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

PubMed Central

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

2014-01-01

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

A Role for Brain Stress Systems in Addiction

PubMed Central

Koob, George F.

2009-01-01

Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate reward and stress. Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms. This review explores the role of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin [hypocretin], vasopressin, dynorphin) and brain antistress systems (neuropeptide Y, nociceptin [orphanin FQ]) in drug dependence, with emphasis on the neuropharmacological function of extrahypothalamic systems in the extended amygdala. The brain stress and antistress systems may play a key role in the transition to and maintenance of drug dependence once initiated. Understanding the role of brain stress and antistress systems in addiction provides novel targets for treatment and prevention of addiction and insights into the organization and function of basic brain emotional circuitry. PMID:18614026

The adenoid as a key factor in upper airway infections.

PubMed

van Cauwenberge, P B; Bellussi, L; Maw, A R; Paradise, J L; Solow, B

1995-06-01

The adenoids (and the nasopharynx) play a key role in the normal functioning and in various pathologies of the upper respiratory tract. In this paper the role of adenoidal pathology and the beneficial effect of adenoidectomy in some upper respiratory tract and facial anomalies and diseases are discussed; otitis media with effusion, recurrent acute otitis media, sinusitis, snoring and sleep apnea and abnormal patterns in the midface growth and development.

Language Ability and Verbal and Nonverbal Executive Functioning in Deaf Students Communicating in Spoken English

ERIC Educational Resources Information Center

Remine, Maria D.; Care, Esther; Brown, P. Margaret

2008-01-01

The internal use of language during problem solving is considered to play a key role in executive functioning. This role provides a means for self-reflection and self-questioning during the formation of rules and plans and a capacity to control and monitor behavior during problem-solving activity. Given that increasingly sophisticated language is…

Role of nuclear progesterone receptor isoforms in uterine pathophysiology

PubMed Central

Patel, Bansari; Elguero, Sonia; Thakore, Suruchi; Dahoud, Wissam; Bedaiwy, Mohamed; Mesiano, Sam

2015-01-01

BACKGROUND Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function. METHODS Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed. RESULTS Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key cellular signaling pathways required for growth. In contrast, progesterone via PR activation appears to increase leiomyoma growth. The exact role of PRs in cervical cancer is unclear. PRs regulate implantation and therefore aberrant PR function may be implicated in recurrent pregnancy loss (RPL). PRs likely regulate key immunogenic factors involved in RPL. However, the exact role of PRs in the pathophysiology of RPL and the use of progesterone for therapeutic benefit remains uncertain. CONCLUSIONS PRs are key mediators of progesterone action in uterine tissues and are essential for normal uterine function. Aberrant PR function (due to abnormal expression and/or function) is a major cause of uterine pathophysiology. Further investigation of the underlying mechanisms of PR isoform action in the uterus is required, as this knowledge will afford the opportunity to create progestin/PR-based therapeutics to treat various uterine pathologies. PMID:25406186

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

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

Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

PubMed Central

Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

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

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

Dynamic features of carboxy cytoglobin distal mutants investigated by molecular dynamics simulations.

PubMed

Zhao, Cong; Du, Weihong

2016-04-01

Cytoglobin (Cgb) is a member of hemoprotein family with roles in NO metabolism, fibrosis, and tumourigenesis. Similar to other hemoproteins, Cgb structure and functions are markedly influenced by distal key residues. The sixth ligand His(81) (E7) is crucial to exogenous ligand binding, heme pocket conformation, and physiological roles of this protein. However, the effects of other key residues on heme pocket and protein biological functions are not well known. In this work, a molecular dynamics (MD) simulation study of two single mutants in CO-ligated Cgb (L46FCgbCO and L46VCgbCO) and two double mutants (L46FH81QCgbCO and L46VH81QCgbCO) was conducted to explore the effects of the key distal residues Leu(46)(B10) and His(81)(E7) on Cgb structure and functions. Results indicated that the distal mutation of B10 and E7 affected CgbCO dynamic properties on loop region fluctuation, internal cavity rearrangement, and heme motion. The distal conformation change was reflected by the distal key residues Gln(62) (CD3) and Arg(84)(E10). The hydrogen bond between heme propionates with CD3 or E10 residues were evidently influenced by B10/E7 mutation. Furthermore, heme pocket rearrangement was also observed based on the distal pocket volume and occurrence rate of inner cavities. The mutual effects of B10 and E7 residues on protein conformational rearrangement and other dynamic features were expressed in current MD studies of CgbCO and its distal mutants, suggesting their crucial role in heme pocket stabilization, ligand binding, and Cgb biological functions. The mutation of distal B10 and E7 residues affects the dynamic features of carboxy cytoglobin.

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

PubMed

Anatchkova, Milena D; Bjorner, Jakob B

2010-02-01

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

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

PubMed

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

2016-01-27

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

Heme oxygenase: the key to renal function regulation

PubMed Central

Cao, Jian; Sacerdoti, David; Li, Xiaoying; Drummond, George

2009-01-01

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function. PMID:19570878

Effects of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction

EPA Science Inventory

The hypothalamus and pituitary are known to play key roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently, the endocrine contro...

School-University Partnership: The Wizard, the Warrior, and the Wagoner

ERIC Educational Resources Information Center

Castelli, Darla; Centeio, Erin; Boehrnsen, Helen; Barclay, Doug; Bundy, Craig

2012-01-01

There are many key players in a functional school-university partnership. The purpose of this article is to provide insight into the establishment of roles within a school-university partnership charged with creating educational reform. Specific details are provided about three key change agents (the Wizard, the Warrior, and the Wagoner) who…

Erythropoietin and the use of a transgenic model of erythropoietin-deficient mice

PubMed Central

Pichon, Aurélien; Jeton, Florine; El Hasnaoui-Saadani, Raja; Hagström, Luciana; Launay, Thierry; Beaudry, Michèle; Marchant, Dominique; Quidu, Patricia; Macarlupu, Jose-Luis; Favret, Fabrice; Richalet, Jean-Paul; Voituron, Nicolas

2016-01-01

Despite its well-known role in red blood cell production, it is now accepted that erythropoietin (Epo) has other physiological functions. Epo and its receptors are expressed in many tissues, such as the brain and heart. The presence of Epo/Epo receptors in these organs suggests other roles than those usually assigned to this protein. Thus, the aim of this review is to describe the effects of Epo deficiency on adaptation to normoxic and hypoxic environments and to suggest a key role of Epo on main physiological adaptive functions. Our original model of Epo-deficient (Epo-TAgh) mice allowed us to improve our knowledge of the possible role of Epo in O2 homeostasis. The use of anemic transgenic mice revealed Epo as a crucial component of adaptation to hypoxia. Epo-TAgh mice survive well in hypoxic conditions despite low hematocrit. Furthermore, Epo plays a key role in neural control of ventilatory acclimatization and response to hypoxia, in deformability of red blood cells, in cerebral and cardiac angiogenesis, and in neuro- and cardioprotection. PMID:27800506

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.

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.

Differential MicroRNA Profiles of Spontaneous and Induced Hepatocellular Carcinomas in Male B6C3F1 Mice.

EPA Science Inventory

Epigenetic processes have key roles in regulating transcriptional patterns and cellular functions related to chemical carcinogenesis. MicroRNAs (miRNAs) are attractive epigenetic biomarkers given their mechanistic roles in tumorigenesis, tissue-specificity, and small size, whi...

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.

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

Unity in diversity: structural and functional insights into the ancient partnerships between plants and fungi.

PubMed

Field, Katie J; Pressel, Silvia

2018-04-26

Contents I. II. III. IV. V. VI. VII. VIII. References SUMMARY: Mycorrhizal symbiosis is an ancient and widespread mutualism between plants and fungi that facilitated plant terrestrialisation > 500 million years ago, with key roles in ecosystem functioning at multiple scales. Central to the symbiosis is the bidirectional exchange of plant-fixed carbon for fungal-acquired nutrients. Within this unifying role of mycorrhizas, considerable diversity in structure and function reflects the diversity of the partners involved. Early diverging plants form mutualisms not only with arbuscular mycorrhizal Glomeromycotina fungi, but also with poorly characterised Mucoromycotina, which may also colonise the roots of 'higher' plants as fine root endophytes. Functional diversity in these symbioses depends on both fungal and plant life histories and is influenced by the environment. Recent studies have highlighted the roles of lipids/fatty acids in plant-to-fungus carbon transport and potential contributions of Glomeromycotina fungi to plant nitrogen nutrition. Together with emerging appreciation of mycorrhizal networks as multi-species resource-sharing systems, these insights are broadening our views on mycorrhizas and their roles in nutrient cycling. It is crucial that the diverse array of biotic and abiotic factors that together shape the dynamics of carbon-for-nutrient exchange between plants and fungi are integrated, in addition to embracing the unfolding and potentially key role of Mucoromycotina fungi in these processes. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Lipid Cell Biology: A Focus on Lipids in Cell Division.

PubMed

Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

2018-06-20

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

Hyaluronic acid: its role in voice.

PubMed

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

2002-09-01

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

School Influences on Child and Youth Development

ERIC Educational Resources Information Center

Osher, David; Kendziora, Kimberly; Spier, Elizabeth; Garibaldi, Mark L.

2014-01-01

Schools play a key role in child and youth development as both social microcosms of the broader society and reciprocally influencing people and communities. As such, schools can function as a protective factor that promotes safety, motivation, relationships, and support for positive student outcomes. However, schools may also function as a risk…

The role of vision processing in prosthetic vision.

PubMed

Barnes, Nick; He, Xuming; McCarthy, Chris; Horne, Lachlan; Kim, Junae; Scott, Adele; Lieby, Paulette

2012-01-01

Prosthetic vision provides vision which is reduced in resolution and dynamic range compared to normal human vision. This comes about both due to residual damage to the visual system from the condition that caused vision loss, and due to limitations of current technology. However, even with limitations, prosthetic vision may still be able to support functional performance which is sufficient for tasks which are key to restoring independent living and quality of life. Here vision processing can play a key role, ensuring that information which is critical to the performance of key tasks is available within the capability of the available prosthetic vision. In this paper, we frame vision processing for prosthetic vision, highlight some key areas which present problems in terms of quality of life, and present examples where vision processing can help achieve better outcomes.

Remote Control of Gene Function by Local Translation

PubMed Central

Jung, Hosung; Gkogkas, Christos G.; Sonenberg, Nahum; Holt, Christine E.

2014-01-01

The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function. PMID:24679524

[Progress in the study on mammalian diacylgycerol acyltransgerase (DGAT) gene and its biological function].

PubMed

Wang, Yan; Xu, Heng-Yong; Zhu, Qing

2007-10-01

Diacylglycerol acyltransferase (DGAT; EC 2.3.1.20) is a microsomal enzyme that plays a central role in the metabolism of cellular glycerolipids. DGAT catalyzes the final step in triacylglycerol (TAG) biosynthesis by converting diacylgycerol (DAG) and fatty acyl-coenzyme A (CoA) into triacylglycero1. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. Therefore, DGAT is not only an key factor for control triglycerides and fatty acids, but also may play a key modulatory role in animal fat deposition.

Integrin-linked kinase: a Scaffold protein unique among its ilk.

PubMed

Dagnino, Lina

2011-06-01

Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be the next key step to understand its distinct biological roles across tissues and species.

Cover cropping frequency is the main driver of soil microbial changes during six years of organic vegetable production

USDA-ARS?s Scientific Manuscript database

Soil microbes play a key role in soil health, and understanding the functional role of this living component of soil organic matter is critical to developing sustainable systems in major vegetable production regions like Salinas, California. Soil microbial community size and composition was evaluat...

Process Consultation: Its Role in Organization Development.

ERIC Educational Resources Information Center

Schein, Edgar H.

This volume focuses on the process by which the consultant builds readiness for organizational development (OD) programs, actually conducts training, and works with the key individuals of an organization as part of an OD program. Part I describes in some detail the human processes in organizations--communication, functional roles of group members,…

What do mouse models of muscular dystrophy tell us about the DAPC and its components?

PubMed

Whitmore, Charlotte; Morgan, Jennifer

2014-12-01

There are over 30 mouse models with mutations or inactivations in the dystrophin-associated protein complex. This complex is thought to play a crucial role in the functioning of muscle, as both a shock absorber and signalling centre, although its role in the pathogenesis of muscular dystrophy is not fully understood. The first mouse model of muscular dystrophy to be identified with a mutation in a component of the dystrophin-associated complex (dystrophin) was the mdx mouse in 1984. Here, we evaluate the key characteristics of the mdx in comparison with other mouse mutants with inactivations in DAPC components, along with key modifiers of the disease phenotype. By discussing the differences between the individual phenotypes, we show that the functioning of the DAPC and consequently its role in the pathogenesis is more complicated than perhaps currently appreciated. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

The bioactive acidic serine- and aspartate-rich motif peptide.

PubMed

Minamizaki, Tomoko; Yoshiko, Yuji

2015-01-01

The organic component of the bone matrix comprises 40% dry weight of bone. The organic component is mostly composed of type I collagen and small amounts of non-collagenous proteins (NCPs) (10-15% of the total bone protein content). The small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a NCP, is considered to play a key role in bone mineralization. SIBLING family of proteins share common structural features and includes the arginine-glycine-aspartic acid (RGD) motif and acidic serine- and aspartic acid-rich motif (ASARM). Clinical manifestations of gene mutations and/or genetically modified mice indicate that SIBLINGs play diverse roles in bone and extraskeletal tissues. ASARM peptides might not be primary responsible for the functional diversity of SIBLINGs, but this motif is suggested to be a key domain of SIBLINGs. However, the exact function of ASARM peptides is poorly understood. In this article, we discuss the considerable progress made in understanding the role of ASARM as a bioactive peptide.

The key role of extracellular vesicles in the metastatic process.

PubMed

Zhao, Hongyun; Achreja, Abhinav; Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Nagrath, Deepak; Fais, Stefano

2018-01-01

Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Beyond microbial community composition: functional activities of the oral microbiome in health and disease

PubMed Central

Duran-Pinedo, Ana E.; Frias-Lopez, Jorge

2015-01-01

The oral microbiome plays a relevant role in the health status of the host and is a key element in a variety of oral and non-oral diseases. Despite advances in our knowledge of changes in microbial composition associated with different health conditions the functional aspects of the oral microbiome that lead to dysbiosis remain for the most part unknown. In this review, we discuss the progress made towards understanding the functional role of the oral microbiome in health and disease and how novel technologies are expanding our knowledge on this subject. PMID:25862077

The E-Business Opportunity: A Key Role for Business Educators.

ERIC Educational Resources Information Center

McGrath, Leanne C.; Lomerson, William L.

2001-01-01

Outlines considerations for pursuing electronic business: website content; cost of authoring, hosting, and registering domains; design (usability, aesthetics, functionality, confidentiality); customer focus; marketing; and maintenance. (Contains 29 references.) (SK)

Insulin: its Role in the Central Control of Reproduction

PubMed Central

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

2014-01-01

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

Insulin: its role in the central control of reproduction.

PubMed

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

2014-06-22

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

Diagnosis and Management of Budd Chiari Syndrome: An Update

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

Copelan, Alexander, E-mail: alexander.copelan@beaumont.edu; Remer, Erick M., E-mail: remere1@ccf.org; Sands, Mark, E-mail: sandsm@ccf.org

Imaging plays a crucial role in the early detection and assessment of the extent of disease in Budd Chiari syndrome (BCS). Early diagnosis and intervention to mitigate hepatic congestion is vital to restoring hepatic function and alleviating portal hypertension. Interventional radiology serves a key role in the management of these patients. The interventionist should be knowledgeable of the clinical presentation as well as key imaging findings, which often dictate the approach to treatment. This article concisely reviews the etiology, pathophysiology, and clinical presentation of BCS and provides a detailed description of imaging and treatment options, particularly interventional management.

Visa Security Policy: Roles of the Departments of State and Homeland Security

DTIC Science & Technology

2011-06-30

Functions in the Major Homeland Security Bills, both by Lisa M. Seghetti and Ruth Ellen Wasem. (Archived reports, available upon request.) 4 Ian Kelly , On...determine who, how many, and the scope of their functions. Then-Assistant Secretary of State for Consular Affairs Maura Harty described several key

Functions in Contemporary Secondary Mathematics Textbook Series in the United States

ERIC Educational Resources Information Center

Ross, Daniel J.

2011-01-01

Textbooks play a central role in US mathematics classrooms (Stein, Remillard, & Smith, 2007) and functions are a key topic in secondary mathematics (Carlson, Jacobs, Coe, Larsen, & Hsu, 2002). This study presents results from an analysis of this essential topic in the latest editions of three textbook series: the Glencoe Mathematics…

Leader Training Conference Report.

ERIC Educational Resources Information Center

Michigan-Ohio Regional Educational Lab., Inc., Detroit.

The purpose of this conference was to prepare key people in the field of education to function as inservice education leaders in their respective settings. It called for participants to learn what the MOREL inservice education program is and what it hopes to accomplish, to identify the role and functions of the inservice education leader, and to…

Glucose metabolism regulates T cell activation, differentiation, and functions.

PubMed

Palmer, Clovis S; Ostrowski, Matias; Balderson, Brad; Christian, Nicole; Crowe, Suzanne M

2015-01-01

The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation, and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The "Warburg effect" originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here, we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

Role of conformational dynamics in the evolution of novel enzyme function.

PubMed

Maria-Solano, Miguel A; Serrano-Hervás, Eila; Romero-Rivera, Adrian; Iglesias-Fernández, Javier; Osuna, Sílvia

2018-05-21

The free energy landscape concept that describes enzymes as an ensemble of differently populated conformational sub-states in dynamic equilibrium is key for evaluating enzyme activity, enantioselectivity, and specificity. Mutations introduced in the enzyme sequence can alter the populations of the pre-existing conformational states, thus strongly modifying the enzyme ability to accommodate alternative substrates, revert its enantiopreferences, and even increase the activity for some residual promiscuous reactions. In this feature article, we present an overview of the current experimental and computational strategies to explore the conformational free energy landscape of enzymes. We provide a series of recent publications that highlight the key role of conformational dynamics for the enzyme evolution towards new functions and substrates, and provide some perspectives on how conformational dynamism should be considered in future computational enzyme design protocols.

Memory-guided attention in the anterior thalamus.

PubMed

Leszczyński, Marcin; Staudigl, Tobias

2016-07-01

The anterior thalamus is densely connected with both the hippocampus and the prefrontal cortex. It is known to play a role in learning and episodic memory. Given its connectivity profile with the prefrontal cortex, it may also be expected to contribute to executive functions. Recent studies in both rodents and humans add to our understanding of anterior thalamic function, suggesting that it is a key region for allocating attention. We discuss the convergence between studies in rodents and humans, both of which imply that the anterior thalamus may play a key role in memory-guided attention. We suggest that efficient allocation of attention to memory representations requires interaction between the memory-related hippocampal and the attention related fronto-parietal networks. We further propose that the anterior thalamus is a hub that connects and modulates both systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

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

Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara

Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations inmore » primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.« less

Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

DOE PAGES

Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; ...

2014-10-07

Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations inmore » primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.« less

Nutrition, frailty, and sarcopenia.

PubMed

Cruz-Jentoft, Alfonso J; Kiesswetter, Eva; Drey, Michael; Sieber, Cornel C

2017-02-01

Frailty and sarcopenia are important concepts in the quest to prevent physical dependence, as geriatrics are shifting towards identifications of early stages of disability. Definitions of both sarcopenia and frailty are still developing, and both concepts clearly overlap in their physical aspects. Malnutrition (both undernutrition and obesity) plays a key role in the pathogenesis of frailty and sarcopenia. The quality of the diet along the lifespan has a close relation with the incidence of both entities, and nutritional interventions may be able to reduce the incidence or revert either of them. This brief review explores the role of energy and protein intake and other key nutrients on muscle function. Nutrition may be a key element of multimodal interventions for frailty and sarcopenia. The results of the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) trial will offer key insights on the effect of such interventions in frail, sarcopenic older individuals.

Roles of EphA2 in Development and Disease

PubMed Central

Park, Jeong Eun; Son, Alexander I.; Zhou, Renping

2013-01-01

The Eph family of receptor tyrosine kinases (RTKs) has been implicated in the regulation of many aspects of mammalian development. Recent analyses have revealed that the EphA2 receptor is a key modulator for a wide variety of cellular functions. This review focuses on the roles of EphA2 in both development and disease. PMID:24705208

The critical role of peptide chemistry in the life sciences.

PubMed

Kent, Stephen B H

2015-03-01

Peptide chemistry plays a key role in the synthesis and study of protein molecules and their functions. Modern ligation methods enable the total synthesis of enzymes and the systematic dissection of the chemical basis of enzyme catalysis. Predicted developments in peptide science are described. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Changing Attitudes over Time: Assessing the Effectiveness of a Workplace Diversity Course

ERIC Educational Resources Information Center

Probst, Tahira M.

2003-01-01

Diversity is increasing within the United States, and higher education will likely play a key role in preparing people to function in this new environment. This study assessed the effectiveness of a semester-long psychology workplace diversity course at changing student levels of ethnocentrism and attitudes regarding gender roles; the disabled;…

Role of Mesenchymal Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases

DTIC Science & Technology

2017-07-01

that IL6 is elevated under these in vitro conditions using an ELISA -based system (Fig 1). We are now investigating the potential functional role of...narrowed our focus on DNMT1 which encodes for a DNA methyltransferase that is key in regulating global epigenetic methylation Figure 1. ELISA

Group Leadership: Understanding, Guiding, & Sharing. Keys to Community Involvement Series: 15.

ERIC Educational Resources Information Center

Druian, Greg

This booklet addresses persons who would like information about leadership of community groups. It is meant to be read both by current community group leaders and by persons who aspire to be leaders. Roles and functions of community group leadership are presented, along with suggestions about how to carry out the leadership role in ways that…

Neurotrophin Propeptides: Biological Functions and Molecular Mechanisms.

PubMed

Rafieva, Lola M; Gasanov, Eugene V

2016-01-01

Neurotrophins constitute a family of growth factors that play a key role in the regulation of the development and function of the central and peripheral nervous systems. A common feature of all the neurotrophins is their synthesis in cells as long precursors (pre-pro-neurotrophins) that contain an N-terminal signal peptide, a following propeptide and the mature neurotrophin. Although the signal peptide functions have been well studied, the role of neurotrophin propeptides is not so clear. Here, we briefly summarize the biochemistry of neurotrophin propeptides, including their role as folding-assistants for the mature factor and their role in processing and in secretion of neurotrophins. In the main part of the review we summarize our current state of knowledge of the biological activity of neurotrophin propeptides, their possible mechanisms of action, and their potential influence on the activity of the mature neurotrophins.

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

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.

Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

PubMed Central

Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

2010-01-01

Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional responses between HIF-α and PHD homologs from oysters and other invertebrate and vertebrate species implies the highly conserved functions of these genes throughout the evolutionary history of animals, in accordance with their critical role in oxygen sensing and homeostasis. PMID:21106446

Coping with "absence-presence": noncustodial fathers' parenting behaviors.

PubMed

Baum, Nehami

2004-07-01

This article is based on the view that the nature of the divorced father's involvement with his children is affected by psychological processes that enable him to separate his parental from his spousal role and identity. It argues that the ability to cope with the simultaneous absence of the spousal role and identity and presence of the paternal role and identity is a key factor in shaping the divorced father's behavior toward his children. The article illustrates the claim in 3 case studies showing (a) parental functioning marred by ongoing conflict with the children's mother, (b) disengagement, and (c) stable and consistent parental functioning within the inevitable limitations of noncustodial fatherhood.

Mitochondria, calcium, and tumor suppressor Fus1: At the crossroad of cancer, inflammation, and autoimmunity

PubMed Central

Uzhachenko, Roman; Shanker, Anil; Yarbrough, Wendell G.; Ivanova, Alla V.

2015-01-01

Mitochondria present a unique set of key intracellular functions such as ATP synthesis, production of reactive oxygen species (ROS) and Ca2+ buffering. Mitochondria both encode and decode Ca2+ signals and these interrelated functions have a direct impact on cell signaling and metabolism. High proliferative potential is a key energy-demanding feature shared by cancer cells and activated T lymphocytes. Switch of a metabolic state mediated by alterations in mitochondrial homeostasis plays a fundamental role in maintenance of the proliferative state. Recent studies show that tumor suppressors have the ability to affect mitochondrial homeostasis controlling both cancer and autoimmunity. Herein, we discuss established and putative mechanisms of calcium–dependent regulation of both T cell and tumor cell activities. We use the mitochondrial protein Fus1 as a case of tumor suppressor that controls immune response and tumor growth via maintenance of mitochondrial homeostasis. We focus on the regulation of mitochondrial Ca2+ handling as a key function of Fus1 and highlight the mechanisms of a crosstalk between Ca2+ accumulation and mitochondrial homeostasis. Given the important role of Ca2+ signaling, mitochondrial Ca2+ transport and ROS production in the activation of NFAT and NF-κB transcription factors, we outline the importance of Fus1 activities in this context. PMID:26246474

Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

PubMed Central

Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

2015-01-01

The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

A core functional region of the RFP1 promoter from Chinese wild grapevine is activated by powdery mildew pathogen and heat stress.

PubMed

Yu, Yihe; Xu, Weirong; Wang, Jie; Wang, Lei; Yao, Wenkong; Xu, Yan; Ding, Jiahua; Wang, Yuejin

2013-01-01

RING-finger proteins (RFP) function as ubiquitin ligases and play key roles in plant responses to biotic and abiotic stresses. However, little information is available on the regulation of RFP expression. Here, we isolate and characterize the RFP promoter sequence from the disease-resistant Chinese wild grape Vitis pseudoreticulata accession Baihe-35-1. Promoter-GUS fusion assays revealed that defense signaling molecules, powdery mildew infection, and heat stress induce VpRFP1 promoter activity. By contrast, the RFP1 promoter isolated from Vitis vinifera was only slightly induced by pathogen infection and heat treatment. By promoter deletion analysis, we found that the -148 bp region of the VpRFP1 promoter was the core functional promoter region. We also found that, in Arabidopsis, VpRFP1 expressed under its own promoter activated defense-related gene expression and improved disease resistance, but the same construct using the VvRFP1 promoter slightly improve disease resistance. Our results demonstrated that the -148 bp region of the VpRFP1 promoter plays a key role in response to pathogen and heat stress, and suggested that expression differences between VpRFP1 and VvRFP1 may be key for the differing disease resistance phenotypes of the two Vitis genotypes.

Leader Training Conference Report. (Second, February 3-19, 1969).

ERIC Educational Resources Information Center

Michigan-Ohio Regional Educational Lab., Inc., Detroit.

The purpose of this conference was to prepare key people in the field of education to function as inservice education leaders in their respective settings. The design called for participants to learn what the MOREL inservice education program is and what it hopes to accomplish, to identify the role and functions of the inservice education leader,…

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…

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

PubMed

Martin, Tracey A; Jiang, Wen G

2009-04-01

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

Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

PubMed Central

Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian

2013-01-01

The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037

PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells

PubMed Central

He, Feng; Chen, Hairong; Probst-Kepper, Michael; Geffers, Robert; Eifes, Serge; del Sol, Antonio; Schughart, Klaus; Zeng, An-Ping; Balling, Rudi

2012-01-01

Human FOXP3+CD25+CD4+ regulatory T cells (Tregs) are essential to the maintenance of immune homeostasis. Several genes are known to be important for murine Tregs, but for human Tregs the genes and underlying molecular networks controlling the suppressor function still largely remain unclear. Here, we describe a strategy to identify the key genes directly from an undirected correlation network which we reconstruct from a very high time-resolution (HTR) transcriptome during the activation of human Tregs/CD4+ T-effector cells. We show that a predicted top-ranked new key gene PLAU (the plasminogen activator urokinase) is important for the suppressor function of both human and murine Tregs. Further analysis unveils that PLAU is particularly important for memory Tregs and that PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways. Our study demonstrates the potential for identifying novel key genes for complex dynamic biological processes using a network strategy based on HTR data, and reveals a critical role for PLAU in Treg suppressor function. PMID:23169000

Categorical counting.

PubMed

Fetterman, J Gregor; Killeen, P Richard

2010-09-01

Pigeons pecked on three keys, responses to one of which could be reinforced after a few pecks, to a second key after a somewhat larger number of pecks, and to a third key after the maximum pecking requirement. The values of the pecking requirements and the proportion of trials ending with reinforcement were varied. Transits among the keys were an orderly function of peck number, and showed approximately proportional changes with changes in the pecking requirements, consistent with Weber's law. Standard deviations of the switch points between successive keys increased more slowly within a condition than across conditions. Changes in reinforcement probability produced changes in the location of the psychometric functions that were consistent with models of timing. Analyses of the number of pecks emitted and the duration of the pecking sequences demonstrated that peck number was the primary determinant of choice, but that passage of time also played some role. We capture the basic results with a standard model of counting, which we qualify to account for the secondary experiments. Copyright 2010 Elsevier B.V. All rights reserved.

Ammonia oxidizer populations vary with nitrogen cycling across a tropical montane mean annual temperature gradient

Treesearch

S. Pierre; I. Hewson; J. P. Sparks; C. M. Litton; C. Giardina; P. M. Groffman; T. J. Fahey

2017-01-01

Functional gene approaches have been used to better understand the roles of microbes in driving forest soil nitrogen (N) cycling rates and bioavailability. Ammonia oxidation is a rate limiting step in nitrification, and is a key area for understanding environmental constraints on N availability in forests. We studied how increasing temperature affects the role of...

Understanding the HRD Role in MNCs: The Imperatives of Social Capital and Networking

ERIC Educational Resources Information Center

Gubbins, Claire; Garavan, Thomas N.

2009-01-01

In an era of increasing global competition, it is argued that knowledge and skills are the key sources of competitive advantage. This places the human resource development (HRD) function in a situation of increased status and power, if HRD professionals adopt roles in a way that adds "value" and facilitates achievement of competitive advantage.…

Evolution of the knowledge system for agricultural development in the Yaqui Valley, Sonora, Mexico.

PubMed

McCullough, Ellen B; Matson, Pamela A

2016-04-26

Knowledge systems-networks of linked actors, organizations, and objects that perform a number of knowledge-related functions that link knowledge and know how with action-have played a key role in fostering agricultural development over the last 50 years. We examine the evolution of the knowledge system of the Yaqui Valley, Mexico, a region often described as the home of the green revolution for wheat, tracing changes in the functions of critical knowledge system participants, information flows, and research priorities. Most of the knowledge system's key players have been in place for many decades, although their roles have changed in response to exogenous and endogenous shocks and trends (e.g., drought, policy shifts, and price trends). The system has been agile and able to respond to challenges, in part because of the diversity of players (evolving roles of actors spanning research-decision maker boundaries) and also because of the strong and consistent role of innovative farmers. Although the agricultural research agenda in the Valley is primarily controlled from within the agricultural sector, outside voices have become an important influence in broadening development- and production-oriented perspectives to sustainability perspectives.

Evolution of the knowledge system for agricultural development in the Yaqui Valley, Sonora, Mexico

PubMed Central

McCullough, Ellen B.; Matson, Pamela A.

2016-01-01

Knowledge systems—networks of linked actors, organizations, and objects that perform a number of knowledge-related functions that link knowledge and know how with action—have played a key role in fostering agricultural development over the last 50 years. We examine the evolution of the knowledge system of the Yaqui Valley, Mexico, a region often described as the home of the green revolution for wheat, tracing changes in the functions of critical knowledge system participants, information flows, and research priorities. Most of the knowledge system's key players have been in place for many decades, although their roles have changed in response to exogenous and endogenous shocks and trends (e.g., drought, policy shifts, and price trends). The system has been agile and able to respond to challenges, in part because of the diversity of players (evolving roles of actors spanning research–decision maker boundaries) and also because of the strong and consistent role of innovative farmers. Although the agricultural research agenda in the Valley is primarily controlled from within the agricultural sector, outside voices have become an important influence in broadening development- and production-oriented perspectives to sustainability perspectives. PMID:21606365

Realization of ActiveX control based on ATL in VC 2008

NASA Astrophysics Data System (ADS)

Li, Shuhua; Tie, Yong

2011-10-01

ActiveX has a key role in web development, this paper realizes the classical program Polygon in the newest Visual C++ environment 2008 and tests each function of control in ActiveX Control Test Container. After that web code is created rapidly via ActiveX Control Pad and it is checked in HTML. Development process and key point attention are summarized systematically which can guide the related developers.

Core areas of practice and associated competencies for nurses working as professional cancer navigators.

PubMed

Cook, Sandra; Fillion, Lise; Fitch, Margaret; Veillette, Anne-Marie; Matheson, Tanya; Aubin, Michèle; de Serres, Marie; Doll, Richard; Rainville, François

2013-01-01

Fillion et al. (2012) recently designed a conceptual framework for professional cancer navigators describing key functions of professional cancer navigation. Building on this framework, this study defines the core areas of practice and associated competencies for professional cancer navigators. The methods used in this study included: literature review, mapping of navigation functions against practice standards and competencies, and validation of this mapping process with professional navigators, their managers and nursing experts and comparison of roles in similar navigation programs. Associated competencies were linked to the three identified core areas of practice, which are: 1) providing information and education, 2) providing emotional and supportive care, and 3) facilitating coordination and continuity of care. Cancer navigators are in a key position to improve patient and family empowerment and continuity of care. This is an important step for advancing the role of oncology nurses in navigator positions and identifying areas for further research.

Astrocytic glycogen metabolism in the healthy and diseased brain.

PubMed

Bak, Lasse K; Walls, Anne B; Schousboe, Arne; Waagepetersen, Helle S

2018-05-11

The brain contains a fairly low amount of glycogen, mostly located in astrocytes, a fact that has prompted the suggestion that glycogen does not have a significant physiological role in the brain. However, glycogen metabolism in astrocytes is essential for several key physiological processes and is adversely affected in disease. For instance, diminished ability to break down glycogen impinges on learning, and epilepsy, Alzheimer's disease, and type 2 diabetes are all associated with abnormal astrocyte glycogen metabolism. Glycogen metabolism supports astrocytic K + and neurotransmitter glutamate uptake and subsequent glutamine synthesis-three fundamental steps in excitatory signaling at most brain synapses. Thus, there is abundant evidence for a key role of glycogen in brain function. Here, we summarize the physiological brain functions that depend on glycogen, discuss glycogen metabolism in disease, and investigate how glycogen breakdown is regulated at the cellular and molecular levels. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

PubMed

Hess, Christoph; Kemper, Claudia

2016-08-16

Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings. Copyright © 2016 Elsevier Inc. All rights reserved.

The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B.

PubMed

Lapinski, Philip E; Oliver, Jennifer A; Bodie, Jennifer N; Marti, Francesc; King, Philip D

2009-11-01

Adapter proteins play key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules. In T lymphocytes, the role of several different types of adapter proteins in T-cell antigen receptor signal transduction is well established. An exception to this is the family of T-cell-specific adapter (TSAd) proteins comprising of TSAd, adapter protein of unknown function (ALX), SH2D4A, and SH2D4B. Only recently has the function of these adapters in T-cell signal transduction been explored. Here, we discuss advances in our understanding of the role of this family of adapter proteins in T cells. Their function as regulators of signal transduction in other cell types is also discussed.

A systematic review of the role of vitamin insufficiencies and supplementation in COPD.

PubMed

Tsiligianni, Ioanna G; van der Molen, Thys

2010-12-06

Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function.

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

PubMed

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

2013-11-01

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

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

PubMed Central

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

2016-01-01

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

Global biodiversity, stoichiometry and ecosystem function responses to human-induced C-N-P imbalances.

PubMed

Carnicer, Jofre; Sardans, Jordi; Stefanescu, Constantí; Ubach, Andreu; Bartrons, Mireia; Asensio, Dolores; Peñuelas, Josep

2015-01-01

Global change analyses usually consider biodiversity as a global asset that needs to be preserved. Biodiversity is frequently analysed mainly as a response variable affected by diverse environmental drivers. However, recent studies highlight that gradients of biodiversity are associated with gradual changes in the distribution of key dominant functional groups characterized by distinctive traits and stoichiometry, which in turn often define the rates of ecosystem processes and nutrient cycling. Moreover, pervasive links have been reported between biodiversity, food web structure, ecosystem function and species stoichiometry. Here we review current global stoichiometric gradients and how future distributional shifts in key functional groups may in turn influence basic ecosystem functions (production, nutrient cycling, decomposition) and therefore could exert a feedback effect on stoichiometric gradients. The C-N-P stoichiometry of most primary producers (phytoplankton, algae, plants) has been linked to functional trait continua (i.e. to major axes of phenotypic variation observed in inter-specific analyses of multiple traits). In contrast, the C-N-P stoichiometry of higher-level consumers remains less precisely quantified in many taxonomic groups. We show that significant links are observed between trait continua across trophic levels. In spite of recent advances, the future reciprocal feedbacks between key functional groups, biodiversity and ecosystem functions remain largely uncertain. The reported evidence, however, highlights the key role of stoichiometric traits and suggests the need of a progressive shift towards an ecosystemic and stoichiometric perspective in global biodiversity analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

PubMed

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

2015-11-01

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

Ecosystem services provided by waterbirds.

PubMed

Green, Andy J; Elmberg, Johan

2014-02-01

Ecosystem services are ecosystem processes that directly or indirectly benefit human well-being. There has been much recent literature identifying different services and the communities and species that provide them. This is a vital first step towards management and maintenance of these services. In this review, we specifically address the waterbirds, which play key functional roles in many aquatic ecosystems, including as predators, herbivores and vectors of seeds, invertebrates and nutrients, although these roles have often been overlooked. Waterbirds can maintain the diversity of other organisms, control pests, be effective bioindicators of ecological conditions, and act as sentinels of potential disease outbreaks. They also provide important provisioning (meat, feathers, eggs, etc.) and cultural services to both indigenous and westernized societies. We identify key gaps in the understanding of ecosystem services provided by waterbirds and areas for future research required to clarify their functional role in ecosystems and the services they provide. We consider how the economic value of these services could be calculated, giving some examples. Such valuation will provide powerful arguments for waterbird conservation. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

Mitochondrial function, ornamentation, and immunocompetence.

PubMed

Koch, Rebecca E; Josefson, Chloe C; Hill, Geoffrey E

2017-08-01

Understanding the mechanisms that link ornamental displays and individual condition is key to understanding the evolution and function of ornaments. Immune function is an aspect of individual quality that is often associated with the expression of ornamentation, but a general explanation for why the expression of some ornaments seems to be consistently linked to immunocompetence remains elusive. We propose that condition-dependent ornaments may be linked to key aspects of immunocompetence through co-dependence on mitochondrial function. Mitochondrial involvement in immune function is rarely considered outside of the biomedical literature, but the role of mitochondria as the primary energy producers of the cell and the centres of biosynthesis, the oxidative stress response, and cellular signalling place them at the hub of a variety of immune pathways. A promising new mechanistic explanation for correlations between a wide range of ornamental traits and the properties of individual quality is that mitochondrial function may be the 'shared pathway' responsible for links between ornament production and individual condition. Herein, we first review the role of mitochondria as both signal transducers and metabolic regulators of immune function. We then describe connections between hormonal pathways and mitochondria, with implications for both immune function and the expression of ornamentation. Finally, we explore the possibility that ornament expression may link directly to mitochondrial function. Considering condition-dependent traits within the framework of mitochondrial function has the potential to unify central tenets within the study of sexual selection, eco-immunology, oxidative stress ecology, stress and reproductive hormone biology, and animal physiology. © 2016 Cambridge Philosophical Society.

A Unifying Theory of Biological Function.

PubMed

van Hateren, J H

2017-01-01

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism's fitness, and modulates the organism's variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories.

Introduction to the special section on "translational models of prefrontal cortical function".

PubMed

Baxter, Mark G

2011-06-01

Impaired functioning of the prefrontal cortex is particularly prominent in many forms of psychopathology and in degenerative brain diseases. Because it is challenging to draw causal links between specific brain abnormalities and impaired cognition in these conditions, research using nonhuman animals has a key role to play in elucidating the neurobiological mechanisms of prefrontal cortex function and aiding the search for treatments. This role is clearly illustrated in the review articles and original research reports in this special section. Taken together, these papers demonstrate the insights that have already been gained from research with nonhuman animals as well as the work that still needs to be done to attain the goal of understanding human prefrontal cortical function in both health and disease.

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.

The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals.

PubMed

Diab, Ahmed; Foca, Adrien; Zoulim, Fabien; Durantel, David; Andrisani, Ourania

2018-01-01

Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis. In this article, we review the diverse roles of HBc in HBV replication and pathogenesis, emphasizing how the unique structure of this protein is key to its various functions. We focus in particular on recent advances in understanding the significance of HBc phosphorylations, its interaction with host proteins and the role of HBc in regulating the transcription of host genes. We also briefly allude to the emerging niche for new direct-acting antivirals targeting HBc, known as Core (protein) Allosteric Modulators (CAMs). Copyright © 2017 Elsevier B.V. All rights reserved.

Prefrontal-Hippocampal Pathways Underlying Inhibitory Control Over Memory

PubMed Central

Anderson, Michael C.; Bunce, Jamie G.; Barbas, Helen

2016-01-01

A key function of the prefrontal cortex is to support inhibitory control over behavior. It is widely believed that this function extends to stopping cognitive processes as well. Consistent with this, mounting evidence establishes the role of the right lateral prefrontal cortex in a clear case of cognitive control: retrieval suppression. Retrieval suppression refers to the ability to intentionally stop the retrieval process that arises when a reminder to a memory appears. Functional imaging data indicates that retrieval suppression involves top-down modulation of hippocampal activity by the dorsolateral prefrontal cortex, but the anatomical pathways supporting this inhibitory modulation remain unclear. Here we bridge this gap by integrating key findings about retrieval suppression observed through functional imaging with a detailed consideration of relevant anatomical pathways observed in non-human primates. Focusing selectively on the potential role of the anterior cingulate cortex, we develop two hypotheses about the pathways mediating interactions between lateral prefrontal cortex and the medial temporal lobes during suppression, and their cellular targets: the entorhinal gating hypothesis, and thalamo-hippocampal modulation via the nucleus reuniens. We hypothesize that whereas entorhinal gating is well situated to stop retrieval proactively, thalamo-hippocampal modulation may interrupt an ongoing act of retrieval reactively. Isolating the pathways that underlie retrieval suppression holds the potential to advance our understanding of a range of psychiatric disorders characterized by persistent intrusive thoughts. More broadly, an anatomical account of retrieval suppression would provide a key model system for understanding inhibitory control over cognition. PMID:26642918

The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.

PubMed

Peterson, Yuri K; Luttrell, Louis M

2017-07-01

The visual/ β -arrestins, a small family of proteins originally described for their role in the desensitization and intracellular trafficking of G protein-coupled receptors (GPCRs), have emerged as key regulators of multiple signaling pathways. Evolutionarily related to a larger group of regulatory scaffolds that share a common arrestin fold, the visual/ β -arrestins acquired the capacity to detect and bind activated GPCRs on the plasma membrane, which enables them to control GPCR desensitization, internalization, and intracellular trafficking. By acting as scaffolds that bind key pathway intermediates, visual/ β -arrestins both influence the tonic level of pathway activity in cells and, in some cases, serve as ligand-regulated scaffolds for GPCR-mediated signaling. Growing evidence supports the physiologic and pathophysiologic roles of arrestins and underscores their potential as therapeutic targets. Circumventing arrestin-dependent GPCR desensitization may alleviate the problem of tachyphylaxis to drugs that target GPCRs, and find application in the management of chronic pain, asthma, and psychiatric illness. As signaling scaffolds, arrestins are also central regulators of pathways controlling cell growth, migration, and survival, suggesting that manipulating their scaffolding functions may be beneficial in inflammatory diseases, fibrosis, and cancer. In this review we examine the structure-function relationships that enable arrestins to perform their diverse roles, addressing arrestin structure at the molecular level, the relationship between arrestin conformation and function, and sites of interaction between arrestins, GPCRs, and nonreceptor-binding partners. We conclude with a discussion of arrestins as therapeutic targets and the settings in which manipulating arrestin function might be of clinical benefit. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Targeting vacuolar H+-ATPases as a new strategy against cancer.

PubMed

Fais, Stefano; De Milito, Angelo; You, Haiyan; Qin, Wenxin

2007-11-15

Growing evidence suggests a key role of tumor acidic microenvironment in cancer development, progression, and metastasis. As a consequence, the need for compounds that specifically target the mechanism(s) responsible for the low pH of tumors is increasing. Among the key regulators of the tumor acidic microenvironment, vacuolar H(+)-ATPases (V-ATPases) play an important role. These proteins cover a number of functions in a variety of normal as well as tumor cells, in which they pump ions across the membranes. We discuss here some recent results showing that a molecular inhibition of V-ATPases by small interfering RNA in vivo as well as a pharmacologic inhibition through proton pump inhibitors led to tumor cytotoxicity and marked inhibition of human tumor growth in xenograft models. These results propose V-ATPases as a key target for new strategies in cancer treatment.

Long–term functional group recovery of lotic macroinvertebrates from logging disturbance.Canadian Journal of Fisheries and Aquatic Sciences

Treesearch

Damon T. Ely; J. Bruce Wallace

2010-01-01

Clear-cut logging rapidly affects stream macroinvertebrates through substantial alteration of terrestrial–aquatic resource linkages; however, lesser known are the long-term influences of forest succession on benthic macroinvertebrate assemblages, which play key roles in stream ecosystem function. We compared secondary production and standing crops of detritus in two...

Light quantity and photosystem function mediate host susceptibility to turnip mosaic virus via a salicylic acid-independent mechanism

USDA-ARS?s Scientific Manuscript database

Evidence going as far back as the early part of the 20th century suggests that both light and chloroplast function may play key roles in host susceptibility to viruses. Despite the long history of such work, confirmation of these phenomena and a determination of the underlying mechanisms remain elu...

An Introduction to Leadership and Its Functions in Further and Higher Education. Information Bank Working Paper Number 2555.

ERIC Educational Resources Information Center

Marsh, D. T.

This short paper surveys some of the key concepts concerning the behavior called "leadership" and explores the role of leadership in the management of further and higher education. It recounts briefly six hypotheses held about the nature of leadership (the trait theory, the situational theory, the social influence theory, the functional or…

Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.

PubMed

Robson, Matthew J; Quinlan, Meagan A; Blakely, Randy D

2017-05-17

Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.

Substrate Binding Process and Mechanistic Functioning of Type 1 11β-Hydroxysteroid Dehydrogenase from Enhanced Sampling Methods

PubMed Central

Recanatini, Maurizio; Cavalli, Andrea

2011-01-01

In humans, type 1 11β-hydroxysteroid dehydrogenase (11β-HSD-1) plays a key role in the regulation of the glucocorticoids balance by converting the inactive hormone cortisone into cortisol. Numerous functional aspects of 11β-HSD-1 have been understood thanks to the availability at the Worldwide Protein Data Bank of a number of X-ray structures of the enzyme either alone or in complex with inhibitors, and to several experimental data. However at present, a complete description of the dynamic behaviour of 11β-HSD-1 upon substrate binding is missing. To this aim we firstly docked cortisone into the catalytic site of 11β-HSD-1 (both wild type and Y177A mutant), and then we used steered molecular dynamics and metadynamics to simulate its undocking. This methodology helped shedding light at molecular level on the complex relationship between the enzyme and its natural substrate. In particular, the work highlights a) the reason behind the functional dimerisation of 11β-HSD-1, b) the key role of Y177 in the cortisone binding event, c) the fine tuning of the active site degree of solvation, and d) the role of the S228-P237 loop in ligand recognition. PMID:21966510

Automatic transfer function design for medical visualization using visibility distributions and projective color mapping.

PubMed

Cai, Lile; Tay, Wei-Liang; Nguyen, Binh P; Chui, Chee-Kong; Ong, Sim-Heng

2013-01-01

Transfer functions play a key role in volume rendering of medical data, but transfer function manipulation is unintuitive and can be time-consuming; achieving an optimal visualization of patient anatomy or pathology is difficult. To overcome this problem, we present a system for automatic transfer function design based on visibility distribution and projective color mapping. Instead of assigning opacity directly based on voxel intensity and gradient magnitude, the opacity transfer function is automatically derived by matching the observed visibility distribution to a target visibility distribution. An automatic color assignment scheme based on projective mapping is proposed to assign colors that allow for the visual discrimination of different structures, while also reflecting the degree of similarity between them. When our method was tested on several medical volumetric datasets, the key structures within the volume were clearly visualized with minimal user intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

RNA Interference for Functional Genomics and Improvement of Cotton (Gossypium sp.)

PubMed Central

Abdurakhmonov, Ibrokhim Y.; Ayubov, Mirzakamol S.; Ubaydullaeva, Khurshida A.; Buriev, Zabardast T.; Shermatov, Shukhrat E.; Ruziboev, Haydarali S.; Shapulatov, Umid M.; Saha, Sukumar; Ulloa, Mauricio; Yu, John Z.; Percy, Richard G.; Devor, Eric J.; Sharma, Govind C.; Sripathi, Venkateswara R.; Kumpatla, Siva P.; van der Krol, Alexander; Kater, Hake D.; Khamidov, Khakimdjan; Salikhov, Shavkat I.; Jenkins, Johnie N.; Abdukarimov, Abdusattor; Pepper, Alan E.

2016-01-01

RNA interference (RNAi), is a powerful new technology in the discovery of genetic sequence functions, and has become a valuable tool for functional genomics of cotton (Gossypium sp.). The rapid adoption of RNAi has replaced previous antisense technology. RNAi has aided in the discovery of function and biological roles of many key cotton genes involved in fiber development, fertility and somatic embryogenesis, resistance to important biotic and abiotic stresses, and oil and seed quality improvements as well as the key agronomic traits including yield and maturity. Here, we have comparatively reviewed seminal research efforts in previously used antisense approaches and currently applied breakthrough RNAi studies in cotton, analyzing developed RNAi methodologies, achievements, limitations, and future needs in functional characterizations of cotton genes. We also highlighted needed efforts in the development of RNAi-based cotton cultivars, and their safety and risk assessment, small and large-scale field trials, and commercialization. PMID:26941765

RNA Interference for Functional Genomics and Improvement of Cotton (Gossypium sp.).

PubMed

Abdurakhmonov, Ibrokhim Y; Ayubov, Mirzakamol S; Ubaydullaeva, Khurshida A; Buriev, Zabardast T; Shermatov, Shukhrat E; Ruziboev, Haydarali S; Shapulatov, Umid M; Saha, Sukumar; Ulloa, Mauricio; Yu, John Z; Percy, Richard G; Devor, Eric J; Sharma, Govind C; Sripathi, Venkateswara R; Kumpatla, Siva P; van der Krol, Alexander; Kater, Hake D; Khamidov, Khakimdjan; Salikhov, Shavkat I; Jenkins, Johnie N; Abdukarimov, Abdusattor; Pepper, Alan E

2016-01-01

RNA interference (RNAi), is a powerful new technology in the discovery of genetic sequence functions, and has become a valuable tool for functional genomics of cotton (Gossypium sp.). The rapid adoption of RNAi has replaced previous antisense technology. RNAi has aided in the discovery of function and biological roles of many key cotton genes involved in fiber development, fertility and somatic embryogenesis, resistance to important biotic and abiotic stresses, and oil and seed quality improvements as well as the key agronomic traits including yield and maturity. Here, we have comparatively reviewed seminal research efforts in previously used antisense approaches and currently applied breakthrough RNAi studies in cotton, analyzing developed RNAi methodologies, achievements, limitations, and future needs in functional characterizations of cotton genes. We also highlighted needed efforts in the development of RNAi-based cotton cultivars, and their safety and risk assessment, small and large-scale field trials, and commercialization.

[Adjuvants in modern anesthesia - magnesium].

PubMed

Picardi, Susanne; Lirk, Philipp; Blobner, Manfred; Schönherr, Marianne E; Hollmann, Markus W

2015-06-01

Magnesium plays a key role in many cellular functions and there is growing interest in its role in perioperative medicine. While experimental studies provided promising results for several disease states, clinical trials mainly gave conflicting results. This review article summarizes current knowledge on the homeostasis of magnesium as well as on its proposed indications and recommendations in the clinical setting. © Georg Thieme Verlag Stuttgart · New York.

14-3-3ζ: A numbers game in adipocyte function?

PubMed Central

Lim, Gareth E.; Johnson, James D.

2016-01-01

ABSTRACT Molecular scaffolds are often viewed as passive signaling molecules that facilitate protein-protein interactions. However, new evidence gained from the use of loss-of-function or gain-of-function models is dispelling this notion. Our own recent discovery of 14-3-3ζ as an essential regulator of adipogenesis highlights the complex roles of this member of the 14-3-3 protein family. Depletion of the 14-3-3ζ isoform affected parallel pathways that drive adipocyte development, including pathways controlling the stability of key adipogenic transcription factors and cell cycle progression. Going beyond adipocyte differentiation, this study opens new avenues of research in the context of metabolism, as 14-3-3ζ binds to a variety of well-established metabolic proteins that harbor its canonical phosphorylation binding motifs. This suggests that 14-3-3ζ may contribute to key metabolic signaling pathways, such as those that facilitate glucose uptake and fatty acid metabolism. Herein, we discuss these novel areas of research, which will undoubtedly shed light onto novel roles of 14-3-3ζ, and perhaps its related family members, on glucose homeostasis. PMID:27386155

Knockdown of Rice microRNA166 by Short Tandem Target Mimic (STTM).

PubMed

Teotia, Sachin; Zhang, Dabing; Tang, Guiliang

2017-01-01

Small RNAs, including microRNAs (miRNAs), are abundant in plants and play key roles in controlling plant development and physiology. miRNAs regulate the expression of the target genes involved in key plant processes. Due to functional redundancy among miRNA family members in plants, an ideal approach to silence the expression of all members simultaneously, for their functional characterization, is desirable. Target mimic (TM) was the first approach to achieve this goal. Short tandem target mimic (STTM) is a potent approach complementing TM for silencing miRNAs in plants. STTMs have been successfully used in dicots to block miRNA functions. Here, we describe in detail the protocol for designing STTM construct to block miRNA functions in rice. Such approach can be applied to silence miRNAs in other monocots as well.

Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

PubMed Central

Pappas, Samuel S.; Leventhal, Daniel K.; Albin, Roger L.; Dauer, William T.

2014-01-01

This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role—Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. PMID:24947237

Caenorhabditis elegans chemical biology: lessons from small molecules

USDA-ARS?s Scientific Manuscript database

How can we complement Caenorhabditis elegans genomics and proteomics with a comprehensive structural and functional annotation of its metabolome? Several lines of evidence indicate that small molecules of largely undetermined structure play important roles in C. elegans biology, including key pathw...

Behind the scenes of JAC: the publisher's role.

PubMed

Orchard, Laura; Jackson, Christopher; Bishop, Phil

2016-12-01

In this brief article, we focus on Oxford University Press's role as the publisher of the JAC and how it supports authors and readers. The article defines the role of the publisher, as opposed to the Editorial team, Editorial Office or Society owner. It reviews three key functions at the publisher, namely, editorial, production and marketing. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Social Networks and Community-Based Natural Resource Management

NASA Astrophysics Data System (ADS)

Lauber, T. Bruce; Decker, Daniel J.; Knuth, Barbara A.

2008-10-01

We conducted case studies of three successful examples of collaborative, community-based natural resource conservation and development. Our purpose was to: (1) identify the functions served by interactions within the social networks of involved stakeholders; (2) describe key structural properties of these social networks; and (3) determine how these structural properties varied when the networks were serving different functions. The case studies relied on semi-structured, in-depth interviews of 8 to 11 key stakeholders at each site who had played a significant role in the collaborative projects. Interview questions focused on the roles played by key stakeholders and the functions of interactions between them. Interactions allowed the exchange of ideas, provided access to funding, and enabled some stakeholders to influence others. The exchange of ideas involved the largest number of stakeholders, the highest percentage of local stakeholders, and the highest density of interactions. Our findings demonstrated the value of tailoring strategies for involving stakeholders to meet different needs during a collaborative, community-based natural resource management project. Widespread involvement of local stakeholders may be most appropriate when ideas for a project are being developed. During efforts to exert influence to secure project approvals or funding, however, involving specific individuals with political connections or influence on possible sources of funds may be critical. Our findings are consistent with past work that has postulated that social networks may require specific characteristics to meet different needs in community-based environmental management.

Group I p21-activated kinases: emerging roles in immune function and viral pathogenesis.

PubMed

Pacheco, Almudena; Chernoff, Jonathan

2010-01-01

Group I p21-activated kinases are a highly conserved three-member family of serine/threonine kinases that act as key effectors for the small GTPases Cdc42 and Rac. In man, these enzymes have been implicated in a wide range of biological processes and are beginning to draw the attention of the pharmaceutical industry as potential therapeutic targets in cancer and in inflammatory processes. In this review, we summarize basic properties of group I Paks and discuss recently uncovered roles for these kinases in immune function and in viral infection.

Role of the nucleolus in neurodegenerative diseases with particular reference to the retina: a review.

PubMed

Sia, Paul I; Wood, John Pm; Chidlow, Glyn; Sharma, Shiwani; Craig, Jamie; Casson, Robert J

2016-04-01

The nucleolus has emerged as a key regulator of cellular growth and the response to stress, in addition to its traditionally understood function in ribosome biogenesis. The association between nucleolar function and neurodegenerative disease is increasingly being explored. There is also recent evidence indicating that the nucleolus may well be crucial in the development of the eye. In this present review, the role of the nucleolus in retinal development as well as in neurodegeneration with an emphasis on the retina is discussed. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

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.

Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the Regulation of Energy and Glucose Homeostasis.

PubMed

Guillaume, Maeva; Montagner, Alexandra; Fontaine, Coralie; Lenfant, Françoise; Arnal, Jean-François; Gourdy, Pierre

2017-01-01

Estrogen receptor alpha (ERα) has been demonstrated to play a key role in reproduction but also to exert numerous functions in nonreproductive tissues. Accordingly, ERα is now recognized as a key regulator of energy homeostasis and glucose metabolism and mediates the protective effects of estrogens against obesity and type 2 diabetes. This chapter attempts to summarize our current understanding of the mechanisms of ERα activation and their involvement in the modulation of energy balance and glucose metabolism. We first focus on the experimental studies that constitute the basis of the understanding of ERα as a nuclear receptor and more specifically on the key roles played by its two activation functions (AFs). We depict the consequences of the selective inactivation of these AFs in mouse models, which further underline the prominent role of nuclear ERα in the prevention of obesity and diabetes, as on the reproductive tract and the vascular system. Besides these nuclear actions, a fraction of ERα is associated with the plasma membrane and activates nonnuclear signaling from this site. Such rapid effects, called membrane-initiated steroid signals (MISS), have been characterized in a variety of cell lines and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS as well as the generation of mice expressing an ERα protein impeded for membrane localization has just begun to unravel the physiological role of MISS in vivo and their contribution to ERα-mediated metabolic protection. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators.

Free-energy simulations reveal molecular mechanism for functional switch of a DNA helicase

PubMed Central

Ma, Wen; Whitley, Kevin D; Schulten, Klaus

2018-01-01

Helicases play key roles in genome maintenance, yet it remains elusive how these enzymes change conformations and how transitions between different conformational states regulate nucleic acid reshaping. Here, we developed a computational technique combining structural bioinformatics approaches and atomic-level free-energy simulations to characterize how the Escherichia coli DNA repair enzyme UvrD changes its conformation at the fork junction to switch its function from unwinding to rezipping DNA. The lowest free-energy path shows that UvrD opens the interface between two domains, allowing the bound ssDNA to escape. The simulation results predict a key metastable 'tilted' state during ssDNA strand switching. By simulating FRET distributions with fluorophores attached to UvrD, we show that the new state is supported quantitatively by single-molecule measurements. The present study deciphers key elements for the 'hyper-helicase' behavior of a mutant and provides an effective framework to characterize directly structure-function relationships in molecular machines. PMID:29664402

Free-energy simulations reveal molecular mechanism for functional switch of a DNA helicase.

PubMed

Ma, Wen; Whitley, Kevin D; Chemla, Yann R; Luthey-Schulten, Zaida; Schulten, Klaus

2018-04-17

Helicases play key roles in genome maintenance, yet it remains elusive how these enzymes change conformations and how transitions between different conformational states regulate nucleic acid reshaping. Here, we developed a computational technique combining structural bioinformatics approaches and atomic-level free-energy simulations to characterize how the Escherichia coli DNA repair enzyme UvrD changes its conformation at the fork junction to switch its function from unwinding to rezipping DNA. The lowest free-energy path shows that UvrD opens the interface between two domains, allowing the bound ssDNA to escape. The simulation results predict a key metastable 'tilted' state during ssDNA strand switching. By simulating FRET distributions with fluorophores attached to UvrD, we show that the new state is supported quantitatively by single-molecule measurements. The present study deciphers key elements for the 'hyper-helicase' behavior of a mutant and provides an effective framework to characterize directly structure-function relationships in molecular machines. © 2018, Ma et al.

Homogalacturonan-modifying enzymes: structure, expression, and roles in plants

PubMed Central

Sénéchal, Fabien; Wattier, Christopher; Rustérucci, Christine; Pelloux, Jérôme

2014-01-01

Understanding the changes affecting the plant cell wall is a key element in addressing its functional role in plant growth and in the response to stress. Pectins, which are the main constituents of the primary cell wall in dicot species, play a central role in the control of cellular adhesion and thereby of the rheological properties of the wall. This is likely to be a major determinant of plant growth. How the discrete changes in pectin structure are mediated is thus a key issue in our understanding of plant development and plant responses to changes in the environment. In particular, understanding the remodelling of homogalacturonan (HG), the most abundant pectic polymer, by specific enzymes is a current challenge in addressing its fundamental role. HG, a polymer that can be methylesterified or acetylated, can be modified by HGMEs (HG-modifying enzymes) which all belong to large multigenic families in all species sequenced to date. In particular, both the degrees of substitution (methylesterification and/or acetylation) and polymerization can be controlled by specific enzymes such as pectin methylesterases (PMEs), pectin acetylesterases (PAEs), polygalacturonases (PGs), or pectate lyases-like (PLLs). Major advances in the biochemical and functional characterization of these enzymes have been made over the last 10 years. This review aims to provide a comprehensive, up to date summary of the recent data concerning the structure, regulation, and function of these fascinating enzymes in plant development and in response to biotic stresses. PMID:25056773

Comparative developmental analysis of Drosophila and Tribolium reveals conserved and diverged roles of abrupt in insect wing evolution.

PubMed

Ravisankar, Padmapriyadarshini; Lai, Yi-Ting; Sambrani, Nagraj; Tomoyasu, Yoshinori

2016-01-15

Morphological innovation is a fundamental process in evolution, yet its molecular basis is still elusive. Acquisition of elytra, highly modified beetle forewings, is an important innovation that has driven the successful radiation of beetles. Our RNAi screening for candidate genes has identified abrupt (ab) as a potential key player in elytron evolution. In this study, we performed a series of RNA interference (RNAi) experiments in both Tribolium and Drosophila to understand the contributions of ab to the evolution of beetle elytra. We found that (i) ab is essential for proper wing vein patterning both in Tribolium and Drosophila, (ii) ab has gained a novel function in determining the unique elytron shape in the beetle lineage, (iii) unlike Hippo and Insulin, other shape determining pathways, the shape determining function of ab is specific to the elytron and not required in the hindwing, (iv) ab has a previously undescribed role in the Notch signal-associated wing formation processes, which appears to be conserved between beetles and flies. These data suggest that ab has gained a new function during elytron evolution in beetles without compromising the conserved wing-related functions. Gaining a new function without losing evolutionarily conserved functions may be a key theme in the evolution of morphologically novel structures. Copyright © 2015 Elsevier Inc. All rights reserved.

National Trauma Institute: A National Coordinating Center for Trauma Research Funding

DTIC Science & Technology

2013-10-01

identified as the key regulator of iron homeostasis, and plays a major role in how and why anemia develops. Hepcidin reduces iron availability by: (1...cells. High levels of hepcidin induce a state of functional iron deficiency . Hepcidin is increased in states of inflammation, and likely plays an...elevated in trauma, this will confirm that inability to use iron stores is key to the anemia of trauma. Dr Napolitano suspects that hepcidin will be

Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example.

PubMed

Antoniali, Giulia; Lirussi, Lisa; Poletto, Mattia; Tell, Gianluca

2014-02-01

An emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions. After nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence. A paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies. A productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world.

Self-averaging in complex brain neuron signals

NASA Astrophysics Data System (ADS)

Bershadskii, A.; Dremencov, E.; Fukayama, D.; Yadid, G.

2002-12-01

Nonlinear statistical properties of Ventral Tegmental Area (VTA) of limbic brain are studied in vivo. VTA plays key role in generation of pleasure and in development of psychological drug addiction. It is shown that spiking time-series of the VTA dopaminergic neurons exhibit long-range correlations with self-averaging behavior. This specific VTA phenomenon has no relation to VTA rewarding function. Last result reveals complex role of VTA in limbic brain.

The Role of PGC-1α in Vascular Regulation: Implications for Atherosclerosis

PubMed Central

Kadlec, Andrew O.; Chabowski, Dawid S.; Ait-Aissa, Karima; Gutterman, David D.

2016-01-01

Mitochondrial dysfunction results in high levels of oxidative stress and mitochondrial damage, leading to disruption of endothelial homeostasis. Recent discoveries have clarified several pathways whereby mitochondrial dysregulation contributes to endothelial dysfunction and vascular disease burden. One such pathway centers around PGC-1α, a transcriptional coactivator linked to mitochondrial biogenesis and antioxidant defense, among other functions. Although primarily investigated for its therapeutic potential in obesity and skeletal muscle differentiation, the ability of PGC-1α to alter a multitude of cellular functions has sparked interest in its role in the vasculature. Within this context, recent studies demonstrate that PGC-1α plays a key role in endothelial cell and smooth muscle cell regulation through effects on oxidative stress, apoptosis, inflammation, and cell proliferation. The ability of PGC-1α to impact these parameters is relevant to vascular disease progression, particularly in relation to atherosclerosis. Upregulation of PGC-1α can prevent the development of, and even encourage regression of, atherosclerotic lesions. Therefore, PGC-1α is poised to serve as a promising target in vascular disease. This review details recent findings related to PGC-1α in vascular regulation, regulation of PGC-1α itself, the role of PGC-1α in atherosclerosis, and therapies that target this key protein. PMID:27312223

Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing.

PubMed

Piperigkou, Zoi; Götte, Martin; Theocharis, Achilleas D; Karamanos, Nikos K

2017-10-24

Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration. Their expression is associated with the distinct phases of wound healing and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

New insights into the pathways initiating and driving pancreatitis

PubMed Central

Gukovskaya, Anna S.; Pandol, Stephen J.; Gukovsky, Ilya

2016-01-01

Purpose of review In this article, we discuss recent studies that advance our understanding of molecular and cellular factors initiating and driving pancreatitis, with the emphasis on the role of acinar cell organelle disorders. Recent findings The central physiologic function of the pancreatic acinar cell – to synthesize, store, and secrete digestive enzymes – critically relies on coordinated actions of the endoplasmic reticulum (ER), the endolysosomal system, mitochondria, and autophagy. Recent studies begin to unravel the roles of these organelles’ disordering in the mechanism of pancreatitis. Mice deficient in key autophagy mediators Atg5 or Atg7, or lysosome-associated membrane protein-2, exhibit dysregulation of multiple signaling and metabolic pathways in pancreatic acinar cells and develop spontaneous pancreatitis. Mitochondrial dysfunction caused by sustained opening of the permeability transition pore is shown to mediate pancreatitis in several clinically relevant experimental models, and its inhibition by pharmacologic or genetic means greatly reduces local and systemic pathologic responses. Experimental pancreatitis is also alleviated with inhibitors of ORAI1, a key component of the plasma membrane channel mediating pathologic rise in acinar cell cytosolic Ca2+. Pancreatitis-promoting mutations are increasingly associated with the ER stress. These findings suggest novel pathways and drug targets for pancreatitis treatment. In addition, the recent studies identify new mediators (e.g., neutrophil extracellular traps) of the inflammatory and other responses of pancreatitis. Summary The recent findings illuminate a critical role of organelles regulating the autophagic, endolysosomal, mitochondrial, and ER pathways in maintaining pancreatic acinar cell homeostasis and secretory function; provide compelling evidence that organelle disordering is a key pathogenic mechanism initiating and driving pancreatitis; and identify molecular and cellular factors that could be targeted to restore organellar functions and thus alleviate or treat pancreatitis. PMID:27428704

Non-Carbohydrate Glycomimetics and Glycoprotein Surrogates as DC-SIGN Antagonists and Agonists

PubMed Central

Prost, Lynne R.; Grim, Joseph C.; Tonelli, Marco; Kiessling, Laura L.

2012-01-01

An understanding of the biological roles of lectins will be advanced by ligands that can inhibit or even recruit lectin function. To this end, glycomimetics, non-carbohydrate ligands that function analogously to endogenous carbohydrates, are being sought. The advantage of having such ligands is illustrated by the many roles of the protein DC-SIGN. DC-SIGN is a C-type lectin displayed on dendritic cells, where it binds to mannosides and fucosides to mediate interactions with other host cells or bacterial or viral pathogens. DC-SIGN engagement can modulate host immune responses (e.g., suppress autoimmunity) or benefit pathogens (e.g., promote HIV dissemination). DC-SIGN can bind to glycoconjugates, internalize glycosylated cargo for antigen processing, and transduce signals. DC-SIGN ligands can serve as inhibitors as well as probes of the lectin’s function, so they are especially valuable for elucidating and controlling DC-SIGN’s roles in immunity. We previously reported a small molecule that embodies key features of the carbohydrates that bind DC-SIGN. Here, we demonstrate that this non-carbohydrate ligand acts as a true glycomimetic. Using NMR HSQC experiments, we found that the compound mimics saccharide ligands: It occupies the same carbohydrate-binding site and interacts with the same side chain residues on DC-SIGN. The glycomimetic also is functional. It had been shown previously to antagonize DC-SIGN function but here we use it to generate DC-SIGN agonists. Specifically, appending this glycomimetic to a protein scaffold affords a conjugate that elicits key cellular signaling responses. Thus, the glycomimetic can give rise to functional glycoprotein surrogates that elicit lectin-mediated signaling. PMID:22747463

Membrane-Mediated Oligomerization of G Protein Coupled Receptors and Its Implications for GPCR Function

PubMed Central

Gahbauer, Stefan; Böckmann, Rainer A.

2016-01-01

The dimerization or even oligomerization of G protein coupled receptors (GPCRs) causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signaling complexes. Recent findings further suggest that the surrounding membrane, i.e., its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function. PMID:27826255

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

PubMed Central

Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

Pericytes of the neurovascular unit: Key functions and signaling pathways

PubMed Central

Sweeney, Melanie D.; Ayyadurai, Shiva; Zlokovic, Berislav V.

2017-01-01

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies. PMID:27227366

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

PubMed

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

2013-01-01

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

Student Development and Campus Ecology: A Rapprochement.

ERIC Educational Resources Information Center

Hurst, James C.

1987-01-01

Investigates campus ecology from several innovative perspectives, considering both theory and practice. Conceptualizes current functions of the student affairs administrator playing a key role in higher education and articulates how campus ecology and student development theories complement each other when applied through a systems approach to…

Gender and Adolescent Development

ERIC Educational Resources Information Center

Perry, David G.; Pauletti, Rachel E.

2011-01-01

This article summarizes and critiques recent trends in research and theory on the role of gender in adolescent development. First, gender differences in key areas of adolescent functioning are reviewed. Second, research on 3 constructs that are especially relevant to the investigation of within-gender individual differences in gender…

Varroa destructor: research avenues towards sustainable control

USDA-ARS?s Scientific Manuscript database

Pollination by honeybees plays a key role in the functioning of ecosystems and optimization of agricultural yields. Severe honeybee colony losses worldwide have raised concerns about the sustainability of these pollination services. In most cases, bee morbidity appears to be the product of many inte...

A systematic review of the role of vitamin insufficiencies and supplementation in COPD

PubMed Central

2010-01-01

Background Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. Methods A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. Conclusions The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. PMID:21134250

A Role for PML in Innate Immunity

PubMed Central

Lunardi, Andrea; Gaboli, Mirella; Giorgio, Marco; Rivi, Roberta; Bygrave, Anne; Antoniou, Michael; Drabek, Dubravka; Dzierzak, Elaine; Fagioli, Marta; Salmena, Leonardo; Botto, Marina; Cordon-Cardo, Carlos; Luzzatto, Lucio; Pelicci, Pier Giuseppe; Grosveld, Frank; Pandolfi, Pier Paolo

2011-01-01

The promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune response to viral infection. Herein, we report that Pml −/− mice spontaneously develop an atypical invasive and lethal granulomatous lesion known as botryomycosis (BTM). In Pml −/− mice, BTM is the result of impaired function of macrophages, whereby they fail to become activated and are thus unable to clear pathogenic microorganisms. Accordingly, Pml −/− mice are resistant to lipopolysaccharide (LPS)–induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-κB prosurvival pathway. These results not only shed light on a new fundamental function of PML in innate immunity, but they also point to a proto-oncogenic role for PML in certain cellular and pathological contexts. PMID:21779477

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

PubMed

Escobedo, Noelia; Oliver, Guillermo

2017-10-03

Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

Exosome cofactor hMTR4 competes with export adaptor ALYREF to ensure balanced nuclear RNA pools for degradation and export.

PubMed

Fan, Jing; Kuai, Bin; Wu, Guifen; Wu, Xudong; Chi, Binkai; Wang, Lantian; Wang, Ke; Shi, Zhubing; Zhang, Heng; Chen, She; He, Zhisong; Wang, Siyuan; Zhou, Zhaocai; Li, Guohui; Cheng, Hong

2017-10-02

The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome-mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap-binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm. Together, our results indicate that the competition between hMTR4 and ALYREF determines exosome recruitment and functions in creating balanced nuclear RNA pools for degradation and export. © 2017 The Authors.

Bruton's Tyrosine Kinase: An Emerging Key Player in Innate Immunity.

PubMed

Weber, Alexander N R; Bittner, Zsofia; Liu, Xiao; Dang, Truong-Minh; Radsak, Markus Philipp; Brunner, Cornelia

2017-01-01

Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thorough basic understanding of the human innate immune system but also as a target to therapeutically modulate innate immunity. We here review the latest developments on the role of BTK in mononuclear innate immune cells in mouse versus man, with specific emphasis on the sensing of infectious agents and the induction of inflammation. Therapeutic implications for modulating innate immunity and critical open questions are also discussed.

Modern approaches to the design of memory and cognitive function stimulants based on AMPA receptor ligands

NASA Astrophysics Data System (ADS)

Grigoriev, V. V.; Proshin, A. N.; Kinzirsky, A. S.; Bachurin, Sergey O.

2009-05-01

Data on the structure and properties of compounds acting on AMPA receptors, the key subtype of ionotropic glutamate receptors of the mammalian central nervous system, are analyzed. Data on the role of these receptors in provision of memory and cognitive function formation and impairment processes are presented. The attention is focused on the modern views on the mechanisms of AMPA receptor desensitization and deactivation and action of substances affecting these processes. The structures of key positive modulators of AMPA receptors are given. The problems of application of these substances as therapeutic means for preventing and treating neurodegenerative and psychoneurological diseases are discussed. Bibliography — 121 references.

Exploring Symmetry to Assist Alzheimer's Disease Diagnosis

NASA Astrophysics Data System (ADS)

Illán, I. A.; Górriz, J. M.; Ramírez, J.; Salas-Gonzalez, D.; López, M.; Padilla, P.; Chaves, R.; Segovia, F.; Puntonet, C. G.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder first affecting memory functions and then gradually affecting all cognitive functions with behavioral impairments and eventually causing death. Functional brain imaging as Single-Photon Emission Computed Tomography (SPECT) is commonly used to guide the clinician's diagnosis. The essential left-right symmetry of human brains is shown to play a key role in coding and recognition. In the present work we explore the implications of this symmetry in AD diagnosis, showing that recognition may be enhanced when considering this latent symmetry.

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis

PubMed Central

Ma, Yi; Liang, A-Juan; Fan, Yu-Ping; Huang, Yi-Ran; Zhao, Xiao-Ming; Sun, Yun; Chen, Xiang-Feng

2016-01-01

Previous studies have reported aberrant expression of the miR-183-96-182 cluster in a variety of tumors, which indicates its' diagnostic or prognostic value. However, a key characteristic of the miR-183-96-182 cluster is its varied expression levels, and pleomorphic functional roles in different tumors or under different conditions. In most tumor types, the cluster is highly expressed and promotes tumorigenesis, cancer progression and metastasis; yet tumor suppressive effects have also been reported in some tumors. In the present study, we discuss the upstream regulators and the downstream target genes of miR-183-96-182 cluster, and highlight the dysregulation and functional roles of this cluster in various tumor cells. Newer insights summarized in this review will help readers understand the different facets of the miR-183-96-182 cluster in cancer development and progression. PMID:27081087

Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

PubMed

Lenz, Kathryn M; Nelson, Lars H

2018-01-01

Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

PubMed Central

Ozier, Annaïg; Allard, Benoit; Bara, Imane; Girodet, Pierre-Olivier; Trian, Thomas; Marthan, Roger; Berger, Patrick

2011-01-01

Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/load coupling. Beyond its contractile function, ASM is also involved in bronchial inflammation and remodelling. Whereas ASM is a target of the inflammatory process, it can also display proinflammatory and immunomodulatory functions, through its synthetic properties and the expression of a wide range of cell surface molecules. ASM remodelling represents a key feature of asthmatic bronchial remodelling. ASM also plays a role in promoting complementary airway structural alterations, in particular by its synthetic function. PMID:22220184

Multiple phytohormone signalling pathways modulate susceptibility of tomato plants to Alternaria alternata f. sp. lycopersici

PubMed Central

Jia, Chengguo; Zhang, Liping; Wang, Qiaomei

2013-01-01

Three phytohormone molecules – ethylene (ET), jasmonic acid (JA) and salicylic acid (SA) – play key roles in mediating disease response to necrotrophic fungal pathogens. This study investigated the roles of the ET, JA, and SA pathways as well as their crosstalk during the interaction between tomato (Solanum lycopersicum) plants and a necrotrophic fungal pathogen Alternaria alternata f. sp. lycopersici (AAL). Both the ET and JASMONIC ACID INSENSITIVE1 (JAI1) receptor-dependent JA signalling pathways are necessary for susceptibility, while SA response promotes resistance to AAL infection. In addition, the role of JA in susceptibility to AAL is partly dependent on ET biosynthesis and perception, while the SA pathway enhances resistance to AAL and antagonizes the ET response. Based on these results, it is proposed that ET, JA, and SA each on their own can influence the susceptibility of tomato to AAL. Furthermore, the functions of JA and SA in susceptibility to the pathogen are correlated with the enhanced or decreased action of ET, respectively. This study has revealed the functional relationship among the three key hormone pathways in tomato defence against AAL. PMID:23264518

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.

The role of the postsynaptic density in the pathology of the fragile X syndrome.

PubMed

Kindler, Stefan; Kreienkamp, Hans-Jürgen

2012-01-01

The protein repertoire of excitatory synapses controls dendritic spine morphology, synaptic plasticity and higher brain functions. In brain neurons, the RNA-associated fragile X mental retardation protein (FMRP) binds in vivo to various transcripts encoding key postsynaptic components and may thereby substantially regulate the molecular composition of dendritic spines. In agreement with this notion functional loss of FMRP in patients affected by the fragile X syndrome (FXS) causes cognitive impairment. Here we address our current understanding of the functional role of individual postsynaptic proteins. We discuss how FMRP controls the abundance of select proteins at postsynaptic sites, which signaling pathways regulate the local activity of FMRP at synapses, and how altered levels of postsynaptic proteins may contribute to FXS pathology.

Comparative functional characterization of the CSR-1 22G-RNA pathway in Caenorhabditis nematodes

PubMed Central

Tu, Shikui; Wu, Monica Z.; Wang, Jie; Cutter, Asher D.; Weng, Zhiping; Claycomb, Julie M.

2015-01-01

As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes, the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes with conserved germline expression, enrichment in operons and more slowly evolving coding sequences than other genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species. PMID:25510497

A conifer ABI3-interacting protein plays important roles during key transitions of the plant life cycle.

PubMed

Zeng, Ying; Zhao, Tiehan; Kermode, Allison R

2013-01-01

ABI3 (for ABSCISIC ACID INSENSITIVE3), a transcription factor of the abscisic acid signal transduction pathway, plays a major role during seed development, dormancy inception, and dormancy maintenance. This protein appears to also function in meristematic and vegetative plant tissues and under certain stress conditions. We have isolated the ABI3 gene ortholog (CnABI3) from yellow cedar (Callitropsis nootkatensis) and found that it was functionally similar to other ABI3 genes of angiosperms. Here, we report that using a yeast (Saccharomyces cerevisiae) two-hybrid approach, we have identified another protein of yellow cedar (CnAIP2; for CnABI3 INTERACTING PROTEIN2) that physically interacts with CnABI3. Functional analyses revealed that CnAIP2 plays important roles during key transitions in the plant life cycle: (1) CnAIP2 impaired seed development and reduced seed dormancy; (2) CnAIP2 promoted root development, particularly the initiation of lateral roots, and the CnAIP2 gene promoter was exquisitely auxin sensitive; and (3) CnAIP2 promoted the transition from vegetative growth to reproductive initiation (i.e. flowering). The nature of the effects of CnAIP2 on these processes and other evidence place CnAIP2 in the category of a "global" regulator, whose actions are antagonistic to those of ABI3.

Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus Epichloë festucae have contrasting roles for ROS production and symbiotic infection synchronized with the host plant

PubMed Central

2018-01-01

Epichloë festucae is an endophytic fungus which systemically colonizes temperate grasses to establish symbiotic associations. Maintaining symptomless infection is a key requirement for endophytes, a feature that distinguishes them from pathogenic fungi. While pathogenic fungi extend their hyphae by tip growth, hyphae of E. festucae systemically colonize the intercellular space of expanding host leaves via a unique mechanism of hyphal intercalary growth. This study reports that two homologous Rho GTPases, Cdc42 and RacA, have distinctive roles in the regulation of E. festucae growth in planta. Here we highlight the vital role of Cdc42 for intercalary hyphal growth, as well as involvement of RacA in regulation of hyphal network formation, and demonstrate the consequences of mutations in these genes on plant tissue infection. Functions of Cdc42 and RacA are mediated via interactions with BemA and NoxR respectively, which are expected components of the ROS producing NOX complex. Symbiotic defects found in the racA mutant were rescued by introduction of a Cdc42 with key amino acids substitutions crucial for RacA function, highlighting the significance of the specific interactions of these GTPases with BemA and NoxR for their functional differentiation in symbiotic infection. PMID:29370294

Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus Epichloë festucae have contrasting roles for ROS production and symbiotic infection synchronized with the host plant.

PubMed

Kayano, Yuka; Tanaka, Aiko; Takemoto, Daigo

2018-01-01

Epichloë festucae is an endophytic fungus which systemically colonizes temperate grasses to establish symbiotic associations. Maintaining symptomless infection is a key requirement for endophytes, a feature that distinguishes them from pathogenic fungi. While pathogenic fungi extend their hyphae by tip growth, hyphae of E. festucae systemically colonize the intercellular space of expanding host leaves via a unique mechanism of hyphal intercalary growth. This study reports that two homologous Rho GTPases, Cdc42 and RacA, have distinctive roles in the regulation of E. festucae growth in planta. Here we highlight the vital role of Cdc42 for intercalary hyphal growth, as well as involvement of RacA in regulation of hyphal network formation, and demonstrate the consequences of mutations in these genes on plant tissue infection. Functions of Cdc42 and RacA are mediated via interactions with BemA and NoxR respectively, which are expected components of the ROS producing NOX complex. Symbiotic defects found in the racA mutant were rescued by introduction of a Cdc42 with key amino acids substitutions crucial for RacA function, highlighting the significance of the specific interactions of these GTPases with BemA and NoxR for their functional differentiation in symbiotic infection.

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

Diagnosing and improving functioning in interdisciplinary health care teams.

PubMed

Blackmore, Gail; Persaud, D David

2012-01-01

Interdisciplinary teams play a key role in the delivery of health care. Team functioning can positively or negatively impact the effective and efficient delivery of health care services as well as the personal well-being of group members. Additionally, teams must be able and willing to work together to achieve team goals within a climate that reflects commitment to team goals, accountability, respect, and trust. Not surprisingly, dysfunctional team functioning can limit the success of interdisciplinary health care teams. The first step in improving dysfunctional team function is to conduct an analysis based on criteria necessary for team success, and this article provides meaningful criteria for doing such an analysis. These are the following: a common team goal, the ability and willingness to work together to achieve team goals, decision making, communication, and team member relationships. High-functioning interdisciplinary teams must exhibit features of good team function in all key domains. If a team functions well in some domains and needs to improve in others, targeted strategies are described that can be used to improve team functioning.

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.

Does oral care contribute to brain activation?: One case of functional near-infrared spectroscopy study in patients with a persistent disturbance of consciousness

PubMed Central

Fujii, Wataru; Kanamori, Daisuke; Nagata, Chisato; Sakaguchi, Kiyomi; Watanabe, Risa

2014-01-01

Key Clinical Message We used functional near-infrared spectroscopy (fNIRS) to measure cerebral blood flow during oral care in a patient with persistent disturbance of consciousness. We experienced that cerebral blood flow to frontal area increased during oral care, suggesting that oral care may have a potential role in rehabilitation for the brain. PMID:25356272

Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling

PubMed Central

Samardzija, Chantel; Greening, David W.; Escalona, Ruth; Chen, Maoshan; Bilandzic, Maree; Luwor, Rodney; Kannourakis, George; Findlay, Jock K.; Ahmed, Nuzhat

2017-01-01

Oct4A is a master regulator of self-renewal and pluripotency in embryonic stem cells. It is a well-established marker for cancer stem cell (CSC) in malignancies. Recently, using a loss of function studies, we have demonstrated key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in vitro and in vivo models of ovarian cancer. In an effort to understand the regulatory role of Oct4A in tumor biology, we employed the use of an ovarian cancer shRNA Oct4A knockdown cell line (HEY Oct4A KD) and a global mass spectrometry (MS)-based proteomic analysis to investigate novel biological targets of Oct4A in HEY samples (cell lysates, secretomes and mouse tumor xenografts). Based on significant differential expression, pathway and protein network analyses, and comprehensive literature search we identified key proteins involved with biologically relevant functions of Oct4A in tumor biology. Across all preparations of HEY Oct4A KD samples significant alterations in protein networks associated with cytoskeleton, extracellular matrix (ECM), proliferation, adhesion, metabolism, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and drug resistance was observed. This comprehensive proteomics study for the first time presents the Oct4A associated proteome and expands our understanding on the biological role of this stem cell regulator in carcinomas. PMID:28406185

Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

PubMed Central

Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

2015-01-01

The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

Epigenetic regulation of hematopoietic stem cell aging

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

Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu; Department of Pediatrics, Harvard Medical School, Boston, MA 02115; Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital, MA 02116

2014-12-10

Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and playmore » a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.« less

Restoration of mitochondria function as a target for cancer therapy

PubMed Central

Bhat, Tariq A.; Kumar, Sandeep; Chaudhary, Ajay K.; Yadav, Neelu; Chandra, Dhyan

2015-01-01

Defective oxidative phosphorylation has a crucial role in the attenuation of mitochondrial function, which confers therapy resistance in cancer. Various factors, including endogenous heat shock proteins (HSPs) and exogenous agents such as dichloroacetate, restore respiratory and other physiological functions of mitochondria in cancer cells. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents. Here, we summarize the key reasons contributing to mitochondria dysfunction in cancer cells and whether and/or how restoration of mitochondrial function could be exploited for cancer therapeutics. PMID:25766095

Use of Landsat-based monitoring of forest change to sample and assess the role of disturbance and regrowth in the carbon cycle at continental scales

Treesearch

Warren B. Cohen; Sean P. Healey; Samuel Goward; Gretchen G. Moisen; Jeffrey G. Masek; Robert E. Kennedy; Scott L. Powell; Chengquan Huang; Nancy Thomas; Karen Schleeweis; Michael A. Wulder

2007-01-01

The exchange of carbon between forests and the atmosphere is a function of forest type, climate, and disturbance history, with previous studies illustrating that forests play a key role in the terrestrial carbon cycle. The North American Carbon Program (NACP) has supported the acquisition of biennial Landsat image time-series for sample locations throughout much of...

Brain abnormalities in antisocial individuals: implications for the law.

PubMed

Yang, Yaling; Glenn, Andrea L; Raine, Adrian

2008-01-01

With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

The role of imagination in experiencing natural environments

Treesearch

Herbert Schroeder

2010-01-01

The experience of natural environments and places is multifaceted, involving psychological functions such as perception, cognition, memory, emotion, and imagination. Environmental perception and cognition were key topics in early research in environmental psychology. More recently, attention has also been directed to affective dimensions of environmental experience,...

Green tea EGCG, T-cell function, and T-cell-mediated autoimmune encephalomyelitis

USDA-ARS?s Scientific Manuscript database

Autoimmune diseases are common, disabling immune disorders affecting millions of people. Recent studies indicate that dysregulated balance of different CD4+ T-cell subpopulations plays a key role in immune pathogenesis of several major autoimmune diseases. Green tea and its active ingredient, epigal...

Exposure to Polychlorinated Biphenyls (PCBs): Implications for School Psychologists

ERIC Educational Resources Information Center

Cook-Cottone, Catherine

2004-01-01

Pediatric exposure to polychlorinated biphynels (PCBs) is a national health concern with significant implications for school psychologists. According to the healthcare collaboration model, the school psychologist plays a key role in the provision of services to children affected by environmental teratogens. To effectively function as healthcare…

Role of acetylcholinesterase in lung cancer

PubMed Central

Xi, Hui-Jun; Wu, Ren-Pei; Liu, Jing-Jing; Zhang, Ling-Juan; Li, Zhao-Shen

2015-01-01

Acetylcholinesterase (AChE) plays a key role in catalytic hydrolysis of cholinergic neurotransmitters. Intensive research has proven the involvement of this protein in novel functions, such as cell adhesion, differentiation, and proliferation. In addition, several recent studies have indicated that acetylcholinesterase is potentially a marker and regulator of apoptosis. Importantly, AChE is also a promising tumor suppressor. In this review, we briefly summarize the involvement of AChE in apoptosis and cancer, focusing on the role of AChE in lung cancer, as well as the therapeutic consideration of AChE for cancer therapy. PMID:26273392

Laboratory Information Systems.

PubMed

Henricks, Walter H

2015-06-01

Laboratory information systems (LISs) supply mission-critical capabilities for the vast array of information-processing needs of modern laboratories. LIS architectures include mainframe, client-server, and thin client configurations. The LIS database software manages a laboratory's data. LIS dictionaries are database tables that a laboratory uses to tailor an LIS to the unique needs of that laboratory. Anatomic pathology LIS (APLIS) functions play key roles throughout the pathology workflow, and laboratories rely on LIS management reports to monitor operations. This article describes the structure and functions of APLISs, with emphasis on their roles in laboratory operations and their relevance to pathologists. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of doublesex in the evolution of exaggerated horns in the Japanese rhinoceros beetle

PubMed Central

Ito, Yuta; Harigai, Ayane; Nakata, Moe; Hosoya, Tadatsugu; Araya, Kunio; Oba, Yuichi; Ito, Akinori; Ohde, Takahiro; Yaginuma, Toshinobu; Niimi, Teruyuki

2013-01-01

Male-specific exaggerated horns are an evolutionary novelty and have diverged rapidly via intrasexual selection. Here, we investigated the function of the conserved sex-determination gene doublesex (dsx) in the Japanese rhinoceros beetle (Trypoxylus dichotomus) using RNA interference (RNAi). Our results show that the sex-specific T. dichotomus dsx isoforms have an antagonistic function for head horn formation and only the male isoform has a role for thoracic horn formation. These results indicate that the novel sex-specific regulation of dsx during horn morphogenesis might have been the key evolutionary developmental event at the transition from sexually monomorphic to sexually dimorphic horns. PMID:23609854

The role of doublesex in the evolution of exaggerated horns in the Japanese rhinoceros beetle.

PubMed

Ito, Yuta; Harigai, Ayane; Nakata, Moe; Hosoya, Tadatsugu; Araya, Kunio; Oba, Yuichi; Ito, Akinori; Ohde, Takahiro; Yaginuma, Toshinobu; Niimi, Teruyuki

2013-06-01

Male-specific exaggerated horns are an evolutionary novelty and have diverged rapidly via intrasexual selection. Here, we investigated the function of the conserved sex-determination gene doublesex (dsx) in the Japanese rhinoceros beetle (Trypoxylus dichotomus) using RNA interference (RNAi). Our results show that the sex-specific T. dichotomus dsx isoforms have an antagonistic function for head horn formation and only the male isoform has a role for thoracic horn formation. These results indicate that the novel sex-specific regulation of dsx during horn morphogenesis might have been the key evolutionary developmental event at the transition from sexually monomorphic to sexually dimorphic horns.

Building a functional artery: issues from the perspective of mechanics.

PubMed

Gleason, Rudolph L; Hu, Jin-Jia; Humphrey, Jay D

2004-09-01

Despite the many successes of arterial tissue engineering, clinically viable implants may be a decade or more away. Fortunately, there is much more that we can learn from native vessels with regard to designing for optimal structure, function, and properties. Herein, we examine recent observations in vascular biology from the perspective of nonlinear mechanics. Moreover, we use a constrained mixture model to study potential contributions of individual wall constituents. In both cases, the unique biological and mechanical roles of elastin come to the forefront, especially its role in generating and modulating residual stress within the wall, which appears to be key to multiple growth and remodeling responses.

Circular RNA: an emerging key player in RNA world.

PubMed

Meng, Xianwen; Li, Xue; Zhang, Peijing; Wang, Jingjing; Zhou, Yincong; Chen, Ming

2017-07-01

Insights into the circular RNA (circRNA) exploration have revealed that they are abundant in eukaryotic transcriptomes. Diverse genomic regions can generate different types of RNA circles, implying their diversity. Covalently closed loop structures elevate the stability of this new type of noncoding RNA. High-throughput sequencing analyses suggest that circRNAs exhibit tissue- and developmental-specific expression, indicating that they may play crucial roles in multiple cellular processes. Strikingly, several circRNAs could function as microRNA sponges and regulate gene transcription, highlighting a new class of important regulators. Here, we review the recent advances in knowledge of endogenous circRNA biogenesis, properties and functions. We further discuss the current findings about circRNAs in human diseases. In plants, the roles of circRNAs remain a mystery. Online resources and bioinformatics identification of circRNAs are essential for the analysis of circRNA biology, although different strategies yield divergent results. The understanding of circRNA functions remains limited; however, circRNAs are enriching the RNA world, acting as an emerging key player. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

PubMed

Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

2016-01-01

Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

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.

Density functional study of molecular interactions in secondary structures of proteins.

PubMed

Takano, Yu; Kusaka, Ayumi; Nakamura, Haruki

2016-01-01

Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

Structural analysis of the Quaking homodimerization interface

PubMed Central

Beuck, Christine; Qu, Song; Fagg, W. Samuel; Ares, Manuel; Williamson, James R.

2012-01-01

Quaking is a prototypical member of the STAR protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences, however, the structural and functional roles of homo- and hetero-dimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 and Sam68, but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels, and impair QkI function in a splicing assay in vivo. Together our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells. PMID:22982292

Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens

NASA Astrophysics Data System (ADS)

Siau, Jia Wei; Coffill, Cynthia R.; Zhang, Weiyun Villien; Tan, Yaw Sing; Hundt, Juliane; Lane, David; Verma, Chandra; Ghadessy, Farid

2016-09-01

The identification of genes encoding a p53 family member and an Mdm2 ortholog in the ancient placozoan Trichoplax adhaerens advocates for the evolutionary conservation of a pivotal stress-response pathway observed in all higher eukaryotes. Here, we recapitulate several key functionalities ascribed to this known interacting protein pair by analysis of the placozoan proteins (Tap53 and TaMdm2) using both in vitro and cellular assays. In addition to interacting with each other, the Tap53 and TaMdm2 proteins are also able to respectively bind human Mdm2 and p53, providing strong evidence for functional conservation. The key p53-degrading function of Mdm2 is also conserved in TaMdm2. Tap53 retained DNA binding associated with p53 transcription activation function. However, it lacked transactivation function in reporter genes assays using a heterologous cell line, suggesting a cofactor incompatibility. Overall, the data supports functional roles for TaMdm2 and Tap53, and further defines the p53 pathway as an evolutionary conserved fulcrum mediating cellular response to stress.

Emerging Roles of the Nucleolus in Regulating the DNA Damage Response: The Noncanonical DNA Repair Enzyme APE1/Ref-1 as a Paradigmatical Example

PubMed Central

Antoniali, Giulia; Lirussi, Lisa; Poletto, Mattia

2014-01-01

Abstract Significance: An emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions. Recent Advances: After nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence. Critical Issues: A paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies. Future Directions: A productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world. Antioxid. Redox Signal. 20, 621–639. PMID:23879289

Glucocorticoid programming of neuroimmune function.

PubMed

Walker, David J; Spencer, Karen A

2018-01-15

Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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.

Theory to Practice: Cultivating Academic Language Proficiency in Developmental Reading Classrooms

ERIC Educational Resources Information Center

Neal, Heather N.

2015-01-01

Academic language plays a key role in reading comprehension, disciplinary thinking, and overall academic success. However, many approaches to teaching academic language, such as a focus on academic vocabulary, overlook other language features that can pose challenges for students. Systemic Functional Linguistics (SFL), arguably one of the three…

Family Life with Children with Disabilities: The Key Role of Rehabilitation.

ERIC Educational Resources Information Center

Rogers, Michelle L.; Hogan, Dennis P.

2003-01-01

Examines the effects of children's medical impairments and functional disabilities and the use of medical care and rehabilitation on three family consequences (job changes, severe financial problems, and sleep disruptions). Finds that the rehabilitation services that children receive account for a large part of the observed association of…

Developmental acquisition of regulomes underlies innate lymphoid cell functionality

USDA-ARS?s Scientific Manuscript database

Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and ·transcription factors. To better understand ILC subsets and their relationship with Th cells, we measur...

Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine

USDA-ARS?s Scientific Manuscript database

Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. Gut microbiota, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease...

Preface to Special Topic: Emerging materials for photonics

NASA Astrophysics Data System (ADS)

Vitiello, Miriam S.; Razeghi, Manijeh

2017-03-01

Photonics plays a major role in all aspects of human life. It revolutionized science by addressing fundamental scientific questions and by enabling key functions in many interdisciplinary fields spanning from quantum technologies to information and communication science, and from biomedical research to industrial process monitoring and life entertainment.

Determination of succession of rumen bacterial species in nursing beef calves

USDA-ARS?s Scientific Manuscript database

Ruminants are typically born with a non-functional rumen essentially devoid of microorganisms. The succession of the microbial population in the rumen from birth to animal maturity is of interest due to the key role that the rumen microbial population plays in the overall health and productivity of ...

Cohesin and related coiled-coil domain-containing complexes physically and functionally connect the dots across the genome

PubMed Central

Poon, Betty P.K

2011-01-01

Interactions between genetic regions located across the genome maintain its three-dimensional organization and function. Recent studies point to key roles for a set of coiled-coil domain-containing complexes (cohibin, cohesin, condensin and monopolin) and related factors in the regulation of DNA-DNA connections across the genome. These connections are critical to replication, recombination, gene expression as well as chromosome segregation. PMID:21822055

Family functioning mediates adaptation in caregivers of individuals with Rett syndrome.

PubMed

Lamb, Amanda E; Biesecker, Barbara B; Umstead, Kendall L; Muratori, Michelle; Biesecker, Leslie G; Erby, Lori H

2016-11-01

The objective of this study was to investigate factors related to family functioning and adaptation in caregivers of individuals with Rett syndrome (RS). A cross-sectional quantitative survey explored the relationships between demographics, parental self-efficacy, coping methods, family functioning and adaptation. A forward-backward, step-wise model selection procedure was used to evaluate variables associated with both family functioning and adaptation. Analyses also explored family functioning as a mediator of the relationship between other variables and adaptation. Bivariate analyses (N=400) revealed that greater parental self-efficacy, a greater proportion of problem-focused coping, and a lesser proportion of emotion-focused coping were associated with more effective family functioning. In addition, these key variables were significantly associated with greater adaptation, as was family functioning, while controlling for confounders. Finally, regression analyses suggest family functioning as a mediator of the relationships between three variables (parental self-efficacy, problem-focused coping, and emotion-focused coping) with adaptation. This study demonstrates the potentially predictive roles of expectations and coping methods and the mediator role of family functioning in adaptation among caregivers of individuals with RS, a chronic developmental disorder. A potential target for intervention is strengthening of caregiver competence in the parenting role to enhance caregiver adaptation. Published by Elsevier Ireland Ltd.

The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?

PubMed

Moulder, David E; Hatoum, Diana; Tay, Enoch; Lin, Yiguang; McGowan, Eileen M

2018-06-08

Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance. The tumor suppressor protein p53 is emerging as a key regulator of metabolic processes and metabolic reprogramming in cancer cells—balancing the pendulum between cell death and survival. This review provides an overview of the classical and emerging non-classical tumor suppressor roles of p53 in regulating mitochondrial dynamics: mitochondrial engagement in cell death processes in the prevention of cancer. On the other hand, we discuss p53 as a key metabolic switch in cellular function and survival. The focus is then on the conceivable roles of p53 in breast cancer metabolism. Understanding the metabolic functions of p53 within breast cancer metabolism will, in due course, reveal critical metabolic hotspots that cancers advantageously re-engineer for sustenance. Illustration of these events will pave the way for finding novel therapeutics that target cancer metabolism and serve to overcome the breast cancer burden.

Oxytocin and experimental therapeutics in autism spectrum disorders.

PubMed

Bartz, Jennifer A; Hollander, Eric

2008-01-01

Autism is a developmental disorder characterized by three core symptom domains: speech and communication abnormalities, social functioning impairments and repetitive behaviours and restricted interests. Oxytocin (OXT) is a nine-amino-acid peptide that is synthesized in the paraventricular and supraoptic nucleus of the hypothalamus and released into the bloodstream by axon terminals in the posterior pituitary where it plays an important role in facilitating uterine contractions during parturition and in milk let-down. In addition, OXT and the structurally similar peptide arginine vasopressin (AVP) are released within the brain where they play a key role in regulating affiliative behaviours, including sexual behaviour, mother-infant and adult-adult pair-bond formation and social memory/recognition. Finally, OXT has been implicated in repetitive behaviours and stress reactivity. Given that OXT is involved in the regulation of repetitive and affiliative behaviours, and that these are key features of autism, it is believed that OXT may play a role in autism and that OXT may be an effective treatment for these two core symptom domains. In this chapter we review evidence to date supporting a relationship between OXT and autism; we then discuss research looking at the functional role of OXT in autism, as well as a pilot study investigating the therapeutic efficacy of OXT in treating core autism symptom domains. Finally, we conclude with a discussion of directions for future research.

Identification of key regulators in glycogen utilization in E. coli based on the simulations from a hybrid functional Petri net model.

PubMed

Tian, Zhongyuan; Fauré, Adrien; Mori, Hirotada; Matsuno, Hiroshi

2013-01-01

Glycogen and glucose are two sugar sources available during the lag phase of E. coli, but the mechanism that regulates their utilization is still unclear. Attempting to unveil the relationship between glucose and glycogen, we propose an integrated hybrid functional Petri net (HFPN) model including glycolysis, PTS, glycogen metabolic pathway, and their internal regulatory systems. By comparing known biological results to this model, basic necessary regulatory mechanism for utilizing glucose and glycogen were identified as a feedback circuit in which HPr and EIIAGlc play key roles. Based on this regulatory HFPN model, we discuss the process of glycogen utilization in E. coli in the context of a systematic understanding of carbohydrate metabolism.

Key properties of expert movement systems in sport : an ecological dynamics perspective.

PubMed

Seifert, Ludovic; Button, Chris; Davids, Keith

2013-03-01

This paper identifies key properties of expertise in sport predicated on the performer-environment relationship. Weaknesses of traditional approaches to expert performance, which uniquely focus on the performer and the environment separately, are highlighted by an ecological dynamics perspective. Key properties of expert movement systems include 'multi- and meta-stability', 'adaptive variability', 'redundancy', 'degeneracy' and the 'attunement to affordances'. Empirical research on these expert system properties indicates that skill acquisition does not emerge from the internal representation of declarative and procedural knowledge, or the imitation of expert behaviours to linearly reduce a perceived 'gap' separating movements of beginners and a putative expert model. Rather, expert performance corresponds with the ongoing co-adaptation of an individual's behaviours to dynamically changing, interacting constraints, individually perceived and encountered. The functional role of adaptive movement variability is essential to expert performance in many different sports (involving individuals and teams; ball games and outdoor activities; land and aquatic environments). These key properties signify that, in sport performance, although basic movement patterns need to be acquired by developing athletes, there exists no ideal movement template towards which all learners should aspire, since relatively unique functional movement solutions emerge from the interaction of key constraints.

Partners in crime: The role of tandem modules in gene transcription.

PubMed

Sharma, Rajal; Zhou, Ming-Ming

2015-09-01

Histones and their modifications play an important role in the regulation of gene transcription. Numerous modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation, have been described. These modifications almost always co-occur and thereby increase the combinatorial complexity of post-translational modification detection. The domains that recognize these histone modifications often occur in tandem in the context of larger proteins and complexes. The presence of multiple modifications can positively or negatively regulate the binding of these tandem domains, influencing downstream cellular function. Alternatively, these tandem domains can have novel functions from their independent parts. Here we summarize structural and functional information known about major tandem domains and their histone binding properties. An understanding of these interactions is key for the development of epigenetic therapy. © 2015 The Protein Society.

Evolutionarily conserved odorant receptor function questions ecological context of octenol role in mosquitoes

PubMed Central

Dekel, Amir; Pitts, Ronald J.; Yakir, Esther; Bohbot, Jonathan D.

2016-01-01

Olfaction is a key insect adaptation to a wide range of habitats. In the last thirty years, the detection of octenol by blood-feeding insects has been primarily understood in the context of animal host-seeking. The recent discovery of a conserved octenol receptor gene in the strictly nectar-feeding elephant mosquito Toxorhynchites amboinensis (TaOr8) suggests a different biological role. Here, we show that TaOR8 is a functional ortholog of its counterparts in blood-feeding mosquitoes displaying selectivity towards the (R)-enantiomer of octenol and susceptibility to the insect repellent DEET. These findings suggest that while the function of OR8 has been maintained throughout mosquito evolution, the context in which this receptor is operating has diverged in blood and nectar-feeding mosquitoes. PMID:27849027

[The role of the public health personnel in the Prevention Department (in the Hygiene Services and Public Health Care and Hygiene of Food and Nutrition): proposal for the future of public health care].

PubMed

Brusaferro, Silvio; Marcolongo, Adriano; Schiava, Flavio; Bggio, Luca; Betta, Alberto; Buzzo, Armando; Cinquetti, Sandro; Coin, Paulo; Dal Fior, Tina; De Battisti, Fabio; De Marchi, Chiara; De Noni, Lucia; Donatoni, Luigi; Ferraresso, Anna; Gallo, Giovanni; Gallo, Lorenza; Gallo, Tolinda; Gottardello, Lorena; Menegon, Tiziana; Minuzzo, Michele; Paussi, Gianna; Pinna, Clara; Poli, Albino; Rossato, Luigi; Sbrogliò, Luca; Simeoni, Josef; Speccini, Manuela; Stoppato, Ugo; Superbi, Piero; Tardivo, Stefano; Urdich, Alessandro; Valsecchi, Massimo; Zamparo, Manuela

2008-01-01

A global and local discussion on Public Health relevance is taking place, including the future role and organization of its services. Noteworthy becomes the role played by Public Health Specialists. This work presents the results of a workshop, carried out following the Guilbert methodology, whose aim was to define Public Health Doctors functions and their related activities. The programme involved 30 professionals from Triveneto area (North Eastern Italy), working in Prevention Departments at National Health Service and Universities. The key-functions identified were: 1) Health status assessment and identification of community risk factors, 2) Health Promotion, 3) Prevention, 4) Protection, 5) Planning, 6) Communication, 7) Professional Training, 8) Alliances and resources for complex Public Health programs, 9) Crisis management in Public Health, 10) Research. For each function activities were identified, meaning concerning areas and contents that must be warranted by professionals. This experience allowed to share existing attitudes and experiences present in Triveneto area, and it can stand as a feasible instrument for different settings. Nevertheless, it appears mandatory explaining at each level in the society role and functions of Prevention Departments.

Why is intelligence correlated with semen quality?: Biochemical pathways common to sperm and neuron function and their vulnerability to pleiotropic mutations.

PubMed

Pierce, Arand; Miller, Geoffrey; Arden, Rosalind; Gottfredson, Linda S

2009-09-01

We recently found positive correlations between human general intelligence and three key indices of semen quality, and hypothesized that these correlations arise through a phenotype-wide 'general fitness factor' reflecting overall mutation load. In this addendum we consider some of the biochemical pathways that may act as targets for pleiotropic mutations that disrupt both neuron function and sperm function in parallel. We focus especially on the inter-related roles of polyunsaturated fatty acids, exocytosis and receptor signaling.

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

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.

Differing Roles of Functional Movement Variability as Experience Increases in Gymnastics

PubMed Central

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

2016-01-01

Current theories, like Ecological Dynamics, propose that inter-trial movement variability is functional when acquiring or refining movement coordination. Here, we examined how age-based experience levels of gymnasts constrained differences in emergent movement pattern variability during task performance. Specifically, we investigated different roles of movement pattern variability when gymnasts in different age groups performed longswings on a high bar, capturing the range of experience from beginner to advanced status. We also investigated the functionality of the relationships between levels of inter-trial variability and longswing amplitude during performance. One-hundred and thirteen male gymnasts in five age groups were observed performing longswings (with three different experience levels: beginners, intermediates and advanced performers). Performance was evaluated by analysis of key events in coordination of longswing focused on the arm-trunk and trunk-thigh segmental relations. Results revealed that 10 of 18 inter-trial variability measures changed significantly as a function of increasing task experience. Four of ten variability measures conformed to a U-shaped function with age implying exploratory strategies amongst beginners and functional adaptive variability amongst advanced performers. Inter-trial variability of arm-trunk coordination variables (6 of 10) conformed to a \\-shaped curve, as values were reduced to complete the longswings. Changes in coordination variability from beginner to intermediate status were largely restrictive, with only one variability measure related to exploration. Data revealed how inter-trial movement variability in gymnastics, relative to performance outcomes, needs careful interpretation, implying different roles as task experience changes. Key points Inter-trial variability while performing longswings on a high bar was assessed in a large sample (113 participants) divided into five age groups (form beginners to advanced gymnasts). Longswing assessment allowed us to evaluate inter-trial variability in representative performance context. Coordination variability presented two different configurations across experience levels depending on the variable of interest: either a U-shaped or a L- or \\-shaped graph. Increased inter-trial variability of the functional phase events offered flexibility to adapt the longswing performance in the advanced gymnasts, while decreasing variability in arm-trunk coordination modes was critical to improve longswing and to achieve the most advanced level. In addition, the relationship between variability measures and the global performance outcome (i.e. the swing amplitude) revealed different functional roles of movement variability (exploratory or restrictive) as a function of changes in experience levels. PMID:27274664

Global functional diversity of freshwater fish is concentrated in the Neotropics while functional vulnerability is widespread.

PubMed

Toussaint, A; Charpin, N; Brosse, S; Villéger, S

2016-03-16

Worldwide biodiversity assessments have mainly focused on species richness but little is known about the diversity of species roles, i.e. functional diversity, while this is a key facet to understanding the consequences of global changes on the ecosystem services to human societies. Here, we report the world pattern of functional diversity of freshwater fish using a database encompassing morphological characteristics of more than 9,000 species. The Neotropical realm hosts more than 75% of global functional diversity while other realms each host less than 25%. This discrepancy is mediated by high functional uniqueness in some diversified Neotropical fish orders. Surprisingly, functional diversity patterns were weakly related to functional vulnerability. In the Neotropics the loss of threatened species will cause a limited loss of functional diversity (<10%) whereas in the Nearctic and Palearctic realms, decline of the functional diversity will reach 43% and 33%, respectively, conferring a high functional vulnerability to these realms. Conservation of the Neotropical fish diversity is a key target to maintain world fish functional diversity, but this should not hide the pressing need to conserve the vulnerable fish faunas of the rest of the world, in which functional diversity is to a large extent supported by threatened species.

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.

VEGF signaling inside vascular endothelial cells and beyond

PubMed Central

Eichmann, Anne; Simons, Michael

2014-01-01

Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles. PMID:22366328

Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.

PubMed

Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing

2016-09-02

Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.

Acute loss of TET function results in aggressive myeloid cancer in mice

PubMed Central

An, Jungeun; González-Avalos, Edahí; Chawla, Ashu; Jeong, Mira; López-Moyado, Isaac F.; Li, Wei; Goodell, Margaret A.; Chavez, Lukas; Ko, Myunggon; Rao, Anjana

2015-01-01

TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumour suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. Here we show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice, pointing to a causative role for TET loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling shows aberrant differentiation of haematopoietic stem/progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observe progressive accumulation of phospho-H2AX and strong impairment of DNA damage repair pathways, suggesting a key role for TET proteins in maintaining genome integrity. PMID:26607761

Functions and regulation of the multitasking FANCM family of DNA motor proteins.

PubMed

Xue, Xiaoyu; Sung, Patrick; Zhao, Xiaolan

2015-09-01

Members of the conserved FANCM family of DNA motor proteins play key roles in genome maintenance processes. FANCM supports genome duplication and repair under different circumstances and also functions in the ATR-mediated DNA damage checkpoint. Some of these roles are shared among lower eukaryotic family members. Human FANCM has been linked to Fanconi anemia, a syndrome characterized by cancer predisposition, developmental disorder, and bone marrow failure. Recent studies on human FANCM and its orthologs from other organisms have provided insights into their biological functions, regulation, and collaboration with other genome maintenance factors. This review summarizes the progress made, with the goal of providing an integrated view of the functions and regulation of these enzymes in humans and model organisms and how they advance our understanding of genome maintenance processes. © 2015 Xue et al.; Published by Cold Spring Harbor Laboratory Press.

Novel functions for the transcription factor E2F4 in development and disease

PubMed Central

Sage, Julien

2016-01-01

ABSTRACT The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer. Some of these new functions are independent of the RB family and involve direct activation of target genes. Here we review the canonical functions of E2F4 and discuss recent evidence expanding the role of this transcription factor, with a focus on cell fate decisions in tissue homeostasis and regeneration. PMID:27753528

Harnessing glycomics technologies: integrating structure with function for glycan characterization

PubMed Central

Robinson, Luke N.; Artpradit, Charlermchai; Raman, Rahul; Shriver, Zachary H.; Ruchirawat, Mathuros; Sasisekharan, Ram

2013-01-01

Glycans, or complex carbohydrates, are a ubiquitous class of biological molecules which impinge on a variety of physiological processes ranging from signal transduction to tissue development and microbial pathogenesis. In comparison to DNA and proteins, glycans present unique challenges to the study of their structure and function owing to their complex and heterogeneous structures and the dominant role played by multivalency in their sequence-specific biological interactions. Arising from these challenges, there is a need to integrate information from multiple complementary methods to decode structure-function relationships. Focusing on acidic glycans, we describe here key glycomics technologies for characterizing their structural attributes, including linkage, modifications, and topology, as well as for elucidating their role in biological processes. Two cases studies, one involving sialylated branched glycans and the other sulfated glycosaminoglycans, are used to highlight how integration of orthogonal information from diverse datasets enables rapid convergence of glycan characterization for development of robust structure-function relationships. PMID:22522536

Structural-Functional Organization of the Eukaryotic Cell Nucleus and Transcription Regulation: Introduction to This Special Issue of Biochemistry (Moscow).

PubMed

Razin, S V

2018-04-01

This issue of Biochemistry (Moscow) is devoted to the cell nucleus and mechanisms of transcription regulation. Over the years, biochemical processes in the cell nucleus have been studied in isolation, outside the context of their spatial organization. Now it is clear that segregation of functional processes within a compartmentalized cell nucleus is very important for the implementation of basic genetic processes. The functional compartmentalization of the cell nucleus is closely related to the spatial organization of the genome, which in turn plays a key role in the operation of epigenetic mechanisms. In this issue of Biochemistry (Moscow), we present a selection of review articles covering the functional architecture of the eukaryotic cell nucleus, the mechanisms of genome folding, the role of stochastic processes in establishing 3D architecture of the genome, and the impact of genome spatial organization on transcription regulation.

Comparative functional characterization of the CSR-1 22G-RNA pathway in Caenorhabditis nematodes.

PubMed

Tu, Shikui; Wu, Monica Z; Wang, Jie; Cutter, Asher D; Weng, Zhiping; Claycomb, Julie M

2015-01-01

As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes, the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes with conserved germline expression, enrichment in operons and more slowly evolving coding sequences than other genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Are the Gut Bacteria Telling Us to Eat or Not to Eat? Reviewing the Role of Gut Microbiota in the Etiology, Disease Progression and Treatment of Eating Disorders

PubMed Central

Lam, Yan Y.; Maguire, Sarah; Palacios, Talia; Caterson, Ian D.

2017-01-01

Traditionally recognized as mental illnesses, eating disorders are increasingly appreciated to be biologically-driven. There is a growing body of literature that implicates a role of the gut microbiota in the etiology and progression of these conditions. Gut bacteria may act on the gut–brain axis to alter appetite control and brain function as part of the genesis of eating disorders. As the illnesses progress, extreme feeding patterns and psychological stress potentially feed back to the gut ecosystem that can further compromise physiological, cognitive, and social functioning. Given the established causality between dysbiosis and metabolic diseases, an altered gut microbial profile is likely to play a role in the co-morbidities of eating disorders with altered immune function, short-chain fatty acid production, and the gut barrier being the key mechanistic links. Understanding the role of the gut ecosystem in the pathophysiology of eating disorders will provide critical insights into improving current treatments and developing novel microbiome-based interventions that will benefit patients with eating disorders. PMID:28613252

Are the Gut Bacteria Telling Us to Eat or Not to Eat? Reviewing the Role of Gut Microbiota in the Etiology, Disease Progression and Treatment of Eating Disorders.

PubMed

Lam, Yan Y; Maguire, Sarah; Palacios, Talia; Caterson, Ian D

2017-06-14

Traditionally recognized as mental illnesses, eating disorders are increasingly appreciated to be biologically-driven. There is a growing body of literature that implicates a role of the gut microbiota in the etiology and progression of these conditions. Gut bacteria may act on the gut-brain axis to alter appetite control and brain function as part of the genesis of eating disorders. As the illnesses progress, extreme feeding patterns and psychological stress potentially feed back to the gut ecosystem that can further compromise physiological, cognitive, and social functioning. Given the established causality between dysbiosis and metabolic diseases, an altered gut microbial profile is likely to play a role in the co-morbidities of eating disorders with altered immune function, short-chain fatty acid production, and the gut barrier being the key mechanistic links. Understanding the role of the gut ecosystem in the pathophysiology of eating disorders will provide critical insights into improving current treatments and developing novel microbiome-based interventions that will benefit patients with eating disorders.

Consensus Paper: Roles of the Cerebellum in Motor Control—The Diversity of Ideas on Cerebellar Involvement in Movement

PubMed Central

Bower, James M.; Conforto, Adriana Bastos; Delgado-García, José M.; da Guarda, Suzete Nascimento Farias; Gerwig, Marcus; Habas, Christophe; Hagura, Nobuhiro; Ivry, Richard B.; Mariën, Peter; Molinari, Marco; Naito, Eiichi; Nowak, Dennis A.; Ben Taib, Nordeyn Oulad; Pelisson, Denis; Tesche, Claudia D.; Tilikete, Caroline; Timmann, Dagmar

2015-01-01

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure. PMID:22161499

Functional Rarity: The Ecology of Outliers.

PubMed

Violle, Cyrille; Thuiller, Wilfried; Mouquet, Nicolas; Munoz, François; Kraft, Nathan J B; Cadotte, Marc W; Livingstone, Stuart W; Mouillot, David

2017-05-01

Rarity has been a central topic for conservation and evolutionary biologists aiming to determine the species characteristics that cause extinction risk. More recently, beyond the rarity of species, the rarity of functions or functional traits, called functional rarity, has gained momentum in helping to understand the impact of biodiversity decline on ecosystem functioning. However, a conceptual framework for defining and quantifying functional rarity is still lacking. We introduce 12 different forms of functional rarity along gradients of species scarcity and trait distinctiveness. We then highlight the potential key role of functional rarity in the long-term and large-scale maintenance of ecosystem processes, as well as the necessary linkage between functional and evolutionary rarity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peroxisome proliferator-activated receptor α ligands and modulators from dietary compounds: Types, screening methods and functions.

PubMed

Yang, Haixia; Xiao, Lei; Wang, Nanping

2017-04-01

Peroxisome proliferator-activated receptor α (PPARα) plays a key role in lipid metabolism and glucose homeostasis and a crucial role in the prevention and treatment of metabolic diseases. Natural dietary compounds, including nutrients and phytochemicals, are PPARα ligands or modulators. High-throughput screening assays have been developed to screen for PPARα ligands and modulators in our diet. In the present review, we discuss recent advances in our knowledge of PPARα, including its structure, function, and ligand and modulator screening assays, and summarize the different types of dietary PPARα ligands and modulators. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Induced pluripotent stem cell-derived myeloid phagocytes: disease modeling and therapeutic applications.

PubMed

Goodridge, Helen S

2014-06-01

Myeloid phagocytes (neutrophils, monocytes, macrophages and dendritic cells) have key roles in immune defense, as well as in tissue repair and remodeling. Defective or dysregulated myeloid phagocyte production or function can cause immune dysfunction, blood cell malignancies and inflammatory diseases. The tumor microenvironment can also condition myeloid phagocytes to promote tumor growth. Studies of their physiological and pathophysiological roles and the mechanisms regulating their production and function are crucial for the identification of novel therapeutic targets. In this review, we examine the use of induced pluripotent stem cells to study myeloid phagocytes in human diseases and develop future therapeutic strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sex Hormones and Healthy Psychological Aging in Women

PubMed Central

Navarro-Pardo, Esperanza; Holland, Carol A.; Cano, Antonio

2018-01-01

Besides their key role in reproduction, estrogens have effects in several organs in the body, as confirmed by the identification of estrogen receptors (ER) in multiple tissues. Experimental evidence has shown that estrogens have significant impacts on the central nervous system (CNS), and a key question is to what extent the fall in estrogen levels in the blood that occurs with increasing age, particularly around and following the menopause, has an impact on the cognitive function and psychological health of women, specifically regarding mood. This review will consider direct effects of menopausal changes in estrogens on the brain, including cognitive function and mood. Secondary pathways whereby health factors affected by changes in estrogens may interact with CNS functions, such as cardiovascular factors, will be reviewed as well insofar as they also have an impact on cognitive function. Finally, because decline in estrogens may induce changes in the CNS, there is interest in clarifying whether hormone therapy may offer a beneficial balance and the impact of hormone therapy on cognition will also be considered. PMID:29375366

Mitochondria and Endothelial Function

PubMed Central

Kluge, Matthew A.; Fetterman, Jessica L.; Vita, Joseph A.

2013-01-01

In contrast to their role in other cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, ROS production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease. PMID:23580773

Why is intelligence correlated with semen quality?

PubMed Central

Miller, Geoffrey; Arden, Rosalind; Gottfredson, Linda S

2009-01-01

We recently found positive correlations between human general intelligence and three key indices of semen quality, and hypothesized that these correlations arise through a phenotype-wide ‘general fitness factor’ reflecting overall mutation load. In this addendum we consider some of the biochemical pathways that may act as targets for pleiotropic mutations that disrupt both neuron function and sperm function in parallel. We focus especially on the inter-related roles of polyunsaturated fatty acids, exocytosis and receptor signaling. PMID:19907694

Targeting protein kinase-b3 (akt3) signaling in melanoma.

PubMed

Madhunapantula, SubbaRao V; Robertson, Gavin P

2017-03-01

Deregulated Akt activity leading to apoptosis inhibition, enhanced proliferation and drug resistance has been shown to be responsible for 35-70% of advanced metastatic melanomas. Of the three isoforms, the majority of melanomas have elevated Akt3 expression and activity. Hence, potent inhibitors targeting Akt are urgently required, which is possible only if (a) the factors responsible for the failure of Akt inhibitors in clinical trials is known; and (b) the information pertaining to synergistically acting targeted therapeutics is available. Areas covered: This review provides a brief introduction of the PI3K-Akt signaling pathway and its role in melanoma development. In addition, the functional role of key Akt pathway members such as PRAS40, GSK3 kinases, WEE1 kinase in melanoma development are discussed together with strategies to modulate these targets. Efficacy and safety of Akt inhibitors is also discussed. Finally, the mechanism(s) through which Akt leads to drug resistance is discussed in this expert opinion review. Expert opinion: Even though Akt play key roles in melanoma tumor progression, cell survival and drug resistance, many gaps still exist that require further understanding of Akt functions, especially in the (a) metastatic spread; (b) circulating melanoma cells survival; and (c) melanoma stem cells growth.

A Native Threonine Coordinates Ordered Water to Tune Light-Oxygen-Voltage (LOV) Domain Photocycle Kinetics and Osmotic Stress Signaling in Trichoderma reesei ENVOY.

PubMed

Lokhandwala, Jameela; Silverman Y de la Vega, Rafael I; Hopkins, Hilary C; Britton, Collin W; Rodriguez-Iglesias, Aroa; Bogomolni, Roberto; Schmoll, Monika; Zoltowski, Brian D

2016-07-08

Light-oxygen-voltage (LOV) domain-containing proteins function as small light-activated modules capable of imparting blue light control of biological processes. Their small modular nature has made them model proteins for allosteric signal transduction and optogenetic devices. Despite intense research, key aspects of their signal transduction mechanisms and photochemistry remain poorly understood. In particular, ordered water has been identified as a possible key mediator of photocycle kinetics, despite the lack of ordered water in the LOV active site. Herein, we use recent crystal structures of a fungal LOV protein ENVOY to interrogate the role of Thr(101) in recruiting water to the flavin active site where it can function as an intrinsic base to accelerate photocycle kinetics. Kinetic and molecular dynamic simulations confirm a role in solvent recruitment to the active site and identify structural changes that correlate with solvent recruitment. In vivo analysis of T101I indicates a direct role of the Thr(101) position in mediating adaptation to osmotic stress, thereby verifying biological relevance of ordered water in LOV signaling. The combined studies identify position 101 as a mediator of both allostery and photocycle catalysis that can impact organism physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A new e-learning platform for radiology education (RadEd).

PubMed

Xiberta, Pau; Boada, Imma

2016-04-01

One of the key elements of e-learning platforms is the content provided to the students. Content creation is a time demanding task that requires teachers to prepare material taking into account that it will be accessed on-line. Moreover, the teacher is restricted by the functionalities provided by the e-learning platforms. In contexts such as radiology where images have a key role, the required functionalities are still more specific and difficult to be provided by these platforms. Our purpose is to create a framework to make teacher's tasks easier, specially when he has to deal with contents where images have a main role. In this paper, we present RadEd, a new web-based teaching framework that integrates a smart editor to create case-based exercises that support image interaction such as changing the window width and the grey scale used to render the image, taking measurements on the image, attaching labels to images and selecting parts of the images, amongst others. It also provides functionalities to prepare courses with different topics, exercises and theory material, and also functionalities to control students' work. Different experts have used RadEd and all of them have considered it a very useful and valuable tool to prepare courses where radiological images are the main component. RadEd provides teachers functionalities to prepare more realistic cases and students the ability to make a more specific diagnosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Maintaining Balance: The Increasing Role of Energy Storage for Renewable Integration

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

Stenclik, Derek; Denholm, Paul; Chalamala, Babu

For nearly a century, global power systems have focused on three key functions: generating, transmitting, and distributing electricity as a real-time commodity. Physics requires that electricity generation always be in real-time balance with load-despite variability in load on time scales ranging from subsecond disturbances to multiyear trends. With the increasing role of variable generation from wind and solar, the retirement of fossil-fuel-based generation, and a changing consumer demand profile, grid operators are using new methods to maintain this balance.

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.

Parts, Cavities, and Object Representation in Infancy

ERIC Educational Resources Information Center

Hayden, Angela; Bhatt, Ramesh S.; Kangas, Ashley; Zieber, Nicole

2011-01-01

Part representation is not only critical to object perception but also plays a key role in a number of basic visual cognition functions, such as figure-ground segregation, allocation of attention, and memory for shapes. Yet, virtually nothing is known about the development of part representation. If parts are fundamental components of object shape…

Post-Larval Developmental Trajectory of Zebrafish Fry is Altered by Exposure to T3 or T4 Analogues

EPA Science Inventory

The thyroid axis plays a key role in development. While the impacts of perturbing thyroid axis development and/or function are documented in embryonic and larval zebrafish, the effects on developmental milestones at later life stages are not well-delineated. To assess potential l...

Focus on Learning, Transform Teaching.

ERIC Educational Resources Information Center

Weimer, Maryellen

2003-01-01

Discusses how a focus on learning can change teaching and identifies five key changes to practice that come out of a focus on learning. They are changes in: (1) the balance of power; (2) the role of the teacher; (3) the responsibility for learning; (4) the function of content; and (5) the purposes and processes of evaluation. (SLD)

CRISPR and piRNAs: Fundamental Mechanisms and Key Applications of the Next Generation of Molecular Technologies in the Field of Toxicology

EPA Science Inventory

" Exploration into the roles of genes, the proteins that they encode, and the functions that they carry out within the cell is a founding pillar in the field of toxicology. Recent breakthroughs in clustered, regularly interspaced, short palindromic repeat (CRISPR) technology...

Sierra Nevada grasslands: interactions between livestock grazing and ecosystem structure and function

Treesearch

Barbara H. Allen-Diaz

2004-01-01

Livestock grazing plays an integral role in the grass-dominated ecosystems of the Sierra Nevada. Grazing has been asserted to influence such key ecological characteristics as water quality, net primary productivity, nutrient cycling, plant and animal diversity, wildlife habitat availability, and oak regeneration (Belsky and others 1999, Kauffmann and Krueger 1984)....

Succession of ruminal bacterial species and fermentation characteristics in nursing Brangus calves

USDA-ARS?s Scientific Manuscript database

Ruminants are typically born with a non-functional rumen essentially devoid of microorganism. The succession of the microbial population in the rumen from birth to animal maturity is of interest due to the key role the rumen microbial population plays in the overall health and productivity of the ho...

School Choice in Spain and the United States: A Comparative Study

ERIC Educational Resources Information Center

Umpstead, Regina; Jankens, Benjamin; Ortega Gil, Pablo; Weiss, Linda; Umpstead, Bruce

2016-01-01

This article explores issues of school choice in Spain and the United States by examining the roles and functions of "centros concertados," publicly funded private schools in Spain, and public charter schools in the United States, to provide key insights into the similarities and differences between them. After making a national…

Role of forage crops and soil microbes in promoting soil health and productivity

USDA-ARS?s Scientific Manuscript database

The United Nations General Assembly has declared 2015 the International Year of Soils (IYS 2015). The IYS 2015 aims to increase awareness and understanding of the importance of soil for food security and essential ecosystem functions. Although often taken for granted, soils are key to human civiliza...

The Anaphase Promoting Complex Is Required for Memory Function in Mice

ERIC Educational Resources Information Center

Kuczera, Tanja; Stilling, Roman Manuel; Hsia, Hung-En; Bahari-Javan, Sanaz; Irniger, Stefan; Nasmyth, Kim; Sananbenesi, Farahnaz; Fischer, Andre

2011-01-01

Learning and memory processes critically involve the orchestrated regulation of de novo protein synthesis. On the other hand it has become clear that regulated protein degradation also plays a major role in neuronal plasticity and learning behavior. One of the key pathways mediating protein degradation is proteosomal protein destruction. The…

Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory.

PubMed

Koob, G F

2009-05-01

Drug addiction is conceptualized as chronic, relapsing compulsive use of drugs with significant dysregulation of brain hedonic systems. Compulsive drug use is accompanied by decreased function of brain substrates for drug positive reinforcement and recruitment of brain substrates mediating the negative reinforcement of motivational withdrawal. The neural substrates for motivational withdrawal ("dark side" of addiction) involve recruitment of elements of the extended amygdala and the brain stress systems, including corticotropin-releasing factor and norepinephrine. These changes, combined with decreased reward function, are hypothesized to persist in the form of an allostatic state that forms a powerful motivational background for relapse. Relapse also involves a key role for the basolateral amygdala in mediating the motivational effects of stimuli previously paired with drug seeking and drug motivational withdrawal. The basolateral amygdala has a key role in mediating emotional memories in general. The hypothesis argued here is that brain stress systems activated by the motivational consequences of drug withdrawal can not only form the basis for negative reinforcement that drives drug seeking, but also potentiate associative mechanisms that perpetuate the emotional state and help drive the allostatic state of addiction.

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

PubMed Central

O’Connor, Sean Timothy Francis; Lan, Jiaqi; North, Matthew; Loguinov, Alexandre; Zhang, Luoping; Smith, Martyn T.; Gu, April Z.; Vulpe, Chris

2012-01-01

Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems. PMID:23403841

The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis.

PubMed

Wu, Fan-Lin; Liu, Yin; Jiang, He-Wei; Luan, Yi-Zhao; Zhang, Hai-Nan; He, Xiang; Xu, Zhao-Wei; Hou, Jing-Li; Ji, Li-Yun; Xie, Zhi; Czajkowsky, Daniel M; Yan, Wei; Deng, Jiao-Yu; Bi, Li-Jun; Zhang, Xian-En; Tao, Sheng-Ce

2017-08-01

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized. In this study, using a Mtb proteome microarray, we have globally identified the binding proteins in Mtb for all of the STPKs, and constructed the first STPK protein interaction (KPI) map that includes 492 binding proteins and 1,027 interactions. Bioinformatics analysis showed that the interacting proteins reflect diverse functions, including roles in two-component system, transcription, protein degradation, and cell wall integrity. Functional investigations confirmed that PknG regulates cell wall integrity through key components of peptidoglycan (PG) biosynthesis, e.g. MurC. The global STPK-KPIs network constructed here is expected to serve as a rich resource for understanding the key signaling pathways in Mtb, thus facilitating drug development and effective control of Mtb. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Soil protists: a fertile frontier in soil biology research.

PubMed

Geisen, Stefan; Mitchell, Edward A D; Adl, Sina; Bonkowski, Michael; Dunthorn, Micah; Ekelund, Flemming; Fernández, Leonardo D; Jousset, Alexandre; Krashevska, Valentyna; Singer, David; Spiegel, Frederick W; Walochnik, Julia; Lara, Enrique

2018-05-01

Protists include all eukaryotes except plants, fungi and animals. They are an essential, yet often forgotten, component of the soil microbiome. Method developments have now furthered our understanding of the real taxonomic and functional diversity of soil protists. They occupy key roles in microbial foodwebs as consumers of bacteria, fungi and other small eukaryotes. As parasites of plants, animals and even of larger protists, they regulate populations and shape communities. Pathogenic forms play a major role in public health issues as human parasites, or act as agricultural pests. Predatory soil protists release nutrients enhancing plant growth. Soil protists are of key importance for our understanding of eukaryotic evolution and microbial biogeography. Soil protists are also useful in applied research as bioindicators of soil quality, as models in ecotoxicology and as potential biofertilizers and biocontrol agents. In this review, we provide an overview of the enormous morphological, taxonomical and functional diversity of soil protists, and discuss current challenges and opportunities in soil protistology. Research in soil biology would clearly benefit from incorporating more protistology alongside the study of bacteria, fungi and animals.

Androgen receptor: structure, role in prostate cancer and drug discovery

PubMed Central

Tan, MH Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

2015-01-01

Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

S100A8 and S100A9: New Insights into Their Roles in Malignancy

PubMed Central

Srikrishna, Geetha

2011-01-01

Recent studies have highlighted key roles played by non-neoplastic host cells of the tumor microenvironment, and by secreted factors from tumor and host cells, in promoting malignancy. In this regard, damage-associated molecular pattern (DAMP) molecules such as S100A8 and S100A9, with well-known functions in inflammation, have been increasingly recognized not only as markers, but also as new candidates with important roles in modulating tumor growth and metastasis. This review focuses on our current understanding of the pro- and anti-tumorigenic functions of S100A8 and S100A9. Elucidating molecular pathways mediated by these proteins promises to provide potential novel targets for the development of cancer therapeutics and to establish valid biomarkers to identify early stages of tumor progression. PMID:21912088

GSK-3β: A Bifunctional Role in Cell Death Pathways.

PubMed

Jacobs, Keith M; Bhave, Sandeep R; Ferraro, Daniel J; Jaboin, Jerry J; Hallahan, Dennis E; Thotala, Dinesh

2012-01-01

Although glycogen synthase kinase-3 beta (GSK-3β) was originally named for its ability to phosphorylate glycogen synthase and regulate glucose metabolism, this multifunctional kinase is presently known to be a key regulator of a wide range of cellular functions. GSK-3β is involved in modulating a variety of functions including cell signaling, growth metabolism, and various transcription factors that determine the survival or death of the organism. Secondary to the role of GSK-3β in various diseases including Alzheimer's disease, inflammation, diabetes, and cancer, small molecule inhibitors of GSK-3β are gaining significant attention. This paper is primarily focused on addressing the bifunctional or conflicting roles of GSK-3β in both the promotion of cell survival and of apoptosis. GSK-3β has emerged as an important molecular target for drug development.

The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

PubMed Central

Schwieterman, Alicia A.; Steves, Alyse N.; Yee, Vivian; Donelson, Cory J.; Bentley, Melissa R.; Santorella, Elise M.; Mehlenbacher, Taylor V.; Pital, Aaron; Howard, Austin M.; Wilson, Melissa R.; Ereddia, Danielle E.; Effrein, Kelsie S.; McMurry, Jonathan L.; Ackley, Brian D.; Chisholm, Andrew D.; Hudson, Martin L.

2016-01-01

The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system. PMID:26645816

Starring role of toll-like receptor-4 activation in the gut-liver axis

PubMed Central

Carotti, Simone; Guarino, Michele Pier Luca; Vespasiani-Gentilucci, Umberto; Morini, Sergio

2015-01-01

Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types. PMID:26600967

Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron.

PubMed

Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta; Ayala-Santiago, Christian; Cruz-Reyes, Nicole; Molina-Castro, Gian Carlo; Clemens, Stefan; Canela, Enric I; Ferré, Sergi; Casadó, Vicent; Díaz-Ríos, Manuel

2018-05-24

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A 1 -dopamine D 1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D 1 receptor-mediated signaling. A 1 -D 1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Intestinal microbiota composition is altered according to nutritional biorhythms in the leopard coral grouper (Plectropomus leopardus).

PubMed

Mekuchi, Miyuki; Asakura, Taiga; Sakata, Kenji; Yamaguchi, Tomofumi; Teruya, Kazuhisa; Kikuchi, Jun

2018-01-01

Aquaculture is currently a major source of fish and has the potential to become a major source of protein in the future. These demands require efficient aquaculture. The intestinal microbiota plays an integral role that benefits the host, providing nutrition and modulating the immune system. Although our understanding of microbiota in fish gut has increased, comprehensive studies examining fish microbiota and host metabolism remain limited. Here, we investigated the microbiota and host metabolism in the coral leopard grouper, which is traded in Asian markets as a superior fish and has begun to be produced via aquaculture. We initially examined the structural changes of the gut microbiota using next-generation sequencing and found that the composition of microbiota changed between fasting and feeding conditions. The dominant phyla were Proteobacteria in fasting and Firmicutes in feeding; interchanging the dominant bacteria required 12 hours. Moreover, microbiota diversity was higher under feeding conditions than under fasting conditions. Multivariate analysis revealed that Proteobacteria are the key bacteria in fasting and Firmicutes and Fusobacteria are the key bacteria in feeding. Subsequently, we estimated microbiota functional capacity. Microbiota functional structure was relatively stable throughout the experiment; however, individual function activity changed according to feeding conditions. Taken together, these findings indicate that the gut microbiota could be a key factor to understanding fish feeding conditions and play a role in interactions with host metabolism. In addition, the composition of microbiota in ambient seawater directly affects the fish; therefore, it is important to monitor the microbiota in rearing tanks and seawater circulating systems.

Restoration using Azolla imbricata increases nitrogen functional bacterial groups and genes in soil.

PubMed

Lu, Xiao-Ming; Lu, Peng-Zhen; Yang, Ke

2017-05-01

Microbial groups are major factors that influence soil function. Currently, there is a lack of studies on microbial functional groups. Although soil microorganisms play an important role in the nitrogen cycle, systematic studies of the effects of environmental factors on microbial populations in relation to key metabolic processes in the nitrogen cycle are seldom reported. In this study, we conducted a systematic analysis of the changes in nitrogen functional groups in mandarin orange garden soil treated with Azolla imbricata. The structures of the major functional bacterial groups and the functional gene abundances involved in key processes of the soil nitrogen cycle were analyzed using high-throughput sequencing (HTS) and quantitative real-time PCR, respectively. The results indicated that returning A. imbricata had an important influence on the composition of soil nitrogen functional bacterial communities. Treatment with A. imbricata increased the diversity of the nitrogen functional bacteria. The abundances of nitrogen functional genes were significantly higher in the treated soil compared with the control soil. Both the diversity of the major nitrogen functional bacteria (nifH bacteria, nirK bacteria, and narG bacteria) and the abundances of nitrogen functional genes in the soil showed significant positive correlations with the soil pH, the organic carbon content, available nitrogen, available phosphorus, and NH 4 + -N and NO 3 - -N contents. Treatment with 12.5 kg fresh A. imbricata per mandarin orange tree was effective to improve the quality of the mandarin orange garden soil. This study analyzed the mechanism of the changes in functional bacterial groups and genes involved in key metabolic processes of the nitrogen cycle in soil treated by A. imbricata.

Practical applications of trace minerals for dairy cattle.

PubMed

Overton, T R; Yasui, T

2014-02-01

Trace minerals have critical roles in the key interrelated systems of immune function, oxidative metabolism, and energy metabolism in ruminants. To date, the primary trace elements of interest in diets for dairy cattle have included Zn, Cu, Mn, and Se although data also support potentially important roles of Cr, Co, and Fe in diets. Trace minerals such as Zn, Cu, Mn, and Se are essential with classically defined roles as components of key antioxidant enzymes and proteins. Available evidence indicates that these trace minerals can modulate aspects of oxidative metabolism and immune function in dairy cattle, particularly during the transition period and early lactation. Chromium has been shown to influence both immune function and energy metabolism of cattle; dairy cows fed Cr during the transition period and early lactation have evidence of improved immune function, increased milk production, and decreased cytological endometritis. Factors that complicate trace mineral nutrition at the farm level include the existence of a large number of antagonisms affecting bioavailability of individual trace minerals and uncertainty in terms of requirements under all physiological and management conditions; therefore, determining the optimum level and source of trace minerals under each specific situation continues to be a challenge. Typical factorial approaches to determine requirements for dairy cattle do not account for nuances in biological function observed with supplementation with various forms and amounts of trace minerals. Trace mineral nutrition modulates production, health, and reproduction in cattle although both formal meta-analysis and informal survey of the literature reveal substantial heterogeneity of response in these outcome variables. The industry has largely moved away from oxide-based programs toward sulfate-based programs; however, some evidence favors shifting supplementation strategies further toward more bioavailable forms of inorganic and organic trace minerals. Furthermore, opportunities for specific modulation of aspects of health, milk production, and reproduction through supplementation strategies for diets of transition dairy cows are attractive because of the known dynamics of energy metabolism, immune function, and oxidative metabolism during this timeframe.

CD14 is a key mediator of both lysophosphatidic acid and lipopolysaccharide induction of foam cell formation.

PubMed

An, Dong; Hao, Feng; Zhang, Fuqiang; Kong, Wei; Chun, Jerold; Xu, Xuemin; Cui, Mei-Zhen

2017-09-01

Macrophage uptake of oxidized low-density lipoprotein (oxLDL) plays an important role in foam cell formation and the pathogenesis of atherosclerosis. We report here that lysophosphatidic acid (LPA) enhances lipopolysaccharide (LPS)-induced oxLDL uptake in macrophages. Our data revealed that both LPA and LPS highly induce the CD14 expression at messenger RNA and protein levels in macrophages. The role of CD14, one component of the LPS receptor cluster, in LPA-induced biological functions has been unknown. We took several steps to examine the role of CD14 in LPA signaling pathways. Knockdown of CD14 expression nearly completely blocked LPA/LPS-induced oxLDL uptake in macrophages, demonstrating for the first time that CD14 is a key mediator responsible for both LPA- and LPS-induced oxLDL uptake/foam cell formation. To determine the molecular mechanism mediating CD14 function, we demonstrated that both LPA and LPS significantly induce the expression of scavenger receptor class A type I (SR-AI), which has been implicated in lipid uptake process, and depletion of CD14 levels blocked LPA/LPS-induced SR-AI expression. We further showed that the SR-AI-specific antibody, which quenches SR-AI function, blocked LPA- and LPS-induced foam cell formation. Thus, SR-AI is the downstream mediator of CD14 in regulating LPA-, LPS-, and LPA/LPS-induced foam cell formation. Taken together, our results provide the first experimental evidence that CD14 is a novel connecting molecule linking both LPA and LPS pathways and is a key mediator responsible for LPA/LPS-induced foam cell formation. The LPA/LPS-CD14-SR-AI nexus might be the new convergent pathway, contributing to the worsening of atherosclerosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment.

PubMed

Huang, Guoyou; Li, Fei; Zhao, Xin; Ma, Yufei; Li, Yuhui; Lin, Min; Jin, Guorui; Lu, Tian Jian; Genin, Guy M; Xu, Feng

2017-10-25

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

Understanding fungal functional biodiversity during the mitigation of environmentally dispersed pentachlorophenol in cork oak forest soils.

PubMed

Varela, Adélia; Martins, Celso; Núñez, Oscar; Martins, Isabel; Houbraken, Jos A M P; Martins, Tiago M; Leitão, M Cristina; McLellan, Iain; Vetter, Walter; Galceran, M Teresa; Samson, Robert A; Hursthouse, Andrew; Silva Pereira, Cristina

2015-08-01

Pentachlorophenol (PCP) is globally dispersed and contamination of soil with this biocide adversely affects its functional biodiversity, particularly of fungi - key colonizers. Their functional role as a community is poorly understood, although a few pathways have been already elucidated in pure cultures. This constitutes here our main challenge - elucidate how fungi influence the pollutant mitigation processes in forest soils. Circumstantial evidence exists that cork oak forests in N. W. Tunisia - economically critical managed forests are likely to be contaminated with PCP, but the scientific evidence has previously been lacking. Our data illustrate significant forest contamination through the detection of undefined active sources of PCP. By solving the taxonomic diversity and the PCP-derived metabolomes of both the cultivable fungi and the fungal community, we demonstrate here that most strains (predominantly penicillia) participate in the pollutant biotic degradation. They form an array of degradation intermediates and by-products, including several hydroquinone, resorcinol and catechol derivatives, either chlorinated or not. The degradation pathway of the fungal community includes uncharacterized derivatives, e.g. tetrachloroguaiacol isomers. Our study highlights fungi key role in the mineralization and short lifetime of PCP in forest soils and provide novel tools to monitor its degradation in other fungi dominated food webs. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

β-Ketoacyl-acyl Carrier Protein Synthase I (KASI) Plays Crucial Roles in the Plant Growth and Fatty Acids Synthesis in Tobacco

PubMed Central

Yang, Tianquan; Xu, Ronghua; Chen, Jianghua; Liu, Aizhong

2016-01-01

Fatty acids serve many functions in plants, but the effects of some key genes involved in fatty acids biosynthesis on plants growth and development are not well understood yet. To understand the functions of 3-ketoacyl-acyl-carrier protein synthase I (KASI) in tobacco, we isolated two KASI homologs, which we have designated NtKASI-1 and NtKASI-2. Expression analysis showed that these two KASI genes were transcribed constitutively in all tissues examined. Over-expression of NtKASI-1 in tobacco changed the fatty acid content in leaves, whereas over-expressed lines of NtKASI-2 exhibited distinct phenotypic features such as slightly variegated leaves and reduction of the fatty acid content in leaves, similar to the silencing plants of NtKASI-1 gene. Interestingly, the silencing of NtKASI-2 gene had no discernibly altered phenotypes compared to wild type. The double silencing plants of these two genes enhanced the phenotypic changes during vegetative and reproductive growth compared to wild type. These results uncovered that these two KASI genes had the partially functional redundancy, and that the KASI genes played a key role in regulating fatty acids synthesis and in mediating plant growth and development in tobacco. PMID:27509494

Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity.

PubMed

Karin, Nathan; Razon, Hila

2018-09-01

Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication. Copyright © 2018 Elsevier Ltd. All rights reserved.

Conserved noncoding sequences conserve biological networks and influence genome evolution.

PubMed

Xie, Jianbo; Qian, Kecheng; Si, Jingna; Xiao, Liang; Ci, Dong; Zhang, Deqiang

2018-05-01

Comparative genomics approaches have identified numerous conserved cis-regulatory sequences near genes in plant genomes. Despite the identification of these conserved noncoding sequences (CNSs), our knowledge of their functional importance and selection remains limited. Here, we used a combination of DNA methylome analysis, microarray expression analyses, and functional annotation to study these sequences in the model tree Populus trichocarpa. Methylation in CG contexts and non-CG contexts was lower in CNSs, particularly CNSs in the 5'-upstream regions of genes, compared with other sites in the genome. We observed that CNSs are enriched in genes with transcription and binding functions, and this also associated with syntenic genes and those from whole-genome duplications, suggesting that cis-regulatory sequences play a key role in genome evolution. We detected a significant positive correlation between CNS number and protein interactions, suggesting that CNSs may have roles in the evolution and maintenance of biological networks. The divergence of CNSs indicates that duplication-degeneration-complementation drives the subfunctionalization of a proportion of duplicated genes from whole-genome duplication. Furthermore, population genomics confirmed that most CNSs are under strong purifying selection and only a small subset of CNSs shows evidence of adaptive evolution. These findings provide a foundation for future studies exploring these key genomic features in the maintenance of biological networks, local adaptation, and transcription.

Understanding the Role of Serotonin in Female Hypoactive Sexual Desire Disorder and Treatment Options.

PubMed

Croft, Harry A

2017-12-01

The neurobiology of sexual response is driven in part by dopamine and serotonin-the former modulating excitatory pathways and the latter regulating inhibitory pathways. Neurobiological underpinnings of hypoactive sexual desire disorder (HSDD) are seemingly related to overactive serotonin activity that results in underactive dopamine activity. As such, pharmacologic agents that decrease serotonin, increase dopamine, or some combination thereof, have therapeutic potential for HSDD. To review the role of serotonin in female sexual function and the effects of pharmacologic interventions that target the serotonin system in the treatment of HSDD. Searches of the Medline database for articles on serotonin and female sexual function. Relevant articles from the peer-reviewed literature were included. Female sexual response is regulated not only by the sex hormones but also by several neurotransmitters. It is postulated that dopamine, norepinephrine, oxytocin, and melanocortins serve as key neuromodulators for the excitatory pathways, whereas serotonin, opioids, and endocannabinoids serve as key neuromodulators for the inhibitory pathways. Serotonin appears to be a key inhibitory modulator of sexual desire, because it decreases the ability of excitatory systems to be activated by sexual cues. Centrally acting drugs that modulate the excitatory and inhibitory pathways involved in sexual desire (eg, bremelanotide, bupropion, buspirone, flibanserin) have been investigated as treatment options for HSDD. However, only flibanserin, a multifunctional serotonin agonist and antagonist (5-hydroxytryptamine [5-HT] 1A receptor agonist and 5-HT 2A receptor antagonist), is currently approved for the treatment of HSDD. The central serotonin system is 1 biochemical target for medications intended to treat HSDD. This narrative review integrates findings from preclinical studies and clinical trials to elucidate neurobiological underpinnings of HSDD but is limited to 1 neurotransmitter system (serotonin). Serotonin overactivity is a putative cause of sexual dysfunction in patients with HSDD. The unique pharmacologic profile of flibanserin tones down inhibitory serotonergic function and restores dopaminergic and noradrenergic function. Croft HA. Understanding the Role of Serotonin in Female Hypoactive Sexual Desire Disorder and Treatment Options. J Sex Med 2017;14:1575-1584. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.

PubMed

Dufresne, Sébastien S; Dumont, Nicolas A; Boulanger-Piette, Antoine; Fajardo, Val A; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M; Pape, Paul C; Tupling, A Russell; Frenette, Jérôme

2016-04-15

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function. Copyright © 2016 the American Physiological Society.

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles

PubMed Central

Dufresne, Sébastien S.; Dumont, Nicolas A.; Boulanger-Piette, Antoine; Fajardo, Val A.; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M.; Pape, Paul C.; Tupling, A. Russell

2016-01-01

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca2+ sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca2+ storage and SERCA activity, ultimately affecting denervated skeletal muscle function. PMID:26825123

Redox Regulation of Endothelial Cell Fate

PubMed Central

Song, Ping; Zou, Ming-Hui

2014-01-01

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

Thumb-loops up for catalysis: a structure/function investigation of a functional loop movement in a GH11 xylanase

PubMed Central

Paës, Gabriel; Cortés, Juan; Siméon, Thierry; O'Donohue, Michael J.; Tran, Vinh

2012-01-01

Dynamics is a key feature of enzyme catalysis. Unfortunately, current experimental and computational techniques do not yet provide a comprehensive understanding and description of functional macromolecular motions. In this work, we have extended a novel computational technique, which combines molecular modeling methods and robotics algorithms, to investigate functional motions of protein loops. This new approach has been applied to study the functional importance of the so-called thumb-loop in the glycoside hydrolase family 11 xylanase from Thermobacillus xylanilyticus (Tx-xyl). The results obtained provide new insight into the role of the loop in the glycosylation/deglycosylation catalytic cycle, and underline the key importance of the nature of the residue located at the tip of the thumb-loop. The effect of mutations predicted in silico has been validated by in vitro site-directed mutagenesis experiments. Overall, we propose a comprehensive model of Tx-xyl catalysis in terms of substrate and product dynamics by identifying the action of the thumb-loop motion during catalysis. PMID:24688637

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

PubMed

McHugh, Patrick C; Buckley, David A

2015-01-01

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

Rac1-PAK2 pathway is essential for zebrafish heart regeneration

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

Peng, Xiangwen; He, Quanze; Li, Guobao

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation duringmore » heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.« less

Leptin regulation of hippocampal synaptic function in health and disease

PubMed Central

Irving, Andrew J.; Harvey, Jenni

2014-01-01

The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD. PMID:24298156

NO buffering and conditional NO release in stress response.

PubMed

Begara-Morales, Juan C; Chaki, Mounira; Valderrama, Raquel; Sánchez-Calvo, Beatriz; Mata-Pérez, Capilla; Padilla, María N; Corpas, Francisco J; Barroso, Juan B

2018-03-01

Nitric oxide (NO) has emerged as an essential biological messenger in plant biology that usually transmits its bioactivity by post-translational modifications such as S-nitrosylation, the reversible addition of a NO group to a protein cysteine residue leading to S-nitrosothiols (SNOs). In last year's, SNOs have emerged as key signalling molecules mainly involved in plant response to stress. Chief among SNOs is S-nitrosoglutathione (GSNO), generated by S-nitrosylation of the key antioxidant glutathione (GSH). GSNO is considered the major NO reservoir and a phloem mobile signal that confers to NO the capacity of a long-distance signalling molecule. GSNO is able to regulate protein function and gene expression resulting in a key role of GSNO in fundamental processes in plant such as development and response to a wide range of environmental stresses. In addition, GSNO is also able to regulate total SNO pool and consequently, it could be considered the storage of NO in cells that may control NO signalling under basal and stress-related responses. Thus, GSNO function could be crucial during plant response to environmental stresses. Besides this importance of GSNO in plant biology, its mode of action has not been widely discussed in the literature. In this review, we will firstly discuss the GSNO turnover in cells and secondly the role of GSNO as mediator of physiological and stress-related processes in plants, highlighting aspects in which there is still some controversy.

X-ray crystal structure of plasmin with tranexamic acid-derived active site inhibitors.

PubMed

Law, Ruby H P; Wu, Guojie; Leung, Eleanor W W; Hidaka, Koushi; Quek, Adam J; Caradoc-Davies, Tom T; Jeevarajah, Devadharshini; Conroy, Paul J; Kirby, Nigel M; Norton, Raymond S; Tsuda, Yuko; Whisstock, James C

2017-05-09

The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO ( trans -4-aminomethylcyclohexanecarbonyl-l-tyrosine- n -octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3' subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S' subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders.

X-ray crystal structure of plasmin with tranexamic acid–derived active site inhibitors

PubMed Central

Wu, Guojie; Leung, Eleanor W. W.; Hidaka, Koushi; Quek, Adam J.; Caradoc-Davies, Tom T.; Jeevarajah, Devadharshini; Kirby, Nigel M.; Norton, Raymond S.; Tsuda, Yuko; Whisstock, James C.

2017-01-01

The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO (trans-4-aminomethylcyclohexanecarbonyl-l-tyrosine-n-octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3′ subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S′ subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders. PMID:29296720

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

Tight junctions in cancer metastasis.

PubMed

Martin, Tracey A; Mason, Malcolm D; Jiang, Wen G

2011-01-01

Tight Junctions (TJ) are well known to function as a control for the paracellular diffusion of ions and certain molecules, it has however, become evident that the TJ has a vital role in maintaining cell to cell integrity. Loss of cohesion of the TJ structure can lead to invasion and ultimately to the metastasis of cancer cells. This review will discuss how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the progression of cancer and progression of metastasis.

Extinction risk of soil biota

PubMed Central

Veresoglou, Stavros D.; Halley, John M.; Rillig, Matthias C.

2015-01-01

No species lives on earth forever. Knowing when and why species go extinct is crucial for a complete understanding of the consequences of anthropogenic activity, and its impact on ecosystem functioning. Even though soil biota play a key role in maintaining the functioning of ecosystems, the vast majority of existing studies focus on aboveground organisms. Many questions about the fate of belowground organisms remain open, so the combined effort of theorists and applied ecologists is needed in the ongoing development of soil extinction ecology. PMID:26593272

Trait-based plant ecology: moving towards a unifying species coexistence theory : Features of the Special Section.

PubMed

Escudero, Adrián; Valladares, Fernando

2016-04-01

Functional traits are the center of recent attempts to unify key ecological theories on species coexistence and assembling in populations and communities. While the plethora of studies on the role of functional traits to explain patterns and dynamics of communities has rendered a complex picture due to the idiosyncrasies of each study system and approach, there is increasing evidence on their actual relevance when aspects such as different spatial scales, intraspecific variability and demography are considered.

Dopamine does double duty in motivating cognitive effort

PubMed Central

Westbrook, Andrew; Braver, Todd S.

2015-01-01

Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: 1) modulating the functional parameters of working memory circuits subserving effortful cognition, and 2) mediating value-learning and decision-making about effortful cognitive action. Here we tie together these two lines of research, proposing how dopamine serves “double duty”, translating incentive information into cognitive motivation. PMID:26889810

MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis

PubMed Central

Lee, Seongju; Chang, Jaerak; Renvoisé, Benoît; Tipirneni, Anita; Yang, Sarah; Blackstone, Craig

2012-01-01

Diverse cellular processes, including multivesicular body formation, cytokinesis, and viral budding, require the sequential functions of endosomal sorting complexes required for transport (ESCRTs) 0 to III. Of these multiprotein complexes, ESCRT-III in particular plays a key role in mediating membrane fission events by forming large, ring-like helical arrays. A number of proteins playing key effector roles, most notably the ATPase associated with diverse cellular activities protein VPS4, harbor present in microtubule-interacting and trafficking molecules (MIT) domains comprising asymmetric three-helical bundles, which interact with helical MIT-interacting motifs in ESCRT-III subunits. Here we assess comprehensively the ESCRT-III interactions of the MIT-domain family member MITD1 and identify strong interactions with charged multivesicular body protein 1B (CHMP1B), CHMP2A, and increased sodium tolerance-1 (IST1). We show that these ESCRT-III subunits are important for the recruitment of MITD1 to the midbody and that MITD1 participates in the abscission phase of cytokinesis. MITD1 also dimerizes through its C-terminal domain. Both types of interactions appear important for the role of MITD1 in negatively regulating the interaction of IST1 with VPS4. Because IST1 binding in turn regulates VPS4, MITD1 may function through downstream effects on the activity of VPS4, which plays a critical role in the processing and remodeling of ESCRT filaments in abscission. PMID:23015756

The Snail Family in Normal and Malignant Haematopoiesis.

PubMed

Carmichael, Catherine L; Haigh, Jody J

2017-01-01

Snail family proteins are key inducers of the epithelial-mesenchymal transition (EMT), a critical process required for normal embryonic development. They have also been strongly implicated in regulating the EMT-like processes required for tumour cell invasion, migration, and metastasis. Whether these proteins also contribute to normal blood cell development, however, remains to be clearly defined. Increasing evidence supports a role for the Snail family in regulating cell survival, migration, and differentiation within the haematopoietic system, as well as potentially an oncogenic role in the malignant transformation of haematopoietic stem cells. This review will provide a broad overview of the Snail family, including key aspects of their involvement in the regulation and development of solid organ cancer, as well as a discussion on our current understanding of Snail family function during normal and malignant haematopoiesis. © 2017 S. Karger AG, Basel.

VEGF signaling inside vascular endothelial cells and beyond.

PubMed

Eichmann, Anne; Simons, Michael

2012-04-01

Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of protected endorsement for online banking using mobile phones

NASA Astrophysics Data System (ADS)

Narayana, Galla; Venkateswarlu, Tammineni; Kumar, G. S. P.; Padmavathamma, Mokkala; Sreekanth, G.; Delhibabu, K.; Prasad, A. R.

2013-03-01

Securing Online Banking transactions for customer is the primary goal of financial institutions that provides Internet banking facility. Mobile phones play an important role in our society as more and more functions having been integrated within mobile phones, such as Internet browsing, mobile banking, and shopping. Mobiles phones can be used to secure ATM card pins by sending to the customer directly rather than in emails or by other means which has a possibility of hacking. In this paper we have proposed method of generating a Private Key Security Token by bank authentication servers which uses IMSI registers and IMEI number of client's mobile registered. The key is generated by implementing RIPE MD160 and Hex Encode Algorithm. Token received is valid only for that client mobile only and can be generated upon request by customer dynamically. The client is given a PIN and a Master Key when registered to the Online Banking Services. If in case a client's mobile is lost, authentication is done using Unique Master Key, else the Private Key Token is used there by making transactions secured and simple without the need of carrying any USB Tokens. The additional functionality provides the client more security on their transactions. Due to this Phishing attacks by the hackers is avoided.

Effect of Processing and Storage on RBC function in vivo

PubMed Central

Doctor, Allan; Spinella, Phil

2012-01-01

Red Blood Cell (RBC) transfusion is indicated to improve oxygen delivery to tissue, and for no other purpose. We have come to appreciate that donor RBCs are fundamentally altered during processing and storage, in a fashion that both impairs oxygen transport efficacy and introduces additional risk by perturbing both immune and coagulation systems. The protean biophysical and physiologic changes in RBC function arising from storage are termed the ‘storage lesion’; many have been understood for some time; for example, we know that the oxygen affinity of stored blood rises during the storage period1 and that intracellular allosteric regulators, notably 2,3-bisphosphoglyceric acid (DPG) and ATP, are depleted during storage. Our appreciation of other storage lesion features has emerged with improved understanding of coagulation, immune and vascular signaling systems. Herein we review key features of the ‘storage lesion’. Additionally, we call particular attention to the newly appreciated role of RBCs in regulating linkage between regional blood flow and regional O2 consumption by regulating the bioavailability of key vasoactive mediators in plasma, as well as discuss how processing and storage disturbs this key signaling function and impairs transfusion efficacy. PMID:22818545

Phase Transitions in the Nucleus: the functional implications of concentration-dependent assembly of a Liquid-like RNA/Protein Body

NASA Astrophysics Data System (ADS)

Zhu, Lian; Weber, Stephanie; Berry, Joel; Vaidya, Nilesh; Haataja, Mikko; Brangwynne, Clifford

2015-03-01

The nucleolus is a liquid-like membrane-less nuclear body which plays an important role in cell growth and size control. By modulating nucleolar component concentration through RNAi conditions that change C. elegans cell size, we find that nucleoli only assemble above a threshold concentration; moreover, the ripening dynamics of nucleated droplets are consistent with the hypothesis that the assembly of the nucleolus represents an intracellular liquid-liquid phase transition. A key question is how this phase-transition is linked to the primary function of the nucleolus, in transcribing and processing ribosomal RNA. To address this, we characterize the localization of RNA Polymerase I, a key transcriptional enzyme, into nucleolar foci as a function of nucleolar component concentration. Our results suggest that there are a small number of key disordered phosphoproteins that may serve as a link between transcription and assembly. Finally, we present preliminary results using a reduced model system consisting of purified nucleolar proteins to assess the ability of nucleolar proteins to drive liquid-liquid phase separation in vitro. These results lay the foundation for a quantitative understanding of intracellular phase transitions and their impact on biomedically-critical RNA-processing steps.

Increases in mean annual temperature do not alter soil bacterial community structure in tropical montane wet forests

Treesearch

Paul C. Selmants; Karen L. Adair; Creighton M. Litton; Christian P. Giardina; Egbert Schwartz

2016-01-01

Soil bacteria play a key role in regulating terrestrial biogeochemical cycling and greenhouse gas fluxes across the soil-atmosphere continuum. Despite their importance to ecosystem functioning, we lack a general understanding of how bacterial communities respond to climate change, especially in relatively understudied ecosystems like tropical montane wet...

Modeling of DNA and Protein Organization Levels with Cn3D Software

ERIC Educational Resources Information Center

Stasinakis, Panagiotis K.; Nicolaou, Despoina

2017-01-01

The molecular structure of living organisms and the complex interactions amongst its components are the basis for the diversity observed at the macroscopic level. Proteins and nucleic acids are some of the major molecular components, and play a key role in several biological functions, such as those of development and evolution. This article…

Functional characterization of a p-coumaroyl quinate/shikimate 3’-hydroxylase from potato (Solanum tuberosum)

USDA-ARS?s Scientific Manuscript database

Chlorogenic acid (CGA) plays an important role in protecting plants against pathogens and promoting human health. Although CGA accumulates to high levels in potato tubers, the key enzyme p-coumaroyl quinate/shikimate 3’-hydroxylase (C3’H) for CGA biosynthesis has not been isolated or characterized i...

The Self-Concept of Spanish Young Adults with Retinitis Pigmentosa

ERIC Educational Resources Information Center

Lopez-Justicia, Maria Dolores; Cordoba, Inmaculada Nieto

2006-01-01

Retinitis pigmentosa (RP) is a degenerative disease of the retina that causes the severe impairment of visual functioning similar to low vision, leading, in many cases, to blindness. Because the construct of self-concept plays a key role in personality, this study was designed to measure self-concept in a group of young adults with RP. The…

Leader Voices: Principals Reflect on the Evolution of Their Leadership

ERIC Educational Resources Information Center

Marcellus, Angela; Flores, Matt; Craig, Anthony

2012-01-01

More than a decade of school leadership research from The Wallace Foundation highlights not only the critical role of the principal but also the practices that effective school leaders undertake. A recent brief (The Wallace Foundation, 2011) distills these practices into five key functions: (1) Shape a vision of academic success for all students;…

78 FR 19713 - Possible Role of Independent Third Parties in Industry-Sponsored Tobacco Product Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... tobacco product research could be subject to third-party governance? For example, could it be applied to... governance? For example, should both the design and conduct of research studies be subject to third-party... more key functions, including the design and conduct of research, the oversight of specific studies...

Viral precursor protein P3 and its processed products perform discrete and essential functions in the poliovirus RNA replication complex

USDA-ARS?s Scientific Manuscript database

The differential use of protein precursors and their products is a key strategy used during poliovirus replication. To characterize the role of protein precursors during replication, we examined the complementation profiles of mutants that inhibited 3D polymerase or 3C-RNA binding activity. We showe...

Does the Document Matter? The Evolving Role of Syllabi in Higher Education

ERIC Educational Resources Information Center

Palmer, Michael S.; Wheeler, Lindsay B.; Aneece, Itiya

2016-01-01

Essentially, the syllabus is a physical artifact outlining key structural elements of a course. It often serves contractual, record keeping, and/or communication functions. It is the place where faculty describe what content they will cover, what books and articles their students will read, the assignments they will complete, dates when things are…

Forest biodiversity and the delivery of ecosystem goods and services: translating science into policy

Treesearch

Ian Thompson; Kimiko Okabe; Jason Tylianakis; Pushpam Kumar; Eckehard G. Brockerhoff; Nancy Schellhorn; John A. Parrotta; Robert Nasi

2011-01-01

Biodiversity is integral to almost all ecosystem processes, with some species playing key functional roles that are essential for maintaining the value of ecosystems to humans. However, many ecosystem services remain nonvalued, and decisionmakers rarely consider biodiversity in policy development, in part because the relationships between biodiversity and the provision...

Dealing with Organizational Silos with Communities of Practice and Human Resource Management

ERIC Educational Resources Information Center

Forsten-Astikainen, Riitta; Hurmelinna-Laukkanen, Pia; Lämsä, Tuija; Heilmann, Pia; Hyrkäs, Elina

2017-01-01

Purpose: Organizational silos that build on the existing organizational structures are often considered to have negative effects in the form of focus on private narrow objectives and organizational fragmentation. To avoid such harmful outcomes, competence management is called for, and in this, the human resources (HR) function takes a key role.…

Barriers and Solutions to HE Progression for Early Years' Practitioners

ERIC Educational Resources Information Center

Kendall, Alexandra; Carey, Danielle; Cramp, Andy; Perkins, Helen

2012-01-01

Shifts in UK social and economic policy have focused on education and care in the Early Years as key to improving social inclusion, skills acquisition and longer term social and economic prosperity. The implications for practitioners in the sector have been significant as roles, functions and foci have been renegotiated through the processes of…

Presenting the Straddle Lemma in an Introductory Real Analysis Course

ERIC Educational Resources Information Center

Soares, A.; dos Santos, A. L.

2017-01-01

In this article, we revisit the concept of strong differentiability of real functions of one variable, underlying the concept of differentiability. Our discussion is guided by the Straddle Lemma, which plays a key role in this context. The proofs of the results presented are designed to meet a young audience in mathematics, typical of students in…

Functional diversity and redundancy across fish gut, sediment and water bacterial communities.

PubMed

Escalas, Arthur; Troussellier, Marc; Yuan, Tong; Bouvier, Thierry; Bouvier, Corinne; Mouchet, Maud A; Flores Hernandez, Domingo; Ramos Miranda, Julia; Zhou, Jizhong; Mouillot, David

2017-08-01

This article explores the functional diversity and redundancy in a bacterial metacommunity constituted of three habitats (sediment, water column and fish gut) in a coastal lagoon under anthropogenic pressure. Comprehensive functional gene arrays covering a wide range of ecological processes and stress resistance genes to estimate the functional potential of bacterial communities were used. Then, diversity partitioning was used to characterize functional diversity and redundancy within (α), between (β) and across (γ) habitats. It was showed that all local communities exhibit a highly diversified potential for the realization of key ecological processes and resistance to various environmental conditions, supporting the growing evidence that macro-organisms microbiomes harbour a high functional potential and are integral components of functional gene dynamics in aquatic bacterial metacommunities. Several levels of functional redundancy at different scales of the bacterial metacommunity were observed (within local communities, within habitats and at the metacommunity level). The results suggested a high potential for the realization of spatial ecological insurance within this ecosystem, that is, the functional compensation among microorganisms for the realization and maintenance of key ecological processes, within and across habitats. Finally, the role of macro-organisms as dispersal vectors of microbes and their potential influence on marine metacommunity dynamics were discussed. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Functional resilience of microbial ecosystems in soil: How important is a spatial analysis?

NASA Astrophysics Data System (ADS)

König, Sara; Banitz, Thomas; Centler, Florian; Frank, Karin; Thullner, Martin

2015-04-01

Microbial life in soil is exposed to fluctuating environmental conditions influencing the performance of microbially mediated ecosystem services such as biodegradation of contaminants. However, as this environment is typically very heterogeneous, spatial aspects can be expected to play a major role for the ability to recover from a stress event. To determine key processes for functional resilience, simple scenarios with varying stress intensities were simulated within a microbial simulation model and the biodegradation rate in the recovery phase monitored. Parameters including microbial growth and dispersal rates were varied over a typical range to consider microorganisms with varying properties. Besides an aggregated temporal monitoring, the explicit observation of the spatio-temporal dynamics proved essential to understand the recovery process. For a mechanistic understanding of the model system, scenarios were also simulated with selected processes being switched-off. Results of the mechanistic and the spatial view show that the key factors for functional recovery with respect to biodegradation after a simple stress event depend on the location of the observed habitats. The limiting factors near unstressed areas are spatial processes - the mobility of the bacteria as well as substrate diffusion - the longer the distance to the unstressed region the more important becomes the process growth. Furthermore, recovery depends on the stress intensity - after a low stress event the spatial configuration has no influence on the key factors for functional resilience. To confirm these results, we repeated the stress scenarios but this time including an additional dispersal network representing a fungal network in soil. The system benefits from an increased spatial performance due to the higher mobility of the degrading microorganisms. However, this effect appears only in scenarios where the spatial distribution of the stressed area plays a role. With these simulations we show that spatial aspects play a main role for recovering after a severe stress event in a highly heterogeneous environment such as soil, and thus the relevance of the exact distribution of the stressed area. In consequence a spatial-mechanistic view is necessary for examining the functional resilience as the aggregated temporal view alone could not have led to these conclusions. Further research should explore the importance of a spatial view for quantifying the recovery of the ecosystem service also after more complex stress regimes.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

PubMed

Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

PubMed Central

Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. PMID:27227331

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.

Roles for Hedgehog signaling in adult organ homeostasis and repair

PubMed Central

Petrova, Ralitsa; Joyner, Alexandra L.

2014-01-01

The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

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

Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression.

PubMed

Oh, Kyu-Seon; Gottschalk, Rachel A; Lounsbury, Nicolas W; Sun, Jing; Dorrington, Michael G; Baek, Songjoon; Sun, Guangping; Wang, Ze; Krauss, Kathleen S; Milner, Joshua D; Dutta, Bhaskar; Hager, Gordon L; Sung, Myong-Hee; Fraser, Iain D C

2018-06-13

Macrophage activation by bacterial LPS leads to induction of a complex inflammatory gene program dependent on numerous transcription factor families. The transcription factor Ikaros has been shown to play a critical role in lymphoid cell development and differentiation; however, its function in myeloid cells and innate immune responses is less appreciated. Using comprehensive genomic analysis of Ikaros-dependent transcription, DNA binding, and chromatin accessibility, we describe unexpected dual repressor and activator functions for Ikaros in the LPS response of murine macrophages. Consistent with the described function of Ikaros as transcriptional repressor, Ikzf1 -/- macrophages showed enhanced induction for select responses. In contrast, we observed a dramatic defect in expression of many delayed LPS response genes, and chromatin immunoprecipitation sequencing analyses support a key role for Ikaros in sustained NF-κB chromatin binding. Decreased Ikaros expression in Ikzf1 +/- mice and human cells dampens these Ikaros-enhanced inflammatory responses, highlighting the importance of quantitative control of Ikaros protein level for its activator function. In the absence of Ikaros, a constitutively open chromatin state was coincident with dysregulation of LPS-induced chromatin remodeling, gene expression, and cytokine responses. Together, our data suggest a central role for Ikaros in coordinating the complex macrophage transcriptional program in response to pathogen challenge.

The structure and function of Alzheimer's gamma secretase enzyme complex.

PubMed

Krishnaswamy, Sudarsan; Verdile, Giuseppe; Groth, David; Kanyenda, Limbikani; Martins, Ralph N

2009-01-01

The production and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer's disease (AD). A multi-subunit enzyme complex, referred to as gamma (gamma) secretase, plays a pivotal role in the generation of Abeta from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Abeta levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of gamma-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the gamma-secretase enzyme and the effects of inhibiting its activity.

New fronts emerge in the influenza cytokine storm.

PubMed

Guo, Xi-Zhi J; Thomas, Paul G

2017-07-01

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33-amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.

PubMed

Walck-Shannon, Elise; Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig; Cochran, Hunter; Bothfeld, William; Hardin, Jeff

2016-11-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation.

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis

PubMed Central

Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig

2016-01-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation. PMID:27861585

Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway

PubMed Central

Matsunaga, Mayu; Takeda, Taka-aki

2017-01-01

More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review. PMID:29048339

Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

PubMed

Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

2017-10-19

More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

Role of calcium permeable channels in dendritic cell migration.

PubMed

Sáez, Pablo J; Sáez, Juan C; Lennon-Duménil, Ana-María; Vargas, Pablo

2018-06-01

Calcium ion (Ca 2+ ) is an essential second messenger involved in multiple cellular and subcellular processes. Ca 2+ can be released and sensed globally or locally within cells, providing complex signals of variable amplitudes and time-scales. The key function of Ca 2+ in the regulation of acto-myosin contractility has provided a simple explanation for its role in the regulation of immune cell migration. However, many questions remain, including the identity of the Ca 2+ stores, channels and upstream signals involved in this process. Here, we focus on dendritic cells (DCs), because their immune sentinel function heavily relies on their capacity to migrate within tissues and later on between tissues and lymphoid organs. Deciphering the mechanisms by which cytoplasmic Ca 2+ regulate DC migration should shed light on their role in initiating and tuning immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

PubMed

Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

2014-09-01

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

Brain glucose sensing, glucokinase and neural control of metabolism and islet function

PubMed Central

Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

2014-01-01

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel – emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. PMID:25200293

Hox Genes: Choreographers in Neural Development, Architects of Circuit Organization

PubMed Central

Philippidou, Polyxeni; Dasen, Jeremy S.

2013-01-01

Summary The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This review highlights the functions and mechanisms of Hox gene networks, and their multifaceted roles during neuronal specification and connectivity. PMID:24094100

Role of Intermediate Filaments in Vesicular Traffic.

PubMed

Margiotta, Azzurra; Bucci, Cecilia

2016-04-25

Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, such as the organization of microtubules and microfilaments, the regulation of nuclear structure and activity, the control of cell cycle and the regulation of signal transduction pathways. Furthermore, a number of intermediate filament proteins have been involved in the acquisition of tumorigenic properties. Over the last years, a strong involvement of intermediate filament proteins in the regulation of several aspects of intracellular trafficking has strongly emerged. Here, we review the functions of intermediate filaments proteins focusing mainly on the recent knowledge gained from the discovery that intermediate filaments associate with key proteins of the vesicular membrane transport machinery. In particular, we analyze the current understanding of the contribution of intermediate filaments to the endocytic pathway.

MOR23 promotes muscle regeneration and regulates cell adhesion and migration

PubMed Central

Griffin, Christine A.; Kafadar, Kimberly A.; Pavlath, Grace K.

2009-01-01

Summary Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and muscle tissue in vivo. MOR23 is necessary for proper skeletal muscle regeneration as loss of MOR23 leads to increased myofiber branching, commonly associated with muscular dystrophy. Together these data identify a functional role for an OR outside of the nose and suggest a larger role for ORs during tissue repair. PMID:19922870

Thioredoxin: a key regulator of cardiovascular homeostasis.

PubMed

Yamawaki, Hideyuki; Haendeler, Judith; Berk, Bradford C

2003-11-28

The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The oxidation mechanism for disease pathogenesis states that an imbalance in cell redox state alters function of multiple cell pathways. In this study, we review the essential role for TRX to limit oxidative stress directly via antioxidant effects and indirectly by protein-protein interaction with key signaling molecules, such as apoptosis signal-regulating kinase 1. We propose that TRX and its endogenous regulators are important future targets to develop clinical therapies for cardiovascular disorders associated with oxidative stress.

Creatine as a booster for human brain function. How might it work?

PubMed

Rae, Caroline D; Bröer, Stefan

2015-10-01

Creatine, a naturally occurring nitrogenous organic acid found in animal tissues, has been found to play key roles in the brain including buffering energy supply, improving mitochondrial efficiency, directly acting as an anti-oxidant and acting as a neuroprotectant. Much of the evidence for these roles has been established in vitro or in pre-clinical studies. Here, we examine the roles of creatine and explore the current status of translation of this research into use in humans and the clinic. Some further possibilities for use of creatine in humans are also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of regulatory T cell in the pathogenesis of inflammatory bowel disease.

PubMed

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Tsunematsu, Takaaki; Kudo, Yasusei; Ishimaru, Naozumi

2016-02-21

Regulatory T (Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports.

LEAFY blossoms.

PubMed

Moyroud, Edwige; Kusters, Elske; Monniaux, Marie; Koes, Ronald; Parcy, François

2010-06-01

The LEAFY (LFY) gene of Arabidopsis and its homologs in other angiosperms encode a unique plant-specific transcription factor that assigns the floral fate of meristems and plays a key role in the patterning of flowers, probably since the origin of flowering plants. LFY-like genes are also found in gymnosperms, ferns and mosses that do not produce flowers, but their role in these plants is poorly understood. Here, we review recent findings explaining how the LFY protein works and how it could have evolved throughout land plant history. We propose that LFY homologs have an ancestral role in regulating cell division and arrangement, and acquired novel functions in seed plants, such as activating reproductive gene networks.

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 religious involvement and spirituality in functioning among African Americans with cancer: testing a mediational model

PubMed Central

Holt, Cheryl L.; Wang, Min Qi; Caplan, Lee; Schulz, Emily; Blake, Victor; Southward, Vivian L.

2013-01-01

The present study tested a mediational model of the role of religious involvement, spirituality, and physical/emotional functioning in a sample of African American men and women with cancer. Several mediators were proposed based on theory and previous research, including sense of meaning, positive and negative affect, and positive and negative religious coping. One hundred patients were recruited through oncologist offices, key community leaders and community organizations, and interviewed by telephone. Participants completed an established measure of religious involvement, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP-12 version 4), the Positive and Negative Affect Schedule (PANAS), the Meaning in Life Scale, the Brief RCOPE, and the SF-12, which assesses physical and emotional functioning. Positive affect completely mediated the relationship between religious behaviors and emotional functioning. Though several other constructs showed relationships with study variables, evidence of mediation was not supported. Mediational models were not significant for the physical functioning outcome, nor were there significant main effects of religious involvement or spirituality for this outcome. Implications for cancer survivorship interventions are discussed. PMID:21222026

The Impact of Reproductive Technologies on Stallion Mitochondrial Function.

PubMed

Peña, F J; Plaza Davila, M; Ball, B A; Squires, E L; Martin Muñoz, P; Ortega Ferrusola, C; Balao da Silva, C

2015-08-01

The traditional assessment of stallion sperm comprises evaluation of sperm motility and membrane integrity and identification of abnormal morphology of the spermatozoa. More recently, the progressive introduction of flow cytometry is increasing the number of tests available. However, compared with other sperm structures and functions, the evaluation of mitochondria has received less attention in stallion andrology. Recent research indicates that sperm mitochondria are key structures in sperm function suffering major changes during biotechnological procedures such as cryopreservation. In this paper, mitochondrial structure and function will be reviewed in the stallion, when possible specific stallion studies will be discussed, and general findings on mammalian mitochondrial function will be argued when relevant. Especial emphasis will be put on their role as source of reactive oxygen species and in their role regulating sperm lifespan, a possible target to investigate with the aim to improve the quality of frozen-thawed stallion sperm. Later on, the impact of current sperm technologies, principally cryopreservation, on mitochondrial function will be discussed pointing out novel areas of research interest with high potential to improve current sperm technologies. © 2015 Blackwell Verlag GmbH.

HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes.

PubMed

Morero, Natalia R; Botti, Horacio; Nitta, Kazuhiro R; Carrión, Federico; Obal, Gonzalo; Picardeau, Mathieu; Buschiazzo, Alejandro

2014-10-01

Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO - haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role. © 2014 John Wiley & Sons Ltd.

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

Heterogeneity of signal transduction by Na-K-ATPase α-isoforms: role of Src interaction.

PubMed

Yu, Hui; Cui, Xiaoyu; Zhang, Jue; Xie, Joe X; Banerjee, Moumita; Pierre, Sandrine V; Xie, Zijian

2018-02-01

Of the four Na-K-ATPase α-isoforms, the ubiquitous α1 Na-K-ATPase possesses both ion transport and Src-dependent signaling functions. Mechanistically, we have identified two putative pairs of domain interactions between α1 Na-K-ATPase and Src that are critical for α1 signaling function. Our subsequent report that α2 Na-K-ATPase lacks these putative Src-binding sites and fails to carry on Src-dependent signaling further supported our proposed model of direct interaction between α1 Na-K-ATPase and Src but fell short of providing evidence for a causative role. This hypothesis was specifically tested here by introducing key residues of the two putative Src-interacting domains present on α1 but not α2 sequence into the α2 polypeptide, generating stable cell lines expressing this mutant, and comparing its signaling properties to those of α2-expressing cells. The mutant α2 was fully functional as a Na-K-ATPase. In contrast to wild-type α2, the mutant gained α1-like signaling function, capable of Src interaction and regulation. Consistently, the expression of mutant α2 redistributed Src into caveolin-1-enriched fractions and allowed ouabain to activate Src-mediated signaling cascades, unlike wild-type α2 cells. Finally, mutant α2 cells exhibited a growth phenotype similar to that of the α1 cells and proliferated much faster than wild-type α2 cells. These findings reveal the structural requirements for the Na-K-ATPase to function as a Src-dependent receptor and provide strong evidence of isoform-specific Src interaction involving the identified key amino acids. The sequences surrounding the putative Src-binding sites in α2 are highly conserved across species, suggesting that the lack of Src binding may play a physiologically important and isoform-specific role.

Maintaining Balance: The Increasing Role of Energy Storage for Renewable Integration

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

Stenclik, Derek; Denholm, Paul; Chalamala, Babu

For nearly a century, global power systems have focused on three key functions: to generate, transmit, and distribute electricity as a real-time commodity. Physics requires that electricity generation always be in real-time balance with load, despite variability in load on timescales ranging from sub-second disturbances to multi-year trends. With the increasing role of variable generation from wind and solar, retirements of fossil fuel-based generation, and a changing consumer demand profile, grid operators are using new methods to maintain this balance.

Skin immune sentinels in health and disease

PubMed Central

Nestle, Frank O.; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J.

2010-01-01

Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103+ dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease. PMID:19763149

Skin immune sentinels in health and disease.

PubMed

Nestle, Frank O; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J

2009-10-01

Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.

Osteoblast role in osteoarthritis pathogenesis.

PubMed

Maruotti, Nicola; Corrado, Addolorata; Cantatore, Francesco P

2017-11-01

Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Arginine Methylation: The Coming of Age.

PubMed

Blanc, Roméo S; Richard, Stéphane

2017-01-05

Arginine methylation is a common post-translational modification functioning as an epigenetic regulator of transcription and playing key roles in pre-mRNA splicing, DNA damage signaling, mRNA translation, cell signaling, and cell fate decision. Recently, a wealth of studies using transgenic mouse models and selective PRMT inhibitors helped define physiological roles for protein arginine methyltransferases (PRMTs) linking them to diseases such as cancer and metabolic, neurodegenerative, and muscular disorders. This review describes the recent molecular advances that have been uncovered in normal and diseased mammalian cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Maintaining Balance: The Increasing Role of Energy Storage for Renewable Integration

DOE PAGES

Stenclik, Derek; Denholm, Paul; Chalamala, Babu

2017-10-17

For nearly a century, global power systems have focused on three key functions: to generate, transmit, and distribute electricity as a real-time commodity. Physics requires that electricity generation always be in real-time balance with load, despite variability in load on timescales ranging from sub-second disturbances to multi-year trends. With the increasing role of variable generation from wind and solar, retirements of fossil fuel-based generation, and a changing consumer demand profile, grid operators are using new methods to maintain this balance.

Food security in older adults: community service provider perceptions of their roles.

PubMed

Keller, Heather H; Dwyer, John J M; Edwards, Vicki; Senson, Christine; Gayle Edward, H

2007-01-01

Food insecurity in older adults is influenced by financial constraints, functional disability, and isolation. Twenty-eight social- and community-service providers participated in four focus groups to report (a) perceptions and experiences with food insecurity in their older clients, (b) beliefs about their potential role(s) in promoting food security, and (c) opinions about constraints that influenced these roles. A constant comparison analysis identified key themes. The formal caregivers reported six roles for improving food security: (a) monitoring, (b) coordination, and (c) promoting services, (d) education, (e) advocacy, and (f) providing a social environment. The final theme summarizes these roles as "the need for personalization of service". Social and community service providers are involved in roles that can promote the health of older adults by addressing their food insecurity. Social service providers need to be acknowledged and supported in this health promotion role.

Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?

PubMed

Mannon, Roslyn B

2012-02-01

Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury, while more recent studies indicate that they may play a reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid-organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage-mediated injury, explore their potential reparative role, and determine if they or their functional products are biomarkers of poor graft outcomes.

Development of an operational manual for a consultation-liaison psychiatry service.

PubMed

Wand, Anne Pf; Sharma, Swapnil; Carpenter, Lindsay J; Gatsi, Mike

2018-02-01

Consultation-liaison psychiatry (CLP) services sit between mental health and the general hospital, and risk being poorly understood by both systems. The aim of this study was to develop an operational manual for a CLP service, which defined functions and governance. The CLP literature was reviewed with a focus on descriptions of CLP roles, organisational processes, quality measures and service development. The CLP team held service planning meetings and met with members of the mental health and hospital executives. Site visits and collaboration with other CLP services occurred in defining the roles of the CLP service and organisational governance. A CLP operational document was developed, including a description of the service, its functions, staff roles and governance. Procedural information such as the CLP timetable, referral process, triage and assessment, documentation, activity recording, quality assurance and relevant policies were outlined. The development of a dedicated operational manual for CLP clarified the roles, functions and governance of CLP within the general hospital and mental health systems. The development process facilitated the engagement of key clinicians and administrators of these systems, the determination of quality improvement targets and greater transparency and accountability.

Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

PubMed

Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

2012-02-26

The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

Inhibition of platelet activation by lachrymatory factor synthase (LFS)-silenced (tearless) onion juice.

PubMed

Thomson, Susan J; Rippon, Paula; Butts, Chrissie; Olsen, Sarah; Shaw, Martin; Joyce, Nigel I; Eady, Colin C

2013-11-06

Onion and garlic are renowned for their roles as functional foods. The health benefits of garlic are attributed to di-2-propenyl thiosulfinate (allicin), a sulfur compound found in disrupted garlic but not found in disrupted onion. Recently, onions have been grown with repressed lachrymatory factor synthase (LFS) activity, which causes these onions to produce increased amounts of di-1-propenyl thiosulfinate, an isomer of allicin. This investigation into the key health attributes of LFS-silenced (tearless) onions demonstrates that they have some attributes more similar to garlic and that this is likely due to the production of novel thiosulfinate or metabolites. The key finding was that collagen-induced in vitro platelet aggregation was significantly reduced by tearless onion extract over normal onion extract. Thiosulfinate or derived compounds were shown not to be responsible for the observed changes in the inflammatory response of AGS (stomach adenocarcinoma) cells to tumor necrosis factor alpha (TNFα) when pretreated with model onion juices. A preliminary rat feeding trial indicated that the tearless onions may also play a key role in reducing weight gain.

Elucidating the Key Role of a Lewis Base Solvent in the Formation of Perovskite Films Fabricated from the Lewis Adduct Approach.

PubMed

Cao, Xiaobing; Zhi, Lili; Li, Yahui; Fang, Fei; Cui, Xian; Yao, Youwei; Ci, Lijie; Ding, Kongxian; Wei, Jinquan

2017-09-27

High-quality perovskite films can be fabricated from Lewis acid-base adducts through molecule exchange. Substantial work is needed to fully understand the formation mechanism of the perovskite films, which helps to further improve their quality. Here, we study the formation of CH 3 NH 3 PbI 3 perovskite films by introducing some dimethylacetamide into the PbI 2 /N,N-dimethylformamide solution. We reveal that there are three key processes during the formation of perovskite films through the Lewis acid-base adduct approach: molecule intercalation of solvent into the PbI 2 lattice, molecule exchange between the solvent and CH 3 NH 3 I, and dissolution-recrystallization of the perovskite grains during annealing. The Lewis base solvents play multiple functions in the above processes. The properties of the solvent, including Lewis basicity and boiling point, play key roles in forming smooth perovskite films with large grains. We also provide some rules for choosing Lewis base additives to prepare high-quality perovskite films through the Lewis adduct approach.

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.

P21 and p27: roles in carcinogenesis and drug resistance.

PubMed

Abukhdeir, Abde M; Park, Ben Ho

2008-07-01

Human cancers arise from an imbalance of cell growth and cell death. Key proteins that govern this balance are those that mediate the cell cycle. Several different molecular effectors have been identified that tightly regulate specific phases of the cell cycle, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors. Notably, loss of expression or function of two G1-checkpoint CDK inhibitors - p21 (CDKN1A) and p27 (CDKN1B) - has been implicated in the genesis or progression of many human malignancies. Additionally, there is a growing body of evidence suggesting that functional loss of p21 or p27 can mediate a drug-resistance phenotype. However, reports in the literature have also suggested p21 and p27 can promote tumours, indicating a paradoxical effect. Here, we review historic and recent studies of these two CDK inhibitors, including their identification, function, importance to carcinogenesis and finally their roles in drug resistance.

Functional Diversity of the Schistosoma mansoni Tyrosine Kinases

PubMed Central

Avelar, Lívia G. A.; Nahum, Laila A.; Andrade, Luiza F.; Oliveira, Guilherme

2011-01-01

Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs. PMID:21776387

The role of endothelial cells on islet function and revascularization after islet transplantation.

PubMed

Del Toro-Arreola, Alicia; Robles-Murillo, Ana Karina; Daneri-Navarro, Adrian; Rivas-Carrillo, Jorge David

2016-01-02

Islet transplantation has become a widely accepted therapeutic option for selected patients with type 1 diabetes mellitus. However, in order to achieve insulin independence a great number of islets are often pooled from 2 to 4 pancreata donors. Mostly, it is due to the massive loss of islets immediately after transplant. The endothelium plays a key role in the function of native islets and during the revascularization process after islet transplantation. However, if a delayed revascularization occurs, even the remaining islets will also undergo to cell death and late graft dysfunction. Therefore, it is essential to understand how the signals are released from endothelial cells, which might regulate both differentiation of pancreatic progenitors and thereby maintenance of the graft function. New strategies to facilitate islet engraftment and a prompt revascularization could be designed to intervene and might lead to improve future results of islet transplantation.

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

Myosin motor function: the ins and outs of actin-based membrane protrusions

PubMed Central

Nambiar, Rajalakshmi; McConnell, Russell E.

2011-01-01

Cells build plasma membrane protrusions supported by parallel bundles of F-actin to enable a wide variety of biological functions, ranging from motility to host defense. Filopodia, microvilli and stereocilia are three such protrusions that have been the focus of intense biological and biophysical investigation in recent years. While it is evident that actin dynamics play a significant role in the formation of these organelles, members of the myosin superfamily have also been implicated as key players in the maintenance of protrusion architecture and function. Based on a simple analysis of the physical forces that control protrusion formation and morphology, as well as our review of available data, we propose that myosins play two general roles within these structures: (1) as cargo transporters to move critical regulatory components toward distal tips and (2) as mediators of membrane-cytoskeleton adhesion. PMID:20107861

Myostatin-like proteins regulate synaptic function and neuronal morphology.

PubMed

Augustin, Hrvoje; McGourty, Kieran; Steinert, Joern R; Cochemé, Helena M; Adcott, Jennifer; Cabecinha, Melissa; Vincent, Alec; Halff, Els F; Kittler, Josef T; Boucrot, Emmanuel; Partridge, Linda

2017-07-01

Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth. © 2017. Published by The Company of Biologists Ltd.

Epigenetic mechanisms in memory and synaptic function

PubMed Central

Sultan, Faraz A; Day, Jeremy J

2011-01-01

Although the term ‘epigenetics’ was coined nearly seventy years ago, its critical function in memory processing by the adult CNS has only recently been appreciated. The hypothesis that epigenetic mechanisms regulate memory and behavior was motivated by the need for stable molecular processes that evade turnover of the neuronal proteome. In this article, we discuss evidence that supports a role for neural epigenetic modifications in the formation, consolidation and storage of memory. In addition, we will review the evidence that epigenetic mechanisms regulate synaptic plasticity, a cellular correlate of memory. We will also examine how the concerted action of multiple epigenetic mechanisms with varying spatiotemporal profiles influence selective gene expression in response to behavioral experience. Finally, we will suggest key areas for future research that will help elucidate the complex, vital and still mysterious, role of epigenetic mechanisms in neural function and behavior. PMID:22122279

The Role of Civil Society Organizations in Monitoring the Global AIDS Response.

PubMed

Smith, Julia; Mallouris, Christoforos; Lee, Kelley; Alfvén, Tobias

2017-07-01

Civil society organizations (CSOs) are recognized as playing an exceptional role in the global AIDS response. However, there is little detailed research to date on how they contribute to specific governance functions. This article uses Haas' framework on global governance functions to map CSO's participation in the monitoring of global commitments to the AIDS response by institutions and states. Drawing on key informant interviews and primary documents, it focuses specifically on CSO participation in Global AIDS Response Progress Reporting and in Global Fund to Fight AIDS, Tuberculosis and Malaria processes. It argues that the AIDS response is unique within global health governance, in that CSOs fulfill both formal and informal monitoring functions, and considers the strengths and weaknesses of these contributions. It concludes that future global health governance arrangements should include provisions and resources for monitoring by CSOs because their participation creates more inclusive global health governance and contributes to strengthening commitments to human rights.

The Extracellular δ-Domain is Essential for the Formation of CD81 Tetraspanin Webs

PubMed Central

Homsi, Yahya; Schloetel, Jan-Gero; Scheffer, Konstanze D.; Schmidt, Thomas H.; Destainville, Nicolas; Florin, Luise; Lang, Thorsten

2014-01-01

CD81 is a ubiquitously expressed member of the tetraspanin family. It forms large molecular platforms, so-called tetraspanin webs that play physiological roles in a variety of cellular functions and are involved in viral and parasite infections. We have investigated which part of the CD81 molecule is required for the formation of domains in the cell membranes of T-cells and hepatocytes. Surprisingly, we find that large CD81 platforms assemble via the short extracellular δ-domain, independent from a strong primary partner binding and from weak interactions mediated by palmitoylation. The δ-domain is also essential for the platforms to function during viral entry. We propose that, instead of stable binary interactions, CD81 interactions via the small δ-domain, possibly involving a dimerization step, play the key role in organizing CD81 into large tetraspanin webs and controlling its function. PMID:24988345

Kidneys: Key Modulators of HDL Levels and Function

PubMed Central

Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

2016-01-01

Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

**1**5N-NMR INVESTIGATION OF HYDROXYLAMINE DERIVATIZED HUMIC SUBSTANCES.

USGS Publications Warehouse

Thorn, Kevin A.; Arterburn, Jeffrey B.; Mikita, Michael A.

1986-01-01

Humic substances are the most abundant naturally occurring refactory organic compounds in soils and water. They have a broad range of physical, chemical and physiological properties. In soils, humic substances contribute to the cation exchange capacity, help maintain the physical structure, and play a role in plant growth and nutrition. In aquatic systems, humic substances serve to regulate the levels of inorganic constituents, yield trihalomethanes upon chlorination, and transport or concentrate organic and inorganic pollutants. The oxygen containing functional groups of humic and fulvic acids are believed to play a key role in the chemical properties of humic substances. This study was undertaken to gain additional information on the specific types of oxygen functionalities in humic substances. Since the analysis of hydroxyl moieties had been earlier established, we focused our attention on the analysis of ketone and aldehyde functional groups in humic substances.

'The ones that turn up are the ones that are responsible': Key stakeholders perspectives on liquor accords.

PubMed

Curtis, Ashlee; Miller, Peter; Droste, Nicolas; McFarlane, Emma; Martino, Florentine; Palmer, Darren

2016-05-01

Liquor accords were introduced as an intervention to reduce alcohol-related harm in and around licensed venues. There have been very few evaluations of the accords, made all the more difficult given the multitude of measures that are often implemented under their banner. This study provides perspectives on the effectiveness of the liquor accords from key stakeholders who were involved in the strategy. In-depth interviews were conducted with 97 key stakeholders as part of a larger study, of which 46 spoke about the effectiveness of liquor accords. Responses were analysed using thematic analysis. Stakeholders reported the greatest benefit of liquor accords to be their ability to improve communication. Many stakeholders recognised the need for mandatory attendance and discussed whether the accords are a waste of time of resources. Stakeholders did not generally view liquor accords as effective means of reducing alcohol-related harm. There was a lack of positive feedback about liquor accords provided by stakeholders, indicating a clear need to better understand the role of liquor accords, and what they aim to achieve. Responsive regulation theory suggests that the dual roles of communication and intervention are confused, leading to some of the inherent problems with accords. The role and aims of liquor accords need to be clearly defined. The findings suggest that separating the communication and regulatory functions from accords will lead to a clearer role for accords, and interventions and regulation might be better placed in the hands of regulators and enforcement. [Curtis A, Miller P, Droste N, McFarlane E, Martino F, Palmer D. 'The ones that turn up are the ones that are responsible': Key stakeholders perspectives on liquor accords. Drug Alcohol Rev 2016;35:273-279]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Physiological roles of taurine in heart and muscle

PubMed Central

2010-01-01

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals. PMID:20804594

Physiological roles of taurine in heart and muscle.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ramila, K C; Azuma, Junichi

2010-08-24

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals.

Plant diversity and root traits benefit physical properties key to soil function in grasslands.

PubMed

Gould, Iain J; Quinton, John N; Weigelt, Alexandra; De Deyn, Gerlinde B; Bardgett, Richard D

2016-09-01

Plant diversity loss impairs ecosystem functioning, including important effects on soil. Most studies that have explored plant diversity effects belowground, however, have largely focused on biological processes. As such, our understanding of how plant diversity impacts the soil physical environment remains limited, despite the fundamental role soil physical structure plays in ensuring soil function and ecosystem service provision. Here, in both a glasshouse and a long-term field study, we show that high plant diversity in grassland systems increases soil aggregate stability, a vital structural property of soil, and that root traits play a major role in determining diversity effects. We also reveal that the presence of particular plant species within mixed communities affects an even wider range of soil physical processes, including hydrology and soil strength regimes. Our results indicate that alongside well-documented effects on ecosystem functioning, plant diversity and root traits also benefit essential soil physical properties. © 2016 The Authors Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration

PubMed Central

Sumagin, Ronen; Parkos, Charles A

2014-01-01

Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function. PMID:25838976

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

PubMed Central

2016-01-01

Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease. PMID:27742732

Volition and conflict in human medial frontal cortex.

PubMed

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2005-01-26

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

AlloRep: A Repository of Sequence, Structural and Mutagenesis Data for the LacI/GalR Transcription Regulators.

PubMed

Sousa, Filipa L; Parente, Daniel J; Shis, David L; Hessman, Jacob A; Chazelle, Allen; Bennett, Matthew R; Teichmann, Sarah A; Swint-Kruse, Liskin

2016-02-22

Protein families evolve functional variation by accumulating point mutations at functionally important amino acid positions. Homologs in the LacI/GalR family of transcription regulators have evolved to bind diverse DNA sequences and allosteric regulatory molecules. In addition to playing key roles in bacterial metabolism, these proteins have been widely used as a model family for benchmarking structural and functional prediction algorithms. We have collected manually curated sequence alignments for >3000 sequences, in vivo phenotypic and biochemical data for >5750 LacI/GalR mutational variants, and noncovalent residue contact networks for 65 LacI/GalR homolog structures. Using this rich data resource, we compared the noncovalent residue contact networks of the LacI/GalR subfamilies to design and experimentally validate an allosteric mutant of a synthetic LacI/GalR repressor for use in biotechnology. The AlloRep database (freely available at www.AlloRep.org) is a key resource for future evolutionary studies of LacI/GalR homologs and for benchmarking computational predictions of functional change. Copyright © 2015 Elsevier Ltd. All rights reserved.

The notochord: structure and functions.

PubMed

Corallo, Diana; Trapani, Valeria; Bonaldo, Paolo

2015-08-01

The notochord is an embryonic midline structure common to all members of the phylum Chordata, providing both mechanical and signaling cues to the developing embryo. In vertebrates, the notochord arises from the dorsal organizer and it is critical for proper vertebrate development. This evolutionary conserved structure located at the developing midline defines the primitive axis of embryos and represents the structural element essential for locomotion. Besides its primary structural function, the notochord is also a source of developmental signals that patterns surrounding tissues. Among the signals secreted by the notochord, Hedgehog proteins play key roles during embryogenesis. The Hedgehog signaling pathway is a central regulator of embryonic development, controlling the patterning and proliferation of a wide variety of organs. In this review, we summarize the current knowledge on notochord structure and functions, with a particular emphasis on the key developmental events that take place in vertebrates. Moreover, we discuss some genetic studies highlighting the phenotypic consequences of impaired notochord development, which enabled to understand the molecular basis of different human congenital defects and diseases.

The Research and Implementation of Vehicle Bluetooth Hands-free Devices Key Parameters Downloading Algorithm

NASA Astrophysics Data System (ADS)

Zhang, Xiao-bo; Wang, Zhi-xue; Li, Jian-xin; Ma, Jian-hui; Li, Yang; Li, Yan-qiang

In order to facilitate Bluetooth function realization and information can be effectively tracked in the process of production, the vehicle Bluetooth hands-free devices need to download such key parameters as Bluetooth address, CVC license and base plate numbers, etc. Therefore, it is the aim to search simple and effective methods to download parameters for each vehicle Bluetooth hands-free device, and to control and record the use of parameters. In this paper, by means of Bluetooth Serial Peripheral Interface programmer device, the parallel port is switched to SPI. The first step is to download parameters is simulating SPI with the parallel port. To perform SPI function, operating the parallel port in accordance with the SPI timing. The next step is to achieve SPI data transceiver functions according to the programming parameters of options. Utilizing the new method, downloading parameters is fast and accurate. It fully meets vehicle Bluetooth hands-free devices production requirements. In the production line, it has played a large role.

Evolution of egg coats: linking molecular biology and ecology.

PubMed

Shu, Longfei; Suter, Marc J-F; Räsänen, Katja

2015-08-01

One central goal of evolutionary biology is to explain how biological diversity emerges and is maintained in nature. Given the complexity of the phenotype and the multifaceted nature of inheritance, modern evolutionary ecological studies rely heavily on the use of molecular tools. Here, we show how molecular tools help to gain insight into the role of egg coats (i.e. the extracellular structures surrounding eggs and embryos) in evolutionary diversification. Egg coats are maternally derived structures that have many biological functions from mediating fertilization to protecting the embryo from environmental hazards. They show great molecular, structural and functional diversity across species, but intraspecific variability and the role of ecology in egg coat evolution have largely been overlooked. Given that much of the variation that influences egg coat function is ultimately determined by their molecular phenotype, cutting-edge molecular tools (e.g. proteomics, glycomics and transcriptomics), combined with functional assays, are needed for rigorous inferences on their evolutionary ecology. Here, we identify key research areas and highlight emerging molecular techniques that can increase our understanding of the role of egg coats in the evolution of biological diversity, from adaptation to speciation. © 2015 John Wiley & Sons Ltd.

Rarity in aquatic microbes: placing protists on the map.

PubMed

Logares, Ramiro; Mangot, Jean-François; Massana, Ramon

2015-12-01

Most microbial richness at any given time tends to be represented by low-abundance (rare) taxa, which are collectively referred to as the "rare biosphere". Here we review works on the rare biosphere using high-throughput sequencing (HTS), with a particular focus on unicellular eukaryotes or protists. Evidence thus far indicates that the rare biosphere encompasses dormant as well as metabolically active microbes that could potentially play key roles in ecosystem functioning. Rare microbes appear to have biogeography, and sometimes the observed patterns can be similar to what is observed among abundant taxa, suggesting similar community-structuring mechanisms. There is limited evidence indicating that the rare biosphere contains taxa that are phylogenetically distantly related to abundant counterparts; therefore, the rare biosphere may act as a reservoir of deep-branching phylogenetic diversity. The potential role of the rare biosphere as a bank of redundant functions that can help to maintain continuous ecosystem function following oscillations in taxonomic abundances is hypothesized as its main ecological role. Future studies focusing on rare microbes are crucial for advancing our knowledge of microbial ecology and evolution and unveiling their links with ecosystem function. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Available nitrogen is the key factor influencing soil microbial functional gene diversity in tropical rainforest.

PubMed

Cong, Jing; Liu, Xueduan; Lu, Hui; Xu, Han; Li, Yide; Deng, Ye; Li, Diqiang; Zhang, Yuguang

2015-08-20

Tropical rainforests cover over 50% of all known plant and animal species and provide a variety of key resources and ecosystem services to humans, largely mediated by metabolic activities of soil microbial communities. A deep analysis of soil microbial communities and their roles in ecological processes would improve our understanding on biogeochemical elemental cycles. However, soil microbial functional gene diversity in tropical rainforests and causative factors remain unclear. GeoChip, contained almost all of the key functional genes related to biogeochemical cycles, could be used as a specific and sensitive tool for studying microbial gene diversity and metabolic potential. In this study, soil microbial functional gene diversity in tropical rainforest was analyzed by using GeoChip technology. Gene categories detected in the tropical rainforest soils were related to different biogeochemical processes, such as carbon (C), nitrogen (N) and phosphorus (P) cycling. The relative abundance of genes related to C and P cycling detected mostly derived from the cultured bacteria. C degradation gene categories for substrates ranging from labile C to recalcitrant C were all detected, and gene abundances involved in many recalcitrant C degradation gene categories were significantly (P < 0.05) different among three sampling sites. The relative abundance of genes related to N cycling detected was significantly (P < 0.05) different, mostly derived from the uncultured bacteria. The gene categories related to ammonification had a high relative abundance. Both canonical correspondence analysis and multivariate regression tree analysis showed that soil available N was the most correlated with soil microbial functional gene structure. Overall high microbial functional gene diversity and different soil microbial metabolic potential for different biogeochemical processes were considered to exist in tropical rainforest. Soil available N could be the key factor in shaping the soil microbial functional gene structure and metabolic potential.

The ApoE receptors Vldlr and Apoer2 in central nervous system function and disease.

PubMed

Lane-Donovan, Courtney; Herz, Joachim

2017-06-01

The LDL receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of ApoE4, an LDLR ligand, as a genetic risk factor for late-onset Alzheimer's disease has focused attention on the role this receptor family plays in the CNS. Surprisingly, it was discovered that two LDLR family members, ApoE receptor 2 (Apoer2) and VLDL receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling. This review focuses on Apoer2 and Vldlr signaling in the CNS and its role in human disease. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Tansley Review No. 104, Calcium Physiology and Terrestrial Ecosystem Processes

Treesearch

S.B. McLaughlin; R. Wimmer

1999-01-01

Calcium occupies a unique position among plant nutrients both chemically and functionally. Its chemical properties allow it to exist in a wide range of binding states and to serve in both structural and messenger roles. Despite its importance in many plant processes, Ca mobility is low, making Ca uptake and distribution rate a limiting process for many key plant...

Natural variation underlies alterations in NRAT1 expression and function that play a key role in rice aluminum tolerance

USDA-ARS?s Scientific Manuscript database

Aluminum (Al) toxicity is a major constraint for crop production on acid soils which comprise approximately 40% of arable land in the tropics and subtropics. Rice is the most Al tolerant cereal crop, and offers a good model for identifying Al tolerance genes and mechanisms. Here we investigated natu...

Technological Developments in Journalism: The Impact of the Computer in the Newsroom.

ERIC Educational Resources Information Center

Garrison, Bruce

A review of the literature for the past 7 years reveals that the computer serves several key functions in the newsroom. Its more dominant role is in word processing, or internal copy processing regardless of the source of the copy. Computers are also useful in reviewing documents for content analysis, for survey research in public opinion polls…

Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

USDA-ARS?s Scientific Manuscript database

A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta plays key roles in nutrient transport and fetal growth. Placental function is dependent on regulation of ...

Functional response of U.S. grasslands to the early 21st-century drought

Treesearch

M. Susan Moran; Guillermo E. Ponce-Campos; Alfredo Huete; Mitchel P. McClaran; Yongguang Zhang; Erik P. Hamerlynck; David J. Augustine; Stacey A. Gunter; Stanley G. Kitchen; Debra P. C. Peters; Patrick J. Starks; Mariano Hernandez

2014-01-01

Grasslands across the United States play a key role in regional livelihood and national food security. Yet, it is still unclear how this important resource will respond to the prolonged warm droughts and more intense rainfall events predicted with climate change. The early 21st-century drought in the southwestern United States resulted in hydroclimatic conditions that...

Islam, National Identity and Public Secondary Education: Perspectives from the Somali Diaspora in Toronto, Canada

ERIC Educational Resources Information Center

Collet, Bruce A.

2007-01-01

Public schools have historically been key sites where children learn of and adopt a common national identity. In states where multiculturalism plays a central role in the articulation of a national identity, schools actively recognize and support the diverse cultures of their students in fulfilling this function. Canada is a state where, via…

The Brain: Our Sense of Self. The NIH Curriculum Supplement Series

ERIC Educational Resources Information Center

Bascobert, Ric, Ed.

2005-01-01

"The Brain: Our Sense of Self" has several objectives. One is to introduce students to the key concept that the sense of self, our sense of identity, is contained within the brain. Through inquiry-based activities, students investigate brain function and the various roles of the brain within the nervous system. A second objective is to allow…

Deaf Education Policy as Language Policy: A Comparative Analysis of Sweden and the United States

ERIC Educational Resources Information Center

Hult, Francis M.; Compton, Sarah E.

2012-01-01

The role of languages is a central issue in deaf education. The function of sign languages in education and deaf students' opportunities to develop linguistic abilities in both sign languages and the dominant language(s) of a society are key considerations (Hogan-Brun 2009; Reagan 2010, 53; Swanwick 2010a). Accordingly, what Kaplan and Baldauf…

Identifying best practices for audit committees.

PubMed

Burke, J V; Luecke, R W; Meeting, D

1996-06-01

Most healthcare organizations have an audit committee of the governing board, or a finance committee, that fulfills the audit oversight function. Financial managers play a key role in shaping the content, agency, and operation of the audit committee. The findings of a recent research study conducted by Arthur Anderson & Co., SC, into the best practices of audit committees have implications for healthcare organizations.

Certificate Structure Study: Do Stackable Certificates Really "Add" up to a Degree? Research Report 17-2

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2017

2017-01-01

The purpose of this study is to answer key questions about the structure of certificates and their function in employability and degree attainment in the Washington State Community and Technical College (CTC) System. Specifically, this study addresses the following: (1) Do certificates play a role in helping students progress along career pathways…

Do myoepithelial cells hold the key for breast tumorprogression?

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

Polyak, Kornelia; Hu, Min

2005-11-18

Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of themore » mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.« less

Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores.

PubMed

Gómez-Sánchez, Rubén; Rose, Jaqueline; Guimarães, Rodrigo; Mari, Muriel; Papinski, Daniel; Rieter, Ester; Geerts, Willie J; Hardenberg, Ralph; Kraft, Claudine; Ungermann, Christian; Reggiori, Fulvio

2018-05-30

The autophagy-related (Atg) proteins play a key role in the formation of autophagosomes, the hallmark of autophagy. The function of the cluster composed by Atg2, Atg18, and transmembrane Atg9 is completely unknown despite their importance in autophagy. In this study, we provide insights into the molecular role of these proteins by identifying and characterizing Atg2 point mutants impaired in Atg9 binding. We show that Atg2 associates to autophagosomal membranes through lipid binding and independently from Atg9. Its interaction with Atg9, however, is key for Atg2 confinement to the growing phagophore extremities and subsequent association of Atg18. Assembly of the Atg9-Atg2-Atg18 complex is important to establish phagophore-endoplasmic reticulum (ER) contact sites. In turn, disruption of the Atg2-Atg9 interaction leads to an aberrant topological distribution of both Atg2 and ER contact sites on forming phagophores, which severely impairs autophagy. Altogether, our data shed light in the interrelationship between Atg9, Atg2, and Atg18 and highlight the possible functional relevance of the phagophore-ER contact sites in phagophore expansion. © 2018 Gómez-Sánchez et al.

Hairpin Folding of HIV gp41 Abrogates Lipid Mixing Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41 Constructs†

PubMed Central

Sackett, Kelly; Nethercott, Matthew J.; Shai, Yechiel; Weliky, David P.

2009-01-01

Conformational changes in the HIV gp41 protein are directly correlated with fusion between the HIV and target cell plasma membranes which is the initial step of infection. Key gp41 fusion conformations include an early extended conformation termed pre-hairpin which contains exposed regions and a final low energy conformation termed hairpin which has compact six-helix bundle structure. Current fusion models debate the roles of hairpin and pre-hairpin conformations in the process of membrane merger. In the present work, gp41 constructs have been engineered which correspond to fusion relevant parts of both pre-hairpin and hairpin conformations, and have been analyzed for their ability to induce lipid mixing between membrane vesicles. The data correlate membrane fusion function with the pre-hairpin conformation and suggest that one of the roles of the final hairpin conformation is sequestration of membrane perturbing gp41 regions with consequent loss of the membrane disruption induced earlier by the pre-hairpin structure. To our knowledge, this is the first biophysical study to delineate the membrane fusion potential of gp41 constructs modeling key fusion conformations. PMID:19222185

An Alternative Pathway for Formononetin Biosynthesis in Pueraria lobata

PubMed Central

Li, Jia; Li, Changfu; Gou, Junbo; Wang, Xin; Fan, Rongyan; Zhang, Yansheng

2016-01-01

The O-methylation is an important tailing process in Pueraria lobata isoflavone metabolism, but the molecular mechanism governing it remains not elucidated. This manuscript describes the mining of key O-methyltransferases (OMTs) involved in the process. Using our previously constructed P. lobata transcriptome, the OMT candidates were searched, extensively analyzed, and their functions were investigated by expression in yeast, Escherichia coli, or Glycine max hairy roots. Here, we report the identification of the key OMT gene responsible for formononetin production in P. lobata (designated as PlOMT9). PlOMT9 primarily functions as an isoflavone-specific 4′-O-methyltransferase, although it shows high sequence identities with isoflavone 7-O-methyltransferases. Moreover, unlike the previously reported OMTs that catalyze the 4′-O-methylation for formononetin biosynthesis at the isoflavanone stage, PlOMT9 performs this modifying step at the isoflavone level, using daidzein rather than 2,7,4′-trihydroxy-isoflavanone as the substrate. Gene expression analyses and metabolite profiling supported its proposed roles in P. lobata. Using the system of transgenic G. max hairy roots, the role of PlOMT9 in the biosynthesis of formononetin was further demonstrated in vivo. PMID:27379141

An Alternative Pathway for Formononetin Biosynthesis in Pueraria lobata.

PubMed

Li, Jia; Li, Changfu; Gou, Junbo; Wang, Xin; Fan, Rongyan; Zhang, Yansheng

2016-01-01

The O-methylation is an important tailing process in Pueraria lobata isoflavone metabolism, but the molecular mechanism governing it remains not elucidated. This manuscript describes the mining of key O-methyltransferases (OMTs) involved in the process. Using our previously constructed P. lobata transcriptome, the OMT candidates were searched, extensively analyzed, and their functions were investigated by expression in yeast, Escherichia coli, or Glycine max hairy roots. Here, we report the identification of the key OMT gene responsible for formononetin production in P. lobata (designated as PlOMT9). PlOMT9 primarily functions as an isoflavone-specific 4'-O-methyltransferase, although it shows high sequence identities with isoflavone 7-O-methyltransferases. Moreover, unlike the previously reported OMTs that catalyze the 4'-O-methylation for formononetin biosynthesis at the isoflavanone stage, PlOMT9 performs this modifying step at the isoflavone level, using daidzein rather than 2,7,4'-trihydroxy-isoflavanone as the substrate. Gene expression analyses and metabolite profiling supported its proposed roles in P. lobata. Using the system of transgenic G. max hairy roots, the role of PlOMT9 in the biosynthesis of formononetin was further demonstrated in vivo.

Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control

PubMed Central

Zhao, Bin; Wei, Xiaomu; Li, Weiquan; Udan, Ryan S.; Yang, Qian; Kim, Joungmok; Xie, Joe; Ikenoue, Tsuneo; Yu, Jindan; Li, Li; Zheng, Pan; Ye, Keqiang; Chinnaiyan, Arul; Halder, Georg; Lai, Zhi-Chun; Guan, Kun-Liang

2007-01-01

The Hippo pathway plays a key role in organ size control by regulating cell proliferation and apoptosis in Drosophila. Although recent genetic studies have shown that the Hippo pathway is regulated by the NF2 and Fat tumor suppressors, the physiological regulations of this pathway are unknown. Here we show that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway. Phosphorylation by the Lats tumor suppressor kinase leads to cytoplasmic translocation and inactivation of the YAP oncoprotein. Furthermore, attenuation of this phosphorylation of YAP or Yorkie (Yki), the Drosophila homolog of YAP, potentiates their growth-promoting function in vivo. Moreover, YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition. Inhibition of YAP function restores contact inhibition in a human cancer cell line bearing deletion of Salvador (Sav), a Hippo pathway component. Interestingly, we observed that YAP protein is elevated and nuclear localized in some human liver and prostate cancers. Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact. PMID:17974916

Selective distribution and dynamic modulation of miRNAs in the synapse and its possible role in Alzheimer's Disease.

PubMed

Garza-Manero, Sylvia; Pichardo-Casas, Israel; Arias, Clorinda; Vaca, Luis; Zepeda, Angélica

2014-10-10

MicroRNAs (miRNAs) are small non-coding RNAs that control a wide range of functions in the cell. They act as post-transcriptional gene regulators throughout in development and in adulthood, although recent evidence suggests their potential role in the onset and development of various diseases and neuropathologies. In neurons miRNAs seem to play a key role as regulators of synaptic function. Synapses are vulnerable structures in neurodegenerative diseases. In particular, synaptic loss has been described as an early event in the pathogenesis of Alzheimer's Disease (AD). MicroRNA-mediated gene silencing represents a candidate event for the repression of specific mRNAs and protein synthesis that could account for synaptic dysfunction. In this work, we review the participation of miRNAs in synaptic function and consider their possible role in synaptic alterations in AD. First we review the biogenesis of miRNAs and their role as post-transcriptional regulators. Then we discuss recently published data on the distribution of miRNAs in the brain as well as their role in dynamic regulation at the synapse. In the second part, we briefly introduce the reader to AD, focusing on synaptic alterations in the progression of the pathology. Then we discuss possible implications of miRNAs in the associated synaptic dysfunction. Copyright © 2013 Elsevier B.V. All rights reserved.

Emerging roles of post-translational modifications in signal transduction and angiogenesis.

PubMed

Rahimi, Nader; Costello, Catherine E

2015-01-01

The vascular endothelial growth factor receptor-2 (VEGFR-2) belongs to the family of receptor tyrosine kinases and is a key player in vasculogenesis and pathological angiogenesis. An emerging picture of PTMs of VEGFR-2 suggests that they play central roles in generating a highly dynamic and complex signaling system that regulates key angiogenic responses ranging from endothelial cell differentiation, proliferation, migration to permeability. Recent MS analysis of VEGFR-2 uncovered previously unrecognized PTMs on VEGFR-2 with a distinct function. The ligand binding extracellular domain of VEGFR-2 is composed of seven immunoglobulin-like domains highly decorated with N-glycosylation, while its cytoplasmic domain is subject to multiple PTMs including Tyr, Ser/Thr phosphorylation, Arg and Lys methylation, acetylation and ubiquitination. Here we review the PTMs on VEGFR-2, their importance in angiogenic signaling relays and possible novel therapeutic potentials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DFT Study on Nitrite Reduction Mechanism in Copper-Containing Nitrite Reductase.

PubMed

Lintuluoto, Masami; Lintuluoto, Juha M

2016-01-12

Dissimilatory reduction of nitrite by copper-containing nitrite reductase (CuNiR) is an important step in the geobiochemical nitrogen cycle. The proposed mechanisms for the reduction of nitrite by CuNiRs include intramolecular electron and proton transfers, and these two events are understood to couple. Proton-coupled electron transfer is one of the key processes in enzyme reactions. We investigated the geometric structure of bound nitrite and the mechanism of nitrite reduction on CuNiR using density functional theory calculations. Also, the proton transfer pathway, the key residues, and their roles in the reaction mechanism were clarified in this study. In our results, the reduction of T2 Cu site promotes the proton transfer, and the hydrogen bond network around the binding site has an important role not only to stabilize the nitrite binding but also to promote the proton transfer to nitrite.

microRNA in Human Reproduction.

PubMed

Eisenberg, Iris; Kotaja, Noora; Goldman-Wohl, Debra; Imbar, Tal

2015-01-01

microRNAs constitute a large family of approximately 21-nucleotide-long, noncoding RNAs. They emerged more than 20 years ago as key posttranscriptional regulators of gene expression. The regulatory role of these small RNA molecules has recently begun to be explored in the human reproductive system. microRNAs have been shown to play an important role in control of reproductive functions, especially in the processes of oocyte maturation, folliculogenesis, corpus luteum function, implantation, and early embryonic development. Knockout of Dicer, the cytoplasmic enzyme that cleaves the pre-miRNA to its mature form, results in postimplantation embryonic lethality in several animal models, attributing to these small RNA vital functions in reproduction and development. Another intriguing characteristic of microRNAs is their presence in body fluids in a remarkably stable form that is protected from endogenous RNase activity. In this chapter we will describe the current knowledge on microRNAs, specifically relating to human gonadal cells. We will focus on their role in the ovarian physiologic process and ovulation dysfunction, regulation of spermatogenesis and male fertility, and putative involvement in human normal and aberrant trophoblast differentiation and invasion through the process of placentation.

DNA methylation in insects: on the brink of the epigenomic era.

PubMed

Glastad, K M; Hunt, Brendan G; Yi, S V; Goodisman, M A D

2011-10-01

DNA methylation plays an important role in gene regulation in animals. However, the evolution and function of DNA methylation has only recently emerged as the subject of widespread study in insects. In this review we profile the known distribution of DNA methylation systems across insect taxa and synthesize functional inferences from studies of DNA methylation in insects and vertebrates. Unlike vertebrate genomes, which tend to be globally methylated, DNA methylation is primarily targeted to genes in insects. Nevertheless, mounting evidence suggests that a specialized role exists for genic methylation in the regulation of transcription, and possibly mRNA splicing, in both insects and mammals. Investigations in several insect taxa further reveal that DNA methylation is preferentially targeted to ubiquitously expressed genes and may play a key role in the regulation of phenotypic plasticity. We suggest that insects are particularly amenable to advancing our understanding of the biological functions of DNA methylation, because insects are evolutionarily diverse, display several lineage-specific losses of DNA methylation and possess tractable patterns of DNA methylation in moderately sized genomes. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.

Eicosanoids: an emerging role in dendritic cell biology.

PubMed

Harizi, Hedi; Gualde, Norbert

2004-01-01

The arachidonic acid (AA)-derived metabolites, termed eicosanoids, are potent lipid mediators with a key role in immune and inflammatory responses. In the immune system, eicosanoids such as prostaglandins (PGs) and leukotrienes (LTs) are produced predominately by antigen-presenting cells (APC), including macrophages and dendritic cells (DC). DC constitute a family of bone marrow-derived professional APC that play a critical role in the induction and modulation of both innate and adaptive immunity. For many years, macrophages were considered as major producers of eicosanoids that are thought to drastically affect their function. Studies concerning the modulation of DC biology by eicosanoids show that PGs and LTs have the potential to affect the maturation, cytokine-producing capacity, Th cell-polarizing ability, and migration of DC. In addition, the development of DC from bone marrow progenitors appears to be under the control of some eicosanoids. Understanding the actions of eicosanoids and their receptors on APC functions is crucial for the generation of efficient DC for therapeutic purposes in patients. In this review, we summarize the current understanding of how DC functions are modulated by eicosanoids.

Hydrolase treatments help unravel the function of intervessel pits in xylem hydraulics.

PubMed

Dusotoit-Coucaud, Anaïs; Brunel, Nicole; Tixier, Aude; Cochard, Hervé; Herbette, Stéphane

2014-03-01

Intervessel pits are structures that play a key role in the efficiency and safety functions of xylem hydraulics. However, little is known about the components of the pit membrane (PM) and their role in hydraulic functions, especially in resistance to cavitation. We tested the effect of commercial chemicals including a cellulase, a hemicellulase, a pectolyase, a proteinase and DTT on xylem hydraulic properties: vulnerability to cavitation (VC) and conductance. The effects were tested on branch segments from Fagus sylvatica (where the effects on pit structure were analyzed using TEM) and Populus tremula. Cellulose hydrolysis resulted in a sharp increase in VC and a significant increase in conductance, related to complete breakdown of the PM. Pectin hydrolysis also induced a sharp increase in VC but with no effect on conductance or pit structure observable by TEM. The other treatments with hemicellulase, proteinase or DTT showed no effect. This study brings evidence that cellulose and pectins are critical components underpinning VC, and that PM components may play distinct roles in the xylem hydraulic safety and efficiency. © 2013 Scandinavian Plant Physiology Society.

Seaweed-microbial interactions: key functions of seaweed-associated bacteria.

PubMed

Singh, Ravindra Pal; Reddy, C R K

2014-05-01

Seaweed-associated bacteria play a crucial role in morphogenesis and growth of seaweeds (macroalgae) in direct and/or indirect ways. Bacterial communities belonging to the phyla Proteobacteria and Firmicutes are generally the most abundant on seaweed surfaces. Associated bacterial communities produce plant growth-promoting substances, quorum sensing signalling molecules, bioactive compounds and other effective molecules that are responsible for normal morphology, development and growth of seaweeds. Also, bioactive molecules of associated bacteria determine the presence of other bacterial strains on seaweeds and protect the host from harmful entities present in the pelagic realm. The ecological functions of cross-domain signalling between seaweeds and bacteria have been reported as liberation of carpospores in the red seaweeds and settlement of zoospores in the green seaweeds. In the present review, the role of extracellular polymeric substances in growth and settlement of seaweeds spores is also highlighted. To elucidate the functional roles of associated bacteria and the molecular mechanisms underlying reported ecological phenomena in seaweeds requires a combined ecological, microbiological and biochemical approach. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family[W][OPEN

PubMed Central

Ren, Lin-Ling; Liu, Yan-Jing; Liu, Hai-Jing; Qian, Ting-Ting; Qi, Li-Wang; Wang, Xiao-Ru; Zeng, Qing-Yin

2014-01-01

Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families. PMID:24934172

Trophic and neurotrophic factors in human pituitary adenomas (Review).

PubMed

Spoletini, Marialuisa; Taurone, Samanta; Tombolini, Mario; Minni, Antonio; Altissimi, Giancarlo; Wierzbicki, Venceslao; Giangaspero, Felice; Parnigotto, Pier Paolo; Artico, Marco; Bardella, Lia; Agostinelli, Enzo; Pastore, Francesco Saverio

2017-10-01

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

Sox9: A Master Regulator of the Pancreatic Program

PubMed Central

Seymour, Philip A.

2014-01-01

Over the last decade, it has been discovered that the transcription factor Sox9 plays several critical roles in governing the development of the embryonic pancreas and the homeostasis of the mature organ. While analysis of pancreata from patients affected by the Sox9 haploinsufficiency syndrome campomelic dysplasia initially alluded to a functional role of Sox9 in pancreatic morphogenesis, transgenic mouse models have been instrumental in mechanistically dissecting such roles. Although initially defined as a marker and maintenance factor for pancreatic progenitors, Sox9 is now considered to fulfill additional indispensable functions during pancreogenesis and in the postnatal organ through its interactions with other transcription factors and signaling pathways such as Fgf and Notch. In addition to maintaining both multipotent and bipotent pancreatic progenitors, Sox9 is also required for initiating endocrine differentiation and maintaining pancreatic ductal identity, and it has recently been unveiled as a key player in the initiation of pancreatic cancer. These functions of Sox9 are discussed in this article, with special emphasis on the knowledge gained from various loss-of-function and lineage tracing mouse models. Also, current controversies regarding Sox9 function in healthy and injured adult pancreas and unanswered questions and avenues of future study are discussed. PMID:25148367

Identification of potential therapeutic target genes, key miRNAs and mechanisms in oral lichen planus by bioinformatics analysis.

PubMed

Gong, Cuihua; Sun, Shangtong; Liu, Bing; Wang, Jing; Chen, Xiaodong

2017-06-01

The study aimed to identify the potential target genes and key miRNAs as well as to explore the underlying mechanisms in the pathogenesis of oral lichen planus (OLP) by bioinformatics analysis. The microarray data of GSE38617 were downloaded from Gene Expression Omnibus (GEO) database. A total of 7 OLP and 7 normal samples were used to identify the differentially expressed genes (DEGs) and miRNAs. The DEGs were then performed functional enrichment analyses. Furthermore, DEG-miRNA network and miRNA-function network were constructed by Cytoscape software. Total 1758 DEGs (598 up- and 1160 down-regulated genes) and 40 miRNAs (17 up- and 23 down-regulated miRNAs) were selected. The up-regulated genes were related to nuclear factor-Kappa B (NF-κB) signaling pathway, while down-regulated genes were mainly enriched in the function of ribosome. Tumor necrosis factor (TNF), caspase recruitment domain family, member 11 (CARD11) and mitochondrial ribosomal protein (MRP) genes were identified in these functions. In addition, miR-302 was a hub node in DEG-miRNA network and regulated cyclin D1 (CCND1). MiR-548a-2 was the key miRNA in miRNA-function network by regulating multiple functions including ribosomal function. The NF-κB signaling pathway and ribosome function may be the pathogenic mechanisms of OLP. The genes such as TNF, CARD11, MRP genes and CCND1 may be potential therapeutic target genes in OLP. MiR-548a-2 and miR-302 may play important roles in OLP development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

PubMed Central

Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

2015-01-01

Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

Novel regulation of Smad3 oligomerization and DNA binding by its linker domain.

PubMed

Vasilaki, Eleftheria; Siderakis, Manos; Papakosta, Paraskevi; Skourti-Stathaki, Konstantina; Mavridou, Sofia; Kardassis, Dimitris

2009-09-08

Smad proteins are key effectors of the transforming growth factor beta (TGFbeta) signaling pathway in mammalian cells. Smads are composed of two highly structured and conserved domains called Mad homology 1 (MH1) and 2 (MH2), which are linked together by a nonconserved linker region. The recent identification of phosphorylation sites and binding sites for ubiquitin ligases in the linker regions of TGFbeta and bone morphogenetic protein (BMP) receptor-regulated Smads suggested that the linker may contribute to the regulation of Smad function by facilitating cross-talks with other signaling pathways. In the present study, we have generated and characterized novel Smad3 mutants bearing individual substitutions of conserved and nonconserved amino acid residues within a previously described transcriptionally active linker fragment. Our analysis showed that the conserved linker amino acids glutamine 222 and proline 229 play important roles in Smad functions such as homo- and hetero-oligomerization, nuclear accumulation in response to TGFbeta stimulation, and DNA binding. Furthermore, a Smad3 mutant bearing a substitution of the nonconserved amino acid asparagine 218 to alanine displayed enhanced transactivation potential relative to wild type Smad3. Finally, Smad3 P229A inhibited TGFbeta signaling when overexpressed in mammalian cells. In conclusion, our data are in line with previous studies supporting an important regulatory role of the linker region of Smads in their function as key transducers of TGFbeta signaling.

Kisspeptin modulates sexual and emotional brain processing in humans.

PubMed

Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

2017-02-01

Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

Circadian clock gene plays a key role on ovarian cycle and spontaneous abortion.

PubMed

Li, Ruiwen; Cheng, Shuting; Wang, Zhengrong

2015-01-01

Circadian locomotor output cycles protein kaput (CLOCK) plays a key role in maintaining circadian rhythms and activation of downstream elements. However, its function on human female reproductive system remains unknown. To investigate the potential role of CLOCK, CLOCK-shRNAs were transfected into mouse 129 ES cells or injected into the ovaries of adult female mice. Western blotting was utilized to analyze the protein interactions and flow cytometry was used to assess apoptosis. The expression of CLOCK peaked at the 6th week in the healthy fetuses. However, an abnormal expression of CLOCK was detected in fetuses from spontaneous miscarriage. To determine the effect of CLOCK on female fertility, a small hairpin RNA (shRNA) strategy was used to specifically knockdown the CLOCK gene expression in vitro and in vivo. Knockdown of CLOCK induced apoptosis in mouse embryonic stem (mES) cells and inhibited the proliferation in mES cells in vitro. CLOCK knockdown also led to decreased release of oocytes and smaller litter size compared with control in vivo. Collectively, theses findings indicate that CLOCK plays an important role in fertility and that the CLOCK knockdown leads to reduction in reproduction and increased miscarriage risk. © 2015 S. Karger AG, Basel.

Type IV secretion system of Brucella spp. and its effectors

PubMed Central

Ke, Yuehua; Wang, Yufei; Li, Wengfeng; Chen, Zeliang

2015-01-01

Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we discuss the roles of Brucella VirB T4SS and 15 effectors that are proposed to be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells. VirB T4SS also plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. Here, we list the key molecular events in the intracellular life cycle of Brucella that are potentially targeted by the VirB T4SS effectors. Elucidating the functions of these effectors will help clarify the molecular role of T4SS during infection. Furthermore, studying the effectors secreted by Brucella spp. might provide insights into the mechanisms used by the bacteria to hijack the host signaling pathways and aid in the development of better vaccines and therapies against brucellosis. PMID:26528442

Type IV secretion system of Brucella spp. and its effectors.

PubMed

Ke, Yuehua; Wang, Yufei; Li, Wengfeng; Chen, Zeliang

2015-01-01

Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we discuss the roles of Brucella VirB T4SS and 15 effectors that are proposed to be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells. VirB T4SS also plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. Here, we list the key molecular events in the intracellular life cycle of Brucella that are potentially targeted by the VirB T4SS effectors. Elucidating the functions of these effectors will help clarify the molecular role of T4SS during infection. Furthermore, studying the effectors secreted by Brucella spp. might provide insights into the mechanisms used by the bacteria to hijack the host signaling pathways and aid in the development of better vaccines and therapies against brucellosis.

The multi-dimensional roles of astrocytes in ALS.

PubMed

Yamanaka, Koji; Komine, Okiru

2018-01-01

Despite significant progress in understanding the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, the precise and comprehensive pathomechanisms remain largely unknown. In addition to motor neuron involvement, recent studies using cellular and animal models of ALS indicate that there is a complex interplay between motor neurons and neighboring non-neuronal cells, such as astrocytes, in non-cell autonomous neurodegeneration. Astrocytes are key homeostatic cells that play numerous supportive roles in maintaining the brain environment. In neurodegenerative diseases such as ALS, astrocytes change their shape and molecular expression patterns and are referred to as reactive or activated astrocytes. Reactive astrocytes in ALS lose their beneficial functions and gain detrimental roles. In addition, interactions between motor neurons and astrocytes are impaired in ALS. In this review, we summarize growing evidence that astrocytes are critically involved in the survival and demise of motor neurons through several key molecules and cascades in astrocytes in both sporadic and inherited ALS. These observations strongly suggest that astrocytes have multi-dimensional roles in disease and are a viable therapeutic target for ALS. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development

PubMed Central

Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

2014-01-01

Background and Aims CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. Methods CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. Key Results CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. Conclusions The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far generally accepted. PMID:24989787

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.

Key factors affecting dying children and their families.

PubMed

Hinds, Pamela S; Schum, Lisa; Baker, Justin N; Wolfe, Joanne

2005-01-01

The death of a child alters the life and health of others immediately and for the rest of their lives. How a child dies influences parents' abilities to continue their role functions as well as siblings' abilities to make and maintain friendships, and may be the basis for health care providers' decisions to exit direct care roles. Thus, facilitating a "good death"-an obvious care priority for all involved with the dying child-ought also to be a priority for the health of bereaved families and affected health care providers. Making this a care priority is complicated by a serious lack of data, as details of the last hours or weeks of a dying child or adolescent's life are largely unknown. The purpose of this paper is to identify key factors that affect the course of dying children and adolescents and that of their bereaved survivors, and to link those key factors to needed research that could produce clinically relevant findings to improve the care of these patients. Key factors described here include suffering (physical, psychological, and spiritual), communication, decision making, prognostic ambiguities, ability of the seriously ill child to give assent to research participation, and educational preparation of health care providers to give competent end-of-life care.

Distinct functions of Crumbs regulating slit diaphragms and endocytosis in Drosophila nephrocytes.

PubMed

Hochapfel, Florian; Denk, Lucia; Mendl, Gudrun; Schulze, Ulf; Maaßen, Christine; Zaytseva, Yulia; Pavenstädt, Hermann; Weide, Thomas; Rachel, Reinhard; Witzgall, Ralph; Krahn, Michael P

2017-12-01

Mammalian podocytes, the key determinants of the kidney's filtration barrier, differentiate from columnar epithelial cells and several key determinants of apical-basal polarity in the conventional epithelia have been shown to regulate podocyte morphogenesis and function. However, little is known about the role of Crumbs, a conserved polarity regulator in many epithelia, for slit-diaphragm formation and podocyte function. In this study, we used Drosophila nephrocytes as model system for mammalian podocytes and identified a conserved function of Crumbs proteins for cellular morphogenesis, nephrocyte diaphragm assembly/maintenance, and endocytosis. Nephrocyte-specific knock-down of Crumbs results in disturbed nephrocyte diaphragm assembly/maintenance and decreased endocytosis, which can be rescued by Drosophila Crumbs as well as human Crumbs2 and Crumbs3, which were both expressed in human podocytes. In contrast to the extracellular domain, which facilitates nephrocyte diaphragm assembly/maintenance, the intracellular FERM-interaction motif of Crumbs is essential for regulating endocytosis. Moreover, Moesin, which binds to the FERM-binding domain of Crumbs, is essential for efficient endocytosis. Thus, we describe here a new mechanism of nephrocyte development and function, which is likely to be conserved in mammalian podocytes.

Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects.

PubMed

Mircsof, Dennis; Langouët, Maéva; Rio, Marlène; Moutton, Sébastien; Siquier-Pernet, Karine; Bole-Feysot, Christine; Cagnard, Nicolas; Nitschke, Patrick; Gaspar, Ludmila; Žnidarič, Matej; Alibeu, Olivier; Fritz, Ann-Kristina; Wolfer, David P; Schröter, Aileen; Bosshard, Giovanna; Rudin, Markus; Koester, Christina; Crestani, Florence; Seebeck, Petra; Boddaert, Nathalie; Prescott, Katrina; Hines, Rochelle; Moss, Steven J; Fritschy, Jean-Marc; Munnich, Arnold; Amiel, Jeanne; Brown, Steven A; Tyagarajan, Shiva K; Colleaux, Laurence

2015-12-01

The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses.

Endosomal protein traffic meets nuclear signal transduction head on.

PubMed

Horazdovsky, Bruce

2004-02-01

Rab5 plays a key role in controlling protein traffic through the early stages of the endocytic pathway. Previous studies on the modulators and effectors of Rab5 protein function have tied the regulation of several signal transduction pathways to the movement of protein through endocytic compartments. In the February 6, 2004, issue of Cell, Miaczynska et al. describe a surprising new link between Rab5 function and the nucleus by uncovering two new Rab5 effectors as potential regulators of the nucleosome remodeling and histone deacetylase protein complex NuRD/MeCP1.

The mysterious light of dark chocolate.

PubMed

Şentürk, Tunay; Günay, Şeyda

2015-03-01

A healthy diet plays a key role in the prevention and management of cardiovascular diseases. Dark chocolate in particular has been shown to improve endothelial functions and lipid profile and to have cardiovascular protective effects via an inhibitory action on platelet functions. Recently, several studies have demonstrated the beneficial effects of chocolate, primarily on hypertension and other conditions such as coronary artery disease and hyperlipidemia. The present review provides a summary of the ingredients, bioavailability and cardiovascular protective effects of chocolate / cocoa and the published effects of chocolate on a number of cardiovascular diseases.

Whole-cell patch clamp recording of voltage-sensitive Ca²+ channel currents: heterologous expression systems and dissociated brain neurons.

PubMed

Hainsworth, Atticus H; Randall, Andrew D; Stefani, Alessandro

2005-01-01

Voltage-sensitive Ca(2+) channels (VSCC) play a central role in an extensive array of physiological processes. Their importance in cellular function arises from their ability both to sense membrane voltage and to conduct Ca(2+) ions, two facets that couple membrane excitability to a key intracellular second messenger. Through this relationship, activation of VSCCs is tightly coupled to the gamut of cellular functions dependent on intracellular Ca(2+), including muscle contraction, energy metabolism, gene expression, and exocytotic/endocytotic cycling.

Symmetry in running.

PubMed

Raibert, M H

1986-03-14

Symmetry plays a key role in simplifying the control of legged robots and in giving them the ability to run and balance. The symmetries studied describe motion of the body and legs in terms of even and odd functions of time. A legged system running with these symmetries travels with a fixed forward speed and a stable upright posture. The symmetries used for controlling legged robots may help in elucidating the legged behavior of animals. Measurements of running in the cat and human show that the feet and body sometimes move as predicted by the even and odd symmetry functions.

IL-15/IL-15 receptor biology: a guided tour through an expanding universe.

PubMed

Budagian, Vadim; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

2006-08-01

The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling. Here, we review recent advances in the IL-15-mediated signaling, and in the functional properties on cells besides T lymphocytes and NK cells. These are discussed in the context of their potential clinical and therapeutic relevance.

Biotechnological synthesis of functional nanomaterials.

PubMed

Lloyd, Jonathan R; Byrne, James M; Coker, Victoria S

2011-08-01

Biological systems, especially those using microorganisms, have the potential to offer cheap, scalable and highly tunable green synthetic routes for the production of the latest generation of nanomaterials. Recent advances in the biotechnological synthesis of functional nano-scale materials are described. These nanomaterials range from catalysts to novel inorganic antimicrobials, nanomagnets, remediation agents and quantum dots for electronic and optical devices. Where possible, the roles of key biological macromolecules in controlling production of the nanomaterials are highlighted, and also technological limitations that must be addressed for widespread implementation are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Distribution of Bathyarchaeota (MCG) archaea in the South China Sea sediments and implication of its ecological roles

NASA Astrophysics Data System (ADS)

Tiantian, Y.; Wang, F.; MingYang, N.

2015-12-01

Tiantian Yu1,2, Mingyang Niu1,2 and Fengping Wang1,2 1State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai, 200240, China; 2State Key Laboratory of Ocean Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China ABSTRACT: Archaea of Bathyarchaeota Phylum (Miscellaneous Crenarchaeotal Group, MCG) are widespread and abundant in various marine and continental environments. However, very little is understood on the metabolisms and ecological roles of this cosmopolitan sedimentary archaea , partly due to obstacles of cultivation. Bathyarchaeota could be divided into large members of subgroups with potentially high genetic heterogeneity, implying different metabolic capabilities and functions in different subgroups. Here, we report our work on investigating Bathyarchaeota abundance and types of subgroups in the South China Sea(SCS) sediments, aim to understand their ecological roles in the carbon cycling. Bathyarchaeota were found the most dominant archaeal group in the sediments of SCS , most of which belong to subgroups MCG-8, MCG-15, MCG-17 and MCG-3. A new pair of 16S rRNA gene primers was designed as the published primers could not cover MCG-15 and MCG-17, which are the most dominant subgroups in the SCS sediments. Comparing with previous primers which used for quantifying the abundance of Bathyarchaeota via Q-PCR, the new primer revealed about an order of magnitude higher abundance in all South China Sea sediments. The relationship of geochemical parameters and MCG subgroups will further be explored to provide the basis for further understanding the metabolic function and biogeochemical roles of these poor-understood sedimentary archaea.

Colonic Butyrate-Producing Communities in Humans: an Overview Using Omics Data

PubMed Central

Pieper, Dietmar H.

2017-01-01

ABSTRACT Given the key role of butyrate for host health, understanding the ecology of intestinal butyrate-producing communities is a top priority for gut microbiota research. To this end, we performed a pooled analysis on 2,387 metagenomic/transcriptomic samples from 15 publicly available data sets that originated from three continents and encompassed eight diseases as well as specific interventions. For analyses, a gene catalogue was constructed from gene-targeted assemblies of all genes from butyrate synthesis pathways of all samples and from an updated reference database derived from genome screenings. We demonstrate that butyrate producers establish themselves within the first year of life and display high abundances (>20% of total bacterial community) in adults regardless of origin. Various bacteria form this functional group, exhibiting a biochemical diversity including different pathways and terminal enzymes, where one carbohydrate-fueled pathway was dominant with butyryl coenzyme A (CoA):acetate CoA transferase as the main terminal enzyme. Subjects displayed a high richness of butyrate producers, and 17 taxa, primarily members of the Lachnospiraceae and Ruminococcaceae along with some Bacteroidetes, were detected in >70% of individuals, encompassing ~85% of the total butyrate-producing potential. Most of these key taxa were also found to express genes for butyrate formation, indicating that butyrate producers occupy various niches in the gut ecosystem, concurrently synthesizing that compound. Furthermore, results from longitudinal analyses propose that diversity supports functional stability during ordinary life disturbances and during interventions such as antibiotic treatment. A reduction of the butyrate-producing potential along with community alterations was detected in various diseases, where patients suffering from cardiometabolic disorders were particularly affected. IMPORTANCE Studies focusing on taxonomic compositions of the gut microbiota are plentiful, whereas its functional capabilities are still poorly understood. Specific key functions deserve detailed investigations, as they regulate microbiota-host interactions and promote host health and disease. The production of butyrate is among the top targets since depletion of this microbe-derived metabolite is linked to several emerging noncommunicable diseases and was shown to facilitate establishment of enteric pathogens by disrupting colonization resistance. In this study, we established a workflow to investigate in detail the composition of the polyphyletic butyrate-producing community from omics data extracting its biochemical and taxonomic diversity. By combining information from various publicly available data sets, we identified universal ecological key features of this functional group and shed light on its role in health and disease. Our results will assist the development of precision medicine to combat functional dysbiosis. PMID:29238752

Minireview: The Role of Nuclear Receptors in Photoreceptor Differentiation and Disease

PubMed Central

Swaroop, Anand

2012-01-01

Rod and cone photoreceptors are specialized sensory cells that mediate vision. Transcriptional controls are critical for the development and long-term survival of photoreceptors; when these controls become ineffective, retinal dysfunction or degenerative disease may result. This review discusses the role of nuclear receptors, a class of ligand-regulated transcription factors, at key stages of photoreceptor life in the mammalian retina. Nuclear receptors with known ligands, such as retinoids or thyroid hormone, together with several orphan receptors without identified physiological ligands, complement other classes of transcription factors in directing the differentiation and functional maintenance of photoreceptors. The potential of nuclear receptors to respond to ligands introduces versatility into the control of photoreceptor development and function and may suggest new opportunities for treatments of photoreceptor disease. PMID:22556342

Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together.

PubMed

Van Houdenhove, Boudewijn; Egle, Ulrich T

2004-01-01

Fibromyalgia (FM) is a controversial syndrome, characterised by persistent widespread pain, abnormal pain sensitivity and additional symptoms such as fatigue and sleep disturbance. The syndrome largely overlaps with other functional somatic disorders, particularly chronic fatigue syndrome (CFS). Although the exact aetiology and pathogenesis of FM are still unknown, it has been suggested that stress may play a key role in the syndrome. This article first reviews the function of the stress response system, placing special emphasis on the relationships between adverse life experiences, stress regulation and pain-processing mechanisms, and summarising the evidence for a possible aetiopathogenetic role of stress in FM. Finally, an integrative biopsychosocial model that conceptualizes FM as a stress disorder is proposed, and the clinical and research implications of the model are discussed.

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

PubMed

Melo-Gonzalez, Felipe; Hepworth, Matthew R

2017-03-01

Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

Cortactin Branches Out: Roles in Regulating Protrusive Actin Dynamics

PubMed Central

Ammer, Amanda Gatesman; Weed, Scott A.

2008-01-01

Since its discovery in the early 1990’s, cortactin has emerged as a key signaling protein in many cellular processes, including cell adhesion, migration, endocytosis, and tumor invasion. While the list of cellular functions influenced by cortactin grows, the ability of cortactin to interact with and alter the cortical actin network is central to its role in regulating these processes. Recently, several advances have been made in our understanding of the interaction between actin and cortactin, providing insight into how these two proteins work together to provide a framework for normal and altered cellular function. This review examines how regulation of cortactin through post-translational modifications and interactions with multiple binding partners elicits changes in cortical actin cytoskeletal organization, impacting the regulation and formation of actin-rich motility structures. PMID:18615630

The role of microRNAs in synaptic development and function

PubMed Central

Corbin, Rachel; Olsson-Carter, Katherine; Slack, Frank

2015-01-01

MicroRNAs control gene expression by inhibiting translation or promoting degradation of their target mRNAs. Since the discovery of the first microRNAs, lin-4 and let-7, in C. elegans, hundreds of microRNAs have been identified as key regulators of cell fate determination, lifespan, and cancer in species ranging from plants to humans. However, while microRNAs have been shown to be particularly abundant in the brain, their role in the development and activity of the nervous system is still largely unknown. In this review, we describe recent advances in our understanding of microRNA function at synapses, the specialized structures required for communication between neurons and their targets. We also propose how these advances might inform the molecular model of memory. PMID:19335998

[Standardization of the terms for Chinese herbal functions based on functional targeting].

PubMed

Xiao, Bin; Tao, Ou; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

2011-03-01

Functional analysis concisely summarizes and concentrates on the therapeutic characteristics and features of Chinese herbal medicine. Standardization of the terms for Chinese herbal functions not only plays a key role in modern research and development of Chinese herbal medicine, but also has far-reaching clinical applications. In this paper, a new method for standardizing the terms for Chinese herbal function was proposed. Firstly, functional targets were collected. Secondly, the pathological conditions and the mode of action of every functional target were determined by analyzing the references. Thirdly, the relationships between the pathological condition and the mode of action were determined based on Chinese medicine theory and data. This three-step approach allows for standardization of the terms for Chinese herbal functions. Promoting the standardization of Chinese medicine terms will benefit the overall clinical application of Chinese herbal medicine.

An Overview of the Quality Function Deployment (QFD) Technique

NASA Technical Reports Server (NTRS)

Sherif, Josef S.; Tran, Tuyet-Lan

1995-01-01

QFD is a product planning tool and a process methodology that enables all organizations, departments, and individuals in a business or a project to systematically focus on the critical performance, functions, and/or characteristics of a product that are the most important to the customer. It is part of the Total Quality Management (TQM) concept.. This presentation describes the objectives of QFD, the process for implementing the technique, the benefits derived from proper implementation, the kinds of systems where QFD is best utilized, what the success factors are, how QFD works, some guidelines for selection of a QFD team, and the functional roles of key team members.

Design of 3-D adipospheres for quantitative metabolic study

PubMed Central

Akama, Takeshi; Leung, Brendan M.; Labuz, Joseph M.; Takayama, Shuichi; Chun, Tae-Hwa

2017-01-01

Quantitative assessment of adipose mitochondrial activity is critical for better understanding of adipose tissue function in obesity and diabetes. While the two-dimensional (2-D) tissue culture method has been sufficient to discover key molecules that regulate adipocyte differentiation and function, the method is insufficient to determine the role of extracellular matrix (ECM) molecules and their modifiers, such as matrix metalloproteinases (MMPs), in regulating adipocyte function in three-dimensional (3-D) in vivo-like microenvironments. By using a 3-D hanging drop tissue culture system, we are able to produce scalable 3-D adipospheres that are suitable for quantitative mitochondrial study in 3-D microenvironment. PMID:28244051

A molecular imaging analysis of C×43 association with Cdo during skeletal myoblast differentiation

NASA Astrophysics Data System (ADS)

Nosi, Daniele; Mercatelli, Raffaella; Chellini, Flaminia; Soria, Silvia; Pini, Alessandro; Formigli, Lucia; Quercioli, Franco

2014-02-01

Cell-to-cell contacts are crucial for cell differentiation. The promyogenic cell surface protein, Cdo, functions as a component of multiprotein clusters to mediate cell adhesion signaling. Connexin43, the main connexin forming gap junctions, also plays a key role in myogenesis. At least part of its effects are independent of the intercellular channel function, but the mechanisms underlying are unknown. Here, using multiple optical approaches, we provided the first evidence that Cx43 physically interacts with Cdo to form dynamic complexes during myoblast differentiation, offering clues for considering this interaction a structural basis of the channel-independent function of Cx43.

Self-Efficacy and Functional Status in Schizophrenia: Relationship to Insight, Cognition and Negative Symptoms

PubMed Central

Kurtz, Matthew M.; Olfson, Rachel; Rose, Jennifer

2016-01-01

Self-efficacy, defined as the confidence one has in the ability to perform a behavior or specific task, has been introduced as a crucial motivational factor for successfully carrying out social and everyday living skills (Bandura, 1977, 1997). Few studies have assessed its role in functioning in schizophrenia. The current study was designed to investigate whether degree of illness insight determined whether self-efficacy was a mediator of the relationship between two key illness features, negative symptoms and cognition, and functional skills. Sixty-nine individuals with schizophrenia were administered measures of self-efficacy, cognition, symptoms, insight and performance-based measure of everyday living and social skill. Results revealed that self-efficacy was only linked to measures of functional skills when illness insight was intact. There was evidence of moderation of confounding effects such that when self-efficacy was controlled, the relationship between negative symptoms and measures of everyday life skills became non-significant, but only when illness insight was intact. These findings emphasize the importance of including illness insight in models of the role of self-efficacy in functioning in schizophrenia. PMID:23375941

Executive Function Capacities, Negative Driving Behavior and Crashes in Young Drivers

PubMed Central

Winston, Flaura K.

2017-01-01

Motor vehicle crashes remain a leading cause of injury and death in adolescents, with teen drivers three times more likely to be in a fatal crash when compared to adults. One potential contributing risk factor is the ongoing development of executive functioning with maturation of the frontal lobe through adolescence and into early adulthood. Atypical development resulting in poor or impaired executive functioning (as in Attention-Deficit/Hyperactivity Disorder) has been associated with risky driving and crash outcomes. However, executive function broadly encompasses a number of capacities and domains (e.g., working memory, inhibition, set-shifting). In this review, we examine the role of various executive function sub-processes in adolescent driver behavior and crash rates. We summarize the state of methods for measuring executive control and driving outcomes and highlight the great heterogeneity in tools with seemingly contradictory findings. Lastly, we offer some suggestions for improved methods and practical ways to compensate for the effects of poor executive function (such as in-vehicle assisted driving devices). Given the key role that executive function plays in safe driving, this review points to an urgent need for systematic research to inform development of more effective training and interventions for safe driving among adolescents. PMID:29143762

Further support for the role of dysfunctional attitudes in models of real-world functioning in schizophrenia.

PubMed

Horan, William P; Rassovsky, Yuri; Kern, Robert S; Lee, Junghee; Wynn, Jonathan K; Green, Michael F

2010-06-01

According to A.T. Beck and colleagues' cognitive formulation of poor functioning in schizophrenia, maladaptive cognitive appraisals play a key role in the expression and persistence of negative symptoms and associated real-world functioning deficits. They provided initial support for this model by showing that dysfunctional attitudes are elevated in schizophrenia and account for significant variance in negative symptoms and subjective quality of life. The current study used structural equation modeling to further evaluate the contribution of dysfunctional attitudes to outcome in schizophrenia. One hundred eleven outpatients and 67 healthy controls completed a Dysfunctional Attitudes Scale, and patients completed a competence measure of functional capacity, clinical ratings of negative symptoms, and interview-based ratings of real-world functioning. Patients reported higher defeatist performance beliefs than controls and these were significantly related to lower functional capacity, higher negative symptoms, and worse community functioning. Consistent with Beck and colleagues' formulation, modeling analyses indicated a significant indirect pathway from functional capacity-->dysfunctional attitudes-->negative symptoms-->real-world functioning. These findings support the value of dysfunctional attitudes for understanding the determinants of outcome in schizophrenia and suggest that therapeutic interventions targeting these attitudes may facilitate functional recovery. (c) 2009 Elsevier Ltd. All rights reserved.

Functional disability in patients with low back pain: the mediator role of suffering and beliefs about pain control in patients receiving physical and chiropractic treatment.

PubMed

Pereira, M Graça; Roios, Edite; Pereira, Marta

Low back pain is the leading cause of disability worldwide. There is evidence that depression, anxiety, and external locus of control are negative predictors of functional disability in low back patients. This study focused on the mediator role of suffering and beliefs about pain control in the relationship between psychological morbidity and functional disability in patients receiving physical therapy and chiropractic treatment for chronic low back pain. The sample included 213 patients receiving chiropractic treatment and 125 receiving physical therapy, who answered the following instruments: Beliefs about Pain Control Questionnaire; Inventory of Subjective Experiences of Suffering in Illness; Oswestry Low Back Pain Disability Questionnaire; and the Hospital Anxiety and Depression Scales. Suffering was a mediator in the relationship between depression and functional disability in both treatment groups. Only beliefs related to external chance events mediated the relationship between depression and functional disability in the physical therapy group, but not in the chiropratic teratment group. Intervention should focus on suffering regardless of the type of treatment and target beliefs about pain control, in patients receiving physical therapy treatment since they seem to play a key role in functional disability in patients with low back pain. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role2

PubMed Central

Yang, Thomas P.; Berry, Robert J; Bailey, Lynn B.

2012-01-01

ABSTRACT DNA methylation is an epigenetic modification critical to normal genome regulation and development. The vitamin folate is a key source of the one carbon group used to methylate DNA. Because normal mammalian development is dependent on DNA methylation, there is enormous interest in assessing the potential for changes in folate intake to modulate DNA methylation both as a biomarker for folate status and as a mechanistic link to developmental disorders and chronic diseases including cancer. This review highlights the role of DNA methylation in normal genome function, how it can be altered, and the evidence of the role of folate/folic acid in these processes. PMID:22332098

Myostatin: expanding horizons.

PubMed

Sharma, Mridula; McFarlane, Craig; Kambadur, Ravi; Kukreti, Himani; Bonala, Sabeera; Srinivasan, Shruti

2015-08-01

Myostatin is a secreted growth and differentiation factor that belongs to the TGF-β superfamily. Myostatin is predominantly synthesized and expressed in skeletal muscle and thus exerts a huge impact on muscle growth and function. In keeping with its negative role in myogenesis, myostatin expression is tightly regulated at several levels including epigenetic, transcriptional, post-transcriptional, and post-translational. New revelations regarding myostatin regulation also offer mechanisms that could be exploited for developing myostatin antagonists. Increasingly, it is becoming clearer that besides its conventional role in muscle, myostatin plays a critical role in metabolism. Hence, molecular mechanisms by which myostatin regulates several key metabolic processes need to be further explored. © 2015 International Union of Biochemistry and Molecular Biology.

Emerging Roles for Eosinophils in the Tumor Microenvironment.

PubMed

Reichman, Hadar; Karo-Atar, Danielle; Munitz, Ariel

2016-11-01

Eosinophils are evolutionary conserved cells largely studied in the context of allergy. Although eosinophils were first described in tumors more than 120 years ago, their roles in cancer are often overlooked. This is puzzling given their potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and recent studies demonstrating key roles for eosinophils in contexts far beyond their 'classical' field (e.g., metabolism, thermogenesis, and tissue regeneration). Recent data suggest that this frequently ignored cell is emerging as a potent immune effector and immune modulator in the tumor microenvironment. This review discusses the relevance of eosinophils to tumorigenesis and the potential to harness their function in cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Osmolytes in Regulating Immune System.

PubMed

Kumar, Tarun; Yadav, Manisha; Singh, Laishram Rajendrakumar

2016-01-01

The immune system has evolved to protect the host organism from diverse range of pathogenic microbes that are themselves constantly evolving. It is a complex network of cells, humoral factors, chemokines and cytokines. Dysregulation of immune system results in various kinds of immunological disorders. There are several external agents which govern the regulation of immune system. Recent studies have indicated the role of osmolytes in regulation of various immunological processes such as Ag-Ab interaction, Ig assembly, Ag presentation etc. In this present review, we have systematically discussed the role of osmolytes involved in regulation of several key immunological processes. Osmolytes are involved in the regulation of several key immunological processes such as immunoglobulin assembly and folding, immune cells proliferation, regulation of immune cells function, Ag-Ab interaction, antigen presentation, inflammatory response and protection against photo-immunosuppression. Hence, osmolytes and their transporters might be used as potential drug and drug targets respectively. This review is therefore designed to help clinicians in development of osmolyte based therapeutic strategies in the treatment of various immunological disorders. Appropriate future perspectives have also been included.

Reaching and Grasping in Autism Spectrum Disorder: A Review of Recent Literature

PubMed Central

Sacrey, Lori-Ann R.; Germani, Tamara; Bryson, Susan E.; Zwaigenbaum, Lonnie

2013-01-01

Impairments in motor functioning, which, until recently, have rarely been a primary focus in autism spectrum disorder (ASD) research, may play a key role in the early expression of biological vulnerability and be associated with key social-communication deficits. This review summarizes current knowledge of motor behavior in ASD, focusing specifically on reaching and grasping. Convergent data across the lifespan indicate that impairments to reaching and grasping emerge early in life, affect the planning and execution of motor programs, and may be impacted by additional impairments to sensory control of motor behavior. The relationship between motor impairments and diagnostic outcomes will be discussed. PMID:24478753

The EVOTION Decision Support System: Utilizing It for Public Health Policy-Making in Hearing Loss.

PubMed

Katrakazas, Panagiotis; Trenkova, Lyubov; Milas, Josip; Brdaric, Dario; Koutsouris, Dimitris

2017-01-01

As Decision Support Systems start to play a significant role in decision making, especially in the field of public-health policy making, we present an initial attempt to formulate such a system in the concept of public health policy making for hearing loss related problems. Justification for the system's conceptual architecture and its key functionalities are presented. The introduction of the EVOTION DSS sets a key innovation and a basis for paradigm shift in policymaking, by incorporating relevant models, big data analytics and generic demographic data. Expected outcomes for this joint effort are discussed from a public-health point of view.

Functional diversity of soil invertebrates: a potential tool to explain N2O emission?

NASA Astrophysics Data System (ADS)

Lubbers, Ingrid; De Deyn, Gerlinde; Drake, Harold; Hunger, Sindy; Oppermann, Timo; van Groenigen, Jan Willem

2017-04-01

Soil biota play a crucial role in the mineralization of nutrients from organic material. However, they can thereby increase emissions of the potent greenhouse gas nitrous oxide (N2O). Our current lack of understanding of the factors controlling N2O production and emission is impeding the development of effective mitigation strategies. It is the challenge to control N2O emissions from production systems without reducing crop yield, and diversity of soil fauna may play a key role. A high functional diversity of soil invertebrates is known to stimulate nitrogen mineralization and thereby plant growth, however, it is unknown whether a high functional diversity of soil invertebrates can concurrently diminish N2O emissions. We hypothesized that increased functional diversity of soil invertebrates reduces faunal-induced N2O emissions by facilitating more complete denitrification through (i) stimulating the activity of denitrifying microbes, and (ii) affecting the distribution of micro and macro pores, creating more anaerobic reaction sites. Using state-of-the-art X-ray tomography and next-generation sequencing, we studied effects of functional diversity on soil structural properties and the diversity of the microbial community (16S rRNA genes and 16S rRNA), and linked these to soil N2O emissions. In a 120-day study we found that the functional composition of the soil invertebrate community determined N2O emissions: earthworm activity was key to faunal-induced N2O emissions (a 32-fold increase after 120 days, P<0.001). No proof was found to explain faunal-induced N2O emissions through differences in stimulated microbial activity. On the other hand, soil structural properties (mean pore size, pore size distribution) were found to be radically altered by earthworm activity. We conclude that the presence of a few functional groups (ecosystem engineers) is more important than overall increased functional diversity in explaining faunal-affected N2O emissions.

Prediction of Geomagnetic Activity and Key Parameters in High-Latitude Ionosphere-Basic Elements

NASA Technical Reports Server (NTRS)

Lyatsky, W.; Khazanov, G. V.

2007-01-01

Prediction of geomagnetic activity and related events in the Earth's magnetosphere and ionosphere is an important task of the Space Weather program. Prediction reliability is dependent on the prediction method and elements included in the prediction scheme. Two main elements are a suitable geomagnetic activity index and coupling function -- the combination of solar wind parameters providing the best correlation between upstream solar wind data and geomagnetic activity. The appropriate choice of these two elements is imperative for any reliable prediction model. The purpose of this work was to elaborate on these two elements -- the appropriate geomagnetic activity index and the coupling function -- and investigate the opportunity to improve the reliability of the prediction of geomagnetic activity and other events in the Earth's magnetosphere. The new polar magnetic index of geomagnetic activity and the new version of the coupling function lead to a significant increase in the reliability of predicting the geomagnetic activity and some key parameters, such as cross-polar cap voltage and total Joule heating in high-latitude ionosphere, which play a very important role in the development of geomagnetic and other activity in the Earth s magnetosphere, and are widely used as key input parameters in modeling magnetospheric, ionospheric, and thermospheric processes.

Oxidative stress-triggered interactions between the succinyl- and acetyl-proteomes of rice leaves.

PubMed

Zhou, Heng; Finkemeier, Iris; Guan, Wenxue; Tossounian, Maria-Armineh; Wei, Bo; Young, David; Huang, Jingjing; Messens, Joris; Yang, Xibin; Zhu, Jun; Wilson, Michael H; Shen, Wenbiao; Xie, Yanjie; Foyer, Christine H

2018-05-01

Protein lysine acylations, such as succinylation and acetylation, are important post-translational modification (PTM) mechanisms, with key roles in cellular regulation. Antibody-based affinity enrichment, high-resolution liquid chromatography mass spectrometry analysis, and integrated bioinformatics analysis were used to characterize the lysine succinylome (K suc ) and acetylome (K ace ) of rice leaves. In total, 2,593 succinylated and 1,024 acetylated proteins were identified, of which 723 were simultaneously acetylated and succinylated. Proteins involved in photosynthetic carbon metabolism such as the large and small subunits of RuBisCO, ribosomal functions, and other key processes were subject to both PTMs. Preliminary insights into oxidant-induced changes to the rice acetylome and succinylome were gained from treatments with hydrogen peroxide. Exposure to oxidative stress did not regulate global changes in the rice acetylome or succinylome but rather led to modifications on a specific subset of the identified sites. De-succinylation of recombinant catalase (CATA) and glutathione S-transferase (OsGSTU6) altered the activities of these enzymes showing that this PTM may have a regulatory function. These findings not only greatly extend the list of acetylated and/or succinylated proteins but they also demonstrate the close cooperation between these PTMs in leaf proteins with key metabolic functions. © 2017 John Wiley & Sons Ltd.

Quantitative proteomic study of Aspergillus Fumigatus secretome revealed deamidation of secretory enzymes.

PubMed

Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

2015-04-24

Aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. This study profiled the secretome of Aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ). Post translational modifications (PTMs) of proteins play a critical role in protein functions. However, our understanding of the PTMs in secretory proteins is limited. Here, we present the identification of PTMs such as deamidation of secreted proteins of A. fumigatus. This study quantified diverse groups of extracellular secreted enzymes and their functional classification revealed cellulases and glycoside hydrolases (32.9%), amylases (0.9%), hemicellulases (16.2%), lignin degrading enzymes (8.1%), peptidases and proteases (11.7%), chitinases, lipases and phosphatases (7.6%), and proteins with unknown function (22.5%). The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulates expression of specific cellulases and hemicellulases, and their abundance level as a function of substrate. In-depth data analysis revealed deamidation as a major PTM of key cellulose hydrolyzing enzymes like endoglucanases, cellobiohydrolases and glucosidases. Hemicellulose degrading endo-1,4-beta-xylanase, monosidases, xylosidases, lignin degrading laccase, isoamyl alcohol oxidase and oxidoreductases were also found to be deamidated. The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by adopting liquid chromatography tandem mass spectrometry. The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulate expression of specific cellulases and hemicellulases, and expression level as a function of substrate. Post translational modifications revealed deamidation of key cellulases including endoglucanases, cellobiohydrolases and glucosidases; and hemicellulases and lignin degrading enzymes. The knowledge on deamidated enzymes along with specific sites of modifications could be crucial information for further functional studies of these enzymes of A. fumigatus. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome-Wide Identification of the Alba Gene Family in Plants and Stress-Responsive Expression of the Rice Alba Genes.

PubMed

Verma, Jitendra Kumar; Wardhan, Vijay; Singh, Deepali; Chakraborty, Subhra; Chakraborty, Niranjan

2018-03-28

Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa , Zea mays , Sorghum bicolor , Cicer arietinum , and Vitis vinifera , and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii , Physcomitrella patens , and Amborella trichopoda , revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A phylogenetic analysis of the genes and of their counterparts in other plant species indicated evolutionary conservation and diversification. In each group, the structural components of the genes and motifs showed significant conservation. The chromosomal location of the Alba genes of rice ( OsAlba ), showed an unequal distribution on 8 of its 12 chromosomes. The expression profiles of the OsAlba genes indicated a distinct tissue-specific expression in the seedling, vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR) analysis of the OsAlba genes confirmed their stress-inducible expression under multivariate environmental conditions and phytohormone treatments. The evaluation of the regulatory elements in 68 Alba genes from the 9 species studied led to the identification of conserved motifs and overlapping microRNA (miRNA) target sites, suggesting the conservation of their function in related proteins and a divergence in their biological roles across species. The 3D structure and the prediction of putative ligands and their binding sites for OsAlba proteins offered a key insight into the structure-function relationship. These results provide a comprehensive overview of the subtle genetic diversification of the OsAlba genes, which will help in elucidating their functional role in plants.

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation*

PubMed Central

Neumayer, Gernot; Helfricht, Angela; Shim, Su Yeon; Le, Hoa Thi; Lundin, Cecilia; Belzil, Camille; Chansard, Mathieu; Yu, Yaping; Lees-Miller, Susan P.; Gruss, Oliver J.; van Attikum, Haico; Helleday, Thomas; Nguyen, Minh Dang

2012-01-01

The microtubule-associated protein targeting protein for Xenopus kinesin-like protein 2 (TPX2) plays a key role in spindle assembly and is required for mitosis in human cells. In interphase, TPX2 is actively imported into the nucleus to prevent its premature activity in microtubule organization. To date, no function has been assigned to nuclear TPX2. We now report that TPX2 plays a role in the cellular response to DNA double strand breaks induced by ionizing radiation. Loss of TPX2 leads to inordinately strong and transient accumulation of ionizing radiation-dependent Ser-139-phosphorylated Histone 2AX (γ-H2AX) at G0 and G1 phases of the cell cycle. This is accompanied by the formation of increased numbers of high intensity γ-H2AX ionizing radiation-induced foci. Conversely, cells overexpressing TPX2 have reduced levels of γ-H2AX after ionizing radiation. Consistent with a role for TPX2 in the DNA damage response, we found that the protein accumulates at DNA double strand breaks and associates with the mediator of DNA damage checkpoint 1 (MDC1) and the ataxia telangiectasia mutated (ATM) kinase, both key regulators of γ-H2AX amplification. Pharmacologic inhibition or depletion of ATM or MDC1, but not of DNA-dependent protein kinase (DNA-PK), antagonizes the γ-H2AX phenotype caused by TPX2 depletion. Importantly, the regulation of γ-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. In sum, our study identifies a novel and the first nuclear function for TPX2 in the cellular responses to DNA damage. PMID:23045526

Nitric Oxide and Mitochondrial Function in Neurological Diseases.

PubMed

Ghasemi, Mehdi; Mayasi, Yunis; Hannoun, Anas; Eslami, Seyed Majid; Carandang, Raphael

2018-04-15

Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology. Moreover, excess NO or the formation of reactive NO species (RNS), e.g., peroxynitrite (ONOO - ), impairs mitochondrial functioning and this, in conjunction with nuclear events, eventually affects neuronal cell metabolism and survival, contributing to the pathogenesis of several neurodegenerative diseases. In this review we highlight the possible mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial function including (i) negative effects on electron transport chain (ETC); (ii) ONOO - -mediated alteration in mitochondrial permeability transition; (iii) enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key proteins involved in this process such as dynamin-related protein 1 (DRP-1) and Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex; (iv) alterations in the mitochondrial metabolic pathways including Krebs cycle, glycolysis, fatty acid metabolism, and urea cycle; and finally (v) mitochondrial ONOO - -induced nuclear toxicity and subsequent release of apoptosis-inducing factor (AIF) from mitochondria, causing neuronal cell death. These proposed mechanisms highlight the multidimensional nature of NO and its signaling in the mitochondrial function. Understanding the mechanisms by which NO mediates mitochondrial (dys)function can provide new insights into the treatment of neurodegenerative diseases. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Miniaturized supercapacitors: key materials and structures towards autonomous and sustainable devices and systems.

PubMed

Soavi, Francesca; Bettini, Luca Giacomo; Piseri, Paolo; Milani, Paolo; Santoro, Carlo; Atanassov, Plamen; Arbizzani, Catia

2016-09-15

Supercapacitors (SCs) are playing a key role for the development of self-powered and self-sustaining integrated systems for different fields ranging from remote sensing, robotics and medical devices. SC miniaturization and integration into more complex systems that include energy harvesters and functional devices are valuable strategies that address system autonomy. Here, we discuss about novel SC fabrication and integration approaches. Specifically, we report about the results of interdisciplinary activities on the development of thin, flexible SCs by an additive technology based on Supersonic Cluster Beam Deposition (SCBD) to be implemented into supercapacitive electrolyte gated transistors and supercapacitive microbial fuel cells. Such systems integrate at materials level the specific functions of devices, like electric switch or energy harvesting with the reversible energy storage capability. These studies might open new frontiers for the development and application of new multifunction-energy storage elements.

Sox proteins in melanocyte development and melanoma

PubMed Central

Harris, Melissa L.; Baxter, Laura L.; Loftus, Stacie K.; Pavan, William J.

2010-01-01

Over ten years has passed since the first Sox gene was implicated in melanocyte development. Since then, we have discovered that SOX5, SOX9, SOX10 and SOX18 all participate as transcription factors that affect key melanocytic genes in both regulatory and modulatory fashions. Both SOX9 and SOX10 play major roles in the establishment and normal function of the melanocyte; SOX10 has been shown to heavily influence melanocyte development and SOX9 has been implicated in melanogenesis in the adult. Despite these advances, the precise cellular and molecular details of how these SOX proteins are regulated and interact during all stages of the melanocyte life cycle remain unknown. Improper regulation of SOX9 or SOX10 is also associated with cancerous transformation, and thus understanding the normal function of SOX proteins in the melanocyte will be key to revealing how these proteins contribute to melanoma. PMID:20444197

Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis

PubMed Central

Nieto-Torres, Jose L.; Verdiá-Báguena, Carmina; Castaño-Rodriguez, Carlos; Aguilella, Vicente M.; Enjuanes, Luis

2015-01-01

Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology. PMID:26151305

Miniaturized supercapacitors: key materials and structures towards autonomous and sustainable devices and systems

NASA Astrophysics Data System (ADS)

Soavi, Francesca; Bettini, Luca Giacomo; Piseri, Paolo; Milani, Paolo; Santoro, Carlo; Atanassov, Plamen; Arbizzani, Catia

2016-09-01

Supercapacitors (SCs) are playing a key role for the development of self-powered and self-sustaining integrated systems for different fields ranging from remote sensing, robotics and medical devices. SC miniaturization and integration into more complex systems that include energy harvesters and functional devices are valuable strategies that address system autonomy. Here, we discuss about novel SC fabrication and integration approaches. Specifically, we report about the results of interdisciplinary activities on the development of thin, flexible SCs by an additive technology based on Supersonic Cluster Beam Deposition (SCBD) to be implemented into supercapacitive electrolyte gated transistors and supercapacitive microbial fuel cells. Such systems integrate at materials level the specific functions of devices, like electric switch or energy harvesting with the reversible energy storage capability. These studies might open new frontiers for the development and application of new multifunction-energy storage elements.

A genomic perspective on the generation and maintenance of genetic diversity in herbivorous insects

PubMed Central

Gloss, Andrew D.; Groen, Simon C.; Whiteman, Noah K.

2017-01-01

Understanding the processes that generate and maintain genetic variation within populations is a central goal in evolutionary biology. Theory predicts that some of this variation is maintained as a consequence of adapting to variable habitats. Studies in herbivorous insects have played a key role in confirming this prediction. Here, we highlight theoretical and conceptual models for the maintenance of genetic diversity in herbivorous insects, empirical genomic studies testing these models, and pressing questions within the realm of evolutionary and functional genomic studies. To address key gaps, we propose an integrative approach combining population genomic scans for adaptation, genome-wide characterization of targets of selection through experimental manipulations, mapping the genetic architecture of traits influencing fitness, and functional studies. We also stress the importance of studying the maintenance of genetic variation across biological scales—from variation within populations to divergence among populations—to form a comprehensive view of adaptation in herbivorous insects. PMID:28736510

Immune heterogeneity in neuroinflammation: dendritic cells in the brain.

PubMed

Colton, Carol A

2013-03-01

Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain's response to neuroinflammatory disease with emphasis on how the brain's microenvironment impacts these actions.

A Practice/Research Collaborative: An Innovative Approach to Identifying and Responding to Psychosocial Functioning Problems and Recidivism Risk among Juvenile Arrestees

ERIC Educational Resources Information Center

Dembo, Richard; Walters, Wansley; Meyers, Kathleen

2005-01-01

Effectively identifying and responding to the psychosocial problems and recidivism risk of arrested youths remain critical needs in the field. Centralized intake facilities, such as juvenile assessment centers (JACs), can play a key role in this process. As part of a U.S. National Demonstration Project, the Miami-Dade JAC, serving a…

An Exploration into the Role of Social Trust as a Mediating Influence in Low-Income Latino/a College Financing Decisions

ERIC Educational Resources Information Center

McDonough, Patricia; Calderone, Shannon

2010-01-01

In the last forty years, federal and state financial aid policy has fundamentally shifted the way in which students and families finance college costs. Whereas grants once served an important function in equalizing college opportunity, loans are now considered a key lever against escalating postsecondary costs (McPherson and Shapiro, 1998). This…

Regulation of endocytic traffic by Rho GTPases.

PubMed Central

Qualmann, Britta; Mellor, Harry

2003-01-01

The members of the Rho subfamily of small GTPases are key regulators of the actin cytoskeleton. However, recent studies have provided evidence for multiple additional roles for these signalling proteins in controlling endocytic traffic. Here we review our current understanding of Rho GTPase action within the endocytic pathway and examine the potential points of convergence with the more established, actin-based functions of these signalling proteins. PMID:12564953

Analysis of JAK-STAT signaling pathway genes and their microRNA in the intestinal mucosa of genetically disparate chicken lines induced with necrotic enteritis

USDA-ARS?s Scientific Manuscript database

The JAK-STAT signaling pathway plays a key role in cytokine and growth factor activation and is involved in several cellular functions and diseases. The main objective of this study was to investigate and evaluate the expression of candidate JAK-STAT pathway genes and their regulators and interactor...

Preparing Future Leaders in Higher Education: Excellence Practices from Staff to Mid-Level Management Role Transitions

ERIC Educational Resources Information Center

Little, Erica Sherese

2016-01-01

Mid-level leadership is key to a functioning university and it is important that mid-level leaders feel they have the tools and resources they need in order to succeed. To be successful in a new mid-level leadership position, entering supervisors must clearly communicate a strong sense of vision, values, and principles to their staff and establish…

Regulation and Function of TIFAB in Myelodysplastic Syndrome

DTIC Science & Technology

2014-08-01

knockdown of TIFAB in human CD34+ hematopoietic stem /progenitor cells results in increased survival and proliferation, TIFAB inhibits TRAF6 protein...regulator of human hematopoietic cells . Our key observations show that knockdown of TIFAB in human CD34+ hematopoietic stem /progenitor cells results in...reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis. (2013). Haematologica,!98(9):!135381358.! PMID:!23716557

Education as a Gateway to Development: Case of Rural Poor at Thabaneng Village in Lesotho

ERIC Educational Resources Information Center

Matsepe, Mokone W.

2015-01-01

The study explores and unfolds the purpose of education in general, its value and the role it plays in helping development of the people in rural areas especially at Thabaneng Village in Lesotho. It reveals that education is the key to development and functions to equip the rural population in Lesotho with knowledge, training and worthwhile skills…

Putting Words in Their Mouths: The Alignment of Identities with System Goals through the Use of Individual Learning Plans

ERIC Educational Resources Information Center

Hamilton, Mary

2009-01-01

This article analyses the role of Individual Learning Plans (ILPs) in teachers' work in the "Skills for Life" sector. It shows how ILPs, originally a means of formative assessment, have become part of a system of performance indicators and function as a key mediating mechanism between local interactions and system goals. The article…

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

PubMed

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

2010-06-01

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

Identification and functional analysis of secreted effectors from phytoparasitic nematodes.

PubMed

Rehman, Sajid; Gupta, Vijai K; Goyal, Aakash K

2016-03-21

Plant parasitic nematodes develop an intimate and long-term feeding relationship with their host plants. They induce a multi-nucleate feeding site close to the vascular bundle in the roots of their host plant and remain sessile for the rest of their life. Nematode secretions, produced in the oesophageal glands and secreted through a hollow stylet into the host plant cytoplasm, are believed to play key role in pathogenesis. To combat these persistent pathogens, the identity and functional analysis of secreted effectors can serve as a key to devise durable control measures. In this review, we will recapitulate the knowledge over the identification and functional characterization of secreted nematode effector repertoire from phytoparasitic nematodes. Despite considerable efforts, the identity of genes encoding nematode secreted proteins has long been severely hampered because of their microscopic size, long generation time and obligate biotrophic nature. The methodologies such as bioinformatics, protein structure modeling, in situ hybridization microscopy, and protein-protein interaction have been used to identify and to attribute functions to the effectors. In addition, RNA interference (RNAi) has been instrumental to decipher the role of the genes encoding secreted effectors necessary for parasitism and genes attributed to normal development. Recent comparative and functional genomic approaches have accelerated the identification of effectors from phytoparasitic nematodes and offers opportunities to control these pathogens. Plant parasitic nematodes pose a serious threat to global food security of various economically important crops. There is a wealth of genomic and transcriptomic information available on plant parasitic nematodes and comparative genomics has identified many effectors. Bioengineering crops with dsRNA of phytonematode genes can disrupt the life cycle of parasitic nematodes and therefore holds great promise to develop resistant crops against plant-parasitic nematodes.

Cooperative Regulatory Functions of miR858 and MYB83 during Cyst Nematode Parasitism1[OPEN

PubMed Central

Piya, Sarbottam; Kihm, Christina; Baum, Thomas J.

2017-01-01

MicroRNAs (miRNAs) recently have been established as key regulators of transcriptome reprogramming that define cell function and identity. Nevertheless, the molecular functions of the greatest number of miRNA genes remain to be determined. Here, we report cooperative regulatory functions of miR858 and its MYB83 transcription factor target gene in transcriptome reprogramming during Heterodera cyst nematode parasitism of Arabidopsis (Arabidopsis thaliana). Gene expression analyses and promoter-GUS fusion assays documented a role of miR858 in posttranscriptional regulation of MYB83 in the Heterodera schachtii-induced feeding sites, the syncytia. Constitutive overexpression of miR858 interfered with H. schachtii parasitism of Arabidopsis, leading to reduced susceptibility, while reduced miR858 abundance enhanced plant susceptibility. Similarly, MYB83 expression increases were conducive to nematode infection because overexpression of a noncleavable coding sequence of MYB83 significantly increased plant susceptibility, whereas a myb83 mutation rendered the plants less susceptible. In addition, RNA-seq analysis revealed that genes involved in hormone signaling pathways, defense response, glucosinolate biosynthesis, cell wall modification, sugar transport, and transcriptional control are the key etiological factors by which MYB83 facilitates nematode parasitism of Arabidopsis. Furthermore, we discovered that miR858-mediated silencing of MYB83 is tightly regulated through a feedback loop that might contribute to fine-tuning the expression of more than a thousand of MYB83-regulated genes in the H. schachtii-induced syncytium. Together, our results suggest a role of the miR858-MYB83 regulatory system in finely balancing gene expression patterns during H. schachtii parasitism of Arabidopsis to ensure optimal cellular function. PMID:28512179

Chapter 3. Coordination and collaboration with interface units. Recommendations and standard operating procedures for intensive care unit and hospital preparations for an influenza epidemic or mass disaster.

PubMed

Joynt, Gavin M; Loo, Shi; Taylor, Bruce L; Margalit, Gila; Christian, Michael D; Sandrock, Christian; Danis, Marion; Leoniv, Yuval; Sprung, Charles L

2010-04-01

To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on enhancing coordination and collaboration between the ICU and other key stakeholders. Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including coordination and collaboration. Key recommendations include: (1) establish an Incident Management System with Emergency Executive Control Groups at facility, local, regional/state or national levels to exercise authority and direction over resource use and communications; (2) develop a system of communication, coordination and collaboration between the ICU and key interface departments within the hospital; (3) identify key functions or processes requiring coordination and collaboration, the most important of these being manpower and resources utilization (surge capacity) and re-allocation of personnel, equipment and physical space; (4) develop processes to allow smooth inter-departmental patient transfers; (5) creating systems and guidelines is not sufficient, it is important to: (a) identify the roles and responsibilities of key individuals necessary for the implementation of the guidelines; (b) ensure that these individuals are adequately trained and prepared to perform their roles; (c) ensure adequate equipment to allow key coordination and collaboration activities; (d) ensure an adequate physical environment to allow staff to properly implement guidelines; (6) trigger events for determining a crisis should be defined. Judicious planning and adoption of protocols for coordination and collaboration with interface units are necessary to optimize outcomes during a pandemic.

Chapter 3. Coordination and collaboration with interface units

PubMed Central

Joynt, Gavin M.; Loo, Shi; Taylor, Bruce L.; Margalit, Gila; Christian, Michael D.; Sandrock, Christian; Danis, Marion; Leoniv, Yuval

2016-01-01

Purpose To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on enhancing coordination and collaboration between the ICU and other key stakeholders. Methods Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including coordination and collaboration. Results Key recommendations include: (1) establish an Incident Management System with Emergency Executive Control Groups at facility, local, regional/state or national levels to exercise authority and direction over resource use and communications; (2) develop a system of communication, coordination and collaboration between the ICU and key interface departments within the hospital; (3) identify key functions or processes requiring coordination and collaboration, the most important of these being manpower and resources utilization (surge capacity) and re-allocation of personnel, equipment and physical space; (4) develop processes to allow smooth inter-departmental patient transfers; (5) creating systems and guidelines is not sufficient, it is important to: (a) identify the roles and responsibilities of key individuals necessary for the implementation of the guidelines; (b) ensure that these individuals are adequately trained and prepared to perform their roles; (c) ensure adequate equipment to allow key coordination and collaboration activities; (d) ensure an adequate physical environment to allow staff to properly implement guidelines; (6) trigger events for determining a crisis should be defined. Conclusions Judicious planning and adoption of protocols for coordination and collaboration with interface units are necessary to optimize outcomes during a pandemic. PMID:20213418

Developmental programming: the role of growth hormone.

PubMed

Oberbauer, Anita M

2015-01-01

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

Histone Arginine Methylation

PubMed Central

Lorenzo, Alessandra Di; Bedford, Mark T.

2012-01-01

Arginine methylation is a common posttranslational modification (PTM). This type of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly abundant on shuttling proteins. In this review, we will focus on one aspect of this PTM: the diverse roles that arginine methylation of the core histone tails play in regulating chromatin function. A family of nine protein arginine methyltransferases (PRMTs) catalyze methylation reactions, and a subset target histones. Importantly, arginine methylation of histone tails can promote or prevent the docking of key transcriptional effector molecules, thus playing a central role in the orchestration of the histone code. PMID:21074527

Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge

PubMed Central

Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben

2013-01-01

We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems. PMID:24155925

The role of executive functions in social impairment in Autism Spectrum Disorder.

PubMed

Leung, Rachel C; Vogan, Vanessa M; Powell, Tamara L; Anagnostou, Evdokia; Taylor, Margot J

2016-01-01

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by socio-communicative impairments. Executive dysfunction may explain some key characteristics of ASD, both social and nonsocial hallmarks. Limited research exists exploring the relations between executive function and social impairment in ASD and few studies have used a comparison control group. Thus, the objective of the present study was to investigate the relations between executive functioning using the Behavioral Rating Inventory of Executive Functioning (BRIEF), social impairment as measured by the Social Responsiveness Scale (SRS), and overall autistic symptomology as measured by the Autism Diagnostic Observation Schedule (ADOS) in children and adolescents with and without ASD. Seventy children and adolescents diagnosed with ASD and 71 typically developing controls were included in this study. Findings showed that behavioral regulation executive processes (i.e., inhibition, shifting, and emotional control) predicted social function in all children. However, metacognitive executive processes (i.e., initiation, working memory, planning, organization, and monitoring) predicted social function only in children with ASD and not in typically developing children. Our findings suggest a distinct metacognitive executive function-social symptom link in ASD that is not present in the typical population. Understanding components of executive functioning that contribute to the autistic symptomology, particularly in the socio-communicative domain, is crucial for developing effective interventions that target key executive processes as well as underlying behavioral symptoms.

Discovering the Deregulated Molecular Functions Involved in Malignant Transformation of Endometriosis to Endometriosis-Associated Ovarian Carcinoma Using a Data-Driven, Function-Based Analysis

PubMed Central

Chang, Chia-Ming; Yang, Yi-Ping; Chuang, Jen-Hua; Chuang, Chi-Mu; Lin, Tzu-Wei; Wang, Peng-Hui; Yu, Mu-Hsien

2017-01-01

The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC. PMID:29113136

DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

PubMed

Moon, Sue Jin; Jeong, Byong Chang; Kim, Hwa Jin; Lim, Joung Eun; Kwon, Ghee Young; Kim, Jeong Hoon

2018-03-01

Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription is limited. Here we report DBC1 as a key regulator of AR-V7 transcriptional activity and stability in CRPC cells. DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. DBC1 is required for recruitment of AR-V7 to its target enhancers and for long-range chromatin looping between the CDH2 enhancer and promoter. Mechanistically, DBC1 enhances DNA-binding activity of AR-V7 by direct interaction and inhibits CHIP E3 ligase-mediated ubiquitination and degradation of AR-V7 by competing with CHIP for AR-V7 binding, thereby stabilizing and activating AR-V7. Importantly, DBC1 depletion suppresses the tumorigenic and metastatic properties of CRPC cells. Our results firmly establish DBC1 as a critical AR-V7 coactivator that plays a key role in the regulation of DNA binding and stability of AR-V7 and has an important physiological role in CRPC progression.

Function key and shortcut key use in airway facilities.

DOT National Transportation Integrated Search

2003-02-01

This document provides information on the function keys and shortcut keys used by systems in the Federal Aviation Administration : Airway Facilities (AF) work environment. It includes a catalog of the function keys and shortcut keys used by each syst...

Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

PubMed

Bischof, Gérard N; Park, Denise C

2015-01-01

This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

Obesity and Aging: Consequences for Cognition, Brain Structure and Brain Function

PubMed Central

Bischof, Gérard N.; Park, Denise C.

2017-01-01

Objective This review focuses on the relationship between obesity and aging and how these interact together to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC; Park & Reuter-Lorenz, 2009—a conceptual model designed to relate brain structure and function to one’s level of cognitive ability. Methods The initial literature search was focused on normal aging and was guided by the key words, “aging, cognition, and obesity” in “PUBMED”. In a second search we added key words related to neuropathology including words “Alzheimer’s Disease”, “Vascular dementia” (VaD) and “Mild Cognitive Impairment” (MCI). Results The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the lifespan. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in mid-life is linked to an increased risk for AD and VaD, most likely via an increased accumulation of AD pathology. Conclusion While it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the lifespan. PMID:26107577

Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases

PubMed Central

Hershberger, Kathleen A.; Martin, Angelical S.; Hirschey, Matthew D.

2017-01-01

The coenzyme nicotinamide adenine dinucleotide (NAD+) has key roles in the regulation of redox status and energy metabolism. NAD+ depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD+ repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD+ enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD+ functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD+-dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD+ supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD+ metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD+-boosting therapies in preclinical animal models. We surmise that modulating the NAD+–sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases. PMID:28163307

Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases.

PubMed

Hershberger, Kathleen A; Martin, Angelical S; Hirschey, Matthew D

2017-04-01

The coenzyme nicotinamide adenine dinucleotide (NAD + ) has key roles in the regulation of redox status and energy metabolism. NAD + depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD + repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD + enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD + functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD + -dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD + supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD + metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD + -boosting therapies in preclinical animal models. We surmise that modulating the NAD + -sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases.

Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

PubMed

Beattie, James; Al-Khafaji, Hasanain; Noer, Pernille R; Alkharobi, Hanaa Esa; Alhodhodi, Aishah; Meade, Josephine; El-Gendy, Reem; Oxvig, Claus

2018-01-01

The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

How the discovery of ribozymes cast RNA in the roles of both chicken and egg in origin-of-life theories.

PubMed

Sankaran, Neeraja

2012-12-01

Scientific theories about the origin-of-life theories have historically been characterized by the chicken-and-egg problem of which essential aspect of life was the first to appear, replication or self-sustenance. By the 1950s the question was cast in molecular terms and DNA and proteins had come to represent the carriers of the two functions. Meanwhile, RNA, the other nucleic acid, had played a capricious role in origin theories. Because it contained building blocks very similar to DNA, biologists recognized early that RNA could store information in its linear sequences. With the discovery in the 1980s that RNA molecules were capable of biological catalysis, a function hitherto ascribed to proteins alone, RNA took on the role of the single entity that could act as both chicken and egg. Within a few years of the discovery of these catalytic RNAs (ribozymes) scientists had formulated an RNA World hypothesis that posited an early phase in the evolution of life where all key functions were performed by RNA molecules. This paper traces the history the role of RNA in origin-of-life theories with a focus on how the discovery of ribozymes influenced the discourse. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum

PubMed Central

Casey, Amanda K.; Chen, Shuliang; Novick, Peter; Ferro-Novick, Susan; Wente, Susan R.

2015-01-01

The nuclear envelope (NE) and endoplasmic reticulum (ER) are components of the same contiguous membrane system and yet have distinct cellular functions. Mounting evidence suggests roles for some ER proteins in the NE for proper nuclear pore complex (NPC) structure and function. In this study, we identify a NE role in Saccharomyces cerevisiae for Lnp1 and Sey1, proteins required for proper cortical ER formation. Both lnp1Δ and sey1Δ mutants exhibit synthetic genetic interactions with mutants in genes encoding key NPC structural components. Both Lnp1 and Sey1 physically associate with other ER components that have established NPC roles, including Rtn1, Yop1, Pom33, and Per33. Of interest, lnp1Δ rtn1Δ mutants but not rtn1Δ sey1Δ mutants exhibit defects in NPC distribution. Furthermore, the essential NPC assembly factor Ndc1 has altered interactions in the absence of Sey1. Lnp1 dimerizes in vitro via its C-terminal zinc finger motif, a property that is required for proper ER structure but not NPC integrity. These findings suggest that Lnp1's role in NPC integrity is separable from functions in the ER and is linked to Ndc1 and Rtn1 interactions. PMID:26041935

Macrophages: Contributors to Allograft Dysfunction, Repair or Innocent Bystanders?

PubMed Central

Mannon, Roslyn B.

2012-01-01

Purpose of this review Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Recent Findings Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury while more recent studies indicate that they may play a reparative role, depending on phenotype—M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. Summary These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage mediated injury, explore their potential reparative role and determine if they or their functional products are biomarkers of poor graft outcomes. PMID:22157320

Key diffusion mechanisms involved in regulating bidirectional water permeation across E. coli outer membrane lectin

PubMed Central

Sachdeva, Shivangi; Kolimi, Narendar; Nair, Sanjana Anilkumar; Rathinavelan, Thenmalarchelvi

2016-01-01

Capsular polysaccharides (CPSs) are major bacterial virulent determinants that facilitate host immune evasion. E. coli group1 K30CPS is noncovalently attached to bacterial surface by Wzi, a lectin. Intriguingly, structure based phylogenetic analysis indicates that Wzi falls into porin superfamily. Molecular dynamics (MD) simulations further shed light on dual role of Wzi as it also functions as a bidirectional passive water specific porin. Such a functional role of Wzi was not realized earlier, due to the occluded pore. While five water specific entry points distributed across extracellular & periplasmic faces regulate the water diffusion involving different mechanisms, a luminal hydrophobic plug governs water permeation across the channel. Coincidently, MD observed open state structure of “YQF” triad is seen in sugar-binding site of sodium-galactose cotransporters, implicating its involvement in K30CPS surface anchorage. Importance of Loop 5 (L5) in membrane insertion is yet another highlight. Change in water diffusion pattern of periplasmic substitution mutants suggests Wzi’s role in osmoregulation by aiding in K30CPS hydration, corroborating earlier functional studies. Water molecules located inside β-barrel of Wzi crystal structure further strengthens the role of Wzi in osmoregulation. Thus, interrupting water diffusion or L5 insertion may reduce bacterial virulence. PMID:27320406

Comparative Genomics and Reverse Genetics Analysis Reveal Indispensable Functions of the Serine Acetyltransferase Gene Family in Arabidopsis[W][OA

PubMed Central

Watanabe, Mutsumi; Mochida, Keiichi; Kato, Tomohiko; Tabata, Satoshi; Yoshimoto, Naoko; Noji, Masaaki; Saito, Kazuki

2008-01-01

Ser acetyltransferase (SERAT), which catalyzes O-acetyl-Ser (OAS) formation, plays a key role in sulfur assimilation and Cys synthesis. Despite several studies on SERATs from various plant species, the in vivo function of multiple SERAT genes in plant cells remains unaddressed. Comparative genomics studies with the five genes of the SERAT gene family in Arabidopsis thaliana indicated that all three Arabidopsis SERAT subfamilies are conserved across five plant species with available genome sequences. Single and multiple knockout mutants of all Arabidopsis SERAT gene family members were analyzed. All five quadruple mutants with a single gene survived, with three mutants showing dwarfism. However, the quintuple mutant lacking all SERAT genes was embryo-lethal. Thus, all five isoforms show functional redundancy in vivo. The developmental and compartment-specific roles of each SERAT isoform were also demonstrated. Mitochondrial SERAT2;2 plays a predominant role in cellular OAS formation, while plastidic SERAT2;1 contributes less to OAS formation and subsequent Cys synthesis. Three cytosolic isoforms, SERAT1;1, SERAT3;1, and SERAT3;2, may play a major role during seed development. Thus, the evolutionally conserved SERAT gene family is essential in cellular processes, and the substrates and products of SERAT must be exchangeable between the cytosol and organelles. PMID:18776059

A conserved role for calpains during myoblast fusion.

PubMed

Buffolo, Marcio; Batista Possidonio, Ana Claudia; Mermelstein, Claudia; Araujo, Helena

2015-07-01

Myoblast fusion is a key step during skeletal muscle differentiation as it enables the formation of contractile fibers. Calpains have been implicated in some aspects of myogenesis in mammals, but whether they exert a conserved function during myoblast fusion has not been investigated. Here, we studied Calpain function in two models of myogenesis: in vitro analysis of chick myogenic cultures and in vivo analysis of Drosophila melanogaster muscle development. First we showed that Calpain A is important for fly muscle function. In addition, Calpain A knockdown reduced lateral body wall muscle length and width, as well as the number of nuclei in dorsal oblique muscles, consistent with fewer cells fusing to form fibers. Treatment of chick cultures with a selective Calpain inhibitor led to the formation of thinner myotubes containing a reduced number of nuclei, consistent with decreased myoblast fusion. Dynamic changes in IκBα labeling and transfection with a dominant-negative IκBα suggest a role for the NFκB pathway during chick myogenesis and a possible role of Calpains in attenuating NFκB signals that restrict myoblast fusion. Our data suggest that different model organisms may be used to study the role of Calpains in regular myogenesis and Calpain-related muscular degenerative disorders. © 2015 Wiley Periodicals, Inc.

Eukaryotic 5S rRNA biogenesis

PubMed Central

Ciganda, Martin; Williams, Noreen

2012-01-01

The ribosome is a large complex containing both protein and RNA which must be assembled in a precise manner to allow proper functioning in the critical role of protein synthesis. 5S rRNA is the smallest of the RNA components of the ribosome, and although it has been studied for decades, we still do not have a clear understanding of its function within the complex ribosome machine. It is the only RNA species that binds ribosomal proteins prior to its assembly into the ribosome. Its transport into the nucleolus requires this interaction. Here we present an overview of some of the key findings concerning the structure and function of 5S rRNA and how its association with specific proteins impacts its localization and function. PMID:21957041

Biological functions of proline in morphogenesis and osmotolerance revealed in antisense transgenic Arabidopsis thaliana.

PubMed

Nanjo, T; Kobayashi, M; Yoshiba, Y; Sanada, Y; Wada, K; Tsukaya, H; Kakubari, Y; Yamaguchi-Shinozaki, K; Shinozaki, K

1999-04-01

Many organisms, including higher plants, accumulate free proline (Pro) in response to osmotic stress. Although various studies have focused on the ability of Pro as a compatible osmolyte involved in osmotolerance, its specific role throughout plant growth is still unclear. It has been reported that Pro is synthesized from Glu catalyzed by a key enzyme, delta 1-pyrroline-5-carboxylate synthetase (P5CS), in plants. To elucidate essential roles of Pro, we generated antisense transgenic Arabidopsis plants with a P5CS cDNA. Several transgenics accumulated Pro at a significantly lower level than wild-type plants, providing direct evidence for a key role of P5CS in Pro production in Arabidopsis. These antisense transgenics showed morphological alterations in leaves and a defect in elongation of inflorescences. Furthermore, transgenic leaves were hypersensitive to osmotic stress. Microscopic analysis of transgenic leaves, in which the mutated phenotype clearly occurred, showed morphological abnormalities of epidermal and parenchymatous cells and retardation of differentiation of vascular systems. These phenotypes were suppressed by exogenous L-Pro but not by D-Pro or other Pro analogues. In addition, Pro deficiency did not broadly affect all proteins but specifically affected structural proteins of cell walls in the antisense transgenic plants. These results indicate that Pro is not just an osmoregulator in stressed plants but has a unique function involved in osmotolerance as well as in morphogenesis as a major constituent of cell wall structural proteins in plants.

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

PubMed

Alshareeda, A T; Negm, O H; Green, A R; Nolan, C C; Tighe, P; Albarakati, N; Sultana, R; Madhusudan, S; Ellis, I O; Rakha, E A

2015-06-09

It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) proteins in breast cancer (BC) is associated with loss-of-function phenotype. This study aims to investigate the biological and clinical significance of the nucleocytoplasmic transport protein karyopherin α-2 (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC. A large (n=1494) and well-characterised series of early-stage invasive BC with a long-term follow-up was assessed for KPNA2 protein by using immunohistochemistry. KPNA2 expression was associated with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, γH2AX, BARD1, UBC9, PIAS1 and CHK1. High level of KPNA2 was associated not only with cytoplasmic localisation of these proteins but also with their low/negative nuclear expression. Positive KPNA2 expression was associated with negative oestrogen receptor and triple-negative phenotype. Survival analysis showed that KPNA2 was associated with poor outcome (P<0.0001), but this effect was not independent of other prognostic variables. This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function.

The physiological roles of arrestin-1 in rod photoreceptor cells.

PubMed

Chen, Jeannie

2014-01-01

Arrestin-1 is the second most abundant protein in rod photoreceptors and is nearly equimolar to rhodopsin. Its well-recognized role is to "arrest" signaling from light-activated, phosphorylated rhodopsin, a prototypical G protein-coupled receptor. In doing so, arrestin-1 plays a key role in the rapid recovery of the light response. Arrestin-1 exists in a basal conformation that is stabilized by two independent sets of intramolecular interactions. The intramolecular constraints are disrupted by encountering (1) active conformation of the receptor (R*) and (2) receptor-attached phosphates. Requirement for these two events ensures its highly specific high-affinity binding to phosphorylated, light-activated rhodopsin (P-R*). In the dark-adapted state, the basal form is further organized into dimers and tetramers. Emerging data suggest pleiotropic roles of arrestin-1 beyond the functional range of rod cells. These include light-induced arrestin-1 translocation from the inner segment to the outer segment, a process that may be protective against cellular damage incurred by constitutive signaling. Its expanding list of binding partners also hints at additional, yet to be characterized functions. Uncovering these novel roles of arrestin-1 is a subject of future studies.

Synapse-specific astrocyte gating of amygdala-related behavior.

PubMed

Martin-Fernandez, Mario; Jamison, Stephanie; Robin, Laurie M; Zhao, Zhe; Martin, Eduardo D; Aguilar, Juan; Benneyworth, Michael A; Marsicano, Giovanni; Araque, Alfonso

2017-11-01

The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A 1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A 2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

Hepcidin in chronic kidney disease: not an anaemia management tool, but promising as a cardiovascular biomarker.

PubMed

van der Weerd, N C; Grooteman, M P C; Nubé, M J; ter Wee, P M; Swinkels, D W; Gaillard, C A J M

2015-03-01

Hepcidin is a key regulator of iron homeostasis and plays a role in the pathogenesis of anaemia of chronic disease. Its levels are increased in patients with chronic kidney disease (CKD) due to diminished renal clearance and an inflammatory state. Increased hepcidin levels in CKD patients are supposed to be responsible for functional iron deficiency in these patients and contribute to renal anaemia and resistance to erythropoiesis-stimulating agents. Therefore, hepcidin was purported to be useful as a management tool guiding treatment of renal anaemia. Furthermore, since hepcidin is associated with iron accumulation in macrophages in the vessel wall inducing oxidative stress and atherosclerosis, it has been speculated that hepcidin might function as a biomarker of cardiovascular disease. In this descriptive review, the merits of hepcidin with respect to its role in the pathophysiology of renal anaemia in CKD patients, its presumptive role as a practical diagnostic tool guiding management of renal anaemia, and its possible usefulness as a prognostic biomarker will be discussed.

Plant parasitic nematode effectors target host defense and nuclear functions to establish feeding cells.

PubMed

Quentin, Michaëel; Abad, Pierre; Favery, Bruno

2013-01-01

Plant parasitic nematodes are microscopic worms, the most damaging species of which have adopted a sedentary lifestyle within their hosts. These obligate endoparasites have a biotrophic relationship with plants, in which they induce the differentiation of root cells into hypertrophied, multinucleate feeding cells (FCs). Effectors synthesized in the esophageal glands of the nematode are injected into the plant cells via the syringe-like stylet and play a key role in manipulating the host machinery. The establishment of specialized FCs requires these effectors to modulate many aspects of plant cell morphogenesis and physiology, including defense responses. This cell reprogramming requires changes to host nuclear processes. Some proteins encoded by parasitism genes target host nuclei. Several of these proteins were immunolocalized within FC nuclei or shown to interact with host nuclear proteins. Comparative genomics and functional analyses are gradually revealing the roles of nematode effectors. We describe here these effectors and their hypothesized roles in the unique feeding behavior of these pests.

The key role of CYC2 during meiosis in Tetrahymena thermophila.

PubMed

Xu, Qianlan; Wang, Ruoyu; Ghanam, A R; Yan, Guanxiong; Miao, Wei; Song, Xiaoyuan

2016-04-01

Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.

A new role for the architecture of microvillar actin bundles in apical retention of membrane proteins.

PubMed

Revenu, Céline; Ubelmann, Florent; Hurbain, Ilse; El-Marjou, Fatima; Dingli, Florent; Loew, Damarys; Delacour, Delphine; Gilet, Jules; Brot-Laroche, Edith; Rivero, Francisco; Louvard, Daniel; Robine, Sylvie

2012-01-01

Actin-bundling proteins are identified as key players in the morphogenesis of thin membrane protrusions. Until now, functional redundancy among the actin-bundling proteins villin, espin, and plastin-1 has prevented definitive conclusions regarding their role in intestinal microvilli. We report that triple knockout mice lacking these microvillar actin-bundling proteins suffer from growth delay but surprisingly still develop microvilli. However, the microvillar actin filaments are sparse and lack the characteristic organization of bundles. This correlates with a highly inefficient apical retention of enzymes and transporters that accumulate in subapical endocytic compartments. Myosin-1a, a motor involved in the anchorage of membrane proteins in microvilli, is also mislocalized. These findings illustrate, in vivo, a precise role for local actin filament architecture in the stabilization of apical cargoes into microvilli. Hence, the function of actin-bundling proteins is not to enable microvillar protrusion, as has been assumed, but to confer the appropriate actin organization for the apical retention of proteins essential for normal intestinal physiology.

CBX3 promotes colon cancer cell proliferation by CDK6 kinase-independent function during cell cycle

PubMed Central

Fan, Yao; Li, Haiping; Liang, Xiaolong; Xiang, Zheng

2017-01-01

Heterochromatin protein 1γ (CBX3) links histone methylation marks to transcriptional silence, DNA repair and RNA splicing, but a role for CBX3 in cancer remains largely unknown. In this study, we show that CBX3 in colon cancer cells promotes the progression of the cell cycle and proliferation in vitro and in vivo. Cell cycle (G1 phase to S phase) related gene CDK6 and p21 were further identified as targets of CBX3. In addition, we found that enhancing CDK6 suppresses cell proliferation by upregulating inhibitor p21 in the absence of CBX3, and this function is independent of the kinase activity of CDK6. Our results demonstrate a key role of CBX3 in colon carcinogenesis via suppressing the expression of CDK6/p21, which may disrupt the role of CDK6 in transcriptionally regulating p21, as part of a negative feedback loop to limit CDK6 excessive activation. PMID:28193906

Skilled Birth Attendants: who is who? A descriptive study of definitions and roles from nine Sub Saharan African countries.

PubMed

Adegoke, Adetoro; Utz, Bettina; Msuya, Sia E; van den Broek, Nynke

2012-01-01

Availability of a Skilled Birth Attendant (SBA) during childbirth is a key indicator for MDG5 and a strategy for reducing maternal and neonatal mortality in Africa. There is limited information on how SBAs and their functions are defined. The aim of this study was to map the cadres of health providers considered SBAs in Sub Saharan Africa (SSA); to describe which signal functions of Essential Obstetric Care (EmOC) they perform and assess whether they are legislated to perform these functions. Key personnel in the Ministries of Health, teaching institutions, referral, regional and district hospitals completed structured questionnaires in nine SSA countries in 2009-2011. A total of 21 different cadres of health care providers (HCP) were reported to be SBA. Type and number of EmOC signal functions reported to be provided, varied substantially between cadres and countries. Parenteral antibiotics, uterotonic drugs and anticonvulsants were provided by most SBAs. Removal of retained products of conception and assisted vaginal delivery were the least provided signal functions. Except for the cadres of obstetricians, medical doctors and registered nurse-midwives, there was lack of clarity regarding signal functions reported to be performed and whether they were legislated to perform these. This was particularly for manual removal of placenta, removal of retained products and assisted vaginal delivery. In some countries, cadres not considered SBA performed deliveries and provided EmOC signal functions. In other settings, cadres reported to be SBA were able to but not legislated to perform key EmOC signal functions. Comparison of cadres of HCPs reported to be SBA across countries is difficult because of lack of standardization in names, training, and functions performed. There is a need for countries to develop clear guidelines defining who is a SBA and which EmOC signal functions each cadre of HCP is expected to provide.

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

PubMed Central

Carroll, Sean Michael; Ortlund, Eric A.; Thornton, Joseph W.

2011-01-01

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functions of GRs—reduced sensitivity to all hormones and increased selectivity for glucocorticoids—are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR–MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and function and reinforce the importance of permissive mutations in protein evolution. PMID:21698144

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.

Nutritional effects on T-cell immunometabolism

PubMed Central

Cohen, Sivan; Danzaki, Keiko; MacIver, Nancie J.

2017-01-01

T cells are highly influenced by nutrient uptake from their environment, and changes in overall nutritional status, such as malnutrition or obesity, can result in altered T-cell metabolism and behavior. In states of severe malnutrition or starvation, T-cell survival, proliferation, and inflammatory cytokine production are all decreased, as is T-cell glucose uptake and metabolism. The altered T-cell function and metabolism seen in malnutrition is associated with altered adipokine levels, most particularly decreased leptin. Circulating leptin levels are low in malnutrition, and leptin has been shown to be a key link between nutrition and immunity. The current view is that leptin signaling is required to upregulate activated T-cell glucose metabolism and thereby fuel T-cell activation. In the setting of obesity, T cells have been found to have a key role in promoting the recruitment of inflammatory macrophages to adipose depots along with the production of inflammatory cytokines that promote the development of insulin resistance leading to diabetes. Deletion of T cells, key T-cell transcription factors, or pro-inflammatory T-cell cytokines prevents insulin resistance in obesity and underscores the importance of T cells in obesity-associated inflammation and metabolic disease. Altogether, T cells have a critical role in nutritional immunometabolism. PMID:28054344

The Arabidopsis transcription factor AtTCP15 regulates endoreduplication by modulating expression of key cell-cycle genes.

PubMed

Li, Zi-Yu; Li, Bin; Dong, Ai-Wu

2012-01-01

Plant cells frequently undergo endoreduplication, a modified cell cycle in which genome is repeatedly replicated without cytokinesis. As the key step to achieve final size and function for cells, endoreduplication is prevalent during plant development. However, mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood. Here, we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes, as well as in rapidly dividing and vascular tissues. Expression of AtTCP15SRDX, AtTCP15 fused with a SRDX repressor domain, induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis. On the contrary, overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells. Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation. AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes, which play key roles in endoreduplication. Taken together, AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

Multimodal connectivity of motor learning-related dorsal premotor cortex.

PubMed

Hardwick, Robert M; Lesage, Elise; Eickhoff, Claudia R; Clos, Mareike; Fox, Peter; Eickhoff, Simon B

2015-12-01

The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has been proposed as a technique that may also allow delineation of functional connectivity. Here, we applied these three approaches to provide a comprehensive characterization of functional connectivity with a seed in the left dPMC that a previous meta-analysis of functional neuroimaging studies has identified as playing a key role in motor learning. Using data from two sources (the Rockland sample, containing resting state data and anatomical scans from 132 participants, and the BrainMap database, which contains peak activation foci from over 10,000 experiments), we conducted independent whole-brain functional connectivity mapping analyses of a dPMC seed. RSFC and MACM revealed similar connectivity maps spanning prefrontal, premotor, and parietal regions, while the SC map identified more widespread frontal regions. Analyses indicated a relatively consistent pattern of functional connectivity between RSFC and MACM that was distinct from that identified by SC. Notably, results indicate that the seed is functionally connected to areas involved in visuomotor control and executive functions, suggesting that the dPMC acts as an interface between motor control and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Epithelial Sodium and Acid-Sensing Ion Channels

NASA Astrophysics Data System (ADS)

Kellenberger, Stephan

The epithelial Na+ channel (ENaC) and acid-sensing ion channels (ASICs) are non-voltage-gated Na+ channels that form their own subfamilies within the ENaC/degenerin ion channel family. ASICs are sensors of extracellular pH, and ENaC, whose main function is trans-epithelial Na+ transport, can sense extra- and intra-cellular Na+. In aldosterone-responsive epithelial cells of the kidney, ENaC plays a critical role in the control of sodium balance, blood volume and blood pressure. In airway epithelia, ENaC has a distinct role in controlling fluid reabsorption at the air-liquid interface, thereby determining the rate of mucociliary transport. In taste receptor cells of the tongue, ENaC is involved in salt taste sensation. ASICs have emerged as key sensors for extracellular protons in central and peripheral neurons. Although not all of their physiological and pathological functions are firmly established yet, there is good evidence for a role of ASICs in the brain in learning, expression of fear, and in neurodegeneration after ischaemic stroke. In sensory neurons, ASICs are involved in nociception and mechanosensation. ENaC and ASIC subunits share substantial sequence homology and the conservation of several functional domains. This chapter summarises our current understanding of the physiological functions and of the mechanisms of ion permeation, gating and regulation of ENaC and ASICs.

Small things considered: the small accessory subunits of RNA polymerase in Gram-positive bacteria

PubMed Central

Weiss, Andy; Shaw, Lindsey N.

2015-01-01

The DNA-dependent RNA polymerase core enzyme in Gram-positive bacteria consists of seven subunits. Whilst four of them (α2ββ′) are essential, three smaller subunits, δ, ε and ω (∼9–21.5 kDa), are considered accessory. Both δ and ω have been viewed as integral components of RNAP for several decades; however, ε has only recently been described. Functionally these three small subunits carry out a variety of tasks, imparting important, supportive effects on the transcriptional process of Gram-positive bacteria. While ω is thought to have a wide range of roles, reaching from maintaining structural integrity of RNAP to σ factor recruitment, the only suggested function for ε thus far is in protecting cells from phage infection. The third subunit, δ, has been shown to have distinct influences in maintaining transcriptional specificity, and thus has a key role in cellular fitness. Collectively, all three accessory subunits, although dispensable under laboratory conditions, are often thought to be crucial for proper RNAP function. Herein we provide an overview of the available literature on each subunit, summarizing landmark findings that have deepened our understanding of these proteins and their function, and outline future challenges in understanding the role of these small subunits in the transcriptional process. PMID:25878038

Morphoregulatory functions of the RNA-binding motif protein 3 in cell spreading, polarity and migration.

PubMed

Pilotte, J; Kiosses, W; Chan, S W; Makarenkova, H P; Dupont-Versteegden, E; Vanderklish, P W

2018-05-09

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 was present in spreading initiation centers, filopodia and blebs that formed during cell spreading in cell lines and primary myoblasts. Reducing RBM3 triggered exaggerated spreading, increased RhoA expression, and a loss of polarity that was rescued by Rho kinase inhibition and overexpression of CRMP2. High RBM3 expression enhanced the motility of cells migrating by a mesenchymal mode involving extension of long protrusions, whereas RBM3 knockdown slowed migration, greatly reducing the ability of cells to extend protrusions and impairing multiple processes that require directional migration. These data establish novel functions of RBM3 of potential significance to tissue repair, metastasis and development.

Contribution of Theory of Mind, Executive Functioning, and Pragmatics to Socialization Behaviors of Children with High-Functioning Autism.

PubMed

Berenguer, Carmen; Miranda, Ana; Colomer, Carla; Baixauli, Inmaculada; Roselló, Belén

2018-02-01

Social difficulties are a key aspect of autism, but the intervening factors are still poorly understood. This study had two objectives: to compare the profile of ToM skills, executive functioning (EF), and pragmatic competence (PC) of children with high-functioning autism (HFA) and children with typical development (TD), and analyze their mediator role in social functioning. The participants were 52 children with HFA and 37 children with TD matched on age, intelligence quotient, and expressive vocabulary. Significant differences were found on measures of ToM, both explicit and applied, EF, and PC between children with HFA and TD. Multiple mediation analysis revealed that applied ToM skills and PC mediated the relations between autism symptoms and social functioning. Implications for social cognitive interventions to address these findings are discussed.

Political economy of decentralising HIV and AIDS treatment services to primary healthcare facilities in three Nigerian states.

PubMed

Mbachu, Chinyere; Onwujekwe, Obinna; Ezumah, Nkoli; Ajayi, Olayinka; Sanwo, Olusola; Uzochukwu, Benjamin

2016-09-01

Decentralisation is defined as the dispersion, distribution or transfer of resources, functions and decision-making power from a central authority to regional and local authorities. It is usually accompanied by assignment of accountability and responsibility for results. Fundamental to understanding decentralisation is learning what motivates central governments to give up power and resources to local governments, and the practical significance of this on their positions regarding decentralisation. This study examined key political and institutional influences on role-players' capacity to support decentralisation of HIV and AIDS treatment services to primary healthcare facilities, and implications for sustainability. In-depth interviews were conducted with 55 purposively selected key informants, drawn from three Nigerian states that were at different stages of decentralising HIV and AIDS treatment services to primary care facilities. Key informants represented different categories of role-players involved in HIV and AIDS control programmes. Thematic framework analysis of data was done. Support for decentralisation of HIV and AIDS treatment services to primary healthcare facilities was substantial among different categories of actors. Political factors such as the local and global agenda for health, political tenure and party affiliations, and institutional factors such as consolidation of decision-making power and improvements in career trajectories, influenced role-players support for decentralisation of HIV and AIDS treatment services. It is feasible and acceptable to decentralise HIV and AIDS treatment services to primary healthcare facilities, to help improve coverage. However, role-players' support largely depends on how well the reform aligns with political structures and current institutional practices.