Lynn GL; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

2016-01-01

Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. DOI: http://dx.doi.org/10.7554/eLife.12631.001 PMID:26999824

Context-dependent consumer control in New England tidal wetlands.

PubMed

Moore, Alexandria

2018-01-01

Recent studies in coastal wetlands have indicated that consumers may play an important role in regulating large-scale ecosystem processes. Predator removal experiments have shown significant differences in above-ground biomass production in the presence of higher level consumers, or predators. These results indicate that predators play an important role in regulating biomass production, but the extent to which this regulation impacts additional ecosystem functions, such as nutrient cycling and organic matter accumulation, is unclear. This study evaluated the impact that consumers have on large-scale ecosystem processes within southern New England tidal wetlands and contributes to the general understanding of trophic control in these systems. I established enclosure cages within three coastal wetlands and manipulated the presence of green crab predators to assess how trophic interactions affect ecosystem functions. Findings suggest that although these consumers may exert some top-down effects, other environmental factors, such as other consumers not studied here or bottom-up interactions, may variably play a larger role in the maintenance of ecosystem processes within the region. These results indicate that the loss of top-down control as an important mechanism influencing ecosystem functions may not hold for all wetlands along the full extent of the New England coastline.

Context-dependent consumer control in New England tidal wetlands

PubMed Central

2018-01-01

Recent studies in coastal wetlands have indicated that consumers may play an important role in regulating large-scale ecosystem processes. Predator removal experiments have shown significant differences in above-ground biomass production in the presence of higher level consumers, or predators. These results indicate that predators play an important role in regulating biomass production, but the extent to which this regulation impacts additional ecosystem functions, such as nutrient cycling and organic matter accumulation, is unclear. This study evaluated the impact that consumers have on large-scale ecosystem processes within southern New England tidal wetlands and contributes to the general understanding of trophic control in these systems. I established enclosure cages within three coastal wetlands and manipulated the presence of green crab predators to assess how trophic interactions affect ecosystem functions. Findings suggest that although these consumers may exert some top-down effects, other environmental factors, such as other consumers not studied here or bottom-up interactions, may variably play a larger role in the maintenance of ecosystem processes within the region. These results indicate that the loss of top-down control as an important mechanism influencing ecosystem functions may not hold for all wetlands along the full extent of the New England coastline. PMID:29771961

E-learning Constructive Role Plays for EFL Learners in China's Tertiary Education

ERIC Educational Resources Information Center

Shen, Lin; Suwanthep, Jitpanat

2011-01-01

Recently, speaking has played an increasingly important role in second/foreign language settings. However, in many Chinese universities, EFL students rarely communicate in English with other people effectively. The existing behavioristic role plays on New Horizon College English (NHCE) e-learning do not function successfully in supplementing EFL…

Mitochondria link metabolism and epigenetics in haematopoiesis.

PubMed

Schell, John C; Rutter, Jared

2017-05-31

Due to their varied metabolic and signalling roles, mitochondria are important in mediating cell behaviour. By altering mitochondrial function, two studies now identify metabolite-induced epigenetic changes that have profound effects on haematopoietic stem cell fate and function.

Aquaporin structure-function relationships: water flow through plant living cells.

PubMed

Zhao, Chang-Xing; Shao, Hong-Bo; Chu, Li-Ye

2008-04-01

Plant aquaporins play an important role in water uptake and movement-an aquaporin that opens and closes a gate that regulates water movement in and out of cells. Some plant aquaporins also play an important role in response to water stress. Since their discovery, advancing knowledge of their structures and properties led to an understanding of the basic features of the water transport mechanism and increased illumination to water relations. Meanwhile, molecular and functional characterization of aquaporins has revealed the significance of their regulation in response to the adverse environments such as salinity and drought. This paper reviews the structure, species diversity, physiology function, regulation of plant aquaporins, and the relations between environmental factors and plant aquaporins. Complete understanding of aquaporin function and regulation is to integrate those mechanisms in time and space and to well regulate the permeation of water across biological membranes under changing environmental and developmental conditions.

Intermediates of Metabolism: From Bystanders to Signalling Molecules.

PubMed

Haas, Robert; Cucchi, Danilo; Smith, Joanne; Pucino, Valentina; Macdougall, Claire Elizabeth; Mauro, Claudio

2016-05-01

The integration of biochemistry into immune cell biology has contributed immensely to our understanding of immune cell function and the associated pathologies. So far, most studies have focused on the regulation of metabolic pathways during an immune response and their contribution to its success. More recently, novel signalling functions of metabolic intermediates are being discovered that might play important roles in the regulation of immunity. Here we describe the three long-known small metabolites lactate, acetyl-CoA, and succinate in the context of immunometabolic signalling. Functions of these ubiquitous molecules are largely dependent on their intra- and extracellular concentrations as well as their subcompartmental localisation. Importantly, the signalling functions of these metabolic intermediates extend beyond self-regulatory roles and include cell-to-cell communication and sensing of microenvironmental conditions to elicit stress responses and cellular adaptation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Brain Sex Matters: estrogen in cognition and Alzheimer’s disease

PubMed Central

Li, Rena; Cui, Jie; Shen, Yong

2014-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer’s disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function. PMID:24418360

Uncovering a role for the tail of the Dictyostelium discoideum SadA protein in cell-substrate adhesion.

PubMed

Kowal, Anthony S; Chisholm, Rex L

2011-05-01

Previous work from our laboratory showed that the Dictyostelium discoideum SadA protein plays a central role in cell-substrate adhesion. SadA null cells exhibit a loss of adhesion, a disrupted actin cytoskeleton, and a cytokinesis defect. How SadA mediates these phenotypes is unknown. This work addresses the mechanism of SadA function, demonstrating an important role for the C-terminal cytoplasmic tail in SadA function. We found that a SadA tailless mutant was unable to rescue the sadA adhesion deficiency, and overexpression of the SadA tail domain reduced adhesion in wild-type cells. We also show that SadA is closely associated with the actin cytoskeleton. Mutagenesis studies suggested that four serine residues in the tail, S924/S925 and S940/S941, may regulate association of SadA with the actin cytoskeleton. Glutathione S-transferase pull-down assays identified at least one likely interaction partner of the SadA tail, cortexillin I, a known actin bundling protein. Thus, our data demonstrate an important role for the carboxy-terminal cytoplasmic tail in SadA function and strongly suggest that a phosphorylation event in this tail regulates an interaction with cortexillin I. Based on our data, we propose a model for the function of SadA.

Signals of speciation: Volatile organic compounds resolve closely related sagebrush taxa, suggesting their importance in evolution

Treesearch

Deidre M. Jaeger; Justin B. Runyon; Bryce A. Richardson

2016-01-01

Volatile organic compounds (VOCs) play important roles in the environmental adaptation and fitness of plants. Comparison of the qualitative and quantitative differences in VOCs among closely related taxa and assessing the effects of environment on their emissions are important steps to deducing VOC function and evolutionary importance.

Role divergence and complexity in gerontological home care.

PubMed

Kaye, L W

1989-01-01

This study documents high levels of role complexity and functional overlap in the field of home health care. Personnel perform a wide range of "professional/organizational" and "community/familial" service functions though the emphasis is on the delivery of a battery of pseudo family-like tasks. The importance of a familial orientation does not significantly decline when controlling for length of employment or organizational rationality. Role orientation is, however, significantly associated with a worker's chronological age. Results lead to program planning recommendations meant to influence staff training paradigms in home health care.

Trends in sensorimotor research and countermeasures for exploration-class space flights.

PubMed

Shelhamer, Mark

2015-01-01

Research in the area of sensorimotor and neurovestibular function has played an important role in enabling human space flight. This role, however, is changing. One of the key aspects of sensorimotor function relevant to this role will build on its widespread connections with other physiological and psychological systems in the body. The firm knowledge base in this area can provide a strong platform to explore these interactions, which can also provide for the development of effective and efficient countermeasures to the deleterious effects of space flight.

Kupffer cell complement receptor clearance function and host defense.

PubMed

Loegering, D J

1986-01-01

Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.

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 microbial functional diversity and PHB degradation suggesting a strong positive correlation ( r  = 0.95) between microbial functional diversity and PHB degradation. Thus, the results demonstrate that microbial functional diversity plays an important role in PHB degradation in soil by exhibiting versatile microbial metabolic potentials that lead to the enhanced degradation of PHB.

Carotenoids, versatile components of oxygenic photosynthesis.

PubMed

Domonkos, Ildikó; Kis, Mihály; Gombos, Zoltán; Ughy, Bettina

2013-10-01

Carotenoids (CARs) are a group of pigments that perform several important physiological functions in all kingdoms of living organisms. CARs serve as protective agents, which are essential structural components of photosynthetic complexes and membranes, and they play an important role in the light harvesting mechanism of photosynthesizing plants and cyanobacteria. The protection against reactive oxygen species, realized by quenching of singlet oxygen and the excited states of photosensitizing molecules, as well as by the scavenging of free radicals, is one of the main biological functions of CARs. X-ray crystallographic localization of CARs revealed that they are present at functionally and structurally important sites of both the PSI and PSII reaction centers. Characterization of a CAR-less cyanobacterial mutant revealed that while the absence of CARs prevents the formation of PSII complexes, it does not abolish the assembly and function of PSI. CAR molecules assist in the formation of protein subunits of the photosynthetic complexes by gluing together their protein components. In addition to their aforementioned indispensable functions, CARs have a substantial role in the formation and maintenance of proper cellular architecture, and potentially also in the protection of the translational machinery under stress conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of leptin in female reproduction.

PubMed

Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

2015-01-01

Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

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.

E3 ubiquitin ligase SP1 regulates peroxisome biogenesis in Arabidopsis

DOE PAGES

Pan, Ronghui; Satkovich, John; Hu, Jianping

2016-10-31

Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite of metabolic processes and often act coordinately with other organelles, such as chloroplasts and mitochondria. Peroxisomes import proteins to the peroxisome matrix by peroxins (PEX proteins), but how the function of the PEX proteins is regulated is poorly understood. In this study, we identified the Arabidopsis RING (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane protein with a regulatory role in peroxisome protein import. SP1 interacts physically with the two components of the peroxisomemore » protein docking complex PEX13–PEX14 and the (RING)-finger peroxin PEX2. Loss of SP1 function suppresses defects of the pex14-2 and pex13-1 mutants, and SP1 is involved in the degradation of PEX13 and possibly PEX14 and all three RING peroxins. An in vivo ubiquitination assay showed that SP1 has the ability to promote PEX13 ubiquitination. Our study has revealed that, in addition to its previously reported function in chloroplast biogenesis, SP1 plays a role in peroxisome biogenesis. The same E3 ubiquitin ligase promotes the destabilization of components of two distinct protein-import machineries, indicating that degradation of organelle biogenesis factors by the ubiquitin–proteasome system may constitute an important regulatory mechanism in coordinating the biogenesis of metabolically linked organelles in eukaryotes.« less

OCTOPUS-LIKE 2, a novel player in Arabidopsis root and vascular development, reveals a key role for OCTOPUS family genes in root metaphloem sieve tube differentiation.

PubMed

Ruiz Sola, M Aguila; Coiro, Mario; Crivelli, Simona; Zeeman, Samuel C; Schmidt Kjølner Hansen, Signe; Truernit, Elisabeth

2017-12-01

Protophloem and metaphloem sieve tubes are essential for transporting carbohydrates and signalling molecules towards sink tissues. OCTOPUS (OPS) was previously identified as an important regulator of protophloem differentiation in Arabidopsis roots. Here, we investigated the role of OCTOPUS-LIKE 2 (OPL2), a gene homologous to OPS. OPL2 expression patterns were analysed, and functional equivalence of OPS and OPL2 was tested. Mutant and double mutant phenotypes were investigated. OPS and OPL2 displayed overlapping expression patterns and a high degree of functional overlap. A mutation in OPL2 revealed redundant functions of OPS and OPL2 in developmental processes in which OPS was known to play a role, notably cotyledon vascular patterning and protophloem development. Moreover, we also uncovered redundant roles for OPS and OPL2 in leaf vascular patterning and, most interestingly, metaphloem sieve tube differentiation. Our results reveal a novel OPS-like protein that, together with OPS, is an important regulator of vascular patterning, root growth and phloem development. OPS and OPL2 are the first genes identified that play a role in metaphloem sieve tube differentiation. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

DOT1L regulates dystrophin expression and is critical for cardiac function

PubMed Central

Nguyen, Anh T.; Xiao, Bin; Neppl, Ronald L.; Kallin, Eric M.; Li, Juan; Chen, Taiping; Wang, Da-Zhi; Xiao, Xiao; Zhang, Yi

2011-01-01

Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice resulted in embryonic lethality. Here we report that cardiac-specific knockout of Dot1L results in increased mortality rate with chamber dilation, increased cardiomyocyte cell death, systolic dysfunction, and conduction abnormalities. These phenotypes mimic those exhibited in patients with dilated cardiomyopathy (DCM). Mechanistic studies reveal that DOT1L performs its function in cardiomyocytes through regulating Dystrophin (Dmd) transcription and, consequently, stability of the Dystrophin–glycoprotein complex important for cardiomyocyte viability. Importantly, expression of a miniDmd can largely rescue the DCM phenotypes, indicating that Dmd is a major target mediating DOT1L function in cardiomyocytes. Interestingly, analysis of available gene expression data sets indicates that DOT1L is down-regulated in idiopathic DCM patient samples compared with normal controls. Therefore, our study not only establishes a critical role for DOT1L-mediated H3K79 methylation in cardiomyocyte function, but also reveals the mechanism underlying the role of DOT1L in DCM. In addition, our study may open new avenues for the diagnosis and treatment of human heart disease. PMID:21289070

Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

PubMed

Thakur, Rupamoni; Mukherjee, Ashis K

2017-06-01

Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

In Vivo Imaging of Flavoprotein Fluorescence During Hypoxia Reveals the Importance of Direct Arterial Oxygen Supply to Cerebral Cortex Tissue.

PubMed

Chisholm, K I; Ida, K K; Davies, A L; Papkovsky, D B; Singer, M; Dyson, A; Tachtsidis, I; Duchen, M R; Smith, K J

2016-01-01

Live imaging of mitochondrial function is crucial to understand the important role played by these organelles in a wide range of diseases. The mitochondrial redox potential is a particularly informative measure of mitochondrial function, and can be monitored using the endogenous green fluorescence of oxidized mitochondrial flavoproteins. Here, we have observed flavoprotein fluorescence in the exposed murine cerebral cortex in vivo using confocal imaging; the mitochondrial origin of the signal was confirmed using agents known to manipulate mitochondrial redox potential. The effects of cerebral oxygenation on flavoprotein fluorescence were determined by manipulating the inspired oxygen concentration. We report that flavoprotein fluorescence is sensitive to reductions in cortical oxygenation, such that reductions in inspired oxygen resulted in loss of flavoprotein fluorescence with the exception of a preserved 'halo' of signal in periarterial regions. The findings are consistent with reports that arteries play an important role in supplying oxygen directly to tissue in the cerebral cortex, maintaining mitochondrial function.

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.

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.

Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

PubMed

Shimokawa, Hiroaki; Satoh, Kimio

2015-05-01

Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

Social Integration and Pulmonary Function in the Elderly

PubMed Central

Crittenden, Crista N.; Pressman, Sarah D.; Cohen, Sheldon; Janicki-Deverts, Denise; Smith, Bruce W.; Seeman, Teresa E.

2014-01-01

Objective This study sought to determine whether social integration, defined as number of social roles, is associated with better pulmonary function in the elderly and which roles are associated with greatest benefit. It also examined pathways that connect social integration to better lung health. Methods High functioning men (N = 518) and women (N = 629) ages 70-79 were recruited as part of the MacArthur Study of Successful Aging and data were collected on social roles as well as pulmonary function as assessed by peak expiratory flow rate (PEFR). Multiple regressions predicting PEFR from the number of social roles controlled for age, sex, race, education, weight and height. Physiological, behavioral, social and psychological factors were tested as mediators of the association between the number of social roles and PEFR. Results More social roles were associated with better PEFR. Analysis of specific roles indicated that marriage was the strongest positive correlate of PEFR. However, greater numbers of roles were also associated with better PEFR independent of marriage. Being a relative or friend were each also individually associated with better PEFR. Even so, greater numbers of social roles were associated with better PEFR independent of relative and friend. The data were consistent with greater happiness, not smoking, and more physical activity acting as pathways linking the number of roles to PEFR. Conclusions Number of social roles is an important correlate of healthy lung function in the elderly. This association may be driven by healthier behaviors and greater feelings of well-being. PMID:24884907

Social integration and pulmonary function in the elderly.

PubMed

Crittenden, Crista N; Pressman, Sarah D; Cohen, Sheldon; Janicki-Deverts, Denise; Smith, Bruce W; Seeman, Teresa E

2014-06-01

This study sought to determine whether social integration, defined as number of social roles, is associated with better pulmonary function in the elderly and which roles are associated with greatest benefit. It also examined pathways that connect social integration to better lung health. High functioning men (n = 518) and women (n = 629) ages 70-79 were recruited as part of the MacArthur Study of Successful Aging, and data were collected on social roles as well as pulmonary function as assessed by peak expiratory flow rate (PEFR). Multiple regressions predicting PEFR from the number of social roles controlled for age, sex, race, education, weight, and height. Physiological, behavioral, social, and psychological factors were tested as mediators of the association between the number of social roles and PEFR. More social roles were associated with better PEFR. Analysis of specific roles indicated that marriage was the strongest positive correlate of PEFR. However, greater numbers of roles were also associated with better PEFR independent of marriage. Being a relative or friend were each also individually associated with better PEFR. Even so, greater numbers of social roles were associated with better PEFR independent of relative and friend. The data were consistent with greater happiness, not smoking, and more physical activity acting as pathways linking the number of roles to PEFR. Number of social roles is an important correlate of healthy lung function in the elderly. This association may be driven by healthier behaviors and greater feelings of well-being. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Dynamics and Context-Dependent Roles of DNA Methylation.

PubMed

Ambrosi, Christina; Manzo, Massimiliano; Baubec, Tuncay

2017-05-19

DNA methylation is one of the most extensively studied epigenetic marks. It is involved in transcriptional gene silencing and plays important roles during mammalian development. Its perturbation is often associated with human diseases. In mammalian genomes, DNA methylation is a prevalent modification that decorates the majority of cytosines. It is found at the promoters and enhancers of inactive genes, at repetitive elements, and within transcribed gene bodies. Its presence at promoters is dynamically linked to gene activity, suggesting that it could directly influence gene expression patterns and cellular identity. The genome-wide distribution and dynamic behaviour of this mark have been studied in great detail in a variety of tissues and cell lines, including early embryonic development and in embryonic stem cells. In combination with functional studies, these genome-wide maps of DNA methylation revealed interesting features of this mark and provided important insights into its dynamic nature and potential functional role in genome regulation. In this review, we discuss how these recent observations, in combination with insights obtained from biochemical and functional genetics studies, have expanded our current knowledge about the regulation and context-dependent roles of DNA methylation in mammalian genomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of the Cellular Immune System of Drosophila Requires the Membrane Attack Complex/Perforin-Like Protein Torso-Like.

PubMed

Forbes-Beadle, Lauren; Crossman, Tova; Johnson, Travis K; Burke, Richard; Warr, Coral G; Whisstock, James C

2016-10-01

Pore-forming members of the membrane attack complex/perforin-like (MACPF) protein superfamily perform well-characterized roles as mammalian immune effectors. For example, complement component 9 and perforin function to directly form pores in the membrane of Gram-negative pathogens or virally infected/transformed cells, respectively. In contrast, the only known MACPF protein in Drosophila melanogaster, Torso-like, plays crucial roles during development in embryo patterning and larval growth. Here, we report that in addition to these functions, Torso-like plays an important role in Drosophila immunity. However, in contrast to a hypothesized effector function in, for example, elimination of Gram-negative pathogens, we find that torso-like null mutants instead show increased susceptibility to certain Gram-positive pathogens such as Staphylococcus aureus and Enterococcus faecalis We further show that this deficit is due to a severely reduced number of circulating immune cells and, as a consequence, an impaired ability to phagocytose bacterial particles. Together these data suggest that Torso-like plays an important role in controlling the development of the Drosophila cellular immune system. Copyright © 2016 by the Genetics Society of America.

R-Function Relationships for Application in the Fractional Calculus

NASA Technical Reports Server (NTRS)

Lorenzo, Carl F.; Hartley, Tom T.

2000-01-01

The F-function, and its generalization the R-function, are of fundamental importance in the fractional calculus. It has been shown that the solution of the fundamental linear fractional differential equation may be expressed in terms of these functions. These functions serve as generalizations of the exponential function in the solution of fractional differential equations. Because of this central role in the fractional calculus, this paper explores various intrarelationships of the R-function, which will be useful in further analysis. Relationships of the R-function to the common exponential function, e(t), and its fractional derivatives are shown. From the relationships developed, some important approximations are observed. Further, the inverse relationships of the exponential function, el, in terms of the R-function are developed. Also, some approximations for the R-function are developed.

R-function relationships for application in the fractional calculus.

PubMed

Lorenzo, Carl F; Hartley, Tom T

2008-01-01

The F-function, and its generalization the R-function, are of fundamental importance in the fractional calculus. It has been shown that the solution of the fundamental linear fractional differential equation may be expressed in terms of these functions. These functions serve as generalizations of the exponential function in the solution of fractional differential equations. Because of this central role in the fractional calculus, this paper explores various intrarelationships of the R-function, which will be useful in further analysis. Relationships of the R-function to the common exponential function, et, and its fractional derivatives are shown. From the relationships developed, some important approximations are observed. Further, the inverse relationships of the exponential function, et, in terms of the R-function are developed. Also, some approximations for the R-function are developed.

Neuromodulation during motor development and behavior.

PubMed

Pflüger, H J

1999-12-01

Important recent advances have been made in understanding the role of aminergic modulation during the maturation of Xenopus larvae swimming rhythms, including effects on particular ion channel types of component neurons, and the role of peptidergic modulation during development of adult central patterns generators in the stomatogastric ganglion of crustaceans. By recording from octopaminergic neuromodulatory neurons during ongoing motor behavior in the locust, new insights into the role of this peripheral neuromodulatory mechanism have been gained. In particular, it is now clear that the octopaminergic neuromodulatory system is automatically activated in parallel to the motor systems, and that both excitation and inhibition play important functional roles.

Eos is redundant for T regulatory cell function, but plays an important role in IL-2 and Th17 production by CD4+ T conventional cells

PubMed Central

Rieder, Sadiye Amcaoglu; Metidji, Amina; Glass, Deborah Dacek; Thornton, Angela M.; Ikeda, Tohru; Morgan, Bruce A.; Shevach, Ethan M.

2015-01-01

Eos is a transcription factor that belongs to the Ikaros family of transcription factors. Eos has been reported to be a T regulatory cell (Treg) signature gene, to play a critical role in Treg suppressor functions, and to maintain Treg stability. We have utilized mice with a global deficiency of Eos to re-examine the role of Eos expression in both Treg and T conventional (Tconv) cells. Treg from Eos deficient (Eos−/−) mice developed normally, displayed a normal Treg phenotype, and exhibited normal suppressor function in vitro. Eos−/− Treg were as effective as Treg from wild type (WT) mice in suppression of inflammation in a model of inflammatory bowel disease. Bone marrow (BM) from Eos−/− mice was as effective as BM from WT mice in controlling T cell activation when used to reconstitute immunodeficient mice in the presence of Scurfy fetal liver cells. Surprisingly, Eos was expressed in activated Tconv cells and was required for IL-2 production, CD25 expression and proliferation in vitro by CD4+ Tconv cells. Eos−/− mice developed more severe Experimental Autoimmune Encephalomyelitis than WT mice, displayed increased numbers of effector T cells in the periphery and CNS, and amplified IL-17 production. In conclusion, our studies are not consistent with a role for Eos in Treg development and function, but demonstrate that Eos plays an important role in the activation and differentiation of Tconv cells. PMID:26062998

Hydrogen sulfide: role in ion channel and transporter modulation in the eye

PubMed Central

Njie-Mbye, Ya F.; Opere, Catherine A.; Chitnis, Madhura; Ohia, Sunny E.

2012-01-01

Hydrogen sulfide (H2S), a colorless gas with a characteristic smell of rotten eggs, has been portrayed for decades as a toxic environmental pollutant. Since evidence of its basal production in mammalian tissues a decade ago, H2S has attracted substantial interest as a potential inorganic gaseous mediator with biological importance in cellular functions. Current research suggests that, next to its counterparts nitric oxide and carbon monoxide, H2S is an important multifunctional signaling molecule with pivotal regulatory roles in various physiological and pathophysiological processes as diverse as learning and memory, modulation of synaptic activities, cell survival, inflammation, and maintenance of vascular tone in the central nervous and cardiovascular systems. In contrast, there are few reports of a regulatory role of H2S in the eye. Accumulating reports on the pharmacological role of H2S in ocular tissues indicate the existence of a functional trans-sulfuration pathway and a potential physiological role for H2S as a gaseous neuromodulator in the eye. Thus, understanding the role of H2S in vision-related processes is imperative to our expanding knowledge of this molecule as a gaseous mediator in ocular tissues. This review aims to provide a comprehensive and current understanding of the potential role of H2S as a signaling molecule in the eye. This objective is achieved by discussing the involvement of H2S in the regulation of (1) ion channels such as calcium (L-type, T-type, and intracellular stores), potassium (KATP and small conductance channels) and chloride channels, (2) glutamate transporters such as EAAT1/GLAST and the L-cystine/glutamate antiporter. The role of H2S as an important mediator in cellular functions and physiological processes that are triggered by its interaction with ion channels/transporters in the eye will also be discussed. PMID:22934046

Geometrical Representations in the Learning of Two-Variable Functions

ERIC Educational Resources Information Center

Trigueros, Maria; Martinez-Planell, Rafael

2010-01-01

This study is part of a project concerned with the analysis of how students work with two-variable functions. This is of fundamental importance given the role of multivariable functions in mathematics and its applications. The portion of the project we report here concentrates on investigating the relationship between students' notion of subsets…

Motor and somatosensory conversion disorder: a functional unawareness syndrome?

PubMed

Perez, David L; Barsky, Arthur J; Daffner, Kirk; Silbersweig, David A

2012-01-01

Although conversion disorder is closely connected to the origins of neurology and psychiatry, it remains poorly understood. In this article, the authors discuss neural and clinical parallels between lesional unawareness disorders and unilateral motor and somatosensory conversion disorder, emphasizing functional neuroimaging/disease correlates. Authors suggest that a functional-unawareness neurobiological framework, mediated by right hemisphere-lateralized, large-scale brain network dysfunction, may play a significant role in the neurobiology of conversion disorder. The perigenual anterior cingulate and the posterior parietal cortices are detailed as important in disease pathophysiology. Further investigations will refine the functional-unawareness concept, clarify the role of affective circuits, and delineate the process through which functional neurologic symptoms emerge.

Biosynthesis, structural, and functional attributes of tocopherols in planta; past, present, and future perspectives.

PubMed

Hussain, Nazim; Irshad, Faiza; Jabeen, Zahra; Shamsi, Imran Haider; Li, Zhilan; Jiang, Lixi

2013-07-03

Tocopherols are lipophilic molecules, ubiquitously synthesized in all photosynthetic organisms. Being a group of vitamin E compounds, they play an essential role in human nutrition and health. Despite their structural and functional attributes as important antioxidants in plants, it would be misleading to ignore the potential roles of tocopherols beyond their antioxidant properties in planta. Detailed characterization of mutants and transgenic plants, including Arabidopsis (vte1, vte2, vte4, and so on), maize (sxd1) mutants, and transgenic potato and tobacco lines altered in tocopherol biosynthesis and contents, has led to surprising outcomes regarding the additional functions of these molecules. Thus, the aim of this review is to highlight the past and present research findings on tocopherols' structural, biosynthesis, and functional properties in plants. Special emphasis is given to their suggested functions in planta, such as cell signaling, hormonal interactions, and coordinated response of tocopherols to other antioxidants under abiotic stresses. Moreover, some important questions about possible new functions of tocopherols will be discussed as future prospects to stimulate further research.

Human RAD50 makes a functional DNA-binding complex.

PubMed

Kinoshita, Eri; van Rossum-Fikkert, Sari; Sanchez, Humberto; Kertokalio, Aryandi; Wyman, Claire

2015-06-01

The MRE11-RAD50-NBS1 (MRN) complex has several distinct functions in DNA repair including important roles in both non-homologous end-joining (NHEJ) and homologous recombination (HR). The biochemical activities of MR(N) have been well characterized implying specific functional roles for the components. The arrangement of proteins in the complex implies interdependence of their biochemical activities making it difficult to separate specific functions. We obtained purified human RAD50 and observed that it binds ATP, undergoes ATP-dependent conformational changes as well as having ATPase activity. Scanning force microscopy analysis clearly showed that RAD50 binds DNA although not as oligomers. RAD50 alone was not functional in tethering DNA molecules. ATP increased formation of RAD50 multimers which were however globular lacking extended coiled coils, in contrast to the MR complex where ATP induced oligomers have obvious coiled coils protruding from a central domain. These results suggest that MRE11 is important in maintaining the structural arrangement of RAD50 in the protein complex and perhaps has a role in reinforcing proper alignment of the coiled coils in the ATP-bound state. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Disentangling the role of management, vegetation structure, and plant quality for Orthoptera in lowland meadows.

PubMed

Schirmel, Jens; Gerlach, Rebekka; Buhk, Constanze

2017-08-17

Seminatural grasslands provide habitats for various species and are important for biodiversity conservation. The understanding of the diverse responses of species and traits to different grassland management methods is therefore urgently needed. We disentangled the role of grassland management (fertilization and irrigation), vegetation structure (biomass, sward height) and plant quality (protein and fiber content) for Orthoptera communities in lowland hay meadows in Germany. We found vegetation structure to be the most important environmental category in explaining community structure of Orthoptera (species richness, total individuals, functional diversity and species composition). Intensively used meadows (fertilized, irrigated, high plant biomass) were characterized by assemblages with few species, low functional diversity, and low conservation value. Thereby, the relatively moderate fertilizer inputs in our study system of up to ∼75 kg N/ha/year reduced functional diversity of Orthoptera, while this negative effect of fertilization was not detectable when solely considering taxonomic aspects. We found strong support for a prominent role of plant quality in shaping Orthoptera communities and especially the trait composition. Our findings demonstrate the usefulness of considering both taxonomic and functional components (functional diversity) in biodiversity research and we suggest a stronger involvement of plant quality measures in Orthoptera studies. © 2017 Institute of Zoology, Chinese Academy of Sciences.

A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites.

PubMed

Ghaedi, Hamid; Bastami, Milad; Jahani, Mohammad Mehdi; Alipoor, Behnam; Tabasinezhad, Maryam; Ghaderi, Omar; Nariman-Saleh-Fam, Ziba; Mirfakhraie, Reza; Movafagh, Abolfazl; Omrani, Mir Davood; Masotti, Andrea

2016-06-01

The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.

Drosophila Ana1 is required for centrosome assembly and centriole elongation

PubMed Central

Saurya, Saroj; Roque, Hélio; Novak, Zsofia A.; Wainman, Alan; Aydogan, Mustafa G.; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano

2016-01-01

ABSTRACT Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP–Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. PMID:27206860

New insights into epididymal biology and function.

PubMed

Cornwall, Gail A

2009-01-01

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions. A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included. While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients. Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

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

Cho, Yoon Sun; Jung, Hye Jin; Seok, Seung Hyeok

2013-04-19

Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levelsmore » in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases.« less

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.

Finite-element modeling of the human neurocranium under functional anatomical aspects.

PubMed

Mall, G; Hubig, M; Koebke, J; Steinbuch, R

1997-08-01

Due to its functional significance the human skull plays an important role in biomechanical research. The present work describes a new Finite-Element model of the human neurocranium. The dry skull of a middle-aged woman served as a pattern. The model was developed using only the preprocessor (Mentat) of a commercial FE-system (Marc). Unlike that of other FE models of the human skull mentioned in the literature, the geometry in this model was designed according to functional anatomical findings. Functionally important morphological structures representing loci minoris resistentiae, especially the foramina and fissures of the skull base, were included in the model. The results of two linear static loadcase analyses in the region of the skull base underline the importance of modeling from the functional anatomical point of view.

Road weather forecast quality analysis

DOT National Transportation Integrated Search

2006-03-01

It is just as important to keep the highways functioning in a safe and efficient manner as it is to construct them in : the first place. Our economy is built around an efficient transportation system. Winter weather plays an important role : in highw...

Integrating the ICF with positive psychology: Factors predicting role participation for mothers with multiple sclerosis.

PubMed

Farber, Ruth S; Kern, Margaret L; Brusilovsky, Eugene

2015-05-01

Being a mother has become a realizable life role for women with disabilities and chronic illnesses, including multiple sclerosis (MS). Identifying psychosocial factors that facilitate participation in important life roles-including motherhood-is essential to help women have fuller lives despite the challenge of their illness. By integrating the International Classification of Functioning, Disability, and Health (ICF) and a positive psychology perspective, this study examined how environmental social factors and positive personal factors contribute to daily role participation and satisfaction with parental participation. One hundred and 11 community-dwelling mothers with MS completed Ryff's Psychological Well-Being Scales, the Medical Outcome Study Social Support Survey, the Short Form-36, and the Parental Participation Scale. Hierarchical regression analyses examined associations between social support and positive personal factors (environmental mastery, self-acceptance, purpose in life) with daily role participation (physical and emotional) and satisfaction with parental participation. One-way ANOVAs tested synergistic combinations of social support and positive personal factors. Social support predicted daily role participation (fewer limitations) and greater satisfaction with parental participation. Positive personal factors contributed additional unique variance. Positive personal factors and social support synergistically predicted better function and greater satisfaction than either alone. Integrating components of the ICF and positive psychology provides a useful model for understanding how mothers with MS can thrive despite challenge or impairment. Both positive personal factors and environmental social factors were important contributors to positive role functioning. Incorporating these paradigms into treatment may help mothers with MS participate more fully in meaningful life roles. (c) 2015 APA, all rights reserved).

Galectin-3 in M2 macrophages plays a protective role in resolution of neuropathology in brain parasitic infection by regulating neutrophil turnover.

PubMed

Quenum Zangbede, Fredice O; Chauhan, Arun; Sharma, Jyotika; Mishra, Bibhuti B

2018-06-26

Macrophages/microglia with M2- activation phenotype are thought to play an important anti-inflammatory and tissue reparative functions in the brain, yet the molecular basis of their functions in the central nervous system (CNS) remain to be clearly defined. In a preclinical model of neurocysticercosis using brain infection with a parasite Mesocestoides corti , we previously reported the presence of large numbers of M2 cells in the CNS. In this study using female mice, we report that M2 macrophages in the parasite-infected brain display abundant galectin-3 expression. Disease severity was increased in Galectin-3 -/- mice correlating with increased neurological defects, augmented cell death and, importantly, massive accumulation of neutrophils and M2 macrophages in the CNS of these mice. Because neutrophil clearance by efferocytosis is an important function of M2 macrophages, we investigated a possible role of galectin-3 in this process. Indeed, galectin-3 deficient M2 macrophages exhibited a defect in efferocytic clearance of neutrophils in-vitro. Furthermore, adoptive transfer of M2 macrophages from Galectin-3 sufficient WT mice reduced neutrophilia in the CNS and ameliorated disease severity in parasite-infected Galectin-3 -/- mice. Together, these results demonstrate for the first time a novel role of galectin-3 in M2 macrophage function in neutrophil turnover and resolution of inflammatory pathology in the CNS. This likely will have implications in neurocysticercosis and neuro-inflammatory diseases. SIGNIFICANCE STATEMENT Macrophages/microglia with M1-activation phenotype are thought to promote CNS pathology, whereas M2-anti-inflammatory phenotype promote CNS repair. However, the mechanisms regulating M2 cell protective functions in the CNS microenvironment are undefined. Quenum Zangbede et. al., report that helminth infection of the brain induces an increased expression of galectin-3 in M2 macrophages accumulated in the CNS. Using multiple experimental models in vivo and in vitro , they show that galectin-3 in M2 macrophages functions to clear neutrophils accumulated in the CNS. Importantly, galectin-3 in M2 macrophages plays a central role in the containment of neuropathology and disease severity. These results provide a direct mechanistic evidence of the protective function of M2- macrophages in the CNS. Copyright © 2018 the authors.

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

DTIC Science & Technology

2008-07-01

identification of new genes may not yield a clear indication of their respective functions , studies on their evolution may allow validation of their...in the elongated Nebenkern (Figure 2H). In addi- tion, Merlin was seen as a bright punctate dot in the acro- somal region, a Golgi apparatus -derived... functions as a tumor suppressor, we have confirmed that Drosophila Merlin plays important roles in the control of mitosis exit and in the

Uncovering a Role for the Tail of the Dictyostelium discoideum SadA Protein in Cell-Substrate Adhesion ▿ †

PubMed Central

Kowal, Anthony S.; Chisholm, Rex L.

2011-01-01

Previous work from our laboratory showed that the Dictyostelium discoideum SadA protein plays a central role in cell-substrate adhesion. SadA null cells exhibit a loss of adhesion, a disrupted actin cytoskeleton, and a cytokinesis defect. How SadA mediates these phenotypes is unknown. This work addresses the mechanism of SadA function, demonstrating an important role for the C-terminal cytoplasmic tail in SadA function. We found that a SadA tailless mutant was unable to rescue the sadA adhesion deficiency, and overexpression of the SadA tail domain reduced adhesion in wild-type cells. We also show that SadA is closely associated with the actin cytoskeleton. Mutagenesis studies suggested that four serine residues in the tail, S924/S925 and S940/S941, may regulate association of SadA with the actin cytoskeleton. Glutathione S-transferase pull-down assays identified at least one likely interaction partner of the SadA tail, cortexillin I, a known actin bundling protein. Thus, our data demonstrate an important role for the carboxy-terminal cytoplasmic tail in SadA function and strongly suggest that a phosphorylation event in this tail regulates an interaction with cortexillin I. Based on our data, we propose a model for the function of SadA. PMID:21441344

The adsorption of CH3 and C6H6 on corundum-type sesquioxides: The role of van der Waals interactions

NASA Astrophysics Data System (ADS)

Dabaghmanesh, Samira; Partoens, Bart; Neyts, Erik

Van der Waals (vdW) interactions play an important role in the adsorption of atoms and molecules on the surface of solids. This role becomes more significant whenever the interaction between the adsorbate and surface is physisorption. Thanks to recent developments in density functional theory (DFT), we are now able to employ different vdW methods that helps us to account for the long-range vdW forces. However, the choice of the most efficient vdW functional for different materials is still an open question. In our study, we examine different vdW approaches to compute bulk and molecular adsorption properties of M2O3 oxides (M: Cr, Fe, and Al) as well-known examples of the corundum family. For the bulk properties, we compare our results for the heat of formation, cohesive energy, lattice parameters and bond distances as obtained using the different vdW functionals and available experimental data. Next we compute the adsorption energies of the benzene molecule (as an example of physisorption) and CH3 (as an example of chemisorption) on top of the (0001) M-terminated and MO-terminated surfaces. Calculating the vdW contributions into the adsorption energies, we find that the vdW functionals play important role not just in the weak adsorptions but even in strong adsorption.

The emerging functions of UCP2 in health, disease, and therapeutics.

PubMed

Mattiasson, Gustav; Sullivan, Patrick G

2006-01-01

The uncoupling proteins (UCPs) are attracting an increased interest as potential therapeutic targets in a number of important diseases. UCP2 is expressed in several tissues, but its physiological functions as well as potential therapeutic applications are still unclear. Unlike UCP1, UCP2 does not seem to be important to thermogenesis or weight control, but appears to have an important role in the regulation of production of reactive oxygen species, inhibition of inflammation, and inhibition of cell death. These are central features in, for example, neurodegenerative and cardiovascular disease, and experimental evidence suggests that an increased expression and activity of UCP2 in models of these diseases has a beneficial effect on disease progression, implicating a potential therapeutic role for UCP2. UCP2 has an important role in the pathogenesis of type 2 diabetes by inhibiting insulin secretion in islet beta cells. At the same time, type 2 diabetes is associated with increased risk of cardiovascular disease and atherosclerosis where an increased expression of UCP2 appears to be beneficial. This illustrates that therapeutic applications involving UCP2 likely will have to regulate expression and activity in a tissue-specific manner.

[Involvement of aquaporin-4 in synaptic plasticity, learning and memory].

PubMed

Wu, Xin; Gao, Jian-Feng

2017-06-25

Aquaporin-4 (AQP-4) is the predominant water channel in the central nervous system (CNS) and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. However, the role of AQP-4 in regulating synaptic plasticity, learning and memory, cognitive function is only beginning to be investigated. It is well known that synaptic plasticity is the prime candidate for mediating of learning and memory. Long term potentiation (LTP) and long term depression (LTD) are two forms of synaptic plasticity, and they share some but not all the properties and mechanisms. Hippocampus is a part of limbic system that is particularly important in regulation of learning and memory. This article is to review some research progresses of the function of AQP-4 in synaptic plasticity, learning and memory, and propose the possible role of AQP-4 as a new target in the treatment of cognitive dysfunction.

An epigenetic view of developmental diseases: new targets, new therapies.

PubMed

Xie, Pei; Zang, Li-Qun; Li, Xue-Kun; Shu, Qiang

2016-08-01

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. Original research articles and literature reviews published in PubMed-indexed journals. DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Primary cilia proteins: ciliary and extraciliary sites and functions.

PubMed

Hua, Kiet; Ferland, Russell J

2018-05-01

Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. As such, elucidating the importance of the primary cilium has attracted researchers from all biological disciplines. As the primary cilia field expands, caution is warranted in attributing biological defects solely to the function of this organelle, since many of these "ciliary" proteins are found at other sites in cells and likely have non-ciliary functions. Indeed, many, if not all, cilia proteins have locations and functions outside the primary cilium. Extraciliary functions are known to include cell cycle regulation, cytoskeletal regulation, and trafficking. Cilia proteins have been observed in the nucleus, at the Golgi apparatus, and even in immune synapses of T cells (interestingly, a non-ciliated cell). Given the abundance of extraciliary sites and functions, it can be difficult to definitively attribute an observed phenotype solely to defective cilia rather than to some defective extraciliary function or a combination of both. Thus, extraciliary sites and functions of cilia proteins need to be considered, as well as experimentally determined. Through such consideration, we will understand the true role of the primary cilium in disease as compared to other cellular processes' influences in mediating disease (or through a combination of both). Here, we review a compilation of known extraciliary sites and functions of "cilia" proteins as a means to demonstrate the potential non-ciliary roles for these proteins.

Moonlighting adenosine deaminase: a target protein for drug development.

PubMed

Cortés, Antoni; Gracia, Eduard; Moreno, Estefania; Mallol, Josefa; Lluís, Carme; Canela, Enric I; Casadó, Vicent

2015-01-01

Interest in adenosine deaminase (ADA) in the context of medicine has mainly focused on its enzymatic activity. This is justified by the importance of the reaction catalyzed by ADA not only for the intracellular purine metabolism, but also for the extracellular purine metabolism as well, because of its capacity as a regulator of the concentration of extracellular adenosine that is able to activate adenosine receptors (ARs). In recent years, other important roles have been described for ADA. One of these, with special relevance in immunology, is the capacity of ADA to act as a costimulator, promoting T-cell proliferation and differentiation mainly by interacting with the differentiation cluster CD26. Another role is the ability of ADA to act as an allosteric modulator of ARs. These receptors have very general physiological implications, particularly in the neurological system where they play an important role. Thus, ADA, being a single chain protein, performs more than one function, consistent with the definition of a moonlighting protein. Although ADA has never been associated with moonlighting proteins, here we consider ADA as an example of this family of multifunctional proteins. In this review, we discuss the different roles of ADA and their pathological implications. We propose a mechanism by which some of their moonlighting functions can be coordinated. We also suggest that drugs modulating ADA properties may act as modulators of the moonlighting functions of ADA, giving them additional potential medical interest. © 2014 Wiley Periodicals, Inc.

Functional importance of Ψ38 and Ψ39 in distinct tRNAs, amplified for tRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification in yeast

PubMed Central

Han, Lu; Kon, Yoshiko

2015-01-01

The numerous modifications of tRNA play central roles in controlling tRNA structure and translation. Modifications in and around the anticodon loop often have critical roles in decoding mRNA and in maintaining its reading frame. Residues U38 and U39 in the anticodon stem–loop are frequently modified to pseudouridine (Ψ) by members of the widely conserved TruA/Pus3 family of pseudouridylases. We investigate here the cause of the temperature sensitivity of pus3Δ mutants of the yeast Saccharomyces cerevisiae and find that, although Ψ38 or Ψ39 is found on at least 19 characterized cytoplasmic tRNA species, the temperature sensitivity is primarily due to poor function of tRNAGln(UUG), which normally has Ψ38. Further investigation reveals that at elevated temperatures there are substantially reduced levels of the s2U moiety of mcm5s2U34 of tRNAGln(UUG) and the other two cytoplasmic species with mcm5s2U34, that the reduced s2U levels occur in the parent strain BY4741 and in the widely used strain W303, and that reduced levels of the s2U moiety are detectable in BY4741 at temperatures as low as 33°C. Additional examination of the role of Ψ38,39 provides evidence that Ψ38 is important for function of tRNAGln(UUG) at permissive temperature, and indicates that Ψ39 is important for the function of tRNATrp(CCA) in trm10Δ pus3Δ mutants and of tRNALeu(CAA) as a UAG nonsense suppressor. These results provide evidence for important roles of both Ψ38 and Ψ39 in specific tRNAs, and establish that modification of the wobble position is subject to change under relatively mild growth conditions. PMID:25505024

Response of Microbial Community Function to Fluctuating Geochemical Conditions within a Legacy Radioactive Waste Trench Environment

PubMed Central

Kinsela, Andrew S.; Bligh, Mark W.; Harrison, Jennifer J.; Payne, Timothy E.

2017-01-01

ABSTRACT During the 1960s, small quantities of radioactive materials were codisposed with chemical waste at the Little Forest Legacy Site (Sydney, Australia) in 3-meter-deep, unlined trenches. Chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a 6-week period immediately after a prolonged rainfall event to assess the impact of changing water levels upon the microbial ecology and contaminant mobility. Collectively, results demonstrated that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the potentially important role that the taxonomically diverse microbial community played in this transition. In particular, aerobes dominated in the first day, followed by an increase of facultative anaerobes/denitrifiers at day 4. Toward the mid-end of the sampling period, the functional and taxonomic profiles depicted an anaerobic community distinguished by a higher representation of dissimilatory sulfate reduction and methanogenesis pathways. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs. IMPORTANCE The role of chemical and microbiological factors in mediating the biogeochemistry of groundwaters from trenches used to dispose of radioactive materials during the 1960s is examined in this study. Specifically, chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a 6-week period immediately after a prolonged rainfall event to assess how changing water levels influence microbial ecology and contaminant mobility. Results demonstrate that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the important role that the taxonomically diverse microbial community played in this transition. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs. PMID:28667104

Response of Microbial Community Function to Fluctuating Geochemical Conditions within a Legacy Radioactive Waste Trench Environment.

PubMed

Vázquez-Campos, Xabier; Kinsela, Andrew S; Bligh, Mark W; Harrison, Jennifer J; Payne, Timothy E; Waite, T David

2017-09-01

During the 1960s, small quantities of radioactive materials were codisposed with chemical waste at the Little Forest Legacy Site (Sydney, Australia) in 3-meter-deep, unlined trenches. Chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a 6-week period immediately after a prolonged rainfall event to assess the impact of changing water levels upon the microbial ecology and contaminant mobility. Collectively, results demonstrated that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the potentially important role that the taxonomically diverse microbial community played in this transition. In particular, aerobes dominated in the first day, followed by an increase of facultative anaerobes/denitrifiers at day 4. Toward the mid-end of the sampling period, the functional and taxonomic profiles depicted an anaerobic community distinguished by a higher representation of dissimilatory sulfate reduction and methanogenesis pathways. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs. IMPORTANCE The role of chemical and microbiological factors in mediating the biogeochemistry of groundwaters from trenches used to dispose of radioactive materials during the 1960s is examined in this study. Specifically, chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a 6-week period immediately after a prolonged rainfall event to assess how changing water levels influence microbial ecology and contaminant mobility. Results demonstrate that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the important role that the taxonomically diverse microbial community played in this transition. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs. Copyright © 2017 Vázquez-Campos et al.

Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

PubMed

Li, Nan; Stein, Richard S L; He, Wei; Komives, Elizabeth; Wang, Wei

2013-10-01

Methylation is one of the important post-translational modifications that play critical roles in regulating protein functions. Proteomic identification of this post-translational modification and understanding how it affects protein activity remain great challenges. We tackled this problem from the aspect of methylation mediating protein-protein interaction. Using the chromodomain of human chromobox protein homolog 6 as a model system, we developed a systematic approach that integrates structure modeling, bioinformatics analysis, and peptide microarray experiments to identify lysine residues that are methylated and recognized by the chromodomain in the human proteome. Given the important role of chromobox protein homolog 6 as a reader of histone modifications, it was interesting to find that the majority of its interacting partners identified via this approach function in chromatin remodeling and transcriptional regulation. Our study not only illustrates a novel angle for identifying methyllysines on a proteome-wide scale and elucidating their potential roles in regulating protein function, but also suggests possible strategies for engineering the chromodomain-peptide interface to enhance the recognition of and manipulate the signal transduction mediated by such interactions.

Diverse roles of leptin in the gastrointestinal tract: Modulation of motility, absorption, growth, and inflammation

PubMed Central

Yarandi, Shadi S.; Hebbar, Gautam; Sauer, Cary G.; Cole, Conrad R.; Ziegler, Thomas R.

2011-01-01

Objective Leptin was discovered in 1994 as a hormone produced by adipose tissue with a modulatory effect on feeding behavior and weight control. Recently, the stomach has been identified as an important source of leptin and growing evidence has shown diverse functions for leptin in the gastrointestinal tract. Methods Using leptin as a keyword in PubMed, more than 17 000 articles were identified, of which more than 500 articles were related to the role of leptin in the gastrointestinal tract. Available abstracts were reviewed and more than 200 original articles were reviewed in detail. Results The available literature demonstrated that leptin can modulate several important functions of the gastrointestinal tract. Leptin interacts with the vagus nerve and cholecystokinin to delay gastric emptying and has a complex effect on motility of the small bowel. Leptin modulates absorption of macronutrients in the gastrointestinal tract differentially in physiologic and pathologic states. In physiologic states, exogenous leptin has been shown to decrease carbohydrate absorption and to increase the absorption of small peptides by the PepT1 di-/tripeptide transporter. In certain pathologic states, leptin has been shown to increase absorption of carbohydrates, proteins, and fat. Leptin has been shown to be upregulated in the colonic mucosa in patients with inflammatory bowel disease. Leptin stimulates gut mucosal cell proliferation and inhibits apoptosis. These functions have led to speculation about the role of leptin in tumorigenesis in the gastrointestinal tract, which is complicated by the multiple immunoregulatory effects of leptin. Conclusion Leptin is an important modulator of major aspects of gastrointestinal tract functions, independent of its more well-described roles in appetite regulation and obesity. PMID:20947298

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.

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.

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

Economic and hydraulic divergences underpin ecological differentiation in the Bromeliaceae.

PubMed

Males, Jamie; Griffiths, Howard

2018-01-01

Leaf economic and hydraulic theories have rarely been applied to the ecological differentiation of speciose herbaceous plant radiations. The role of character trait divergences and network reorganization in the differentiation of the functional types in the megadiverse Neotropical Bromeliaceae was explored by quantifying a range of leaf economic and hydraulic traits in 50 diverse species. Functional types, which are defined by combinations of C 3 or Crassulacean acid metabolism (CAM) photosynthesis, terrestrial or epiphytic habits, and non-specialized, tank-forming or atmospheric morphologies, segregated clearly in trait space. Most classical leaf economic relationships were supported, but they were weakened by the presence of succulence. Functional types differed in trait-network architecture, suggesting that rewiring of trait-networks caused by innovations in habit and photosynthetic pathway is an important aspect of ecological differentiation. The hydraulic data supported the coupling of leaf hydraulics and gas exchange, but not the hydraulic safety versus efficiency hypothesis, and hinted at an important role for the extra-xylary compartment in the control of bromeliad leaf hydraulics. Overall, our findings highlight the fundamental importance of structure-function relationships in the generation and maintenance of ecological diversity. © 2017 The Authors Plant, Cell & Environment Published by John Wiley & Sons Ltd.

Brain Structure and Resting-State Functional Connectivity in University Professors with High Academic Achievement

ERIC Educational Resources Information Center

Li, Weiwei; Yang, Wenjing; Li, Wenfu; Li, Yadan; Wei, Dongtao; Li, Huimin; Qiu, Jiang; Zhang, Qinglin

2015-01-01

Creative persons play an important role in technical innovation and social progress. There is little research on the neural correlates with researchers with high academic achievement. We used a combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity analysis, rsFC) approach to examine the…

Methods and Models for the Construction of Weakly Parallel Tests. Research Report 90-4.

ERIC Educational Resources Information Center

Adema, Jos J.

Methods are proposed for the construction of weakly parallel tests, that is, tests with the same test information function. A mathematical programing model for constructing tests with a prespecified test information function and a heuristic for assigning items to tests such that their information functions are equal play an important role in the…

The effect of claustrum lesions on human consciousness and recovery of function.

PubMed

Chau, Aileen; Salazar, Andres M; Krueger, Frank; Cristofori, Irene; Grafman, Jordan

2015-11-01

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness. Copyright © 2015 Elsevier Inc. All rights reserved.

[Friend or Foe in the Pocket? - The Role of the Individual, Peergroup and Parents for (dys)functional Mobile Phone Use].

PubMed

Knop, Karin; Hefner, Dorothée

2018-02-01

Friend or Foe in the Pocket? - The Role of the Individual, Peergroup and Parents for (dys)functional Mobile Phone Use In order to provide consultative support to parents as well as to children and young people, background knowledge regarding the motives of mobile phone use, functions of usage, comprehension of the attraction of this all-round medium also as knowledge about potential hazards are essential. This study offers empirical results about potentials and risks. The peergroup plays an important role for riskful and problematic mobile phone involvement. Parents function as a role model and the explicit parental mediation practices and their impact on the child are in focus. Data was acquired from a quota-sample survey with 500 children between the age of 8 and 14 years and one of their parents, qualitative interviews (20 children and their parents) and eight peergroup-discussions (52 participants). The present paper illuminates the above mentioned aspects and derives implications for guidance practice.

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).

A Copyright Primer for Small Undergraduate Libraries

ERIC Educational Resources Information Center

Cottrell, Terry

2010-01-01

Campus librarians play a central role in conversations revolving around copyright compliance. The sheer volume of information provided within library physical and virtual spaces affirms the role libraries play in current copyright debates. Regardless of the function of librarians on any particular campus, it is important to confront the myriad of…

Sustainability in Recruitment and Selection: Building a Framework of Practices

ERIC Educational Resources Information Center

Jepsen, Denise M.; Grob, Suzanne

2015-01-01

Much has been written about the role of human resources professionals in creating sustainable organizations. However, despite recognition that organizational human resources functions have an important role to play in sustainability, researchers tend to focus on strategic issues and sustainability. This higher-order focus has often meant that…

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.

The role of NSD family histone lysine methyltransferases in cancer

PubMed Central

Bennett, Richard L.; Swaroop, Alok; Troche, Catalina; Licht, Jonathan D.

2017-01-01

The Nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyl transferases is comprised of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1). These enzymes recognize and catalyze methylation of histone lysine marks to regulate chromatin integrity and gene expression. The growing number of reports demonstrating that alterations or translocations of these genes fundamentally affect cell growth and differentiation leading to developmental defects illustrates the importance of this family. In addition, overexpression, gain of function somatic mutations and translocations of NSDs are associated with human cancer and can trigger cellular transformation in model systems. Here we review the functions of NSD family members and the accumulating evidence that these proteins play key roles in tumorigenesis. Since epigenetic therapy is an important emerging anti-cancer strategy, understanding the function of NSD family members may lead to the development of novel therapies. PMID:28193767

Non-metabolic functions of glycolytic enzymes in tumorigenesis.

PubMed

Yu, X; Li, S

2017-05-11

Cancer cells reprogram their metabolism to meet the requirement for survival and rapid growth. One hallmark of cancer metabolism is elevated aerobic glycolysis and reduced oxidative phosphorylation. Emerging evidence showed that most glycolytic enzymes are deregulated in cancer cells and play important roles in tumorigenesis. Recent studies revealed that all essential glycolytic enzymes can be translocated into nucleus where they participate in tumor progression independent of their canonical metabolic roles. These noncanonical functions include anti-apoptosis, regulation of epigenetic modifications, modulation of transcription factors and co-factors, extracellular cytokine, protein kinase activity and mTORC1 signaling pathway, suggesting that these multifaceted glycolytic enzymes not only function in canonical metabolism but also directly link metabolism to epigenetic and transcription programs implicated in tumorigenesis. These findings underscore our understanding about how tumor cells adapt to nutrient and fuel availability in the environment and most importantly, provide insights into development of cancer therapy.

Placental sulphate transport: a review of functional and molecular studies.

PubMed

Shennan, D B

2012-08-01

Sulphate is required by the feto-placental unit for a number of important conjugation and biosynthetic pathways. Functional studies performed several decades ago established that sulphate transport in human placental microvillus and basal membrane vesicles was mainly via a DIDS-sensitive anion-exchange mechanism. In contrast, no evidence was found for Na⁺-dependent transport. Studies performed using isolated human placental tissue confirmed anion-exchange as the main mechanism. More recently, molecular studies have established the presence of anion-exchange proteins which could play a role in transplacental sulphate movement. However, the presence of transcripts for NaS2 has been reported and has prompted the suggestion that Na⁺-sulphate cotransport may play an important role in maternal-fetal sulphate transport. This article reviews our present knowledge of placental sulphate transport, both functional and molecular, and attempts to form a model based on the available evidence. Copyright © 2012 Elsevier Ltd. All rights reserved.

Emergence of complex chemistry on an organic monolayer.

PubMed

Prins, Leonard J

2015-07-21

In many origin-of-life scenarios, inorganic materials, such as FeS or mineral clays, play an important role owing to their ability to concentrate and select small organic molecules on their surface and facilitate their chemical transformations into new molecules. However, considering that life is made up of organic matter, at a certain stage during the evolution the role of the inorganic material must have been taken over by organic molecules. How this exactly happened is unclear, and, indeed, a big gap separates the rudimentary level of organization involving inorganic materials and the complex organization of cells, which are the building blocks of life. Over the past years, we have extensively studied the interaction of small molecules with monolayer-protected gold nanoparticles (Au NPs) for the purpose of developing innovative sensing and catalytic systems. During the course of these studies, we realized that the functional role of this system is very similar to that typically attributed to inorganic surfaces in the early stages of life, with the important being difference that the functional properties (molecular recognition, catalysis, signaling, adaptation) originate entirely from the organic monolayer rather than the inorganic support. This led us to the proposition that this system may serve as a model that illustrates how the important role of inorganic surfaces in dictating chemical processes in the early stages of life may have been taken over by organic matter. Here, we reframe our previously obtained results in the context of the origin-of-life question. The following functional roles of Au NPs will be discussed: the ability to concentrate small molecules and create different local populations, the ability to catalyze the chemical transformation of bound molecules, and, finally, the ability to install rudimentary signaling pathways and display primitive adaptive behavior. In particular, we will show that many of the functional properties of the system originate from two features: the presence of metal ions that are complexed in the organic monolayer and the multivalent nature of the system. Complexed metal ions play an important role in determining the affinity and selectivity of the interaction with small molecules, but serve also as regulatory elements for determining how many molecules are bound simultaneously. Importantly, neighboring metal ion complexes also create catalytic pockets in which two metal ions cooperatively catalyze the cleavage of an RNA-model compound. The multivalent nature of the system permits multiple noncovalent interactions with small molecules that enhances the affinity, but is also at the basis of simple signal transduction pathways and adaptive behavior.

Proteins and Their Interacting Partners: An Introduction to Protein-Ligand Binding Site Prediction Methods.

PubMed

Roche, Daniel Barry; Brackenridge, Danielle Allison; McGuffin, Liam James

2015-12-15

Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein-ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein-ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein-ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

Perceived reciprocity in social exchange and health functioning in early old age: prospective findings from the GAZEL study.

PubMed

Wahrendorf, Morten; Ribet, Celine; Zins, Marie; Goldberg, Marcel; Siegrist, Johannes

2010-05-01

To assess prospectively the effects of perceived non-reciprocity of exchange in three different types of social engagement on health functioning in early old age. In the frame of the prospective French GAZEL cohort study, data on reciprocity in three types of role-related social engagement (principal regular activity in everyday life, marital role relationship, trusting relationships in civic life) were collected from 8679 men and 2742 women (mean age: 60.4 years) in 2005. Two years later, health functioning was assessed using the SF-36 mental and physical component scores, as well as self-perceived health. Multivariate regressions were calculated, controlling for important confounders including baseline self-perceived health. Consistent effects of perceived non-reciprocity in all three types of social exchange on mental and physical health functioning were observed. After adjustment for relevant confounders including baseline self-perceived, health effects were attenuated, but largely remained significant. Findings underline the importance of the quality of social exchange (reciprocity vs. non-reciprocity) for health functioning in early old age.

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

PubMed

Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-12-01

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

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

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.

RNA-Sequencing Analysis Reveals a Regulatory Role for Transcription Factor Fezf2 in the Mature Motor Cortex

PubMed Central

Clare, Alison J.; Wicky, Hollie E.; Empson, Ruth M.; Hughes, Stephanie M.

2017-01-01

Forebrain embryonic zinc finger (Fezf2) encodes a transcription factor essential for the specification of layer 5 projection neurons (PNs) in the developing cerebral cortex. As with many developmental transcription factors, Fezf2 continues to be expressed into adulthood, suggesting it remains crucial to the maintenance of neuronal phenotypes. Despite the continued expression, a function has yet to be explored for Fezf2 in the PNs of the developed cortex. Here, we investigated the role of Fezf2 in mature neurons, using lentiviral-mediated delivery of a shRNA to conditionally knockdown the expression of Fezf2 in the mouse primary motor cortex (M1). RNA-sequencing analysis of Fezf2-reduced M1 revealed significant changes to the transcriptome, identifying a regulatory role for Fezf2 in the mature M1. Kyoto Encyclopedia Genes and Genomes (KEGG) pathway analyses of Fezf2-regulated genes indicated a role in neuronal signaling and plasticity, with significant enrichment of neuroactive ligand-receptor interaction, cell adhesion molecules and calcium signaling pathways. Gene Ontology analysis supported a functional role for Fezf2-regulated genes in neuronal transmission and additionally indicated an importance in the regulation of behavior. Using the mammalian phenotype ontology database, we identified a significant overrepresentation of Fezf2-regulated genes associated with specific behavior phenotypes, including associative learning, social interaction, locomotor activation and hyperactivity. These roles were distinct from that of Fezf2-regulated genes identified in development, indicating a dynamic transition in Fezf2 function. Together our findings demonstrate a regulatory role for Fezf2 in the mature brain, with Fezf2-regulated genes having functional roles in sustaining normal neuronal and behavioral phenotypes. These results support the hypothesis that developmental transcription factors are important for maintaining neuron transcriptomes and that disruption of their expression could contribute to the progression of disease phenotypes. PMID:28936162

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.

Acidic Ca2+ stores in neurodegeneration

PubMed Central

Lloyd-Evans, Emyr

2017-01-01

Lysosomes have emerged in the last decade as an immensely important intracellular site of Ca2+ storage and signalling. More recently there has been an increase in the number of new ion channels found to be functional on lysosomes and the potential roles that these signalling pathways might play in fundamental cellular processes are being uncovered. Defects in lysosomal function have been shown to result in changes in lysosomal Ca2+ homeostasis and ultimately can result in cell death. Several neurodegenerative diseases, from rare lysosomal storage diseases through to more common diseases of ageing, have recently been identified as having alterations in lysosomal Ca2+ homeostasis that may play an important role in neuronal excitotoxicity and ultimately cell death. This review will critically summarise these recent findings. PMID:28593104

Fathers Matter: The Role of Father Autonomy Support and Control in Preschoolers' Executive Function Development

PubMed Central

Meuwissen, Alyssa S.; Carlson, Stephanie M.

2015-01-01

Although previous work has shown that mothers' parenting influences the development of child executive function (important self-control skills developed in the preschool years) the role of fathers' parenting has not been thoroughly investigated. We observed fathers' autonomy support and control in dyadic play with their 3-year-old children (N pairs = 110), and measured father and child EF independently with laboratory tasks. We found that fathers' controlling parenting was significantly inversely related to the child EF composite, above and beyond family income and child verbal ability. These results are consistent with the hypothesis that fathers are important for the development of EF in their children, and suggest fathers should be included in both research and parenting interventions. PMID:26209884

The R-spondin family of proteins: emerging regulators of WNT signaling

PubMed Central

Jin, Yong-Ri; Yoon, Jeong Kyo

2012-01-01

Recently, the R-spondin (RSPO) family of proteins has emerged as important regulators of WNT signaling. Considering the wide spectrum of WNT signaling functions in normal biological processes and disease conditions, there has been a significantly growing interest in understanding the functional roles of RSPOs in multiple biological processes and determining the molecular mechanisms by which RSPOs regulate the WNT signaling pathway. Recent advances in the RSPO research field revealed some of the in vivo functions of RSPOs and provided new information regarding the mechanistic roles of RSPO activity in regulation of WNT signaling. Herein, we review recent progress in RSPO research with an emphasis on signaling mechanisms and biological functions. PMID:22982762

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.

[Epidemiology of infections after liver transplantation in children].

PubMed

Pawłowska, J

2001-01-01

One of the most important problems after solid organ transplantation including liver, remains infections. Multiple risk factors play a role among which the most important are: general patients health before transplantation, prolong operative time, graft function and type of immunosuppression. The most important problems with bacterial, fungal and viral infections was described as well as treatment and profilaxis.

Physiology in perspective: The Wisdom of the Body. Neural control of the kidney.

PubMed

DiBona, Gerald F

2005-09-01

Cannon equated the fluid matrix of the body with Bernard's concept of the internal environment and emphasized the importance of "the safe-guarding of an effective fluid matrix." He further emphasized the important role of the autonomic nervous system in the establishment and maintenance of homeostasis in the internal environment. This year's Cannon Lecture discusses the important role of the renal sympathetic nerves to regulate various aspects of overall renal function and to serve as one of the major "self-regulatory agencies which operate to preserve the constancy of the fluid matrix."

Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

PubMed Central

Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

2011-01-01

Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

Electrophysiology and Beyond: Multiple roles of Na+ channel β subunits in development and disease

PubMed Central

Patino, Gustavo A.; Isom, Lori L.

2010-01-01

Voltage-gated Na+ channel (VGSC) β subunits are not “auxiliary.” These multifunctional molecules not only modulate Na+ current (INa), but also function as cell adhesion molecules (CAMs) – playing roles in aggregation, migration, invasion, neurite outgrowth, and axonal fasciculation. β subunits are integral members of VGSC signaling complexes at nodes of Ranvier, axon initial segments, and cardiac intercalated disks, regulating action potential propagation through critical intermolecular and cell-cell communication events. At least in vitro, many β subunit cell adhesive functions occur both in the presence and absence of pore-forming VGSC α subunits, and in vivo β subunits are expressed in excitable as well as non-excitable cells, thus β subunits may play important functional roles on their own, in the absence of α subunits. VGSC β1 subunits are essential for life and appear to be especially important during brain development. Mutations in β subunit genes result in a variety of human neurological and cardiovascular diseases. Moreover, some cancer cells exhibit alterations in β subunit expression during metastasis. In short, these proteins, originally thought of as merely accessory to α subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC β subunits in the nervous system. PMID:20600605

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

Important roles of P2Y receptors in the inflammation and cancer of digestive system.

PubMed

Wan, Han-Xing; Hu, Jian-Hong; Xie, Rei; Yang, Shi-Ming; Dong, Hui

2016-05-10

Purinergic signaling is important for many biological processes in humans. Purinoceptors P2Y are widely distributed in human digestive system and different subtypes of P2Y receptors mediate different physiological functions from metabolism, proliferation, differentiation to apoptosis etc. The P2Y receptors are essential in many gastrointestinal functions and also involve in the occurrence of some digestive diseases. Since different subtypes of P2Y receptors are present on the same cell of digestive organs, varying subtypes of P2Y receptors may have opposite or synergetic functions on the same cell. Recently, growing lines of evidence strongly suggest the involvement of P2Y receptors in the pathogenesis of several digestive diseases. In this review, we will focus on their important roles in the development of digestive inflammation and cancer. We anticipate that as the special subtypes of P2Y receptors are studied in depth, specific modulators for them will have good potentials to become promising new drugs to treat human digestive diseases in the near future.

Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development

PubMed Central

2010-01-01

Background The J-domain-containing protein auxilin, a critical regulator in clathrin-mediated transport, has been implicated in Drosophila Notch signaling. To ask if this role of auxilin is conserved and whether auxilin has additional roles in development, we have investigated the functions of auxilin orthologs in zebrafish. Results Like mammals, zebrafish has two distinct auxilin-like molecules, auxilin and cyclin G-associated kinase (GAK), differing in their domain structures and expression patterns. Both zebrafish auxilin and GAK can functionally substitute for the Drosophila auxilin, suggesting that they have overlapping molecular functions. Still, they are not completely redundant, as morpholino-mediated knockdown of the ubiquitously expressed GAK alone can increase the specification of neuronal cells, a known Notch-dependent process, and decrease the expression of Her4, a Notch target gene. Furthermore, inhibition of GAK function caused an elevated level of apoptosis in neural tissues, resulting in severe degeneration of neural structures. Conclusion In support of the notion that endocytosis plays important roles in Notch signaling, inhibition of zebrafish GAK function affects embryonic neuronal cell specification and Her4 expression. In addition, our analysis suggests that zebrafish GAK has at least two functions during the development of neural tissues: an early Notch-dependent role in neuronal patterning and a late role in maintaining the survival of neural cells. PMID:20082716

The role of non-need factors in individual GP utilisation analysis and their implications for the pursuance of equity: a cross-country comparison.

PubMed

McGregor, P; McKee, P; O'Neill, C

2008-05-01

A substantial amount of health care resources is allocated within the UK using formulae that relate funding to measures of population need. The aim of this paper is to demonstrate the importance of non-need factors in determining utilisation of services at an individual level and explore the implications inclusion of such factors has in the consideration of equity. In the paper we develop a utility model that accords a role to non-health factors in the determination of service use. A series of functions incorporating non-health factors as explanatory variables in GP utilisation functions are estimated using data from the British Household Panel Survey. The functions are decomposed to ascertain the role of service structure and examine the role of income across the four countries of the UK in explaining utilisation. The implications of our findings for the pursuance of equity in the NHS when individual choice has an explicit role are discussed.

NK cell recruitment and exercise: Potential immunotherapeutic role of shear stress and endothelial health.

PubMed

Evans, William

2017-11-01

Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium. Additionally, shear stress may play a role in improving NK cell function by decreasing oxidative stress. The relationship between shear stress and NK cell count and function can be tested by utilizing exercise and local heating with cuff inflation. If shear stress does play an important role, NK cell count and function will be improved in the non-cuffed exercise group, but not the cuffed limb. This paper will explore the mechanisms potentially explaining exercise-induced improvements in NK cell count and function, and propose a model for investigating these mechanisms. This mechanistic insight could aid in providing a novel, safe, relatively inexpensive, and non-invasive target for immunotherapy in cancer patients. Copyright © 2017. Published by Elsevier Ltd.

Strong Poison Revisited

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

Prince, R.C.; Gailer, J.; Gunson, D.E.

2009-06-04

Selenium in the form of selenocysteine plays an essential role in a number of proteins, but its role in non-enzymatic biochemistry is also important. In this short review we discuss the interactions between inorganic selenium, arsenic and mercury under physiological conditions, especially in the presence of glutathione. This chemistry is obviously important in making the arsenic and mercury unavailable for more toxic interactions, but in the process it suggests that a side-effect of chronic arsenic and/or mercury exposure is likely to be functional selenium deficiency.

[Neurological and psychiatric aspects of some endocrine diseases. The role of neurosteroids and neuroactive steroids].

PubMed

Aszalós, Zsuzsa

2007-10-14

Regardless of their origin, neuroactive steroids are capable of modifying neural activities by modulating different types of membrane receptors. Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic enzymes are found in the central nervous system. Classical steroid receptors are localized in the cytoplasm, they exert regulatory actions on the genome, and their activation causes medium- and long-term effects. Non-classical receptors are located within the membrane and act as mediators of short-term effects. Other important players are co-repressors and co-activators that can interfere with or enhance the activity of steroid receptors. Beyond their function in stress, corticosteroids play a very important role in fear, anxiety, and memory functions. Patients with Cushing's syndrome frequently develop mood disorder, reversible brain atrophy with transient memory loss, rarely delirium or psychosis. Well-known peripheral symptom is steroidal myopathy. In patients with Addison's disease the main signs are weakness of muscles, lack of energy, decreased mental functions and reduced quality of life. Estrogen and progesterone have their own respective hormone receptors, whereas allopregnanolone acts via the GABA receptors. These hormones have significant role in the development of brain, the architecture of neural circuits and dendrites, density of axonal connections, and the number of neurons. They influence maturation, neuroprotection, seizures, cognitive functions, mood, anxiety, pain, and restitution of peripheral nerves. Androgens also affect cognitive functions, pain, anxiety, mood, and additionally aggression.

The roles of gender, age and cognitive development in children's pedestrian route selection.

PubMed

Barton, B K; Ulrich, T; Lyday, B

2012-03-01

Thousands of American children under the age of 10 years are injured annually as pedestrians. Despite the scope of this public health problem, knowledge about behavioural control and developmental factors involved in the aetiology of child pedestrian safety is limited. The present study examined the roles of gender, age and two aspects of cognitive development (visual search and efficiency of processing) in children's safe pedestrian route selection. Measures of cognitive functioning (visual search and efficiency) and selections of risky pedestrian routes were collected from 65 children aged 5-9 years. Boys, younger children and those with less developed cognitive functioning selected riskier pedestrian routes. Cognitive functioning also subsumed age as a predictor of risky route selections. Our findings suggest developmental differences, specifically less developed cognitive functioning, play important roles in children's pedestrian decision making. Directions for future examination are discussed. © 2011 Blackwell Publishing Ltd.

Indications for quantum computation requirements from comparative brain analysis

NASA Astrophysics Data System (ADS)

Bernroider, Gustav; Baer, Wolfgang

2010-04-01

Whether or not neuronal signal properties can engage 'non-trivial', i.e. functionally significant, quantum properties, is the subject of an ongoing debate. Here we provide evidence that quantum coherence dynamics can play a functional role in ion conduction mechanism with consequences on the shape and associative character of classical membrane signals. In particular, these new perspectives predict that a specific neuronal topology (e.g. the connectivity pattern of cortical columns in the primate brain) is less important and not really required to explain abilities in perception and sensory-motor integration. Instead, this evidence is suggestive for a decisive role of the number and functional segregation of ion channel proteins that can be engaged in a particular neuronal constellation. We provide evidence from comparative brain studies and estimates of computational capacity behind visual flight functions suggestive for a possible role of quantum computation in biological systems.

A painful reminder: the role of level and salience of attitude importance in cognitive dissonance.

PubMed

Starzyk, Katherine B; Fabrigar, Leandre R; Soryal, Ashley S; Fanning, Jessie J

2009-01-01

In his seminal book, L. Festinger (1957) emphasized the role of attitude importance in cognitive dissonance. This study (N = 308) explored whether people's use of dissonance reduction strategies differs as a function of level of attitude importance and whether the personal importance of an attitude is salient. Results showed that level and salience of attitude importance interacted to affect high-choice (HC) participants' tendency to use attitude change and trivialization to reduce dissonance. When HC participants were not reminded of the personal importance of their attitude (i.e., it was not salient), they changed their attitudes equally irrespective of attitude importance, but engaged in greater trivialization with increasing levels of importance. In contrast, when attitude importance was salient, HC participants changed their attitudes less with increasing attitude importance and showed no evidence of trivializing under any level of importance.

Self-efficacy: Implications for Physical Activity, Function, and Functional Limitations in Older Adults.

PubMed

McAuley, Edward; Szabo, Amanda; Gothe, Neha; Olson, Erin A

2011-07-01

Attenuating the physical decline and increases in disability associated with the aging process is an important public health priority. Evidence suggests that regular physical activity participation improves functional performance, such as walking, standing balance, flexibility, and getting up out of a chair, and also plays an important role in the disablement process by providing a protective effect against functional limitations. Whether these effects are direct or indirect has yet to be reliably established. In this review, the authors take the perspective that such relationships are indirect and operate through self-efficacy expectations. They first provide an introduction to social cognitive theory followed by an overview of self-efficacy's reciprocal relationship with physical activity. They then consider the literature that documents the effects of physical activity on functional performance and functional limitations in older adults and the extent to which self-efficacy might mediate these relationships. Furthermore, they also present evidence that suggests that self-efficacy plays a pivotal role in a model in which the protective effects conferred by physical activity on functional limitations operate through functional performance. The article concludes with a brief section making recommendations for the development of strategies within physical activity and rehabilitative programs for maximizing the major sources of efficacy information.

Self-efficacy: Implications for Physical Activity, Function, and Functional Limitations in Older Adults

PubMed Central

McAuley, Edward; Szabo, Amanda; Gothe, Neha; Olson, Erin A.

2013-01-01

Attenuating the physical decline and increases in disability associated with the aging process is an important public health priority. Evidence suggests that regular physical activity participation improves functional performance, such as walking, standing balance, flexibility, and getting up out of a chair, and also plays an important role in the disablement process by providing a protective effect against functional limitations. Whether these effects are direct or indirect has yet to be reliably established. In this review, the authors take the perspective that such relationships are indirect and operate through self-efficacy expectations. They first provide an introduction to social cognitive theory followed by an overview of self-efficacy's reciprocal relationship with physical activity. They then consider the literature that documents the effects of physical activity on functional performance and functional limitations in older adults and the extent to which self-efficacy might mediate these relationships. Furthermore, they also present evidence that suggests that self-efficacy plays a pivotal role in a model in which the protective effects conferred by physical activity on functional limitations operate through functional performance. The article concludes with a brief section making recommendations for the development of strategies within physical activity and rehabilitative programs for maximizing the major sources of efficacy information. PMID:24353482

Uridine Nucleoside Thiation: Gas-Phase Structures and Energetics

NASA Astrophysics Data System (ADS)

Hamlow, Lucas; Lee, Justin; Rodgers, M. T.; Berden, Giel; Oomens, Jos

2016-06-01

The naturally occurring thiated uridine nucleosides, 4-thiouridine (s4Urd) and 2-thiouridine (s2Urd), play important roles in the function and analysis of a variety of RNAs. 2-Thiouridine and its C5 modified analogues are commonly found in tRNAs and are believed to play an important role in codon recognition possibly due to their different structure, which has been shown by NMR to be predominantly C3'-endo. 2-Thiouridine may also play an important role in facilitating nonenzymatic RNA replication and transcription. 4-Thiouridine is a commonly used photoactivatable crosslinker that is often used to study RNA-RNA and RNA-protein cross-linking behavior. Differences in the base pairing between uracil and 4-thiouracil with adenine and guanine are an important factor in their role as a cross linker. The photoactivity of s4Urd may also aid in preventing near-UV lethality in cells. An understanding of their intrinsic structure in the gas-phase may help further elucidate the roles these modified nucleosides play in the regulation of RNAs. In this work, infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of s2Urd and s4Urd were collected in the IR fingerprint region. Structural information is determined by comparison with theoretical linear IR spectra generated from density functional theory calculations using molecular modeling to generate low-energy candidate structures. Present results are compared with analogous results for the protonated forms of uridine and 2'-deoxyuridine as well as solution phase NMR data and crystal structures.

Adenosine A2A receptor inhibition restores the normal transport of endothelial glutamate transporters in the brain.

PubMed

Bai, Wei; Li, Ping; Ning, Ya-Lei; Peng, Yan; Xiong, Ren-Ping; Yang, Nan; Chen, Xing; Zhou, Yuan-Guo

2018-04-15

Excitatory amino acid transporters (EAATs) on cerebral vascular endothelial cells play an important role in maintaining glutamate homeostasis in the brain. The dysfunction of endothelial EAATs is an important reason for the dramatically elevated brain glutamate levels after brain injury, such as traumatic brain injury (TBI). The adenosine A 2A receptor (A 2A R) plays an important role in regulating the brain glutamate level after brain injury; however, researchers have not clearly determined whether this role was related to its ability to regulate endothelial EAATs. Activation of A 2A R in vitro not only decreased the PKA- and glutamate level-dependent strengthening of the interaction between NKA-α1 and the FXYD1 subunit and the subsequent decrease in the activity of Na + /K + -ATPases (NKAs) but also enhanced its interaction with EAATs and ultimately aggravated the reverse transport function of endothelial EAATs under oxygen-glucose deprivation (OGD) conditions. Conversely, inhibition of A 2A R restored the normal transport of EAAT. Moreover, A 2A R inhibition increased NKA activity and decreased its interaction with EAATs in isolated brain capillaries after TBI, further confirming its role in endothelial EAATs in vivo. Based on our results, A 2A R played an important role in regulating endothelial EAAT function, and strategies that restore the normal transport of endothelial EAATs through the inhibition of A 2A R might serve as an effective treatment for brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Sulfur amino acids are necessary for normal intestinal mucosal growth in neonatal piglets

USDA-ARS?s Scientific Manuscript database

Sulfur amino acids (SAAs) methionine and cysteine play important metabolic and functional role in human health and disease. Gastrointestinal tract is an important site of transmethylation and transsulfuration of methionine and metabolizes approx. 20% of the dietary methionine intake (Riedijk et al. ...

The impact of Polycomb group (PcG) and Trithorax group (TrxG) epigenetic factors in plant plasticity.

PubMed

de la Paz Sanchez, Maria; Aceves-García, Pamela; Petrone, Emilio; Steckenborn, Stefan; Vega-León, Rosario; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana; García-Ponce, Berenice

2015-11-01

Current advances indicate that epigenetic mechanisms play important roles in the regulatory networks involved in plant developmental responses to environmental conditions. Hence, understanding the role of such components becomes crucial to understanding the mechanisms underlying the plasticity and variability of plant traits, and thus the ecology and evolution of plant development. We now know that important components of phenotypic variation may result from heritable and reversible epigenetic mechanisms without genetic alterations. The epigenetic factors Polycomb group (PcG) and Trithorax group (TrxG) are involved in developmental processes that respond to environmental signals, playing important roles in plant plasticity. In this review, we discuss current knowledge of TrxG and PcG functions in different developmental processes in response to internal and environmental cues and we also integrate the emerging evidence concerning their function in plant plasticity. Many such plastic responses rely on meristematic cell behavior, including stem cell niche maintenance, cellular reprogramming, flowering and dormancy as well as stress memory. This information will help to determine how to integrate the role of epigenetic regulation into models of gene regulatory networks, which have mostly included transcriptional interactions underlying various aspects of plant development and its plastic response to environmental conditions. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Gas what: NO is not the only answer to sexual function

PubMed Central

Yetik-Anacak, G; Sorrentino, R; Linder, A E; Murat, N

2015-01-01

The ability to get and keep an erection is important to men for several reasons and the inability is known as erectile dysfunction (ED). ED has started to be accepted as an early indicator of systemic endothelial dysfunction and subsequently of cardiovascular diseases. The role of NO in endothelial relaxation and erectile function is well accepted. The discovery of NO as a small signalling gasotransmitter led to the investigation of the role of other endogenously derived gases, carbon monoxide (CO) and hydrogen sulphide (H2S) in physiological and pathophysiological conditions. The role of NO and CO in sexual function and dysfunction has been investigated more extensively and, recently, the involvement of H2S in erectile function has also been confirmed. In this review, we focus on the role of these three sister gasotransmitters in the physiology, pharmacology and pathophysiology of sexual function in man, specifically erectile function. We have also reviewed the role of soluble guanylyl cyclase/cGMP pathway as a common target of these gasotransmitters. Several studies have proposed alternative therapies targeting different mechanisms in addition to PDE-5 inhibition for ED treatment, since some patients do not respond to these drugs. This review highlights complementary and possible coordinated roles for these mediators and treatments targeting these gasotransmitters in erectile function/ED. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:24661203

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

PubMed Central

Jeschke, Marc G

2009-01-01

Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury. PMID:19603107

New Insights into the Role of Zinc Acquisition and Zinc Tolerance in Group A Streptococcal Infection.

PubMed

Ong, Cheryl-Lynn Y; Berking, Olga; Walker, Mark J; McEwan, Alastair G

2018-06-01

Zinc plays an important role in host innate immune function. However, the innate immune system also utilizes zinc starvation ("nutritional immunity") to combat infections. Here, we investigate the role of zinc import and export in the protection of Streptococcus pyogenes (group A Streptococcus ; GAS), a Gram-positive bacterial pathogen responsible for a wide spectrum of human diseases, against challenge from host innate immune defense. In order to determine the role of GAS zinc import and export during infection, we utilized zinc import (Δ adcA Δ adcAII ) and export (Δ czcD ) deletion mutants in competition with the wild type in both in vitro and in vivo virulence models. We demonstrate that nutritional immunity is deployed extracellularly, while zinc toxicity is utilized upon phagocytosis of GAS by neutrophils. We also show that lysosomes and azurophilic granules in neutrophils contain zinc stores for use against intracellular pathogens. Copyright © 2018 American Society for Microbiology.

An emerging role for p21-activated kinases (Paks) in viral infections.

PubMed

Van den Broeke, Celine; Radu, Maria; Chernoff, Jonathan; Favoreel, Herman W

2010-03-01

p21-activated protein kinases (Paks) are cytosolic serine/threonine protein kinases that act as effectors for small (p21) GTPases of the Cdc42 and Rac families. It has long been established that Paks play a major role in a host of vital cellular functions such as proliferation, survival and motility, and abnormal Pak function is associated with a number of human diseases. Here, we discuss emerging evidence that these enzymes also play a major role in the entry, replication and spread of many important pathogenic human viruses, including HIV. Careful assessment of the potential role of Paks in antiviral immunity will be pivotal to evaluate thoroughly the potential of agents that inhibit Pak as a new class of anti-viral therapeutics.

Drosophila Ana1 is required for centrosome assembly and centriole elongation.

PubMed

Saurya, Saroj; Roque, Hélio; Novak, Zsofia A; Wainman, Alan; Aydogan, Mustafa G; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano; Raff, Jordan W

2016-07-01

Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP-Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. © 2016. Published by The Company of Biologists Ltd.

Beadex Function in the Motor Neurons Is Essential for Female Reproduction in Drosophila melanogaster

PubMed Central

Kairamkonda, Subhash; Nongthomba, Upendra

2014-01-01

Drosophila melanogaster has served as an excellent model system for understanding the neuronal circuits and molecular mechanisms regulating complex behaviors. The Drosophila female reproductive circuits, in particular, are well studied and can be used as a tool to understand the role of novel genes in neuronal function in general and female reproduction in particular. In the present study, the role of Beadex, a transcription co-activator, in Drosophila female reproduction was assessed by generation of mutant and knock down studies. Null allele of Beadex was generated by transposase induced excision of P-element present within an intron of Beadex gene. The mutant showed highly compromised reproductive abilities as evaluated by reduced fecundity and fertility, abnormal oviposition and more importantly, the failure of sperm release from storage organs. However, no defect was found in the overall ovariole development. Tissue specific, targeted knock down of Beadex indicated that its function in neurons is important for efficient female reproduction, since its neuronal knock down led to compromised female reproductive abilities, similar to Beadex null females. Further, different neuronal class specific knock down studies revealed that Beadex function is required in motor neurons for normal fecundity and fertility of females. Thus, the present study attributes a novel and essential role for Beadex in female reproduction through neurons. PMID:25396431

Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis.

PubMed

Chen, Xi

2015-01-01

The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. © 2015 Elsevier Inc. All rights reserved.

A dual role for integrin-linked kinase in platelets: regulating integrin function and α-granule secretion

PubMed Central

Sage, Tanya; Stevens, Joanne M.; Jordan, Peter A.; Jones, Sarah; Barrett, Natasha E.; St-Arnaud, Rene; Frampton, Jonathan; Dedhar, Shoukat; Gibbins, Jonathan M.

2008-01-01

Integrin-linked kinase (ILK) has been implicated in the regulation of a range of fundamental biological processes such as cell survival, growth, differentiation, and adhesion. In platelets ILK associates with β1- and β3-containing integrins, which are of paramount importance for the function of platelets. Upon stimulation of platelets this association with the integrins is increased and ILK kinase activity is up-regulated, suggesting that ILK may be important for the coordination of platelet responses. In this study a conditional knockout mouse model was developed to examine the role of ILK in platelets. The ILK-deficient mice showed an increased bleeding time and volume, and despite normal ultrastructure the function of ILK-deficient platelets was decreased significantly. This included reduced aggregation, fibrinogen binding, and thrombus formation under arterial flow conditions. Furthermore, although early collagen stimulated signaling such as PLCγ2 phosphorylation and calcium mobilization were unaffected in ILK-deficient platelets, a selective defect in α-granule, but not dense-granule, secretion was observed. These results indicate that as well as involvement in the control of integrin affinity, ILK is required for α-granule secretion and therefore may play a central role in the regulation of platelet function. PMID:18772455

The Role of Stakeholders Related to the Management of Ecological Function of Urban Green Open Space. Case Study: City of Depok, Indonesia

NASA Astrophysics Data System (ADS)

Mangopa Malik, Andy Anton

2017-12-01

Urban green open space is one of the assets that provide substantial benefits to the urban community. One important function of urban green open space is a function of ecology. This study will provide initial explanation on the various studies related to the ecological function of urban green open space. The study of urban space management approach related to ecological function will explain the extent of the role of stakeholders in the urban areas that will further strengthen the importance of the existence of green open space, especially in city of Depok. With so many problems related to the supply and use of green open space in the city of Depok. This approach was originally applied by the private sector and many applications made a great contribution, so it began to be used by the government in managing public assets there. This study will use descriptive method, at the beginning of the study will explain the existence of the reality of urban green open space as part of the urban space by viewing it from theoretical overview of space, function and role of the various problems that occur in it. The results of this study indicate there are six problems in the management of green open spaces in city of Depok. Using the stages in asset management will provide space for participation of existing stakeholders in the management of green open spaces in city of Depok.

The functional value of Caribbean coral reef, seagrass and mangrove habitats to ecosystem processes.

PubMed

Harborne, Alastair R; Mumby, Peter J; Micheli, Fiorenza; Perry, Christopher T; Dahlgren, Craig P; Holmes, Katherine E; Brumbaugh, Daniel R

2006-01-01

Caribbean coral reef habitats, seagrass beds and mangroves provide important goods and services both individually and through functional linkages. A range of anthropogenic factors are threatening the ecological and economic importance of these habitats and it is vital to understand how ecosystem processes vary across seascapes. A greater understanding of processes will facilitate further insight into the effects of disturbances and assist with assessing management options. Despite the need to study processes across whole seascapes, few spatially explicit ecosystem-scale assessments exist. We review the empirical literature to examine the role of different habitat types for a range of processes. The importance of each of 10 generic habitats to each process is defined as its "functional value" (none, low, medium or high), quantitatively derived from published data wherever possible and summarised in a single figure. This summary represents the first time the importance of habitats across an entire Caribbean seascape has been assessed for a range of processes. Furthermore, we review the susceptibility of each habitat to disturbances to investigate spatial patterns that might affect functional values. Habitat types are considered at the scale discriminated by remotely-sensed imagery and we envisage that functional values can be combined with habitat maps to provide spatially explicit information on processes across ecosystems. We provide examples of mapping the functional values of habitats for populations of three commercially important species. The resulting data layers were then used to generate seascape-scale assessments of "hot spots" of functional value that might be considered priorities for conservation. We also provide an example of how the literature reviewed here can be used to parameterise a habitat-specific model investigating reef resilience under different scenarios of herbivory. Finally, we use multidimensional scaling to provide a basic analysis of the overall functional roles of different habitats. The resulting ordination suggests that each habitat has a unique suite of functional values and, potentially, a distinct role within the ecosystem. This review shows that further data are required for many habitat types and processes, particularly forereef and escarpment habitats on reefs and for seagrass beds and mangroves. Furthermore, many data were collected prior to the regional mass mortality of Diadema and Acropora, and subsequent changes to benthic communities have, in many cases, altered a habitat's functional value, hindering the use of these data for parameterising maps and models. Similarly, few data exist on how functional values change when environmental parameters, such as water clarity, are altered by natural or anthropogenic influences or the effects of a habitat's spatial context within the seascape. Despite these limitations, sufficient data are available to construct maps and models to better understand tropical marine ecosystem processes and assist more effective mitigation of threats that alter habitats and their functional values.

Identification, RNAi Knockdown and Functional Analysis of an Ejaculate Protein that Mediates a Postmating, Prezgotic Phenotype in a cricket

USDA-ARS?s Scientific Manuscript database

Male ejaculate proteins, including both sperm and seminal fluid proteins, play an important role in mediating reproductive biology. The function of ejaculate proteins can include enabling sperm-egg interactions, enhancing sperm storage, mediating female attractiveness, and even regulating female lif...

Calmodulin gene expression in response to mechanical wounding and Botrytis cinerea infection in tomato fruit

USDA-ARS?s Scientific Manuscript database

Calmodulin, a ubiquitous calcium sensor, plays an important role in decoding the stress-triggered intracellular calcium changes and regulates the functions of numerous target proteins involved in various physiological responses in plants. To determine the functional significance of calmodulin in fl...

The Linkage between Community Services and College Development.

ERIC Educational Resources Information Center

Mays, Sylvia A.; Vogler, Daniel E.

1985-01-01

Provides a summary of a 1984 study of the importance of 40 functions for community college resource development officers. Concludes that development officers are responsible for making friends for the college in the community, sharing this responsibility with others. Sees a role for community services personnel in development functions. (AYC)

How lichens impact on terrestrial community and ecosystem properties.

PubMed

Asplund, Johan; Wardle, David A

2017-08-01

Lichens occur in most terrestrial ecosystems; they are often present as minor contributors, but in some forests, drylands and tundras they can make up most of the ground layer biomass. As such, lichens dominate approximately 8% of the Earth's land surface. Despite their potential importance in driving ecosystem biogeochemistry, the influence of lichens on community processes and ecosystem functioning have attracted relatively little attention. Here, we review the role of lichens in terrestrial ecosystems and draw attention to the important, but often overlooked role of lichens as determinants of ecological processes. We start by assessing characteristics that vary among lichens and that may be important in determining their ecological role; these include their growth form, the types of photobionts that they contain, their key functional traits, their water-holding capacity, their colour, and the levels of secondary compounds in their thalli. We then assess how these differences among lichens influence their impacts on ecosystem and community processes. As such, we consider the consequences of these differences for determining the impacts of lichens on ecosystem nutrient inputs and fluxes, on the loss of mass and nutrients during lichen thallus decomposition, and on the role of lichenivorous invertebrates in moderating decomposition. We then consider how differences among lichens impact on their interactions with consumer organisms that utilize lichen thalli, and that range in size from microfauna (for which the primary role of lichens is habitat provision) to large mammals (for which lichens are primarily a food source). We then address how differences among lichens impact on plants, through for example increasing nutrient inputs and availability during primary succession, and serving as a filter for plant seedling establishment. Finally we identify areas in need of further work for better understanding the role of lichens in terrestrial ecosystems. These include understanding how the high intraspecific trait variation that characterizes many lichens impacts on community assembly processes and ecosystem functioning, how multiple species mixtures of lichens affect the key community- and ecosystem-level processes that they drive, the extent to which lichens in early succession influence vascular plant succession and ecosystem development in the longer term, and how global change drivers may impact on ecosystem functioning through altering the functional composition of lichen communities. © 2016 Cambridge Philosophical Society.

Transendothelial Transport and Its Role in Therapeutics

PubMed Central

Upadhyay, Ravi Kant

2014-01-01

Present review paper highlights role of BBB in endothelial transport of various substances into the brain. More specifically, permeability functions of BBB in transendothelial transport of various substances such as metabolic fuels, ethanol, amino acids, proteins, peptides, lipids, vitamins, neurotransmitters, monocarbxylic acids, gases, water, and minerals in the peripheral circulation and into the brain have been widely explained. In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. Both diffusion and carrier mediated transport mechanisms which facilitate molecular trafficking through transcellular route to maintain influx and outflux of important nutrients and metabolic substances are elucidated. Present review paper aims to emphasize role of important transport systems with their recent advancements in CNS protection mainly for providing a rapid clinical aid to patients. This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients. PMID:27355037

Identification of the Essential Role of Viral Bcl-2 for Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication

PubMed Central

Liang, Qiming; Chang, Brian; Lee, Patrick; Brulois, Kevin F.; Ge, Jianning; Shi, Mude; Rodgers, Mary A.; Feng, Pinghui; Oh, Byung-Ha; Liang, Chengyu

2015-01-01

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) evades host defenses through tight suppression of autophagy by targeting each step of its signal transduction: by viral Bcl-2 (vBcl-2) in vesicle nucleation, by viral FLIP (vFLIP) in vesicle elongation, and by K7 in vesicle maturation. By exploring the roles of KSHV autophagy-modulating genes, we found, surprisingly, that vBcl-2 is essential for KSHV lytic replication, whereas vFLIP and K7 are dispensable. Knocking out vBcl-2 from the KSHV genome resulted in decreased lytic gene expression at the mRNA and protein levels, a lower viral DNA copy number, and, consequently, a dramatic reduction in the amount of progeny infectious viruses, as also described in the accompanying article (A. Gelgor, I. Kalt, S. Bergson, K. F. Brulois, J. U. Jung, and R. Sarid, J Virol 89:5298–5307, 2015). More importantly, the antiapoptotic and antiautophagic functions of vBcl-2 were not required for KSHV lytic replication. Using a comprehensive mutagenesis analysis, we identified that glutamic acid 14 (E14) of vBcl-2 is critical for KSHV lytic replication. Mutating E14 to alanine totally blocked KSHV lytic replication but showed little or no effect on the antiapoptotic and antiautophagic functions of vBcl-2. Our study indicates that vBcl-2 harbors at least three important and genetically separable functions to modulate both cellular signaling and the virus life cycle. IMPORTANCE The present study shows for the first time that vBcl-2 is essential for KSHV lytic replication. Removal of the vBcl-2 gene results in a lower level of KSHV lytic gene expression, impaired viral DNA replication, and consequently, a dramatic reduction in the level of progeny production. More importantly, the role of vBcl-2 in KSHV lytic replication is genetically separated from its antiapoptotic and antiautophagic functions, suggesting that the KSHV Bcl-2 carries a novel function in viral lytic replication. PMID:25740994

The Regulatory Functions of Calcium and the Potential Role of Calcium in Mediating Gravitational Responses in Cells and Tissues

NASA Technical Reports Server (NTRS)

Roux, S. J. (Editor)

1983-01-01

The hypothesis that calcium plays an important part in regulating cellular response to gravity and to other environmental stimuli is explored. Topics covered include the role of calmodulin and other proteins, gravitropic responses, bone demineralization during space flight, and intracellular communication.

Strategic Enrollment Management's Ambassadors: The Changing Role of Admissions Counselors

ERIC Educational Resources Information Center

Mathis, Daniel

2010-01-01

Road runner. File jockey. Advisor. Public speaker. Recruiter. At any given time, an admissions counselor fits one, some, or all of these descriptors. While all of these descriptors indicate an important function within a college or university, none reflects the increasingly complex nature of the role of an admissions counselor in strategic…

Spatial and temporal variation in invertebrate consumer diets in forested and herbaceous wetlands

Treesearch

Alani N. Taylor; Darold P. Batzer

2010-01-01

Macroinvertebrates have important functional roles in wetland ecosystems, but these roles are not always well understood. This study assessed which foods invertebrate consumers assimilate within a set of wetland habitats. During 2006 and 2007, non-Tanypodinae chironomid larvae and select crustaceans (Crangonyx amphipods, Caecidotea isopods, Simocephalus cladocerans)...

An Atlas of Academic Practice in Digital Times

ERIC Educational Resources Information Center

Decuypere, Mathias; Simons, Maarten

2014-01-01

In the current literature on the university it is generally accepted that processes of digitization play an important role regarding both the daily functioning of the university as an institution and the academics that give shape to it. This article contributes to our understanding of the role that digitization plays in contemporary academic…

Role of ubiquitin-proteasome in protein quality control and signaling: implication in the pathogenesis of eye diseases

USDA-ARS?s Scientific Manuscript database

The ubiquitin–proteasome pathway (UPP) plays important roles in many cellular functions, such as protein quality control, cell cycle control, and signal transduction. The selective degradation of aberrant proteins by the UPP is essential for the timely removal of potential cytotoxic damaged or other...

Private University Librarian's Experience on Procurement of Books in Bangladesh

ERIC Educational Resources Information Center

Chowdhury, Muhammad Hossam Haider

2011-01-01

The private universities in Bangladesh are playing an important role in modernizing the higher education system in the country and the role of librarians is also different and challenging. Specially, procuring books and monographs is an exigent function being this lost its demand very quickly. In some cases, titles bear only one semester…

Science Teacher Candidates' Perceptions about Roles and Nature of Scientific Models

ERIC Educational Resources Information Center

Yenilmez Turkoglu, Ayse; Oztekin, Ceren

2016-01-01

Background: Scientific models have important roles in science and science education. For scientists, they provide a means for generating new knowledge or function as an accessible summary of scientific studies. In science education, on the other hand, they are accessible representations of abstract concepts, and are also organizational frameworks…

Caveolins and caveolae in ocular physiology and pathophysiology.

PubMed

Gu, Xiaowu; Reagan, Alaina M; McClellan, Mark E; Elliott, Michael H

2017-01-01

Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Müller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., "lipid rafts") have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signaling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Caveolins and caveolae in ocular physiology and pathophysiology

PubMed Central

Gu, Xiaowu; Reagan, Alaina M.; McClellan, Mark E.; Elliott, Michael H.

2016-01-01

Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Müller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., “lipid rafts”) have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signalling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function. PMID:27664379

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.

Assessing disease-modifying effects of norepinephrine in Down syndrome and Alzheimer's disease.

PubMed

Ponnusamy, Ravikumar; McNerney, M Windy; Moghadam, Shahrzad; Salehi, Ahmad

2017-11-08

Building upon the knowledge that a number of important brain circuits undergo significant degeneration in Alzheimer's disease, numerous recent studies suggest that the norepinephrine-ergic system in the brainstem undergoes significant alterations early in the course of both Alzheimer's disease and Down syndrome. Massive projections from locus coeruleus neurons to almost the entire brain, extensive innervation of brain capillaries, and widespread distribution of noradrenergic receptors enable the norepinephrine-ergic system to play a crucial role in neural processes, including cognitive function. These anatomical and functional characteristics support the role of the norepinephrine-ergic system as an important target for developing new therapies for cognitive dysfunction. Careful neuropathological examinations using postmortem samples from individuals with Alzheimer's disease have implicated the role of the norepinephrine-ergic system in the etiopathogenesis of Alzheimer's disease. Furthermore, numerous studies have supported the existence of a strong interaction between norepinephrine-ergic and neuroimmune systems. We explore the interaction between the two systems that could play a role in the disease-modifying effects of norepinephrine in Alzheimer's disease and Down syndrome. Copyright © 2017. Published by Elsevier B.V.

NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer

PubMed Central

Kisseleva, Tatiana; Song, Li; Vorontchikhina, Marina; Feirt, Nikki; Kitajewski, Jan; Schindler, Christian

2006-01-01

The transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-κB in endothelial tissues, Tie2 promoter/enhancer–IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress. PMID:17053836

The complex roles of space and environment in structuring functional, taxonomic and phylogenetic beta diversity of frogs in the Atlantic Forest

PubMed Central

Luiz, Amom Mendes; Sawaya, Ricardo J.

2018-01-01

Ecological communities are complex entities that can be maintained and structured by niche-based processes such as environmental conditions, and spatial processes such as dispersal. Thus, diversity patterns may be shaped simultaneously at different spatial scales by very distinct processes. Herein we assess whether and how functional, taxonomic, and phylogenetic beta diversities of frog tadpoles are explained by environmental and/or spatial predictors. We implemented a distance–based redundancy analysis to explore variation in components of beta diversity explained by pure environmental and pure spatial predictors, as well as their interactions, at both fine and broad spatial scales. Our results indicated important but complex roles of spatial and environmental predictors in structuring phylogenetic, taxonomic and functional beta diversities. The pure fine-scales spatial fraction was more important in structuring all beta diversity components, especially to functional and taxonomical spatial turnover. Environmental variables such as canopy cover and vegetation structure were important predictors of all components, but especially to functional and taxonomic beta diversity. We emphasize that distinct factors related to environment and space are affecting distinct components of beta diversity in different ways. Although weaker, phylogenetic beta diversity, which is structured more on biogeographical scales, and thus can be represented by spatially structured processes, was more related to broad spatial processes than other components. However, selected fine-scale spatial predictors denoted negative autocorrelation, which may be revealing the existence of differences in unmeasured habitat variables among samples. Although overall important, local environmental-based processes explained better functional and taxonomic beta diversity, as these diversity components carry an important ecological value. We highlight the importance of assessing different components of diversity patterns at different scales by spatially explicit models in order to improve our understanding of community structure and help to unravel the complex nature of biodiversity. PMID:29672575

Mechanotransduction in Endothelial Cells Studied with Fluorescence Imaging

NASA Astrophysics Data System (ADS)

Chien, Shu

2011-01-01

Mechanotransduction involves the conversion of mechanical stimuli to intracellular signaling to modulate gene and protein expressions and hence cellular functions in endothelial cells, thus playing importance roles in the regulation of homeostasis in health and disease. The aim of this paper is to investigate the dynamics of mechanotransduction in endothelial cells by the use of fluorescent resonance energy transfer (FRET) to study the temporal and spatial activation of Src kinase and focal adhesion kinase, both of which play critical roles in many cellular processes. The results have contributed to the elucidation of the roles of these two important signaling molecules and their interactions in mediating mechanotransduction.

Suppressor of cytokine signaling 1 interacts with oncogenic lymphocyte-specific protein tyrosine kinase.

PubMed

Venkitachalam, Srividya; Chueh, Fu-Yu; Leong, King-Fu; Pabich, Samantha; Yu, Chao-Lan

2011-03-01

Lymphocyte-specific protein tyrosine kinase (Lck) plays a key role in T cell signal transduction and is tightly regulated by phosphorylation and dephosphorylation. Lck can function as an oncoprotein when overexpressed or constantly activated by mutations. Our previous studies showed that Lck-induced cellular transformation could be suppressed by enforced expression of suppressor of cytokine signaling 1 (SOCS1), a SOCS family member involved in the negative feedback control of cytokine signaling. We observed attenuated Lck kinase activity in SOCS1-expressing cells, suggesting an important role of SOCS in regulating Lck functions. It remains largely unknown whether and how SOCS proteins interact with the oncogenic Lck kinase. Here, we report that among four SOCS family proteins, SOCS1, SOCS2, SOCS3 and CIS (cytokine-inducible SH2 domain containing protein), SOCS1 has the highest affinity in binding to the oncogenic Lck kinase. We identified the positive regulatory phosphotyrosine 394 residue in the kinase domain as the key interacting determinant in Lck. Additionally, the Lck kinase domain alone is sufficient to bind SOCS1. While the SH2 domain in SOCS1 is important in its association with the oncogenic Lck kinase, other functional domains may also contribute to overall binding affinity. These findings provide important mechanistic insights into the role of SOCS proteins as tumor suppressors in cells transformed by oncogenic protein tyrosine kinases.

Suppressor of cytokine signaling 1 interacts with oncogenic lymphocyte-specific protein tyrosine kinase

PubMed Central

VENKITACHALAM, SRIVIDYA; CHUEH, FU-YU; LEONG, KING-FU; PABICH, SAMANTHA; YU, CHAO-LAN

2011-01-01

Lymphocyte-specific protein tyrosine kinase (Lck) plays a key role in T cell signal transduction and is tightly regulated by phosphorylation and dephosphorylation. Lck can function as an oncoprotein when overexpressed or constantly activated by mutations. Our previous studies showed that Lck-induced cellular transformation could be suppressed by enforced expression of suppressor of cytokine signaling 1 (SOCS1), a SOCS family member involved in the negative feedback control of cytokine signaling. We observed attenuated Lck kinase activity in SOCS1-expressing cells, suggesting an important role of SOCS in regulating Lck functions. It remains largely unknown whether and how SOCS proteins interact with the oncogenic Lck kinase. Here we report that, among four SOCS family proteins, SOCS1, SOCS2, SOCS3 and CIS (cytokine–inducible SH2 domain containing protein), SOCS1 has the highest affinity in binding to the oncogenic Lck kinase. We identify the positive regulatory phospho-tyrosine 394 residue in the kinase domain as the key interacting determinant in Lck. Additionally, the Lck kinase domain alone is sufficient to bind SOCS1. While the SH2 domain in SOCS1 is important in its association with the oncogenic Lck kinase, other functional domains may also contribute to overall binding affinity. These findings provide important mechanistic insights into the role of SOCS proteins as tumor suppressors in cells transformed by oncogenic protein tyrosine kinases. PMID:21234523

JPRS Report China

DTIC Science & Technology

1988-02-18

only 3 percent; by 1900 it exceeded 20 percent. On the other hand, there has been a fundamental change in the status, role , function, nature, and...groups should be actively developed and play leading roles in the city system. In the industrial age, JPRS-CAR-88-005 18 February 1988 ECONOMIC new...commodity economy. The law of value plays a regulatory role . The market mechanism is an important mechanism that regulates social reproduction

Plant cell membranes as a marker for light-dependent and light-independent herbicide mechanisms of action

USDA-ARS?s Scientific Manuscript database

Plant cells possess a number of membrane bound organelles that play important roles in compartmentalizing a large number of biochemical pathways and physiological functions that have potentially harmful intermediates or by-products. The plasma membrane is particularly important as it holds the enti...

Quantifying livestock effects on bunchgrass vegetation with Landsat ETM+ data across a single growing season

USDA-ARS?s Scientific Manuscript database

Working grassland systems provide important habitat for native biodiversity and forage for livestock, with proper livestock grazing playing an important role for sustainable ecosystem function. Traditional in-field techniques to monitor the effects of grazing on vegetation are costly and limited to ...

FATTY ACID STABLE ISOTOPE INDICATORS OF MICROBIAL CARBON SOURCE IN TROPICAL SOILS

EPA Science Inventory

The soil microbial community plays an important role in tropical ecosystem functioning because of its importance in the soil organic matter (SOM) cycle. We have measured the stable carbon isotopic ratio (delta13C) of individual phospholipid fatty acids (PLFAs) in a variety of tr...

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.

The importance of bees in natural and agricultural ecosystems

Treesearch

Paul Rhoades

2013-01-01

As the world’s most important group of pollinators, bees are a crucial part of agricultural production and natural ecosystem function. Bees and the pollination they provide are relevant to the nursery industry because of their role in the performance of seed increase plots as well as the importance of pollination in supporting persistent plant communities in restored...

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

Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.

Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associatedmore » proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.« less

Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence.

PubMed

Romano, Jacob; Nimrod, Guy; Ben-Tal, Nir; Shadkchan, Yona; Baruch, Koti; Sharon, Haim; Osherov, Nir

2006-07-01

The ECM33/SPS2 family of glycosylphosphatidylinositol-anchored proteins plays an important role in maintaining fungal cell wall integrity and virulence. However, the precise molecular role of these proteins is unknown. In this work, AfuEcm33, the gene encoding the ECM33 homologue in the important pathogenic fungus Aspergillus fumigatus, has been cloned and its function analysed. It is shown that disruption of AfuEcm33 results in rapid conidial germination, increased cell-cell adhesion, resistance to the antifungal agent caspofungin and increased virulence in an immunocompromised mouse model for disseminated aspergillosis. These results suggest that the protein encoded by AfuEcm33 is involved in key aspects of cell wall morphogenesis and plays an important role in A. fumigatus virulence.

Relationship between involvement and functional milk desserts intention to purchase. Influence on attitude towards packaging characteristics.

PubMed

Ares, Gastón; Besio, Mariángela; Giménez, Ana; Deliza, Rosires

2010-10-01

Consumers perceive functional foods as member of the particular food category to which they belong. In this context, apart from health and sensory characteristics, non-sensory factors such as packaging might have a key role on determining consumers' purchase decisions regarding functional foods. The aims of the present work were to study the influence of different package attributes on consumer willingness to purchase regular and functional chocolate milk desserts; and to assess if the influence of these attributes was affected by consumers' level of involvement with the product. A conjoint analysis task was carried out with 107 regular milk desserts consumers, who were asked to score their willingness to purchase of 16 milk dessert package concepts varying in five features of the package, and to complete a personal involvement inventory questionnaire. Consumers' level of involvement with the product affected their interest in the evaluated products and their reaction towards the considered conjoint variables, suggesting that it could be a useful segmentation tool during food development. Package colour and the presence of a picture on the label were the variables with the highest relative importance, regardless of consumers' involvement with the product. The importance of these variables was higher than the type of dessert indicating that packaging may play an important role in consumers' perception and purchase intention of functional foods.

The versatile nature of miR-9/9* in human cancer.

PubMed

Nowek, Katarzyna; Wiemer, Erik A C; Jongen-Lavrencic, Mojca

2018-04-17

miR-9 and miR-9 * (miR-9/9 * ) were first shown to be expressed in the nervous system and to function as versatile regulators of neurogenesis. The variable expression levels of miR-9/9 * in human cancer prompted researchers to investigate whether these small RNAs may also have an important role in the deregulation of physiological and biochemical networks in human disease. In this review, we present a comprehensive overview of the involvement of miR-9/9 * in various human malignancies focusing on their opposing roles in supporting or suppressing tumor development and metastasis. Importantly, it is shown that the capacity of miR-9/9 * to impact tumor formation is independent from their influence on the metastatic potential of tumor cells. Moreover, data suggest that miR-9/9 * may increase malignancy of one cancer cell population at the expense of another. The functional versatility of miR-9/9 * emphasizes the complexity of studying miRNA function and the importance to perform functional studies of both miRNA strands in a relevant cellular context. The possible application of miR-9/9 * as targets for miRNA-based therapies is discussed, emphasizing the need to obtain a better understanding of the functional properties of these miRNAs and to develop safe delivery methods to target specific cell populations.

The versatile nature of miR-9/9* in human cancer

PubMed Central

Nowek, Katarzyna; Wiemer, Erik A.C.; Jongen-Lavrencic, Mojca

2018-01-01

miR-9 and miR-9* (miR-9/9*) were first shown to be expressed in the nervous system and to function as versatile regulators of neurogenesis. The variable expression levels of miR-9/9* in human cancer prompted researchers to investigate whether these small RNAs may also have an important role in the deregulation of physiological and biochemical networks in human disease. In this review, we present a comprehensive overview of the involvement of miR-9/9* in various human malignancies focusing on their opposing roles in supporting or suppressing tumor development and metastasis. Importantly, it is shown that the capacity of miR-9/9* to impact tumor formation is independent from their influence on the metastatic potential of tumor cells. Moreover, data suggest that miR-9/9* may increase malignancy of one cancer cell population at the expense of another. The functional versatility of miR-9/9* emphasizes the complexity of studying miRNA function and the importance to perform functional studies of both miRNA strands in a relevant cellular context. The possible application of miR-9/9* as targets for miRNA-based therapies is discussed, emphasizing the need to obtain a better understanding of the functional properties of these miRNAs and to develop safe delivery methods to target specific cell populations. PMID:29755694

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

Genes Important for Schizosaccharomyces pombe Meiosis Identified Through a Functional Genomics Screen

PubMed Central

Blyth, Julie; Makrantoni, Vasso; Barton, Rachael E.; Spanos, Christos; Rappsilber, Juri; Marston, Adele L.

2018-01-01

Meiosis is a specialized cell division that generates gametes, such as eggs and sperm. Errors in meiosis result in miscarriages and are the leading cause of birth defects; however, the molecular origins of these defects remain unknown. Studies in model organisms are beginning to identify the genes and pathways important for meiosis, but the parts list is still poorly defined. Here we present a comprehensive catalog of genes important for meiosis in the fission yeast, Schizosaccharomyces pombe. Our genome-wide functional screen surveyed all nonessential genes for roles in chromosome segregation and spore formation. Novel genes important at distinct stages of the meiotic chromosome segregation and differentiation program were identified. Preliminary characterization implicated three of these genes in centrosome/spindle pole body, centromere, and cohesion function. Our findings represent a near-complete parts list of genes important for meiosis in fission yeast, providing a valuable resource to advance our molecular understanding of meiosis. PMID:29259000

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.

Fathers matter: The role of father parenting in preschoolers' executive function development.

PubMed

Meuwissen, Alyssa S; Carlson, Stephanie M

2015-12-01

Although previous work has shown that mothers' parenting influences the development of child executive function (EF; important self-control skills developed during the preschool years), the role of fathers' parenting has not been thoroughly investigated. We observed fathers' autonomy support and control in dyadic play with their 3-year-old children (N pairs=110) and measured father and child EF independently with laboratory tasks. We found that fathers' controlling parenting was significantly inversely related to the child EF composite, above and beyond family income and child verbal ability. These results are consistent with the hypothesis that fathers are important for the development of EF in their children and suggest that fathers should be included in both research and parenting interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Paradoxical roles of dual oxidases in cancer biology.

PubMed

Little, Andrew C; Sulovari, Arvis; Danyal, Karamatullah; Heppner, David E; Seward, David J; van der Vliet, Albert

2017-09-01

Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

[Connective tissue and inflammation].

PubMed

Jakab, Lajos

2014-03-23

The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

SEPT9_v1 Functions in Breast Cancer Cell Division

DTIC Science & Technology

2012-01-01

the regulation and function of septin filaments, and define new mechanisms regulating important cellular functions. BODY: 1). Study the effects...ciliogenesis. However, mechanisms for retaining these proteins and lipids in the primary cilia are not clear. We directly tested the presence of a diffusion...polarity and morphogenesis;  Defined mechanisms involving the roles of septins and microtubules in vesicle trafficking and epithelial morphogenesis

A class of solution-invariant transformations of cost functions for minimum cost flow phase unwrapping.

PubMed

Hubig, Michael; Suchandt, Steffen; Adam, Nico

2004-10-01

Phase unwrapping (PU) represents an important step in synthetic aperture radar interferometry (InSAR) and other interferometric applications. Among the different PU methods, the so called branch-cut approaches play an important role. In 1996 M. Costantini [Proceedings of the Fringe '96 Workshop ERS SAR Interferometry (European Space Agency, Munich, 1996), pp. 261-272] proposed to transform the problem of correctly placing branch cuts into a minimum cost flow (MCF) problem. The crucial point of this new approach is to generate cost functions that represent the a priori knowledge necessary for PU. Since cost functions are derived from measured data, they are random variables. This leads to the question of MCF solution stability: How much can the cost functions be varied without changing the cheapest flow that represents the correct branch cuts? This question is partially answered: The existence of a whole linear subspace in the space of cost functions is shown; this subspace contains all cost differences by which a cost function can be changed without changing the cost difference between any two flows that are discharging any residue configuration. These cost differences are called strictly stable cost differences. For quadrangular nonclosed networks (the most important type of MCF networks for interferometric purposes) a complete classification of strictly stable cost differences is presented. Further, the role of the well-known class of node potentials in the framework of strictly stable cost differences is investigated, and information on the vector-space structure representing the MCF environment is provided.

Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure: does ejection fraction matter?

PubMed

Andrade, David C; Arce-Alvarez, Alexis; Toledo, Camilo; Díaz, Hugo S; Lucero, Claudia; Quintanilla, Rodrigo A; Schultz, Harold D; Marcus, Noah J; Amann, Markus; Del Rio, Rodrigo

2018-03-01

Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.

Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction

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

Qiu, Gui-Zhen; Tian, Wei; Fu, Hai-Tao

Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainlymore » mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. - Highlights: • LncRNA-MEG3 level is down-regulated upon diabetic stress. • MEG3 knockdown aggravates retinal vascular dysfunction in vivo. • MEG3 regulates retinal endothelial cell function in vitro. • MEG3 regulates endothelial cell function through PI3k/Akt signaling.« less

In Vivo Function of Tryptophans in the Arabidopsis UV-B Photoreceptor UVR8[W

PubMed Central

O’Hara, Andrew; Jenkins, Gareth I.

2012-01-01

Arabidopsis thaliana UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor specifically for UV-B light that initiates photomorphogenic responses in plants. UV-B exposure causes rapid conversion of UVR8 from dimer to monomer, accumulation in the nucleus, and interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), which functions with UVR8 in UV-B responses. Studies in yeast and with purified UVR8 implicate several tryptophan amino acids in UV-B photoreception. However, their roles in UV-B responses in plants, and the functional significance of all 14 UVR8 tryptophans, are not known. Here we report the functions of the UVR8 tryptophans in vivo. Three tryptophans in the β-propeller core are important in maintaining structural stability and function of UVR8. However, mutation of three other core tryptophans and four at the dimeric interface has no apparent effect on function in vivo. Mutation of three tryptophans implicated in UV-B photoreception, W233, W285, and W337, impairs photomorphogenic responses to different extents. W285 is essential for UVR8 function in plants, whereas W233 is important but not essential for function, and W337 has a lesser role. Ala mutants of these tryptophans appear monomeric and constitutively bind COP1 in plants, but their responses indicate that monomer formation and COP1 binding are not sufficient for UVR8 function. PMID:23012433

The importance of biodiversity and dominance for multiple ecosystem functions in a human-modified tropical landscape.

PubMed

Lohbeck, Madelon; Bongers, Frans; Martinez-Ramos, Miguel; Poorter, Lourens

2016-10-01

Many studies suggest that biodiversity may be particularly important for ecosystem multifunctionality, because different species with different traits can contribute to different functions. Support, however, comes mostly from experimental studies conducted at small spatial scales in low-diversity systems. Here, we test whether different species contribute to different ecosystem functions that are important for carbon cycling in a high-diversity human-modified tropical forest landscape in Southern Mexico. We quantified aboveground standing biomass, primary productivity, litter production, and wood decomposition at the landscape level, and evaluated the extent to which tree species contribute to these ecosystem functions. We used simulations to tease apart the effects of species richness, species dominance and species functional traits on ecosystem functions. We found that dominance was more important than species traits in determining a species' contribution to ecosystem functions. As a consequence of the high dominance in human-modified landscapes, the same small subset of species mattered across different functions. In human-modified landscapes in the tropics, biodiversity may play a limited role for ecosystem multifunctionality due to the potentially large effect of species dominance on biogeochemical functions. However, given the spatial and temporal turnover in species dominance, biodiversity may be critically important for the maintenance and resilience of ecosystem functions. © 2016 The Authors. Ecology, published by Wiley Periodicals, Inc., on behalf of the Ecological Society of America.

HvHMA2, a P1B-ATPase from Barley, Is Highly Conserved among Cereals and Functions in Zn and Cd Transport

PubMed Central

Mills, Rebecca F.; Peaston, Kerry A.; Runions, John; Williams, Lorraine E.

2012-01-01

Manipulation of crops to improve their nutritional value (biofortification) and optimisation of plants for removal of toxic metals from contaminated soils (phytoremediation) are major goals. Identification of membrane transporters with roles in zinc and cadmium transport would be useful for both aspects. The P1B-ATPases play important roles in heavy metal allocation and detoxification in Arabidopsis and it is now important to elucidate their roles in monocots. We identified nine P1B-ATPases in barley and this study focuses on the functional characterization of HvHMA2, providing evidence for its role in heavy metal transport. HvHMA2 was cloned using information from EST analysis and 5′ RACE. It possesses the conserved aspartate that is phosphorylated during the reaction cycle of P-type pumps and has motifs and key residues characteristic of P1B-ATPases, falling into the P1B-2 subclass. Homologous sequences occur in three major sub-families of the Poaceae (Gramineae). Heterologous expression in Saccharomyces cerevisiae demonstrates that HvHMA2 functions as a Zn and Cd pump. Mutagenesis studies show that proposed cation coordination sites of the P1B-2 pumps are crucial for the metal responses conferred by HvHMA2 in yeast. HvHMA2 expression suppresses the Zn-deficient phenotype of the Arabidopsis hma2hma4 mutant indicating that HvHMA2 functions as a Zn pump in planta and could play a role in root to shoot Zn transport. When expressed in Arabidopsis, HvHMA2 localises predominantly to the plasma membrane. PMID:22880063

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.

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.

A review of HPRT and its emerging role in cancer.

PubMed

Townsend, Michelle H; Robison, Richard A; O'Neill, Kim L

2018-05-05

Hypoxanthine guanine phosphoribosyltransferase (HPRT) is a common salvage housekeeping gene with a historically important role in cancer as a mutational biomarker. As an established and well-known human reporter gene for the evaluation of mutational frequency corresponding to cancer development, HPRT is most commonly used to evaluate cancer risk within individuals and determine potential carcinogens. In addition to its use as a reporter gene, HPRT also has important functionality in the body in relation to purine regulation as demonstrated by Lesch-Nyhan patients whose lack of functional HPRT leads to significant purine overproduction and further neural complications. This regulatory role, in addition to an established connection between other salvage enzymes and cancer development, points to HPRT as an emerging influence in cancer. Recent work has shown that not only is the enzyme upregulated within malignant tumors, it also has significant surface localization within some cancer cells. With this is mind, HPRT has the potential to become a significant biomarker not only for the characterization of cancer, but also for its potential treatment.

Role of antioxidants and trace elements in health and immunity of transition dairy cows.

PubMed

Spears, Jerry W; Weiss, William P

2008-04-01

A number of antioxidants and trace minerals have important roles in immune function and may affect health in transition dairy cows. Vitamin E and beta-carotene are important cellular antioxidants. Selenium (Se) is involved in the antioxidant system via its role in the enzyme glutathione peroxidase. Inadequate dietary vitamin E or Se decreases neutrophil function during the perpariturient period. Supplementation of vitamin E and/or Se has reduced the incidence of mastitis and retained placenta, and reduced duration of clinical symptoms of mastitis in some experiments. Research has indicated that beta-carotene supplementation may enhance immunity and reduce the incidence of retained placenta and metritis in dairy cows. Marginal copper deficiency resulted in reduced neutrophil killing and decreased interferon production by mononuclear cells. Copper supplementation of a diet marginal in copper reduced the peak clinical response during experimental Escherichia coli mastitis. Limited research indicated that chromium supplementation during the transition period may increase immunity and reduce the incidence of retained placenta.

Role of Histone Acetylation in the Assembly and Modulation of Chromatin Structures

PubMed Central

Annunziato, Anthony T.; Hansen, Jeffrey C.

2000-01-01

The acetylation of the core histone N-terminal “tail” domains is now recognized as a highly conserved mechanism for regulating chromatin functional states. The following article examines possible roles of acetylation in two critically important cellular processes: replication-coupled nucleosome assembly, and reversible transitions in chromatin higher order structure. After a description of the acetylation of newly synthesized histones, and of the likely acetyltransferases involved, an overview of histone octamer assembly is presented. Our current understanding of the factors thought to assemble chromatin in vivo is then described. Genetic and biochemical investigations of the function the histone tails, and their acetylation, in nucleosome assembly are detailed, followed by an analysis of the importance of histone deacetylation in the maturation of newly replicated chromatin. In the final section the involvement of the histone tail domains in chromatin higher order structures is addressed, along with the role of histone acetylation in chromatin folding. Suggestions for future research are offered in the concluding remarks. PMID:11097424

A Framework to Describe, Analyze and Generate Interactive Motor Behaviors

PubMed Central

Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

2012-01-01

While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks. PMID:23226231

A framework to describe, analyze and generate interactive motor behaviors.

PubMed

Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

2012-01-01

While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks.

The role of the DLPFC in inductive reasoning of MCI patients and normal agings: an fMRI study.

PubMed

Yang, YanHui; Liang, PeiPeng; Lu, ShengFu; Li, KunCheng; Zhong, Ning

2009-08-01

Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal aging, and whether the activation pattern of this region was different between MCI patients and normal aging. The fMRI results indicated that MCI patients had no difference from normal aging in behavior performance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD response of the DLPFC region for MCI patients was weaker than that for normal aging, and the functional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal aging. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of aging, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.

Sociodemographic Factors Differentiating the Consumer and the Motivations for Functional Food Consumption.

PubMed

Kraus, Artur; Annunziata, Azzurra; Vecchio, Riccardo

2017-02-01

The aim of this study was to determine the (1) role of gender, age, and education in the evaluation of multidimensional criteria of the purchase of functional products, which were (a) quality and organoleptic attributes, (b) attributes of packaging and labeling, (c) healthful properties, (d) functional components, (e) base product (carrier) and (2) most important motives for the purchase and consumption of functional food among consumers of different sociodemographic profiles. The data were collected in direct interviews. The sample (n = 200) consisted of 137 women and 63 men age 18-60 years. The research tool was a questionnaire divided into 4 sections. The first one included quality attributes. The second one included healthful properties, functional components, and carriers. The third one concerned the motives for purchasing functional food and included the consequences and values. In the fourth section the participants were asked about gender, age, and education. Gender, age, and education differentiated the criteria influencing the decision to purchase functional food. Women, older people (35-60 years), and those with university education attach the greatest importance to naturalness, nutritional value, freshness, food safety, and quality guarantee. Clear differences between men and women appear in the field of functional components, which are significantly more important for women than for men. Gender, age, and education essentially differentiate the preferences for base product (carrier). Young men prefer meat products in the role of functional carriers. In turn, women and older men prefer cereal products as basic functional carriers. Young consumers are more open to high-technology food processing. Motivations are differentiated by age and gender. Young men, as opposed to women and older men, attach less importance to functional and psychological consequences: improvement of health, healthy eating, conscious choice, and health promotion. Women and older men are more interested in health safety and are more responsible for their health. Among young men, lower self-esteem can be found. The analysis conducted revealed that groups of consumers are significantly different from each other in the evaluation of the significance of each of the variables in the selection of functional food. Sociodemographic factors differentiate the motivations for consumption of functional food.

Delineation of the function of a major gamma delta T cell subset during infection.

PubMed

Andrew, Elizabeth M; Newton, Darren J; Dalton, Jane E; Egan, Charlotte E; Goodwin, Stewart J; Tramonti, Daniela; Scott, Philip; Carding, Simon R

2005-08-01

Gammadelta T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among gammadelta T cells. Using mice deficient in Vgamma1+ T cells which are a major component of the gammadelta T cell response to microbial infection, a specific immunoregulatory role for Vgamma1+ T cells in macrophage and gammadelta T cell homeostasis during infection has been established. By contrast, Vgamma1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vgamma1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vgamma1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for gammadelta T cell subsets in infection and establish the complexity and adaptability of a single population of gammadelta T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

PubMed

Speirs, Jennifer J; van der Ent, Cornelis K; Beekman, Jeffrey M

2012-11-01

Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

Pulmonary function response and effects of antioxidant genetic polymorphisms in healthy young adults exposed to low concentration ozone.

EPA Science Inventory

Rational: Ozone is known to induce a variety of pulmonary effects including decrement of spirometric lung function and inflammatory reaction, and antioxidant genes are known to play an important role in modulating the effects. It is unclear, however, if such effects may occur at...

How Do Siamese Cats Get Their Color?

ERIC Educational Resources Information Center

Todd, Amber; Kenyon, Lisa

2016-01-01

When asked about protein, students often mention meat, protein bars, and protein's role in building muscles. Many students are not aware of the most basic function of protein: linking genes and traits. Because of its importance in molecular genetics, protein function is included in the life sciences section of the "Next Generation Science…

Sex steroids effects in normal endocrine pancreatic function and diabetes.

PubMed

Morimoto, Sumiko; Jiménez-Trejo, Francisco; Cerbón, Marco

2011-01-01

Traditionally the role of sexual steroid hormones was focused primarily on reproductive organs: the breast, female reproductive tract (uterus, mammary gland, and ovary), and male reproductive tract (testes, epididymis and prostate), however our current understanding of tissue-specific effects of sex steroids has elucidated new aspects in its functionality. Recent data have shown that many other tissues are targets of those hormones in addition to classical reproductive organs. The pancreas (which performs both endocrine and exocrine functions), has proven to be an extragonadal target of sexual steroid hormone action. The endocrine pancreas has a pivotal role on carbohydrate homeostasis and deterioration in function produces diabetes. Diabetes is a metabolic disorder that has high prevalence worldwide, particularly in developing countries. It has been shown that steroid hormones have an important role in susceptibility and development of diabetes in animal models, in humans its role is less clear, however the most evident effect is on the perimenopausal women, in this stage the decrease in gonadal steroids produces an increase on susceptibility to develop diabetes mellitus; in men, hypoandrogenism is associated with an increased prevalence of insulin resistance. This review focused on the effects of sexual steroids on pancreatic function and diabetes.

Cdk-related kinase 9 regulates RNA polymerase II mediated transcription in Toxoplasma gondii.

PubMed

Deshmukh, Abhijit S; Mitra, Pallabi; Kolagani, Ashok; Gurupwar, Rajkumar

2018-06-01

Cyclin-dependent kinases are an essential part of eukaryotic transcriptional machinery. In Apicomplexan parasites, the role and relevance of the kinases in the multistep process of transcription seeks more attention given the absence of full repertoire of canonical Cdks and cognate cyclin partners. In this study, we functionally characterize T. gondii Cdk-related kinase 9 (TgCrk9) showing maximal homology to eukaryotic Cdk9. An uncanonical cyclin, TgCyclin L, colocalizes with TgCrk9 in the parasite nucleus and co-immunoprecipitate, could activate the kinase in-vitro. We identify two threonines in conserved T-loop domain of TgCrk9 that are important for its activity. The activated TgCrk9 phosphorylates C-terminal domain (CTD) of TgRpb1, the largest subunit of RNA polymerase II highlighting its role in transcription. Selective chemical inhibition of TgCrk9 affected serine 2 phosphorylation in the heptapeptide repeats of TgRpb1-CTD towards 3' end of genes consistent with a possible role in transcription elongation. Interestingly, TgCrk9 kinase activity is regulated by the upstream TgCrk7 based CAK complex. TgCrk9 was found to functionally complement the role of its yeast counterpart Bur1 establishing its role as an important transcriptional kinase. In this study, we provide robust evidence that TgCrk9 is an important part of transcription machinery regulating gene expression in T. gondii. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of type III effectors from Xanthomonas axonopodis pv. manihotis in virulence and suppression of plant immunity.

PubMed

Medina, Cesar Augusto; Reyes, Paola Andrea; Trujillo, Cesar Augusto; Gonzalez, Juan Luis; Bejarano, David Alejandro; Montenegro, Nathaly Andrea; Jacobs, Jonathan M; Joe, Anna; Restrepo, Silvia; Alfano, James R; Bernal, Adriana

2018-03-01

Xanthomonas axonopodis pv. manihotis (Xam) causes cassava bacterial blight, the most important bacterial disease of cassava. Xam, like other Xanthomonas species, requires type III effectors (T3Es) for maximal virulence. Xam strain CIO151 possesses 17 predicted T3Es belonging to the Xanthomonas outer protein (Xop) class. This work aimed to characterize nine Xop effectors present in Xam CIO151 for their role in virulence and modulation of plant immunity. Our findings demonstrate the importance of XopZ, XopX, XopAO1 and AvrBs2 for full virulence, as well as a redundant function in virulence between XopN and XopQ in susceptible cassava plants. We tested their role in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) using heterologous systems. AvrBs2, XopR and XopAO1 are capable of suppressing PTI. ETI suppression activity was only detected for XopE4 and XopAO1. These results demonstrate the overall importance and diversity in functions of major virulence effectors AvrBs2 and XopAO1 in Xam during cassava infection. © 2017 BSPP AND JOHN WILEY & SONS LTD.

The reduction of occupational stress among elderly lawyers: the creation of a functional niche.

PubMed

Meltzer, M W

1981-01-01

The question of how older lawyers function in the context of what is generally a high stress occupation is examined from data drawn from a random stratified sample of 130 members of the legal profession. It is shown that elderly lawyers are able to reduce work stress (largely deriving from volume, responsibility, clients, and trials) by control over the quantity and focus of their work, as well as through client selection. Elderly lawyers are able to create a relatively stress free work role, which is in fact a functional niche for them within the profession. The result is high job satisfaction and low rates of retirement among elderly practitioners. Two factors: work role compensation and work role autonomy, are isolated from the legal data and proposed as important variables in a general theory of retirement behavior.

Ants and termites increase crop yield in a dry climate.

PubMed

Evans, Theodore A; Dawes, Tracy Z; Ward, Philip R; Lo, Nathan

2011-03-29

Agricultural intensification has increased crop yields, but at high economic and environmental cost. Harnessing ecosystem services of naturally occurring organisms is a cheaper but under-appreciated approach, because the functional roles of organisms are not linked to crop yields, especially outside the northern temperate zone. Ecosystem services in soil come from earthworms in these cooler and wetter latitudes; what may fulfill their functional role in agriculture in warmer and drier habitats, where they are absent, is unproven. Here we show in a field experiment that ants and termites increase wheat yield by 36% from increased soil water infiltration due to their tunnels and improved soil nitrogen. Our results suggest that ants and termites have similar functional roles to earthworms, and that they may provide valuable ecosystem services in dryland agriculture, which may become increasingly important for agricultural sustainability in arid climates.

Roles of Attention Shifting and Inhibitory Control in Fourth-Grade Reading Comprehension

ERIC Educational Resources Information Center

Kieffer, Michael J.; Vukovic, Rose K.; Berry, Daniel

2013-01-01

Executive functioning (EF) refers to a set of higher order, core cognitive processes that facilitate planning, problem solving, and the initiation and maintenance of goal-directed behavior. Although recent research has established the importance of EF for word reading development in early childhood, few studies have investigated the role of EF in…

An fMRI Investigation of Covertly and Overtly Produced Mono- And Multisyllabic Words

ERIC Educational Resources Information Center

Shuster, Linda I.; Lemieux, Susan K.

2005-01-01

Studies suggest that the left insula may play an important role in speech motor programming. We used functional magnetic resonance imaging to investigate the role of the left insula in the production of monosyllabic or multisyllabic words during overt and covert speech conditions. The left insula did not show a BOLD response for multisyllabic…

Governing Bodies, Headteacher Performance and Pay: The Role of External Advisers

ERIC Educational Resources Information Center

Earley, P.; Bubb, S.; Eddy-Spicer, D.; Crawford, M.; James, C.

2016-01-01

This article reports on the role of the external adviser to school governing bodies in relation to headteacher performance management (HTPM) in England. School leaders are crucially important for the effective functioning of schools and there is an ever-growing body of inspection and research evidence which shows this to be the case--leadership…

Tolerance of Frogs among High School Students: Influences of Disgust and Culture

ERIC Educational Resources Information Center

Prokop, Pavol; Medina-Jerez, William; Coleman, Joy; Fancovicová, Jana; Özel, Murat; Fedor, Peter

2016-01-01

Amphibians play an important role in the functioning of ecosystems and some of them inhabit human gardens where they can successfully reproduce. The decline of amphibian diversity worldwide suggests that people may play a crucial role in their survival. We conducted a cross-cultural study on high school students' tolerance of frogs in Chile,…

The multifaceted functions of C/EBPα in normal and malignant haematopoiesis.

PubMed

Ohlsson, E; Schuster, M B; Hasemann, M; Porse, B T

2016-04-01

The process of blood formation, haematopoiesis, depends upon a small number of haematopoietic stem cells (HSCs) that reside in the bone marrow. Differentiation of HSCs is characterised by decreased expression of genes associated with self-renewal accompanied by a stepwise activation of genes promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation. CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML), was recognised and has been the focus of intense studies by a number of investigators. More recent work has revisited the role of C/EBPα in normal haematopoiesis, especially its function in HSCs, and also started to provide more mechanistic insights into its role in normal and malignant haematopoiesis. In particular, the differential actions of C/EBPα isoforms, as well as its importance in chromatin remodelling and cellular reprogramming, are beginning to be elucidated. Finally, recent work has also shed light on the dichotomous function of C/EBPα in AML by demonstrating its ability to act as both a tumour suppressor and promoter. In the present review, we will summarise the current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on the recent work.

'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells.

PubMed

Toda, Mitsunori; Kawamoto, Teruya; Ueha, Takeshi; Kishimoto, Kenta; Hara, Hitomi; Fukase, Naomasa; Onishi, Yasuo; Harada, Risa; Minoda, Masaya; Kurosaka, Masahiro; Akisue, Toshihiro

2013-09-01

Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a 'decoy' for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has 'non-decoy' functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.

Phosphoinositides: Key modulators of energy metabolism☆

PubMed Central

Bridges, Dave; Saltiel, Alan R.

2014-01-01

Phosphoinositides are key players in many trafficking and signaling pathways. Recent advances regarding the synthesis, location and functions of these lipids have dramatically improved our understanding of how and when these lipids are generated and what their roles are in animal physiology. In particular, phosphoinositides play a central role in insulin signaling, and manipulation of PtdIns(3,4,5)P3 levels in particular, may be an important potential therapeutic target for the alleviation of insulin resistance associated with obesity and the metabolic syndrome. In this article we review the metabolism, regulation and functional roles of phosphoinositides in insulin signaling and the regulation of energy metabolism. This article is part of a Special Issue entitled Phosphoinositides. PMID:25463477

Boron in plants: deficiency and toxicity.

PubMed

Camacho-Cristóbal, Juan J; Rexach, Jesús; González-Fontes, Agustín

2008-10-01

Boron (B) is an essential nutrient for normal growth of higher plants, and B availability in soil and irrigation water is an important determinant of agricultural production. To date, a primordial function of B is undoubtedly its structural role in the cell wall; however, there is increasing evidence for a possible role of B in other processes such as the maintenance of plasma membrane function and several metabolic pathways. In recent years, the knowledge of the molecular basis of B deficiency and toxicity responses in plants has advanced greatly. The aim of this review is to provide an update on recent findings related to these topics, which can contribute to a better understanding of the role of B in plants.

Current opinion in Microbiology Roles of adaptor proteins in regulation of bacterial proteolysis

PubMed Central

Battesti, Aurelia; Gottesman, Susan

2013-01-01

Elimination of non-functional or unwanted proteins is critical for cell growth and regulation. In bacteria, ATP-dependent proteases target cytoplasmic proteins for degradation, contributing to both protein quality control and regulation of specific proteins, thus playing roles parallel to that of the proteasome in eukaryotic cells. Adaptor proteins provide a way to modulate the substrate specificity of the proteases and allow regulated proteolysis. Advances over the past few years have provided new insight into how adaptor proteins interact with both substrates and proteases and how adaptor functions are regulated. An important advance has come with the recognition of the critical roles of anti-adaptor proteins in regulating adaptor availability. PMID:23375660

Functional hierarchy of the N-terminal tyrosines of SLP-76.

PubMed

Jordan, Martha S; Sadler, Jeffrey; Austin, Jessica E; Finkelstein, Lisa D; Singer, Andrew L; Schwartzberg, Pamela L; Koretzky, Gary A

2006-02-15

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a central role in T cell activation and T cell development. SLP-76 has three functional modules: an acidic domain with three key tyrosines, a central proline-rich domain, and a C-terminal Src homology 2 domain. Of these, mutation of the three N-terminal tyrosines (Y112, Y128, and Y145) results in the most profound effects on T cell development and function. Y112 and Y128 associate with Vav and Nck, two proteins shown to be important for TCR-induced phosphorylation of proximal signaling substrates, Ca(2+) flux, and actin reorganization. Y145 has been shown to be important for optimal association of SLP-76 with inducible tyrosine kinase, a key regulator of T cell function. To investigate further the role of the phosphorylatable tyrosines of SLP-76 in TCR signaling, cell lines and primary T cells expressing SLP-76 with mutations in individual or paired tyrosine residues were analyzed. These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo.

Selection, periodicity and potential function for Highly Iterative Palindrome-1 (HIP1) in cyanobacterial genomes.

PubMed

Xu, Minli; Lawrence, Jeffrey G; Durand, Dannie

2018-03-16

Highly Iterated Palindrome 1 (HIP1, GCGATCGC) is hyper-abundant in most cyanobacterial genomes. In some cyanobacteria, average HIP1 abundance exceeds one motif per gene. Such high abundance suggests a significant role in cyanobacterial biology. However, 20 years of study have not revealed whether HIP1 has a function, much less what that function might be. We show that HIP1 is 15- to 300-fold over-represented in genomes analyzed. More importantly, HIP1 sites are conserved both within and between open reading frames, suggesting that their overabundance is maintained by selection rather than by continual replenishment by neutral processes, such as biased DNA repair. This evidence for selection suggests a functional role for HIP1. No evidence was found to support a functional role as a peptide or RNA motif or a role in the regulation of gene expression. Rather, we demonstrate that the distribution of HIP1 along cyanobacterial chromosomes is significantly periodic, with periods ranging from 10 to 90 kb, consistent in scale with periodicities reported for co-regulated, co-expressed and evolutionarily correlated genes. The periodicity we observe is also comparable in scale to chromosomal interaction domains previously described in other bacteria. In this context, our findings imply HIP1 functions associated with chromosome and nucleoid structure.

Selection, periodicity and potential function for Highly Iterative Palindrome-1 (HIP1) in cyanobacterial genomes

PubMed Central

Xu, Minli; Lawrence, Jeffrey G; Durand, Dannie

2018-01-01

Abstract Highly Iterated Palindrome 1 (HIP1, GCGATCGC) is hyper-abundant in most cyanobacterial genomes. In some cyanobacteria, average HIP1 abundance exceeds one motif per gene. Such high abundance suggests a significant role in cyanobacterial biology. However, 20 years of study have not revealed whether HIP1 has a function, much less what that function might be. We show that HIP1 is 15- to 300-fold over-represented in genomes analyzed. More importantly, HIP1 sites are conserved both within and between open reading frames, suggesting that their overabundance is maintained by selection rather than by continual replenishment by neutral processes, such as biased DNA repair. This evidence for selection suggests a functional role for HIP1. No evidence was found to support a functional role as a peptide or RNA motif or a role in the regulation of gene expression. Rather, we demonstrate that the distribution of HIP1 along cyanobacterial chromosomes is significantly periodic, with periods ranging from 10 to 90 kb, consistent in scale with periodicities reported for co-regulated, co-expressed and evolutionarily correlated genes. The periodicity we observe is also comparable in scale to chromosomal interaction domains previously described in other bacteria. In this context, our findings imply HIP1 functions associated with chromosome and nucleoid structure. PMID:29432573

Dopamine, Working Memory, and Training Induced Plasticity: Implications for Developmental Research

ERIC Educational Resources Information Center

Soderqvist, Stina; Bergman Nutley, Sissela; Peyrard-Janvid, Myriam; Matsson, Hans; Humphreys, Keith; Kere, Juha; Klingberg, Torkel

2012-01-01

Cognitive deficits and particularly deficits in working memory (WM) capacity are common features in neuropsychiatric disorders. Understanding the underlying mechanisms through which WM capacity can be improved is therefore of great importance. Several lines of research indicate that dopamine plays an important role not only in WM function but also…

Production supervisor impacts on subordinates' safety outcomes: an investigation of leader-member exchange and safety communication

Treesearch

Judd H. Michael; Zhen George Guo; Janice K. Wiedenbeck; Charles D. Ray

2006-01-01

Problem: Supervisors are increasingly important to the functioning of manufacturing operations, in large part due to their role as leaders. While supervisors' relations and communication with their subordinates are known to be important in influencing subordinates' behavior, little is known about how these two factors will impact...

Characterization and expression analysis of genes involved in SUMOylation during embryogenesis in rainbow trout (Oncorhynchus mykiss)

USDA-ARS?s Scientific Manuscript database

SUMOylation is the post-translational modification of proteins by the addition of the small ubiquitin-like modifier (SUMO), which plays an important role in various cellular processes. It has been reported that SUMO and its related proteins are important in diverse reproductive functions such as ovu...

The SLIT/ROBO pathway: a regulator of cell function with implications for the reproductive system

PubMed Central

Dickinson, Rachel E; Duncan, W Colin

2010-01-01

The secreted SLIT glycoproteins and their Roundabout (ROBO) receptors were originally identified as important axon guidance molecules. They function as a repulsive cue with an evolutionarily conserved role in preventing axons from migrating to inappropriate locations during the assembly of the nervous system. In addition the SLIT-ROBO interaction is involved in the regulation of cell migration, cell death and angiogenesis and, as such, has a pivotal role during the development of other tissues such as the lung, kidney, liver and breast. The cellular functions that the SLIT/ROBO pathway controls during tissue morphogenesis are processes that are dysregulated during cancer development. Therefore inactivation of certain SLITs and ROBOs is associated with advanced tumour formation and progression in disparate tissues. Recent research has indicated that the SLIT/ROBO pathway could also have important functions in the reproductive system. The fetal ovary expresses most members of the SLIT and ROBO families. The SLITs and ROBOs also appear to be regulated by steroid hormones and regulate physiological cell functions in adult reproductive tissues such as the ovary and endometrium. Furthermore several SLITs and ROBOs are aberrantly expressed during the development of ovarian, endometrial, cervical and prostate cancer. This review will examine the roles this pathway could have in the development, physiology and pathology of the reproductive system and highlight areas for future research that could further dissect the influence of the SLIT/ROBO pathway in reproduction. PMID:20100881

The SLIT-ROBO pathway: a regulator of cell function with implications for the reproductive system.

PubMed

Dickinson, Rachel E; Duncan, W Colin

2010-04-01

The secreted SLIT glycoproteins and their Roundabout (ROBO) receptors were originally identified as important axon guidance molecules. They function as a repulsive cue with an evolutionarily conserved role in preventing axons from migrating to inappropriate locations during the assembly of the nervous system. In addition the SLIT-ROBO interaction is involved in the regulation of cell migration, cell death and angiogenesis and, as such, has a pivotal role during the development of other tissues such as the lung, kidney, liver and breast. The cellular functions that the SLIT/ROBO pathway controls during tissue morphogenesis are processes that are dysregulated during cancer development. Therefore inactivation of certain SLITs and ROBOs is associated with advanced tumour formation and progression in disparate tissues. Recent research has indicated that the SLIT/ROBO pathway could also have important functions in the reproductive system. The fetal ovary expresses most members of the SLIT and ROBO families. The SLITs and ROBOs also appear to be regulated by steroid hormones and regulate physiological cell functions in adult reproductive tissues such as the ovary and endometrium. Furthermore several SLITs and ROBOs are aberrantly expressed during the development of ovarian, endometrial, cervical and prostate cancer. This review will examine the roles this pathway could have in the development, physiology and pathology of the reproductive system and highlight areas for future research that could further dissect the influence of the SLIT/ROBO pathway in reproduction.

The phylogenetic analysis of tetraspanins projects the evolution of cell-cell interactions from unicellular to multicellular organisms.

PubMed

Huang, Shengfeng; Yuan, Shaochun; Dong, Meiling; Su, Jing; Yu, Cuiling; Shen, Yang; Xie, Xiaojin; Yu, Yanhong; Yu, Xuesong; Chen, Shangwu; Zhang, Shicui; Pontarotti, Pierre; Xu, Anlong

2005-12-01

In animals, the tetraspanins are a large superfamily of membrane proteins that play important roles in organizing various cell-cell and matrix-cell interactions and signal pathways based on such interactions. However, their origin and evolution largely remain elusive and most of the family's members are functionally unknown or less known due to difficulties of study, such as functional redundancy. In this study, we rebuilt the family's phylogeny with sequences retrieved from online databases and our cDNA library of amphioxus. We reveal that, in addition to in metazoans, various tetraspanins are extensively expressed in protozoan amoebae, fungi, and plants. We also discuss the structural evolution of tetraspanin's major extracellular domain and the relation between tetraspanin's duplication and functional redundancy. Finally, we elucidate the coevolution of tetraspanins and eukaryotes and suggest that tetraspanins play important roles in the unicell-to-multicell transition. In short, the study of tetraspanin in a phylogenetic context helps us understand the evolution of intercellular interactions.

Rap G protein signal in normal and disordered lymphohematopoiesis

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

Minato, Nagahiro, E-mail: minato@imm.med.kyoto-u.ac.jp

2013-09-10

Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the developmentmore » and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy.« less

The role of the posterior cingulate cortex in cognition and disease

PubMed Central

Sharp, David J.

2014-01-01

The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer’s disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region’s function (the ‘Arousal, Balance and Breadth of Attention’ model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by ‘tuning’ whole-brain metastability and so adjusts how stable brain network activity is over time. PMID:23869106

High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss.

PubMed

Zeng, Heng; Vaka, Venkata Ramana; He, Xiaochen; Booz, George W; Chen, Jian-Xiong

2015-08-01

Mitochondrial dysfunction plays an important role in obesity-induced cardiac impairment. SIRT3 is a mitochondrial protein associated with increased human life span and metabolism. This study investigated the functional role of SIRT3 in obesity-induced cardiac dysfunction. Wild-type (WT) and SIRT3 knockout (KO) mice were fed a normal diet (ND) or high-fat diet (HFD) for 16 weeks. Body weight, fasting glucose levels, reactive oxygen species (ROS) levels, myocardial capillary density, cardiac function and expression of hypoxia-inducible factor (HIF)-1α/-2α were assessed. HFD resulted in a significant reduction in SIRT3 expression in the heart. Both HFD and SIRT3 KO mice showed increased ROS formation, impaired HIF signalling and reduced capillary density in the heart. HFD induced cardiac hypertrophy and impaired cardiac function. SIRT3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT3 KO mice on ND. Thus, the adverse effects of HFD on cardiac function were not attributable to SIRT3 loss alone. However, HFD did not further reduce capillary density in SIRT3 KO hearts, implicating SIRT3 loss in HFD-induced capillary rarefaction. Our study demonstrates the importance of SIRT3 in preserving heart function and capillary density in the setting of obesity. Thus, SIRT3 may be a potential therapeutic target for obesity-induced heart failure. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Executive functions in morality, religion, and paranormal beliefs.

PubMed

Wain, Omar; Spinella, Marcello

2007-01-01

Moral, religious, and paranormal beliefs share some degree of overlap and play important roles in guiding peoples' behavior. Although partly cultural phenomena, they also have neurobiological components based on functional neuroimaging studies and research in clinical populations. Because all three show relationships to prefrontal system functioning, the current study examined whether they related to executive functions as measured by the Executive Function Inventory in a community sample. As in previous research, religious beliefs related positively to both moral attitudes and paranormal beliefs. Moral attitudes, however, did not relate to paranormal beliefs. Paranormal beliefs related inversely to impulse control and organization, whereas small positive correlations occurred between traditional religious beliefs, impulse control, and empathy. Moral attitudes, on the other hand, showed consistent positive correlations with all executive functions measured, independent of demographic influences. These findings concordantly support that prefrontal systems play a role in morality, religion, and paranormal beliefs.

Genetic regulation of maize flower development and sex determination.

PubMed

Li, Qinglin; Liu, Baoshen

2017-01-01

The determining process of pistil fate are central to maize sex determination, mainly regulated by a genetic network in which the sex-determining genes SILKLESS 1 , TASSEL SEED 1 , TASSEL SEED 2 and the paramutagenic locus Required to maintain repression 6 play pivotal roles. Maize silks, which emerge from the ear shoot and derived from the pistil, are the functional stigmas of female flowers and play a pivotal role in pollination. Previous studies on sex-related mutants have revealed that sex-determining genes and phytohormones play an important role in the regulation of flower organogenesis. The processes determining pistil fate are central to flower development, where a silk identified gene SILKLESS 1 (SK1) is required to protect pistil primordia from a cell death signal produced by two commonly known genes, TASSEL SEED 1 (TS1) and TASSEL SEED 2 (TS2). In this review, maize flower developmental process is presented together with a focus on important sex-determining mutants and hormonal signaling affecting pistil development. The role of sex-determining genes, microRNAs, phytohormones, and the paramutagenic locus Required to maintain repression 6 (Rmr6), in forming a regulatory network that determines pistil fate, is discussed. Cloning SK1 and clarifying its function were crucial in understanding the regulation network of sex determination. The signaling mechanisms of phytohormones in sex determination are also an important research focus.

MACF1, versatility in tissue-specific function and in human disease.

PubMed

Hu, Lifang; Xiao, Yunyun; Xiong, Zhipeng; Zhao, Fan; Yin, Chong; Zhang, Yan; Su, Peihong; Li, Dijie; Chen, Zhihao; Ma, Xiaoli; Zhang, Ge; Qian, Airong

2017-09-01

Spectraplakins are a family of evolutionarily conserved gigantic proteins and play critical roles in many cytoskeleton-related processes. Microtubule actin crosslinking factor 1 (MACF1) is one of the most versatile spectraplakin with multiple isoforms. As a broadly expressed mammalian spectraplakin, MACF1 is important in maintaining normal functions of many tissues. The loss-of-function studies using knockout mouse models reveal the pivotal roles of MACF1 in embryo development, skin integrity maintenance, neural development, bone formation, and colonic paracellular permeability. Mutation in the human MACF1 gene causes a novel myopathy genetic disease. In addition, abnormal expression of MACF1 is associated with schizophrenia, Parkinson's disease, cancer and osteoporosis. This demonstrates the crucial roles of MACF1 in physiology and pathology. Here, we review the research advances of MACF1's roles in specific tissue and in human diseases, providing the perspectives of MACF1 for future studies. Copyright © 2017. Published by Elsevier Ltd.

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.

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 roles of plant phenolics in defence and communication during Agrobacterium and Rhizobium infection.

PubMed

Bhattacharya, Amita; Sood, Priyanka; Citovsky, Vitaly

2010-09-01

Phenolics are aromatic benzene ring compounds with one or more hydroxyl groups produced by plants mainly for protection against stress. The functions of phenolic compounds in plant physiology and interactions with biotic and abiotic environments are difficult to overestimate. Phenolics play important roles in plant development, particularly in lignin and pigment biosynthesis. They also provide structural integrity and scaffolding support to plants. Importantly, phenolic phytoalexins, secreted by wounded or otherwise perturbed plants, repel or kill many microorganisms, and some pathogens can counteract or nullify these defences or even subvert them to their own advantage. In this review, we discuss the roles of phenolics in the interactions of plants with Agrobacterium and Rhizobium.

Genetics Home Reference: Greenberg dysplasia

MedlinePlus

... domain, plays an important role in the production (synthesis) of cholesterol. Cholesterol is a type of fat ... of certain hormones and digestive acids. During cholesterol synthesis, the sterol reductase function of the lamin B ...

The project scientist's role in scientific spacecraft project management. M.S. Thesis - George Washington Univ.

NASA Technical Reports Server (NTRS)

Eller, E. L.

1976-01-01

The project scientists is in a position which rates very high in terms of behavioral study recommendations. His influence over objectives is generally considered to be important. He is highly autonomous in a moderately coordinated environment. He has diverse managerial and technical functions and the performance of these functions require him to grow beyond his role as an experimenter. However, the position within the line organization for those interviewed is also very stimulating, rating almost as high by the same criteria. The role of project scientist may not be the dominant means of professional growth for the experienced scientific investigators. The influence which the project scientist exerts on the project and the stimulation of that position for him are determined largely by his position outside the defined project scientist role. The role of the project scientist is changing because the environment of those who become project scientists is changing.

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.

Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome.

PubMed

Sidhu, Vishaldeep K; Huang, Bill X; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong

2016-05-01

Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. Published by Elsevier Inc.

Clarifying the role of the mental health peer specialist in Massachusetts, USA: insights from peer specialists, supervisors and clients.

PubMed

Cabral, Linda; Strother, Heather; Muhr, Kathy; Sefton, Laura; Savageau, Judith

2014-01-01

Mental health peer specialists develop peer-to-peer relationships of trust with clients to improve their health and well-being, functioning in ways similar to community health workers. Although the number of peer specialists in use has been increasing, their role in care teams is less defined than that of the community health worker. This qualitative study explored how the peer specialist role is defined across different stakeholder groups, the expectations for this role and how the peer specialist is utilised and integrated across different types of mental health services. Data were collected through interviews and focus groups conducted in Massachusetts with peer specialists (N = 44), their supervisors (N = 14) and clients (N = 10) between September 2009 and January 2011. A consensus coding approach was used and all data outputs were reviewed by the entire team to identify themes. Peer specialists reported that their most important role is to develop relationships with clients and that having lived mental health experience is a key element in creating that bond. They also indicated that educating staff about the recovery model and peer role is another important function. However, they often felt a lack of clarity about their role within their organisation and care team. Supervisors valued the unique experience that peer specialists bring to an organisation. However, without a defined set of expectations for this role, they struggled with training, guiding and evaluating their peer specialist staff. Clients reported that the shared lived experience is important for the relationship and that working with a peer specialist has improved their mental health. With increasing support for person-centred integrated healthcare delivery models, the demand for mental health peer specialist services will probably increase. Therefore, clearer role definition, as well as workforce development focused on team orientation, is necessary for peer specialists to be fully integrated and supported in care teams. © 2013 John Wiley & Sons Ltd.

Emotion and Theory of Mind in Schizophrenia-Investigating the Role of the Cerebellum.

PubMed

Mothersill, Omar; Knee-Zaska, Charlotte; Donohoe, Gary

2016-06-01

Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks.

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.

[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.

A strong pelvic floor: how nurses can spread the word.

PubMed

Berzuk, Kelli

2007-02-01

The pelvic floor contains muscles that support continence, sexual functioning, childbirth and more. Yet, few people even know these muscles exist or how important they are to overall health and well-being. This article explains in detail the anatomy, functions and importance of the pelvic floor musculature (PFM) and how nurses can educate and empower women of all ages about its important role in many aspects of their health and well-being. Accompanying this article is a patient education page with specific instructions on how to exercise the PFM. 2007 The Association of Womens Health, Obstetric and Neonatal Nurses (AWHONN). All rights reserved.

Chromatin Pioneers | Center for Cancer Research

Cancer.gov

Taking advantage of their ability to explore provocative ideas, NCI investigators pioneered the study of chromatin to demonstrate its functional importance and lay the groundwork for understanding its role in cancer and other diseases.

Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

PubMed Central

Lucas, James E; Siegel, Justin B

2015-01-01

Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

A Perspective on Efflux Transport Proteins in the Liver

PubMed Central

Kock, K; Brouwer, K.L.R

2013-01-01

Detailed knowledge regarding the influence of hepatic transport proteins on drug disposition has advanced at a rapid pace over the past decade. Efflux transport proteins located in the basolateral and apical (canalicular) membranes of hepatocytes play an important role in the hepatic elimination of many endogenous and exogenous compounds, including drugs and metabolites. This review focuses on the role of these efflux transporters in hepatic drug excretion. The impact of these proteins as underlying factors for disease is highlighted, and the importance of hepatic efflux proteins in the efficacy and toxicity of drugs is discussed. In addition, a brief overview of methodology to evaluate the function of hepatic efflux transport proteins is provided. Current challenges in predicting the impact of altered efflux protein function on systemic, intestinal and hepatocyte exposure to drugs and metabolites are highlighted. PMID:22948894

Photobiomodulation on senescence

NASA Astrophysics Data System (ADS)

Liu, Timon Cheng-Yi; Cheng, Lei; Rong, Dong-Liang; Xu, Xiao-Yang; Cui, Li-Ping; Lu, Jian; Deng, Xiao-Yuan; Liu, Song-Hao

2006-09-01

Photobiomodulation (PBM) is an effect oflow intensity monochromatic light or laser irradiation (LIL) on biological systems. which stimulates or inhibits biological functions but does not result in irreducible damage. It has been observed that PBM can suppress cellular senescence, reverse skin photoageing and improve fibromyalgia. In this paper, the biological information model of photobiomodulation (BIMP) is used to discuss its mechanism. Cellular senescence can result from short, dysfunctional telomeres, oxidative stress, or oncogene expression, and may contribute to aging so that it can be seen as a decline of cellular function in which cAMP plays an important role, which provide a foundation for PBM on senescence since cellular senescence is a reasonable model of senescence and PBM is a cellular rehabilitation in which cAMP also plays an important role according to BIMP. The PBM in reversing skin photoageing and improving fibromyalgia are then discussed in detail.

Evolution under canalization and the dual roles of microRNAs—A hypothesis

PubMed Central

Wu, Chung-I; Shen, Yang; Tang, Tian

2009-01-01

Canalization refers to the process by which phenotypes are stabilized within species. Evolution by natural selection can proceed efficiently only when phenotypes are canalized. The existence and identity of canalizing genes have thus been an important, but controversial topic. Recent evidence has increasingly hinted that microRNAs may be involved in canalizing gene expression. Their paradoxical properties (e.g., strongly conserved but functionally dispensable) suggest unconventional regulatory roles. We synthesized published and unpublished results and hypothesize that miRNAs may have dual functions—in gene expression tuning and in expression buffering. In tuning, miRNAs modify the mean expression level of their targets, but in buffering they merely reduce the variance around a preset mean. In light of the constant emergence of new miRNAs, we further discuss the relative importance of these two functions in evolution. PMID:19411598

The emerging complexity of ubiquitin architecture.

PubMed

Ohtake, Fumiaki; Tsuchiya, Hikaru

2017-02-01

Ubiquitylation is an essential post-translational modification (PTM) of proteins with diverse cellular functions. Polyubiquitin chains with different topologies have different cellular roles, and are referred to as a 'ubiquitin code'. Recent studies have begun to reveal that more complex ubiquitin architectures function as important signals in several biological pathways. These include PTMs of ubiquitin itself, such as acetylated ubiquitin and phospho-ubiquitin. Moreover, important roles for heterogeneous polyubiquitin chains, such as mixed or branched chains, have been reported, which significantly increase the diversity of the ubiquitin code. In this review, we describe mass spectrometry-based methods to characterize the ubiquitin signal. We also describe recent advances in our understanding of complex ubiquitin architectures, including our own findings concerning ubiquitin acetylation and branching within polyubiquitin chains. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

The Protective Role of Melanin Against UV Damage in Human Skin

PubMed Central

Brenner, Michaela; Hearing, Vincent J.

2009-01-01

Human skin is repeatedly exposed to ultraviolet radiation (UVR) that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, since melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UV radiation on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention. PMID:18435612

A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.

PubMed

Yu, Qilin; Dong, Yijie; Xu, Ning; Qian, Kefan; Chen, Yulu; Zhang, Biao; Xing, Laijun; Li, Mingchun

2014-11-01

Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Functional Assessment: Old Wine in New Bottles.

ERIC Educational Resources Information Center

Ervin, Ruth A.; Ehrhardt, Kristal E.; Poling, Alan

2001-01-01

Traces functional assessment (FA) in school settings to early contributions by B. F. Skinner. FA plays an important role in behavior analysis, and the value of this approach in dealing with behavior problems in many settings has long been evident. Although interest in FA in school settings has only recently become widespread, FA in education has a…

Predictors of Behavioral Regulation in Kindergarten: Household Chaos, Parenting, and Early Executive Functions

ERIC Educational Resources Information Center

Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael

2016-01-01

Behavioral regulation is an important school readiness skill that has been linked to early executive function (EF) and later success in learning and school achievement. Although poverty and related risks, as well as negative parenting, have been associated with poorer EF and behavioral regulation, chaotic home environments may also play a role in…

Differential Item Functioning Analysis of High-Stakes Test in Terms of Gender: A Rasch Model Approach

ERIC Educational Resources Information Center

Alavi, Seyed Mohammad; Bordbar, Soodeh

2017-01-01

Differential Item Functioning (DIF) analysis is a key element in evaluating educational test fairness and validity. One of the frequently cited sources of construct-irrelevant variance is gender which has an important role in the university entrance exam; therefore, it causes bias and consequently undermines test validity. The present study aims…

The Correlates of Healthy Family Functioning: The Role of Consensus and Conflict in the Practice of Family Therapy.

ERIC Educational Resources Information Center

Green, Robert G.; Kolevzon, Michael F.

1986-01-01

Explored the relative importance of individual, dyadic, and triadic measures of intrafamily functioning in predicting family health. Dyadic measures pertaining to marital quality and parent-child relationships were more powerful predictors than either individual measures of emotional maturity, anxiety, self-esteem or locus of control, or triadic…

Functional role of the herbaceous layer in eastern deciduous forest

Treesearch

Katherine J. Elliott; James M. Vose; Jennifer D. Knoepp; Barton D. Clinton; Brian D. Kloeppel

2014-01-01

The importance of the herbaceous layer in regulating ecosystem processes in deciduous forests is generally unknown. We use a manipulative study in a rich, mesophytic cove forest in the southern Appalachians to test the following hypotheses: (i) the herbaceous functional group (HFG) in mesophytic coves accelerates carbon and nutrient cycling, (ii) high litter quality...

Preschoolers' Free Play--Connections with Emotional and Social Functioning

ERIC Educational Resources Information Center

Veiga, Guida; Neto, Carlos; Rieffe, Carolien

2016-01-01

Play has an important role in various aspects of children's development. However, time for free play has declined substantially over the last decades. To date, few studies have focused on the relationship between opportunities for free play and children's social functioning. The aims of this study are to examine whether children´s free play is…

Structure and functioning of dryland ecosystems in a changing world.

PubMed

Maestre, Fernando T; Eldridge, David J; Soliveres, Santiago; Kéfi, Sonia; Delgado-Baquerizo, Manuel; Bowker, Matthew A; García-Palacios, Pablo; Gaitán, Juan; Gallardo, Antonio; Lázaro, Roberto; Berdugo, Miguel

2016-11-01

Understanding how drylands respond to ongoing environmental change is extremely important for global sustainability. Here we review how biotic attributes, climate, grazing pressure, land cover change and nitrogen deposition affect the functioning of drylands at multiple spatial scales. Our synthesis highlights the importance of biotic attributes (e.g. species richness) in maintaining fundamental ecosystem processes such as primary productivity, illustrate how N deposition and grazing pressure are impacting ecosystem functioning in drylands worldwide, and highlight the importance of the traits of woody species as drivers of their expansion in former grasslands. We also emphasize the role of attributes such as species richness and abundance in controlling the responses of ecosystem functioning to climate change. This knowledge is essential to guide conservation and restoration efforts in drylands, as biotic attributes can be actively managed at the local scale to increase ecosystem resilience to global change.

Structure and functioning of dryland ecosystems in a changing world

PubMed Central

Maestre, Fernando T.; Eldridge, David J.; Soliveres, Santiago; Kéfi, Sonia; Delgado-Baquerizo, Manuel; Bowker, Matthew A.; García-Palacios, Pablo; Gaitán, Juan; Gallardo, Antonio; Lázaro, Roberto; Berdugo, Miguel

2017-01-01

Understanding how drylands respond to ongoing environmental change is extremely important for global sustainability. Here we review how biotic attributes, climate, grazing pressure, land cover change and nitrogen deposition affect the functioning of drylands at multiple spatial scales. Our synthesis highlights the importance of biotic attributes (e.g. species richness) in maintaining fundamental ecosystem processes such as primary productivity, illustrate how N deposition and grazing pressure are impacting ecosystem functioning in drylands worldwide, and highlight the importance of the traits of woody species as drivers of their expansion in former grasslands. We also emphasize the role of attributes such as species richness and abundance in controlling the responses of ecosystem functioning to climate change. This knowledge is essential to guide conservation and restoration efforts in drylands, as biotic attributes can be actively managed at the local scale to increase ecosystem resilience to global change. PMID:28239303

The TRPM2 channel: A thermo-sensitive metabolic sensor.

PubMed

Kashio, Makiko; Tominaga, Makoto

2017-09-03

Living organisms continually experience changes in ambient temperature. To detect such temperature changes for adaptive behavioral responses, we evolved the ability to sense temperature. Thermosensitive transient receptor potential (TRP) channels, so-called thermo-TRPs, are involved in many physiologic functions in diverse organisms and constitute important temperature sensors. One of the important roles of thermo-TRPs is detecting ambient temperature in sensory neurons. Importantly, the functional expression of thermo-TRPs is observed not only in sensory neurons but also in tissues and cells that are not exposed to drastic temperature changes, indicating that thermo-TRPs are involved in many physiologic functions within the body's normal temperature range. Among such thermo-TRPs, this review focuses on one thermo-sensitive metabolic sensor in particular, TRPM2, and summarizes recent progress to clarify the regulatory mechanisms and physiologic functions of TRPM2 at body temperature under various metabolic states.

Positron Emission Tomography of the Heart

DOE R&D Accomplishments Database

Schelbert, H. R.; Phelps, M. E.; Kuhl, D. E.

1979-01-01

Positron emission computed tomography (PCT) represents an important new tool for the noninvasive evaluation and, more importantly, quantification of myocardial performance. Most currently available techniques permit assessment of only one aspect of cardiac function, i.e., myocardial perfusion by gamma scintillation camera imaging with Thallium-201 or left ventricular function by echocardiography or radionuclide angiocardiography. With PCT it may become possible to study all three major segments of myocardial performance, i.e., regional blood flow, mechanical function and, most importantly, myocardial metabolism. Each of these segments can either be evaluated separately or in combination. This report briefly describes the principles and technological advantages of the imaging device, reviews currently available radioactive tracers and how they can be employed for the assessment of flow, function and metabolism; and, lastly, discusses possible applications of PCT for the study of cardiac physiology or its potential role in the diagnosis of cardiac disease.

Roles of Principals in the Preparing Students to Life

ERIC Educational Resources Information Center

Arslan, Hasan; Bingul, Murat

2006-01-01

This article explores the impacts of school leaders on the school curriculums of preparing students to life. Even if the school leaders and teachers are expert in their area related to the functions of the schools, it seems that schools are failing in the preparation of the students to life. The school leaders may play an important role to…

The Development Officer in Higher Education: Toward an Understanding of the Role. ASHE-ERIC Higher Education Report No. 4.

ERIC Educational Resources Information Center

Worth, Michael J.; Asp, James W., II

Despite growth in the scope and importance of the college or university chief development officer's role, it remains relatively unexamined and the subject of differing perceptions. This report reviews the history and current status of the development function. Major authors on the subject are reviewed and placed into four "schools of…

A Snapshot of the Role of the Textbook in English Secondary Mathematics Classrooms

ERIC Educational Resources Information Center

O'Keeffe, Lisa; White, Bruce

2017-01-01

The role and function of the mathematics textbook has been widely discussed since its inclusion in the Trends in International Mathematics and Science study (TIMSS) in the late nineties. It is a common feature in many classrooms worldwide and has been identified as an important vehicle for the promotion of curricula. However, there has also been…

Vocal coordination and vocal imitation: a role for mirror neurons?

PubMed

Newman, John D

2014-04-01

Some birds and mammals have vocal communication systems in which coordination between individuals is important. Examples would include duetting or antiphonal calling in some birds and mammals, rapid exchanges of the same vocalization, and vocal exchanges between paired individuals and other nearby pairs. Mirror neurons may play a role in such systems but become functional only after experience.

Coverage of Major Topics in Economics in the Undergraduate Curriculum: Economists as Gatekeepers.

ERIC Educational Resources Information Center

Prescott, Suzanne

Over the last 25 years, less attention has been devoted to the role of the economist as teacher or professor than to the role of economist as scholar or researcher. Teachers have been seen as passive recipients of advances in economics research that they simply hand on to their students. Yet teachers perform an important gatekeeping function when…

Role of PSMA in Aberrant Cell Cycle Progression in Prostate Cancer

DTIC Science & Technology

2004-12-01

playing a role in nutrient uptake, and a peptidase involved in signal transduction in prostate epithelial cells. Insights into possible functions of PSMA...should improve the diagnostic and therapeutic values of this clinically important molecule. prostate cancer; receptor; peptidase ; endocytosis 2 OVERVIEW... peptidase activities hydrolyze gamma-peptide bonds between N-acetylaspartate and glutamate in the abundant neuropeptide N-acetylaspartylglutamate

Underground Management: An Examination of World War II Resistance Movements

DTIC Science & Technology

1994-03-24

127 1. Background .................................... 128 2. Role of the Leader ............................ 132 3. Who Were the Underground... leaders of these organizations towards underground activity had a major impact on the course its followers would pursue. Thus, instead of alienating...first section will explore the environment in which the underground leadership functioned, the importance of leadership, the role of the leader , who

The role of the leptin in reproduction.

PubMed

Cervero, Ana; Domínguez, Francisco; Horcajadas, José A; Quiñonero, Alicia; Pellicer, Antonio; Simón, Carlos

2006-06-01

Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function. This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo-pituitary-gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reproductive tissues, indicating that this system could be also implicated in several processes such as embryo development, implantation and pregnancy. Moreover, disorders of the leptin system have been related to some reproductive pathologies such as pre-eclampsia and polycystic ovary syndrome. However, controversy surrounds several aspects of the action of leptin in reproduction that require a deeper investigation of this system. Results to date suggest that this system could be implicated in important reproductive processes such as embryonic development and implantation. Moreover, understanding the role of leptin might be useful for new treatments in reproductive pathologies.

Mutational analysis of TRAF6 reveals a conserved functional role of the RING dimerization interface and a potentially necessary but insufficient role of RING-dependent TRAF6 polyubiquitination towards NF-κB activation

PubMed Central

Megas, Charilaos; Hatzivassiliou, Eudoxia G.; Yin, Qian; Vignali, Dario A.A.; Mosialos, George

2011-01-01

TRAF6 is an E3 ubiquitin ligase that plays a pivotal role in the activation of NF-κB by innate and adaptive immunity stimuli. TRAF6 consists of a highly conserved carboxyl terminal TRAF-C domain which is preceded by a coiled coil domain and an amino terminal region that contains a RING domain and a series of putative zinc-finger motifs. The TRAF-C domain contributes to TRAF6 oligomerization and mediates the interaction of TRAF6 with upstream signaling molecules whereas the RING domain comprises the core of the ubiquitin ligase catalytic domain. In order to identify structural elements that are important for TRAF6-induced NF-κB activation, mutational analysis of the TRAF-C and RING domains was performed. Alterations of highly conserved residues of the TRAF-C domain of TRAF6 did not affect significantly the ability of the protein to activate NF-κB. On the other hand a number of functionally important residues (L77, Q82, R88, F118, N121 and E126) for the activation of NF-κB were identified within the RING domain of TRAF6. Interestingly, several homologues of these residues in TRAF2 were shown to have a conserved functional role in TRAF2-induced NF-κB activation and lie at the dimerization interface of the RING domain. Finally, whereas alteration of Q82, R88 and F118 compromised both the K63-linked polyubiquitination of TRAF6 and its ability to activate NF-κB, alteration of L77, N121 and E126 diminished the NF-κB activating function of TRAF6 without affecting TRAF6 K63-linked polyubiquitination. Our results support a conserved functional role of the TRAF RING domain dimerization interface and a potentially necessary but insufficient role for RING-dependent TRAF6 K63-linked polyubiquitination towards NF-κB activation in cells. PMID:21185369

Mutational analysis of TRAF6 reveals a conserved functional role of the RING dimerization interface and a potentially necessary but insufficient role of RING-dependent TRAF6 polyubiquitination towards NF-κB activation.

PubMed

Megas, Charilaos; Hatzivassiliou, Eudoxia G; Yin, Qian; Marinopoulou, Elli; Hadweh, Paul; Vignali, Dario A A; Mosialos, George

2011-05-01

TRAF6 is an E3 ubiquitin ligase that plays a pivotal role in the activation of NF-κB by innate and adaptive immunity stimuli. TRAF6 consists of a highly conserved carboxyl terminal TRAF-C domain which is preceded by a coiled coil domain and an amino terminal region that contains a RING domain and a series of putative zinc-finger motifs. The TRAF-C domain contributes to TRAF6 oligomerization and mediates the interaction of TRAF6 with upstream signaling molecules whereas the RING domain comprises the core of the ubiquitin ligase catalytic domain. In order to identify structural elements that are important for TRAF6-induced NF-κB activation, mutational analysis of the TRAF-C and RING domains was performed. Alterations of highly conserved residues of the TRAF-C domain of TRAF6 did not affect significantly the ability of the protein to activate NF-κB. On the other hand a number of functionally important residues (L77, Q82, R88, F118, N121 and E126) for the activation of NF-κB were identified within the RING domain of TRAF6. Interestingly, several homologues of these residues in TRAF2 were shown to have a conserved functional role in TRAF2-induced NF-κB activation and lie at the dimerization interface of the RING domain. Finally, whereas alteration of Q82, R88 and F118 compromised both the K63-linked polyubiquitination of TRAF6 and its ability to activate NF-κB, alteration of L77, N121 and E126 diminished the NF-κB activating function of TRAF6 without affecting TRAF6 K63-linked polyubiquitination. Our results support a conserved functional role of the TRAF RING domain dimerization interface and a potentially necessary but insufficient role for RING-dependent TRAF6 K63-linked polyubiquitination towards NF-κB activation in cells. Copyright © 2010 Elsevier Inc. All rights reserved.

The Role of Food Antioxidants, Benefits of Functional Foods, and Influence of Feeding Habits on the Health of the Older Person: An Overview.

PubMed

Wilson, Douglas W; Nash, Paul; Buttar, Harpal Singh; Griffiths, Keith; Singh, Ram; De Meester, Fabien; Horiuchi, Rie; Takahashi, Toru

2017-10-28

This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer's disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer's disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today's new older person generation.

The Role of Food Antioxidants, Benefits of Functional Foods, and Influence of Feeding Habits on the Health of the Older Person: An Overview

PubMed Central

Wilson, Douglas W.; Nash, Paul; Buttar, Harpal Singh; Griffiths, Keith; De Meester, Fabien; Horiuchi, Rie; Takahashi, Toru

2017-01-01

This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer’s disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer’s disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today’s new older person generation. PMID:29143759

The value of eutherian-marsupial comparisons for understanding the function of glucocorticoids in female mammal reproduction.

PubMed

Fanson, Kerry V; Parrott, Marissa L

2015-11-01

This article is part of a Special Issue "SBN 2014". Chronic stress is known to inhibit female reproductive function. Consequently, it is often assumed that glucocorticoid (GC) concentrations should be negatively correlated with reproductive success because of the role they play in stress physiology. In contrast, a growing body of evidence indicates that GCs play an active role in promoting reproductive function. It is precisely because GCs are so integral to the entire process that disruptions to adrenal activity have negative consequences for reproduction. The goal of this paper is to draw attention to the increasing evidence showing that increases in adrenal activity are important for healthy female reproduction. Furthermore, we outline several hypotheses about the functional role(s) that GCs may play in mediating reproduction and argue that comparative studies between eutherian and marsupial mammals, which exhibit some pronounced differences in reproductive physiology, may be particularly useful for testing different hypotheses about the functional role of GCs in reproduction. Much of our current thinking about GCs and reproduction comes from research involving stress-induced levels of GCs and has led to broad assumptions about the effects of GCs on reproduction. Unfortunately, this has left a gaping hole in our knowledge about basal GC levels and how they may influence reproductive function, thereby preventing a broader understanding of adrenal physiology and obscuring potential solutions for reproductive dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Personal reflections on a galvanizing trail.

PubMed

O'Dell, B L

1998-01-01

This article encompasses my perception of, and experience in, an exciting segment of the trace element era in nutrition research: the role of zinc in the nutrition of animals and humans. Zinc has been a major player on the stage of trace element research, and it has left a trail that galvanized the attention of many researchers, including myself. It is ubiquitous in biological systems, and it plays a multitude of physiologic and biochemical functions. A brief historical overview is followed by a discussion of the contributions the work done in my laboratory has made toward understanding the physiological and biochemical functions of zinc. The effort of 40 years has led to the belief that one of zinc's major roles, and perhaps its first limiting role, is to preserve plasma-membrane function as regards ion channels and signal transduction. Although substantial knowledge has been gained relating to the importance of zinc in nutrition, much remains to be discovered.

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.

A review on cardiovascular diseases originated from subclinical hypothyroidism.

PubMed

Mansourian, Azad Reza

2012-01-15

Thyroid hormones play an important role on the cardiovascular systems and thyroid disorder ultimately have a profound adverse effects on myocardium and vascular functions. There are extensive reports on the role of overt thyroid dysfunction which adversely can modify the cardiovascular metabolism but even at the present of some controversial reports, the subclinical thyroid disorders are able also to manipulate cardiovascular system to some extent. The aim of this study is to review the cardiovascular disorders accompanied with subclinical hypothyroidism. It is concluded that adverse effect of thyroid malfunction on myocardium and vascular organs are through the direct role of thyroid hormone and dyslipidemia on heart muscle cells at nuclear level and vascular system, respectively. It seems many cardiovascular disorders initially would not have been occurred in the first place if the thyroid of affected person had functioned properly, therefore thyroid function tests should be one of a prior laboratory examinations in cardiovascular disorders.

The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

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

Tsukamoto, Yuta; Katayama, Chisako; Shinohara, Miki

Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our datamore » strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions.« less

Cannabinoids and atherosclerosis.

PubMed

Fisar, Zdenek

2009-01-01

The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid. The study of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis. Basic information about function and role of the endocannabinoid system is summarized in the paper; possible therapeutic action of cannabinoids, effects on atherosclerosis specially, is described at the close.

STAT6: its role in interleukin 4-mediated biological functions.

PubMed

Takeda, K; Kishimoto, T; Akira, S

1997-05-01

Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

A compensatory role for declarative memory in neurodevelopmental disorders.

PubMed

Ullman, Michael T; Pullman, Mariel Y

2015-04-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

A compensatory role for declarative memory in neurodevelopmental disorders

PubMed Central

Ullman, Michael T.; Pullman, Mariel Y.

2015-01-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

Ants and termites increase crop yield in a dry climate

PubMed Central

Evans, Theodore A.; Dawes, Tracy Z.; Ward, Philip R.; Lo, Nathan

2011-01-01

Agricultural intensification has increased crop yields, but at high economic and environmental cost. Harnessing ecosystem services of naturally occurring organisms is a cheaper but under-appreciated approach, because the functional roles of organisms are not linked to crop yields, especially outside the northern temperate zone. Ecosystem services in soil come from earthworms in these cooler and wetter latitudes; what may fulfill their functional role in agriculture in warmer and drier habitats, where they are absent, is unproven. Here we show in a field experiment that ants and termites increase wheat yield by 36% from increased soil water infiltration due to their tunnels and improved soil nitrogen. Our results suggest that ants and termites have similar functional roles to earthworms, and that they may provide valuable ecosystem services in dryland agriculture, which may become increasingly important for agricultural sustainability in arid climates. PMID:21448161

Interactions of Kraft lignin and wheat gluten during biomaterial processing: evidence for the role of phenolic groups.

PubMed

Kaewtatip, Kaewta; Menut, Paul; Auvergne, Remi; Tanrattanakul, Varaporn; Morel, Marie-Helene; Guilbert, Stephane

2010-04-14

The chemical interactions between Kraft lignin and wheat gluten under processing conditions were investigated by determining the extent of the protein network formation. To clarify the role of different chemical functions found in lignin, the effect of Kraft lignin was compared with that of an esterified lignin, in which hydroxyl groups had been suppressed by esterification, and with a series of simple aromatics and phenolic structures with different functionalities (conjugated double bonds, hydroxyl, carboxylic acid, and aldehyde). The protein solubility was determined by using the Kjeldahl method. The role of the hydroxyl function was assessed by the significantly lower effect of esterified lignin. The importance of the phenolic radical scavenging structure is evidenced by the effect of guaiacol, which results in a behavior similar to that of the Kraft lignin. In addition, the significant effect of conjugated double bonds on gluten reactivity, through nucleophilic addition, was demonstrated.

Identification of Tyrosine 972 as a Novel Site of Jak2 Tyrosine Kinase Phosphorylation and its Role in Jak2 Activation

PubMed Central

McDoom, Issam; Ma, Xianyue; Kirabo, Annet; Lee, Kuang-Yung; Ostrov, David A.; Sayeski, Peter P.

2013-01-01

Jak2 is a 130 kDa tyrosine kinase that is important in a number of cellular signaling pathways. Its function is intrinsically regulated by the phosphorylation of a handful of its 49 tyrosines. Here, we report that tyrosine 972 (Y972) is a novel site of Jak2 phosphorylation, and hence auto-regulation. Specifically, we found that Y972 is phosphorylated and confirmed that this residue resides on the surface of the protein. Using expression plasmids that expressed either wild type Jak2 or a full length Jak2 cDNA containing a single Y972F substitution mutation, we investigated the consequences of losing Y972 phosphorylation on Jak2 function. We determined that the loss of Y972 phosphorylation significantly reduced both Jak2 total tyrosine phosphorylation and phosphorylation of Y1007/Y1008. Additionally, Y972 phosphorylation was shown to be important for maximal kinase function. Interestingly, in response to classical cytokine activation, the Jak2-Y972F mutant exhibited a moderately impaired level of activation when compared to wild type protein. However, when Jak2 was activated via a GPCR ligand, the ability of the Y972F mutant to activate was completely lost, therefore suggesting a differential role of Y972 in Jak2 activation. Finally, we found that phosphorylation of Y972 enhances Jak2 kinase function via a mechanism that appears to stabilize the active conformation of the protein. Collectively, our results suggest that Y972 is a novel site of Jak2 phosphorylation and plays an important differential role in ligand-dependent Jak2 activation via a mechanism that involves stabilization of the Jak2 active conformation. PMID:18636744

The role of identification in dynamic psychiatry and psychotherapy.

PubMed

Corradi, Richard B

2011-01-01

Identification-a psychic process in which a person takes on characteristics of another-is a concept important to the understanding of human nature. It plays an important role in how our personalities develop, in our ability to deal with life's stresses, and in how we interact with other people. Knowledge of its manifestations is essential to dynamic psychiatry and to its applications in psychotherapy. This article defines identification and reviews its role in development and as a defense. It discusses its role in the psychopathology of disorders commonly encountered in psychotherapy practice-depression and anxiety states reactive to losses in life, and borderline states. Clinical vignettes illustrate how identification functions in these conditions, and also how identifications reveal themselves in the transference and are utilized in psychotherapy. A teaching vignette illustrates how important it is that residents learning the art of psychotherapy appreciate the therapeutic potential of identification. The article maintains that, although it often goes unrecognized, identification with the therapist is one of the most effective therapeutic devices in the transference.

Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

Functional roles and metabolic niches in the honey bee gut microbiota.

PubMed

Bonilla-Rosso, Germán; Engel, Philipp

2018-06-01

Gut microbiota studies on diverse animals facilitate our understanding of the general principles governing microbiota-host interactions. The honey bee adds a relevant study system due to the simplicity and experimental tractability of its gut microbiota, but also because bees are important pollinators that suffer from population declines worldwide. The use of gnotobiotic bees combined with genetic tools, 'omics' analysis, and experimental microbiology has recently provided important insights about the impact of the microbiota on bee health and the general functioning of gut ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nitrilase enzymes and their role in plant–microbe interactions

PubMed Central

Howden, Andrew J. M.; Preston, Gail M.

2009-01-01

Summary Nitrilase enzymes (nitrilases) catalyse the hydrolysis of nitrile compounds to the corresponding carboxylic acid and ammonia, and have a wide range of industrial and biotechnological applications, including the synthesis of industrially important carboxylic acids and bioremediation of cyanide and toxic nitriles. Nitrilases are produced by a wide range of organisms, including plants, bacteria and fungi, but despite their biotechnological importance, the role of these enzymes in living organisms is relatively underexplored. Current research suggests that nitrilases play important roles in a range of biological processes. In the context of plant–microbe interactions they may have roles in hormone synthesis, nutrient assimilation and detoxification of exogenous and endogenous nitriles. Nitrilases are produced by both plant pathogenic and plant growth‐promoting microorganisms, and their activities may have a significant impact on the outcome of plant–microbe interactions. In this paper we review current knowledge of the role of nitriles and nitrilases in plants and plant‐associated microorganisms, and discuss how greater understanding of the natural functions of nitrilases could be applied to benefit both industry and agriculture. PMID:21255276

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications

PubMed Central

Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

2017-01-01

Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lncRNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). Certain lncRNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lncRNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lncRNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC. PMID:28932078

Spatial Tourist and Functional Diversity on the Volcanic Island of Gran Canaria

NASA Astrophysics Data System (ADS)

Gonda-Soroczyńska, Eleonora; Olczyk, Hanna

2017-10-01

The conducted research is focused on spatial, functional and landscape diversity, the existing tourist potential and the possibilities for further development of a small, volcanic island of Gran Canaria. The discussed island was compared against other islands of the Canarian archipelago (Lanzarote, Fuerteventura, Tenerife, La Palma, El Hierro). Similarly to the remaining Canary Islands, the economy of Gran Canaria is predominantly based on tourism (approx. 4,5-5,0 million tourists visit the Canary Island annually and approx. 2,8 million come to Gran Canaria). Additionally, Puerto de la Luz transhipment centre in Las Palmas plays a very important role because of the goods imported from overseas. It is one of the largest ports in Spain (it reloads almost 2 million containers per year) also being an important Atlantic refuelling station. Apart from tourism, an important role is played here by agriculture, primarily the cultivation of bananas and tomatoes, which represent the most significant export good of the archipelago. The conducted spatial research showed an extensive diversity. This situation is, to a great extent, influenced by the climate. The northern part is cooler and dominated by agriculture, whereas the southern one is much warmer and characterized by a well-developed tourism infrastructure. Site inspections performed out along the outer contour of the island resembling a circle. Numerous architectural and urban sketches, urban analyses and photographic documentation were made. Community surveys were carried out. For a researcher, it was extremely interesting to answer the questions whether Gran Canaria is different from the other Canary Islands, especially in the functional and landscape context, and if so what exactly these differences consist of. What is Gran Canaria in particular characterized by and what kind of role it plays in the economic sector of Spain?

TMBP200, a XMAP215 homologue of tobacco BY-2 cells, has an essential role in plant mitosis.

PubMed

Yasuhara, Hiroki; Oe, Yuki

2011-07-01

TMBP200 from tobacco BY-2 cells is a member of the highly conserved family of microtubule-associated proteins that includes Xenopus XMAP215, human TOGp, and Arabidopsis MOR1/GEM1. XMAP215 homologues have an essential role in spindle assembly and function in animals and yeast, but their role in plant mitosis is not fully clarified. Here, we show by immunoblot analysis that TMBP200 levels in synchronously cultured BY-2 cells increased when the cells entered mitosis, thus indicating that TMBP200 plays an important role in mitosis in tobacco. To investigate the role of TMBP200 in mitosis, we employed inducible RNA interference to silence TMBP200 expression in BY-2 cells. The resulting depletion of TMBP200 caused severe defects in bipolar spindle formation and resulted in the appearance of multinucleated cells with variable-sized nuclei. This finding indicates that TMBP200 has an essential role in bipolar spindle formation and function.

Progranulin, lysosomal regulation and neurodegenerative disease.

PubMed

Kao, Aimee W; McKay, Andrew; Singh, Param Priya; Brunet, Anne; Huang, Eric J

2017-06-01

The discovery that heterozygous and homozygous mutations in the gene encoding progranulin are causally linked to frontotemporal dementia and lysosomal storage disease, respectively, reveals previously unrecognized roles of the progranulin protein in regulating lysosome biogenesis and function. Given the importance of lysosomes in cellular homeostasis, it is not surprising that progranulin deficiency has pleiotropic effects on neural circuit development and maintenance, stress response, innate immunity and ageing. This Progress article reviews recent advances in progranulin biology emphasizing its roles in lysosomal function and brain innate immunity, and outlines future avenues of investigation that may lead to new therapeutic approaches for neurodegeneration.

A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure.

PubMed

Margolis, Kara Gross

2017-10-01

Many disease conditions considered CNS-predominant harbor significant intestinal comorbidities. Serotonin (5-HT) and the serotonin reuptake transporter (SERT) have increasingly been shown to play important roles in both brain and intestinal development and long-term function. 5-HT and SERT may thus modulate critical functions in the development and perpetuation of brain-gut axis disease. We discuss the potential roles of 5-HT and SERT in the brain and intestinal manifestations of autism spectrum disorders and developmental antidepressant exposure. The potential therapeutic value of 5-HT 4 modulation in the subsequent treatment of these conditions is also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Histamine and motivation

PubMed Central

Torrealba, Fernando; Riveros, Maria E.; Contreras, Marco; Valdes, Jose L.

2012-01-01

Brain histamine may affect a variety of different behavioral and physiological functions; however, its role in promoting wakefulness has overshadowed its other important functions. Here, we review evidence indicating that brain histamine plays a central role in motivation and emphasize its differential involvement in the appetitive and consummatory phases of motivated behaviors. We discuss the inputs that control histaminergic neurons of the tuberomamillary nucleus (TMN) of the hypothalamus, which determine the distinct role of these neurons in appetitive behavior, sleep/wake cycles, and food anticipatory responses. Moreover, we review evidence supporting the dysfunction of histaminergic neurons and the cortical input of histamine in regulating specific forms of decreased motivation (apathy). In addition, we discuss the relationship between the histamine system and drug addiction in the context of motivation. PMID:22783171

Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.

PubMed

Danhauser, Katharina; Herebian, Diran; Haack, Tobias B; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

2016-03-01

Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in COQ9. Functional studies in patient fibroblasts showed that the absence of the COQ9 protein was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone10. At the same time, the total amount of CoQ10 was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (complex II/III) activity. Lentiviral expression of COQ9 restored all these parameters, confirming the causal role of the variant. Our report on the second COQ9 patient expands the clinical spectrum associated with COQ9 variants, indicating the importance of COQ9 already during prenatal development. Moreover, the rescue of cellular CoQ10 levels and respiratory chain complex activities by CoQ10 supplementation points to the importance of an early diagnosis and immediate treatment.

Conceptual model of consumer’s willingness to eat functional foods

PubMed

Babicz-Zielinska, Ewa; Jezewska-Zychowicz, Maria

The functional foods constitute the important segment of the food market. Among factors that determine the intentions to eat functional foods, the psychological factors play very important roles. Motives, attitudes and personality are key factors. The relationships between socio-demographic characteristics, attitudes and willingness to purchase functional foods were not fully confirmed. Consumers’ beliefs about health benefits from eaten foods seem to be a strong determinant of a choice of functional foods. The objective of this study was to determine relations between familiarity, attitudes, and beliefs in benefits and risks about functional foods and develop some conceptual models of willingness to eat. The sample of Polish consumers counted 1002 subjects at age 15+. The foods enriched with vitamins or minerals, and cholesterol-lowering margarine or drinks were considered. The questionnaire focused on familiarity with foods, attitudes, beliefs about benefits and risks of their consumption was constructed. The Pearson’s correlations and linear regression equations were calculated. The strongest relations appeared between attitudes, high health value and high benefits, (r = 0.722 and 0.712 for enriched foods, and 0.664 and 0.693 for cholesterol-lowering foods), and between high health value and high benefits (0.814 for enriched foods and 0.758 for cholesterol-lowering foods). The conceptual models based on linear regression of relations between attitudes and all other variables, considering or not the familiarity with the foods, were developed. The positive attitudes and declared consumption are more important for enriched foods. The beliefs on high health value and high benefits play the most important role in the purchase. The interrelations between different variables may be described by new linear regression models, with the beliefs in high benefits, positive attitudes and familiarity being most significant predictors. Health expectations and trust to functional foods are the key factors in their choice.

Regulation of sympathetic nervous system function after cardiovascular deconditioning

NASA Technical Reports Server (NTRS)

Hasser, E. M.; Moffitt, J. A.

2001-01-01

Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.

Ecosystem functions including soil organic carbon, total nitrogen and available potassium are crucial for vegetation recovery.

PubMed

Qiu, Kaiyang; Xie, Yingzhong; Xu, Dongmei; Pott, Richard

2018-05-15

The effects of biodiversity on ecosystem functions have been extensively studied, but little is known about the effects of ecosystem functions on biodiversity. This knowledge is important for understanding biodiversity-ecosystem functioning relationships. Desertification reversal is a significant global challenge, but the factors that play key roles in this process remain unclear. Here, using data sampled from areas undergoing desertification reversal, we identify the dominant soil factors that play a role in vegetation recovery with ordinary least squares and structural equation modelling. We found that ecosystem functions related to the cycling of soil carbon (organic C, SOC), nitrogen (total N, TN), and potassium (available K, AK) had the most substantial effects on vegetation recovery. The effects of these ecosystem functions were simultaneously influenced by the soil clay, silt and coarse sand fractions and the soil water content. Our findings suggest that K plays a critical role in ecosystem functioning and is a limiting factor in desertification reversal. Our results provide a scientific basis for desertification reversal. Specifically, we found that plant biodiversity may be regulated by N, phosphorus (P) and K cycling. Collectively, biodiversity may respond to ecosystem functions, the conservation and enhancement of which can promote the recovery of vegetation.

Functional Abstraction as a Method to Discover Knowledge in Gene Ontologies

PubMed Central

Ultsch, Alfred; Lötsch, Jörn

2014-01-01

Computational analyses of functions of gene sets obtained in microarray analyses or by topical database searches are increasingly important in biology. To understand their functions, the sets are usually mapped to Gene Ontology knowledge bases by means of over-representation analysis (ORA). Its result represents the specific knowledge of the functionality of the gene set. However, the specific ontology typically consists of many terms and relationships, hindering the understanding of the ‘main story’. We developed a methodology to identify a comprehensibly small number of GO terms as “headlines” of the specific ontology allowing to understand all central aspects of the roles of the involved genes. The Functional Abstraction method finds a set of headlines that is specific enough to cover all details of a specific ontology and is abstract enough for human comprehension. This method exceeds the classical approaches at ORA abstraction and by focusing on information rather than decorrelation of GO terms, it directly targets human comprehension. Functional abstraction provides, with a maximum of certainty, information value, coverage and conciseness, a representation of the biological functions in a gene set plays a role. This is the necessary means to interpret complex Gene Ontology results thus strengthening the role of functional genomics in biomarker and drug discovery. PMID:24587272

Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases.

PubMed

Zhou, Zhi-Dong; Saw, Wuan-Ting; Tan, Eng-King

2017-09-01

The coiled-coil-helix-coiled-coil-helix domain (CHCHD)-containing proteins are evolutionarily conserved nucleus-encoded small mitochondrial proteins with important functions. So far, nine members have been identified in this protein family. All CHCHD proteins have at least one functional coiled-coil-helix-coiled-coil-helix (CHCH) domain, which is stabilized by two pairs of disulfide bonds between two helices. CHCHD proteins have various important pathophysiological roles in mitochondria and other key cellular processes. Mutations of CHCHD proteins have been associated with various human neurodegenerative diseases. Mutations of CHCHD10 are associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal lobe dementia (FTD), motor neuron disease, and late-onset spinal muscular atrophy and autosomal dominant mitochondrial myopathy. CHCHD10 stabilizes mitochondrial crista ultrastructure and maintains its integrity. In patients with CHCHD10 mutations, there are abnormal mitochondrial crista structure, deficiencies of respiratory chain complexes, impaired mitochondrial respiration, and multiple mitochondrial DNA (mtDNA) deletions. Recently, CHCHD2 mutations are linked with autosomal dominant and sporadic Parkinson's disease (PD). The CHCHD2 is a multifunctional protein and plays roles in regulation of mitochondrial metabolism, synthesis of respiratory chain components, and modulation of cell apoptosis. With a better understanding of the pathophysiologic roles of CHCHD proteins, they may be potential novel therapeutic targets for human neurodegenerative diseases.

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide.

PubMed

Amirtharaj, G Jayakumar; Natarajan, Sathish Kumar; Pulimood, Anna; Balasubramanian, K A; Venkatraman, Aparna; Ramachandran, Anup

2017-04-01

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Functional impacts of the intestinal microbiome in the pathogenesis of inflammatory bowel disease.

PubMed

Li, Jennifer; Butcher, James; Mack, David; Stintzi, Alain

2015-01-01

: The human intestinal microbiome plays a critical role in human health and disease, including the pathogenesis of inflammatory bowel disease (IBD). Numerous studies have identified altered bacterial diversity and abundance at varying taxonomic levels through biopsies and fecal samples of patients with IBD and diseased model animals. However, inconsistent observations regarding the microbial compositions of such patients have hindered the efforts in assessing the etiological role of specific bacterial species in the pathophysiology of IBD. These observations highlight the importance of minimizing the confounding factors associated with IBD and the need for a standardized methodology to analyze well-defined microbial sampling sources in early IBD diagnosis. Furthermore, establishing the linkage between microbiota compositions with their function within the host system can provide new insights on the pathogenesis of IBD. Such research has been greatly facilitated by technological advances that include functional metagenomics coupled with proteomic and metabolomic profiling. This review provides updates on the composition of the microbiome in IBD and emphasizes microbiota dysbiosis-involved mechanisms. We highlight functional roles of specific bacterial groups in the development and management of IBD. Functional analyses of the microbiome may be the key to understanding the role of microbiota in the development and chronicity of IBD and reveal new strategies for therapeutic intervention.

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).

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.

Assessing the role of Hartree-Fock exchange, correlation energy and long range corrections in evaluating ionization potential, and electron affinity in density functional theory.

PubMed

Vikramaditya, Talapunur; Lin, Shiang-Tai

2017-06-05

Accurate determination of ionization potentials (IPs), electron affinities (EAs), fundamental gaps (FGs), and HOMO, LUMO energy levels of organic molecules play an important role in modeling and predicting the efficiencies of organic photovoltaics, OLEDs etc. In this work, we investigate the effects of Hartree Fock (HF) Exchange, correlation energy, and long range corrections in predicting IP and EA in Hybrid Functionals. We observe increase in percentage of HF exchange results in increase of IPs and decrease in EAs. Contrary to the general expectations inclusion of both HF exchange and correlation energy (from the second order perturbation theory MP2) leads to poor prediction. Range separated Hybrid Functionals are found to be more reliable among various DFT Functionals investigated. DFT Functionals predict accurate IPs whereas post HF methods predict accurate EAs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Role of Bioreactors in Microbial Biomass and Energy Conversion

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

Zhang, Liang; Zhang, Biao; Zhu, Xun

Bioenergy is the world’s largest contributor to the renewable and sustainable energy sector, and it plays a significant role in various energy industries. A large amount of research has contributed to the rapidly evolving field of bioenergy and one of the most important topics is the use of the bioreactor. Bioreactors play a critical role in the successful development of technologies for microbial biomass cultivation and energy conversion. In this chapter, after a brief introduction to bioreactors (basic concepts, configurations, functions, and influencing factors), the applications of the bioreactor in microbial biomass, microbial biofuel conversion, and microbial electrochemical systems aremore » described. Importantly, the role and significance of the bioreactor in the bioenergy process are discussed to provide a better understanding of the use of bioreactors in managing microbial biomass and energy conversion.« less

Recent advances in understanding the role of the hypothalamic circuit during aggression

PubMed Central

Falkner, Annegret L.; Lin, Dayu

2014-01-01

The hypothalamus was first implicated in the classic “fight or flight” response nearly a century ago, and since then, many important strides have been made in understanding both the circuitry and the neural dynamics underlying the generation of these behaviors. In this review, we will focus on the role of the hypothalamus in aggression, paying particular attention to recent advances in the field that have allowed for functional identification of relevant hypothalamic subnuclei. Recent progress in this field has been aided by the development of new techniques for functional manipulation including optogenetics and pharmacogenetics, as well as advances in technology used for chronic in vivo recordings during complex social behaviors. We will examine the role of the hypothalamus through the complimentary lenses of (1) loss of function studies, including pharmacology and pharmacogenetics; (2) gain of function studies, including specific comparisons between results from classic electrical stimulation studies and more recent work using optogenetics; and (3) neural activity, including both immediate early gene and awake-behaving recordings. Lastly, we will outline current approaches to identifying the precise role of the hypothalamus in promoting aggressive motivation and aggressive action. PMID:25309351

Solitary Soulmates: The Marginalized Role of Intellectuals and Artists within American Higher Education--From an Address to the Newly Invested Members of Emory University Chapter of Phi Beta Kappa, 11 November 2002

ERIC Educational Resources Information Center

Flannery, James W.

2004-01-01

The author makes the case that the role of the intellectual is to effect change, to challenge vested interests that would limit dialogue on matters of grave importance and to function as a public witness-bearer to personal and public forms of truth. He goes on to state, however, that this role cannot be properly fulfilled unless narrow, purely…

Cell-Mediated Immunity and Its Role in Resistance to Infection

PubMed Central

Wing, Edward J.; Remington, Jack S.

1977-01-01

The recently acquired knowledge of the importance of cell-mediated immunity in many illnesses and the discovery of a variety of substances that can restore certain cell-mediated immune functions has served to focus the attention of physicians on this area of immunity. It is important for practicing physicians to have a clear understanding of current knowledge of the role of cell-mediated immunity in resistance to infection and how this arm of the immune system relates to the diagnosis and therapy of infectious diseases. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. PMID:318786

Genomic imprinting—an epigenetic gene-regulatory model

PubMed Central

Koerner, Martha V; Barlow, Denise P

2010-01-01

Epigenetic mechanisms (Box 1) are considered to play major gene-regulatory roles in development, differentiation and disease. However, the relative importance of epigenetics in defining the mammalian transcriptome in normal and disease states is unknown. The mammalian genome contains only a few model systems where epigenetic gene regulation has been shown to play a major role in transcriptional control. These model systems are important not only to investigate the biological function of known epigenetic modifications but also to identify new and unexpected epigenetic mechanisms in the mammalian genome. Here we review recent progress in understanding how epigenetic mechanisms control imprinted gene expression. PMID:20153958

Neural regulation of renal tubular sodium reabsorption and renin secretion: integrative aspects.

PubMed

DiBona, G F

1987-01-01

Efferent renal sympathetic nerve activity plays an important role in the regulation of renal function. Via its direct influence on renal tubular sodium reabsorption throughout the entire mammalian nephron, alterations in efferent renal sympathetic nerve activity represent an important physiological contribution to the overall role of the kidney in the regulation of external sodium balance and the defense against sodium deficit and surfeit. Abnormalities of this mechanism can lead to inappropriate renal sodium retention and augmentation of renin secretion, two factors which are capable of contributing to the development and maintenance of hypertension.

Transforming the Delivery of Care in the Post–Health Reform Era: What Role Will Community Health Workers Play?

PubMed Central

Ro, Marguerite; Villa, Normandy William; Powell, Wayne; Knickman, James R.

2011-01-01

The Patient Protection and Affordable Care Act (PPACA) affords opportunities to sustain the role of community health workers (CHWs). Among myriad strategies encouraged by PPACA are prevention and care coordination, particularly for chronic diseases, chief drivers of increased health care costs. Prevention and care coordination are functions that have been performed by CHWs for decades, particularly among underserved populations. The two key delivery models promoted in the PPACA are accountable care organizations and health homes. Both stress the importance of interdisciplinary, interprofessional health care teams, the ideal context for integrating CHWs. Equally important, the payment structures encouraged by PPACA to support these delivery models offer the vehicles to sustain the role of these valued workers. PMID:22021289

The role of stereopsis (three-dimensional vision) in dentistry: review of the current literature.

PubMed

Syrimi, M; Ali, N

2015-05-22

Clinical dental work is placing increasing demands on a clinician's vision as new techniques that require fine detail become more common. High hand-eye coordination requires good visual acuity as well as other psychological and neurological qualities such as stereopsis. Stereopsis (three-dimensional vision) is the highest form of depth perception obtained by visual disparity of images formed in the retinas of two eyes. It is believed to confer functional benefits on everyday tasks such as hand-eye coordination. Although its role in depth perception has long been established, little is known regarding the importance of stereopsis in dentistry. This article reviews the role of stereopsis in everyday life and the available literature on the importance of stereopsis in dentistry.

Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections

PubMed Central

Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

2015-01-01

Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters. PMID:25714877

Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections.

PubMed

Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

2015-01-01

Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters.

Potential Roles of Protease Inhibitors in Cancer Progression.

PubMed

Yang, Peng; Li, Zhuo-Yu; Li, Han-Qing

2015-01-01

Proteases are important molecules that are involved in many key physiological processes. Protease signaling pathways are strictly controlled, and disorders in protease activity can result in pathological changes such as cardiovascular and inflammatory diseases, cancer and neurological disorders. Many proteases have been associated with increasing tumor metastasis in various human cancers, suggesting important functional roles in the metastatic process because of their ability to degrade the extracellular matrix barrier. Proteases are also capable of cleaving non-extracellular matrix molecules. Inhibitors of proteases to some extent can reduce invasion and metastasis of cancer cells, and slow down cancer progression. In this review, we focus on the role of a few proteases and their inhibitors in tumors as a basis for cancer prognostication and therapy.

Healthcare in Disasters and the Role of RFID.

PubMed

Madanian, Samaneh; Parry, David; Norris, Tony

2015-01-01

Disasters either natural or man-made are inevitable, and therefore disaster management has always been an important function of government. Since during a disaster healthcare is often adversely affected, a lot of effort has been made in terms of researching effective responses and ways of improving the quality of delivered care to direct casualties and the rest of the community. In this regard, information technology plays an important role to help healthcare systems achieve this goal. One of these technologies that has become popular recently is Radio-Frequency Identification (RFID). This paper explores the relationship between emergency management and disaster healthcare and examines the role of RFID. It is suggested that RFID will become an integral part of disaster healthcare and a means of improving response performance.

Prions, prionoid complexes and amyloids: the bad, the good and something in between.

PubMed

Hafner Bratkovič, Iva

2017-04-19

Prions are infectious agents causing transmissible spongiform encephalopathies in humans and animals. These protein-based particles template conformational changes in a host-encoded prion protein to an insoluble self-like conformation. Prions are also present in yeast, where they support protein-based epigenetic inheritance. There is emerging evidence that prion-like (prionoid) particles can support a variety of pathological and beneficial functions. The recent data on the prionoid spread of other pathological amyloids are discussed in light of differences between prions and prion-like aggregates. On the other hand, prion-like action has also been found to support important functions such as memory, and amyloids were shown to have a variety of physiological roles from storage to scaffolding in simple organisms and in humans. Higher-order protein complexes play important roles in signalling. Many death-fold domains can polymerise upon nucleation to enhance sensitivity and induce a robust response. Although these polymers are structurally different from amyloids, some of them are characterised by prionoid activities, such as intercellular spread. The initial activation of these complexes is vital for organismal health, whereas prolonged activation leading to unresolved inflammation underlies autoinflammatory and other diseases. Prionoid complexes play important roles far beyond prion diseases and neurodegeneration.

Novel bone metabolism-associated hormones: the importance of the pre-analytical phase for understanding their physiological roles.

PubMed

Lombardi, Giovanni; Barbaro, Mosè; Locatelli, Massimo; Banfi, Giuseppe

2017-06-01

The endocrine function of bone is now a recognized feature of this tissue. Bone-derived hormones that modulate whole-body homeostasis, are being discovered as for the effects on bone of novel and classic hormones produced by other tissues become known. Often, however, the data regarding these last generation bone-derived or bone-targeting hormones do not give about a clear picture of their physiological roles or concentration ranges. A certain degree of uncertainty could stem from differences in the pre-analytical management of biological samples. The pre-analytical phase comprises a series of decisions and actions (i.e., choice of sample matrix, methods of collection, transportation, treatment and storage) preceding analysis. Errors arising in this phase will inevitably be carried over to the analytical phase where they can reduce the measurement accuracy, ultimately, leading discrepant results. While the pre-analytical phase is all important, in routine laboratory medicine, it is often not given due consideration in research and clinical trials. This is particularly true for novel molecules, such as the hormones regulating the endocrine function of bone. In this review we discuss the importance of the pre-analytical variables affecting the measurement of last generation bone-associated hormones and describe their, often debated and rarely clear physiological roles.

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder.

PubMed

de Sousa, Rafael T; Machado-Vieira, Rodrigo; Zarate, Carlos A; Manji, Husseini K

2014-10-01

Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca²⁺) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca²⁺ dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents.

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder

PubMed Central

de Sousa, Rafael T; Machado-Vieira, Rodrigo; Zarate, Carlos A

2014-01-01

Introduction Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. Areas covered This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca2+) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca2+ dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Expert opinion Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents. PMID:25056514

Systematic CRISPR-Cas9-Mediated Modifications of Plasmodium yoelii ApiAP2 Genes Reveal Functional Insights into Parasite Development

PubMed Central

Zhang, Cui; Li, Zhenkui; Cui, Huiting; Jiang, Yuanyuan; Yang, Zhenke; Wang, Xu; Gao, Han; Liu, Cong; Zhang, Shujia

2017-01-01

ABSTRACT Malaria parasites have a complex life cycle with multiple developmental stages in mosquito and vertebrate hosts, and different developmental stages express unique sets of genes. Unexpectedly, many transcription factors (TFs) commonly found in eukaryotic organisms are absent in malaria parasites; instead, a family of genes encoding proteins similar to the plant Apetala2 (ApiAP2) transcription factors is expanded in the parasites. Several malaria ApiAP2 genes have been shown to play a critical role in parasite development; however, the functions of the majority of the ApiAP2 genes remain to be elucidated. In particular, no study on the Plasmodium yoelii ApiAP2 (PyApiAP2) gene family has been reported so far. This study systematically investigated the functional roles of PyApiAP2 genes in parasite development. Twenty-four of the 26 PyApiAP2 genes were selected for disruption, and 12 were successfully knocked out using the clustered regularly interspaced short palindromic repeat–CRISPR-associated protein 9 (CRISPR-Cas9) method. The effects of gene knockout (KO) on parasite development in mouse and mosquito stages were evaluated. Ten of 12 successfully disrupted genes, including two genes that have not been functionally characterized in any Plasmodium species previously, were shown to be critical for P. yoelii development of sexual and mosquito stages. Additionally, seven of the genes were labeled for protein expression analysis, revealing important information supporting their functions. This study represents the first systematic functional characterization of the P. yoelii ApiAP2 gene family and discovers important insights on the roles of the ApiAP2 genes in parasite development. PMID:29233900

Duration of attenuated positive and negative symptoms in individuals at clinical high risk: Associations with risk of conversion to psychosis and functional outcome

PubMed Central

Carrión, Ricardo E.; Demmin, Docia; Auther, Andrea M.; McLaughlin, Danielle; Olsen, Ruth; Lencz, Todd; Correll, Christoph U.; Cornblatt, Barbara A.

2016-01-01

Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability. PMID:27424062

Biomimetic oral mucin from polymer micelle networks

NASA Astrophysics Data System (ADS)

Authimoolam, Sundar Prasanth

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated using affinity-based interactions on synthetic and biological surfaces. Unlike conventional polyelectrolyte-based LBL methods, pre-assembled biotin-functionalized filamentous (worm-like) micelles was utilized as the network building block, which from complementary additions of streptavidin generated synthetic networks of desired thickness. The biomimetic nature in those synthetic networks are studied by evaluating its structural and bio-functional properties. Structurally, synthetic networks formed a nanoporous mesh. The networks demonstrated excellent surface hydration property and were able capable of microbial capture. Those functional properties are akin to that of natural mucin networks. Further, the role of synthetic mucin as a drug delivery vehicle, capable of providing localized and tunable release was demonstrated. By incorporating antibacterial curcumin drug loading within synthetic networks, bacterial growth inhibition was also demonstrated. Thus, such bioactive interfaces can serve as a model for independently characterizing mucin network properties and through its role as a drug carrier vehicle it presents exciting future opportunities for localized drug delivery, in regenerative applications and as bio-functional implant coats. KEYWORDS: Biomimic, Bioapplication, Drug delivery, Filomicelle, Mucin, Polymer networks.

Protein subcellular localization prediction using artificial intelligence technology.

PubMed

Nair, Rajesh; Rost, Burkhard

2008-01-01

Proteins perform many important tasks in living organisms, such as catalysis of biochemical reactions, transport of nutrients, and recognition and transmission of signals. The plethora of aspects of the role of any particular protein is referred to as its "function." One aspect of protein function that has been the target of intensive research by computational biologists is its subcellular localization. Proteins must be localized in the same subcellular compartment to cooperate toward a common physiological function. Aberrant subcellular localization of proteins can result in several diseases, including kidney stones, cancer, and Alzheimer's disease. To date, sequence homology remains the most widely used method for inferring the function of a protein. However, the application of advanced artificial intelligence (AI)-based techniques in recent years has resulted in significant improvements in our ability to predict the subcellular localization of a protein. The prediction accuracy has risen steadily over the years, in large part due to the application of AI-based methods such as hidden Markov models (HMMs), neural networks (NNs), and support vector machines (SVMs), although the availability of larger experimental datasets has also played a role. Automatic methods that mine textual information from the biological literature and molecular biology databases have considerably sped up the process of annotation for proteins for which some information regarding function is available in the literature. State-of-the-art methods based on NNs and HMMs can predict the presence of N-terminal sorting signals extremely accurately. Ab initio methods that predict subcellular localization for any protein sequence using only the native amino acid sequence and features predicted from the native sequence have shown the most remarkable improvements. The prediction accuracy of these methods has increased by over 30% in the past decade. The accuracy of these methods is now on par with high-throughput methods for predicting localization, and they are beginning to play an important role in directing experimental research. In this chapter, we review some of the most important methods for the prediction of subcellular localization.

Emergence of Rich-Club Topology and Coordinated Dynamics in Development of Hippocampal Functional Networks In Vitro

PubMed Central

Charlesworth, Paul; Kitzbichler, Manfred G.; Paulsen, Ole

2015-01-01

Recent studies demonstrated that the anatomical network of the human brain shows a “rich-club” organization. This complex topological feature implies that highly connected regions, hubs of the large-scale brain network, are more densely interconnected with each other than expected by chance. Rich-club nodes were traversed by a majority of short paths between peripheral regions, underlining their potential importance for efficient global exchange of information between functionally specialized areas of the brain. Network hubs have also been described at the microscale of brain connectivity (so-called “hub neurons”). Their role in shaping synchronous dynamics and forming microcircuit wiring during development, however, is not yet fully understood. The present study aimed to investigate the role of hubs during network development, using multi-electrode arrays and functional connectivity analysis during spontaneous multi-unit activity (MUA) of dissociated primary mouse hippocampal neurons. Over the first 4 weeks in vitro, functional connectivity significantly increased in strength, density, and size, with mature networks demonstrating a robust modular and small-world topology. As expected by a “rich-get-richer” growth rule of network evolution, MUA graphs were found to form rich-clubs at an early stage in development (14 DIV). Later on, rich-club nodes were a consistent topological feature of MUA graphs, demonstrating high nodal strength, efficiency, and centrality. Rich-club nodes were also found to be crucial for MUA dynamics. They often served as broker of spontaneous activity flow, confirming that hub nodes and rich-clubs may play an important role in coordinating functional dynamics at the microcircuit level. PMID:25855164

PDZ-containing proteins: alternative splicing as a source of functional diversity.

PubMed

Sierralta, Jimena; Mendoza, Carolina

2004-12-01

Scaffold proteins allow specific protein complexes to be assembled in particular regions of the cell at which they organize subcellular structures and signal transduction complexes. This characteristic is especially important for neurons, which are highly polarized cells. Among the domains contained by scaffold proteins, the PSD-95, Discs-large, ZO-1 (PDZ) domains are of particular relevance in signal transduction processes and maintenance of neuronal and epithelial polarity. These domains are specialized in the binding of the carboxyl termini of proteins allowing membrane proteins to be localized by the anchoring to the cytoskeleton mediated by PDZ-containing scaffold proteins. In vivo studies carried out in Drosophila have taught that the role of many scaffold proteins is not limited to a single process; thus, in many cases the same genes are expressed in different tissues and participate in apparently very diverse processes. In addition to the differential expression of interactors of scaffold proteins, the expression of variants of these molecular scaffolds as the result of the alternative processing of the genes that encode them is proving to be a very important source of variability and complexity on a main theme. Alternative splicing in the nervous system is well documented, where specific isoforms play roles in neurotransmission, ion channel function, neuronal cell recognition, and are developmentally regulated making it a major mechanism of functional diversity. Here we review the current state of knowledge about the diversity and the known function of PDZ-containing proteins in Drosophila with emphasis in the role played by alternatively processed forms in the diversity of functions attributed to this family of proteins.

The roles of peptide hormones during plant root development.

PubMed

Yamada, Masashi; Sawa, Shinichiro

2013-02-01

Peptide hormones are a key mechanism that plants use for cell-cell interactions; these interactions function to coordinate development, growth, and environmental responses among different cells. Peptide signals are produced by one cell and received by receptors in neighboring cells. It has previously been reported that peptide hormones regulate various aspects of plant development. The mechanism of action of peptides in the shoot is well known. However, the function of peptides in the root has been relatively uncharacterized. Recent studies have discovered important roles for peptide hormones in the development of the root meristem, lateral roots, and nodules. In this review, we focus on current findings regarding the function of peptide hormones in root development. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Molecular Approach to Mitophagy and Mitochondrial Dynamics

PubMed Central

Yoo, Seung-Min; Jung, Yong-Keun

2018-01-01

Mitochondrial quality control systems are essential for the maintenance of functional mitochondria. At the organelle level, they include mitochondrial biogenesis, fusion and fission, to compensate for mitochondrial function, and mitophagy, for degrading damaged mitochondria. Specifically, in mitophagy, the target mitochondria are recognized by the autophagosomes and delivered to the lysosome for degradation. In this review, we describe the mechanisms of mitophagy and the factors that play an important role in this process. In particular, we focus on the roles of mitophagy adapters and receptors in the recognition of damaged mitochondria by autophagosomes. In addition, we also address a functional association of mitophagy with mitochondrial dynamics through the interaction of mitophagy adaptor and receptor proteins with mitochondrial fusion and fission proteins. PMID:29370689

Minireview: roles of the forkhead transcription factor FOXL2 in granulosa cell biology and pathology.

PubMed

Pisarska, Margareta D; Barlow, Gillian; Kuo, Fang-Ting

2011-04-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells.

Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

PubMed Central

Barlow, Gillian; Kuo, Fang-Ting

2011-01-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells. PMID:21248146

Morphological dynamics of mitochondria--a special emphasis on cardiac muscle cells.

PubMed

Hom, Jennifer; Sheu, Shey-Shing

2009-06-01

Mitochondria play a critical role in cellular energy metabolism, Ca(2+) homeostasis, reactive oxygen species generation, apoptosis, aging, and development. Many recent publications have shown that a continuous balance of fusion and fission of these organelles is important in maintaining their proper function. Therefore, there is a steep correlation between the form and function of mitochondria. Many major proteins involved in mitochondrial fusion and fission have been identified in different cell types, including heart. However, the functional role of mitochondrial dynamics in the heart remains, for the most part, unexplored. In this review we will cover the recent field of mitochondrial dynamics and its physiological and pathological implications, with a particular emphasis on the experimental and theoretical basis of mitochondrial dynamics in the heart.

Infrared Dielectric Properties of Low-Stress Silicon Oxide

NASA Technical Reports Server (NTRS)

Cataldo, Giuseppe; Wollack, Edward J.; Brown, Ari D.; Miller, Kevin H.

2016-01-01

Silicon oxide thin films play an important role in the realization of optical coatings and high-performance electrical circuits. Estimates of the dielectric function in the far- and mid-infrared regime are derived from the observed transmittance spectrum for a commonly employed low-stress silicon oxide formulation. The experimental, modeling, and numerical methods used to extract the dielectric function are presented.

Understanding the Function of Visual Short-Term Memory: Transsaccadic Memory, Object Correspondence, and Gaze Correction

ERIC Educational Resources Information Center

Hollingworth, Andrew; Richard, Ashleigh M.; Luck, Steven J.

2008-01-01

Visual short-term memory (VSTM) has received intensive study over the past decade, with research focused on VSTM capacity and representational format. Yet, the function of VSTM in human cognition is not well understood. Here, the authors demonstrate that VSTM plays an important role in the control of saccadic eye movements. Intelligent human…

Measuring Emotional Intelligence in Early Adolescence with the MSCEIT-YV: Psychometric Properties and Relationship with Academic Performance and Psychosocial Functioning

ERIC Educational Resources Information Center

Rivers, Susan E.; Brackett, Marc A.; Reyes, Maria R.; Mayer, John D.; Caruso, David R.; Salovey, Peter

2012-01-01

Emotional intelligence (EI) theory provides a framework to study the role of emotion skills in social, personal, and academic functioning. Reporting data validating the importance of EI among youth have been limited due to a dearth of measurement instruments. In two studies, the authors examined the reliability and validity of the…

Lifting the nebula: novel insights into skeletal muscle contractility.

PubMed

Ottenheijm, Coen A C; Granzier, Henk

2010-10-01

Nebulin is a giant protein and a constituent of the skeletal muscle sarcomere. The name of this protein refers to its unknown (i.e., nebulous) function. However, recent rapid advances reveal that nebulin plays important roles in the regulation of muscle contraction. When these functions of nebulin are compromised, muscle weakness ensues, as is the case in patients with nemaline myopathy.

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling

PubMed Central

Phillips, Cristy; Baktir, Mehmet Akif; Srivatsan, Malathi; Salehi, Ahmad

2014-01-01

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations. PMID:24999318

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling.

PubMed

Phillips, Cristy; Baktir, Mehmet Akif; Srivatsan, Malathi; Salehi, Ahmad

2014-01-01

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

Effect of dietary antioxidant supplementation (Cuminum cyminum) on bacterial susceptibility of diabetes-induced rats.

PubMed

Moubarz, Gehan; Embaby, Mohamed A; Doleib, Nada M; Taha, Mona M

2016-01-01

Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1β and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes.

Effect of dietary antioxidant supplementation (Cuminum cyminum) on bacterial susceptibility of diabetes-induced rats

PubMed Central

Embaby, Mohamed A.; Doleib, Nada M.; Taha, Mona M.

2016-01-01

Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1β and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes. PMID:27536197

Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega-6 Fatty Acids

PubMed Central

Watts, Jennifer L.

2016-01-01

The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids. PMID:26848697

Myeloid leukemia factor functions in anti-WSSV immune reaction of kuruma shrimp, Marsupenaeus japonicus.

PubMed

Feng, Xiao-Wu; Huo, Li-Jie; Sun, Jie-Jie; Xu, Ji-Dong; Niu, Guo-Juan; Wang, Jin-Xing; Shi, Xiu-Zhen

2017-11-01

Myeloid leukemia factor (MLF) plays an important role in development, cell cycle, myeloid differentiation, and regulates the RUNX transcription factors. However, the function of MLF in immunity is still unclear. In this study, an MLF was identified and characterized in kuruma shrimp Marsupenaeus japonicus, and named as MjMLF. The full-length cDNA of MjMLF contained 1111 nucleotides, which had an opening reading frame of 816 bp encoding a protein of 272 amino acids with an MLF1-interacting protein domain. MjMLF could be ubiquitously detected in different tissues of shrimp at the transcriptional level. The expression pattern analysis showed that MjMLF could be upregulated in shrimp hemocytes and hepatopancreas after white spot syndrome virus challenge. The RNA interference and protein injection assay showed that MjMLF could inhibit WSSV replication in vivo. Flow cytometry assay showed that MjMLF could induce hemocytes apoptosis which functioned in the shrimp antiviral reaction. All the results suggested that MjMLF played an important role in the antiviral immune reaction of kuruma shrimp. The research indicated that MjMLF might function as a novel regulator to inhibit WSSV replication in shrimp. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resting-state functional connectivity of the default mode network associated with happiness

PubMed Central

Luo, Yangmei; Kong, Feng; Qi, Senqing; You, Xuqun

2016-01-01

Happiness refers to people’s cognitive and affective evaluation of their life. Why are some people happier than others? One reason might be that unhappy people are prone to ruminate more than happy people. The default mode network (DMN) is normally active during rest and is implicated in rumination. We hypothesized that unhappiness may be associated with increased default-mode functional connectivity during rest, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC) and inferior parietal lobule (IPL). The hyperconnectivity of these areas may be associated with higher levels of rumination. One hundred forty-eight healthy participants underwent a resting-state fMRI scan. A group-independent component analysis identified the DMNs. Results indicated increased functional connectivity in the DMN was associated with lower levels of happiness. Specifically, relative to happy people, unhappy people exhibited greater functional connectivity in the anterior medial cortex (bilateral MPFC), posterior medial cortex regions (bilateral PCC) and posterior parietal cortex (left IPL). Moreover, the increased functional connectivity of the MPFC, PCC and IPL, correlated positively with the inclination to ruminate. These results highlight the important role of the DMN in the neural correlates of happiness, and suggest that rumination may play an important role in people’s perceived happiness. PMID:26500289

History, anatomical nomenclature, comparative anatomy and functions of the hippocampal formation.

PubMed

El-Falougy, H; Benuska, J

2006-01-01

The complex structures in the cerebral hemispheres is included under one term, the limbic system. Our conception of this system and its special functions rises from the comparative neuroanatomical and neurophysiological studies. The components of the limbic system are the hippocampus, gyrus parahippocampalis, gyrus dentatus, gyrus cinguli, corpus amygdaloideum, nuclei anteriores thalami, hypothalamus and gyrus paraterminalis Because of its unique macroscopic and microscopic structure, the hippocampus is a conspicuous part of the limbic system. During phylogenetic development, the hippocampus developed from a simple cortical plate in amphibians into complex three-dimensional convoluted structure in mammals. In the last few decades, structures of the limbic system were extensively studied. Attention was directed to the physiological functions and pathological changes of the hippocampus. Experimental studies proved that the hippocampus has a very important role in the process of learning and memory. Another important functions of the hippocampus as a part of the limbic system is its role in regulation of sexual and emotional behaviour. The term "hippocampal formation" is defined as the complex of six structures: gyrus dentatus, hippocampus proprius, subiculum proprium, presubiculum, parasubiculum and area entorhinalis In this work we attempt to present a brief review of knowledge about the hippocampus from the point of view of history, anatomical nomenclature, comparative anatomy and functions (Tab. 1, Fig. 2, Ref. 33).

Complementary aspects of diffusion imaging and fMRI; I: structure and function.

PubMed

Mulkern, Robert V; Davis, Peter E; Haker, Steven J; Estepar, Raul San Jose; Panych, Lawrence P; Maier, Stephan E; Rivkin, Michael J

2006-05-01

Studying the intersection of brain structure and function is an important aspect of modern neuroscience. The development of magnetic resonance imaging (MRI) over the last 25 years has provided new and powerful tools for the study of brain structure and function. Two tools in particular, diffusion imaging and functional MRI (fMRI), are playing increasingly important roles in elucidating the complementary aspects of brain structure and function. In this work, we review basic technical features of diffusion imaging and fMRI for studying the integrity of white matter structural components and for determining the location and extent of cortical activation in gray matter, respectively. We then review a growing body of literature in which the complementary aspects of diffusion imaging and fMRI, applied as separate examinations but analyzed in tandem, have been exploited to enhance our knowledge of brain structure and function.

[Functional childhood gastrointestinal disorders. III. Constipation and solitary encopresis; diagnostic work-up and therapy].

PubMed

van Ginkel, R; Büller, H A; Heymans, H S; Taminiau, J A; Boeckxstaens, G E; Benninga, M A

2003-06-28

A detailed medical history in combination with a thorough physical examination, including rectal examination, form the cornerstone in the diagnostic work-up for children with functional defecation disorders. Additional investigations are often not informative and have only minor diagnostic or therapeutic implications. Medical therapy in children with functional constipation and solitary encopresis is primarily based on clinical experience. In both patient groups, the role of education, the use of diary cards and toilet training is important. In some patients behaviour interventions are important. Oral laxatives are the basis of treatment of children with functional constipation, whereas they are contra-indicated in children with solitary encopresis. In both groups, biofeedback training appears to be of little additional benefit. Long-term follow-up of children with functional defecation disorders shows that complaints continue far beyond puberty in many children.

Architecture of the Suprahyoid Muscles: A Volumetric Musculoaponeurotic Analysis.

PubMed

Shaw, Stephanie M; Martino, Rosemary; Mahdi, Ali; Sawyer, Forrest Kip; Mathur, Sunita; Hope, Andrew; Agur, Anne M

2017-10-17

Suprahyoid muscles play a critical role in swallowing. The arrangement of the fiber bundles and aponeuroses has not been investigated volumetrically, even though muscle architecture is an important determinant of function. Thus, the purpose was to digitize, model in three dimensions, and quantify the architectural parameters of the suprahyoid muscles to determine and compare their relative functional capabilities. Fiber bundles and aponeuroses from 11 formalin-embalmed specimens were serially dissected and digitized in situ. Data were reconstructed in three dimensions using Autodesk Maya. Architectural parameters were quantified, and data were compared using independent samples t-tests and analyses of variance. Based on architecture and attachment sites, suprahyoid muscles were divided into 3 groups: anteromedial, superolateral, and superoposterior. Architectural parameters differed significantly (p < .05) across muscles and across the 3 groups, suggesting differential roles in hyoid movement during swallowing. When activated simultaneously, anteromedial and superoposterior muscle groups could work together to elevate the hyoid. The results suggest that the suprahyoid muscles can have individualized roles in hyoid excursion during swallowing. Muscle balance may be important for identifying and treating hyolaryngeal dysfunction in patients with dysphagia.

Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis.

PubMed

Nandi, Sayan; Alviña, Karina; Lituma, Pablo J; Castillo, Pablo E; Hébert, Jean M

2018-01-15

Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Characterization and Expression Analysis of Common Bean Histone Deacetylase 6 during Development and Cold Stress Response

PubMed Central

Ligaba-Osena, Ayalew; Subramani, Mayavan; Brown, Adrianne; Melmaiee, Kalpalatha; Hossain, Khwaja

2017-01-01

Histone deacetylases (HDACs) are important regulators of gene transcription thus controlling multiple cellular processes. Despite its essential role in plants, HDA6 is yet to be validated in common bean. In this study, we show that HDA6 is involved in plant development and stress response. Differential expression of HDA6 was determined in various tissues and the expression was seen to be upregulated with plant age (seedling < flowering < maturity). Higher expression was observed in flowers and pods than in stem, leaf, and root. Upregulation of HDA6 gene during cold stress implies its prominent role in abiotic stress. Furthermore, the HDA6 gene was isolated from three common bean genotypes and sequence analyses revealed homology with functionally characterized homologs in model species. The 53 kDa translated product was detected using an HDA6 specific antibody and recombinant protein overexpressed in Escherichia coli showed HDAC activity in vitro. To our knowledge, this is the first report in the agriculturally important crop common bean describing the functional characterization and biological role of HDA6. PMID:28127547

Emerging Roles of BAI Adhesion-GPCRs in Synapse Development and Plasticity.

PubMed

Duman, Joseph G; Tu, Yen-Kuei; Tolias, Kimberley F

2016-01-01

Synapses mediate communication between neurons and enable the brain to change in response to experience, which is essential for learning and memory. The sites of most excitatory synapses in the brain, dendritic spines, undergo rapid remodeling that is important for neural circuit formation and synaptic plasticity. Abnormalities in synapse and spine formation and plasticity are associated with a broad range of brain disorders, including intellectual disabilities, autism spectrum disorders (ASD), and schizophrenia. Thus, elucidating the mechanisms that regulate these neuronal processes is critical for understanding brain function and disease. The brain-specific angiogenesis inhibitor (BAI) subfamily of adhesion G-protein-coupled receptors (adhesion-GPCRs) has recently emerged as central regulators of synapse development and plasticity. In this review, we will summarize the current knowledge regarding the roles of BAIs at synapses, highlighting their regulation, downstream signaling, and physiological functions, while noting the roles of other adhesion-GPCRs at synapses. We will also discuss the relevance of BAIs in various neurological and psychiatric disorders and consider their potential importance as pharmacological targets in the treatment of these diseases.

The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells.

PubMed

Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang

2017-06-15

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of intestinal health by branched-chain amino acids.

PubMed

Zhou, Hua; Yu, Bing; Gao, Jun; Htoo, John Khun; Chen, Daiwen

2018-01-01

Besides its primary role in the digestion and absorption of nutrients, the intestine also interacts with a complex external milieu, and is the first defense line against noxious pathogens and antigens. Dysfunction of the intestinal barrier is associated with enhanced intestinal permeability and development of various gastrointestinal diseases. The branched-chain amino acids (BCAAs) are important nutrients, which are the essential substrates for protein biosynthesis. Recently, emerging evidence showed that BCAAs are involved in maintaining intestinal barrier function. It has been reported that dietary supplementation with BCAAs promotes intestinal development, enhances enterocyte proliferation, increases intestinal absorption of amino acids (AA) and glucose, and improves the immune defenses of piglets. The underlying mechanism of these effects is mediated by regulating expression of genes and proteins associate with various signaling pathways. In addition, BCAAs promote the production of beneficial bacteria in the intestine of mice. Compelling evidence supports the notion that BCAAs play important roles in both nutrition and intestinal health. Therefore, as functional amino acids with various physiological effects, BCAAs hold key roles in promoting intestinal development and health in animals and humans. © 2017 Japanese Society of Animal Science.

Stretch-activated TRPV2 channels: Role in mediating cardiopathies.

PubMed

Aguettaz, Elizabeth; Bois, Patrick; Cognard, Christian; Sebille, Stéphane

2017-11-01

Transient receptor potential vanilloid type 2, TRPV2, is a calcium-permeable cation channel belonging to the TRPV channel family. Although this channel has been first characterized as a noxious heat sensor, its mechanosensor property recently gained importance in various physiological functions. TRPV2 has been described as a stretch-mediated channel and a regulator of calcium homeostasis in several cell types and has been shown to be involved in the stretch-dependent responses in cardiomyocytes. Hence, several studies in the last years support the idea that TRPV2 play a key role in the function and structure of the heart, being involved in the cardiac compensatory mechanisms in response to pathologic or exercise-induced stress. We present here an overview of the current literature and concepts of TRPV2 channels involvement (i) in the mechanical coupling mechanisms in heart and (ii) in the mechanisms that lead to cardiomyopathies. All these studies lead us to think that TRPV2 may also be an important cardiac drug target based on its major physiological roles in heart. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

The Role of Transporters in Toxicity and Disease

PubMed Central

Swaan, Peter W.; Tweedie, Donald J.

2014-01-01

The significance of transporters in the disposition, metabolism, and elimination of drugs is well recognized. One gap in our knowledge is a comprehensive understanding of how drug transporters change functionality (their amount and activity) in response to disease and how disease and its inevitable pathology change transporter expression. In this issue of Drug Metabolism and Disposition a series of review and primary research articles are presented to highlight the importance of transporters in toxicity and disease. Because of the central role of the liver in drug metabolism, many of the articles in this theme issue focus on transporters in the liver and how pathology or alterations in physiology affects transporter expression. The contributing authors have also considered the role of transporters in drug interactions as well as drug-induced liver injury. Noninvasive approaches to assessing transporter function in vivo are also described. Several articles highlight important issues in oncology where toxicity must be balanced against efficacy. In total, this theme issue will provide a stepping-stone to future studies that will establish a more comprehensive understanding of transporters in disease. PMID:24598705

The role of maxiK channels in carotid body chemotransduction.

PubMed

Peers, Chris; Wyatt, Christopher N

2007-07-01

MaxiK channels are a unique class of K(+) channels activated by both voltage and intracellular Ca(2+). Derived from a single gene, their diversity arises from extensive splicing, and their wide distribution has led to their implication in a large variety of cellular functions. In the carotid body, they have been proposed to contribute to the resting membrane potential of type I cells, and also to be O(2) sensitive. Thus, they have been suggested to have an important role in hypoxic chemotransduction. Their O(2) sensitivity is preserved when the channels are expressed in HEK 293 cells, permitting detailed studies of candidate mechanisms underlying hypoxic inhibition of maxiK channels. In this article, we review evidence for and against an important role for maxiK channels in chemotransduction. We also consider different mechanisms proposed to account for hypoxic channel inhibition and suggest that, although our understanding of this important physiological process has advanced significantly in recent years, there remain important, unanswered questions as to the importance of maxiK in carotid body chemoreception.

The role of syntax in complex networks: Local and global importance of verbs in a syntactic dependency network

NASA Astrophysics Data System (ADS)

Čech, Radek; Mačutek, Ján; Žabokrtský, Zdeněk

2011-10-01

Syntax of natural language has been the focus of linguistics for decades. The complex network theory, being one of new research tools, opens new perspectives on syntax properties of the language. Despite numerous partial achievements, some fundamental problems remain unsolved. Specifically, although statistical properties typical for complex networks can be observed in all syntactic networks, the impact of syntax itself on these properties is still unclear. The aim of the present study is to shed more light on the role of syntax in the syntactic network structure. In particular, we concentrate on the impact of the syntactic function of a verb in the sentence on the complex network structure. Verbs play the decisive role in the sentence structure (“local” importance). From this fact we hypothesize the importance of verbs in the complex network (“global” importance). The importance of verb in the complex network is assessed by the number of links which are directed from the node representing verb to other nodes in the network. Six languages (Catalan, Czech, Dutch, Hungarian, Italian, Portuguese) were used for testing the hypothesis.

IMPORTANCE OF ENZYMATIC BIOTRANSFORMATION IN IMMUNOTOXICOLOGY

EPA Science Inventory

Many immunotoxic compounds, such as benzene and other organic solvents, pesticides, mycotoxins and polycyclic aromatic hydrocarbons, can alter immune function only after undergoing enzyme-mediated reactions within various tissues. In the review that follows, the role of enzymatic...

The Child Welfare Agency as the Extended Family

ERIC Educational Resources Information Center

Taylor, Joseph L.

1972-01-01

In helping disturbed, deprived children and their families, an agency's concept of its treatment task is of vital importance. An effective approach focuses on an agency's functioning as an extended family, and assuming a parenting role. (Editor)

Does perturbative quantum chromodynamics imply a Regge singularity above unity

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

Bishari, M.

1982-07-15

It is investigated whether perturbative quantum chromodynamics can have some implications on Regge behavior of deep-inelastic structure functions. The possible indirect but important role of unitarity, in constraining the theory, is pointed out.

Dnmt1 regulates the myogenic lineage specification of muscle stem cells.

PubMed

Liu, Renjing; Kim, Kun-Yong; Jung, Yong-Wook; Park, In-Hyun

2016-10-18

DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle. These mice were born runted, with smaller body weights, and reduced ability to form myotubes in vitro. We show that expression of Id-1, a negative regulator of myogenesis, is enhanced in Dnmt1-deficient cultures, leading to enhanced transdifferentiation of myoblasts toward the osteogenic lineage. Thus, these studies demonstrate that Dnmt1 influences cellular identity and determines lineage fidelity.

Dnmt1 regulates the myogenic lineage specification of muscle stem cells

PubMed Central

Liu, Renjing; Kim, Kun-Yong; Jung, Yong-Wook; Park, In-Hyun

2016-01-01

DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle. These mice were born runted, with smaller body weights, and reduced ability to form myotubes in vitro. We show that expression of Id-1, a negative regulator of myogenesis, is enhanced in Dnmt1-deficient cultures, leading to enhanced transdifferentiation of myoblasts toward the osteogenic lineage. Thus, these studies demonstrate that Dnmt1 influences cellular identity and determines lineage fidelity. PMID:27752090

The multidimensional ionotropic receptors of Drosophila melanogaster.

PubMed

Rimal, S; Lee, Y

2018-02-01

Ionotropic receptors (IRs), which form ion channels, can be categorized into conserved 'antennal IRs', which define the first olfactory receptor family of insects, and species-specific 'divergent IRs', which are expressed in gustatory receptor neurones. These receptors are located primarily in cell bodies and dendrites, and are highly enriched in the tips of the dendritic terminals that convey sensory information to higher brain centres. Antennal IRs play important roles in odour and thermosensation, whereas divergent IRs are involved in other important biological processes such as taste sensation. Some IRs are known to play specific biological roles in the perception of various molecules; however, many of their functions have not yet been defined. Although progress has been made in this field, many functions and mechanisms of these receptors remain unknown. In this review, we provide a comprehensive summary of the current state of knowledge in this field. © 2017 The Royal Entomological Society.

Functional expression of SCL/TAL1 interrupting locus (Stil) protects retinal dopaminergic cells from neurotoxin-induced degeneration.

PubMed

Li, Jingling; Li, Ping; Carr, Aprell; Wang, Xiaokai; DeLaPaz, April; Sun, Lei; Lee, Eric; Tomei, Erika; Li, Lei

2013-01-11

We previously isolated a dominant mutation, night blindness b (nbb), which causes a late onset of retinal dopaminergic cell degeneration in zebrafish. In this study, we cloned the zebrafish nbb locus. Sequencing results revealed that nbb is a homolog of the vertebrate SCL/TAL1 interrupting locus (Stil). The Stil gene has been shown to play important roles in the regulation of vertebrate embryonic neural development and human cancer cell proliferation. In this study, we demonstrate that functional expression of Stil is also required for neural survival. In zebrafish, decreased expression of Stil resulted in increased toxic susceptibility of retinal dopaminergic cells to 6-hydroxydopamine. Increases in Stil-mediated Shh signaling transduction (i.e. by knocking down the Shh repressor Sufu) prevented dopaminergic cell death induced by neurotoxic insult. The data suggest that the oncogene Stil also plays important roles in neural protection.

Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

NASA Technical Reports Server (NTRS)

Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

1995-01-01

A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

Ultraweak photon emission in the brain.

PubMed

Salari, V; Valian, H; Bassereh, H; Bókkon, I; Barkhordari, A

2015-09-01

Besides the low-frequency electromagnetic body-processes measurable through the electroencephalography (EEG), electrocardiography (ECG), etc. there are processes that do not need external excitation, emitting light within or close to the visible spectra. Such ultraweak photon emission (UPE), also named biophoton emission, reflects the cellular (and body) oxidative status. Recently, a growing body of evidence shows that UPE may play an important role in the basic functioning of living cells. Moreover, interesting evidences are beginning to emerge that UPE may well play an important role in neuronal functions. In fact, biophotons are byproducts in cellular metabolism and produce false signals (e.g., retinal discrete dark noise) but on the other side neurons contain many light sensitive molecules that makes it hard to imagine how they might not be influenced by UPE, and thus UPE may carry informational contents. Here, we investigate UPE in the brain from different points of view such as experimental evidences, theoretical modeling, and physiological significance.

The role of perceived family social support and parental solicitous responses in adjustment to bothersome pain in young people with physical disabilities.

PubMed

Miró, Jordi; de la Vega, Rocío; Gertz, Kevin J; Jensen, Mark P; Engel, Joyce M

2017-11-12

Family social support and parental solicitous responses have been hypothesised to play an important role in paediatric pain. However, research testing the hypothesised associations between these social domains and measures of adjustment to pain in youths with disabilities and chronic pain is non-existent. About 111 youths with physical disabilities and bothersome pain were interviewed and asked to complete measures of average pain intensity, pain interference, family social support, parent solicitous responding, and catastrophising. Children's perceptions of pain-related solicitous responses from their parent/guardian were associated both with more pain interference and greater pain-related catastrophising; perceived social support was negatively associated with pain interference. The findings provide new information regarding the role that psychosocial factors have in predicting function and adjustment, and have important implications as to how youth with physical disabilities with pain might be most effectively treated. Implications for rehabilitation Little is known about the role of perceived family social support or parental solicitous responses in the adjustment to chronic pain in young people with physical disabilities. This study provides new and important findings that have significant theoretical and practical implications that could help to understand and manage function in these patients. Results show that it matters how parents respond to their children with disabilities who have pain, and raise the possibility that interventions which target these responses may result in significant benefits for the children.

[Cytokines and their role in reproductive system].

PubMed

Ianchiĭ, R I; Voznesens'ka, T Iu; Shepel', O A

2007-01-01

In this review we analyze the involvement of cytokines in regulation of ovarian function. A growing body of evidence suggests that the ovary is a site of inflammatory reactions. Immune-competent cells present within the ovary may constitute potential in-situ modulators of ovarian function that act through local secretion of regulatory soluble factors cytokines. In addition many over cell in the ovary also produce cytokines independently of the presence of leukocytes, thus ovaries are sites of cytokine action and production. There are many evidences that cytokines are involved in the ovarian control of follicular development and are surveyed as the important regulators of steroidogenesis and gamete production. It is established that cytokines generally inhibit gonadotropin-stimulated production of steroids. However ovarian steroids, in turn, reduce the cytokine production by immunecompetent cells. There are some data about participation of cytokines in regulating the proliferation and differentiation of granulose cells. Most cytokines appear in mammalian follicles only a short time before ovulation and play the important role in process of ovulation and luteinization. Thus a variety of clinical situations may be due to cytokine action in the gonads, and therapeutic manipulation of the immune system may affect reproductive function. Moreover the findings about the expression of some cytokines by oocytes and their presence in follicular fluid provide further evidence and substantiate the physiologic role for their in ovarian function, and may lead to clinical applications in programs of in vitro fertilization and in diagnosis and treatment of infertility in women, especially in cases attributed to ovarian dysfunction.

Cardiac Fibroblast: The Renaissance Cell

PubMed Central

Souders, Colby A.; Bowers, Stephanie L.K.; Baudino, Troy A.

2012-01-01

The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell-cell communication with myocytes, cell-cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. While a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart. PMID:19959782

Modulation of GABAergic receptor binding by activation of calcium and calmodulin-dependent kinase II membrane phosphorylation.

PubMed

Churn, S B; DeLorenzo, R J

1998-10-26

gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). Because of the important role that GABA plays in the CNS, alteration of GABAA receptor function would significantly affect neuronal excitability. Protein phosphorylation is a major mechanism for regulating receptor function in the brain and has been implicated in modulating GABAA receptor function. Therefore, this study was initiated to determine the role of calmodulin-dependent kinase II (CaM kinase II) membrane phosphorylation on GABAA receptor binding. Synaptosomal membrane fractions were tested for CaM kinase II activity towards endogenous substrates. In addition, muscimol binding was evaluated under equilibrium conditions in synaptosomal membrane fractions subjected to either basal (Mg2+ alone) or maximal CaM kinase II-dependent phosphorylation. Activation of endogenous CaM kinase II-dependent phosphorylation resulted in a significant enhancement of the apparent Bmax for muscimol binding without significantly altering the apparent binding affinity. The enhanced muscimol binding could be increased further by the addition of exogenous CaM kinase II to synaptosomal membrane fractions. Co-incubation with inhibitors of kinase activity during the phosphorylation reactions blocked the CaM kinase II-dependent increase in muscimol binding. The data support the hypothesis that activation of CaM kinase II-dependent phosphorylation caused an increased GABAA receptor binding and may play an important role in modulating the function of this inhibitory receptor/chloride ion channel complex. Copyright 1998 Elsevier Science B.V.

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

Nagata, Takayuki; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575; Murata, Kazuko, E-mail: murata-k@iwakimu.ac.jp

Highlights: •ESCRT-0 protein regulates the development of peripheral B-cells. •BCR expression on cell surface should be controlled by the endosomal-sorting system. •Hrs plays important roles in responsiveness to Ag stimulation in B lymphocytes. -- Abstract: Hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) is a vesicular sorting protein that functions as one of the endosomal-sorting proteins required for transport (ESCRT). Hrs, which binds to ubiquitinated proteins through its ubiquitin-interacting motif (UIM), contributes to the lysosomal transport and degradation of ubiquitinated membrane proteins. However, little is known about the relationship between B-cell functions and ESCRT proteins in vivo. Here we examinedmore » the immunological roles of Hrs in B-cell development and functions using B-cell-specific Hrs-deficient (Hrs{sup flox/flox};mb1{sup cre/+}:Hrs-cKO) mice, which were generated using a cre-LoxP recombination system. Hrs deficiency in B-cells significantly reduced T-cell-dependent antibody production in vivo and impaired the proliferation of B-cells treated in vitro with an anti-IgM monoclonal antibody but not with LPS. Although early development of B-cells in the bone marrow was normal in Hrs-cKO mice, there was a significant decrease in the number of the peripheral transitional B-cells and marginal zone B-cells in the spleen of Hrs-cKO mice. These results indicate that Hrs plays important roles during peripheral development and physiological functions of B lymphocytes.« less

Barley has two peroxisomal ABC transporters with multiple functions in β-oxidation

PubMed Central

Mendiondo, Guillermina M.; Medhurst, Anne; van Roermund, Carlo W.; Zhang, Xuebin; Devonshire, Jean; Scholefield, Duncan; Fernández, José; Axcell, Barry; Ramsay, Luke; Waterham, Hans R.; Waugh, Robbie; Theodoulou, Frederica L.; Holdsworth, Michael J.

2014-01-01

In oilseed plants, peroxisomal β-oxidation functions not only in lipid catabolism but also in jasmonate biosynthesis and metabolism of pro-auxins. Subfamily D ATP-binding cassette (ABC) transporters mediate import of β-oxidation substrates into the peroxisome, and the Arabidopsis ABCD protein, COMATOSE (CTS), is essential for this function. Here, the roles of peroxisomal ABCD transporters were investigated in barley, where the main storage compound is starch. Barley has two CTS homologues, designated HvABCD1 and HvABCD2, which are widely expressed and present in embryo and aleurone tissues during germination. Suppression of both genes in barley RNA interference (RNAi) lines indicated roles in metabolism of 2,4-dichlorophenoxybutyrate (2,4-DB) and indole butyric acid (IBA), jasmonate biosynthesis, and determination of grain size. Transformation of the Arabidopsis cts-1 null mutant with HvABCD1 and HvABCD2 confirmed these findings. HvABCD2 partially or completely complemented all tested phenotypes of cts-1. In contrast, HvABCD1 failed to complement the germination and establishment phenotypes of cts-1 but increased the sensitivity of hypocotyls to 100 μM IBA and partially complemented the seed size phenotype. HvABCD1 also partially complemented the yeast pxa1/pxa2Δ mutant for fatty acid β-oxidation. It is concluded that the core biochemical functions of peroxisomal ABC transporters are largely conserved between oilseeds and cereals but that their physiological roles and importance may differ. PMID:24913629

Intra-amniotic administration (Gallus gallus) of cicer arietinum and lens culinaris prebiotics extracts and duck egg white peptides affects calcium status and intestinal functionality

USDA-ARS?s Scientific Manuscript database

Calcium (Ca) is one of the most abundant inorganic elements in the human body and has many important physiological roles. Prebiotics and bioactive peptides are two important substances used to promote calcium uptake. However, the difference in mechanisms of the calcium uptake from these two suppleme...

The Study of Learners' Preference for Visual Complexity on Small Screens of Mobile Computers Using Neural Networks

ERIC Educational Resources Information Center

Wang, Lan-Ting; Lee, Kun-Chou

2014-01-01

The vision plays an important role in educational technologies because it can produce and communicate quite important functions in teaching and learning. In this paper, learners' preference for the visual complexity on small screens of mobile computers is studied by neural networks. The visual complexity in this study is divided into five…

Re-Examining the Role of Teacher Quality in the Educational Production Function. Working Paper 2007-03

ERIC Educational Resources Information Center

Koedel, Cory; Betts, Julian R.

2007-01-01

This study uses administrative data linking students and teachers at the classroom level to estimate teacher value-added to student test scores. We find that variation in teacher quality is an important contributor to student achievement--more important than has been implied by previous work. This result is attributable, at least in part, to the…

2015 Survey of Board Professionals: Who They Are, What They Do, and Their Important Role in Governance

ERIC Educational Resources Information Center

Hodge-Clark, Kristen

2015-01-01

Board professionals provide critical support, planning, and coordination of important board functions. Their work is often unheralded and conducted behind the scenes, but it is critical to the success and performance of the board. Since 1991, the Association of Governing Boards (AGB) has surveyed this group to capture the changing nature of their…

Quantifying Similarity and Distance Measures for Vector-Based Datasets: Histograms, Signals, and Probability Distribution Functions

DTIC Science & Technology

2017-02-01

note, a number of different measures implemented in both MATLAB and Python as functions are used to quantify similarity/distance between 2 vector-based...this technical note are widely used and may have an important role when computing the distance and similarity of large datasets and when considering high...throughput processes. In this technical note, a number of different measures implemented in both MAT- LAB and Python as functions are used to

More Than Defense in Daily Experience of Privacy: The Functions of Privacy in Digital and Physical Environments

PubMed Central

Lombardi, Debora Benedetta; Ciceri, Maria Rita

2016-01-01

The purpose of the current study was to investigate the experience of privacy, focusing on its functional role in personal well-being. A sample (N = 180) comprised subjects between 18 and 50 years of age were asked to spontaneously provide accounts of their experiences with privacy and answer close-ended questions to acquire a description of a daily experience of privacy. The results showed the importance attributed to the function of privacy related to the “defense from social threats”, and the twofold function of privacy related to an “achieved state of privacy”, in the terms of both “system maintenance” and “system development”. The results also shed light on the role of the environment in shaping one’s experience of privacy. Specifically, the participants recognized more easily the function of defense from threats related to seeking privacy while interacting in digital environments, whereas they seemed to benefit from positive functions related to an achieved state of privacy in physical environments. The findings sustain the notion of privacy as a supportive condition for some psychological processes involved in the positive human functioning and confirm previous studies conducted on the role of privacy in human well-being. PMID:27247696

[Family medicine and functional somatic syndromes].

PubMed

Nago, Naoki

2009-09-01

Between psychosomatic medicine and psychiatry, FSS (functional somatic syndromes) patients are often visiting a family doctor. For FSS, the role of family physicians is large, but the family physicians are not required for the role of diagnosis and treatment of FSS. Rather, appropriate referral to a specialist to exclude organic disease is important and a role as the coordinator is large to the patient to refuse a psychiatric consultation. To serve as a role for such coordination, a family physician has to response the patient's emotional side and focus on the construction of the doctor-patient relationship and response. I also think of structuralism medicine approach to describe disease from the meta-level as a new procedure to the patient. This approach consists of 4 components, 'entity', 'phenomenon', 'words', and 'I'. This may be a useful approach to family physicians who coordinate the overall for FSS patients' management.

Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing.

PubMed

Zhang, Rui; Deng, Patricia; Jacobson, Dionna; Li, Jin Billy

2017-02-01

Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements. Furthermore, editing events that arose early in the species tree tend to be more highly edited in clusters and enriched in slowly-evolved neuronal genes, thus suggesting that the main role of RNA editing is for fine-tuning neurological functions. While nonsynonymous editing events have been long recognized as playing a functional role, in addition to nonsynonymous editing sites, a large fraction of 3'UTR editing sites is evolutionarily constrained, highly edited, and thus likely functional. We find that these 3'UTR editing events can alter mRNA stability and affect miRNA binding and thus highlight the functional roles of noncoding RNA editing. Our work, through evolutionary analyses of RNA editing in Drosophila, uncovers novel insights of RNA editing regulation as well as its functions in both coding and non-coding regions.

A premeiotic function for boule in the planarian Schmidtea mediterranea.

PubMed

Iyer, Harini; Issigonis, Melanie; Sharma, Prashant P; Extavour, Cassandra G; Newmark, Phillip A

2016-06-21

Mutations in Deleted in Azoospermia (DAZ), a Y chromosome gene, are an important cause of human male infertility. DAZ is found exclusively in primates, limiting functional studies of this gene to its homologs: boule, required for meiotic progression of germ cells in invertebrate model systems, and Daz-like (Dazl), required for early germ cell maintenance in vertebrates. Dazl is believed to have acquired its premeiotic role in a vertebrate ancestor following the duplication and functional divergence of the single-copy gene boule. However, multiple homologs of boule have been identified in some invertebrates, raising the possibility that some of these genes may play other roles, including a premeiotic function. Here we identify two boule paralogs in the freshwater planarian Schmidtea mediterranea Smed-boule1 is necessary for meiotic progression of male germ cells, similar to the known function of boule in invertebrates. By contrast, Smed-boule2 is required for the maintenance of early male germ cells, similar to vertebrate Dazl To examine if Boule2 may be functionally similar to vertebrate Dazl, we identify and functionally characterize planarian homologs of human DAZL/DAZ-interacting partners and DAZ family mRNA targets. Finally, our phylogenetic analyses indicate that premeiotic functions of planarian boule2 and vertebrate Dazl evolved independently. Our study uncovers a premeiotic role for an invertebrate boule homolog and offers a tractable invertebrate model system for studying the premeiotic functions of the DAZ protein family.

Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing

PubMed Central

Jacobson, Dionna

2017-01-01

Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements. Furthermore, editing events that arose early in the species tree tend to be more highly edited in clusters and enriched in slowly-evolved neuronal genes, thus suggesting that the main role of RNA editing is for fine-tuning neurological functions. While nonsynonymous editing events have been long recognized as playing a functional role, in addition to nonsynonymous editing sites, a large fraction of 3’UTR editing sites is evolutionarily constrained, highly edited, and thus likely functional. We find that these 3’UTR editing events can alter mRNA stability and affect miRNA binding and thus highlight the functional roles of noncoding RNA editing. Our work, through evolutionary analyses of RNA editing in Drosophila, uncovers novel insights of RNA editing regulation as well as its functions in both coding and non-coding regions. PMID:28166241

Predisposition to Cancer Caused by Genetic and Functional Defects of Mammalian Atad5

PubMed Central

Bell, Daphne W.; Chatterjee, Raghunath; Park, Hee-Dong; Fox, Jennifer; Ishiai, Masamichi; Rudd, Meghan L.; Pollock, Lana M.; Fogoros, Sarah K.; Mohamed, Hassan; Hanigan, Christin L.; Zhang, Suiyuan; Cruz, Pedro; Renaud, Gabriel; Hansen, Nancy F.; Cherukuri, Praveen F.; Borate, Bhavesh; McManus, Kirk J.; Stoepel, Jan; Sipahimalani, Payal; Godwin, Andrew K.; Sgroi, Dennis C.; Merino, Maria J.; Elliot, Gene; Elkahloun, Abdel; Vinson, Charles; Takata, Minoru; Mullikin, James C.; Wolfsberg, Tyra G.; Hieter, Philip; Lim, Dae-Sik; Myung, Kyungjae

2011-01-01

ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination. Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be important for suppression of genomic instability in mammals in vivo. To test this hypothesis, we generated heterozygous (Atad5+/m) mice that were haploinsuffficient for Atad5. Atad5+/m mice displayed high levels of genomic instability in vivo, and Atad5+/m mouse embryonic fibroblasts (MEFs) exhibited molecular defects in PCNA deubiquitination in response to DNA damage, as well as DNA damage hypersensitivity and high levels of genomic instability, apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient Atad5+/m mice developed tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20 months of age. High levels of genomic alterations were evident in tumors that arose in the Atad5+/m mice. Consistent with a role for Atad5 in suppressing tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6% of sporadic human endometrial tumors, including two nonsense mutations that resulted in loss of proper ATAD5 function. Taken together, our findings indicate that loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis. PMID:21901109

Acid sphingomyelinase mediates human CD4+ T-cell signaling: potential roles in T-cell responses and diseases

PubMed Central

Bai, Aiping; Guo, Yuan

2017-01-01

Acid sphingomyelinase (ASM) is a lipid hydrolase. By generating ceramide, ASM had been reported to have an important role in regulating immune cell functions inclusive of macrophages, NK cells, and CD8+ T cells, whereas the role of ASM bioactivity in regulation of human CD4+ T-cell functions remained uncertain. Recent studies have provided novel findings in this field. Upon stimulation of CD3 and/or CD28, ASM-dependent ceramide signaling mediates intracellular downstream signal cascades of CD3 and CD28, and regulates CD4+ T-cell activation and proliferation. Meanwhile, CD39 and CD161 have direct interactions with ASM, which mediates downstream signals inclusive of STAT3 and mTOR and thus defines human Th17 cells. Intriguingly, ASM mediates Th1 responses, but negatively regulates Treg functions. In this review, we summarized the pivotal roles of ASM in regulation of human CD4+ T-cell activation and responses. ASM/sphingolipid signaling may be a novel target for the therapy of human autoimmune diseases. PMID:28749465

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

Roles of long non-coding RNAs in gastric cancer metastasis

PubMed Central

Yang, Zi-Guo; Gao, Ling; Guo, Xiao-Bo; Shi, Yu-Long

2015-01-01

Gastric cancer is the second leading cause of cancer-related deaths. Metastasis, which is an important element of gastric cancer, leads to a high mortality rate and to a poor prognosis. Gastric cancer metastasis has a complex progression that involves multiple biological processes. The comprehensive mechanisms of metastasis remain unclear, though traditional regulation modulates the molecular functions associated with metastasis. Long non-coding RNAs (lncRNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation. lncRNAs participate in various diseases, including Alzheimer’s disease, cardiovascular disease, and cancer. The altered expressions of certain lncRNAs are linked to gastric cancer metastasis and invasion, as with tumor suppressor genes or oncogenes. Studies have partly elucidated the roles of lncRNAs as biomarkers and in therapies, as well as their gene regulatory mechanisms. However, comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce. To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer, we reviewed the functions of lncRNAs and their regulatory roles in gastric cancer metastasis. PMID:25954095

Cardiovascular and Hemostatic Disorders: Role of STIM and Orai Proteins in Vascular Disorders.

PubMed

Tanwar, Jyoti; Trebak, Mohamed; Motiani, Rajender K

2017-01-01

Store-operated Ca 2+ entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca 2+ storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca 2+ levels and transmits the message to plasma membrane Ca 2+ channels constituted by Orai family members (Orai1/2/3) resulting in Ca 2+ influx into the cells. This increase in cytosolic Ca 2+ in turn activates a variety of signaling cascades to regulate a plethora of cellular functions. Evidence from the literature suggests that SOCE dysregulation is associated with several pathophysiologies, including vascular disorders. Interestingly, recent studies have suggested that STIM proteins may also regulate vascular functions independent of their contribution to SOCE. In this updated book chapter, we will focus on the physiological role of STIM and Orai proteins in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in vascular disease.

Nonparametric Stochastic Model for Uncertainty Quantifi cation of Short-term Wind Speed Forecasts

NASA Astrophysics Data System (ADS)

AL-Shehhi, A. M.; Chaouch, M.; Ouarda, T.

2014-12-01

Wind energy is increasing in importance as a renewable energy source due to its potential role in reducing carbon emissions. It is a safe, clean, and inexhaustible source of energy. The amount of wind energy generated by wind turbines is closely related to the wind speed. Wind speed forecasting plays a vital role in the wind energy sector in terms of wind turbine optimal operation, wind energy dispatch and scheduling, efficient energy harvesting etc. It is also considered during planning, design, and assessment of any proposed wind project. Therefore, accurate prediction of wind speed carries a particular importance and plays significant roles in the wind industry. Many methods have been proposed in the literature for short-term wind speed forecasting. These methods are usually based on modeling historical fixed time intervals of the wind speed data and using it for future prediction. The methods mainly include statistical models such as ARMA, ARIMA model, physical models for instance numerical weather prediction and artificial Intelligence techniques for example support vector machine and neural networks. In this paper, we are interested in estimating hourly wind speed measures in United Arab Emirates (UAE). More precisely, we predict hourly wind speed using a nonparametric kernel estimation of the regression and volatility functions pertaining to nonlinear autoregressive model with ARCH model, which includes unknown nonlinear regression function and volatility function already discussed in the literature. The unknown nonlinear regression function describe the dependence between the value of the wind speed at time t and its historical data at time t -1, t - 2, … , t - d. This function plays a key role to predict hourly wind speed process. The volatility function, i.e., the conditional variance given the past, measures the risk associated to this prediction. Since the regression and the volatility functions are supposed to be unknown, they are estimated using nonparametric kernel methods. In addition, to the pointwise hourly wind speed forecasts, a confidence interval is also provided which allows to quantify the uncertainty around the forecasts.

Molecular chaperones and photoreceptor function

PubMed Central

Kosmaoglou, Maria; Schwarz, Nele; Bett, John S.; Cheetham, Michael E.

2008-01-01

Molecular chaperones facilitate and regulate protein conformational change within cells. This encompasses many fundamental cellular processes: including the correct folding of nascent chains; protein transport and translocation; signal transduction and protein quality control. Chaperones are, therefore, important in several forms of human disease, including neurodegeneration. Within the retina, the highly specialized photoreceptor cell presents a fascinating paradigm to investigate the specialization of molecular chaperone function and reveals unique chaperone requirements essential to photoreceptor function. Mutations in several photoreceptor proteins lead to protein misfolding mediated neurodegeneration. The best characterized of these are mutations in the molecular light sensor, rhodopsin, which cause autosomal dominant retinitis pigmentosa. Rhodopsin biogenesis is likely to require chaperones, while rhodopsin misfolding involves molecular chaperones in quality control and the cellular response to protein aggregation. Furthermore, the specialization of components of the chaperone machinery to photoreceptor specific roles has been revealed by the identification of mutations in molecular chaperones that cause inherited retinal dysfunction and degeneration. These chaperones are involved in several important cellular pathways and further illuminate the essential and diverse roles of molecular chaperones. PMID:18490186

Citrate chemistry and biology for biomaterials design.

PubMed

Ma, Chuying; Gerhard, Ethan; Lu, Di; Yang, Jian

2018-05-04

Leveraging the multifunctional nature of citrate in chemistry and inspired by its important role in biological tissues, a class of highly versatile and functional citrate-based materials (CBBs) has been developed via facile and cost-effective polycondensation. CBBs exhibiting tunable mechanical properties and degradation rates, together with excellent biocompatibility and processability, have been successfully applied in vitro and in vivo for applications ranging from soft to hard tissue regeneration, as well as for nanomedicine designs. We summarize in the review, chemistry considerations for CBBs design to tune polymer properties and to introduce functionality with a focus on the most recent advances, biological functions of citrate in native tissues with the new notion of degradation products as cell modulator highlighted, and the applications of CBBs in wound healing, nanomedicine, orthopedic, cardiovascular, nerve and bladder tissue engineering. Given the expansive evidence for citrate's potential in biology and biomaterial science outlined in this review, it is expected that citrate based materials will continue to play an important role in regenerative engineering. Copyright © 2018 Elsevier Ltd. All rights reserved.

The role of bile acids in metabolic regulation.

PubMed

Vítek, Libor; Haluzík, Martin

2016-03-01

Bile acids (BA), long believed to only have lipid-digestive functions, have emerged as novel metabolic modulators. They have important endocrine effects through multiple cytoplasmic as well as nuclear receptors in various organs and tissues. BA affect multiple functions to control energy homeostasis, as well as glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor and the cytoplasmic G protein-coupled BA receptor TGR5 in a variety of tissues. However, BA also are aimed at many other cellular targets in a wide array of organs and cell compartments. Their role in the pathogenesis of diabetes, obesity and other 'diseases of civilization' becomes even more clear. They also interact with the gut microbiome, with important clinical implications, further extending the complexity of their biological functions. Therefore, it is not surprising that BA metabolism is substantially modulated by bariatric surgery, a phenomenon contributing favorably to the therapeutic effects of these surgical procedures. Based on these data, several therapeutic approaches to ameliorate obesity and diabetes have been proposed to affect the cellular targets of BA. © 2016 Society for Endocrinology.

Regulation of FOXO1-mediated transcription and cell proliferation by PARP-1

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

Sakamaki, Jun-ichi; Daitoku, Hiroaki; Yoshimochi, Kenji

2009-05-08

Forkhead box O (FOXO) transcription factors play an important role in a wide range of biological processes, including cell cycle control, apoptosis, detoxification of reactive oxygen species, and gluconeogenesis through regulation of gene expression. In this study, we demonstrated that PARP-1 functions as a negative regulator of FOXO1. We showed that PARP-1 directly binds to and poly(ADP-ribosyl)ates FOXO1 protein. PARP-1 represses FOXO1-mediated expression of cell cycle inhibitor p27{sup Kip1} gene. Notably, poly(ADP-ribosyl)ation activity was not required for the repressive effect of PARP-1 on FOXO1 function. Furthermore, knockdown of PARP-1 led to a decrease in cell proliferation in a manner dependentmore » on FOXO1 function. Chromatin immunoprecipitation experiments confirmed that PARP-1 is recruited to the p27{sup Kip1} gene promoter through a binding to FOXO1. These results suggest that PARP-1 acts as a corepressor for FOXO1, which could play an important role in proper cell proliferation by regulating p27{sup Kip1} gene expression.« less

The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

PubMed

Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

2018-01-29

Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain.

PubMed

Bouchard, Jean-François; Casanova, Christian; Cécyre, Bruno; Redmond, William John

2016-01-01

Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.

Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

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

Shi, Yongguo, E-mail: 1138303166@qq.com; Lu, Jianwei, E-mail: jianwei2010077@163.com; Zhou, Jing, E-mail: 2310848@163.com

2014-04-04

Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question,more » we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.« less

On the role of inter-basin surface salinity contrasts in global ocean circulation

NASA Astrophysics Data System (ADS)

Seidov, D.; Haupt, B. J.

2002-08-01

The role of sea surface salinity (SSS) contrasts in maintaining vigorous global ocean thermohaline circulation (TOC) is revisited. Relative importance of different generalizations of sea surface conditions in climate studies is explored. Ocean-wide inter-basin SSS contrasts serve as the major controlling element in global TOC. These contrasts are shown to be at least as important as high-latitudinal freshwater impacts. It is also shown that intra-basin longitudinal distribution of sea surface salinity, as well as intra- and inter-basin longitudinal distribution of sea surface temperature, is not crucial to conveyor functionality if only inter-basin contrasts in sea surface salinity are retained. This is especially important for paleoclimate and future climate simulations.

Employee customer orientation in manufacturing organizations: joint influences of customer proximity and the senior leadership team.

PubMed

Liao, Hui; Subramony, Mahesh

2008-03-01

Pursuing a customer-focused strategy in manufacturing organizations requires employees across functions to embrace the importance of understanding customer needs and to align their everyday efforts with the goal of satisfying and retaining customers. Little prior research has examined what factors influence employee customer orientation in manufacturing settings. Drawing on the attraction-selection-attrition model, upper-echelons theory, and contingency theories of leadership, this study investigated the joint influences of functional roles' proximity to external customers and the senior leadership team's customer orientation on employee customer orientation. Hierarchical linear modeling results based on data obtained from 4,299 employees and 403 senior leaders from 42 facilities of a global manufacturer operating in 16 countries revealed that employees occupying customer-contact roles had the highest level of customer orientation, followed by employees occupying production roles, and then by those in support roles. In addition, there was a positive relationship between the senior leadership team's customer orientation and employee customer orientation for all 3 functional roles. The positive relationship between the senior leadership team and employee customer orientation was the strongest for employees in support roles, suggesting that lower levels of proximity to external customers may create a greater need for leadership in developing employees' customer-oriented attitudes. Copyright 2008 APA

Assemblage and functional categorization of dung beetles (Coleoptera: Scarabaeinae) from the Pantanal

PubMed Central

Izzo, Thiago J.; Vaz-de-Mello, Fernando Z.

2017-01-01

The Pantanal is one of the world’s largest tropical wetland areas and harbors high mammal biomass. There is no formal list of dung beetle species, and studies on their functional roles have never being carried out in Pantanal. In this study, we identified dung beetle species occurring in the north Pantanal region (Poconé sub-region, Brazil) and studied their functional organization, by measuring morphological, behavioral and phenological traits. We collected 25,278 individuals belonging to 17 genera and 35 species. We identified eight functional groups in the habitat: Noturnal Telecoprids, Diurnal Telecoprids, Nesting Endocoprids, Small Nonrollers, Nocturnal Nester Paracoprids, Big Nesters Paracoprids, Non Nesters Paracoprids and Diurnal Nesters Paracoprids. The functional groups were defined mostly by two reproductive traits and two niche differentiation traits related to the use of fecal resources. This high diversification of both species and functional roles shows the importance of the group in a habitat with strong variation in availability of habitat and resources. PMID:29134142

Functional defect in regulatory T cells in myasthenia gravis

PubMed Central

Thiruppathi, Muthusamy; Rowin, Julie; Jiang, Qin Li; Sheng, Jian Rong; Prabhakar, Bellur S.; Meriggioli, Matthew N.

2012-01-01

Forkhead box P3 (FOXP3)+ is a transcription factor necessary for the function of regulatory T cells (Treg cells). Treg cells maintain immune homeostasis and self-tolerance, and play an important role in the prevention of autoimmune disease. Here, we discuss the role of Treg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in Treg cell in vitro suppressive function exists in MG patients, without an alteration in circulating frequency. This functional defect is associated with a reduced expression of key functional molecules such as FOXP3 on isolated Treg cells and appears to be more pronounced in immunosuppression-naive MG patients. In vitro administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the suppressive function of Treg cells and up-regulated FOXP3 expression. These findings indicate a clinically relevant Treg cell–intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target. PMID:23252899

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.

Putative terminator and/or effector functions of Arf GAPs in the trafficking of clathrin-coated vesicles.

PubMed

Kon, Shunsuke; Funaki, Tomo; Satake, Masanobu

2011-05-01

The role of ArfGAP1 as a terminator or effector in COPi-vesicle formation has been the subject of ongoing discussions. Here, the discussion on the putative terminator/effector functions has been enlarged to include Arf GAP members involved in the formation of clathrin-coated vesicles. ACAP1, whose role has been studied extensively, enhances the recycling of endocytosed proteins to the plasma membrane. Importantly, this positive role appears to be an overall reflection of both the terminator and effector activities attributed to ACAP1. Other Arf GAP subtypes have also been suggested to possess both terminator and effector activities. Interestingly, while most Arf GAP proteins regulate membrane trafficking by acting as facilitators, a few Arf GAP subtypes act as inhibitors.

Cancer rehabilitation in Austria--aspects of Physical Medicine and Rehabilitation.

PubMed

Maehr, Bruno; Keilani, Mohammad; Wiltschke, Christoph; Hassler, Marco; Licht, Thomas; Marosi, Christine; Huetterer, Elisabeth; Cenik, Fadime; Crevenna, Richard

2016-02-01

In Austria, cancer rehabilitation is an important issue in the management of cancer patients. Survival rates and survival time of cancer patients are increasing, and cancer rehabilitation is an important part in the treatment and care of cancer patients with the goal to improve functional status, quality of life, and (social) participation. Today, in Austria there are approximately 600 beds for inpatient rehabilitation. The field of outpatient rehabilitation will maybe be expanded after evaluating the existing pilot projects. Beside other specialities, the field of Physical Medicine and Rehabilitation (PM&R) plays an important role in cancer rehabilitation. In cancer rehabilitation, especially activating modalities from PM&R such as exercise are very important and well-accepted parts to improve functional status, quality of life, and participation of patients.

Domestic and International Best Practice Case Studies

DOT National Transportation Integrated Search

2001-02-01

Air transportation plays a vital role in the Texas economy. Air passenger/cargo traffic is projected to continue to increase considerably at many of the state's large airports. Ground access to airports is an important function that must be provided ...

Importance of Conserved Cysteine Residues in the Coronavirus Envelope Protein▿

PubMed Central

Lopez, Lisa A.; Riffle, Ambere J.; Pike, Steven L.; Gardner, Douglas; Hogue, Brenda G.

2008-01-01

Coronavirus envelope (E) proteins play an important, not fully understood role(s) in the virus life cycle. All E proteins have conserved cysteine residues located on the carboxy side of the long hydrophobic domain, suggesting functional significance. In this study, we confirmed that mouse hepatitis coronavirus A59 E protein is palmitoylated. To understand the role of the conserved residues and the necessity of palmitoylation, three cysteines at positions 40, 44, and 47 were changed singly and in various combinations to alanine. Double- and triple-mutant E proteins resulted in decreased virus-like particle output when coexpressed with the membrane (M) protein. Mutant E proteins were also studied in the context of a full-length infectious clone. Single-substitution viruses exhibited growth characteristics virtually identical to those of the wild-type virus, while the double-substitution mutations gave rise to viruses with less robust growth phenotypes indicated by smaller plaques and decreased virus yields. In contrast, replacement of all three cysteines resulted in crippled virus with significantly reduced yields. Triple-mutant viruses did not exhibit impairment in entry. Mutant E proteins localized properly in infected cells. A comparison of intracellular and extracellular virus yields suggested that release is only slightly impaired. E protein lacking all three cysteines exhibited an increased rate of degradation compared to that of the wild-type protein, suggesting that palmitoylation is important for the stability of the protein. Altogether, the results indicate that the conserved cysteines and presumably palmitoylation are functionally important for virus production. PMID:18184703

The role of WOX genes in flower development

PubMed Central

Costanzo, Enrico; Trehin, Christophe; Vandenbussche, Michiel

2014-01-01

Background WOX (Wuschel-like homeobOX) genes form a family of plant-specific HOMEODOMAIN transcription factors, the members of which play important developmental roles in a diverse range of processes. WOX genes were first identified as determining cell fate during embryo development, as well as playing important roles in maintaining stem cell niches in the plant. In recent years, new roles have been identified in plant architecture and organ development, particularly at the flower level. Scope In this review, the role of WOX genes in flower development and flower architecture is highlighted, as evidenced from data obtained in the last few years. The roles played by WOX genes in different species and different flower organs are compared, and differential functional recruitment of WOX genes during flower evolution is considered. Conclusions This review compares available data concerning the role of WOX genes in flower and organ architecture among different species of angiosperms, including representatives of monocots and eudicots (rosids and asterids). These comparative data highlight the usefulness of the WOX gene family for evo–devo studies of floral development. PMID:24973416