Adaptive Coping under Conditions of Extreme Stress: Multilevel Influences on the Determinants of Resilience in Maltreated Children

ERIC Educational Resources Information Center

Cicchetti, Dante; Rogosch, Fred A.

2009-01-01

The study of resilience in maltreated children reveals the possibility of coping processes and resources on multiple levels of analysis as children strive to adapt under conditions of severe stress. In a maltreating context, aspects of self-organization, including self-esteem, self-reliance, emotion regulation, and adaptable yet reserved…

Regulation of cell fate determination by single-repeat R3 MYB transcription factors in Arabidopsis

PubMed Central

Wang, Shucai; Chen, Jin-Gui

2014-01-01

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYBs are characterized by their short sequence (<120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulation of cell type specification in the model plant Arabidopsis. PMID:24782874

Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

PubMed Central

Jackson, William F.

2017-01-01

Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca2+ channels (VGCC), Ca2+ influx through VGCC, intracellular Ca2+ and VSM contraction. Membrane potential also affects release of Ca2+ from internal stores and the Ca2+ sensitivity of the contractile machinery such that K+ channels participate in all aspects of regulation of VSM contraction. Potassium channels also regulate proliferation of VSM cells through membrane potential-dependent and membrane potential-independent mechanisms. Vascular smooth muscle cells express multiple isoforms of at least five classes of K+ channels contribute to the regulation of contraction and cell proliferation (growth). This review will examine the structure, expression and function of large-conductance, Ca2+-activated K+ (BKCa) channels, intermediate-conductance Ca2+-activated K+ (KCa3.1) channels, multiple isoforms of voltage-gated K+ (KV) channels, ATP-sensitive K+ (KATP) channels, and inward-rectifier K+ (KIR) channels in both contractile and proliferating VSM cells. PMID:28212804

DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.

PubMed

Kim, Ju Young; Duan, Xin; Liu, Cindy Y; Jang, Mi-Hyeon; Guo, Junjie U; Pow-anpongkul, Nattapol; Kang, Eunchai; Song, Hongjun; Ming, Guo-li

2009-09-24

Disrupted-in-schizophrenia 1 (DISC1), a susceptibility gene for major mental illnesses, regulates multiple aspects of embryonic and adult neurogenesis. Here, we show that DISC1 suppression in newborn neurons of the adult hippocampus leads to overactivated signaling of AKT, another schizophrenia susceptibility gene. Mechanistically, DISC1 directly interacts with KIAA1212, an AKT binding partner that enhances AKT signaling in the absence of DISC1, and DISC1 binding to KIAA1212 prevents AKT activation in vitro. Functionally, multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development that can be rescued by pharmacological inhibition of mammalian target of rapamycin (mTOR), an AKT downstream effector. Our study identifies the AKT-mTOR signaling pathway as a critical DISC1 target in regulating neuronal development and provides a framework for understanding how multiple susceptibility genes may functionally converge onto a common pathway in contributing to the etiology of certain psychiatric disorders.

Regulation of GMOs in China.

PubMed

Liu, Yinliang

2008-12-01

Genetically modified organisms (GMOs) are created by biotechnology to serve people with much benefit while may impose risks to ecological environment and human health and therefore need careful regulation. During the past two decades, GMOs have been well developed in China and so has their corresponding regulation. This paper reviews and comments the multiple aspects of mainly the agricultural GMOs, including their safety assessment, control measures, trade activities, import, labels, and GM food, which have been prescribed by the corresponding laws, regulations and administrative measures. It is held that till present a framework for regulation of agricultural GMOs and GM food has been established basically in China, while a more comprehensive system for regulation of all kinds of GMOs and all kinds of related activities is still needed at present and in the future.

HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

PubMed Central

Rutkowski, Timothy P.; Kohn, Anat; Sharma, Deepika; Ren, Yinshi; Mirando, Anthony J.

2016-01-01

ABSTRACT RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders. PMID:27160681

Neuregulin in Cardiovascular Development and Disease

PubMed Central

Odiete, Oghenerukevwe; Hill, Michael F.; Sawyer, Douglas B.

2013-01-01

Studies in genetically modified mice have demonstrated that neuregulin-1 (NRG-1), along with the erythroblastic leukemia viral oncogene homolog (ErbB) 2, 3, and 4 receptor tyrosine kinases, is necessary for multiple aspects of cardiovascular development. These observations stimulated in vitro and in vivo animal studies, implicating NRG-1/ErbB signaling in the regulation of cardiac cell biology throughout life. Cardiovascular effects of ErbB2-targeted cancer therapies provide evidence in humans that ErbB signaling plays a role in the maintenance of cardiac function. These and other studies suggest a conceptual model in which a key function of NRG-1/ErbB signaling is to mediate adaptations of the heart to physiological and pathological stimuli through activation of intracellular kinase cascades that regulate tissue plasticity. Recent work implicates NRG-1/ErbB signaling in the regulation of multiple aspects of cardiovascular biology, including angiogenesis, blood pressure, and skeletal muscle responses to exercise. The therapeutic potential of recombinant NRG-1 as a potential treatment for heart failure has been demonstrated in animal models and is now being explored in clinical studies. NRG-1 is found in human serum and plasma, and it correlates with some clinical parameters, suggesting that it may have value as an indicator of prognosis. In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease. PMID:23104879

Behavioral and Emotional Regulation and Adolescent Substance Use Problems: A Test of Moderation Effects in a Dual-Process Model

PubMed Central

Wills, Thomas A.; Pokhrel, Pallav; Morehouse, Ellen; Fenster, Bonnie

2011-01-01

In a structural model, we tested how relations of predictors to level of adolescent substance use (tobacco, alcohol, marijuana), and to substance-related impaired-control and behavior problems, are moderated by good self-control and poor regulation in behavioral and emotional domains. The participants were a sample of 1,116 public high-school students. In a multiple-group analysis for good self-control, the paths from negative life events to substance use level and from level to behavior problems were lower among persons scoring higher on good behavioral self-control. In a multiple-group analysis for poor regulation, the paths from negative life events to level and from peer substance use to level were greater among persons scoring higher on poor behavioral (but not emotional) regulation; an inverse path from academic competence to level was greater among persons scoring higher on both aspects of poor regulation. Paths from level to impaired-control and behavior problems were greater among persons scoring higher on both poor behavioral and poor emotional regulation. Theoretical implications for the basis of moderation effects are discussed. PMID:21443302

Regulation and Mindful Resident Care in Nursing Homes

PubMed Central

Colón-Emeric, Cathleen S.; Plowman, Donde; Bailey, Donald; Corazzini, Kirsten; Utley-Smith, Queen; Ammarell, Natalie; Toles, Mark; Anderson, Ruth

2009-01-01

Regulatory oversight is intended to improve the health outcomes of nursing home residents, yet evidence suggests that regulations can inhibit mindful staff behaviors that are associated with effective care. We explored the influence of regulations on mindful staff behavior as it relates to resident health outcomes, and offer a theoretical explanation of why regulations sometimes enhance mindfulness and other times inhibit it. We analyzed data from an in-depth, multiple case study including field notes, interviews, and documents collected in 8 nursing homes. We completed a conceptual/thematic description using the concept of mindfulness to reframe the observations. Shared facility mission strongly impacted staff perceptions of the purpose and utility of regulations. In facilities with a resident-centered culture, regulations increased mindful behavior, whereas in facilities with a cost-focused culture, regulations reduced mindful care practices. When managers emphasized the punitive aspects of regulation we observed a decrease in mindful practices in all facilities. PMID:20479137

Regulation of Cell Fate Determination by Single-Repeat R3 MYB Transcription Factors in Arabidopsis

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

Wang, Shucai; Chen, Jay

2014-01-01

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYB are characterized by their short sequence (<120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulationmore » of cell type specification in the model plant Arabidopsis.« less

Regulation of alternative mRNA splicing: old players and new perspectives.

PubMed

Dvinge, Heidi

2018-06-01

Nearly all human multi-exon genes are subject to alternative splicing in one or more cell types. The splicing machinery, therefore, has to select between multiple splice sites in a context-dependent manner, relying on sequence features in cis and trans-acting splicing regulators that either promote or repress splice site recognition and spliceosome assembly. However, the functional coupling between multiple gene regulatory layers signifies that splicing can also be modulated by transcriptional or epigenetic characteristics. Other, less obvious, aspects of alternative splicing have come to light in recent years, often involving core components of the spliceosome previously thought to perform a basal rather than a regulatory role in splicing. Together this paints a highly dynamic picture of splicing regulation, where the final splice site choice is governed by the entire transcriptional environment of a gene and its cellular context. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract

PubMed Central

Wocławek-Potocka, Izabela; Rawińska, Paulina; Kowalczyk-Zieba, Ilona; Boruszewska, Dorota; Sinderewicz, Emilia; Waśniewski, Tomasz; Skarzynski, Dariusz Jan

2014-01-01

Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1–6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance. PMID:24744506

[The clinical history in surgical processes. Bioethical aspects and basic professional ethics].

PubMed

Collazo Chao, Eliseo

2008-11-01

Surgeons are increasingly facing multiple civil liability claims from their patients. Against this background and taking any eventual liability claims into account, surgeons must be increasingly aware of the importance of maintaining patient medical histories, which raises numerous questions on the length of time and form of keeping them. Ethical and legal obligations need to be taken into account in order to identify the controversial aspects related to patients and their environment, as well as shedding light on the most appropriate behaviour in each case. We must never forget the case history is a clinical document, subjected to the medical art and medical ethics which regulate it.

[Role of nitric oxide as a regulator of cell processes in the formation of multiple organ failure].

PubMed

Riabov, G A; Azisov, Iu M

2001-01-01

Main aspects of functional activity of nitric oxide (NO) are discussed. Physicochemical properties of NO, routes of its formation in man, and mechanism of its effects on physiological processes are described. In human body NO is formed as a result of activity of a specific enzyme, nitric oxide synthase. Three isoforms of the enzyme are known: neuronal, inducible, and endothelial. NO regulates vascular tone, cell adhesion, neurotransmission, bronchodilatation, and platelet aggregation. NO can protect and damage cells under different conditions. The effect of NO can be direct and mediated. Mechanisms of vasodilating effect of NO and of its effect on apoptosis are discussed. The role of NO in regulation of the functional activity of hepatocytes is described. Regulation of NO level in human organism is discussed.

TACC3 is a microtubule plus end–tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types

PubMed Central

Nwagbara, Belinda U.; Faris, Anna E.; Bearce, Elizabeth A.; Erdogan, Burcu; Ebbert, Patrick T.; Evans, Matthew F.; Rutherford, Erin L.; Enzenbacher, Tiffany B.; Lowery, Laura Anne

2014-01-01

Microtubule plus end dynamics are regulated by a conserved family of proteins called plus end–tracking proteins (+TIPs). It is unclear how various +TIPs interact with each other and with plus ends to control microtubule behavior. The centrosome-associated protein TACC3, a member of the transforming acidic coiled-coil (TACC) domain family, has been implicated in regulating several aspects of microtubule dynamics. However, TACC3 has not been shown to function as a +TIP in vertebrates. Here we show that TACC3 promotes axon outgrowth and regulates microtubule dynamics by increasing microtubule plus end velocities in vivo. We also demonstrate that TACC3 acts as a +TIP in multiple embryonic cell types and that this requires the conserved C-terminal TACC domain. Using high-resolution live-imaging data on tagged +TIPs, we show that TACC3 localizes to the extreme microtubule plus end, where it lies distal to the microtubule polymerization marker EB1 and directly overlaps with the microtubule polymerase XMAP215. TACC3 also plays a role in regulating XMAP215 stability and localizing XMAP215 to microtubule plus ends. Taken together, our results implicate TACC3 as a +TIP that functions with XMAP215 to regulate microtubule plus end dynamics. PMID:25187649

Roles of the Sodium-Translocating NADH:Quinone Oxidoreductase (Na+-NQR) on Vibrio cholerae Metabolism, Motility and Osmotic Stress Resistance

PubMed Central

Minato, Yusuke; Halang, Petra; Quinn, Matthew J.; Faulkner, Wyatt J.; Aagesen, Alisha M.; Steuber, Julia; Stevens, Jan F.; Häse, Claudia C.

2014-01-01

The Na+ translocating NADH:quinone oxidoreductase (Na+-NQR) is a unique respiratory enzyme catalyzing the electron transfer from NADH to quinone coupled with the translocation of sodium ions across the membrane. Typically, Vibrio spp., including Vibrio cholerae, have this enzyme but lack the proton-pumping NADH:ubiquinone oxidoreductase (Complex I). Thus, Na+-NQR should significantly contribute to multiple aspects of V. cholerae physiology; however, no detailed characterization of this aspect has been reported so far. In this study, we broadly investigated the effects of loss of Na+-NQR on V. cholerae physiology by using Phenotype Microarray (Biolog), transcriptome and metabolomics analyses. We found that the V. cholerae ΔnqrA-F mutant showed multiple defects in metabolism detected by Phenotype Microarray. Transcriptome analysis revealed that the V. cholerae ΔnqrA-F mutant up-regulates 31 genes and down-regulates 55 genes in both early and mid-growth phases. The most up-regulated genes included the cadA and cadB genes, encoding a lysine decarboxylase and a lysine/cadaverine antiporter, respectively. Increased CadAB activity was further suggested by the metabolomics analysis. The down-regulated genes include sialic acid catabolism genes. Metabolomic analysis also suggested increased reductive pathway of TCA cycle and decreased purine metabolism in the V. cholerae ΔnqrA-F mutant. Lack of Na+-NQR did not affect any of the Na+ pumping-related phenotypes of V. cholerae suggesting that other secondary Na+ pump(s) can compensate for Na+ pumping activity of Na+-NQR. Overall, our study provides important insights into the contribution of Na+-NQR to V. cholerae physiology. PMID:24811312

The role of hypoxia-inducible factor-2 in digestive system cancers.

PubMed

Zhao, J; Du, F; Shen, G; Zheng, F; Xu, B

2015-01-15

Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies.

The role of hypoxia-inducible factor-2 in digestive system cancers

PubMed Central

Zhao, J; Du, F; Shen, G; Zheng, F; Xu, B

2015-01-01

Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies. PMID:25590810

Thermal control of virulence factors in bacteria: A hot topic

PubMed Central

Lam, Oliver; Wheeler, Jun; Tang, Christoph M

2014-01-01

Pathogenic bacteria sense environmental cues, including the local temperature, to control the production of key virulence factors. Thermal regulation can be achieved at the level of DNA, RNA or protein and although many virulence factors are subject to thermal regulation, the exact mechanisms of control are yet to be elucidated in many instances. Understanding how virulence factors are regulated by temperature presents a significant challenge, as gene expression and protein production are often influenced by complex regulatory networks involving multiple transcription factors in bacteria. Here we highlight some recent insights into thermal regulation of virulence in pathogenic bacteria. We focus on bacteria which cause disease in mammalian hosts, which are at a significantly higher temperature than the outside environment. We outline the mechanisms of thermal regulation and how understanding this fundamental aspect of the biology of bacteria has implications for pathogenesis and human health. PMID:25494856

Neuroendocrine regulation of somatic growth in fishes.

PubMed

Dai, XiangYan; Zhang, Wei; Zhuo, ZiJian; He, JiangYan; Yin, Zhan

2015-02-01

Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

Guaranteeing a captive audience: coordinated regulation of gene transfer agent (GTA) production and recipient capability by cellular regulators.

PubMed

Westbye, Alexander B; Beatty, J Thomas; Lang, Andrew S

2017-08-01

Gene transfer agents (GTAs) are bacteriophage-like particles produced by many prokaryotes. Several members of the Alphaproteobacteria produce a class of genetically-related GTAs that is best studied in Rhodobacter capsulatus. DNA transfer by the R. capsulatus GTA (RcGTA) combines aspects of both transduction and natural transformation, as recipient cells require a natural transformation-like system to incorporate donated DNA. The genes involved in RcGTA production and recipient capability are located at multiple loci in the bacterial genome; however, a conserved phosphorelay containing the response regulator CtrA and a quorum sensing system regulate both RcGTA production and recipient capability. This review highlights recent discoveries in RcGTA biology, and focuses on the co-regulation of genes involved in RcGTA production and recipient capability. Copyright © 2017 Elsevier Ltd. All rights reserved.

p53 regulates the mevalonate pathway in human glioblastoma multiforme

PubMed Central

Laezza, C; D'Alessandro, A; Di Croce, L; Picardi, P; Ciaglia, E; Pisanti, S; Malfitano, A M; Comegna, M; Faraonio, R; Gazzerro, P; Bifulco, M

2015-01-01

The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3′-hydroxy-3′-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression. PMID:26469958

Hepatitis B Virus Infection, MicroRNAs and Liver Disease.

PubMed

Sarkar, Neelakshi; Chakravarty, Runu

2015-08-03

Hepatitis B virus (HBV) attacks the liver and can cause both acute as well as chronic liver diseases which might lead to liver cirrhosis and hepatocellular carcinoma. Regardless of the availability of a vaccine and numerous treatment options, HBV is a major cause of morbidity and mortality across the world. Recently,microRNAs (miRNAs) have emerged as important modulators of gene function. Studies on the role of miRNA in the regulation of hepatitis B virus gene expression have been the focus of modern antiviral research. miRNAs can regulate viral replication and pathogenesis in a number of different ways, which includefacilitation, direct or indirect inhibition, activation of immune response, epigenetic modulation, etc. Nevertheless, these mechanisms can appropriately be used with a diagnosticand/or therapeutic approach. The present review is an attempt to classify specific miRNAs that are reported to be associated with various aspects of hepatitis B biology, in order to precisely present the participation of individual miRNAs in multiple aspects relating to HBV.

Stressing Escherichia coli to educate students about research: A CURE to investigate multiple levels of gene regulation.

PubMed

McDonough, Janet; Goudsouzian, Lara K; Papaj, Agllai; Maceli, Ashley R; Klepac-Ceraj, Vanja; Peterson, Celeste N

2017-09-01

Course-based undergraduate research experiences (CUREs) have been shown to increase student retention and learning in the biological sciences. Most CURES cover only one aspect of gene regulation, such as transcriptional control. Here we present a new inquiry-based lab that engages understanding of gene expression from multiple perspectives. Students carry out a forward genetic screen to identify regulators of the stationary phase master regulator RpoS in the model organism Escherichia coli and then use a series of reporter fusions to determine if the regulation is at the level of transcription or the post-transcription level. This easy-to-implement course has been run both as a 9-week long project and a condensed 5-6 week version in three different schools and types of courses. A majority of the genes found in the screen are novel, thus giving students the opportunity to contribute to original findings to the field. Assessments of this CURE show student gains in learning in many knowledge areas. In addition, attitudinal surveys suggest the students are enthusiastic about the screen and their learning about gene regulation. In summary, this lab would be an appropriate addition to an intermediate or advanced level Molecular Biology, Genetics, or Microbiology curriculum. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):449-458, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

PubMed Central

Fung, Rowena K. Y.; Grenga, Lucia; Trampari, Eleftheria; Pepe, Simona

2017-01-01

Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate. PMID:28658302

Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks

NASA Astrophysics Data System (ADS)

White, Forest M.; Wolf-Yadlin, Alejandro

2016-06-01

Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

A specific role for serotonin in overcoming effort cost.

PubMed

Meyniel, Florent; Goodwin, Guy M; Deakin, Jf William; Klinge, Corinna; MacFadyen, Christine; Milligan, Holly; Mullings, Emma; Pessiglione, Mathias; Gaillard, Raphaël

2016-11-08

Serotonin is implicated in many aspects of behavioral regulation. Theoretical attempts to unify the multiple roles assigned to serotonin proposed that it regulates the impact of costs, such as delay or punishment, on action selection. Here, we show that serotonin also regulates other types of action costs such as effort. We compared behavioral performance in 58 healthy humans treated during 8 weeks with either placebo or the selective serotonin reuptake inhibitor escitalopram. The task involved trading handgrip force production against monetary benefits. Participants in the escitalopram group produced more effort and thereby achieved a higher payoff. Crucially, our computational analysis showed that this effect was underpinned by a specific reduction of effort cost, and not by any change in the weight of monetary incentives. This specific computational effect sheds new light on the physiological role of serotonin in behavioral regulation and on the clinical effect of drugs for depression. ISRCTN75872983.

How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans?

PubMed

Dempsey, D'Maris Amick; Klessig, Daniel F

2017-03-23

Salicylic acid (SA) is an important plant hormone that regulates many aspects of plant growth and development, as well as resistance to (a)biotic stress. Efforts to identify SA effector proteins have revealed that SA binds to and alters the activity of multiple plant proteins-this represents a shift from the paradigm that hormones mediate their functions via one or a few receptors. SA and its derivatives also have multiple targets in animals; some of these proteins, like their plant counterparts, are associated with pathological processes. Together, these findings suggest that SA exerts its defense-associated effects in both kingdoms via a large number of targets.

Genetic insights into the mechanisms of Fgf signaling

PubMed Central

Brewer, J. Richard; Mazot, Pierre; Soriano, Philippe

2016-01-01

The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo. PMID:27036966

Mitochondrial Dynamics in Diabetes

PubMed Central

Galloway, Chad A.; Jhun, Bong Sook; Yu, Tianzheng

2011-01-01

Abstract Mitochondria are at the center of cellular energy metabolism and regulate cell life and death. The cell biological aspect of mitochondria, especially mitochondrial dynamics, has drawn much attention through implications in human pathology, including neurological disorders and metabolic diseases. Mitochondrial fission and fusion are the main processes governing the morphological plasticity and are controlled by multiple factors, including mechanochemical enzymes and accessory proteins. Emerging evidence suggests that mitochondrial dynamics plays an important role in metabolism–secretion coupling in pancreatic β-cells as well as complications of diabetes. This review describes an overview of mechanistic and functional aspects of mitochondrial fission and fusion, and comments on the recent advances connecting mitochondrial dynamics with diabetes and diabetic complications. Antioxid. Redox Signal. 14, 439–457. PMID:20518704

More Than Just Accuracy: A Novel Method to Incorporate Multiple Test Attributes in Evaluating Diagnostic Tests Including Point of Care Tests.

PubMed

Thompson, Matthew; Weigl, Bernhard; Fitzpatrick, Annette; Ide, Nicole

2016-01-01

Current frameworks for evaluating diagnostic tests are constrained by a focus on diagnostic accuracy, and assume that all aspects of the testing process and test attributes are discrete and equally important. Determining the balance between the benefits and harms associated with new or existing tests has been overlooked. Yet, this is critically important information for stakeholders involved in developing, testing, and implementing tests. This is particularly important for point of care tests (POCTs) where tradeoffs exist between numerous aspects of the testing process and test attributes. We developed a new model that multiple stakeholders (e.g., clinicians, patients, researchers, test developers, industry, regulators, and health care funders) can use to visualize the multiple attributes of tests, the interactions that occur between these attributes, and their impacts on health outcomes. We use multiple examples to illustrate interactions between test attributes (test availability, test experience, and test results) and outcomes, including several POCTs. The model could be used to prioritize research and development efforts, and inform regulatory submissions for new diagnostics. It could potentially provide a way to incorporate the relative weights that various subgroups or clinical settings might place on different test attributes. Our model provides a novel way that multiple stakeholders can use to visualize test attributes, their interactions, and impacts on individual and population outcomes. We anticipate that this will facilitate more informed decision making around diagnostic tests.

Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

PubMed Central

Yohn, Samantha E.; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

2016-01-01

Abstract Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson’s disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort-based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson’s disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology. PMID:27189581

Electrical Hyperexcitation of Lateral Ventral Pacemaker Neurons Desynchronizes Downstream Circadian Oscillators in the Fly Circadian Circuit and Induces Multiple Behavioral Periods

PubMed Central

Nitabach, Michael N.; Wu, Ying; Sheeba, Vasu; Lemon, William C.; Strumbos, John; Zelensky, Paul K.; White, Benjamin H.; Holmes, Todd C.

2008-01-01

Coupling of autonomous cellular oscillators is an essential aspect of circadian clock function but little is known about its circuit requirements. Functional ablation of the pigment-dispersing factor-expressing lateral ventral subset (LNV ) of Drosophila clock neurons abolishes circadian rhythms of locomotor activity. The hypothesis that LNVs synchronize oscillations in downstream clock neurons was tested by rendering the LNVs hyperexcitable via transgenic expression of a low activation threshold voltage-gated sodium channel. When the LNVs are made hyperexcitable, free-running behavioral rhythms decompose into multiple independent superimposed oscillations and the clock protein oscillations in the dorsal neuron 1 and 2 subgroups of clock neurons are phase-shifted. Thus, regulated electrical activity of the LNVs synchronize multiple oscillators in the fly circadian pacemaker circuit. PMID:16407545

Excessive expression of miR-27 impairs Treg-mediated immunological tolerance

PubMed Central

Cruz, Leilani O.; Hashemifar, Somaye Sadat; Wu, Cheng-Jang; Cho, Sunglim; Nguyen, Duc T.; Lin, Ling-Li; Khan, Aly Azeem

2017-01-01

MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell–specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner. Rather, dysregulation of Th1 responses and autoimmunity resulted from a perturbed Treg compartment. Excessive miR-27 expression in murine T cells severely impaired Treg differentiation. Moreover, Tregs with exaggerated miR-27–mediated gene regulation exhibited diminished homeostasis and suppressor function in vivo. Mechanistically, we determined that miR-27 represses several known as well as previously uncharacterized targets that play critical roles in controlling multiple aspects of Treg biology. Collectively, our data show that miR-27 functions as a key regulator in Treg development and function and suggest that proper regulation of miR-27 is pivotal to safeguarding Treg-mediated immunological tolerance. PMID:28067667

Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin in Drosophila melanogaster

PubMed Central

Chen, Audrey; Ng, Fanny; Lebestky, Tim; Grygoruk, Anna; Djapri, Christine; Lawal, Hakeem O.; Zaveri, Harshul A.; Mehanzel, Filmon; Najibi, Rod; Seidman, Gabriel; Murphy, Niall P.; Kelly, Rachel L.; Ackerson, Larry C.; Maidment, Nigel T.; Jackson, F. Rob; Krantz, David E.

2013-01-01

To investigate the regulation of Drosophila melanogaster behavior by biogenic amines, we have exploited the broad requirement of the vesicular monoamine transporter (VMAT) for the vesicular storage and exocytotic release of all monoamine neurotransmitters. We used the Drosophila VMAT (dVMAT) null mutant to globally ablate exocytotic amine release and then restored DVMAT activity in either individual or multiple aminergic systems, using transgenic rescue techniques. We find that larval survival, larval locomotion, and female fertility rely predominantly on octopaminergic circuits with little apparent input from the vesicular release of serotonin or dopamine. In contrast, male courtship and fertility can be rescued by expressing DVMAT in octopaminergic or dopaminergic neurons, suggesting potentially redundant circuits. Rescue of major aspects of adult locomotion and startle behavior required octopamine, but a complementary role was observed for serotonin. Interestingly, adult circadian behavior could not be rescued by expression of DVMAT in a single subtype of aminergic neurons, but required at least two systems, suggesting the possibility of unexpected cooperative interactions. Further experiments using this model will help determine how multiple aminergic systems may contribute to the regulation of other behaviors. Our data also highlight potential differences between behaviors regulated by standard exocytotic release and those regulated by other mechanisms. PMID:23086220

CAR-T cells are serial killers

PubMed Central

Davenport, Alexander J; Jenkins, Misty R; Ritchie, David S; Prince, H Miles; Trapani, Joseph A; Kershaw, Michael H; Darcy, Phillip K; Neeson, Paul J

2015-01-01

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours. PMID:26587330

CAR-T cells are serial killers.

PubMed

Davenport, Alexander J; Jenkins, Misty R; Ritchie, David S; Prince, H Miles; Trapani, Joseph A; Kershaw, Michael H; Darcy, Phillip K; Neeson, Paul J

2015-12-01

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours.

Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

PubMed

Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

2011-08-01

Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

Foxp2 regulates neuronal differentiation and neuronal subtype specification.

PubMed

Chiu, Yi-Chi; Li, Ming-Yang; Liu, Yuan-Hsuan; Ding, Jing-Ya; Yu, Jenn-Yah; Wang, Tsu-Wei

2014-07-01

Mutations of the transcription factor FOXP2 in humans cause a severe speech and language disorder. Disruption of Foxp2 in songbirds or mice also leads to deficits in song learning or ultrasonic vocalization, respectively. These data suggest that Foxp2 plays important roles in the developing nervous system. However, the mechanism of Foxp2 in regulating neural development remains elusive. In the current study, we found that Foxp2 increased neuronal differentiation without affecting cell proliferation and cell survival in primary neural progenitors from embryonic forebrains. Foxp2 induced the expression of platelet-derived growth factor receptor α, which mediated the neurognic effect of Foxp2. In addition, Foxp2 positively regulated the differentiation of medium spiny neurons derived from the lateral ganglionic eminence and negatively regulated the formation of interneurons derived from dorsal medial ganglionic eminence by interacting with the Sonic hedgehog pathway. Taken together, our results suggest that Foxp2 regulates multiple aspects of neuronal development in the embryonic forebrain. © 2014 Wiley Periodicals, Inc.

Cross-regulation among arabinose, xylose and rhamnose utilization systems in E. coli.

PubMed

Choudhury, D; Saini, S

2018-02-01

Bacteria frequently encounter multiple sugars in their natural surroundings. While the dynamics of utilization of glucose-containing sugar mixtures have been well investigated, there are few reports addressing regulation of utilization of glucose-free mixtures particularly pentoses. These sugars comprise a considerable fraction in hemicellulose which can be converted by suitable biocatalysts to biofuels and other value-added products. Hence, understanding of transcriptional cross-regulation among different pentose sugar utilization systems is essential for successful development of industrial strains. In this work, we study mixed-sugar utilization with respect to three secondary carbon sources - arabinose, xylose and rhamnose at single-cell resolution in Escherichia coli. Our results reveal that hierarchical utilization among these systems is not strict but rather can be eliminated or reversed by altering the relative ratios of the preferred and nonpreferred sugars. Since transcriptional cross-regulation among pentose sugar systems operates through competitive binding of noncognate sugar-regulator complex, altering sugar concentrations is thought to eliminate nonspecific binding by affecting concentration of the regulator - sugar complexes. Plant biomass comprises of hexose and pentose sugar mixtures. These sugars are processed by micro-organisms to form products like biofuels, polymers etc. One of the major challenges with mixed-sugar processing by micro-organisms is hierarchical utilization of sugars due to cross-regulation among sugar systems. In this work, we discuss cross-regulation among three secondary carbon sources - arabinose, xylose and rhamnose. Our results show that cross-regulation between pentose sugars is complex with multiple layers of regulation. These aspects need to be addressed for effective design of processes to extract energy from biomass. © 2017 The Society for Applied Microbiology.

Quantifying and Generalizing Hydrologic Responses to Dam Regulation using a Statistical Modeling Approach

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

McManamay, Ryan A

2014-01-01

Despite the ubiquitous existence of dams within riverscapes, much of our knowledge about dams and their environmental effects remains context-specific. Hydrology, more than any other environmental variable, has been studied in great detail with regard to dam regulation. While much progress has been made in generalizing the hydrologic effects of regulation by large dams, many aspects of hydrology show site-specific fidelity to dam operations, small dams (including diversions), and regional hydrologic regimes. A statistical modeling framework is presented to quantify and generalize hydrologic responses to varying degrees of dam regulation. Specifically, the objectives were to 1) compare the effects ofmore » local versus cumulative dam regulation, 2) determine the importance of different regional hydrologic regimes in influencing hydrologic responses to dams, and 3) evaluate how different regulation contexts lead to error in predicting hydrologic responses to dams. Overall, model performance was poor in quantifying the magnitude of hydrologic responses, but performance was sufficient in classifying hydrologic responses as negative or positive. Responses of some hydrologic indices to dam regulation were highly dependent upon hydrologic class membership and the purpose of the dam. The opposing coefficients between local and cumulative-dam predictors suggested that hydrologic responses to cumulative dam regulation are complex, and predicting the hydrology downstream of individual dams, as opposed to multiple dams, may be more easy accomplished using statistical approaches. Results also suggested that particular contexts, including multipurpose dams, high cumulative regulation by multiple dams, diversions, close proximity to dams, and certain hydrologic classes are all sources of increased error when predicting hydrologic responses to dams. Statistical models, such as the ones presented herein, show promise in their ability to model the effects of dam regulation effects at large spatial scales as to generalize the directionality of hydrologic responses.« less

Regulation of flower development in Arabidopsis by SCF complexes.

PubMed

Ni, Weimin; Xie, Daoxin; Hobbie, Lawrence; Feng, Baomin; Zhao, Dazhong; Akkara, Joseph; Ma, Hong

2004-04-01

SCF complexes are the largest and best studied family of E3 ubiquitin protein ligases that facilitate the ubiquitylation of proteins targeted for degradation. The SCF core components Skp1, Cul1, and Rbx1 serve in multiple SCF complexes involving different substrate-specific F-box proteins that are involved in diverse processes including cell cycle and development. In Arabidopsis, mutations in the F-box gene UNUSUAL FLORAL ORGANS (UFO) result in a number of defects in flower development. However, functions of the core components Cul1 and Rbx1 in flower development are poorly understood. In this study we analyzed floral phenotypes caused by altering function of Cul1 or Rbx1, as well as the effects of mutations in ASK1 and ASK2. Plants homozygous for a point mutation in the AtCUL1 gene showed reduced floral organ number and several defects in each of the four whorls. Similarly, plants with reduced AtRbx1 expression due to RNA interference also exhibited floral morphological defects. In addition, compared to the ask1 mutant, plants homozygous for ask1 and heterozygous for ask2 displayed enhanced reduction of B function, as well as other novel defects of flower development, including carpelloid sepals and an inhibition of petal development. Genetic analyses demonstrate that AGAMOUS (AG) is required for the novel phenotypes observed in the first and second whorls. Furthermore, the genetic interaction between UFO and AtCUL1 supports the idea that UFO regulates multiple aspects of flower development as a part of SCF complexes. These results suggest that SCF complexes regulate several aspects of floral development in Arabidopsis.

Mediator complex dependent regulation of cardiac development and disease.

PubMed

Grueter, Chad E

2013-06-01

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. The risk factors for CVD include environmental and genetic components. Human mutations in genes involved in most aspects of cardiovascular function have been identified, many of which are involved in transcriptional regulation. The Mediator complex serves as a pivotal transcriptional regulator that functions to integrate diverse cellular signals by multiple mechanisms including recruiting RNA polymerase II, chromatin modifying proteins and non-coding RNAs to promoters in a context dependent manner. This review discusses components of the Mediator complex and the contribution of the Mediator complex to normal and pathological cardiac development and function. Enhanced understanding of the role of this core transcriptional regulatory complex in the heart will help us gain further insights into CVD. Copyright © 2013. Production and hosting by Elsevier Ltd.

Examination of Clock and Adcyap1 gene variation in a neotropical migratory passerine

PubMed Central

Bridge, Eli S.; Ross, Jeremy D.; Shipley, J. Ryan; Kelly, Jeffrey F.

2018-01-01

Complex behavioral traits, such as those making up a migratory phenotype, are regulated by multiple environmental factors and multiple genes. We investigated possible relationships between microsatellite variation at two candidate genes implicated in the control of migratory behavior, Clock and Adcyap1, and several aspects of migratory life-history and evolutionary divergence in the Painted Bunting (Passerina ciris), a species that shows wide variation in migratory and molting strategies across a disjunct distribution. We focused on Clock and Adcyap1 microsatellite variation across three Painted Bunting populations in Oklahoma, Louisiana, and North Carolina, and for the Oklahoma breeding population we used published migration tracking data on adult males to explore phenotypic variation in individual migratory behavior. We found no correlation between microsatellite allele size within either Clock and Adcyap1 relative to the initiation or duration of fall migration in adult males breeding in Oklahoma. We also show the lack of significant correlations with aspects of the migratory phenotype for the Louisiana population. Our research highlights the limitations of studying microsatellite allelic mutations that are of undetermined functional influence relative to complex behavioral phenotypes. PMID:29324772

Socioeconomic Status, Subjective Social Status, and Perceived Stress: Associations with Stress Physiology and Executive Functioning.

PubMed

Ursache, Alexandra; Noble, Kimberly G; Blair, Clancy

2015-01-01

Several studies have investigated associations between socioeconomic status (SES) and indicators of children's physiological and cognitive self-regulation. Although objective measures of family SES may be good proxies for families' experiences of disadvantage, less is known about subjective aspects of families' experiences. We hypothesize that subjective social status (SSS) and perceived stress may be important independent predictors of children's stress physiology and executive functioning (EF). Eighty-two children from diverse SES backgrounds were administered EF measures and provided saliva samples for cortisol assay. Caregivers reported on objective SES, SSS, and perceived stress. Results suggest that SES and SSS are both independently and positively related to EF. In models predicting stress physiology, higher perceived stress was associated with lower baseline cortisol. Moreover, SES and age interacted to predict cortisol levels such that among younger children, lower SES was associated with higher cortisol, whereas among older children, lower SES was associated with lower cortisol. Results highlight the importance of considering both objective and subjective indicators of families' SES and stressful experiences in relation to multiple aspects of children's self-regulation.

The Rise of Mitochondria in Medicine

PubMed Central

Picard, Martin; Wallace, Douglas C; Burelle, Yan

2016-01-01

Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential cellular functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel “mitopathogenic” mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to – and likely will continue to enhance the progress of modern medicine. PMID:27423788

Synthesis of the sulfur amino acids: cysteine and methionine.

PubMed

Wirtz, Markus; Droux, Michel

2005-12-01

This review will assess new features reported for the molecular and biochemical aspects of cysteine and methionine biosynthesis in Arabidopsis thaliana with regards to early published data from other taxa including crop plants and bacteria (Escherichia coli as a model). By contrast to bacteria and fungi, plant cells present a complex organization, in which the sulfur network takes place in multiple sites. Particularly, the impact of sulfur amino-acid biosynthesis compartmentalization will be addressed in respect to localization of sulfur reduction. To this end, the review will focus on regulation of sulfate reduction by synthesis of cysteine through the cysteine synthase complex and the synthesis of methionine and its derivatives. Finally, regulatory aspects of sulfur amino-acid biosynthesis will be explored with regards to interlacing processes such as photosynthesis, carbon and nitrogen assimilation.

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging

PubMed Central

Pocock, Ginger M.; Zimdars, Laraine L.; Yuan, Ming; Eliceiri, Kevin W.; Ahlquist, Paul; Sherer, Nathan M.

2017-01-01

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include “burst” RNA nuclear export dynamics regulated by HIV-1’s Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element–specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. PMID:27903772

The Role of Self-regulation and Affective Control in Predicting Interpersonal Reactivity of Drug Addicts

PubMed Central

Abolghasemi, Abbas; Rajabi, Saeed

2013-01-01

Background Due to its progressive nature in all aspects of life, addiction endangers the health of individuals, families and the society. Objectives The purpose of this study was to determine the role of self-regulation and affective control in predicting interpersonal reactivity of drug addicts. Materials and Methods This research is a correlation study. The statistical population of this study includes all drug addicts who were referred to addiction treatment centers of Ardabil in 2011 of whom 160 addicts were selected through convenience sampling. A self-regulation questionnaire, interpersonal reactivity questionnaire and affective control scale were used for data collection. Results Research results showed that self-regulation (r = -0.40) and affective control (r = -0.29) have a significant relationship with interpersonal reactivity of addicts (P < 0.001). The results of the multiple regression analysis indicated that 19 percent of interpersonal reactivity can be predicted by self-regulation and affective control. Conclusion These results suggest that self-regulation and affective control play an important role in exacerbating as well as reducing interpersonal reactivity of addicts. PMID:24971268

How and why multiple MCMs are loaded at origins of DNA replication.

PubMed

Das, Shankar P; Rhind, Nicholas

2016-07-01

Recent work suggests that DNA replication origins are regulated by the number of multiple mini-chromosome maintenance (MCM) complexes loaded. Origins are defined by the loading of MCM - the replicative helicase which initiates DNA replication and replication kinetics determined by origin's location and firing times. However, activation of MCM is heterogeneous; different origins firing at different times in different cells. Also, more MCMs are loaded in G1 than are used in S phase. These aspects of MCM biology are explained by the observation that multiple MCMs are loaded at origins. Having more MCMs at early origins makes them more likely to fire, effecting differences in origin efficiency that define replication timing. Nonetheless, multiple MCM loading raises new questions, such as how they are loaded, where these MCMs reside at origins, and how their presence affects replication timing. In this review, we address these questions and discuss future avenues of research. © 2016 WILEY Periodicals, Inc.

Evaluation of multiple emission point facilities

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

Miltenberger, R.P.; Hull, A.P.; Strachan, S.

In 1970, the New York State Department of Environmental Conservation (NYSDEC) assumed responsibility for the environmental aspect of the state's regulatory program for by-product, source, and special nuclear material. The major objective of this study was to provide consultation to NYSDEC and the US NRC to assist NYSDEC in determining if broad-based licensed facilities with multiple emission points were in compliance with NYCRR Part 380. Under this contract, BNL would evaluate a multiple emission point facility, identified by NYSDEC, as a case study. The review would be a nonbinding evaluation of the facility to determine likely dispersion characteristics, compliance withmore » specified release limits, and implementation of the ALARA philosophy regarding effluent release practices. From the data collected, guidance as to areas of future investigation and the impact of new federal regulations were to be developed. Reported here is the case study for the University of Rochester, Strong Memorial Medical Center and Riverside Campus.« less

The essential aspect in sewerage regulation in Indonesia

NASA Astrophysics Data System (ADS)

Siami, L.

2018-01-01

Several cities in Indonesia have the sewerage local regulation such as Banjarmasin, Bantul, Surakarta and Denpasar. Meanwhile, The National Government have guideline in composing domestic sewerage regulation. Each city have their own characteristic and issues that need to be carried out by the local regulation. By using SWOT analysis, this study tries to figure out several aspect that need to be included in the local regulation. International references from developed and developing countries like Japan, Phillipines, Malaysia and Thailand were also used as benchmark without neglecting the local conditions of cities in Indonesia. Several crucial aspect of local regulation are institutional authority, composition on-site and off-site system, tariff, evaluation and monitoring, as well as punishment and rewards. Both tariff and evaluation aspects need to be narrowed down into specific regulations.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

PubMed

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

PubMed Central

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-01-01

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

Regulation of pyruvate metabolism and human disease.

PubMed

Gray, Lawrence R; Tompkins, Sean C; Taylor, Eric B

2014-07-01

Pyruvate is a keystone molecule critical for numerous aspects of eukaryotic and human metabolism. Pyruvate is the end-product of glycolysis, is derived from additional sources in the cellular cytoplasm, and is ultimately destined for transport into mitochondria as a master fuel input undergirding citric acid cycle carbon flux. In mitochondria, pyruvate drives ATP production by oxidative phosphorylation and multiple biosynthetic pathways intersecting the citric acid cycle. Mitochondrial pyruvate metabolism is regulated by many enzymes, including the recently discovered mitochondria pyruvate carrier, pyruvate dehydrogenase, and pyruvate carboxylase, to modulate overall pyruvate carbon flux. Mutations in any of the genes encoding for proteins regulating pyruvate metabolism may lead to disease. Numerous cases have been described. Aberrant pyruvate metabolism plays an especially prominent role in cancer, heart failure, and neurodegeneration. Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.

HOPE, SELF-ESTEEM, AND SELF-REGULATION: POSITIVE CHARACTERISTICS AMONG MEN AND WOMEN IN RECOVERY

PubMed Central

Ferrari, Joseph R.; Stevens, Edward B.; Legler, Raymond; Jason, Leonard A.

2014-01-01

Hopefulness remains unclear in relation to aspects of self-control and self-esteem among adults in substance abuse recovery. The present study explored the relationship between dispositional hope (agency and pathway) with self-esteem (self-liking, self-competency, and self-confidence) and self-regulation (impulse control and self-discipline), using a latent variable measurement model and structural equation modeling among adults (n = 601) residing in a communal living setting for persons in substance abuse recovery. Results showed that multiple dimensions of these constructs were significant as individual predictors. With persons in recovery, self-regulation included impulsivity control and self-discipline, while self-esteem reflected self-liking, competence, and a sense of self-confidence. Furthermore, both hope-pathways and hope-agency significantly related to self-control/impulse control but not self-control/discipline, and self-esteem/competency was associated with hope-pathways but not hope-agency. PMID:25382880

Large clusters of co-expressed genes in the Drosophila genome.

PubMed

Boutanaev, Alexander M; Kalmykova, Alla I; Shevelyov, Yuri Y; Nurminsky, Dmitry I

2002-12-12

Clustering of co-expressed, non-homologous genes on chromosomes implies their co-regulation. In lower eukaryotes, co-expressed genes are often found in pairs. Clustering of genes that share aspects of transcriptional regulation has also been reported in higher eukaryotes. To advance our understanding of the mode of coordinated gene regulation in multicellular organisms, we performed a genome-wide analysis of the chromosomal distribution of co-expressed genes in Drosophila. We identified a total of 1,661 testes-specific genes, one-third of which are clustered on chromosomes. The number of clusters of three or more genes is much higher than expected by chance. We observed a similar trend for genes upregulated in the embryo and in the adult head, although the expression pattern of individual genes cannot be predicted on the basis of chromosomal position alone. Our data suggest that the prevalent mechanism of transcriptional co-regulation in higher eukaryotes operates with extensive chromatin domains that comprise multiple genes.

Strigolactone regulates shoot development through a core signalling pathway

PubMed Central

Müller, Dörte

2016-01-01

ABSTRACT Strigolactones are a recently identified class of hormone that regulate multiple aspects of plant development. The DWARF14 (D14) α/β fold protein has been identified as a strigolactone receptor, which can act through the SCFMAX2 ubiquitin ligase, but the universality of this mechanism is not clear. Multiple proteins have been suggested as targets for strigolactone signalling, including both direct proteolytic targets of SCFMAX2, and downstream targets. However, the relevance and importance of these proteins to strigolactone signalling in many cases has not been fully established. Here we assess the contribution of these targets to strigolactone signalling in adult shoot developmental responses. We find that all examined strigolactone responses are regulated by SCFMAX2 and D14, and not by other D14-like proteins. We further show that all examined strigolactone responses likely depend on degradation of SMXL proteins in the SMXL6 clade, and not on the other proposed proteolytic targets BES1 or DELLAs. Taken together, our results suggest that in the adult shoot, the dominant mode of strigolactone signalling is D14-initiated, MAX2-mediated degradation of SMXL6-related proteins. We confirm that the BRANCHED1 transcription factor and the PIN-FORMED1 auxin efflux carrier are plausible downstream targets of this pathway in the regulation of shoot branching, and show that BRC1 likely acts in parallel to PIN1. PMID:27793831

miRegulome: a knowledge-base of miRNA regulomics and analysis.

PubMed

Barh, Debmalya; Kamapantula, Bhanu; Jain, Neha; Nalluri, Joseph; Bhattacharya, Antaripa; Juneja, Lucky; Barve, Neha; Tiwari, Sandeep; Miyoshi, Anderson; Azevedo, Vasco; Blum, Kenneth; Kumar, Anil; Silva, Artur; Ghosh, Preetam

2015-08-05

miRNAs regulate post transcriptional gene expression by targeting multiple mRNAs and hence can modulate multiple signalling pathways, biological processes, and patho-physiologies. Therefore, understanding of miRNA regulatory networks is essential in order to modulate the functions of a miRNA. The focus of several existing databases is to provide information on specific aspects of miRNA regulation. However, an integrated resource on the miRNA regulome is currently not available to facilitate the exploration and understanding of miRNA regulomics. miRegulome attempts to bridge this gap. The current version of miRegulome v1.0 provides details on the entire regulatory modules of miRNAs altered in response to chemical treatments and transcription factors, based on validated data manually curated from published literature. Modules of miRegulome (upstream regulators, downstream targets, miRNA regulated pathways, functions, diseases, etc) are hyperlinked to an appropriate external resource and are displayed visually to provide a comprehensive understanding. Four analysis tools are incorporated to identify relationships among different modules based on user specified datasets. miRegulome and its tools are helpful in understanding the biology of miRNAs and will also facilitate the discovery of biomarkers and therapeutics. With added features in upcoming releases, miRegulome will be an essential resource to the scientific community. http://bnet.egr.vcu.edu/miRegulome.

Prefrontal Cortical GABA Transmission Modulates Discrimination and Latent Inhibition of Conditioned Fear: Relevance for Schizophrenia

PubMed Central

Piantadosi, Patrick T; Floresco, Stan B

2014-01-01

Inhibitory gamma-aminobutyric acid (GABA) transmission within the prefrontal cortex (PFC) regulates numerous functions, and perturbations in GABAergic transmission within this region have been proposed to contribute to some of the cognitive and behavioral abnormalities associated with disorders such as schizophrenia. These abnormalities include deficits in emotional regulation and aberrant attributions of affective salience. Yet, how PFC GABA regulates these types of emotional processes are unclear. To address this issue, we investigated the contribution of PFC GABA transmission to different aspects of Pavlovian emotional learning in rats using translational discriminative fear conditioning and latent inhibition (LI) assays. Reducing prelimbic PFC GABAA transmission via infusions of the antagonist bicuculline before the acquisition or expression of fear conditioning eliminated the ability to discriminate between an aversive conditioned stimulus (CS+) paired with footshock vs a neutral CS–, resembling similar deficits observed in schizophrenic patients. In a separate experiment, blockade of PFC GABAA receptors before CS preexposure (PE) and conditioning did not affect subsequent expression of LI, but did enhance fear in rats that were not preexposed to the CS. In contrast, PFC GABA-blockade before a fear expression test disrupted the recall of learned irrelevance and abolished LI. These data suggest that normal PFC GABA transmission is critical for regulating and mitigating multiple aspects of aversive learning, including discrimination between fear vs safety signals and recall of information about the irrelevance of stimuli. Furthermore, they suggest that similar deficits in emotional regulation observed in schizophrenia may be driven in part by deficient PFC GABA activity. PMID:24784549

Prefrontal cortical GABA transmission modulates discrimination and latent inhibition of conditioned fear: relevance for schizophrenia.

PubMed

Piantadosi, Patrick T; Floresco, Stan B

2014-09-01

Inhibitory gamma-aminobutyric acid (GABA) transmission within the prefrontal cortex (PFC) regulates numerous functions, and perturbations in GABAergic transmission within this region have been proposed to contribute to some of the cognitive and behavioral abnormalities associated with disorders such as schizophrenia. These abnormalities include deficits in emotional regulation and aberrant attributions of affective salience. Yet, how PFC GABA regulates these types of emotional processes are unclear. To address this issue, we investigated the contribution of PFC GABA transmission to different aspects of Pavlovian emotional learning in rats using translational discriminative fear conditioning and latent inhibition (LI) assays. Reducing prelimbic PFC GABAA transmission via infusions of the antagonist bicuculline before the acquisition or expression of fear conditioning eliminated the ability to discriminate between an aversive conditioned stimulus (CS+) paired with footshock vs a neutral CS-, resembling similar deficits observed in schizophrenic patients. In a separate experiment, blockade of PFC GABAA receptors before CS preexposure (PE) and conditioning did not affect subsequent expression of LI, but did enhance fear in rats that were not preexposed to the CS. In contrast, PFC GABA-blockade before a fear expression test disrupted the recall of learned irrelevance and abolished LI. These data suggest that normal PFC GABA transmission is critical for regulating and mitigating multiple aspects of aversive learning, including discrimination between fear vs safety signals and recall of information about the irrelevance of stimuli. Furthermore, they suggest that similar deficits in emotional regulation observed in schizophrenia may be driven in part by deficient PFC GABA activity.

Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology.

PubMed

Salamone, John D; Yohn, Samantha E; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

2016-05-01

Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort-based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson's disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response

PubMed Central

Maréchal, Alexandre; Zou, Lee

2015-01-01

The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications. PMID:25403473

RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response.

PubMed

Maréchal, Alexandre; Zou, Lee

2015-01-01

The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications.

Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development

NASA Technical Reports Server (NTRS)

Cervantes, Emilio; Tocino, Angel

2005-01-01

Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bezier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

Visualization and dissemination of multidimensional proteomics data comparing protein abundance during Caenorhabditis elegans development.

PubMed

Riffle, Michael; Merrihew, Gennifer E; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N; Noble, William S; MacCoss, Michael J

2015-11-01

Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/ . Graphical Abstract ᅟ.

Visualization and Dissemination of Multidimensional Proteomics Data Comparing Protein Abundance During Caenorhabditis elegans Development

NASA Astrophysics Data System (ADS)

Riffle, Michael; Merrihew, Gennifer E.; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N.; Noble, William S.; MacCoss, Michael J.

2015-11-01

Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/.

Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure.

PubMed

Shields, Grant S; Moons, Wesley G; Slavich, George M

2017-07-01

Self-regulation is a fundamental human process that refers to multiple complex methods by which individuals pursue goals in the face of distractions. Whereas superior self-regulation predicts better academic achievement, relationship quality, financial and career success, and lifespan health, poor self-regulation increases a person's risk for negative outcomes in each of these domains and can ultimately presage early mortality. Given its centrality to understanding the human condition, a large body of research has examined cognitive, emotional, and behavioral aspects of self-regulation. In contrast, relatively little attention has been paid to specific biologic processes that may underlie self-regulation. We address this latter issue in the present review by examining the growing body of research showing that components of the immune system involved in inflammation can alter neural, cognitive, and motivational processes that lead to impaired self-regulation and poor health. Based on these findings, we propose an integrated, multilevel model that describes how inflammation may cause widespread biobehavioral alterations that promote self-regulatory failure. This immunologic model of self-regulatory failure has implications for understanding how biological and behavioral factors interact to influence self-regulation. The model also suggests new ways of reducing disease risk and enhancing human potential by targeting inflammatory processes that affect self-regulation.

Paraspeckles: Where Long Noncoding RNA Meets Phase Separation.

PubMed

Fox, Archa H; Nakagawa, Shinichi; Hirose, Tetsuro; Bond, Charles S

2018-02-01

Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles - protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA-protein and protein-protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular locks and keys: the role of small molecules in phytohormone research

PubMed Central

Fonseca, Sandra; Rosado, Abel; Vaughan-Hirsch, John; Bishopp, Anthony; Chini, Andrea

2014-01-01

Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds. PMID:25566283

Identification of Circular RNAs from the Parental Genes Involved in Multiple Aspects of Cellular Metabolism in Barley

PubMed Central

Darbani, Behrooz; Noeparvar, Shahin; Borg, Søren

2016-01-01

RNA circularization made by head-to-tail back-splicing events is involved in the regulation of gene expression from transcriptional to post-translational levels. By exploiting RNA-Seq data and down-stream analysis, we shed light on the importance of circular RNAs in plants. The results introduce circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes including protein coding transcripts, microRNA, rRNA, and long non-coding/microprotein coding RNAs. The results shed light on the mitochondrial exonic circular RNAs and imply the importance of circular RNAs for regulation of mitochondrial genes. Importantly, we introduce circular RNAs in barley and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs' functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear transcripts. PMID:27375638

Transient Receptor Potential Channels in the Vasculature

PubMed Central

Earley, Scott; Brayden, Joseph E.

2015-01-01

The mammalian genome encodes 28 distinct members of the transient receptor potential (TRP) superfamily of cation channels, which exhibit varying degrees of selectivity for different ionic species. Multiple TRP channels are present in all cells and are involved in diverse aspects of cellular function, including sensory perception and signal transduction. Notably, TRP channels are involved in regulating vascular function and pathophysiology, the focus of this review. TRP channels in vascular smooth muscle cells participate in regulating contractility and proliferation, whereas endothelial TRP channel activity is an important contributor to endothelium-dependent vasodilation, vascular wall permeability, and angiogenesis. TRP channels are also present in perivascular sensory neurons and astrocytic endfeet proximal to cerebral arterioles, where they participate in the regulation of vascular tone. Almost all of these functions are mediated by changes in global intracellular Ca2+ levels or subcellular Ca2+ signaling events. In addition to directly mediating Ca2+ entry, TRP channels influence intracellular Ca2+ dynamics through membrane depolarization associated with the influx of cations or through receptor- or store-operated mechanisms. Dysregulation of TRP channels is associated with vascular-related pathologies, including hypertension, neointimal injury, ischemia-reperfusion injury, pulmonary edema, and neurogenic inflammation. In this review, we briefly consider general aspects of TRP channel biology and provide an in-depth discussion of the functions of TRP channels in vascular smooth muscle cells, endothelial cells, and perivascular cells under normal and pathophysiological conditions. PMID:25834234

Novel interactive partners of neuroligin 3: new aspects for pathogenesis of autism.

PubMed

Shen, Chen; Huo, Li-rong; Zhao, Xin-liang; Wang, Pei-rong; Zhong, Nanbert

2015-05-01

Autism is a neurodevelopmental disorder with a strong genetic predisposition. Neurolign 3 (NLGN3) as a postsynaptic transmembrane protein, functions in both neuron synaptogenesis and glia-neuron communications. Previously, a gain of function mutation (R451C) in NLGN3 was identified in autistic patients, which illustrates the involvement of NLGN3 in autism pathogenesis. As proper synaptic targeting and functioning are controlled by intracellular protein interactions, in the current study, we tried to discover the intracellular regulation network in which NLGN3 might be involved by a yeast two-hybrid-based interactor identification. Fifty-one protein candidate partners were identified after screening a human fetal complementary DNA (cDNA) library with an intracellular fragment of NLGN3. The interactions of NLGN3 with a subset of candidates, including EEF1A1, FLNA, ITPRIP, CYP11A1, MT-CO2, GPR175, ACOT2, and QPRT, were further validated in human neuroblastoma cells or brain tissues. Furthermore, our study suggested that NLGN3 was functioning in cytosolic calcium balance and participating in calcium-regulated cellular processes. Our findings of novel NLGN3 binding partners provide evidences of involvement of NLGN3 in multiple biological pathways, especially calcium regulating and mitochondrial function, thus suggesting further significance. This new data not only leads to a better understanding of the physiological functions of NLGN3, but also provide new aspects for pathogenesis of autism.

Sleep and emotion regulation: An organizing, integrative review.

PubMed

Palmer, Cara A; Alfano, Candice A

2017-02-01

A growing body of research suggests that disrupted sleep is a robust risk and maintenance factor for a range of psychiatric conditions. One explanatory mechanism linking sleep and psychological health is emotion regulation. However, numerous components embedded within this construct create both conceptual and empirical challenges to the study of emotion regulation. These challenges are reflected in most sleep-emotion research by way of poor delineation of constructs and insufficient distinction among emotional processes. Most notably, a majority of research has focused on emotions generated as a consequence of inadequate sleep rather than underlying regulatory processes that may alter these experiences. The current review utilizes the process model of emotion regulation as an organizing framework for examining the impact of sleep upon various aspects of emotional experiences. Evidence is provided for maladaptive changes in emotion at multiple stages of the emotion generation and regulation process. We conclude with a call for experimental research designed to clearly explicate which points in the emotion regulation process appear most vulnerable to sleep loss as well as longitudinal studies to follow these processes in relation to the development of psychopathological conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative regulation of BMP signaling by the ski oncoprotein.

PubMed

Luo, Kunxin

2003-01-01

The bone morphogenetic proteins (BMPs) play important roles in the regulation of multiple aspects of vertebrate development. BMPs signal through the cell surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. The activity of this signal pathway can be modulated both by extracellular factors that regulate the binding of BMPs to the receptor and by intracellular proteins that interact with the Smad proteins. We have shown that Ski is an important negative regulator of the Smad proteins. Ski can bind to the BMP-Smad protein complexes in response to BMP and repress their ability to activate BMP target genes through disruption of a functional Smad complex and through recruitment of transcriptional co-repressors. The antagonism of BMP signaling by Ski results in neural specification in Xenopus embryos and inhibition of osteoblast differentiation in mouse bone-marrow stromal progenitor cells. This ability to modulate BMP signaling by Ski may play an important role in the regulation of craniofacial, neuronal, and skeletal muscle development.

Molecular and Cellular Aspects of Calcific Aortic Valve Disease

PubMed Central

Towler, Dwight A.

2014-01-01

Calcific aortic valve disease (CAVD) increasingly afflicts our aging population. One-third of our elderly have echocardiographic or radiological evidence of aortic valve sclerosis (CAVS), an early and subclinical form of CAVD. Age, gender, tobacco use, hypercholesterolemia, hypertension, and type II diabetes all contribute to the risk of disease that has worldwide distribution. Upon progression to its most severe form --- calcific aortic stenosis (CAS) --- CAVD becomes debilitating and devastating, and 2% of individuals over age 60 suffer from CAS to the extent that surgical intervention is required. No effective pharmacotherapies exist for treating those at risk for clinical progression. It is becoming increasingly apparent that a diverse spectrum of cellular and molecular mechanisms converge to regulate valvular calcium load; this is evidenced not only in histopathologic heterogeneity of CAVD but also from the multiplicity of cell types that can participate in valve biomineralization. In this review, we highlight our current understanding of CAVD disease biology, emphasizing molecular and cellular aspects of its regulation. We end by pointing to important biological and clinical questions that must be answered to enable sophisticated disease staging and the development of new strategies to medically treat CAVD. PMID:23833294

How Elementary School Students' Motivation Is Connected to Self-Regulation

ERIC Educational Resources Information Center

Jarvela, Sanna; Jarvenoja, Hanna; Malmberg, Jonna

2012-01-01

Empirical research reveals that students face difficulties engaging in learning and achieving their goals in a variety of learning contexts. To study effectively, students need to regulate their learning process. In spite of increased understanding of cognitive aspects of self-regulation, motivational aspects of regulation have not yet been…

Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

PubMed Central

Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

2013-01-01

The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism.

PubMed

Yang, Ying; Hsu, Phillip J; Chen, Yu-Sheng; Yang, Yun-Gui

2018-05-22

N 6 -methyladenosine (m 6 A) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m 6 A have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the m 6 A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs.

Integer Linear Programming for Constrained Multi-Aspect Committee Review Assignment

PubMed Central

Karimzadehgan, Maryam; Zhai, ChengXiang

2011-01-01

Automatic review assignment can significantly improve the productivity of many people such as conference organizers, journal editors and grant administrators. A general setup of the review assignment problem involves assigning a set of reviewers on a committee to a set of documents to be reviewed under the constraint of review quota so that the reviewers assigned to a document can collectively cover multiple topic aspects of the document. No previous work has addressed such a setup of committee review assignments while also considering matching multiple aspects of topics and expertise. In this paper, we tackle the problem of committee review assignment with multi-aspect expertise matching by casting it as an integer linear programming problem. The proposed algorithm can naturally accommodate any probabilistic or deterministic method for modeling multiple aspects to automate committee review assignments. Evaluation using a multi-aspect review assignment test set constructed using ACM SIGIR publications shows that the proposed algorithm is effective and efficient for committee review assignments based on multi-aspect expertise matching. PMID:22711970

Regulations and guidelines governing stem cell based products: Clinical considerations

PubMed Central

George, Bobby

2011-01-01

The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US) and European Union (EU) regulations are in place, in India, we do not have a well-defined regulatory framework for “stem cell based products (SCBP)”. There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects. PMID:21897884

Actin Out: Regulation of the Synaptic Cytoskeleton

PubMed Central

Spence, Erin F.; Soderling, Scott H.

2015-01-01

The small size of dendritic spines belies the elaborate role they play in excitatory synaptic transmission and ultimately complex behaviors. The cytoskeletal architecture of the spine is predominately composed of actin filaments. These filaments, which at first glance might appear simple, are also surprisingly complex. They dynamically assemble into different structures and serve as a platform for orchestrating the elaborate responses of the spine during spinogenesis and experience-dependent plasticity. Multiple mutations associated with human neurodevelopmental and psychiatric disorders involve genes that encode regulators of the synaptic cytoskeleton. A major, unresolved question is how the disruption of specific actin filament structures leads to the onset and progression of complex synaptic and behavioral phenotypes. This review will cover established and emerging mechanisms of actin cytoskeletal remodeling and how this influences specific aspects of spine biology that are implicated in disease. PMID:26453304

Dynamics of H3K27me3 methylation and demethylation in plant development

PubMed Central

Gan, Eng-Seng; Xu, Yifeng; Ito, Toshiro

2015-01-01

Epigenetic regulation controls multiple aspects of the plant development. The N-terminal tail of histone can be differently modified to regulate various chromatin activities. One of them, the trimethylation of histone H3 lysine 27 (H3K27me3) confers a repressive chromatin state with gene silencing. H3K27me3 is dynamically deposited and removed throughout development. While components of the H3K27me3 writer, Polycomb repressive complex 2 (PRC2), have been reported for almost 2 decades, it is only recently that JUMONJI (JMJ) proteins are reported as H3K27me3 demethylases, affirming the dynamic nature of histone modifications. This review highlights recent progress in plant epigenetic research, focusing on the H3K27me3 demethylases. PMID:26313233

Endothelial Response to Glucocorticoids in Inflammatory Diseases

PubMed Central

Zielińska, Karolina A.; Van Moortel, Laura; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

2016-01-01

The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients. PMID:28018358

Structure of the kinase domain of Gilgamesh from Drosophila melanogaster

PubMed Central

Han, Ni; Chen, CuiCui; Shi, Zhubing; Cheng, Dianlin

2014-01-01

The CK1 family kinases regulate multiple cellular aspects and play important roles in Wnt/Wingless and Hedgehog signalling. The kinase domain of Drosophila Gilgamesh isoform I (Gilgamesh-I), a homologue of human CK1-γ, was purified and crystallized. Crystals of methylated Gilgamesh-I kinase domain with a D210A mutation diffracted to 2.85 Å resolution and belonged to space group P43212, with unit-cell parameters a = b = 52.025, c = 291.727 Å. The structure of Gilgamesh-I kinase domain, which was determined by molecular replacement, has conserved catalytic elements and an active conformation. Structural comparison indicates that an extended loop between the α1 helix and the β4 strand exists in the Gilgamesh-I kinase domain. This extended loop may regulate the activity and function of Gilgamesh-I. PMID:24699734

MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

PubMed Central

Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

2013-01-01

One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex

PubMed Central

Liu, Jun; McConnell, Kristopher; Dixon, Michael; Calvi, Brian R.

2012-01-01

Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID:22049023

Oligomerization of the E. coli Core RNA Polymerase: Formation of (α2ββ'ω)2–DNA Complexes and Regulation of the Oligomerization by Auxiliary Subunits

PubMed Central

Kansara, Seema G.; Sukhodolets, Maxim V.

2011-01-01

In this work, using multiple, dissimilar physico-chemical techniques, we demonstrate that the Escherichia coli RNA polymerase core enzyme obtained through a classic purification procedure forms stable (α2ββ'ω)2 complexes in the presence or absence of short DNA probes. Multiple control experiments indicate that this self-association is unlikely to be mediated by RNA polymerase-associated non-protein molecules. We show that the formation of (α2ββ'ω)2 complexes is subject to regulation by known RNA polymerase interactors, such as the auxiliary SWI/SNF subunit of RNA polymerase RapA, as well as NusA and σ70. We also demonstrate that the separation of the core RNA polymerase and RNA polymerase holoenzyme species during Mono Q chromatography is likely due to oligomerization of the core enzyme. We have analyzed the oligomeric state of the polymerase in the presence or absence of DNA, an aspect that was missing from previous studies. Importantly, our work demonstrates that RNA polymerase oligomerization is compatible with DNA binding. Through in vitro transcription and in vivo experiments (utilizing a RapAR599/Q602 mutant lacking transcription-stimulatory function), we demonstrate that the formation of tandem (α2ββ'ω)2–DNA complexes is likely functionally significant and beneficial for the transcriptional activity of the polymerase. Taken together, our findings suggest a novel structural aspect of the E. coli elongation complex. We hypothesize that transcription by tandem RNA polymerase complexes initiated at hypothetical bidirectional “origins of transcription” may explain recurring switches of the direction of transcription in bacterial genomes. PMID:21533049

Nutriproteomics: facts, concepts, and perspectives.

PubMed

Sauer, Sascha; Luge, Toni

2015-03-01

Nutrition is a basic component of life. Nowadays, human nutrition research focuses amongst others on health-related aspects of food ingredients and extracts, and on analyzing the outcomes of specific diets. Usually, food ingredients such as bioactive peptides come in complex matrices. Single compounds, multiple interactions thereof and the underlying food matrix can vary physiological response of the organism. Proteins and peptides derived from food and beverages can cause adverse allergic reactions but are in general required for multiple functions such as growth and homeostatic regulation. Endogenously expressed human proteins and peptides can be used as biomarkers to monitor physiological deregulation and the effects of food consumption. The intestinal microbiome seems to play a fundamental role in establishing and maintaining physiological regulation and in digesting proteins and peptides and other biomolecules derived from food. Notably, the subtle interplay of flavor naturals in food and beverages with olfactory receptors can result in establishing human taste preferences, which again influences overall physiology. This article presents basic approaches and concepts to address scientific questions in nutritional proteomics and discusses potential benefits of proteomics-based methodologies to help advance the field of molecular nutrition research. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shrimp miR-12 Suppresses White Spot Syndrome Virus Infection by Synchronously Triggering Antiviral Phagocytosis and Apoptosis Pathways

PubMed Central

Shu, Le; Zhang, Xiaobo

2017-01-01

Growing evidence has indicated that the innate immune system can be regulated by microRNAs (miRNAs). However, the mechanism underlying miRNA-mediated simultaneous activation of multiple immune pathways remains unknown. To address this issue, the role of host miR-12 in shrimp (Marsupenaeus japonicus) antiviral immune responses was characterized in the present study. The results indicated that miR-12 participated in virus infection, host phagocytosis, and apoptosis in defense against white spot syndrome virus invasion. miR-12 could simultaneously trigger phagocytosis, apoptosis, and antiviral immunity through the synchronous downregulation of the expression of shrimp genes [PTEN (phosphatase and tensin homolog) and BI-1(transmembrane BAX inhibitor motif containing 6)] and the viral gene (wsv024). Further analysis showed that miR-12 could synchronously mediate the 5′–3′ exonucleolytic degradation of its target mRNAs, and this degradation terminated in the vicinity of the 3′ untranslated region sequence complementary to the seed sequence of miR-12. Therefore, the present study showed novel aspects of the miRNA-mediated simultaneous regulation of multiple immune pathways. PMID:28824612

The Conference Proceedings of the 1999 Air Transport Research Group (ATRG) of the WCTR Society. Volume 2

NASA Technical Reports Server (NTRS)

Zhang, Anming (Editor); Bowen Brent D. (Editor)

1999-01-01

In this paper, we develop a model with which allows us to measure not only the changes in equilibrium outcomes and welfare consequences of liberalizing a bilateral air transport agreement, but also the distribution of the gains and losses to carriers and consumers of each bilateral country and those of the third foreign countries. Our model also allows to measure the effects of changes in a bilateral agreement on the amount of traffic diversion between the direct bilateral routes and the indirect routes via a third country. We also provide an extension of our model to a case of oligopoly market outcome (Coumot Nash equilibrium). In our model, quality aspects are treated in the framework of hedonic price theory by specifying the quality-adjusted price (quantity) as a multiplication of the observed price (quantity) by the reciprocal quality index function (the quality index function). Numerical simulations were conducted to measure the effects of changing the following major policy levers in a bilateral air transport agreement: 1) Removing price regulation while retaining frequency and entry restrictions; 2) Removing price and entry regulation while retaining frequency restrictions; 3) Removing frequency regulations while retaining price and entry regulations; 4) Removing frequency and entry regulations while retaining price regulation; 5) Removing price and frequency regulations while retaining entry restriction; and 6) Removing all price, frequency and entry regulations (de facto, open skies).

Ghrelin: an emerging player in the regulation of reproduction in non-mammalian vertebrates.

PubMed

Unniappan, Suraj

2010-07-01

The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of multiple endocrine factors mainly produced from the brain, pituitary, and gonads. In addition to these, several other tissues including the fat and gut produce factors that have reproductive effects. Ghrelin is one such gut/brain hormone with species-specific effects in the regulation of mammalian reproduction. Recent studies have shown that ghrelin and ghrelin receptor mRNAs, and protein are expressed in the ovary and testis of mammals, indicating a direct effect for ghrelin in the control of reproduction. Ghrelin regulates mammalian reproduction by modulating hormone secretion from the brain and pituitary, and by acting directly on the gonads to influence reproductive tissue development and steroid hormone release. Based on the studies reported so far, ghrelin seems to have a predominantly inhibitory role on mammalian reproduction. The presence of ghrelin and ghrelin receptor has been found in the brain, pituitary and gonads of several non-mammalian vertebrates. In contrast to mammals, ghrelin seems to have a stimulatory role in the regulation of non-mammalian reproduction. The main objective of this review is to do a perspective analysis of the comparative aspects of ghrelin regulation of reproduction. (c) 2009 Elsevier Inc. All rights reserved.

Gender-, Race-, and Income-Based Stereotype Threat: The Effects of Multiple Stigmatized Aspects of Identity on Math Performance and Working Memory Function

ERIC Educational Resources Information Center

Tine, Michele; Gotlieb, Rebecca

2013-01-01

This study compared the relative impact of gender-, race-, and income-based stereotype threat and examined if individuals with multiple stigmatized aspects of identity experience a larger stereotype threat effect on math performance and working memory function than people with one stigmatized aspect of identity. Seventy-one college students of the…

Transcriptional regulation of neuronal polarity and morphogenesis in the mammalian brain

PubMed Central

de la Torre-Ubieta, Luis; Bonni, Azad

2012-01-01

The highly specialized morphology of a neuron, typically consisting of a long axon and multiple branching dendrites, lies at the core of the principle of dynamic polarization, whereby information flows from dendrites toward the soma and to the axon. For more than a century neuroscientists have been fascinated by how shape is important for neuronal function and how neurons acquire their characteristic morphology. During the past decade, substantial progress has been made in our understanding of the molecular underpinnings of neuronal polarity and morphogenesis. In these studies, transcription factors have emerged as key players governing multiple aspects of neuronal morphogenesis from neuronal polarization and migration to axon growth and pathfinding to dendrite growth and branching to synaptogenesis. In this review, we will highlight the role of transcription factors in shaping neuronal morphology with emphasis on recent literature in mammalian systems. PMID:21982366

Neuropeptides, Microbiota, and Behavior.

PubMed

Holzer, P

2016-01-01

The gut microbiota and the brain interact with each other through multiple bidirectional signaling pathways in which neuropeptides and neuroactive peptide messengers play potentially important mediator roles. Currently, six particular modes of a neuropeptide link are emerging. (i) Neuropeptides and neurotransmitters contribute to the mutual microbiota-host interaction. (ii) The synthesis of neuroactive peptides is influenced by microbial control of the availability of amino acids. (iii) The activity of neuropeptides is tempered by microbiota-dependent autoantibodies. (iv) Peptide signaling between periphery and brain is modified by a regulatory action of the gut microbiota on the blood-brain barrier. (v) Within the brain, gut hormones released under the influence of the gut microbiota turn into neuropeptides that regulate multiple aspects of brain activity. (vi) Cerebral neuropeptides participate in the molecular, behavioral, and autonomic alterations which the brain undergoes in response to signals from the gut microbiota. © 2016 Elsevier Inc. All rights reserved.

The CRISPR/Cas Immune System Is an Operon Regulated by LeuO, H-NS, and Leucine-Responsive Regulatory Protein in Salmonella enterica Serovar Typhi ▿ †

PubMed Central

Medina-Aparicio, L.; Rebollar-Flores, J. E.; Gallego-Hernández, A. L.; Vázquez, A.; Olvera, L.; Gutiérrez-Ríos, R. M.; Calva, E.; Hernández-Lucas, I.

2011-01-01

Prokaryotes have developed multiple strategies to survive phage attack and invasive DNA. Recently, a novel genetic program denominated the CRISPR/Cas system was demonstrated to have a role in these biological processes providing genetic immunity. This defense mechanism is widespread in the Archaea and Bacteria, suggesting an ancient origin. In the last few years, progress has been made regarding the functionality of the CRISPR/Cas system; however, many basic aspects of the system remain unknown. For instance, there are few studies about the conditions and regulators involved in its transcriptional control. In this work, we analyzed the transcriptional organization of the CRISPR/Cas system as well as the positive and negative regulators involved in its genetic expression in Salmonella enterica serovar Typhi. The results obtained show that in S. Typhi the CRISPR/Cas system is a LeuO-dependent operon silenced by the global regulator LRP, in addition to the previously known nucleoid-associated protein H-NS; both LRP and H-NS bind upstream and downstream of the transcriptional start site of casA. In this study, relevant nucleotides of the casA regulatory region that mediate its LeuO transcriptional activation were identified. Interestingly, specific growth conditions (N-minimal medium) were found for the LeuO-independent expression of the CRISPR/Cas system in S. Typhi. Thus, our work provides evidence that there are multiple modulators involved in the genetic expression of this immune system in S. Typhi IMSS-1. PMID:21398529

Synaptic plasticity in drug reward circuitry.

PubMed

Winder, Danny G; Egli, Regula E; Schramm, Nicole L; Matthews, Robert T

2002-11-01

Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB.

PubMed

Willis, Simon N; Tellier, Julie; Liao, Yang; Trezise, Stephanie; Light, Amanda; O'Donnell, Kristy; Garrett-Sinha, Lee Ann; Shi, Wei; Tarlinton, David M; Nutt, Stephen L

2017-11-10

Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation. PU.1 and SpiB regulate the expression of many components of the B cell receptor signaling pathway and the receptors for CD40L, BAFF and TLR ligands. Thus, PU.1 and SpiB enable B cells to appropriately respond to environmental cues.

Biological properties of 6-gingerol: a brief review.

PubMed

Wang, Shaopeng; Zhang, Caihua; Yang, Guang; Yang, Yanzong

2014-07-01

Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.

Inhibition and Avoidance of mRNA Degradation by RNA Viruses

PubMed Central

Moon, Stephanie L.; Barnhart, Michael D.; Wilusz, Jeffrey

2012-01-01

The cellular mRNA decay machinery plays a major role in regulating the quality and quantity of gene expression in cells. This machinery involves multiple enzymes and pathways that converge to promote the exonucleolytic decay of mRNAs. The transcripts made by RNA viruses are susceptible to degradation by this machinery and, in fact, can be actively targeted. Thus, to maintain gene expression and replication, RNA viruses have evolved a number of strategies to avoid and/or inactivate aspects of the cellular mRNA decay machinery. Recent work uncovering the mechanisms used by RNA viruses to maintain the stability of their transcripts is described below. PMID:22626865

The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics.

PubMed

Camara-Lemarroy, Carlos R; Metz, Luanne; Meddings, Jonathan B; Sharkey, Keith A; Wee Yong, V

2018-05-30

Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.

Risky Roads.

ERIC Educational Resources Information Center

Gusfield, Joseph R.

1991-01-01

Examines multiple perspectives and multiple communities involved in the study of drinking and driving and traffic safety. Discusses the following aspects of the question: (1) informal social controls on the driving event; (2) contexts of traffic safety; (3) institutional aspects; (4) social movements; (5) the social and cultural environment; (6)…

Photoperiod- and Triiodothyronine-dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

PubMed

Banks, Ruth; Delibegovic, Mirela; Stevenson, Tyler J

2016-06-01

Seasonal trade-offs in reproduction and immunity are ubiquitous in nature. The mechanisms that govern transitions across seasonal physiological states appear to involve reciprocal switches in the local synthesis of thyroid hormone. In long-day (LD) summer-like conditions, increased hypothalamic triiodothyronine (T3) stimulates gonadal development. Alternatively, short-day (SD) winter-like conditions increase peripheral leukocytes and enhance multiple aspects of immune function. These data indicate that the localized effects of T3 in the hypothalamus and leukocytes are photoperiod dependent. We tested the hypothesis that increased peripheral T3 in SD conditions would increase aspects of reproductive physiology and inhibit immune function, whereas T3 injections in LD conditions would facilitate aspects of immune function (i.e., leukocytes). In addition, we also examined whether T3 regulates hypothalamic neuropeptide expression as well as hypothalamic and splenic proinflammatory cytokine expression. Adult male Siberian hamsters were maintained in LD (15L:9D) or transferred to SD (9L:15D) for 8 weeks. A subset of LD and SD hamsters was treated daily with 5 µg T3 for 2 weeks. LD and SD controls were injected with saline. Daily T3 administration in SD hamsters (SD+T3) resulted in a rapid and substantial decrease in peripheral leukocyte concentrations and stimulated gonadal development. T3 treatment in LD (LD+T3) had no effect on testicular volumes but significantly increased leukocyte concentrations. Molecular analyses revealed that T3 stimulated interleukin 1β messenger RNA (mRNA) expression in the spleen and inhibited RFamide Related Peptide-3 mRNA expression in the hypothalamus. Moreover, there was a photoperiod-dependent decrease in splenic tumor necrosis factor-α mRNA expression. These findings reveal that T3 has tissue-specific and photoperiod-dependent regulation of seasonal rhythms in reproduction and immune function. © 2016 The Author(s).

Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

PubMed

Wason, James M S; Stecher, Lynne; Mander, Adrian P

2014-09-17

Multi-arm trials enable the evaluation of multiple treatments within a single trial. They provide a way of substantially increasing the efficiency of the clinical development process. However, since multi-arm trials test multiple hypotheses, some regulators require that a statistical correction be made to control the chance of making a type-1 error (false-positive). Several conflicting viewpoints are expressed in the literature regarding the circumstances in which a multiple-testing correction should be used. In this article we discuss these conflicting viewpoints and review the frequency with which correction methods are currently used in practice. We identified all multi-arm clinical trials published in 2012 by four major medical journals. Summary data on several aspects of the trial design were extracted, including whether the trial was exploratory or confirmatory, whether a multiple-testing correction was applied and, if one was used, what type it was. We found that almost half (49%) of published multi-arm trials report using a multiple-testing correction. The percentage that corrected was higher for trials in which the experimental arms included multiple doses or regimens of the same treatments (67%). The percentage that corrected was higher in exploratory than confirmatory trials, although this is explained by a greater proportion of exploratory trials testing multiple doses and regimens of the same treatment. A sizeable proportion of published multi-arm trials do not correct for multiple-testing. Clearer guidance about whether multiple-testing correction is needed for multi-arm trials that test separate treatments against a common control group is required.

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis.

PubMed

Rajamani, Deepa; Bhasin, Manoj K

2016-05-03

Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression. Multidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis. Rank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities. It is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.

Unique Associations Between Big Five Personality Aspects and Multiple Dimensions of Well-Being.

PubMed

Sun, Jessie; Kaufman, Scott Barry; Smillie, Luke D

2018-04-01

Personality traits are associated with well-being, but the precise correlates vary across well-being dimensions and within each Big Five domain. This study is the first to examine the unique associations between the Big Five aspects (rather than facets) and multiple well-being dimensions. Two samples of U.S. participants (total N = 706; M age  = 36.17; 54% female) recruited via Amazon's Mechanical Turk completed measures of the Big Five aspects and subjective, psychological, and PERMA well-being. One aspect within each domain was more strongly associated with well-being variables. Enthusiasm and Withdrawal were strongly associated with a broad range of well-being variables, but other aspects of personality also had idiosyncratic associations with distinct forms of positive functioning (e.g., Compassion with positive relationships, Industriousness with accomplishment, and Intellect with personal growth). An aspect-level analysis provides an optimal (i.e., parsimonious yet sufficiently comprehensive) framework for describing the relation between personality traits and multiple ways of thriving in life. © 2016 Wiley Periodicals, Inc.

Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung

PubMed Central

Chuang, Pao-Tien; Kawcak, T'Nay; McMahon, Andrew P.

2003-01-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue is how negative regulation of Hh signaling might contribute to generating differential responses over tens of cell diameters. In cells that respond to Hh, two proteins that are up-regulated are Patched1 (Ptch1), the Hh receptor, a general target in both invertebrate and vertebrate organisms, and Hip1, a Hh-binding protein that is vertebrate specific. To address the developmental role of Hip1 in the context of Hh signaling, we generated Hip1 mutants in the mouse. Loss of Hip1 function results in specific defects in two Hh target issues, the lung, a target of Sonic hedgehog (Shh) signaling, and the endochondral skeleton, a target of Indian hedgehog (Ihh) signaling. Hh signaling was up-regulated in Hip1 mutants, substantiating Hip1's general role in negatively regulating Hh signaling. Our studies focused on Hip1 in the lung. Here, a dynamic interaction between Hh and fibroblast growth factor (Fgf) signaling, modulated at least in part by Hip1, controls early lung branching. PMID:12569124

Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung.

PubMed

Chuang, Pao-Tien; Kawcak, T'Nay; McMahon, Andrew P

2003-02-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue is how negative regulation of Hh signaling might contribute to generating differential responses over tens of cell diameters. In cells that respond to Hh, two proteins that are up-regulated are Patched1 (Ptch1), the Hh receptor, a general target in both invertebrate and vertebrate organisms, and Hip1, a Hh-binding protein that is vertebrate specific. To address the developmental role of Hip1 in the context of Hh signaling, we generated Hip1 mutants in the mouse. Loss of Hip1 function results in specific defects in two Hh target issues, the lung, a target of Sonic hedgehog (Shh) signaling, and the endochondral skeleton, a target of Indian hedgehog (Ihh) signaling. Hh signaling was up-regulated in Hip1 mutants, substantiating Hip1's general role in negatively regulating Hh signaling. Our studies focused on Hip1 in the lung. Here, a dynamic interaction between Hh and fibroblast growth factor (Fgf) signaling, modulated at least in part by Hip1, controls early lung branching.

Identification of critical functional residues of receptor-like kinase ERECTA.

PubMed

Kosentka, Pawel Z; Zhang, Liang; Simon, Yonas A; Satpathy, Binita; Maradiaga, Richard; Mitoubsi, Omar; Shpak, Elena D

2017-03-01

In plants, extracellular signals are primarily sensed by plasma membrane-localized receptor-like kinases (RLKs). ERECTA is a leucine-rich repeat RLK that together with its paralogs ERECTA-like 1 (ERL1) and ERL2 regulates multiple aspects of plant development. ERECTA forms complexes with a range of co-receptors and senses secreted cysteine-rich small proteins from the EPF/EPFL family. Currently the mechanism of the cytoplasmic domain activation and transmission of the signal by ERECTA is unclear. To gain a better understanding we performed a structure-function analysis by introducing altered ERECTA genes into erecta and erecta erl1 erl2 mutants. These experiments indicated that ERECTA's ability to phosphorylate is functionally significant, and that while the cytoplasmic juxtamembrane domain is important for ERECTA function, the C-terminal tail is not. An analysis of multiple putative phosphorylation sites identified four amino acids in the activation segment of the kinase domain as functionally important. Homology of those residues to functionally significant amino acids in multiple other plant RLKs emphasizes similarities in RLK function. Specifically, our data predicts Thr812 as a primary site of phosphor-activation and potential inhibitory phosphorylation of Tyr815 and Tyr820. In addition, our experiments suggest that there are differences in the molecular mechanism of ERECTA function during regulation of stomata development and in elongation of above-ground organs. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Osthole decreases beta amyloid levels through up-regulation of miR-107 in Alzheimer's disease.

PubMed

Jiao, Yanan; Kong, Liang; Yao, Yingjia; Li, Shaoheng; Tao, Zhenyu; Yan, Yuhui; Yang, Jingxian

2016-09-01

Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). Although osthole has been shown to neuroprotective activity in AD, the exact molecular mechanism of its neuroprotective effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of AD development and progression, indicating that targeting miRNAs could be a novel strategy to treat AD. In the current study, we investigated whether a natural coumarin derivative osthole could up-regulate miR-107, resulting in facilitating the cells survival, reducing LDH leakage, inhibiting apoptosis and reducing beta amyloid (Aβ) production in AD. We found that osthole treatment significantly up-regulate miR-107 expression and inhibited BACE1, one of the targets of miR-107. Administration of osthole to APP/PS1 transgenic mice resulted in a significant improvement in learning and memory function, which was associated with a significant a decrease in Aβ in the hippocampal and cortex region of the brain. Our findings demonstrated that osthole plays a neuroprotective activity role in part through up-regulate miR-107 in AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module.

PubMed

Oldenburg, Joppe; van der Krogt, Gerard; Twiss, Floor; Bongaarts, Annika; Habani, Yasmin; Slotman, Johan A; Houtsmuller, Adriaan; Huveneers, Stephan; de Rooij, Johan

2015-11-27

Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics.

A Network of Chromatin Factors Is Regulating the Transition to Postembryonic Development in Caenorhabditis elegans

PubMed Central

Erdelyi, Peter; Wang, Xing; Suleski, Marina; Wicky, Chantal

2016-01-01

Mi2 proteins are evolutionarily conserved, ATP-dependent chromatin remodelers of the CHD family that play key roles in stem cell differentiation and reprogramming. In Caenorhabditis elegans, the let-418 gene encodes one of the two Mi2 homologs, which is part of at least two chromatin complexes, namely the Nucleosome Remodeling and histone Deacetylase (NuRD) complex and the MEC complex, and functions in larval development, vulval morphogenesis, lifespan regulation, and cell fate determination. To explore the mechanisms involved in the action of LET-418/Mi2, we performed a genome-wide RNA interference (RNAi) screen for suppressors of early larval arrest associated with let-418 mutations. We identified 29 suppressor genes, of which 24 encode chromatin regulators, mostly orthologs of proteins present in transcriptional activator complexes. The remaining five genes vary broadly in their predicted functions. All suppressor genes could suppress multiple aspects of the let-418 phenotype, including developmental arrest and ectopic expression of germline genes in the soma. Analysis of available transcriptomic data and quantitative PCR revealed that LET-418 and the suppressors of early larval arrest are regulating common target genes. These suppressors might represent direct competitors of LET-418 complexes for chromatin regulation of crucial genes involved in the transition to postembryonic development. PMID:28007841

A Network of Chromatin Factors Is Regulating the Transition to Postembryonic Development in Caenorhabditis elegans.

PubMed

Erdelyi, Peter; Wang, Xing; Suleski, Marina; Wicky, Chantal

2017-02-09

Mi2 proteins are evolutionarily conserved, ATP-dependent chromatin remodelers of the CHD family that play key roles in stem cell differentiation and reprogramming. In Caenorhabditis elegans , the let-418 gene encodes one of the two Mi2 homologs, which is part of at least two chromatin complexes, namely the Nucleosome Remodeling and histone Deacetylase (NuRD) complex and the MEC complex, and functions in larval development, vulval morphogenesis, lifespan regulation, and cell fate determination. To explore the mechanisms involved in the action of LET-418/Mi2, we performed a genome-wide RNA interference (RNAi) screen for suppressors of early larval arrest associated with let-418 mutations. We identified 29 suppressor genes, of which 24 encode chromatin regulators, mostly orthologs of proteins present in transcriptional activator complexes. The remaining five genes vary broadly in their predicted functions. All suppressor genes could suppress multiple aspects of the let-418 phenotype, including developmental arrest and ectopic expression of germline genes in the soma. Analysis of available transcriptomic data and quantitative PCR revealed that LET-418 and the suppressors of early larval arrest are regulating common target genes. These suppressors might represent direct competitors of LET-418 complexes for chromatin regulation of crucial genes involved in the transition to postembryonic development. Copyright © 2017 Erdelyi et al.

VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module

PubMed Central

Oldenburg, Joppe; van der Krogt, Gerard; Twiss, Floor; Bongaarts, Annika; Habani, Yasmin; Slotman, Johan A.; Houtsmuller, Adriaan; Huveneers, Stephan; de Rooij, Johan

2015-01-01

Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics. PMID:26611125

[Communication on health and safety risk control in contemporary society: an interdisciplinary approach].

PubMed

Rangel-S, Maria Ligia

2007-01-01

This paper discusses communication as a technology for risk control with health and safety protection and promotion, within the context of a "risk society". As a component of Risk Analysis, risk communication is a technology that appears in risk literature, with well defined objectives, principles and models. These aspects are described and the difficulties are stressed, taking into consideration the multiple rationales related to risks in the culture and the many different aspects of risk regulation and control in the so-called "late modernity". Consideration is also given to the complexity of the communications process, guided by theoretical and methodological discussions in the field. In order to understand the true value of the communications field for risk control with health and safety protection and promotion, this paper also offers an overview of communication theories that support discussions of this matter, proposing a critical approach to models that include the dimensions of power and culture in the context of a capitalist society.

Specifying and Refining a Measurement Model for a Computer-Based Interactive Assessment

ERIC Educational Resources Information Center

Levy, Roy; Mislevy, Robert J.

2004-01-01

The challenges of modeling students' performance in computer-based interactive assessments include accounting for multiple aspects of knowledge and skill that arise in different situations and the conditional dependencies among multiple aspects of performance. This article describes a Bayesian approach to modeling and estimating cognitive models…

Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways*

PubMed Central

Rispal, Delphine; Eltschinger, Sandra; Stahl, Michael; Vaga, Stefania; Bodenmiller, Bernd; Abraham, Yann; Filipuzzi, Ireos; Movva, N. Rao; Aebersold, Ruedi; Helliwell, Stephen B.; Loewith, Robbie

2015-01-01

Target of rapamycin is a Ser/Thr kinase that operates in two conserved multiprotein complexes, TORC1 and TORC2. Unlike TORC1, TORC2 is insensitive to rapamycin, and its functional characterization is less advanced. Previous genetic studies demonstrated that TORC2 depletion leads to loss of actin polarization and loss of endocytosis. To determine how TORC2 regulates these readouts, we engineered a yeast strain in which TORC2 can be specifically and acutely inhibited by the imidazoquinoline NVP-BHS345. Kinetic analyses following inhibition of TORC2, supported with quantitative phosphoproteomics, revealed that TORC2 regulates these readouts via distinct pathways as follows: rapidly through direct protein phosphorylation cascades and slowly through indirect changes in the tensile properties of the plasma membrane. The rapid signaling events are mediated in large part through the phospholipid flippase kinases Fpk1 and Fpk2, whereas the slow signaling pathway involves increased plasma membrane tension resulting from a gradual depletion of sphingolipids. Additional hits in our phosphoproteomic screens highlight the intricate control TORC2 exerts over diverse aspects of eukaryote cell physiology. PMID:25882841

The postsynaptic t-SNARE Syntaxin 4 controls traffic of Neuroligin 1 and Synaptotagmin 4 to regulate retrograde signaling.

PubMed

Harris, Kathryn P; Zhang, Yao V; Piccioli, Zachary D; Perrimon, Norbert; Littleton, J Troy

2016-05-25

Postsynaptic cells can induce synaptic plasticity through the release of activity-dependent retrograde signals. We previously described a Ca(2+)-dependent retrograde signaling pathway mediated by postsynaptic Synaptotagmin 4 (Syt4). To identify proteins involved in postsynaptic exocytosis, we conducted a screen for candidates that disrupted trafficking of a pHluorin-tagged Syt4 at Drosophila neuromuscular junctions (NMJs). Here we characterize one candidate, the postsynaptic t-SNARE Syntaxin 4 (Syx4). Analysis of Syx4 mutants reveals that Syx4 mediates retrograde signaling, modulating the membrane levels of Syt4 and the transsynaptic adhesion protein Neuroligin 1 (Nlg1). Syx4-dependent trafficking regulates synaptic development, including controlling synaptic bouton number and the ability to bud new varicosities in response to acute neuronal stimulation. Genetic interaction experiments demonstrate Syx4, Syt4, and Nlg1 regulate synaptic growth and plasticity through both shared and parallel signaling pathways. Our findings suggest a conserved postsynaptic SNARE machinery controls multiple aspects of retrograde signaling and cargo trafficking within the postsynaptic compartment.

INPP5E Preserves Genomic Stability through Regulation of Mitosis.

PubMed

Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

2017-03-15

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

Different aspects of multiplicity distribution of shower particles in central collisions with AgBr target

NASA Astrophysics Data System (ADS)

Bhattacharyya, Swarnapratim; Haiduc, Maria; Neagu, Alina Tania; Firu, Elena

Different aspects like multiplicity moments, Dq moments and multiplicity fluctuations in terms of scaled variance of the shower particles has been carried out for central events of 16O-AgBr, 22Ne-AgBr and 32S-AgBr interactions at (4.1-4.5) AGeV/c. Comparison of our results with different experimental analysis of central collisions of emulsion data has been performed whenever available.

Ethylene Signaling Negatively Regulates Freezing Tolerance by Repressing Expression of CBF and Type-A ARR Genes in Arabidopsis[W][OA

PubMed Central

Shi, Yiting; Tian, Shouwei; Hou, Lingyan; Huang, Xiaozhen; Zhang, Xiaoyan; Guo, Hongwei; Yang, Shuhua

2012-01-01

The phytohormone ethylene regulates multiple aspects of plant growth and development and responses to environmental stress. However, the exact role of ethylene in freezing stress remains unclear. Here, we report that ethylene negatively regulates plant responses to freezing stress in Arabidopsis thaliana. Freezing tolerance was decreased in ethylene overproducer1 and by the application of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid but increased by the addition of the ethylene biosynthesis inhibitor aminoethoxyvinyl glycine or the perception antagonist Ag+. Furthermore, ethylene-insensitive mutants, including etr1-1, ein4-1, ein2-5, ein3-1, and ein3 eil1, displayed enhanced freezing tolerance. By contrast, the constitutive ethylene response mutant ctr1-1 and EIN3-overexpressing plants exhibited reduced freezing tolerance. Genetic and biochemical analyses revealed that EIN3 negatively regulates the expression of CBFs and type-A Arabidopsis response regulator5 (ARR5), ARR7, and ARR15 by binding to specific elements in their promoters. Overexpression of these ARR genes enhanced the freezing tolerance of plants. Thus, our study demonstrates that ethylene negatively regulates cold signaling at least partially through the direct transcriptional control of cold-regulated CBFs and type-A ARR genes by EIN3. Our study also provides evidence that type-A ARRs function as key nodes to integrate ethylene and cytokinin signaling in regulation of plant responses to environmental stress. PMID:22706288

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

PubMed

Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

2017-02-01

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Clinical research regulation in India-history, development, initiatives, challenges and controversies: Still long way to go.

PubMed

Imran, Mohammed; Najmi, Abul K; Rashid, Mohammad F; Tabrez, Shams; Shah, Mushtaq A

2013-01-01

The Central Drugs Standard Control Organisation and its chairman Drug Controller general of India are bequeathed to protect the citizens from the marketing of unsafe medication. The startling findings, of the 59(th)report of the Parliamentary Standing Committee on Health and Family Welfare, have uncovered the lax standards followed by the regulatory authorities in India. The growing clinical research after the product patents rights for the pharmaceutical industries as per the trade related aspects of intellectual property rights agreement and adverse drug reaction monitoring of the marketed drugs have raised many ethical and regulatory issues regarding the promotion of new drugs in Indian markets. Many controversial group of medicines; unauthorised and irrational FDCs not relevant to India's medical needs, are available which are not sold in any of the countries with matured regulatory bodies. It becomes vital to understand the history, growth and evolution of the regulatory aspects of drugs which are handled by multiple Ministries and Departments of the Government of India. Although amendment to Schedule Y, registration of Contract Research Organisations, registration of Clinical Trials, Speeding up review process, Pharmacovigilance (PhV) programme for India and Inspection of clinical trial sites have been started by the various regulatory agencies. However due to casual approach in marketing approval for sale of the drugs, the unethical steps taken by some pharmaceutical companies and medical practitioners has reiterated the need to get appropriate understanding of present regulation of drugs and clinical research especially regarding the practical rules and regulations.

Neuroscience of Childhood Poverty: Evidence of Impacts and Mechanisms as Vehicles of Dialog With Ethics.

PubMed

Lipina, Sebastián J; Evers, Kathinka

2017-01-01

Several studies have identified associations between poverty and development of self-regulation during childhood, which is broadly defined as those skills involved in cognitive, emotional, and stress self-regulation. These skills are influenced by different individual and contextual factors at multiple levels of analysis (i.e., individual, family, social, and cultural). Available evidence suggests that the influences of those biological, psychosocial, and sociocultural factors on emotional and cognitive development can vary according to the type, number, accumulation of risks, and co-occurrence of adverse circumstances that are related to poverty, the time in which these factors exert their influences, and the individual susceptibility to them. Complementary, during the past three decades, several experimental interventions that were aimed at optimizing development of self-regulation of children who live in poverty have been designed, implemented, and evaluated. Their results suggest that it is possible to optimize different aspects of cognitive performance and that it would be possible to transfer some aspects of these gains to other cognitive domains and academic achievement. We suggest that it is an important task for ethics, notably but not exclusively neuroethics, to engage in this interdisciplinary research domain to contribute analyses of key concepts, arguments, and interpretations. The specific evidence that neuroscience brings to the analyses of poverty and its implications needs to be spelled out in detail and clarified conceptually, notably in terms of causes of and attitudes toward poverty, implications of poverty for brain development, and for the possibilities to reduce and reverse these effects.

Neuroscience of Childhood Poverty: Evidence of Impacts and Mechanisms as Vehicles of Dialog With Ethics

PubMed Central

Lipina, Sebastián J.; Evers, Kathinka

2017-01-01

Several studies have identified associations between poverty and development of self-regulation during childhood, which is broadly defined as those skills involved in cognitive, emotional, and stress self-regulation. These skills are influenced by different individual and contextual factors at multiple levels of analysis (i.e., individual, family, social, and cultural). Available evidence suggests that the influences of those biological, psychosocial, and sociocultural factors on emotional and cognitive development can vary according to the type, number, accumulation of risks, and co-occurrence of adverse circumstances that are related to poverty, the time in which these factors exert their influences, and the individual susceptibility to them. Complementary, during the past three decades, several experimental interventions that were aimed at optimizing development of self-regulation of children who live in poverty have been designed, implemented, and evaluated. Their results suggest that it is possible to optimize different aspects of cognitive performance and that it would be possible to transfer some aspects of these gains to other cognitive domains and academic achievement. We suggest that it is an important task for ethics, notably but not exclusively neuroethics, to engage in this interdisciplinary research domain to contribute analyses of key concepts, arguments, and interpretations. The specific evidence that neuroscience brings to the analyses of poverty and its implications needs to be spelled out in detail and clarified conceptually, notably in terms of causes of and attitudes toward poverty, implications of poverty for brain development, and for the possibilities to reduce and reverse these effects. PMID:28184204

Clinical research regulation in India-history, development, initiatives, challenges and controversies: Still long way to go

PubMed Central

Imran, Mohammed; Najmi, Abul K.; Rashid, Mohammad F.; Tabrez, Shams; Shah, Mushtaq A.

2013-01-01

The Central Drugs Standard Control Organisation and its chairman Drug Controller general of India are bequeathed to protect the citizens from the marketing of unsafe medication. The startling findings, of the 59threport of the Parliamentary Standing Committee on Health and Family Welfare, have uncovered the lax standards followed by the regulatory authorities in India. The growing clinical research after the product patents rights for the pharmaceutical industries as per the trade related aspects of intellectual property rights agreement and adverse drug reaction monitoring of the marketed drugs have raised many ethical and regulatory issues regarding the promotion of new drugs in Indian markets. Many controversial group of medicines; unauthorised and irrational FDCs not relevant to India's medical needs, are available which are not sold in any of the countries with matured regulatory bodies. It becomes vital to understand the history, growth and evolution of the regulatory aspects of drugs which are handled by multiple Ministries and Departments of the Government of India. Although amendment to Schedule Y, registration of Contract Research Organisations, registration of Clinical Trials, Speeding up review process, Pharmacovigilance (PhV) programme for India and Inspection of clinical trial sites have been started by the various regulatory agencies. However due to casual approach in marketing approval for sale of the drugs, the unethical steps taken by some pharmaceutical companies and medical practitioners has reiterated the need to get appropriate understanding of present regulation of drugs and clinical research especially regarding the practical rules and regulations. PMID:23559817

Risk assessment and adaptive runoff utilization in water resource system considering the complex relationship among water supply, electricity generation and environment

NASA Astrophysics Data System (ADS)

Zhou, J.; Zeng, X.; Mo, L.; Chen, L.; Jiang, Z.; Feng, Z.; Yuan, L.; He, Z.

2017-12-01

Generally, the adaptive utilization and regulation of runoff in the source region of China's southwest rivers is classified as a typical multi-objective collaborative optimization problem. There are grim competitions and incidence relation in the subsystems of water supply, electricity generation and environment, which leads to a series of complex problems represented by hydrological process variation, blocked electricity output and water environment risk. Mathematically, the difficulties of multi-objective collaborative optimization focus on the description of reciprocal relationships and the establishment of evolving model of adaptive systems. Thus, based on the theory of complex systems science, this project tries to carry out the research from the following aspects: the changing trend of coupled water resource, the covariant factor and driving mechanism, the dynamic evolution law of mutual feedback dynamic process in the supply-generation-environment coupled system, the environmental response and influence mechanism of coupled mutual feedback water resource system, the relationship between leading risk factor and multiple risk based on evolutionary stability and dynamic balance, the transfer mechanism of multiple risk response with the variation of the leading risk factor, the multidimensional coupled feedback system of multiple risk assessment index system and optimized decision theory. Based on the above-mentioned research results, the dynamic method balancing the efficiency of multiple objectives in the coupled feedback system and optimized regulation model of water resources is proposed, and the adaptive scheduling mode considering the internal characteristics and external response of coupled mutual feedback system of water resource is established. In this way, the project can make a contribution to the optimal scheduling theory and methodology of water resource management under uncertainty in the source region of Southwest River.

Shared regulatory sites are abundant in the human genome and shed light on genome evolution and disease pleiotropy.

PubMed

Tong, Pin; Monahan, Jack; Prendergast, James G D

2017-03-01

Large-scale gene expression datasets are providing an increasing understanding of the location of cis-eQTLs in the human genome and their role in disease. However, little is currently known regarding the extent of regulatory site-sharing between genes. This is despite it having potentially wide-ranging implications, from the determination of the way in which genetic variants may shape multiple phenotypes to the understanding of the evolution of human gene order. By first identifying the location of non-redundant cis-eQTLs, we show that regulatory site-sharing is a relatively common phenomenon in the human genome, with over 10% of non-redundant regulatory variants linked to the expression of multiple nearby genes. We show that these shared, local regulatory sites are linked to high levels of chromatin looping between the regulatory sites and their associated genes. In addition, these co-regulated gene modules are found to be strongly conserved across mammalian species, suggesting that shared regulatory sites have played an important role in shaping human gene order. The association of these shared cis-eQTLs with multiple genes means they also appear to be unusually important in understanding the genetics of human phenotypes and pleiotropy, with shared regulatory sites more often linked to multiple human phenotypes than other regulatory variants. This study shows that regulatory site-sharing is likely an underappreciated aspect of gene regulation and has important implications for the understanding of various biological phenomena, including how the two and three dimensional structures of the genome have been shaped and the potential causes of disease pleiotropy outside coding regions.

EBF factors drive expression of multiple classes of target genes governing neuronal development.

PubMed

Green, Yangsook S; Vetter, Monica L

2011-04-30

Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

PubMed Central

Volpe, Elisabetta; Sambucci, Manolo; Battistini, Luca; Borsellino, Giovanna

2016-01-01

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas–FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas–FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas–FasL in regulating Th17 and Treg cells’ functions, in the context of MS. PMID:27729910

Fas-Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis.

PubMed

Volpe, Elisabetta; Sambucci, Manolo; Battistini, Luca; Borsellino, Giovanna

2016-01-01

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas-FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas-FasL in regulating Th17 and Treg cells' functions, in the context of MS.

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

PubMed Central

Henao-Mejia, Jorge; Elinav, Eran; Jin, Cheng-Cheng; Hao, Liming; Mehal, Wajahat Z.; Strowig, Till; Thaiss, Christoph A.; Kau, Andrew L.; Eisenbarth, Stephanie C.; Jurczak, Michael J.; Camporez, Joao-Paulo; Shulman, Gerald I.; Gordon, Jeffrey I.; Hoffman, Hal M.; Flavell, Richard A.

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty percent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different animal models reveal that inflammasome deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic TNF-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient animals to wild type mice results in exacerbation of hepatic steatosis, glucose intolerance, and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. PMID:22297845

Isl1 Is required for multiple aspects of motor neuron development

PubMed Central

Liang, Xingqun; Song, Mi-Ryoung; Xu, ZengGuang; Lanuza, Guillermo M.; Liu, Yali; Zhuang, Tao; Chen, Yihan; Pfaff, Samuel L.; Evans, Sylvia M.; Sun, Yunfu

2011-01-01

The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons. PMID:21569850

Multiple roles of the cell cycle inhibitor p21(CDKN1A) in the DNA damage response.

PubMed

Cazzalini, Ornella; Scovassi, A Ivana; Savio, Monica; Stivala, Lucia A; Prosperi, Ennio

2010-01-01

Among cell cycle regulatory proteins that are activated following DNA damage, the cyclin-dependent kinase inhibitor p21(CDKN1A) plays essential roles in the DNA damage response, by inducing cell cycle arrest, direct inhibition of DNA replication, as well as by regulating fundamental processes, like apoptosis and transcription. These functions are performed through the ability of p21 to interact with a number of proteins involved in these processes. Despite an initial controversy, during the last years several lines of evidence have also indicated that p21 may be directly involved in DNA repair. In particular, the participation of p21 in nucleotide excision repair (NER), base excision repair (BER), and DNA translesion synthesis (TLS), has been suggested to occur thanks to its interaction with proliferating cell nuclear antigen (PCNA), a crucial protein involved in several aspects of DNA metabolism, and cell-cycle regulation. In this review, the multiple roles of p21 in the DNA damage response, including regulation of cell cycle, apoptosis and gene transcription, are discussed together with the most recent findings supporting the direct participation of p21 protein in DNA repair processes. In particular, spatio-temporal dynamics of p21 recruitment to sites of DNA damage will be considered together with several lines of evidence indicating a regulatory role for p21. In addition, the relevance of post-translational regulation in the fate (e.g. degradation) of p21 protein after cell exposure to DNA damaging agents will be analyzed. Both sets of evidence will be discussed in terms of the overall DNA damage response. 2010 Elsevier B.V. All rights reserved.

Integrating multiple disturbance aspects: management of an invasive thistle, Carduus nutans.

PubMed

Zhang, Rui; Shea, Katriona

2012-11-01

Disturbances occur in most ecological systems, and play an important role in biological invasions. We delimit five key disturbance aspects: intensity, frequency, timing, duration and extent. Few studies address more than one of these aspects, yet interactions and interdependence between aspects may lead to complex outcomes. In a two-cohort experimental study, we examined how multiple aspects (intensity, frequency and timing) of a mowing disturbance regime affect the survival, phenology, growth and reproduction of an invasive thistle Carduus nutans (musk thistle). Our results show that high intensity and late timing strongly delay flowering phenology and reduce plant survival, capitulum production and plant height. A significant interaction between intensity and timing further magnifies the main effects. Unexpectedly, high frequency alone did not effectively reduce reproduction. However, a study examining only frequency and intensity, and not timing, would have erroneously attributed the importance of timing to frequency. We used management of an invasive species as an example to demonstrate the importance of a multiple-aspect disturbance framework. Failure to consider possible interactions, and the inherent interdependence of certain aspects, could result in misinterpretation and inappropriate management efforts. This framework can be broadly applied to improve our understanding of disturbance effects on individual responses, population dynamics and community composition.

Specifying and Refining a Measurement Model for a Simulation-Based Assessment. CSE Report 619.

ERIC Educational Resources Information Center

Levy, Roy; Mislevy, Robert J.

2004-01-01

The challenges of modeling students' performance in simulation-based assessments include accounting for multiple aspects of knowledge and skill that arise in different situations and the conditional dependencies among multiple aspects of performance in a complex assessment. This paper describes a Bayesian approach to modeling and estimating…

On the structure of cellular solutions in Rayleigh-Benard-Marangoni flows in small-aspect-ratio containers

NASA Technical Reports Server (NTRS)

Dijkstra, Henk A.

1992-01-01

Multiple steady flow patterns occur in surface-tension/buoyancy-driven convection in a liquid layer heated from below (Rayleigh-Benard-Marangoni flows). Techniques of numerical bifurcation theory are used to study the multiplicity and stability of two-dimensional steady flow patterns (rolls) in rectangular small-aspect-ratio containers as the aspect ratio is varied. For pure Marangoni flows at moderate Biot and Prandtl number, the transitions occurring when paths of codimension 1 singularities intersect determine to a large extent the multiplicity of stable patterns. These transitions also lead, for example, to Hopf bifurcations and stable periodic flows for a small range in aspect ratio. The influence of the type of lateral walls on the multiplicity of steady states is considered. 'No-slip' lateral walls lead to hysteresis effects and typically restrict the number of stable flow patterns (with respect to 'slippery' sidewalls) through the occurrence of saddle node bifurcations. In this way 'no-slip' sidewalls induce a selection of certain patterns, which typically have the largest Nusselt number, through secondary bifurcation.

The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases.

PubMed

Wang, Tao; Xiong, Jian-Qiong

2016-02-01

The human TLX gene encodes an orphan nuclear receptor predominantly expressed in the central nervous system. Tailess and Tlx, the TLX homologues in Drosophila and mouse, play essential roles in body-pattern formation and neurogenesis during early embryogenesis and perform crucial functions in maintaining stemness and controlling the differentiation of adult neural stem cells in the central nervous system, especially the visual system. Multiple target genes and signaling pathways are regulated by TLX and its homologues in specific tissues during various developmental stages. This review aims to summarize previous studies including many recent updates from different aspects concerning TLX and its homologues in Drosophila and mouse.

Current research in aging: a report from the 2015 Ageing Summit.

PubMed

Moyse, Emmanuel; Lahousse, Lies; Krantic, Slavica

2015-01-01

Ageing Summit, London, UK, 10-12 February 2015 The Ageing Summit 2015 held on 10-12 February 2015 in London (UK) provided an extensive update to our knowledge of the 'Biology of Ageing' and a forum to discuss the participants' latest research progress. The meeting was subdivided into four thematic sessions: cellular level research including the aging brain; slowing down progression, rejuvenation and self-repair; genetic and epigenetic regulation; and expression and pathology of age-related diseases. Each session included multiple key presentations, three to five short research communications and ongoing poster presentations. The meeting provided an exciting multidisciplinary overview of the aging process from cellular and molecular mechanisms to medico-social aspects of human aging.

Epigenetic Aspects of Systemic Lupus Erythematosus.

PubMed

Relle, Manfred; Foehr, Bernd; Schwarting, Andreas

2015-06-01

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis, and inflammatory bowel disease have complex pathogeneses and the courses of events leading to these diseases are not well understood. The immune surveillance is a delicate balance between self and foreign as well as between tolerance and immune response. Exposure to certain environmental factors may impair this equilibrium, leading to autoimmune diseases, cancer, and the so-called "lifestyle diseases" such as atherosclerosis, heart attack, stroke, and obesity, among others. These external stimuli may also alter the epigenetic status quo and may trigger autoimmune diseases such as SLE in genetically susceptible individuals. This review aims to highlight the role of epigenetic (dys-)regulation in the pathogenesis of SLE.

Abscisic acid and other plant hormones: Methods to visualize distribution and signaling

PubMed Central

Waadt, Rainer; Hsu, Po-Kai; Schroeder, Julian I.

2015-01-01

The exploration of plant behavior on a cellular scale in a minimal invasive manner is key to understanding plant adaptations to their environment. Plant hormones regulate multiple aspects of growth and development and mediate environmental responses to ensure a successful life cycle. To monitor the dynamics of plant hormone actions in intact tissue, we need qualitative and quantitative tools with high temporal and spatial resolution. Here, we describe a set of biological instruments (reporters) for the analysis of the distribution and signaling of various plant hormones. Furthermore, we provide examples of their utility for gaining novel insights into plant hormone action with a deeper focus on the drought hormone abscisic acid. PMID:26577078

Plant KT/KUP/HAK Potassium Transporters: Single Family – Multiple Functions

PubMed Central

Grabov, Alexander

2007-01-01

Background and Aims Potassium transporters belonging to the KT/KUP/HAK family are important for various aspects of plant life including mineral nutrition and the regulation of development. Genes encoding these transporters are present in the genomes of all plants, but have not been found in the genomes of Protista or Animalia. The aim of this Botanical Briefing is to analyse the function of KT/KUP/HAK transporters from evolutionary, molecular and physiological perspectives. Scope This Briefing covers the phylogeny and evolution of KT/KUP/HAK transporters, the role of transporters in plant mineral nutrition and potassium homeostasis, and the role of KT/KUP/HAK transporters in plant development. PMID:17495982

The Architecture of the Pollen Hoarding Syndrome in Honey Bees: Implications for Understanding Social Evolution, Behavioral Syndromes, and Selective Breeding

PubMed Central

Rueppell, Olav

2014-01-01

Social evolution has influenced every aspect of contemporary honey bee biology, but the details are difficult to reconstruct. The reproductive ground plan hypothesis of social evolution proposes that central regulators of the gonotropic cycle of solitary insects have been coopted to coordinate social complexity in honey bees, such as the division of labor among workers. The predicted trait associations between reproductive physiology and social behavior have been identified in the context of the pollen hoarding syndrome, a larger suite of interrelated traits. The genetic architecture of this syndrome is characterized by a partially overlapping genetic architecture with several consistent, pleiotropic QTL. Despite these central QTL and an integrated hormonal regulation, separate aspects of the pollen hoarding syndrome may evolve independently due to peripheral QTL and additionally segregating genetic variance. The characterization of the pollen hoarding syndrome has also demonstrated that this syndrome involves many non-behavioral traits, which may be the case for numerous “behavioral” syndromes. Furthermore, the genetic architecture of the pollen hoarding syndrome has implications for breeding programs for improving honey health and other desirable traits: If these traits are comparable to the pollen hoarding syndrome, consistent pleiotropic QTL will enable marker assisted selection, while sufficient additional genetic variation may permit the dissociation of trade-offs for efficient multiple trait selection. PMID:25506100

The Architecture of the Pollen Hoarding Syndrome in Honey Bees: Implications for Understanding Social Evolution, Behavioral Syndromes, and Selective Breeding.

PubMed

Rueppell, Olav

2014-05-01

Social evolution has influenced every aspect of contemporary honey bee biology, but the details are difficult to reconstruct. The reproductive ground plan hypothesis of social evolution proposes that central regulators of the gonotropic cycle of solitary insects have been coopted to coordinate social complexity in honey bees, such as the division of labor among workers. The predicted trait associations between reproductive physiology and social behavior have been identified in the context of the pollen hoarding syndrome, a larger suite of interrelated traits. The genetic architecture of this syndrome is characterized by a partially overlapping genetic architecture with several consistent, pleiotropic QTL. Despite these central QTL and an integrated hormonal regulation, separate aspects of the pollen hoarding syndrome may evolve independently due to peripheral QTL and additionally segregating genetic variance. The characterization of the pollen hoarding syndrome has also demonstrated that this syndrome involves many non-behavioral traits, which may be the case for numerous "behavioral" syndromes. Furthermore, the genetic architecture of the pollen hoarding syndrome has implications for breeding programs for improving honey health and other desirable traits: If these traits are comparable to the pollen hoarding syndrome, consistent pleiotropic QTL will enable marker assisted selection, while sufficient additional genetic variation may permit the dissociation of trade-offs for efficient multiple trait selection.

Mining Multi-Aspect Reflection of News Events in Twitter: Discovery, Linking and Presentation

PubMed Central

Wang, Jingjing; Tong, Wenzhu; Yu, Hongkun; Li, Min; Ma, Xiuli; Cai, Haoyan; Hanratty, Tim; Han, Jiawei

2015-01-01

A major event often has repercussions on both news media and microblogging sites such as Twitter. Reports from mainstream news agencies and discussions from Twitter complement each other to form a complete picture. An event can have multiple aspects (sub-events) describing it from multiple angles, each of which attracts opinions/comments posted on Twitter. Mining such reflections is interesting to both policy makers and ordinary people seeking information. In this paper, we propose a unified framework to mine multi-aspect reflections of news events in Twitter. We propose a novel and efficient dynamic hierarchical entity-aware event discovery model to learn news events and their multiple aspects. The aspects of an event are linked to their reflections in Twitter by a bootstrapped dataless classification scheme, which elegantly handles the challenges of selecting informative tweets under overwhelming noise and bridging the vocabularies of news and tweets. In addition, we demonstrate that our framework naturally generates an informative presentation of each event with entity graphs, time spans, news summaries and tweet highlights to facilitate user digestion. PMID:27034625

Mining Multi-Aspect Reflection of News Events in Twitter: Discovery, Linking and Presentation.

PubMed

Wang, Jingjing; Tong, Wenzhu; Yu, Hongkun; Li, Min; Ma, Xiuli; Cai, Haoyan; Hanratty, Tim; Han, Jiawei

2015-11-01

A major event often has repercussions on both news media and microblogging sites such as Twitter. Reports from mainstream news agencies and discussions from Twitter complement each other to form a complete picture. An event can have multiple aspects (sub-events) describing it from multiple angles, each of which attracts opinions/comments posted on Twitter. Mining such reflections is interesting to both policy makers and ordinary people seeking information. In this paper, we propose a unified framework to mine multi-aspect reflections of news events in Twitter. We propose a novel and efficient dynamic hierarchical entity-aware event discovery model to learn news events and their multiple aspects. The aspects of an event are linked to their reflections in Twitter by a bootstrapped dataless classification scheme, which elegantly handles the challenges of selecting informative tweets under overwhelming noise and bridging the vocabularies of news and tweets. In addition, we demonstrate that our framework naturally generates an informative presentation of each event with entity graphs, time spans, news summaries and tweet highlights to facilitate user digestion.

An Overview of Multiple Sclerosis: Medical, Psychosocial, and Vocational Aspects of a Chronic and Unpredictable Neurological Disorder

ERIC Educational Resources Information Center

Rumrill, Phillip D., Jr.; Roessler, Richard T.

2015-01-01

This article presents an overview of multiple sclerosis (MS), one of the most common neurological disorders in the western hemisphere. Medical and psychosocial aspects of the disease such as causes and risk factors, diagnosis, incidence and prevalence, symptoms, courses, and treatment are described. Existing research regarding the employment…

Isl1 is required for multiple aspects of motor neuron development.

PubMed

Liang, Xingqun; Song, Mi-Ryoung; Xu, ZengGuang; Lanuza, Guillermo M; Liu, Yali; Zhuang, Tao; Chen, Yihan; Pfaff, Samuel L; Evans, Sylvia M; Sun, Yunfu

2011-07-01

The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons. Copyright © 2011 Elsevier Inc. All rights reserved.

Targeting agr- and agr-Like Quorum Sensing Systems for Development of Common Therapeutics to Treat Multiple Gram-Positive Bacterial Infections

PubMed Central

Gray, Brian; Hall, Pamela; Gresham, Hattie

2013-01-01

Invasive infection by the Gram-positive pathogen Staphylococcus aureus is controlled by a four gene operon, agr that encodes a quorum sensing system for the regulation of virulence. While agr has been well studied in S. aureus, the contribution of agr homologues and analogues in other Gram-positive pathogens is just beginning to be understood. Intriguingly, other significant human pathogens, including Clostridium perfringens, Listeria monocytogenes, and Enterococcus faecalis contain agr or analogues linked to virulence. Moreover, other significant human Gram-positive pathogens use peptide based quorum sensing systems to establish or maintain infection. The potential for commonality in aspects of these signaling systems across different species raises the prospect of identifying therapeutics that could target multiple pathogens. Here, we review the status of research into these agr homologues, analogues, and other peptide based quorum sensing systems in Gram-positive pathogens as well as the potential for identifying common pathways and signaling mechanisms for therapeutic discovery. PMID:23598501

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

PubMed

Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

2016-08-18

Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of normal aging on multiple aspects of financial decision-making.

PubMed

Bangma, Dorien F; Fuermaier, Anselm B M; Tucha, Lara; Tucha, Oliver; Koerts, Janneke

2017-01-01

Financial decision-making (FDM) is crucial for independent living. Due to cognitive decline that accompanies normal aging, older adults might have difficulties in some aspects of FDM. However, an improved knowledge, personal experience and affective decision-making, which are also related to normal aging, may lead to a stable or even improved age-related performance in some other aspects of FDM. Therefore, the present explorative study examines the effects of normal aging on multiple aspects of FDM. One-hundred and eighty participants (range 18-87 years) were assessed with eight FDM tests and several standard neuropsychological tests. Age effects were evaluated using hierarchical multiple regression analyses. The validity of the prediction models was examined by internal validation (i.e. bootstrap resampling procedure) as well as external validation on another, independent, sample of participants (n = 124). Multiple regression and correlation analyses were applied to investigate the mediation effect of standard measures of cognition on the observed effects of age on FDM. On a relatively basic level of FDM (e.g., paying bills or using FDM styles) no significant effects of aging were found. However more complex FDM, such as making decisions in accordance with specific rules, becomes more difficult with advancing age. Furthermore, an older age was found to be related to a decreased sensitivity for impulsive buying. These results were confirmed by the internal and external validation analyses. Mediation effects of numeracy and planning were found to explain parts of the association between one aspect of FDM (i.e. Competence in decision rules) and age; however, these cognitive domains were not able to completely explain the relation between age and FDM. Normal aging has a negative influence on a complex aspect of FDM, however, other aspects appear to be unaffected by normal aging or improve.

Genome Engineering and Modification Toward Synthetic Biology for the Production of Antibiotics.

PubMed

Zou, Xuan; Wang, Lianrong; Li, Zhiqiang; Luo, Jie; Wang, Yunfu; Deng, Zixin; Du, Shiming; Chen, Shi

2018-01-01

Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics. © 2017 Wiley Periodicals, Inc.

Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels

PubMed Central

Gopal, Sandeep; Søgaard, Pernille; Multhaupt, Hinke A.B.; Pataki, Csilla; Okina, Elena; Xian, Xiaojie; Pedersen, Mikael E.; Stevens, Troy; Griesbeck, Oliver; Park, Pyong Woo; Pocock, Roger

2015-01-01

Transmembrane heparan sulfate proteoglycans regulate multiple aspects of cell behavior, but the molecular basis of their signaling is unresolved. The major family of transmembrane proteoglycans is the syndecans, present in virtually all nucleated cells, but with mostly unknown functions. Here, we show that syndecans regulate transient receptor potential canonical (TRPCs) channels to control cytosolic calcium equilibria and consequent cell behavior. In fibroblasts, ligand interactions with heparan sulfate of syndecan-4 recruit cytoplasmic protein kinase C to target serine714 of TRPC7 with subsequent control of the cytoskeleton and the myofibroblast phenotype. In epidermal keratinocytes a syndecan–TRPC4 complex controls adhesion, adherens junction composition, and early differentiation in vivo and in vitro. In Caenorhabditis elegans, the TRPC orthologues TRP-1 and -2 genetically complement the loss of syndecan by suppressing neuronal guidance and locomotory defects related to increases in neuronal calcium levels. The widespread and conserved syndecan–TRPC axis therefore fine tunes cytoskeletal organization and cell behavior. PMID:26391658

Enhancements Needed in GE Crop and Food Regulation in the U.S.

PubMed Central

Benbrook, Charles

2016-01-01

Genetically engineered (GE) crops, multi-ingredient foods derived from one or more GE ingredients, and GE agricultural inputs are regulated in the United States under a “Coordinated Framework” that was literally cobbled together in the early 1990s. Via this Framework, responsibility is spread across three federal agencies for the assessment and management of potential risks arising from the planting of GE crops, the raising of GE animals, or uses of GE inputs. The Framework was incomplete and conceptually flawed from the beginning. Despite multiple, piecemeal efforts to update aspects of GE risk assessment and regulatory policy, the Coordinated Framework survives to this day largely unchanged. Its shortcomings are recognized in both the scientific and legal communities, but meaningful reforms thus far remain out of reach, blocked by the intense controversy now surrounding all things biotech. Five generic reforms and another five specific initiatives are described to create a more robust, science-driven GE regulatory infrastructure in the U.S. PMID:27066473

Eighty phenomena about the self: representation, evaluation, regulation, and change

PubMed Central

Thagard, Paul; Wood, Joanne V.

2015-01-01

We propose a new approach for examining self-related aspects and phenomena. The approach includes (1) a taxonomy and (2) an emphasis on multiple levels of mechanisms. The taxonomy categorizes approximately eighty self-related phenomena according to three primary functions involving the self: representing, effecting, and changing. The representing self encompasses the ways in which people depict themselves, either to themselves or to others (e.g., self-concepts, self-presentation). The effecting self concerns ways in which people facilitate or limit their own traits and behaviors (e.g., self-enhancement, self-regulation). The changing self is less time-limited than the effecting self; it concerns phenomena that involve lasting alterations in how people represent and control themselves (e.g., self-expansion, self-development). Each self-related phenomenon within these three categories may be examined at four levels of interacting mechanisms (social, individual, neural, and molecular). We illustrate our approach by focusing on seven self-related phenomena. PMID:25870574

Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

PubMed Central

Kaplan, Joshua M.

2008-01-01

Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling. PMID:19043554

An examination of dynamics crosstalk between SH2 and SH3 domains by hydrogen/deuterium exchange and mass spectrometry

PubMed Central

Hochrein, James M.; Lerner, Edwina C.; Schiavone, Anthony P.; Smithgall, Thomas E.; Engen, John R.

2006-01-01

The ability of proteins to regulate their own enzymatic activity can be facilitated by changes in structure or protein dynamics in response to external regulators. Because many proteins contain SH2 and SH3 domains, transmission of information between the domains is a potential method of allosteric regulation. To determine if ligand binding to one modular domain may alter structural dynamics in an adjacent domain, allowing potential transmission of information through the protein, we used hydrogen exchange and mass spectrometry to measure changes in protein dynamics in the SH3 and SH2 domains of hematopoietic cell kinase (Hck). Ligand binding to either domain had little or no effect on hydrogen exchange in the adjacent domain, suggesting that changes in protein structure or dynamics are not a means of SH2/SH3 crosstalk. Furthermore, ligands of varying affinity covalently attached to SH3/SH2 altered dynamics only in the domain to which they bind. Such results demonstrate that ligand binding may not structurally alter adjacent SH3/SH2 domains and implies that other aspects of protein architecture contribute to the multiple levels of regulation in proteins containing SH3 and SH2 domains. PMID:16322569

Coordination of meristem and boundary functions by transcription factors in the SHOOT MERISTEMLESS regulatory network.

PubMed

Scofield, Simon; Murison, Alexander; Jones, Angharad; Fozard, John; Aida, Mitsuhiro; Band, Leah R; Bennett, Malcolm; Murray, James A H

2018-04-30

The Arabidopsis homeodomain transcription factor SHOOT MERISTEMLESS (STM) is crucial for shoot apical meristem (SAM) function, yet the components and structure of the STM gene regulatory network (GRN) are largely unknown. Here, we show that transcriptional regulators are overrepresented among STM-regulated genes and, using these as GRN components in Bayesian network analysis, we infer STM GRN associations and reveal regulatory relationships between STM and factors involved in multiple aspects of SAM function. These include hormone regulation, TCP-mediated control of cell differentiation, AIL/PLT-mediated regulation of pluripotency and phyllotaxis, and specification of meristem-organ boundary zones via CUC1. We demonstrate a direct positive transcriptional feedback loop between STM and CUC1, despite their distinct expression patterns in the meristem and organ boundary, respectively. Our further finding that STM activates expression of the CUC1-targeting microRNA miR164c combined with mathematical modelling provides a potential solution for this apparent contradiction, demonstrating that these proposed regulatory interactions coupled with STM mobility could be sufficient to provide a mechanism for CUC1 localisation at the meristem-organ boundary. Our findings highlight the central role for the STM GRN in coordinating SAM functions. © 2018. Published by The Company of Biologists Ltd.

The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea.

PubMed

Sasidharan, Vidyanand; Marepally, Srujan; Elliott, Sarah A; Baid, Srishti; Lakshmanan, Vairavan; Nayyar, Nishtha; Bansal, Dhiru; Sánchez Alvarado, Alejandro; Vemula, Praveen Kumar; Palakodeti, Dasaradhi

2017-09-15

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is crucial for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family ( miR-124 ) is highly conserved in animals and regulates neurogenesis by facilitating neural differentiation, yet its role in neural wiring and brain organization is not known. We developed a novel method for delivering anti-miRs using liposomes for the functional knockdown of microRNAs. Smed-miR-124 knockdown revealed a key role for these microRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1 , which encodes an axon guidance protein, either by targeting slit-1 mRNA or, potentially, by modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system. © 2017. Published by The Company of Biologists Ltd.

The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea

PubMed Central

Sasidharan, Vidyanand; Marepally, Srujan; Elliott, Sarah A.; Baid, Srishti; Lakshmanan, Vairavan; Nayyar, Nishtha; Bansal, Dhiru; Sánchez Alvarado, Alejandro; Vemula, Praveen Kumar

2017-01-01

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is crucial for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family (miR-124) is highly conserved in animals and regulates neurogenesis by facilitating neural differentiation, yet its role in neural wiring and brain organization is not known. We developed a novel method for delivering anti-miRs using liposomes for the functional knockdown of microRNAs. Smed-miR-124 knockdown revealed a key role for these microRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1, which encodes an axon guidance protein, either by targeting slit-1 mRNA or, potentially, by modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system. PMID:28807895

Electroosmotic flow and ionic conductance in a pH-regulated rectangular nanochannel

NASA Astrophysics Data System (ADS)

Sadeghi, Morteza; Saidi, Mohammad Hassan; Sadeghi, Arman

2017-06-01

Infinite series solutions are obtained for electrical potential, electroosmotic velocity, ionic conductance, and surface physicochemical properties of long pH-regulated rectangular nanochannels of low surface potential utilizing the double finite Fourier transform method. Closed form expressions are also obtained for channels of large height to width ratio for which the depthwise variations vanish. Neglecting the Stern layer impact, the effects of EDL (Electric Double Layer) overlap, multiple ionic species, and association/dissociation reactions on the surface are all taken into account. Moreover, finite-element-based numerical simulations are conducted to account for the end effects as well as to validate the analytical solutions. We show that, with the exception of the migratory ionic conductivity, all the physicochemical parameters are strong functions of the channel aspect ratio. Accordingly, a slit geometry is not a good representative of a rectangular channel when the width is comparable to the height. It is also observed that the distribution of the electrical potential is not uniform over the surface of a charge-regulated channel. In addition, unlike ordinary channels for which an increase in the background salt concentration is always accompanied by higher flow rates, quite the opposite may be true for a pH-regulated duct at higher salt concentrations.

MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival.

PubMed

Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher

2010-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.

GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

PubMed

Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

2016-06-16

As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.

The evolution of transcriptional regulation in eukaryotes

NASA Technical Reports Server (NTRS)

Wray, Gregory A.; Hahn, Matthew W.; Abouheif, Ehab; Balhoff, James P.; Pizer, Margaret; Rockman, Matthew V.; Romano, Laura A.

2003-01-01

Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.

Identification of a molecular pH sensor in coral.

PubMed

Barott, Katie L; Barron, Megan E; Tresguerres, Martin

2017-11-15

Maintaining stable intracellular pH (pHi) is essential for homeostasis, and requires the ability to both sense pH changes that may result from internal and external sources, and to regulate downstream compensatory pH pathways. Here we identified the cAMP-producing enzyme soluble adenylyl cyclase (sAC) as the first molecular pH sensor in corals. sAC protein was detected throughout coral tissues, including those involved in symbiosis and calcification. Application of a sAC-specific inhibitor caused significant and reversible pHi acidosis in isolated coral cells under both dark and light conditions, indicating sAC is essential for sensing and regulating pHi perturbations caused by respiration and photosynthesis. Furthermore, pHi regulation during external acidification was also dependent on sAC activity. Thus, sAC is a sensor and regulator of pH disturbances from both metabolic and external origin in corals. Since sAC is present in all coral cell types, and the cAMP pathway can regulate virtually every aspect of cell physiology through post-translational modifications of proteins, sAC is likely to trigger multiple homeostatic mechanisms in response to pH disturbances. This is also the first evidence that sAC modulates pHi in any non-mammalian animal. Since corals are basal metazoans, our results indicate this function is evolutionarily conserved across animals. © 2017 The Author(s).

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

PubMed Central

Plaza-Zabala, Ainhoa; Sierra-Torre, Virginia; Sierra, Amanda

2017-01-01

Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer’s, Parkinson’s, and Huntington’s diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence. PMID:28282924

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging.

PubMed

Plaza-Zabala, Ainhoa; Sierra-Torre, Virginia; Sierra, Amanda

2017-03-09

Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer's, Parkinson's, and Huntington's diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence.

Multiple developmental mechanisms regulate species-specific jaw size

PubMed Central

Fish, Jennifer L.; Sklar, Rachel S.; Woronowicz, Katherine C.; Schneider, Richard A.

2014-01-01

Variation in jaw size during evolution has been crucial for the adaptive radiation of vertebrates, yet variation in jaw size during development is often associated with disease. To test the hypothesis that early developmental events regulating neural crest (NC) progenitors contribute to species-specific differences in size, we investigated mechanisms through which two avian species, duck and quail, achieve their remarkably different jaw size. At early stages, duck exhibit an anterior shift in brain regionalization yielding a shorter, broader, midbrain. We find no significant difference in the total number of pre-migratory NC; however, duck concentrate their pre-migratory NC in the midbrain, which contributes to an increase in size of the post-migratory NC population allocated to the mandibular arch. Subsequent differences in proliferation lead to a progressive increase in size of the duck mandibular arch relative to that of quail. To test the role of pre-migratory NC progenitor number in regulating jaw size, we reduced and augmented NC progenitors. In contrast to previous reports of regeneration by NC precursors, we find that neural fold extirpation results in a loss of NC precursors. Despite this reduction in their numbers, post-migratory NC progenitors compensate, producing a symmetric and normal-sized jaw. Our results suggest that evolutionary modification of multiple aspects of NC cell biology, including NC allocation within the jaw primordia and NC-mediated proliferation, have been important to the evolution of jaw size. Furthermore, our finding of NC post-migratory compensatory mechanisms potentially extends the developmental time frame for treatments of disease or injury associated with NC progenitor loss. PMID:24449843

Endogenous CNS Expression of Neurotensin and Neurotensin Receptors Is Altered during the Postpartum Period in Outbred Mice

PubMed Central

Driessen, Terri M.; Zhao, Changjiu; Whittlinger, Anna; Williams, Horecia; Gammie, Stephen C.

2014-01-01

Neurotensin (NT) is a neuropeptide identical in mice and humans that is produced and released in many CNS regions associated with maternal behavior. NT has been linked to aspects of maternal care and previous studies have indirectly suggested that endogenous NT signaling is altered in the postpartum period. In the present study, we directly examine whether NT and its receptors exhibit altered gene expression in maternal relative to virgin outbred mice using real time quantitative PCR (qPCR) across multiple brain regions. We also examine NT protein levels using anti-NT antibodies and immunohistochemistry in specific brain regions. In the medial preoptic area (MPOA), which is critical for maternal behaviors, mRNA of NT and NT receptor 3 (Sort1) were significantly up-regulated in postpartum mice compared to virgins. NT mRNA was also elevated in postpartum females in the bed nucleus of the stria terminalis dorsal. However, in the lateral septum, NT mRNA was down-regulated in postpartum females. In the paraventricular nucleus of the hypothalamus (PVN), Ntsr1 expression was down-regulated in postpartum females. Neurotensin receptor 2 (Ntsr2) expression was not altered in any brain region tested. In terms of protein expression, NT immunohistochemistry results indicated that NT labeling was elevated in the postpartum brain in the MPOA, lateral hypothalamus, and two subregions of PVN. Together, these findings indicate that endogenous changes occur in NT and its receptors across multiple brain regions, and these likely support the emergence of some maternal behaviors. PMID:24416154

Emotion control in collaborative learning situations: do students regulate emotions evoked by social challenges?

PubMed

Järvenoja, Hanna; Järvelä, Sanna

2009-09-01

During recent decades, self-regulated learning (SRL) has become a major research field. SRL successfully integrates the cognitive and motivational components of learning. Self-regulation is usually seen as an individual process, with the social aspects of regulation conceptualized as one aspect of the context. However, recent research has begun to investigate whether self-regulation processes are complemented by socially shared regulation processes. The presented study investigated what kind of socio-emotional challenges students experience during collaborative learning and whether the students regulate the emotions evoked during these situations. The interplay of the emotion regulation processes between the individual and the group was also studied. The sample for this study was 63 teacher education students who studied in groups of three to five during three collaborative learning tasks. Students' interpretations of experienced social challenges and their attempts to regulate emotions evoked by these challenges were collected following each task using the Adaptive Instrument for the Regulation of Emotions. The results indicated that students experienced a variety of social challenges. Students also reported the use of shared regulation in addition to self-regulation. Finally, the results suggested that intrinsic group dynamics are derived from both individual and social elements of collaborative situations. The findings of the study support the assumption that students can regulate emotions collaboratively as well as individually. The study contributes to our understanding of the social aspects of emotional regulation in collaborative learning contexts.

Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins.

PubMed

Ratti, Antonia; Buratti, Emanuele

2016-08-01

The multiple roles played by RNA binding proteins in neurodegeneration have become apparent following the discovery of TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) involvement in amyotrophic lateral sclerosis and frontotemporal lobar dementia. In these two diseases, the majority of patients display the presence of aggregated forms of one of these proteins in their brains. The study of their functional properties currently represents a very promising target for developing the effective therapeutic options that are still lacking. This aim, however, must be preceded by an accurate evaluation of TDP-43 and FUS/TLS biological functions, both in physiological and disease conditions. Recent findings have uncovered several aspects of RNA metabolism that can be affected by misregulation of these two proteins. Progress has also been made in starting to understand how the aggregation of these proteins occurs and spreads from cell to cell. The aim of this review will be to provide a general overview of TDP-43 and FUS/TLS proteins and to highlight their physiological functions. At present, the emerging picture is that TDP-43 and FUS/TLS control several aspects of an mRNA's life, but they can also participate in DNA repair processes and in non-coding RNA metabolism. Although their regulatory activities are similar, they regulate mainly distinct RNA targets and show different pathogenetic mechanisms in amyotrophic lateral sclerosis/frontotemporal lobar dementia diseases. The identification of key events in these processes represents today the best chance of finding targetable options for therapeutic approaches that might actually make a difference at the clinical level. The two major RNA Binding Proteins involved in Amyotrophic Lateral Sclerosisi and Frontotemporal Dementia are TDP-43 and FUST/TLS. Both proteins are involved in regulating all aspects of RNA and RNA life cycle within neurons, from transcription, processing, and transport/stability to the formation of cytoplasmic and nuclear stress granules. For this reason, the aberrant aggregation of these factors during disease can impair multiple RNA metabolic pathways and eventually lead to neuronal death/inactivation. The purpose of this review is to provide an up-to-date perspective on what we know about this issue at the molecular level. This article is part of the Frontotemporal Dementia special issue. © 2016 International Society for Neurochemistry.

A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings.

PubMed

Seabra, Catarina M; Szoko, Nicholas; Erdin, Serkan; Ragavendran, Ashok; Stortchevoi, Alexei; Maciel, Patrícia; Lundberg, Kathleen; Schlatzer, Daniela; Smith, Janice; Talkowski, Michael E; Gusella, James F; Natowicz, Marvin R

2017-09-01

Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic, and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech/language disorder with full scale IQ scores 78-98 and scattered academic skill levels, expanding the phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the ARID1B copy number gain. Principal component analysis revealed marked differentiation of the subject's lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1014 were significantly up- or down-regulated compared to controls (q < 0.01). Pathway analysis revealed highly significant enrichment for canonical pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and chromosomal replication, among others. Network analyses revealed down-regulation of: (1) intracellular components involved in organization of membranes, organelles, and vesicles; (2) aspects of cell cycle control, signal transduction, and nuclear protein export; (3) ubiquitination and proteosomal function; and (4) aspects of mRNA synthesis/splicing. Further studies are needed to determine the detailed molecular and cellular mechanisms by which constitutional haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental disabilities. © 2017 Wiley Periodicals, Inc.

Developing Connections for Affective Regulation: Age-Related Changes in Emotional Brain Connectivity

ERIC Educational Resources Information Center

Perlman, Susan B.; Pelphrey, Kevin A.

2011-01-01

The regulation of affective arousal is a critical aspect of children's social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of "hot" executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional…

Interplay between sugar and hormone signaling pathways modulate floral signal transduction

PubMed Central

Matsoukas, Ianis G.

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research. PMID:25165468

Interplay between sugar and hormone signaling pathways modulate floral signal transduction.

PubMed

Matsoukas, Ianis G

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research.

Comparative Aspects of Multiple Processes of Attention.

DTIC Science & Technology

1988-05-01

8217’ - % % -.. -. % $. Neisser , U . (1968). The processes of vision. Scientific American, 219, 201-214. Olson, R., & Attneave, F. (1970). What...AD-ft." M~ COMPARATIVE ASPECTS OF MULTIPLE PROCESSES OF ATTENTION 1/1 ( U ) DAYTON UNIV ON RESEARCH INST N CNEAL NAY U USI FE AFNRL-TR-9?-53 F3613-64-C...0% FOV9 M IR;. 2.2s 11U, XV11Y L. IIMrV % u AFHRL-TR-87-53 ~IF r- AIR FORCE R COMPARATIVE ASPECiS OF MULTIPLE PROCESSES OF ATTENTION _H U ’) U MaryLou

A distal 594 bp ECR specifies Hmx1 expression in pinna and lateral facial morphogenesis and is regulated by the Hox-Pbx-Meis complex

DOE PAGES

Rosin, Jessica M.; Li, Wenjie; Cox, Liza L.; ...

2016-07-19

Hmx1 encodes a homeodomain transcription factor expressed in the developing lateral craniofacial mesenchyme, retina and sensory ganglia. Mutation or mis-regulation of Hmx1 underlies malformations of the eye and external ear in multiple species. Deletion or insertional duplication of an evolutionarily conserved region (ECR) downstream of Hmx1 has recently been described in rat and cow, respectively. Here, we demonstrate that the impact of Hmx1 loss is greater than previously appreciated, with a variety of lateral cranioskeletal defects, auriculofacial nerve deficits, and duplication of the caudal region of the external ear. Using a transgenic approach, we demonstrate that a 594 bp sequencemore » encompassing the ECR recapitulates specific aspects of the endogenous Hmx1 lateral facial expression pattern. Moreover, we show that Hoxa2, Meis and Pbx proteins act cooperatively on the ECR, via a core 32 bp sequence, to regulate Hmx1 expression. In conclusion, these studies highlight the conserved role for Hmx1 in BA2-derived tissues and provide an entry point for improved understanding of the causes of the frequent lateral facial birth defects in humans.« less

BamHI-A rightward frame 1, an Epstein–Barr virus-encoded oncogene and immune modulator

PubMed Central

Hoebe, Eveline K; Le Large, Tessa Y S; Greijer, Astrid E; Middeldorp, Jaap M

2013-01-01

Epstein–Barr virus (EBV) causes several benign and malignant disorders of lymphoid and epithelial origin. EBV-related tumors display distinct patterns of viral latent gene expression, of which the BamHI-A rightward frame 1 (BARF1) is selectively expressed in carcinomas, regulated by cellular differentiation factors including ΔNp63α. BARF1 functions as a viral oncogene, immortalizing and transforming epithelial cells of different origin by acting as a mitogenic growth factor, inducing cyclin-D expression, and up-regulating antiapoptotic Bcl-2, stimulating host cell growth and survival. In addition, secreted hexameric BARF1 has immune evasive properties, functionally corrupting macrophage colony stimulating factor, as supported by recent functional and structural data. Therefore, BARF1, an intracellular and secreted protein, not only has multiple pathogenic functions but also can function as a target for immune responses. Deciphering the role of BARF1 in EBV biology will contribute to novel diagnostic and treatment options for EBV-driven carcinomas. Herein, we discuss recent insights on the regulation of BARF1 expression and aspects of structure-function relating to its oncogenic and immune suppressive properties. © 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd. PMID:23996634

Dock and Pak regulate olfactory axon pathfinding in Drosophila.

PubMed

Ang, Lay-Hong; Kim, Jenny; Stepensky, Vitaly; Hing, Huey

2003-04-01

The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.

Research advances on microbial genetics in China in 2015.

PubMed

Xie, Jian-ping; Han, Yu-bo; Liu, Gang; Bai, Lin-quan

2016-09-01

In 2015, there are significant progresses in many aspects of the microbial genetics in China. To showcase the contribution of Chinese scientists in microbial genetics, this review surveys several notable progresses in microbial genetics made largely by Chinese scientists, and some key findings are highlighted. For the basic microbial genetics, the components, structures and functions of many macromolecule complexes involved in gene expression regulation have been elucidated. Moreover, the molecular basis underlying the recognition of foreign nucleic acids by microbial immune systems was unveiled. We also illustrated the biosynthetic pathways and regulators of multiple microbial compounds, novel enzyme reactions, and new mechanisms regulating microbial gene expression. And new findings were obtained in the microbial development, evolution and population genetics. For the industrial microbiology, more understanding on the molecular basis of the microbial factory has been gained. For the pathogenic microbiology, the genetic circuits of several pathogens were depicted, and significant progresses were achieved for understanding the pathogen-host interaction and revealing the genetic mechanisms underlying antimicrobial resistance, emerging pathogens and environmental microorganisms at the genomic level. In future, the genetic diversity of microbes can be used to obtain specific products, while gut microbiome is gathering momentum.

A distal 594 bp ECR specifies Hmx1 expression in pinna and lateral facial morphogenesis and is regulated by the Hox-Pbx-Meis complex

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

Rosin, Jessica M.; Li, Wenjie; Cox, Liza L.

Hmx1 encodes a homeodomain transcription factor expressed in the developing lateral craniofacial mesenchyme, retina and sensory ganglia. Mutation or mis-regulation of Hmx1 underlies malformations of the eye and external ear in multiple species. Deletion or insertional duplication of an evolutionarily conserved region (ECR) downstream of Hmx1 has recently been described in rat and cow, respectively. Here, we demonstrate that the impact of Hmx1 loss is greater than previously appreciated, with a variety of lateral cranioskeletal defects, auriculofacial nerve deficits, and duplication of the caudal region of the external ear. Using a transgenic approach, we demonstrate that a 594 bp sequencemore » encompassing the ECR recapitulates specific aspects of the endogenous Hmx1 lateral facial expression pattern. Moreover, we show that Hoxa2, Meis and Pbx proteins act cooperatively on the ECR, via a core 32 bp sequence, to regulate Hmx1 expression. In conclusion, these studies highlight the conserved role for Hmx1 in BA2-derived tissues and provide an entry point for improved understanding of the causes of the frequent lateral facial birth defects in humans.« less

Seven-pass transmembrane cadherins: roles and emerging mechanisms in axonal and dendritic patterning.

PubMed

Berger-Müller, Sandra; Suzuki, Takashi

2011-12-01

The Flamingo/Celsr seven-transmembrane cadherins represent a conserved subgroup of the cadherin superfamily involved in multiple aspects of development. In the developing nervous system, Fmi/Celsr control axonal blueprint and dendritic morphogenesis from invertebrates to mammals. As expected from their molecular structure, seven-transmembrane cadherins can induce cell-cell homophilic interactions but also intracellular signaling. Fmi/Celsr is known to regulate planar cell polarity (PCP) through interactions with PCP proteins. In the nervous system, Fmi/Celsr can function in collaboration with or independently of other PCP genes. Here, we focus on recent studies which show that seven-transmembrane cadherins use distinct molecular mechanisms to achieve diverse functions in the development of the nervous system.

Current emotion research in cultural neuroscience

PubMed Central

Chiao, Joan Y.

2013-01-01

Classical theories of emotion have long debated the extent to which human emotion is a universal or culturally-constructed experience. Recent advances in emotion research in cultural neuroscience highlight several aspects of emotional generation and experience that are both phylogenetically conserved as well as constructed within human cultural contexts. This review highlights theories and methods from cultural neuroscience that examine how cultural and biological processes shape emotional generation, experience and regulation across multiple time scales. Recent advances in the neurobiological basis of culture-bound syndromes, such as Hwa-Byung (fire illness), provide further novel insights into emotion and mental health across cultures. Implications of emotion research in cultural neuroscience for population health disparities in psychopathology and global mental health will be discussed. PMID:26346827

The CRISPR-Cas system in Enterobacteriaceae.

PubMed

Medina-Aparicio, Liliana; Dávila, Sonia; Rebollar-Flores, Javier E; Calva, Edmundo; Hernández-Lucas, Ismael

2018-02-01

In nature, microorganisms are constantly exposed to multiple viral infections and thus have developed many strategies to survive phage attack and invasion by foreign DNA. One of such strategies is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) bacterial immunological system. This defense mechanism is widespread in prokaryotes including several families such as Enterobacteriaceae. Much knowledge about the CRISPR-Cas system has been generated, including its biological functions, transcriptional regulation, distribution, utility as a molecular marker and as a tool for specific genome editing. This review focuses on these aspects and describes the state of the art of the CRISPR-Cas system in the Enterobacteriaceae bacterial family. © FEMS 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Politics and Policies of Regulating Generics in Latin America: A Survey of Seventeen States.

PubMed

Sweet, Cassandra M

2017-06-01

When patents expire, are equivalent generic alternatives available to citizens? This article contributes to current discussion on access to medicine in the aftermath of the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). The focus is on off-patent or "generic" medicines: their product definitions, quality standards and prescription procedures. Drawing from a survey conducted of seventeen countries across the Latin American region, this article examines the differences in definition of off-patent products and the paradox of their relatively lower consumption across multiple developing states. The findings point to pathways for improving standards, consumer information, and access in off-patent pharmaceutical markets. Copyright © 2017 by Duke University Press.

Using Aspects of the TEACCH Structured Teaching Approach with Students with Multiple Disabilities and Visual Impairment: Reflections on Practice

ERIC Educational Resources Information Center

Taylor, Kim; Preece, David

2010-01-01

This article reflects on how the first author has adapted aspects of the TEACCH structured teaching approach--developed for use with students with autism--in her work with students with multiple disabilities and visual impairment (MDVI) in a special secondary school for students with severe learning difficulties in England. A brief overview of the…

Regulations and guidelines should be strengthened urgently for re-evaluation on post-marketing medicines in China.

PubMed

Xie, Yan-Ming; Tian, Feng

2013-07-01

This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and techniques on postmarketing surveillance (also named pharmacovigilance), therefore, their regulation systems are nearly perfect. In China, the regulations on post-marketing re-evaluation and relative technical guidelines do not cover the whole aspects, even lack in some important aspects, and long-term risk management mechanisms have not been established. So it is urgent to establish new regulations and improve the regulatory system in China based on the existing regulations and guidelines, by learning from the ideas of foreign advanced regulations, then fully integrating them with China's actual conditions, and cooperating with multidisciplinary researchers.

Modulation of the mesolimbic dopamine system by leptin.

PubMed

Opland, Darren M; Leinninger, Gina M; Myers, Martin G

2010-09-02

Nutritional status modulates many forms of reward-seeking behavior, with caloric restriction increasing the drive for drugs of abuse as well as for food. Understanding the interactions between the mesolimbic dopamine (DA) system (which mediates the incentive salience of natural and artificial rewards) and the neural and hormonal systems that sense and regulate energy balance is thus of significant importance. Leptin, which is produced by adipocytes in proportion to fat content as a hormonal signal of long-term energy stores, acts via its receptor (LepRb) on multiple populations of central nervous system neurons to modulate neural circuits in response to body energy stores. Leptin suppresses feeding and plays a central role in the control of energy balance. In addition to demonstrating that leptin modulates hypothalamic and brainstem circuits to promote satiety, recent work has begun to explore the mechanisms by which leptin influences the mesolimbic DA system and related behaviors. Indeed, leptin diminishes several measures of drug and food reward, and promotes a complex set of changes in the mesolimbic DA system. While many of the details remain to be worked out, several lines of evidence suggest that leptin regulates the mesolimbic DA system via multiple neural pathways and processes, and that distinct sets of LepRb neurons each modulate unique aspects of the mesolimbic DA system and behavior in response to leptin. 2010 Elsevier B.V. All rights reserved.

Notch Signaling and Alloreactivity.

PubMed

Radojcic, Vedran; Maillard, Ivan

2016-12-01

Solid organ and allogeneic hematopoietic cell transplantation have become standard therapeutic interventions that save patient lives and improve quality of life. Our enhanced understanding of transplantation immunobiology has refined clinical management and improved outcomes. However, organ rejection and graft-versus-host disease remain major obstacles to the broader successful application of these therapeutic procedures. Notch signaling regulates multiple aspects of adaptive and innate immunity. Preclinical studies identified Notch signaling as a promising target in autoimmune diseases, as well as after allogeneic hematopoietic cell and solid organ transplantation. Notch was found to be a central regulator of alloreactivity across clinically relevant models of transplantation. Notch inhibition in T cells prevented graft-versus-host disease and organ rejection, establishing organ tolerance by skewing CD4 T helper polarization away from a proinflammatory response toward suppressive regulatory T cells. Notch ligand blockade also dampened alloantibody deposition and prevented chronic rejection through humoral mechanisms. Toxicities of systemic Notch blockade were observed with γ-secretase inhibitors in preclinical and early clinical trials across different indications, but they did not arise upon preclinical targeting of Delta-like Notch ligands, a strategy sufficient to confer full benefits of Notch ablation in T cell alloimmunity. Because multiple clinical grade reagents have been developed to target individual Notch ligands and receptors, the benefits of Notch blockade in transplantation are calling for translation of preclinical findings into human transplantation medicine.

Meiosis: An Overview of Key Differences from Mitosis

PubMed Central

Ohkura, Hiroyuki

2015-01-01

Meiosis is the specialized cell division that generates gametes. In contrast to mitosis, molecular mechanisms and regulation of meiosis are much less understood. Meiosis shares mechanisms and regulation with mitosis in many aspects, but also has critical differences from mitosis. This review highlights these differences between meiosis and mitosis. Recent studies using various model systems revealed differences in a surprisingly wide range of aspects, including cell-cycle regulation, recombination, postrecombination events, spindle assembly, chromosome–spindle interaction, and chromosome segregation. Although a great degree of diversity can be found among organisms, meiosis-specific processes, and regulation are generally conserved. PMID:25605710

Acquisition of the Korean Imperfective Aspect Markers "-ko iss-" and "-a iss-" by Japanese Learners: A Multiple-Factor Account

ERIC Educational Resources Information Center

Ryu, Ju-Yeon; Horie, Kaoru; Shirai, Yasuhiro

2015-01-01

Although cross-linguistic research on second language tense-aspect acquisition has uncovered universal tendencies concerning the association between verbal semantics and tense-aspect markers, it is still unclear what mechanisms underlie this link. This study investigates the acquisition of two imperfective aspect markers ("-ko iss-" and…

EBF proteins participate in transcriptional regulation of Xenopus muscle development.

PubMed

Green, Yangsook Song; Vetter, Monica L

2011-10-01

EBF proteins have diverse functions in the development of multiple lineages, including neurons, B cells and adipocytes. During Drosophila muscle development EBF proteins are expressed in muscle progenitors and are required for muscle cell differentiation, but there is no known function of EBF proteins in vertebrate muscle development. In this study, we examine the expression of ebf genes in Xenopus muscle tissue and show that EBF activity is necessary for aspects of Xenopus skeletal muscle development, including somite organization, migration of hypaxial muscle anlagen toward the ventral abdomen, and development of jaw muscle. From a microarray screen, we have identified multiple candidate targets of EBF activity with known roles in muscle development. The candidate targets we have verified are MYOD, MYF5, M-Cadherin and SEB-4. In vivo overexpression of the ebf2 and ebf3 genes leads to ectopic expression of these candidate targets, and knockdown of EBF activity causes downregulation of the endogenous expression of the candidate targets. Furthermore, we found that MYOD and MYF5 are likely to be direct targets. Finally we show that MYOD can upregulate the expression of ebf genes, indicating the presence of a positive feedback loop between EBF and MYOD that we find to be important for maintenance of MYOD expression in Xenopus. These results suggest that EBF activity is important for both stabilizing commitment and driving aspects of differentiation in Xenopus muscle cells. Copyright © 2010 Elsevier Inc. All rights reserved.

The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review

PubMed Central

Rocha, André M.; Carvalho, Filomena M.; Pereira, Ricardo M. A.; Taylor, Hugh S.; Motta, Eduardo L. A.; Baracat, Edmund C.; Serafini, Paulo C.

2010-01-01

Purpose Endometriosis and its associated infertility have been the object of continuous research for over a century. To understand the molecular mechanisms underlying the disease, it has become necessary to determine the aspects of its etiology that are not explained by the retrograde menstruation theory. This could in turn elucidate how various clinical and surgical treatments might affect the evolution and remission of the disease. Methods This review is focused on the most recent clinical and laboratory findings regarding the association of HOXA10 with endometriosis and infertility. Result The homebox (Hox/HOX) proteins are highly conserved transcription factors that determine segmental body identities in multiple species, including humans. Hoxa10/HOXA10 is directly involved in the embryogenesis of the uterus and embryo implantation via regulation of downstream genes. Cyclical endometrial expression of Hoxa10/HOXA10, with a peak of expression occurring during the window of implantation, is observed in the adult in response to estrogen and progesterone. Women with endometriosis do not demonstrate the expected mid-luteal rise of HOXA10 expression, which might partially explain the infertility observed in many of these patients. Recent studies also demonstrated HOXA10 expression in endometriotic foci outside the Müllerian tract. Conclusions Multiple lines of evidence suggest that the actions of the homeobox A10 (Hoxa10/HOXA10) gene could account for some aspects of endometriosis. PMID:20821045

The Acquisition of Progressive and Resultative Meanings of the Imperfective Aspect Marker by L2 Learners of Japanese: Transfer, Universals, or Multiple Factors?

ERIC Educational Resources Information Center

Sugaya, Natsue; Shirai, Yasuhiro

2007-01-01

It has been observed that there is a strong association between the inherent (lexical) aspect of verbs and the acquisition of tense-aspect morphology (the aspect hypothesis; Andersen & Shirai, 1994). To investigate why such an association is observed, this study examined the influence of inherent aspect and learners' first language (L1) on the…

Effects of Goal Relations on Self-Regulated Learning in Multiple Goal Pursuits: Performance, the Self-Regulatory Process, and Task Enjoyment

ERIC Educational Resources Information Center

Lee, Hyunjoo

2012-01-01

The purpose of this study was to investigate the effects of goal relations on self-regulation in the pursuit of multiple goals, focusing on self-regulated performance, the self-regulatory process, and task enjoyment. The effect of multiple goal relations on self-regulation was explored in a set of three studies. Goal relations were divided into…

Features in visual search combine linearly

PubMed Central

Pramod, R. T.; Arun, S. P.

2014-01-01

Single features such as line orientation and length are known to guide visual search, but relatively little is known about how multiple features combine in search. To address this question, we investigated how search for targets differing in multiple features (intensity, length, orientation) from the distracters is related to searches for targets differing in each of the individual features. We tested race models (based on reaction times) and co-activation models (based on reciprocal of reaction times) for their ability to predict multiple feature searches. Multiple feature searches were best accounted for by a co-activation model in which feature information combined linearly (r = 0.95). This result agrees with the classic finding that these features are separable i.e., subjective dissimilarity ratings sum linearly. We then replicated the classical finding that the length and width of a rectangle are integral features—in other words, they combine nonlinearly in visual search. However, to our surprise, upon including aspect ratio as an additional feature, length and width combined linearly and this model outperformed all other models. Thus, length and width of a rectangle became separable when considered together with aspect ratio. This finding predicts that searches involving shapes with identical aspect ratio should be more difficult than searches where shapes differ in aspect ratio. We confirmed this prediction on a variety of shapes. We conclude that features in visual search co-activate linearly and demonstrate for the first time that aspect ratio is a novel feature that guides visual search. PMID:24715328

Novel mechanisms of G-protein-coupled receptors functions: AT1 angiotensin receptor acts as a signaling hub and focal point of receptor cross-talk.

PubMed

Tóth, András D; Turu, Gábor; Hunyady, László; Balla, András

2018-04-01

AT 1 angiotensin receptor (AT 1 R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT 1 R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT 1 R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses. Growing amount of evidence shows that AT 1 R is a versatile GPCR, which has multiple unique faces with distinct conformations and signaling properties providing new opportunities for functionally selective pharmacological targeting of the receptor. Biased ligands of AT 1 R have been developed to selectively activate the β-arrestin pathway, which may have therapeutic benefits compared to the conventional angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we provide a summary about the most recent findings and novel aspects of the AT 1 R function, signaling, regulation, dimerization or oligomerization and its cross-talk with other receptors, including epidermal growth factor (EGF) receptor, adrenergic receptors and CB 1 cannabinoid receptor. Better understanding of the mechanisms and structural aspects of AT 1 R activation and cross-talk can lead to the development of novel type of drugs for the treatment of cardiovascular and other diseases. Copyright © 2018. Published by Elsevier Ltd.

Nosology, ontology and promiscuous realism.

PubMed

Binney, Nicholas

2015-06-01

Medics may consider worrying about their metaphysics and ontology to be a waste of time. I will argue here that this is not the case. Promiscuous realism is a metaphysical position which holds that multiple, equally valid, classification schemes should be applied to objects (such as patients) to capture different aspects of their complex and heterogeneous nature. As medics at the bedside may need to capture different aspects of their patients' problems, they may need to use multiple classification schemes (multiple nosologies), and thus consider adopting a different metaphysics to the one commonly in use. © 2014 John Wiley & Sons, Ltd.

The effects of normal aging on multiple aspects of financial decision-making

PubMed Central

Bangma, Dorien F.; Fuermaier, Anselm B. M.; Tucha, Lara; Tucha, Oliver; Koerts, Janneke

2017-01-01

Objectives Financial decision-making (FDM) is crucial for independent living. Due to cognitive decline that accompanies normal aging, older adults might have difficulties in some aspects of FDM. However, an improved knowledge, personal experience and affective decision-making, which are also related to normal aging, may lead to a stable or even improved age-related performance in some other aspects of FDM. Therefore, the present explorative study examines the effects of normal aging on multiple aspects of FDM. Methods One-hundred and eighty participants (range 18–87 years) were assessed with eight FDM tests and several standard neuropsychological tests. Age effects were evaluated using hierarchical multiple regression analyses. The validity of the prediction models was examined by internal validation (i.e. bootstrap resampling procedure) as well as external validation on another, independent, sample of participants (n = 124). Multiple regression and correlation analyses were applied to investigate the mediation effect of standard measures of cognition on the observed effects of age on FDM. Results On a relatively basic level of FDM (e.g., paying bills or using FDM styles) no significant effects of aging were found. However more complex FDM, such as making decisions in accordance with specific rules, becomes more difficult with advancing age. Furthermore, an older age was found to be related to a decreased sensitivity for impulsive buying. These results were confirmed by the internal and external validation analyses. Mediation effects of numeracy and planning were found to explain parts of the association between one aspect of FDM (i.e. Competence in decision rules) and age; however, these cognitive domains were not able to completely explain the relation between age and FDM. Conclusion Normal aging has a negative influence on a complex aspect of FDM, however, other aspects appear to be unaffected by normal aging or improve. PMID:28792973

The Role of Hypothalamic Estrogen Receptors in Metabolic Regulation

PubMed Central

Frank, Aaron; Brown, Lynda M.; Clegg, Deborah J.

2014-01-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ”classical“ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. PMID:24882636

The role of hypothalamic estrogen receptors in metabolic regulation.

PubMed

Frank, Aaron; Brown, Lynda M; Clegg, Deborah J

2014-10-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two 'classical' estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1(-/-)); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Combining ecosystem service relationships and DPSIR framework to manage multiple ecosystem services.

PubMed

Xue, Hui; Li, Shiyu; Chang, Jie

2015-03-01

Ecosystem service (ES) relationship occurs due to two types of mechanisms: (1) interact directly or (2) interact through the impact of a shared factor. Identifying such mechanisms behind ES relationship within a single land-use/land-cover category and combining it with a system thinking framework is especially necessary for effective decision-making to manage multiple ESs generated by this land-use/land-cover. In this study, we use tea plantations in China to investigate mechanisms behind ES relationships. We find that tea production is positively correlated with four regulating services (i.e., carbon sequestration, soil N protection, soil P protection, and water conservation). Several regulating services, such as carbon sequestration and soil N, P, and K protection, have positive correlations with each other. Tea production, carbon sequestration, and soil retention are significantly correlated with local annual mean temperature and precipitation. We then establish driver-pressure-state-impact-response (DPSIR) framework for tea plantations, which has been widely used for environmental management issues. Integrating our findings of ES relationship into DPSIR framework, we can estimate how ES change is responding to two types of responses: response to control drivers and response to maintain or restore state. Scenario analysis showed that the responses to control drivers have a larger impact on ES. We discuss that DPSIR would favor managing multiple ES because it enables a more precise understanding of how ES interacts through the effects of factors from various hierarchies. Finally, we suggest integrating ES direct interaction into DPSIR framework. We think such integration could improve the ability of DPSIR framework to support decision-making in multiple ES management, specifically in at least three aspects: (1) favor to identify all possible response alternatives, (2) enable us to evaluate ES which cannot be assessed if without such combining, and (3) help to identify ecological leverage points where small management investment can yield substantial benefits.

Conceptual Learning with Multiple Graphical Representations: Intelligent Tutoring Systems Support for Sense-Making and Fluency-Building Processes

ERIC Educational Resources Information Center

Rau, Martina A.

2013-01-01

Most learning environments in the STEM disciplines use multiple graphical representations along with textual descriptions and symbolic representations. Multiple graphical representations are powerful learning tools because they can emphasize complementary aspects of complex learning contents. However, to benefit from multiple graphical…

Creating the Multiple Personality: An Experiential Demonstration for an Undergraduate Abnormal Psychology Class.

ERIC Educational Resources Information Center

Rabinowitz, Fredric E.

1989-01-01

Discusses a classroom role-playing exercise in which students and teacher re-enact interviewing techniques that cause subjects to assume characteristics of the multiple personality. Demonstrates the social psychological aspects of multiple personality disorder. Considers the pedagogical and ethical implications of creating the multiple personality…

Conceptualizing gambling disorder with the process model of emotion regulation.

PubMed

Rogier, Guyonne; Velotti, Patrizia

2018-06-25

Introduction Nowadays, gambling disorder (GD) is a worldwide health issue and there is a growing need to both improve our understanding of this disorder and to tailor specific interventions for its treatment. Moreover, theoretical models and preliminary empirical results suggest that difficulty in regulating emotional states might be involved in GD. However, literature describing clinical and theoretical aspects of emotional dysregulation among pathological gamblers (PGs) shows a lack of systematic description. Objectives We aimed to provide, within an exhaustive theoretical framework of emotion regulation (ER) processing, empirical evidence supporting a conceptual model of GD as an ER affliction. Methods We commented on empirical evidence on the relationship between ER and GD in the light of two main conceptual models of emotion (dys)regulation. Results The results suggest there are actual deficits of ER processing among PGs, manifesting themselves through different ways and in different steps of the ER timeline. In addition, dysregulation of positive emotions may play a central role in GD. From a clinical point of view, we pointed out that deficits in ER might be multiple in nature and an assessment for GD should be accurate to identify the specific components accounting for the development and maintenance of the disorder. It should also orientate the clinician in selecting therapeutic objectives. Conclusions The nature of emotional states that are difficult to regulate might account for the GD severity and indicate the subtype of PGs the patient belongs to. Treatment programs should be tailored on the specificity of PGs.

Histone Methylation and microRNA-dependent Regulation of Epigenetic Activities in Neural Progenitor Self-Renewal and Differentiation.

PubMed

Cacci, Emanuele; Negri, Rodolfo; Biagioni, Stefano; Lupo, Giuseppe

2017-01-01

Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages.

Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells.

PubMed

Tsurudome, M; Ito, Y

2000-01-01

Two molecules that regulate cell fusion have been identified and designated fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a glycosylated heavy chain and a nonglycosylated light chain that are disulfide linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional molecule: that is, fusion regulator, amino acid transporter, integrin regulator, comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several aspects of the structure and function of the FRP-1 system are reviewed: fusion regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant cell formation of blood monocytes. Monoclonal antibodies against human FRP-1 heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy chain supports amino acid transport activity and the FRP-1 light chains have recently been cloned as amino acid transporters that require association with the heavy chain to exhibit their activity. Novel pathways for monocyte-dependent regulation of T-cell activation have recently been found that are mediated by the FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic cellular functions.

Elsevier Trophoblast Research Award lecture: Molecular mechanisms underlying estrogen functions in trophoblastic cells--focus on leptin expression.

PubMed

Gambino, Y P; Maymó, J L; Pérez Pérez, A; Calvo, J C; Sánchez-Margalet, V; Varone, C L

2012-02-01

The steroid hormone 17β-estradiol is an estrogen that influences multiple aspects of placental function and fetal development in humans. During early pregnancy it plays a role in the regulation of blastocyst implantation, trophoblast differentiation and invasiveness, remodeling of uterine arteries, immunology and trophoblast production of hormones such as leptin. Estradiol exerts some effects through the action of classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors and regulate gene expression. In addition, estradiol can elicit rapid responses from membrane-associated receptors, like activation of protein-kinase pathways. Thus, the cellular effects of estradiol will depend on the specific receptors expressed and the integration of their signaling events. Leptin, the 16,000MW protein product of the obese gene, was originally considered an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy. The leptin gene is expressed in placenta, where leptin promotes proliferation and survival of trophoblastic cells. Expression of leptin in placenta is highly regulated by key pregnancy molecules as hCG and estradiol. The aim of this paper is to review the molecular mechanisms underlying estrogen functions in trophoblastic cells; focusing on mechanisms involved in estradiol regulation of placental leptin expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Up-regulation of OLR1 expression by TBC1D3 through activation of TNFα/NF-κB pathway promotes the migration of human breast cancer cells.

PubMed

Wang, Bei; Zhao, Huzi; Zhao, Lei; Zhang, Yongchen; Wan, Qing; Shen, Yong; Bu, Xiaodong; Wan, Meiling; Shen, Chuanlu

2017-11-01

Metastatic spread of cancer cells is the most life-threatening aspect of breast cancer and involves multiple steps including cell migration. We recently found that the TBC1D3 oncogene promotes the migration of breast cancer cells, and its interaction with CaM enhances the effects of TBC1D3. However, little is known regarding the mechanism by which TBC1D3 induces the migration of cancer cells. Here, we demonstrated that TBC1D3 stimulated the expression of oxidized low density lipoprotein receptor 1 (OLR1), a stimulator of cell migration, in breast cancer cells at the transcriptional level. Depletion of OLR1 by siRNAs or down-regulation of OLR1 expression using pomalidomide, a TNFα inhibitor, significantly decreased TBC1D3-induced migration of these cells. Notably, TBC1D3 overexpression activated NF-κB, a major effector of TNFα signaling, while inhibition of TNFα signaling suppressed the effects of TBC1D3. Consistent with this, NF-κB inhibition using its specific inhibitor caffeic acid phenethyl ester decreased both TBC1D3-induced OLR1 expression and cell migration, suggesting a critical role for TNFα/NF-κB signaling in TBC1D3-induced migration of breast cancer cells. Mechanistically, TBC1D3 induced activation of this signaling pathway on multiple levels, including by increasing the release of TNFα, elevating the transcription of TNFR1, TRAF1, TRAF5 and TRAF6, and decreasing the degradation of TNFR1. In summary, these studies identify the TBC1D3 oncogene as a novel regulator of TNFα/NF-κB signaling that mediates this oncogene-induced migration of human breast cancer cells by up-regulating OLR1. Copyright © 2017 Elsevier B.V. All rights reserved.

Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

PubMed

Golan, Matan; Zelinger, Einat; Zohar, Yonathan; Levavi-Sivan, Berta

2015-11-01

The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.

Advancing Stem Cell Models of Alpha-Synuclein Gene Regulation in Neurodegenerative Disease.

PubMed

Piper, Desiree A; Sastre, Danuta; Schüle, Birgitt

2018-01-01

Alpha-synuclein ( non A4 component of amyloid precursor, SNCA, NM_000345.3 ) plays a central role in the pathogenesis of Parkinson's disease (PD) and related Lewy body disorders such as Parkinson's disease dementia, Lewy body dementia, and multiple system atrophy. Since its discovery as a disease-causing gene in 1997, alpha-synuclein has been a central point of scientific interest both at the protein and gene level. Mutations, including copy number variants, missense mutations, short structural variants, and single nucleotide polymorphisms, can be causative for PD and affect conformational changes of the protein, can contribute to changes in expression of alpha-synuclein and its isoforms, and can influence regulation of temporal as well as spatial levels of alpha-synuclein in different tissues and cell types. A lot of progress has been made to understand both the physiological transcriptional and epigenetic regulation of the alpha-synuclein gene and whether changes in transcriptional regulation could lead to disease and neurodegeneration in PD and related alpha-synucleinopathies. Although the histopathological changes in these neurodegenerative disorders are similar, the temporal and spatial presentation and progression distinguishes them which could be in part due to changes or disruption of transcriptional regulation of alpha-synuclein. In this review, we describe different genetic alterations that contribute to PD and neurodegenerative conditions and review aspects of transcriptional regulation of the alpha-synuclein gene in the context of the development of PD. New technologies, advanced gene engineering and stem cell modeling, are on the horizon to shed further light on a better understanding of gene regulatory processes and exploit them for therapeutic developments.

Context and Auditory Fear are Differentially Regulated by HDAC3 Activity in the Lateral and Basal Subnuclei of the Amygdala

PubMed Central

Kwapis, Janine L; Alaghband, Yasaman; López, Alberto J; White, André O; Campbell, Rianne R; Dang, Richard T; Rhee, Diane; Tran, Ashley V; Carl, Allison E; Matheos, Dina P; Wood, Marcelo A

2017-01-01

Histone acetylation is a fundamental epigenetic mechanism that is dynamically regulated during memory formation. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) compete to modulate histone acetylation, allowing for rapid changes in acetylation in response to a learning event. HDACs are known to be powerful negative regulators of memory formation, but it is not clear whether this function depends on HDAC enzymatic activity per se. Here, we tested whether the enzymatic activity of an individual Class I HDAC, HDAC3, has a role in fear memory formation in subregions of the hippocampus and amygdala. We found that fear conditioning drove expression of the immediate early genes cFos and Nr4a2 in the hippocampus, which coincided with reduced HDAC3 occupancy at these promoters. Using a dominant-negative, deacetylase-dead point mutant virus (AAV-HDAC3(Y298H)-v5), we found that selectively blocking HDAC3 deacetylase activity in either the dorsal hippocampus or basal nucleus of the amygdala enhanced context fear without affecting tone fear. Blocking HDAC3 activity in the lateral nucleus of the amygdala, on the other hand, enhanced tone, but not context fear memory. These results show for the first time that the enzymatic activity of HDAC3 functions to negatively regulate fear memory formation. Further, HDAC3 activity regulates different aspects of fear memory in the basal and lateral subregions of the amygdala. Thus, the deacetylase activity of HDAC3 is a powerful negative regulator of fear memory formation in multiple subregions of the fear circuit. PMID:27924874

76 FR 23504 - Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 207 RIN 0750-AH12 Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS Case 2011-D016) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY...

Extracellular vesicle communication pathways as regulatory targets of oncogenic transformation.

PubMed

Choi, Dongsic; Lee, Tae Hoon; Spinelli, Cristiana; Chennakrishnaiah, Shilpa; D'Asti, Esterina; Rak, Janusz

2017-07-01

Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids. Biological effects of these processes have been implicated in several aspects of cancer-related pathology, including tumour growth, invasion, angiogenesis, metastasis, immunity and thrombosis. Notably, the emerging evidence suggests that oncogenic mutations may impact several aspects of EV-mediated cell-cell communication including: (i) EV release rate and protein content; (ii) molecular composition of cancer EVs; (iii) the inclusion of oncogenic and mutant macromolecules in the EV cargo; (iv) EV-mediated release of genomic DNA; (v) deregulation of mechanisms responsible for EV biogenesis (vesiculome) and (vi) mechanisms of EV uptake by cancer cells. Intriguingly, EV-mediated intercellular transfer of mutant and oncogenic molecules between subpopulations of cancer cells, their indolent counterparts and stroma may exert profound biological effects that often resemble (but are not tantamount to) oncogenic transformation, including changes in cell growth, clonogenicity and angiogenic phenotype, or cause cell stress and death. However, several biological barriers likely curtail a permanent horizontal transformation of normal cells through EV-mediated mechanisms. The ongoing analysis and targeting of EV-mediated intercellular communication pathways can be viewed as a new therapeutic paradigm in cancer, while the analysis of oncogenic cargo contained in EVs released from cancer cells into biofluids is being developed for clinical use as a biomarker and companion diagnostics. Indeed, studies are underway to further explore the multiple links between molecular causality in cancer and various aspects of cellular vesiculation. Copyright © 2017 Elsevier Ltd. All rights reserved.

GeneNetFinder2: Improved Inference of Dynamic Gene Regulatory Relations with Multiple Regulators.

PubMed

Han, Kyungsook; Lee, Jeonghoon

2016-01-01

A gene involved in complex regulatory interactions may have multiple regulators since gene expression in such interactions is often controlled by more than one gene. Another thing that makes gene regulatory interactions complicated is that regulatory interactions are not static, but change over time during the cell cycle. Most research so far has focused on identifying gene regulatory relations between individual genes in a particular stage of the cell cycle. In this study we developed a method for identifying dynamic gene regulations of several types from the time-series gene expression data. The method can find gene regulations with multiple regulators that work in combination or individually as well as those with single regulators. The method has been implemented as the second version of GeneNetFinder (hereafter called GeneNetFinder2) and tested on several gene expression datasets. Experimental results with gene expression data revealed the existence of genes that are not regulated by individual genes but rather by a combination of several genes. Such gene regulatory relations cannot be found by conventional methods. Our method finds such regulatory relations as well as those with multiple, independent regulators or single regulators, and represents gene regulatory relations as a dynamic network in which different gene regulatory relations are shown in different stages of the cell cycle. GeneNetFinder2 is available at http://bclab.inha.ac.kr/GeneNetFinder and will be useful for modeling dynamic gene regulations with multiple regulators.

Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

PubMed

Mawad, Damia; Figtree, Gemma; Gentile, Carmine

2017-01-01

The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease

PubMed Central

Berchtold, Nicole C.; Coleman, Paul D.; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

2014-01-01

Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer’s disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20–99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD. PMID:23273601

What Can We Learn from Rodents about Prolactin in Humans?

PubMed Central

Ben-Jonathan, Nira; LaPensee, Christopher R.; LaPensee, Elizabeth W.

2008-01-01

Prolactin (PRL) is a 23-kDa protein hormone that binds to a single-span membrane receptor, a member of the cytokine receptor superfamily, and exerts its action via several interacting signaling pathways. PRL is a multifunctional hormone that affects multiple reproductive and metabolic functions and is also involved in tumorigenicity. In addition to being a classical pituitary hormone, PRL in humans is produced by many tissues throughout the body where it acts as a cytokine. The objective of this review is to compare and contrast multiple aspects of PRL, from structure to regulation, and from physiology to pathology in rats, mice, and humans. At each juncture, questions are raised whether, or to what extent, data from rodents are relevant to PRL homeostasis in humans. Most current knowledge on PRL has been obtained from studies with rats and, more recently, from the use of transgenic mice. Although this information is indispensable for understanding PRL in human health and disease, there is sufficient disparity in the control of the production, distribution, and physiological functions of PRL among these species to warrant careful and judicial extrapolation to humans. PMID:18057139

Capillarics: pre-programmed, self-powered microfluidic circuits built from capillary elements.

PubMed

Safavieh, Roozbeh; Juncker, David

2013-11-07

Microfluidic capillary systems employ surface tension effects to manipulate liquids, and are thus self-powered and self-regulated as liquid handling is structurally and chemically encoded in microscale conduits. However, capillary systems have been limited to perform simple fluidic operations. Here, we introduce complex capillary flow circuits that encode sequential flow of multiple liquids with distinct flow rates and flow reversal. We first introduce two novel microfluidic capillary elements including (i) retention burst valves and (ii) robust low aspect ratio trigger valves. These elements are combined with flow resistors, capillary retention valves, capillary pumps, and open and closed reservoirs to build a capillary circuit that, following sample addition, autonomously delivers a defined sequence of multiple chemicals according to a preprogrammed and predetermined flow rate and time. Such a circuit was used to measure the concentration of C-reactive protein. This work illustrates that as in electronics, complex capillary circuits may be built by combining simple capillary elements. We define such circuits as "capillarics", and introduce symbolic representations. We believe that more complex circuits will become possible by expanding the library of building elements and formulating abstract design rules.

Multiple Pathways Linking Racism to Health Outcomes

PubMed Central

Harrell, Camara Jules P.; Burford, Tanisha I.; Cage, Brandi N.; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

2012-01-01

This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism’s impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society. PMID:22518195

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

PubMed

He, H; Chen, C; Xie, Y; Asea, A; Calderwood, S K

2000-11-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

Suicide Prevention in the Dot Com Era: Technological Aspects of a University Suicide Prevention Program

ERIC Educational Resources Information Center

Manning, Jessica; VanDeusen, Karen

2011-01-01

Western Michigan University's Suicide Prevention Program utilizes multiple technological components, including an online training course, a Web site, and 2 social networking Web site profiles, as integral aspects of a comprehensive program. This article discusses the development, maintenance, use, and impact of the technological aspects of this…

Separate necdin domains bind ARNT2 and HIF1{alpha} and repress transcription

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

Friedman, Eitan R.; Fan Chenming

2007-11-09

PWS is caused by the loss of expression of a set of maternally imprinted genes including NECDIN (NDN). NDN is expressed in post-mitotic neurons and plays an essential role in PWS as mouse models lacking only the Ndn gene mimic aspects of this disease. Patients haploid for SIM1 develop a PW-like syndrome. Here, we report that NDN directly interacts with ARNT2, a bHLH-PAS protein and dimer partner for SIM1. We also found that NDN can interact with HIF1{alpha}. We showed that NDN can repress transcriptional activation mediated by ARNT2:SIM1 as well as ARNT2:HIF1{alpha}. The N-terminal 115 residues of NDN aremore » sufficient for interaction with the bHLH domains of ARNT2 or HIF1{alpha} but not for transcriptional repression. Using GAL4-NDN fusion proteins, we determined that NDN possesses multiple repression domains. We thus propose that NDN regulates neuronal function and hypoxic response by regulating the activities of the ARNT2:SIM1 and ARNT2:HIF1{alpha} dimers, respectively.« less

Genome-wide identification and expression analysis of the ClTCP transcription factors in Citrullus lanatus.

PubMed

Shi, Pibiao; Guy, Kateta Malangisha; Wu, Weifang; Fang, Bingsheng; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-04-12

The plant-specific TCP transcription factor family, which is involved in the regulation of cell growth and proliferation, performs diverse functions in multiple aspects of plant growth and development. However, no comprehensive analysis of the TCP family in watermelon (Citrullus lanatus) has been undertaken previously. A total of 27 watermelon TCP encoding genes distributed on nine chromosomes were identified. Phylogenetic analysis clustered the genes into 11 distinct subgroups. Furthermore, phylogenetic and structural analyses distinguished two homology classes within the ClTCP family, designated Class I and Class II. The Class II genes were differentiated into two subclasses, the CIN subclass and the CYC/TB1 subclass. The expression patterns of all members were determined by semi-quantitative PCR. The functions of two ClTCP genes, ClTCP14a and ClTCP15, in regulating plant height were confirmed by ectopic expression in Arabidopsis wild-type and ortholog mutants. This study represents the first genome-wide analysis of the watermelon TCP gene family, which provides valuable information for understanding the classification and functions of the TCP genes in watermelon.

Chemicals to enhance microalgal growth and accumulation of high-value bioproducts

PubMed Central

Yu, Xinheng; Chen, Lei; Zhang, Weiwen

2015-01-01

Photosynthetic microalgae have attracted significant attention as they can serve as important sources for cosmetic, food and pharmaceutical products, industrial materials and even biofuel biodiesels. However, current productivity of microalga-based processes is still very low, which has restricted their scale-up application. In addition to various efforts in strain improvement and cultivation optimization, it was proposed that the productivity of microalga-based processes can also be increased using various chemicals to trigger or enhance cell growth and accumulation of bioproducts. Herein, we summarized recent progresses in applying chemical triggers or enhancers to improve cell growth and accumulation of bioproducts in algal cultures. Based on their enhancing mechanisms, these chemicals can be classified into four categories:chemicals regulating biosynthetic pathways, chemicals inducing oxidative stress responses, phytohormones and analogs regulating multiple aspects of microalgal metabolism, and chemicals directly as metabolic precursors. Taken together, the early researches demonstrated that the use of chemical stimulants could be a very effective and economical way to improve cell growth and accumulation of high-value bioproducts in large-scale cultivation of microalgae. PMID:25741321

Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease

PubMed Central

Simon, Matthew J.; Iliff, Jeffrey J.

2015-01-01

Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer’s disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the ‘glymphatic’ system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. PMID:26499397

Brassinosteroids

PubMed Central

Clouse, Steven D.

2011-01-01

Brassinosteroids (BRs) are endogenous plant hormones essential for the proper regulation of multiple physiological processes required for normal plant growth and development. Since their discovery more than 30 years ago, extensive research on the mechanisms of BR action using biochemistry, mutant studies, proteomics and genome-wide transcriptome analyses, has helped refine the BR biosynthetic pathway, identify the basic molecular components required to relay the BR signal from perception to gene regulation, and expand the known physiological responses influenced by BRs. These mechanistic advances have helped answer the intriguing question of how BRs can have such dramatic pleiotropic effects on a broad range of diverse developmental pathways and have further pointed to BR interactions with other plant hormones and environmental cues. This chapter briefly reviews historical aspects of BR research and then summarizes the current state of knowledge on BR biosynthesis, metabolism and signal transduction. Recent studies uncovering novel phosphorelays and gene regulatory networks through which BR influences both vegetative and reproductive development are examined and placed in the context of known BR physiological responses including cell elongation and division, vascular differentiation, flowering, pollen development and photomorphogenesis. PMID:22303275

Sonic hedgehog signaling in kidney fibrosis: a master communicator.

PubMed

Zhou, Dong; Tan, Roderick J; Liu, Youhua

2016-09-01

The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial- mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients.

Sonic hedgehog signaling in kidney fibrosis: a master communicator

PubMed Central

Zhou, Dong; Tan, Roderick J.; Liu, Youhua

2017-01-01

The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial-mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients. PMID:27333788

Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective.

PubMed

Figlewicz, Dianne P

2015-01-01

Palatable foods are frequently high in energy density. Chronic consumption of high-energy density foods can contribute to the development of cardiometabolic pathology including obesity, diabetes, and cardiovascular disease. This article reviews the contributions of extrinsic and intrinsic factors that influence the reward components of food intake. A narrative review was conducted to determine the behavioral and central nervous system (CNS) related processes involved in the reward components of high-energy density food intake. The rewarding aspects of food, particularly palatable and preferred foods, are regulated by CNS circuitry. Overlaying this regulation is modulation by intrinsic endocrine systems and metabolic hormones relating to energy homeostasis, developmental stage, or gender. It is now recognized that extrinsic or environmental factors, including ambient diet composition and the provocation of stress or anxiety, also contribute substantially to the expression of food reward behaviors such as motivation for, and seeking of, preferred foods. High-energy density food intake is influenced by both physiological and pathophysiological processes. Contextual, behavioral, and psychological factors and CNS-related processes represent potential targets for multiple types of therapeutic intervention.

48 CFR 22.503 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Policy. 22.503 Section 22.503 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS... require multiple construction contractors and/or subcontractors employing workers in multiple crafts or...

Multiple shell fusion targets

DOEpatents

Lindl, J.D.; Bangerter, R.O.

1975-10-31

Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

[Medical and biologic aspects of regulation and evaluation of microclimate: results and prospects of further studies].

PubMed

Afanas'eva, R F

2008-01-01

The article deals with basic points concerning influence of microclimate on humans and tasks of its regulation in contemporary conditions. The authors described universality of microclimate from viewpoint of producing functional state and health state of human, so microclimate should be assessed consistently and systematically through all aspects of its influence, with complex approach to evaluation (clothing, physical activity, etc.).

Telecommunications Policy Research Conference. Regulation, Deregulation & Competition Section. Papers.

ERIC Educational Resources Information Center

Telecommunications Policy Research Conference, Inc., Washington, DC.

Three papers discuss aspects of telecommunications regulation in a deregulated environment. The first paper, "Implementing Telephone Deregulation: The Political Economy of State Regulation in the Post-Divestiture Era" (Paul E. Teske), analyzed the variation in state regulation of local telephone operating companies using regression…

B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells.

PubMed

Seda, Vaclav; Mraz, Marek

2015-03-01

The physiology of B cells is intimately connected with the function of their B-cell receptor (BCR). B-cell lymphomas frequently (dys)regulate BCR signalling and thus take advantage of this pre-existing pathway for B-cell proliferation and survival. This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR-associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect. Here we describe the current knowledge of the specific aspects of BCR signalling in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia (CLL) and normal B cells. Multiple factors can contribute to BCR pathway (dys)regulation in these malignancies and the activation of 'chronic' or 'tonic' BCR signalling. In lymphoma B cells, the balance of initiation, amplitude and duration of BCR activation can be influenced by a specific immunoglobulin structure, the expression and mutations of adaptor molecules (like GAB1, BLNK, GRB2, CARD11), the activity of kinases (like LYN, SYK, PI3K) or phosphatases (like SHIP-1, SHP-1 and PTEN) and levels of microRNAs. We also discuss the crosstalk of BCR with other signalling pathways (NF-κB, adhesion through integrins, migration and chemokine signalling) to emphasise that the 'BCR inhibitors' target multiple pathways interconnected with BCR, which might explain some of their clinical activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Routes to DNA accessibility: alternative pathways for nucleosome unwinding.

PubMed

Schlingman, Daniel J; Mack, Andrew H; Kamenetska, Masha; Mochrie, Simon G J; Regan, Lynne

2014-07-15

The dynamic packaging of DNA into chromatin is a key determinant of eukaryotic gene regulation and epigenetic inheritance. Nucleosomes are the basic unit of chromatin, and therefore the accessible states of the nucleosome must be the starting point for mechanistic models regarding these essential processes. Although the existence of different unwound nucleosome states has been hypothesized, there have been few studies of these states. The consequences of multiple states are far reaching. These states will behave differently in all aspects, including their interactions with chromatin remodelers, histone variant exchange, and kinetic properties. Here, we demonstrate the existence of two distinct states of the unwound nucleosome, which are accessible at physiological forces and ionic strengths. Using optical tweezers, we measure the rates of unwinding and rewinding for these two states and show that the rewinding rates from each state are different. In addition, we show that the probability of unwinding into each state is dependent on the applied force and ionic strength. Our results demonstrate not only that multiple unwound states exist but that their accessibility can be differentially perturbed, suggesting possible roles for these states in gene regulation. For example, different histone variants or modifications may facilitate or suppress access to DNA by promoting unwinding into one state or the other. We anticipate that the two unwound states reported here will be the basis for future models of eukaryotic transcriptional control. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Affective brain areas and sleep disordered breathing

PubMed Central

Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Woo, Mary A.; Ogren, Jennifer A.

2014-01-01

The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing found in obstructive sleep apnea, heart failure (HF), and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude- distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, raphé, ventrolateral medulla, basal ganglia and, in CCHS, the locus coeruleus. Raphé and locus coeruleus injury may modify serotonergic and adrenergic modulation of upper airway and arousal characteristics. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several affected rostral sites, including the insular and cingulate cortices and hippocampus, mediate aspects of dyspnea, especially in CCHS, while others, including the anterior cingulate and thalamus, participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation. PMID:24746053

Critical care in the surgical global period.

PubMed

Painter, Julie R

2013-03-01

This article explores the rules and regulations from Current Procedural Terminology (CPT) code set and US Medicare and Medicaid Services (Medicare) regarding multiple physicians reporting critical care services during the global period. The article takes into account the critical care definitions, regulations, documentation requirements, and services each provider can report to Medicare. A clinical scenario based on literature supporting the types of complications and care that might typically be included in the post-operative period for a patient who is surgically treated for a type A aortic dissection was analyzed. It was determined that multiple physicians may provide critical care services to a single patient during the global period. The physician who performed the primary procedure cannot report critical care separately unless documentation supporting use of modifier 25 (significant, separately identifiable services) or 24 (unrelated services) supports that critical care is unrelated to the global period. Other physicians may report critical care services separately if specific criteria are met. To report critical care services to Medicare, the patient's condition must meet the Medicare definition of critical care and the physicians should generally represent different specialties providing different aspects of care to the critically ill or injured patient as defined by Medicare. There should be no overlap in time of services provided by each physician. Each physician's documentation should clearly support medical necessity with the diagnosis demonstrating the critical nature of the patients' illness, the total time spent providing critical care, the critical care service provided, and other contributing factors.

Drosophila Protein Kinase CK2: Genetics, Regulatory Complexity and Emerging Roles during Development

PubMed Central

Bandyopadhyay, Mohna; Arbet, Scott; Bishop, Clifton P.; Bidwai, Ashok P.

2016-01-01

CK2 is a Ser/Thr protein kinase that is highly conserved amongst all eukaryotes. It is a well-known oncogenic kinase that regulates vital cell autonomous functions and animal development. Genetic studies in the fruit fly Drosophila are providing unique insights into the roles of CK2 in cell signaling, embryogenesis, organogenesis, neurogenesis, and the circadian clock, and are revealing hitherto unknown complexities in CK2 functions and regulation. Here, we review Drosophila CK2 with respect to its structure, subunit diversity, potential mechanisms of regulation, developmental abnormalities linked to mutations in the gene encoding CK2 subunits, and emerging roles in multiple aspects of eye development. We examine the Drosophila CK2 “interaction map” and the eye-specific “transcriptome” databases, which raise the prospect that this protein kinase has many additional targets in the developing eye. We discuss the possibility that CK2 functions during early retinal neurogenesis in Drosophila and mammals bear greater similarity than has been recognized, and that this conservation may extend to other developmental programs. Together, these studies underscore the immense power of the Drosophila model organism to provide new insights and avenues to further investigate developmentally relevant targets of this protein kinase. PMID:28036067

Validity evidence for the adaptation of the State Mindfulness Scale for Physical Activity (SMS-PA) in Spanish youth.

PubMed

Ullrich-French, Sarah; González Hernández, Juan; Hidalgo Montesinos, María D

2017-02-01

Mindfulness is an increasingly popular construct with promise in enhancing multiple positive health outcomes. Physical activity is an important behavior for enhancing overall health, but no Spanish language scale exists to test how mindfulness during physical activity may facilitate physical activity motivation or behavior. This study examined the validity of a Spanish adaption of a new scale, the State Mindfulness Scale for Physical Activity, to assess mindfulness during a specific experience of physical activity. Spanish youths (N = 502) completed a cross-sectional survey of state mindfulness during physical activity and physical activity motivation regulations based on Self-Determination Theory. A high-order model fit the data well and supports the use of one general state mindfulness factor or the use of separate subscales of mindfulness of mental (e.g., thoughts, emotions) and body (physical movement, muscles) aspects of the experience. Internal consistency reliability was good for the general scale and both sub-scales. The pattern of correlations with motivation regulations provides further support for construct validity with significant and positive correlations with self-determined forms of motivation and significant and negative correlations with external regulation and amotivation. Initial validity evidence is promising for the use of the adapted measure.

A Bir1p–Sli15p Kinetochore Passenger Complex Regulates Septin Organization during Anaphase

PubMed Central

Thomas, Scott

2007-01-01

Kinetochore–passenger complexes in metazoans have been proposed to coordinate the segregation of chromosomes in anaphase with the induction of cytokinesis. Passenger protein homologues in the budding yeast Saccharomyces cerevisiae play a critical role early in mitosis, ensuring proper biorientation of kinetochore–microtubule attachments. Our recent work has implicated the passenger protein Bir1p (Survivin) and the inner kinetochore complex centromere binding factor 3 (CBF3) in the regulation of septin dynamics during anaphase. Here, we present data that is consistent with there being multiple passenger protein complexes. Our data show that Bir1p links together a large passenger complex containing Ndc10p, Sli15p (INCENP), and Ipl1p (Aurora B) and that the interaction between Bir1p and Sli15p is specifically involved in regulating septin dynamics during anaphase. Neither conditional alleles nor mutants of BIR1 that disrupt the interaction between Bir1p and Sli15p resulted in mono-attached kinetochores, suggesting that the Bir1p–Sli15p complex functions in anaphase and independently from Sli15p–Ipl1p complexes. We present a model for how discrete passenger complexes coordinate distinct aspects of mitosis. PMID:17652458

MicroRNAs: regulators of gene expression and cell differentiation

PubMed Central

Shivdasani, Ramesh A.

2006-01-01

The existence and roles of a class of abundant regulatory RNA molecules have recently come into sharp focus. Micro-RNAs (miRNAs) are small (approximately 22 bases), non–protein-coding RNAs that recognize target sequences of imperfect complementarity in cognate mRNAs and either destabilize them or inhibit protein translation. Although mechanisms of miRNA biogenesis have been elucidated in some detail, there is limited appreciation of their biological functions. Reported examples typically focus on miRNA regulation of a single tissue-restricted transcript, often one encoding a transcription factor, that controls a specific aspect of development, cell differentiation, or physiology. However, computational algorithms predict up to hundreds of putative targets for individual miRNAs, single transcripts may be regulated by multiple miRNAs, and miRNAs may either eliminate target gene expression or serve to finetune transcript and protein levels. Theoretical considerations and early experimental results hence suggest diverse roles for miRNAs as a class. One appealing possibility, that miRNAs eliminate low-level expression of unwanted genes and hence refine unilineage gene expression, may be especially amenable to evaluation in models of hematopoiesis. This review summarizes current understanding of miRNA mechanisms, outlines some of the important outstanding questions, and describes studies that attempt to define miRNA functions in hematopoiesis. PMID:16882713

The sulfiredoxin-peroxiredoxin (Srx-Prx) axis in cell signal transduction and cancer development.

PubMed

Mishra, Murli; Jiang, Hong; Wu, Lisha; Chawsheen, Hedy A; Wei, Qiou

2015-10-01

Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Peroxiredoxin (Prx) is a family of thiol-based peroxidase that acts as a regulator of redox signaling. Members of Prx family can act as antioxidants and chaperones. Sulfiredoxin (Srx) is an antioxidant protein that exclusively reduces over-oxidized typical 2-Cys Prx. Srx has different affinities for individual Prx and it also catalyzes the deglutathionylation of variety of substrates. Individual component of the Srx-Prx system plays critical role in carcinogenesis by modulating cell signaling pathways involved in cell proliferation, migration and metastasis. Expression levels of individual component of the Srx-Prx axis have been correlated with patient survival outcome in multiple cancer types. This review will summarize the molecular basis of differences in the affinity of Srx for individual Prx and the role of individual component of the Srx-Prx system in tumor progression and metastasis. This enhanced understanding of molecular aspects of Srx-Prx interaction and its role in cell signal transduction will help define the Srx-Prx system as a future therapeutic target in human cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Expert Voices in Learning Improvisation: Shaping Regulation Processes through Experiential Influence

ERIC Educational Resources Information Center

de Bruin, Leon R.

2017-01-01

Interpersonal and collaborative activity plays an important role in the social aspects of self-regulated learning (SRL) development. Peer, teacher and group interactions facilitate support for self-regulation, co-regulation and socially shared regulatory processes. Situated and experiential interplay facilitates personal, co-constructed and…

The Relationships between Human Fatigue and Public Health: A Brief Commentary on Selected Papers from the 9th International Conference on Managing Fatigue in Transportation, Resources and Health.

PubMed

Sargent, Charli; Roberts, Paul; Dawson, Drew; Ferguson, Sally; Meuleners, Lynn; Brook, Libby; Roach, Gregory D

2016-08-24

The 9th International Conference on Managing Fatigue in Transportation, Resources and Health was held in Fremantle, Western Australia in March 2015. The purpose of the conferences in this series is to provide a forum for industry representatives, regulators, and scientists to discuss recent advances in the field of fatigue research. We have produced a Special Issue of the International Journal of Environmental Research and Public Health based on papers from the conference that were focused on various aspects of public health. First, the Special Issue highlights the fact that working long shifts and/or night shifts can affect not only cognitive functioning, but also physical health. In particular, three papers examined the potential relationships between shiftwork and different aspects of health, including the cardiovascular system, sleep disordered breathing, and eating behaviour. Second, the Special Issue highlights the move away from controlling fatigue through prescriptive hours of service rules and toward the application of risk management principles. In particular, three papers indicated that best-practice fatigue risk management systems should contain multiple redundant layers of defense against fatigue-related errors and accidents.

Brain temperature and its fundamental properties: a review for clinical neuroscientists

PubMed Central

Wang, Huan; Wang, Bonnie; Normoyle, Kieran P.; Jackson, Kevin; Spitler, Kevin; Sharrock, Matthew F.; Miller, Claire M.; Best, Catherine; Llano, Daniel; Du, Rose

2014-01-01

Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature's spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically “expensive” organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective. PMID:25339859

Interventional procedures and future drug therapy for hypertension

PubMed Central

Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

2017-01-01

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

Circadian rhythms accelerate wound healing in female Siberian hamsters

PubMed Central

Cable, Erin J.; Onishi, Kenneth G.; Prendergast, Brian J.

2017-01-01

Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are absent in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3 h after light onset (ZT03) or 2 h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing. PMID:27998755

Protecting Privacy and Confidentiality in a Multiple Use, Multiple User Mental Health Information System.

ERIC Educational Resources Information Center

Bank, Rheta; Laska, Eugene M.

1978-01-01

These aspects of maintaining the security of computer-processed information concerning mental health patients are discussed: legal protection, technological safeguards, and managerial responsibility. (CTM)

Using Alternative Multiplication Algorithms to "Offload" Cognition

ERIC Educational Resources Information Center

Jazby, Dan; Pearn, Cath

2015-01-01

When viewed through a lens of embedded cognition, algorithms may enable aspects of the cognitive work of multi-digit multiplication to be "offloaded" to the environmental structure created by an algorithm. This study analyses four multiplication algorithms by viewing different algorithms as enabling cognitive work to be distributed…

77 FR 74631 - General Services Administration Acquisition Regulation: Modifications (Multiple Award Schedules...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

...-0001; Sequence 21] General Services Administration Acquisition Regulation: Modifications (Multiple... Modifications (Multiple Award Schedule). DATES: Submit comments on or before: February 15, 2013. FOR FURTHER INFORMATION CONTACT: Ms. Dana Munson, General Services Acquisition Policy Division, GSA, (202) 357-9652 or...

Unique associations between young adult men's emotional functioning and their body dissatisfaction and disordered eating.

PubMed

Griffiths, Scott; Angus, Douglas; Murray, Stuart B; Touyz, Stephen

2014-03-01

Research on emotional functioning, body dissatisfaction, and disordered eating in males is predominated by studies of negative affect and emotion regulation. Other aspects of emotional functioning, namely emotion recognition and attentional biases toward emotional stimuli, have received little empirical attention. The present study investigated the unique associations between different aspects of men's emotional functioning and their disordered eating attitudes, muscularity dissatisfaction, and body fat dissatisfaction. Results from 132 male undergraduates showed that muscularity dissatisfaction was uniquely associated with both emotion regulation difficulties and an attentional bias toward rejecting faces. Body fat dissatisfaction was not uniquely associated with any aspect of emotional functioning. Disordered eating was uniquely associated with emotion regulation difficulties. Collectively, the results indicate differences in the patterns of associations between men's emotional functioning and their body dissatisfaction and disordered eating. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measuring students' self-regulated learning in professional education: bridging the gap between event and aptitude measurements.

PubMed

Endedijk, Maaike D; Brekelmans, Mieke; Sleegers, Peter; Vermunt, Jan D

Self-regulated learning has benefits for students' academic performance in school, but also for expertise development during their professional career. This study examined the validity of an instrument to measure student teachers' regulation of their learning to teach across multiple and different kinds of learning events in the context of a postgraduate professional teacher education programme. Based on an analysis of the literature, we developed a log with structured questions that could be used as a multiple-event instrument to determine the quality of student teachers' regulation of learning by combining data from multiple learning experiences. The findings showed that this structured version of the instrument measured student teachers' regulation of their learning in a valid and reliable way. Furthermore, with the aid of the Structured Learning Report individual differences in student teachers' regulation of learning could be discerned. Together the findings indicate that a multiple-event instrument can be used to measure regulation of learning in multiple contexts for various learning experiences at the same time, without the necessity of relying on students' ability to rate themselves across all these different experiences. In this way, this instrument can make an important contribution to bridging the gap between two dominant approaches to measure SRL, the traditional aptitude and event measurement approach.

48 CFR - Unknown Title

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Section Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Constructio...

48 CFR - Unknown Title

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Section Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Constructio...

The Use of Learning Study in Designing Examples for Teaching Physics

NASA Astrophysics Data System (ADS)

Guo, Jian-Peng; Yang, Ling-Yan; Ding, Yi

2017-07-01

Researchers have consistently demonstrated that studying multiple examples is more effective than studying one example because comparing multiple examples can promote schema construction and facilitate discernment of critical aspects. Teachers, however, are usually absent from those self-led text-based studies. In this experimental study, a learning study approach based on variation theory was adopted to examine the effectiveness of teachers' different ways of designing multiple examples in helping students learn a physics principle. Three hundred and fifty-one tenth-grade students learned to distinguish action-reaction from equilibrium (a) by comparing examples that varied critical aspects first separately and then simultaneously, or (b) by comparing examples that separately varied critical aspects only. Results showed that students with average academic attainment benefited more from comparing examples in the first condition. Students with higher academic attainment learned equally within both conditions. This finding supports the advantage of simultaneous variation. The characteristics of students and instructional support should be taken into account when considering the effectiveness of patterns of variation.

Regulation of Motivation: Contextual and Social Aspects

ERIC Educational Resources Information Center

Wolters, Christopher A.

2011-01-01

Background: Models of self-regulated learning have been used extensively as a way of understanding how students understand, monitor, and manage their own academic functioning. The regulation of motivation is a facet of self-regulated learning that describes students' efforts to control their own motivation or motivational processing. The…

In regulation we trust.

PubMed

Wiig, Siri; Tharaldsen, Jorunn Elise

2012-01-01

The role of trust has been argued to play an increasingly important role in modern, complex, and ambivalent risk societies. Trust within organizational research is anticipated to have a general strategic impact on aspects such as organizational performance, communication and knowledge exchange, and learning from accidents. Trust is also an important aspect related to regulation of risk. Diverse regulatory regimes, their contexts and risks influence regulators use of trust and distrust in regulatory practice. The aim of this paper is to discuss the relationship between risk regulation and trust across diverse risk regulation regimes. By drawing from studies of risk regulation, risk perception, and trust the purpose is to discuss how regulation and trust are linked and used in practice to control risk across system levels in socio-technical systems in high risk industries. This paper provides new knowledge on 1) how functional and dysfunctional trust and distrust are grounded in the empirical realities of high risk industries, 2) how different perspectives on trust and distrust act together and bring new knowledge on how society control risk.

“Humanized mice for HIV and AIDS research”

PubMed Central

Garcia, J. Victor

2016-01-01

HIV has a very limited species tropism that prevents the use of most conventional small animal models for AIDS research. The in vivo analysis of HIV/AIDS has benefited extensively from novel chimeric animal models that accurately recapitulate key aspects of the human condition. Specifically, immunodeficient mice that are systemically repopulated with human hematolymphoid cells offer a viable alternative for the study of a multitude of highly relevant aspects of HIV replication, pathogenesis, therapy, transmission, prevention, and eradication. This article summarizes some of the multiple contributions that humanized mouse models of HIV infection have made to the field of AIDS research. These models have proven to be highly informative and hold great potential for accelerating multiple aspects of HIV research in the future. PMID:27447446

Multiple Intelligences: Curriculum and Assessment Project. Final Report

ERIC Educational Resources Information Center

Hyland, Aine, Ed.

2011-01-01

The "Multiple Intelligences, Curriculum and Assessment Project" at University College Cork was a collaborative project carried out between 1995 and 1999. The key research question focused on whether Howard Gardner's theory of Multiple Intelligences could be applied to, and enhance, aspects of curriculum and assessment at primary and…

Alternative Multiple Imputation Inference for Mean and Covariance Structure Modeling

ERIC Educational Resources Information Center

Lee, Taehun; Cai, Li

2012-01-01

Model-based multiple imputation has become an indispensable method in the educational and behavioral sciences. Mean and covariance structure models are often fitted to multiply imputed data sets. However, the presence of multiple random imputations complicates model fit testing, which is an important aspect of mean and covariance structure…

48 CFR 46.707 - Pricing aspects of fixed-price incentive contract warranties.

Code of Federal Regulations, 2010 CFR

2010-10-01

... FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Warranties 46.707 Pricing aspects of... the total final price. Contractor compliance with the warranty after the establishment of the total...

48 CFR 46.707 - Pricing aspects of fixed-price incentive contract warranties.

Code of Federal Regulations, 2011 CFR

2011-10-01

... FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Warranties 46.707 Pricing aspects of... the total final price. Contractor compliance with the warranty after the establishment of the total...

VIEWIT: computation of seen areas, slope, and aspect for land-use planning

Treesearch

Michael R. Travis; Gary H. Elsner; Wayne D. Iverson; Christine G. Johnson

1975-01-01

This user's guide provides instructions for using VIEWIT--a computerized technique for delineating the terrain visible from a single point or from multiple observer points, and for doing slope and aspect analyses. Results are in tabular or in overlay map form. VIEWIT can do individual view-area, slope, or aspect analyses or combined analyses, and can produce...

Manduca Contactin Regulates Amyloid Precursor Protein-Dependent Neuronal Migration

PubMed Central

Ramaker, Jenna M.; Swanson, Tracy L.

2016-01-01

Amyloid precursor protein (APP) was originally identified as the source of β-amyloid peptides that accumulate in Alzheimer's disease (AD), but it also has been implicated in the control of multiple aspects of neuronal motility. APP belongs to an evolutionarily conserved family of transmembrane proteins that can interact with a variety of adapter and signaling molecules. Recently, we showed that both APP and its insect ortholog [APPL (APP-Like)] directly bind the heterotrimeric G-protein Goα, supporting the model that APP can function as an unconventional Goα-coupled receptor. We also adapted a well characterized assay of neuronal migration in the hawkmoth, Manduca sexta, to show that APPL–Goα signaling restricts ectopic growth within the developing nervous system, analogous to the role postulated for APP family proteins in controlling migration within the mammalian cortex. Using this assay, we have now identified Manduca Contactin (MsContactin) as an endogenous ligand for APPL, consistent with previous work showing that Contactins interact with APP family proteins in other systems. Using antisense-based knockdown protocols and fusion proteins targeting both proteins, we have shown that MsContactin is selectively expressed by glial cells that ensheath the migratory neurons (expressing APPL), and that MsContactin–APPL interactions normally prevent inappropriate migration and outgrowth. These results provide new evidence that Contactins can function as authentic ligands for APP family proteins that regulate APP-dependent responses in the developing nervous system. They also support the model that misregulated Contactin–APP interactions might provoke aberrant activation of Goα and its effectors, thereby contributing to the neurodegenerative sequelae that typify AD. SIGNIFICANCE STATEMENT Members of the amyloid precursor protein (APP) family participate in many aspects of neuronal development, but the ligands that normally activate APP signaling have remained controversial. This research provides new evidence that members of the Contactin family function as authentic ligands for APP and its orthologs, and that this evolutionarily conserved class of membrane-attached proteins regulates key aspects of APP-dependent migration and outgrowth in the embryonic nervous system. By defining the normal role of Contactin–APP signaling during development, these studies also provide the framework for investigating how the misregulation of Contactin–APP interactions might contribute to neuronal dysfunction in the context of both normal aging and neurodegenerative conditions, including Alzheimer's disease. PMID:27535920

Obesity: Current and potential pharmacotherapeutics and targets.

PubMed

Narayanaswami, Vidya; Dwoskin, Linda P

2017-02-01

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Silicon Regulates Potential Genes Involved in Major Physiological Processes in Plants to Combat Stress

PubMed Central

Manivannan, Abinaya; Ahn, Yul-Kuyn

2017-01-01

Silicon (Si), the quasi-essential element occurs as the second most abundant element in the earth's crust. Biological importance of Si in plant kingdom has become inevitable particularly under stressed environment. In general, plants are classified as high, medium, and low silicon accumulators based on the ability of roots to absorb Si. The uptake of Si directly influence the positive effects attributed to the plant but Si supplementation proves to mitigate stress and recover plant growth even in low accumulating plants like tomato. The application of Si in soil as well as soil-less cultivation systems have resulted in the enhancement of quantitative and qualitative traits of plants even under stressed environment. Silicon possesses several mechanisms to regulate the physiological, biochemical, and antioxidant metabolism in plants to combat abiotic and biotic stresses. Nevertheless, very few reports are available on the aspect of Si-mediated molecular regulation of genes with potential role in stress tolerance. The recent advancements in the era of genomics and transcriptomics have opened an avenue for the determination of molecular rationale associated with the Si amendment to the stress alleviation in plants. Therefore, the present endeavor has attempted to describe the recent discoveries related to the regulation of vital genes involved in photosynthesis, transcription regulation, defense, water transport, polyamine synthesis, and housekeeping genes during abiotic and biotic stress alleviation by Si. Furthermore, an overview of Si-mediated modulation of multiple genes involved in stress response pathways such as phenylpropanoid pathway, jasmonic acid pathway, ABA-dependent or independent regulatory pathway have been discussed in this review. PMID:28824681

Obesity: Current and Potential Pharmacotherapeutics and Targets

PubMed Central

Narayanaswami, Vidya; Dwoskin, Linda P.

2016-01-01

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. PMID:27773782

Chemotactic Cues for NOTCH1-Dependent Leukemia

PubMed Central

Piovan, Erich; Tosello, Valeria; Amadori, Alberto; Zanovello, Paola

2018-01-01

The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL. Leukemia patients often present with high-blood cell counts, diffuse disease with infiltration of the bone marrow, secondary lymphoid organs, and diffusion to the central nervous system (CNS). Chemokines are chemotactic cytokines that regulate migration of cells between tissues and the positioning and interactions of cells within tissue. Homeostatic chemokines and their receptors have been implicated in regulating organ-specific infiltration, but may also directly and indirectly modulate tumor growth. Recently, oncogenic NOTCH1 has been shown to regulate infiltration of leukemic cells into the CNS hijacking the CC-chemokine ligand 19/CC-chemokine receptor 7 chemokine axis. In addition, a crucial role for the homing receptor axis CXC-chemokine ligand 12/CXC-chemokine receptor 4 has been demonstrated in leukemia maintenance and progression. Moreover, the CCL25/CCR9 axis has been implicated in the homing of leukemic cells into the gut, particularly in the presence of phosphatase and tensin homolog tumor suppressor loss. In this review, we summarize the latest developments regarding the role of NOTCH signaling in regulating the chemotactic microenvironmental cues involved in the generation and progression of T-ALL and compare these findings to B-CLL. PMID:29666622

Expression Profiling Identifies Klf15 as a Glucocorticoid Target That Regulates Airway Hyperresponsiveness

PubMed Central

Masuno, Kiriko; Haldar, Saptarsi M.; Jeyaraj, Darwin; Mailloux, Christina M.; Huang, Xiaozhu; Panettieri, Rey A.; Jain, Mukesh K.

2011-01-01

Glucocorticoids (GCs), which activate GC receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. GCs exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM (HASM) gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7,500 genes had statistically distinguishable changes in expression; quantitative PCR validation of a 40-gene subset of putative GR-regulated genes in 6 HASM cell lines suggested that the early transcriptional targets of GR signaling are similar in independent HASM lines. Gene ontology analysis implicated GR targets in controlling multiple aspects of ASM function. One GR-regulated gene, the transcription factor, Kruppel-like factor 15 (Klf15), was already known to modulate vascular smooth and cardiac muscle function, but had no known role in the lung. We therefore analyzed the pulmonary phenotype of Klf15−/− mice after ovalbumin sensitization and challenge. We found diminished airway responses to acetylcholine in ovalbumin-challenged Klf15−/− mice without a significant change in the induction of asthmatic inflammation. In cultured cells, overexpression of Klf15 reduced proliferation of HASM cells, whereas apoptosis in Klf15−/− murine ASM cells was increased. Together, these results further characterize the GR-regulated gene network in ASM and establish a novel role for the GR target, Klf15, in modulating airway function. PMID:21257922

What Health-Related Functions Are Regulated by the Nervous System?

MedlinePlus

... What health-related functions are regulated by the nervous system? The nervous system plays a role in nearly every aspect of ... feeling emotions. Functions that are regulated by the nervous system include (but are not limited to): Brain growth ...

International regulations regarding exchange of Rubus plant material

USDA-ARS?s Scientific Manuscript database

This article summarizes the international quarantine regulations regarding plant material exchange for Rubus. US federal importation regulations are summarized along with aspects of Rubus that presented as noxious weed. Requirements for exporting Rubus to foreign countries are also described. Proper...

A randomized waitlist-controlled trial of cognitive behavior therapy to improve emotion regulation in children with autism.

PubMed

Weiss, Jonathan A; Thomson, Kendra; Burnham Riosa, Priscilla; Albaum, Carly; Chan, Victoria; Maughan, Andrea; Tablon, Paula; Black, Karen

2018-04-23

Mental health problems are common among individuals with autism spectrum disorder (ASD), and difficulties with emotion regulation processes may underlie these issues. Cognitive behavior therapy (CBT) is considered an efficacious treatment for anxiety in children with ASD. Additional research is needed to examine the efficacy of a transdiagnostic treatment approach, whereby the same treatment can be applied to multiple emotional problems, beyond solely anxiety. The purpose of the present study was to examine the efficacy of a manualized and individually delivered 10-session, transdiagnostic CBT intervention, aimed at improving emotion regulation and mental health difficulties in children with ASD. Sixty-eight children (M age = 9.75, SD = 1.27) and their parents participated in the study, randomly allocated to either a treatment immediate (n = 35) or waitlist control condition (n = 33) (ISRCTN #67079741). Parent-, child-, and clinician-reported measures of emotion regulation and mental health were administered at baseline, postintervention/postwaitlist, and at 10-week follow-up. Children in the treatment immediate condition demonstrated significant improvements on measures of emotion regulation (i.e., emotionality, emotion regulation abilities with social skills) and aspects of psychopathology (i.e., a composite measure of internalizing and externalizing symptoms, adaptive behaviors) compared to those in the waitlist control condition. Treatment gains were maintained at follow-up. This study is the first transdiagnostic CBT efficacy trial for children with ASD. Additional investigations are needed to further establish its relative efficacy compared to more traditional models of CBT for children with ASD and other neurodevelopmental conditions. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

NTL8 Regulates Trichome Formation in Arabidopsis by Directly Activating R3 MYB Genes TRY and TCL11[OPEN

PubMed Central

Tian, Hainan; Wang, Xianling; Guo, Hongyan; Cheng, Yuxin; Hou, Chunjiang

2017-01-01

The NAM, ATAF1/2, and CUC (NAC) are plant-specific transcription factors that regulate multiple aspects of plant growth and development and plant response to environmental stimuli. We report here the identification of NTM1-LIKE8 (NTL8), a membrane-associated NAC transcription factor, as a novel regulator of trichome formation in Arabidopsis (Arabidopsis thaliana). From an activation-tagged Arabidopsis population, we identified a dominant, gain-of-function mutant with glabrous inflorescence stem. By using plasmid rescue and RT-PCR analyses, we found that NTL8 was tagged; thus, the mutant was named ntl8-1 Dominant (ntl8-1D). Recapitulation experiment further confirmed that the phenotype observed in the ntl8-1D mutant was caused by elevated expression of NTL8. Quantitative RT-PCR results showed that the expression level of the single-repeat R3 MYB genes TRIPTYCHON (TRY) and TRICHOMELESS1 (TCL1) was elevated in the ntl8-1D mutant. Genetic analyses demonstrated that NTL8 acts upstream of TRY and TCL1 in the regulation of trichome formation. When recruited to the promoter region of the reporter gene Gal4:GUS by a fused GAL4 DNA-binding domain, NTL8 activated the expression of the reporter gene. Chromatin immunoprecipitation results indicated that TRY and TCL1 are direct targets of NTL8. However, NTL8 did not interact with SQUAMOSA PROMOTER BINDING PROTEIN LIKE9, another transcription factor that regulates the expression of TRY and TCL1, in yeast and plant cells. Taken together, our results suggest that NTL8 negatively regulates trichome formation in Arabidopsis by directly activating the expression of TRY and TCL1. PMID:28649093

Summary of the EMA Joint Regulators/Industry QbD workshop (London, UK; 28-29 January 2014).

PubMed

Cook, Graham; France, Georges; Holte, Øyvind; Lorenti, Giampiero; Tainsh, David

2016-01-01

This paper summarizes the discussions and insights gained from the key themes that emerged during the Quality by Design (QbD) Workshop held at the European Medicines Agency (EMA) offices in London, UK, on 28-29 January 2014. Industry and regulators shared practical experiences from six case studies (five approved small molecule products and one phase 3 biotechnological product) based on QbD submissions by five companies (AstraZeneca, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer).The case studies covered a range of different development, regulatory submission, and post-approval aspects of QbD and were developed through confidential discussions between the company representatives and regulators. Key themes that emerged from the workshop discussions were: 1. presentation of information in submissions (development story and the presentation of information in marketing authorization applications; risk assessment and criticality); 2. development aspects (design space; use of models; control strategy); and 3. post-approval aspects (lifecycle management; dossier-quality system interactions; handling of deviations). Many aspects of QbD for biotechnological products are similar to small molecules, but there are some important differences highlighted in this paper.The final section of the paper discusses some proposals for future developments to address the issues that were identified. This paper summarizes the discussions and insights gained from the key themes that emerged during the Quality by Design (QbD) Workshop held at the European Medicines Agency offices in London, UK, on 28-29 January 2014. Industry and regulators shared practical experiences from six case studies (five approved small-molecule products and one phase 3 biotechnological product) based on QbD submissions by five companies (AstraZeneca, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer).The case studies covered a range of different development, regulatory submission, and post-approval aspects of QbD and were developed through confidential discussions between the company representatives and regulators. Key themes that emerged from the workshop discussions were: 1. presentation of information in submissions (development story and the presentation of information in marketing authorization applications; risk assessment and criticality); 2. development aspects (design space; use of models; control strategy); and 3. post-approval aspects (lifecycle management; dossier-quality system interactions; handling of deviations). Many aspects of QbD for biotechnological products are similar to small molecules, but there are some important differences highlighted in this paper.The final section of the paper discusses some proposals for future developments to address the issues that were identified. © PDA, Inc. 2016.

Regulatory RNAs and control of epigenetic mechanisms: expectations for cognition and cognitive dysfunction.

PubMed

Butler, Anderson A; Webb, William M; Lubin, Farah D

2016-01-01

The diverse functions of noncoding RNAs (ncRNAs) can influence virtually every aspect of the transcriptional process including epigenetic regulation of genes. In the CNS, regulatory RNA networks and epigenetic mechanisms have broad relevance to gene transcription changes involved in long-term memory formation and cognition. Thus, it is becoming increasingly clear that multiple classes of ncRNAs impact neuronal development, neuroplasticity, and cognition. Currently, a large gap exists in our knowledge of how ncRNAs facilitate epigenetic processes, and how this phenomenon affects cognitive function. In this review, we discuss recent findings highlighting a provocative role for ncRNAs including lncRNAs and piRNAs in the control of epigenetic mechanisms involved in cognitive function. Furthermore, we discuss the putative roles for these ncRNAs in cognitive disorders such as schizophrenia and Alzheimer's disease.

RNA mobility in parasitic plant - host interactions.

PubMed

Westwood, James H; Kim, Gunjune

2017-04-03

The parasitic plant Cuscuta exchanges mRNAs with its hosts. Systemic mobility of mRNAs within plants is well documented, and has gained increasing attention as studies using grafted plant systems have revealed new aspects of mobile mRNA regulation and function. But parasitic plants take this phenomenon to a new level by forming seamless connections to a wide range of host species, and raising questions about how mRNAs might function after transfer to a different species. Cuscuta and other parasitic plant species also take siRNAs from their hosts, indicating that multiple types of RNA are capable of trans-specific movement. Parasitic plants are intriguing systems for studying RNA mobility, in part because such exchange opens new possibilities for control of parasitic weeds, but also because they provide a fresh perspective into understanding roles of RNAs in inter-organismal communication.

Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses.

PubMed

Wasser, Catherine R; Herz, Joachim

2017-01-27

Over half a century ago, D. S. Falconer first reported a mouse with a reeling gate. Four decades later, the Reln gene was isolated and identified as the cause of the reeler phenotype. Initial studies found that loss of Reelin, a large, secreted glycoprotein encoded by the Reln gene, results in abnormal neuronal layering throughout several regions of the brain. In the years since, the known functions of Reelin signaling in the brain have expanded to include multiple postdevelopmental neuromodulatory roles, revealing an ever increasing body of evidence to suggest that Reelin signaling is a critical player in the modulation of synaptic function. In writing this review, we intend to highlight the most fundamental aspects of Reelin signaling and integrate how these various neuromodulatory effects shape and protect synapses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Executive function, approach sensitivity, and emotional decision making as influences on risk behaviors in young adults.

PubMed

Patrick, Megan E; Blair, Clancy; Maggs, Jennifer L

2008-05-01

Relations among executive function, behavioral approach sensitivity, emotional decision making, and risk behaviors (alcohol use, drug use, and delinquent behavior) were examined in single female college students (N = 72). Hierarchical multiple regressions indicated a significant Approach Sensitivity x Working Memory interaction in which higher levels of alcohol use were associated with the combination of greater approach tendency and better working memory. This Approach Sensitivity x Working Memory interaction was also marginally significant for drug use and delinquency. Poor emotional decision making, as measured by a gambling task, was also associated with higher levels of alcohol use, but only for individuals low in inhibitory control. Findings point to the complexity of relations among aspects of self-regulation and personality and provide much needed data on neuropsychological correlates of risk behaviors in a nonclinical population.

Transcriptome profiling of Zymomonas mobilis under furfural stress.

PubMed

He, Ming-xiong; Wu, Bo; Shui, Zong-xia; Hu, Qi-chun; Wang, Wen-guo; Tan, Fu-rong; Tang, Xiao-yu; Zhu, Qi-li; Pan, Ke; Li, Qing; Su, Xiao-hong

2012-07-01

Furfural from lignocellulosic hydrolysates is the prevalent inhibitor to microorganisms during cellulosic ethanol production, but the molecular mechanisms of tolerance to this inhibitor in Zymomonas mobilis are still unclear. In this study, genome-wide transcriptional responses to furfural were investigated in Z. mobilis using microarray analysis. We found that 433 genes were differentially expressed in response to furfural. Furfural up- or down-regulated genes related to cell wall/membrane biogenesis, metabolism, and transcription. However, furfural has a subtle negative effect on Entner-Doudoroff pathway mRNAs. Our results revealed that furfural had effects on multiple aspects of cellular metabolism at the transcriptional level and that membrane might play important roles in response to furfural. This research has provided insights into the molecular response to furfural in Z. mobilis, and it will be helpful to construct more furfural-resistant strains for cellulosic ethanol production.

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene

PubMed Central

He, Haiying; Chen, Changmin; Xie, Yue; Asea, Alexzander; Calderwood, Stuart K.

2000-01-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation. PMID:11189444

Biosynthesis, Trafficking and Secretion of Pro-opiomelanocortin-derived peptides

PubMed Central

Cawley, Niamh X.; Li, Zhaojin; Loh, Y. Peng

2016-01-01

Pro-opiomelanocortin (POMC) is a prohormone that encodes multiple smaller peptide hormones within its structure. These peptide hormones can be generated by cleavage of POMC at basic-residue cleavage sites by prohormone converting enzymes in the regulated secretory pathway of POMC synthesizing endocrine cells and neurons. The peptides are stored inside the cells in dense core secretory granules until released in a stimulus dependent manner. The complexity of the regulation of the biosynthesis, trafficking and secretion of POMC and its peptides reflect an impressive level of control over many factors involved in the ultimate role of POMC expressing cells, i.e. to produce a range of different biologically active peptide hormones ready for action when signaled by the body. From the discovery of POMC as the precursor to ACTH and β-Lipotropin in the late 1970s to our current knowledge, the understanding of POMC physiology remains a monumental body of work that has provided insight into many aspects of molecular endocrinology. In this chapter, we describe the intracellular trafficking of POMC in endocrine cells, its sorting into dense core secretory granules and transport of these granules to the regulated secretory pathway. Additionally, we review the enzymes involved in the maturation of POMC to its various peptides and the mechanisms involved in the differential processing of POMC in different cell types. Finally, we highlight studies pertaining to the regulation of ACTH secretion in the anterior and intermediate pituitary and POMC neurons of the hypothalamus. PMID:26880796

Handbook of Self-Regulation of Learning and Performance

ERIC Educational Resources Information Center

Zimmerman, Barry J., Ed.; Schunk, Dale H., Ed.

2011-01-01

Self-regulated learning (or self-regulation) refers to the process whereby learners personally activate and sustain cognitions, affects, and behaviours that are systematically oriented toward the attainment of learning goals. This is the first volume to integrate into a single volume all aspects of the field of self-regulation of learning and…

Self-Regulation: Relations with Theory of Mind and Social Behaviour

ERIC Educational Resources Information Center

Korucu, Irem; Selcuk, Bilge; Harma, Mehmet

2017-01-01

It is argued that self-regulation skill is necessary both for displaying constructive behaviour and for controlling negative social behaviour, and self-regulation might affect social behaviours by increasing the ability to understand others' minds. In this research, in order to examine different aspects of self-regulation and their similarities…

The Regulation of Title IX: Sex Discrimination in Student Affairs

ERIC Educational Resources Information Center

Malloy, Michele

1976-01-01

The aspects of student affairs covered by Title IX and its final regulation are emphasized since that area represents new vistas of sexual equality. The Regulation of Title IX is examined for accomplishments and oversights, effects and exemptions. (Author/LBH)

Ecosystem services capacity across heterogeneous forest types: understanding the interactions and suggesting pathways for sustaining multiple ecosystem services.

PubMed

Alamgir, Mohammed; Turton, Stephen M; Macgregor, Colin J; Pert, Petina L

2016-10-01

As ecosystem services supply from tropical forests is declining due to deforestation and forest degradation, much effort is essential to sustain ecosystem services supply from tropical forested landscapes, because tropical forests provide the largest flow of multiple ecosystem services among the terrestrial ecosystems. In order to sustain multiple ecosystem services, understanding ecosystem services capacity across heterogeneous forest types and identifying certain ecosystem services that could be managed to leverage positive effects across the wider bundle of ecosystem services are required. We sampled three forest types, tropical rainforests, sclerophyll forests, and rehabilitated plantation forests, over an area of 32,000m(2) from Wet Tropics bioregion, Australia, aiming to compare supply and evaluate interactions and patterns of eight ecosystem services (global climate regulation, air quality regulation, erosion regulation, nutrient regulation, cyclone protection, habitat provision, energy provision, and timber provision). On average, multiple ecosystem services were highest in the rainforests, lowest in sclerophyll forests, and intermediate in rehabilitated plantation forests. However, a wide variation was apparent among the plots across the three forest types. Global climate regulation service had a synergistic impact on the supply of multiple ecosystem services, while nutrient regulation service was found to have a trade-off impact. Considering multiple ecosystem services, most of the rehabilitated plantation forest plots shared the same ordination space with rainforest plots in the ordination analysis, indicating that rehabilitated plantation forests may supply certain ecosystem services nearly equivalent to rainforests. Two synergy groups and one trade-off group were identified. Apart from conserving rainforests and sclerophyll forests, our findings suggest two additional integrated pathways to sustain the supply of multiple ecosystem services from a heterogeneous tropical forest landscape: (i) rehabilitation of degraded forests aiming to provide global climate regulation and habitat provision ecosystem services and (ii) management intervention to sustain global climate regulation and habitat provision ecosystem services. Copyright © 2016 Elsevier B.V. All rights reserved.

The hormonal control of ejaculation.

PubMed

Corona, Giovanni; Jannini, Emmanuele A; Vignozzi, Linda; Rastrelli, Giulia; Maggi, Mario

2012-09-01

Hormones regulate all aspects of male reproduction, from sperm production to sexual drive. Although emerging evidence from animal models and small clinical studies in humans clearly point to a role for several hormones in controlling the ejaculatory process, the exact endocrine mechanisms are unclear. Evidence shows that oxytocin is actively involved in regulating orgasm and ejaculation via peripheral, central and spinal mechanisms. Associations between delayed and premature ejaculation with hypothyroidism and hyperthyroidism, respectively, have also been extensively documented. Some models suggest that glucocorticoids are involved in the regulation of the ejaculatory reflex, but corresponding data from human studies are scant. Oestrogens regulate epididymal motility, whereas testosterone can affect the central and peripheral aspects of the ejaculatory process. Overall, the data of the endocrine system in regulating the ejaculatory reflex suggest that widely available endocrine therapies might be effective in treating sexual disorders in these men. Indeed, substantial evidence has documented that treatments of thyroid diseases are able to improve some ejaculatory difficulties.

Multiple Sensing Application on Wireless Sensor Network Simulation using NS3

NASA Astrophysics Data System (ADS)

Kurniawan, I. F.; Bisma, R.

2018-01-01

Hardware enhancement provides opportunity to install various sensor device on single monitoring node which then enables users to acquire multiple data simultaneously. Constructing multiple sensing application in NS3 is a challenging task since numbers of aspects such as wireless communication, packet transmission pattern, and energy model must be taken into account. Despite of numerous types of monitoring data available, this study only considers two types such as periodic, and event-based data. Periodical data will generate monitoring data follows configured interval, while event-based transmit data when certain determined condition is met. Therefore, this study attempts to cover mentioned aspects in NS3. Several simulations are performed with different number of nodes on arbitrary communication scheme.

Multiple Giant Cell Tumor of Tendon Sheath Involving Both Flexor and Extensor Tendons in a Single Digit: A Case Report and Review of the Literatures.

PubMed

Min, Hak Jin; Kim, Jeong Hwan; Kim, Jae Woo; Yeom, Jae Woo

2018-06-01

Giant cell tumor of the tendon sheath (GCTTS) is a common neoplasm of the hand. This tumor is usually solitary. Multi focal origin of the tumor is considered unusual and very few cases of multiple GCTTS have been reported. We report a 48-year-old female patient who presented with three separate painless nodules in same index finger since three years. The two masses located on dorsal aspect, and the other one located on volar aspect. The imaging studies revealed three separated masses without any connection. We performed excisional biopsy and found multiple tumors, attached to flexor and extensor tendon. The final histopathologic diagnosis was GCTTS.

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

Huang, Er-Wen; Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou; Xue, Sheng-Jiang

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation,more » facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.« less

System for Training Aviation Regulations (STAR): Using Multiple Vantage Points To Learn Complex Information through Scenario-Based Instruction and Multimedia Techniques.

ERIC Educational Resources Information Center

Chandler, Terrell N.

1996-01-01

The System for Training of Aviation Regulations (STAR) provides comprehensive training in understanding and applying Federal aviation regulations. STAR gives multiple vantage points with multimedia presentations and storytelling within four categories of learning environments: overviews, scenarios, challenges, and resources. Discusses the…

In vivo contributions of BH3-only proteins to neuronal death following seizures, ischemia, and traumatic brain injury

PubMed Central

Engel, Tobias; Plesnila, Nikolaus; Prehn, Jochen H M; Henshall, David C

2011-01-01

The Bcl-2 homology (BH) domain 3-only proteins are a proapoptotic subgroup of the Bcl-2 gene family, which regulate cell death via effects on mitochondria. The BH3-only proteins react to various cell stressors and promote cell death by binding and inactivating antiapoptotic Bcl-2 family members and direct activation of proapoptotic multi-BH domain proteins such as Bax. Here, we review the in vivo evidence for their involvement in the pathophysiology of status epilepticus and contrast it to ischemia and traumatic brain injury. Seizures in rodents activate three potent proapoptotic BH3-only proteins: Bid, Bim, and Puma. Analysis of damage after seizures in mice singly deficient for each BH3-only protein supports a causal role for Puma and to a lesser extent Bim but, surprisingly, not Bid. In ischemia and trauma, where core aspects of the pathophysiology of cell death overlap, multiple BH3-only proteins are also activated and Bid has been shown to be required for neuronal death. The findings suggest that while each neurologic insult activates multiple BH3-only proteins, there may be specificity in their functional contribution. Future challenges include evaluating the remaining BH3-only proteins, explaining different causal contributions, and, if possible, exploring neurologic outcomes in mouse models deficient for multiple BH3-only proteins. PMID:21364604

48 CFR 1601.301 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. 1601.301 Section... Regulation (FEHBAR) 1601.301 Policy. (a) Procedures, contract clauses, and other aspects of the acquisition... policies and procedures contained in this regulation as implemented and supplemented from time to time; and...

48 CFR 1601.301 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. 1601.301 Section... Regulation (FEHBAR) 1601.301 Policy. (a) Procedures, contract clauses, and other aspects of the acquisition... policies and procedures contained in this regulation as implemented and supplemented from time to time; and...

48 CFR 1601.301 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. 1601.301 Section... Regulation (FEHBAR) 1601.301 Policy. (a) Procedures, contract clauses, and other aspects of the acquisition... policies and procedures contained in this regulation as implemented and supplemented from time to time; and...

The Regulation of Technology-Assisted Distance Counseling and Supervision in the United States: An Analysis of Current Extent, Trends, and Implications

ERIC Educational Resources Information Center

McAdams, Charles R.; Wyatt, Kristi Lee

2010-01-01

Counseling licensure boards report emerging needs to regulate technology-assisted distance counseling and supervision. An analysis of published regulations and telephone interviews with board administrators nationwide suggests that boards agree generally on 7 aspects of technology-assisted distance practice that need to be regulated. Nevertheless,…

Self-Regulation, Coregulation, and Socially Shared Regulation: Exploring Perspectives of Social in Self-Regulated Learning Theory

ERIC Educational Resources Information Center

Hadwin, Allyson; Oshige, Mika

2011-01-01

Background/Context: Models of self-regulated learning (SRL) have increasingly acknowledged aspects of social context influence in its process; however, great diversity exists in the theoretical positioning of "social" in these models. Purpose/Objective/Research Question/Focus of Study: The purpose of this review article is to introduce and…

Serine Protease Inhibitors in Ticks: An Overview of Their Role in Tick Biology and Tick-Borne Pathogen Transmission.

PubMed

Blisnick, Adrien A; Foulon, Thierry; Bonnet, Sarah I

2017-01-01

New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated. Among the multiple active substances secreted during tick feeding, SPIs have been shown to be directly involved in regulation of inflammation, blood clotting, wound healing, vasoconstriction and the modulation of host defense mechanisms. In light of these activities, several SPIs were examined and were experimentally confirmed to facilitate tick pathogen transmission. In addition, to prevent coagulation of the ingested blood meal within the tick alimentary canal, SPIs are also involved in blood digestion and nutrient extraction from the meal. The presence of SPIs in tick hemocytes and their involvement in tick innate immune defenses have also been demonstrated, as well as their implication in hemolymph coagulation and egg development. Considering the involvement of SPIs in multiple crucial aspects of tick-host-pathogen interactions, as well as in various aspects of the tick parasitic lifestyle, these molecules represent highly suitable and attractive targets for the development of effective tick control strategies. Here we review the current knowledge regarding this class of inhibitors in tick biology and tick-borne pathogen transmission, and their potential as targets for future tick control trials.

Serine Protease Inhibitors in Ticks: An Overview of Their Role in Tick Biology and Tick-Borne Pathogen Transmission

PubMed Central

Blisnick, Adrien A.; Foulon, Thierry; Bonnet, Sarah I.

2017-01-01

New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated. Among the multiple active substances secreted during tick feeding, SPIs have been shown to be directly involved in regulation of inflammation, blood clotting, wound healing, vasoconstriction and the modulation of host defense mechanisms. In light of these activities, several SPIs were examined and were experimentally confirmed to facilitate tick pathogen transmission. In addition, to prevent coagulation of the ingested blood meal within the tick alimentary canal, SPIs are also involved in blood digestion and nutrient extraction from the meal. The presence of SPIs in tick hemocytes and their involvement in tick innate immune defenses have also been demonstrated, as well as their implication in hemolymph coagulation and egg development. Considering the involvement of SPIs in multiple crucial aspects of tick-host-pathogen interactions, as well as in various aspects of the tick parasitic lifestyle, these molecules represent highly suitable and attractive targets for the development of effective tick control strategies. Here we review the current knowledge regarding this class of inhibitors in tick biology and tick-borne pathogen transmission, and their potential as targets for future tick control trials. PMID:28589099

The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

PubMed

Lanni, C; Stanga, S; Racchi, M; Govoni, S

2010-01-01

Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. An important role in this balancement is played by neurotrophic factors, which are central to many aspects of nervous system function since they regulate the development, maintenance and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. A vast amount of evidence indicates that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to aging as well as to the pathogenesis of diseases of abnormal trophic support (such as neurodegenerative diseases and depression) and diseases of abnormal excitability (such as epilepsy and central pain sensitization). Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during aging.

Microbial engineering for the production of fatty acids and fatty acid derivatives

DOEpatents

Stephanopoulos, Gregory; Abidi, Syed Hussain Imam

2014-07-01

Some aspects of this invention relate to methods useful for the conversion of a carbon source to a biofuel or biofuel precursor using engineered microbes. Some aspects of this invention relate to the discovery of a key regulator of lipid metabolism in microbes. Some aspects of this invention relate to engineered microbes for biofuel or biofuel precursor production.

CRISPR-Cas Adaptive Immune Systems of the Sulfolobales: Unravelling Their Complexity and Diversity

PubMed Central

Garrett, Roger A.; Shah, Shiraz A.; Erdmann, Susanne; Liu, Guannan; Mousaei, Marzieh; León-Sobrino, Carlos; Peng, Wenfang; Gudbergsdottir, Soley; Deng, Ling; Vestergaard, Gisle; Peng, Xu; She, Qunxin

2015-01-01

The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive structural and functional diversity. They carry large and multiple CRISPR loci and often multiple copies of diverse Type I and Type III interference modules as well as more homogeneous adaptation modules. These acidothermophilic organisms have recently provided seminal insights into both the adaptation process, the diverse modes of interference, and their modes of regulation. The functions of the adaptation and interference modules tend to be loosely coupled and the stringency of the crRNA-DNA sequence matching during DNA interference is relatively low, in contrast to some more streamlined CRISPR-Cas systems of bacteria. Despite this, there is evidence for a complex and differential regulation of expression of the diverse functional modules in response to viral infection. Recent work also supports critical roles for non-core Cas proteins, especially during Type III-directed interference, and this is consistent with these proteins tending to coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of the Sulfolobales are considered including an alternative spacer acquisition mechanism, reversible spacer acquisition, the formation and significance of antisense CRISPR RNAs, and a novel mechanism for avoidance of CRISPR-Cas defense. Finally, questions regarding the basis for the complexity, diversity, and apparent redundancy, of the intracellular CRISPR-Cas systems are discussed. PMID:25764276

Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

PubMed Central

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

2012-01-01

Objective Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a Bootstrapping procedure to test the indirect effects. Results Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally-based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. Conclusion The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse, and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, while affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. PMID:22390410

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

PubMed

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

Neural and Molecular Mechanisms Involved in Controlling the Quality of Feeding Behavior: Diet Selection and Feeding Patterns

PubMed Central

2017-01-01

We are what we eat. There are three aspects of feeding: what, when, and how much. These aspects represent the quantity (how much) and quality (what and when) of feeding. The quantitative aspect of feeding has been studied extensively, because weight is primarily determined by the balance between caloric intake and expenditure. In contrast, less is known about the mechanisms that regulate the qualitative aspects of feeding, although they also significantly impact the control of weight and health. However, two aspects of feeding quality relevant to weight loss and weight regain are discussed in this review: macronutrient-based diet selection (what) and feeding pattern (when). This review covers the importance of these two factors in controlling weight and health, and the central mechanisms that regulate them. The relatively limited and fragmented knowledge on these topics indicates that we lack an integrated understanding of the qualitative aspects of feeding behavior. To promote better understanding of weight control, research efforts must focus more on the mechanisms that control the quality and quantity of feeding behavior. This understanding will contribute to improving dietary interventions for achieving weight control and for preventing weight regain following weight loss. PMID:29053636

Quantity and Quality of Motivational Regulation among University Students

ERIC Educational Resources Information Center

Engelschalk, Tobias; Steuer, Gabriele; Dresel, Markus

2017-01-01

Effective regulation of motivation can be theoretically explained by both the extent of motivational regulation strategies used (quantity) and their optimal implementation (quality). Researchers have not yet analysed the significance of both aspects for learning success simultaneously. In the present study, 188 students were presented with…

Emotion Regulation in Children with Down Syndrome.

ERIC Educational Resources Information Center

Smith, Maureen C.; Walden, Tedra A.

This study presents a preliminary exploration of emotion regulation in a sample of 20 children (ages 3-18 years) with Down Syndrome. Three aspects of emotion regulation (modulation, organization, flexibility) were predicted from emotion variables (affect intensity, affective expression, and autonomy-curiosity and motivation) in backward regression…

Supporting Affect Regulation in Children with Multiple Disabilities during Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment

ERIC Educational Resources Information Center

Schuengel, C.; Sterkenburg, P. S.; Jeczynski, P.; Janssen, C. G. C.; Jongbloed, G.

2009-01-01

In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase, children had sessions with an experimental therapist…

Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

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

Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang

2013-03-01

In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from enteringmore » S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering cell cycles. ► It led to apoptosis of activated T cells through mitochondrial pathway. ► It down-regulated ERK and AKT signaling pathways in Con A-activated T cells. ► It significantly ameliorated picryl chloride-induced ear swelling.« less

Multiple Dimensions of Teacher Identity Development from Pre-Service to Early Years of Teaching: A Longitudinal Study

ERIC Educational Resources Information Center

Hong, Ji; Greene, Barbara; Lowery, Jennifer

2017-01-01

Based on dialogical self theory framework that highlights three dimensions of identity construction (multiplicity vs. unity; social vs. individual; discontinuity vs. continuity), this study explored multiple aspects of teacher identity development over time, in relation to the unity of self, the way the social environment is negotiated, and the…

The complexities of HIPAA and administration simplification.

PubMed

Mozlin, R

2000-11-01

The Health Insurance Portability and Accessibility Act (HIPAA) was signed into law in 1996. Although focused on information technology issues, HIPAA will ultimately impact day-to-day operations at multiple levels within any clinical setting. Optometrists must begin to familiarize themselves with HIPAA in order to prepare themselves to practice in a technology-enriched environment. Title II of HIPAA, entitled "Administration Simplification," is intended to reduce the costs and administrative burden of healthcare by standardizing the electronic transmission of administrative and financial transactions. The Department of Health and Human Services is expected to publish the final rules and regulations that will govern HIPAA's implementation this year. The rules and regulations will cover three key aspects of healthcare delivery: electronic data interchange (EDI), security and privacy. EDI will standardize the format for healthcare transactions. Health plans must accept and respond to all transactions in the EDI format. Security refers to policies and procedures that protect the accuracy and integrity of information and limit access. Privacy focuses on how the information is used and disclosure of identifiable health information. Security and privacy regulations apply to all information that is maintained and transmitted in a digital format and require administrative, physical, and technical safeguards. HIPAA will force the healthcare industry to adopt an e-commerce paradigm and provide opportunities to improve patient care processes. Optometrists should take advantage of the opportunity to develop more efficient and profitable practices.

Live imaging reveals a conserved role of fatty acid β-oxidation in early lymphatic development in zebrafish.

PubMed

Zecchin, Annalisa; Wong, Brian W; Tembuyser, Bieke; Souffreau, Joris; Van Nuffelen, An; Wyns, Sabine; Vinckier, Stefan; Carmeliet, Peter; Dewerchin, Mieke

2018-06-18

During embryonic development, lymphatic endothelial cells (LECs) differentiate from venous endothelial cells (VECs), a process that is tightly regulated by several genetic signals. While the aquatic zebrafish model is regularly used for studying lymphangiogenesis and offers the unique advantage of time-lapse video-imaging of lymphatic development, some aspects of lymphatic development in this model differ from those in the mouse. It therefore remained to be determined whether fatty acid β-oxidation (FAO), which we showed to regulate lymphatic formation in the mouse, also co-determines lymphatic development in this aquatic model. Here, we took advantage of the power of the zebrafish embryo model to visualize the earliest steps of lymphatic development through time-lapse video-imaging. By targeting zebrafish isoforms of carnitine palmitoyltransferase 1a (cpt1a), a rate controlling enzyme of FAO, with multiple morpholinos, we demonstrate that reducing CPT1A levels and FAO flux during zebrafish development impairs lymphangiogenic secondary sprouting, the initiation of lymphatic development in the zebrafish trunk, and the formation of the first lymphatic structures. These findings not only show evolutionary conservation of the importance of FAO for lymphatic development, but also suggest a role for FAO in co-regulating the process of VEC-to-LEC differentiation in zebrafish in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative Glycoproteomic Analysis Identifies Platelet-Induced Increase of Monocyte Adhesion via the Up-Regulation of Very Late Antigen 5.

PubMed

Huang, Jiqing; Kast, Juergen

2015-08-07

Physiological stimuli, such as thrombin, or pathological stimuli, such as lysophosphatidic acid (LPA), activate platelets circulating in blood. Once activated, platelets bind to monocytes via P-selectin-PSGL-1 interactions but also release the stored contents of their granules. These platelet releasates, in addition to direct platelet binding, activate monocytes and facilitate their recruitment to atherosclerotic sites. Consequently, understanding the changes platelet releasates induce in monocyte membrane proteins is critical. We studied the glyco-proteome changes of THP-1 monocytic cells affected by LPA- or thrombin-induced platelet releasates. We employed lectin affinity chromatography combined with filter aided sample preparation to achieve high glyco- and membrane protein and protein sequence coverage. Using stable isotope labeling by amino acids in cell culture, we quantified 1715 proteins, including 852 membrane and 500 glycoproteins, identifying the up-regulation of multiple proteins involved in monocyte extracellular matrix binding and transendothelial migration. Flow cytometry indicated expression changes of integrin α5, integrin β1, PECAM-1, and PSGL-1. The observed increase in monocyte adhesion to fibronectin was determined to be mediated by the up-regulation of very late antigen 5 via a P-selectin-PSGL-1 independent mechanism. This novel aspect could be validated on CD14+ human primary monocytes, highlighting the benefits of the improved enrichment method regarding high membrane protein coverage and reliable quantification.

Regulation of Skeletal Muscle Plasticity by Protein Arginine Methyltransferases and Their Potential Roles in Neuromuscular Disorders

PubMed Central

Stouth, Derek W.; vanLieshout, Tiffany L.; Shen, Nicole Y.; Ljubicic, Vladimir

2017-01-01

Protein arginine methyltransferases (PRMTs) are a family of enzymes that catalyze the methylation of arginine residues on target proteins, thereby mediating a diverse set of intracellular functions that are indispensable for survival. Indeed, full-body knockouts of specific PRMTs are lethal and PRMT dysregulation has been implicated in the most prevalent chronic disorders, such as cancers and cardiovascular disease (CVD). PRMTs are now emerging as important mediators of skeletal muscle phenotype and plasticity. Since their first description in muscle in 2002, a number of studies employing wide varieties of experimental models support the hypothesis that PRMTs regulate multiple aspects of skeletal muscle biology, including development and regeneration, glucose metabolism, as well as oxidative metabolism. Furthermore, investigations in non-muscle cell types strongly suggest that proteins, such as peroxisome proliferator-activated receptor-γ coactivator-1α, E2F transcription factor 1, receptor interacting protein 140, and the tumor suppressor protein p53, are putative downstream targets of PRMTs that regulate muscle phenotype determination and remodeling. Recent studies demonstrating that PRMT function is dysregulated in Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), and amyotrophic lateral sclerosis (ALS) suggests that altering PRMT expression and/or activity may have therapeutic value for neuromuscular disorders (NMDs). This review summarizes our understanding of PRMT biology in skeletal muscle, and identifies uncharted areas that warrant further investigation in this rapidly expanding field of research. PMID:29163212

A multicontext approach to promoting transfer of strategy use and self regulation after brain injury: An exploratory study.

PubMed

Toglia, Joan; Johnston, Mark V; Goverover, Yael; Dain, Barry

2010-01-01

Persons with brain injury frequently demonstrate decreased ability to monitor and apply strategies learned in treatment to everyday situations. The aim of this study is to refine, explore and provide preliminary testing of the multicontext approach in promoting strategy use across situations and increasing self-regulation, awareness and functional performance. This study used a single-subject design with repeated measures pre- and post-intervention, with data analysed descriptively and graphically. Four persons with difficulty following multi-step directions, 3-5 years post-TBI, received a nine session intervention programme. Outcome measures included the Awareness Questionnaire, Self-Regulation Skills Interview, Behavior Rating Inventory of Executive Function, Multiple Errands Test and an Executive Function Performance Test sub-task. The process of change within each treatment session was examined with strategy and awareness ratings. All participants demonstrated positive changes in self-regulatory skills and strategy use that was observed across tasks. As expected, general awareness of deficits remained unchanged. Examination of individual participants revealed important, varying patterns of change in strategy use, learning transfer and self-awareness across intervention. Results provide preliminary support for the feasibility and efficacy of the multicontext approach in promoting transfer of strategy use to enhance functional performance and selective aspects of awareness. Further investigation, including a larger controlled study, is needed to confirm or limit these observations.

Arranging a Library to Support Adolescent Development

ERIC Educational Resources Information Center

Cesari, Lindsay

2014-01-01

When designing a school library space and deciding how to arrange resources, it is important to consider multiple components of adolescent development, including social, emotional, and behavioral aspects. Acknowledging these developmental facets and their importance can provide additional justification for some of the more controversial aspects of…

Omics Approaches for Understanding Grapevine Berry Development: Regulatory Networks Associated with Endogenous Processes and Environmental Responses

PubMed Central

Serrano, Alejandra; Espinoza, Carmen; Armijo, Grace; Inostroza-Blancheteau, Claudio; Poblete, Evelyn; Meyer-Regueiro, Carlos; Arce, Anibal; Parada, Francisca; Santibáñez, Claudia; Arce-Johnson, Patricio

2017-01-01

Grapevine fruit development is a dynamic process that can be divided into three stages: formation (I), lag (II), and ripening (III), in which physiological and biochemical changes occur, leading to cell differentiation and accumulation of different solutes. These stages can be positively or negatively affected by multiple environmental factors. During the last decade, efforts have been made to understand berry development from a global perspective. Special attention has been paid to transcriptional and metabolic networks associated with the control of grape berry development, and how external factors affect the ripening process. In this review, we focus on the integration of global approaches, including proteomics, metabolomics, and especially transcriptomics, to understand grape berry development. Several aspects will be considered, including seed development and the production of seedless fruits; veraison, at which anthocyanin accumulation begins in the berry skin of colored varieties; and hormonal regulation of berry development and signaling throughout ripening, focusing on the transcriptional regulation of hormone receptors, protein kinases, and genes related to secondary messenger sensing. Finally, berry responses to different environmental factors, including abiotic (temperature, water-related stress and UV-B radiation) and biotic (fungi and viruses) stresses, and how they can significantly modify both, development and composition of vine fruit, will be discussed. Until now, advances have been made due to the application of Omics tools at different molecular levels. However, the potential of these technologies should not be limited to the study of single-level questions; instead, data obtained by these platforms should be integrated to unravel the molecular aspects of grapevine development. Therefore, the current challenge is the generation of new tools that integrate large-scale data to assess new questions in this field, and to support agronomical practices. PMID:28936215

The plant cell cycle: Pre-Replication complex formation and controls

PubMed Central

Brasil, Juliana Nogueira; Costa, Carinne N. Monteiro; Cabral, Luiz Mors; Ferreira, Paulo C. G.; Hemerly, Adriana S.

2017-01-01

Abstract The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes. PMID:28304073

Experimental and computational analysis of a large protein network that controls fat storage reveals the design principles of a signaling network.

PubMed

Al-Anzi, Bader; Arpp, Patrick; Gerges, Sherif; Ormerod, Christopher; Olsman, Noah; Zinn, Kai

2015-05-01

An approach combining genetic, proteomic, computational, and physiological analysis was used to define a protein network that regulates fat storage in budding yeast (Saccharomyces cerevisiae). A computational analysis of this network shows that it is not scale-free, and is best approximated by the Watts-Strogatz model, which generates "small-world" networks with high clustering and short path lengths. The network is also modular, containing energy level sensing proteins that connect to four output processes: autophagy, fatty acid synthesis, mRNA processing, and MAP kinase signaling. The importance of each protein to network function is dependent on its Katz centrality score, which is related both to the protein's position within a module and to the module's relationship to the network as a whole. The network is also divisible into subnetworks that span modular boundaries and regulate different aspects of fat metabolism. We used a combination of genetics and pharmacology to simultaneously block output from multiple network nodes. The phenotypic results of this blockage define patterns of communication among distant network nodes, and these patterns are consistent with the Watts-Strogatz model.

Endothelial C-type natriuretic peptide maintains vascular homeostasis

PubMed Central

Moyes, Amie J.; Khambata, Rayomand S.; Villar, Inmaculada; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne-Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F.; Djordjevic, Snezana; Caulfield, Mark J.; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

2014-01-01

The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders. PMID:25105365

Evolution of Salmonella-Host Cell Interactions through a Dynamic Bacterial Genome

PubMed Central

Ilyas, Bushra; Tsai, Caressa N.; Coombes, Brian K.

2017-01-01

Salmonella Typhimurium has a broad arsenal of genes that are tightly regulated and coordinated to facilitate adaptation to the various host environments it colonizes. The genome of Salmonella Typhimurium has undergone multiple gene acquisition events and has accrued changes in non-coding DNA that have undergone selection by regulatory evolution. Together, at least 17 horizontally acquired pathogenicity islands (SPIs), prophage-associated genes, and changes in core genome regulation contribute to the virulence program of Salmonella. Here, we review the latest understanding of these elements and their contributions to pathogenesis, emphasizing the regulatory circuitry that controls niche-specific gene expression. In addition to an overview of the importance of SPI-1 and SPI-2 to host invasion and colonization, we describe the recently characterized contributions of other SPIs, including the antibacterial activity of SPI-6 and adhesion and invasion mediated by SPI-4. We further discuss how these fitness traits have been integrated into the regulatory circuitry of the bacterial cell through cis-regulatory evolution and by a careful balance of silencing and counter-silencing by regulatory proteins. Detailed understanding of regulatory evolution within Salmonella is uncovering novel aspects of infection biology that relate to host-pathogen interactions and evasion of host immunity. PMID:29034217

Phylogenetic analysis reveals conservation and diversification of micro RNA166 genes among diverse plant species.

PubMed

Barik, Suvakanta; SarkarDas, Shabari; Singh, Archita; Gautam, Vibhav; Kumar, Pramod; Majee, Manoj; Sarkar, Ananda K

2014-01-01

Similar to the majority of the microRNAs, mature miR166s are derived from multiple members of MIR166 genes (precursors) and regulate various aspects of plant development by negatively regulating their target genes (Class III HD-ZIP). The evolutionary conservation or functional diversification of miRNA166 family members remains elusive. Here, we show the phylogenetic relationships among MIR166 precursor and mature sequences from three diverse model plant species. Despite strong conservation, some mature miR166 sequences, such as ppt-miR166m, have undergone sequence variation. Critical sequence variation in ppt-miR166m has led to functional diversification, as it targets non-HD-ZIPIII gene transcript (s). MIR166 precursor sequences have diverged in a lineage specific manner, and both precursors and mature osa-miR166i/j are highly conserved. Interestingly, polycistronic MIR166s were present in Physcomitrella and Oryza but not in Arabidopsis. The nature of cis-regulatory motifs on the upstream promoter sequences of MIR166 genes indicates their possible contribution to the functional variation observed among miR166 species. Copyright © 2013 Elsevier Inc. All rights reserved.

Queen pheromones

PubMed Central

2010-01-01

Group-living species produce signals that alter the behavior and even the physiology of their social partners. Social insects possess especially sophisticated chemical communication systems that govern every aspect of colony life, including the defining feature of eusociality: reproductive division of labor. Current evidence hints at the central importance of queen pheromones, but progress has been hindered by the fact that such pheromones have only been isolated in honeybees. In a pair of papers on the ant Lasius niger, we identified and investigated a queen pheromone regulating worker sterility. The cuticular hydrocarbon 3-methylhentriacontane (3-MeC31) is correlated with queen maturity and fecundity and workers are also more likely to execute surplus queens that have low amounts of this chemical. Experiments with synthetic 3-MeC31 found that it inhibits ovarian development in queenless workers and lowers worker aggression towards objects coated with it. Production of 3-MeC31 by queens was depressed by an experimental immune challenge, and the same chemical was abundant on queenlaid eggs, suggesting that the workers' responses to the queen are conditional on her health and fecundity. Together with other studies, these results indicate that queen pheromones are honest signals of quality that simultaneously regulate multiple social behaviors. PMID:21331238

Serotonin homeostasis and serotonin receptors as actors of cortical construction: special attention to the 5-HT3A and 5-HT6 receptor subtypes

PubMed Central

Vitalis, Tania; Ansorge, Mark S.; Dayer, Alexandre G.

2013-01-01

Cortical circuits control higher-order cognitive processes and their function is highly dependent on their structure that emerges during development. The construction of cortical circuits involves the coordinated interplay between different types of cellular processes such as proliferation, migration, and differentiation of neural and glial cell subtypes. Among the multiple factors that regulate the assembly of cortical circuits, 5-HT is an important developmental signal that impacts on a broad diversity of cellular processes. 5-HT is detected at the onset of embryonic telencephalic formation and a variety of serotonergic receptors are dynamically expressed in the embryonic developing cortex in a region and cell-type specific manner. Among these receptors, the ionotropic 5-HT3A receptor and the metabotropic 5-HT6 receptor have recently been identified as novel serotonergic targets regulating different aspects of cortical construction including neuronal migration and dendritic differentiation. In this review, we focus on the developmental impact of serotonergic systems on the construction of cortical circuits and discuss their potential role in programming risk for human psychiatric disorders. PMID:23801939

Tissue engineering and microRNAs: future perspectives in regenerative medicine.

PubMed

Gori, Manuele; Trombetta, Marcella; Santini, Daniele; Rainer, Alberto

2015-01-01

Tissue engineering is a growing area of biomedical research, holding great promise for a broad range of potential applications in the field of regenerative medicine. In recent decades, multiple tissue engineering strategies have been adopted to mimic and improve specific biological functions of tissues and organs, including biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems. MicroRNAs (miRNAs), noncoding small RNAs that negatively regulate the expression of downstream target mRNAs, are considered a novel class of molecular targets and therapeutics that may play an important role in tissue engineering. Herein, we highlight the latest achievements in regenerative medicine, focusing on the role of miRNAs as key modulators of gene expression, stem cell self-renewal, proliferation and differentiation, and eventually in driving cell fate decisions. Finally, we will discuss the contribution of miRNAs in regulating the rearrangement of the tissue microenvironment and angiogenesis, and the range of strategies for miRNA delivery into target cells and tissues. Manipulation of miRNAs is an alternative approach and an attractive strategy for controlling several aspects of tissue engineering, although some issues concerning their in vivo effects and optimal delivery methods still remain uncovered.

Rice early flowering1, a CKI, phosphorylates DELLA protein SLR1 to negatively regulate gibberellin signalling.

PubMed

Dai, Cheng; Xue, Hong-Wei

2010-06-02

The plant hormone gibberellin (GA) is crucial for multiple aspects of plant growth and development. To study the relevant regulatory mechanisms, we isolated a rice mutant earlier flowering1, el1, which is deficient in a casein kinase I that has critical roles in both plants and animals. el1 had an enhanced GA response, consistent with the suppression of EL1 expression by exogenous GA(3). Biochemical characterization showed that EL1 specifically phosphorylates the rice DELLA protein SLR1, proving a direct evidence for SLR1 phosphorylation. Overexpression of SLR1 in wild-type plants caused a severe dwarf phenotype, which was significantly suppressed by EL1 deficiency, indicating the negative effect of SLR1 on GA signalling requires the EL1 function. Further studies showed that the phosphorylation of SLR1 is important for maintaining its activity and stability, and mutation of the candidate phosphorylation site of SLR1 results in the altered GA signalling. This study shows EL1 a novel and key regulator of the GA response and provided important clues on casein kinase I activities in GA signalling and plant development.

Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease.

PubMed

Simon, Matthew J; Iliff, Jeffrey J

2016-03-01

Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer's disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the 'glymphatic' system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. Copyright © 2015 Elsevier B.V. All rights reserved.

Morton et al. Reply

NASA Technical Reports Server (NTRS)

Morton, Douglas C.; Nagol, Jyoteshwar; Carabajal, Claudia C.; Rosette, Jacqueline; Palace, Michael; Cook, Bruce D.; Vermote, Eric F.; Harding, David J.; North, Peter R. J.

2016-01-01

Multiple mechanisms could lead to up-regulation of dry-season photosynthesis in Amazon forests, including canopy phenology and illumination geometry. We specifically tested two mechanisms for phenology-driven changes in Amazon forests during dry-season months, and the combined evidence from passive optical and lidar satellite data was incompatible with large net changes in canopy leaf area or leaf reflectance suggested by previous studies. We therefore hypothesized that seasonal changes in the fraction of sunlit and shaded canopies, one aspect of bidirectional reflectance effects in Moderate Resolution Imaging Spectroradiometer (MODIS) data, could alter light availability for dry-season photosynthesis and the photosynthetic capacity of Amazon forests without large net changes in canopy composition. Subsequent work supports the hypothesis that seasonal changes in illumination geometry and diffuse light regulate light saturation in Amazon forests. These studies clarify the physical mechanisms that govern light availability in Amazon forests from seasonal variability in direct and diffuse illumination. Previously, in the debate over light limitation of Amazon forest productivity, seasonal changes in the distribution of light within complex Amazon forest canopies were confounded with dry-season increases in total incoming photosynthetically active radiation. In the accompanying Comment, Saleska et al. do not fully account for this confounding effect of forest structure on photosynthetic capacity.

Neonatal immune challenge does not affect body weight regulation in rats.

PubMed

Spencer, Sarah J; Mouihate, Abdeslam; Galic, Michael A; Ellis, Shaun L; Pittman, Quentin J

2007-08-01

The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter long-term body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 microg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 microg/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge.

PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

PubMed

Dunn, Henry A; Ferguson, Stephen S G

2015-10-01

G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC homology 3 domain and multiple ankyrin repeat domain (Shank) proteins (Shank1, Shank2, and Shank3), partitioning defective proteins 3 and 6, multiple PDZ protein 1, Tamalin, neuronal nitric oxide synthase, syntrophins, protein interacting with protein kinase C α 1, syntenin-1, and sorting nexin 27. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Emotion Regulation in Young Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Berkovits, Lauren; Eisenhower, Abbey; Blacher, Jan

2017-01-01

There has been little research connecting underlying emotion processes (e.g., emotion regulation) to frequent behavior problems in young children with autism spectrum disorder (ASD). This study examined the stability of emotion regulation and its relationship with other aspects of child functioning. Participants included 108 children with ASD,…

Affect and Self-Regulation

ERIC Educational Resources Information Center

Malmivuori, Marja-Liisa

2006-01-01

This paper presents affect as an essential aspect of students' self-reflection and self-regulation. The introduced concepts of self-system and self-system process stress the importance of self-appraisals of personal competence and agency in affective responses and self-regulation in problem solving. Students are viewed as agents who constantly…

Self-Entrustment: How Trainees' Self-Regulated Learning Supports Participation in the Workplace

ERIC Educational Resources Information Center

Sagasser, Margaretha H.; Kramer, Anneke W. M.; Fluit, Cornelia R. M. G.; van Weel, Chris; van der Vleuten, Cees P. M.

2017-01-01

Clinical workplaces offer postgraduate trainees a wealth of opportunities to learn from experience. To promote deliberate and meaningful learning self-regulated learning skills are foundational. We explored trainees' learning activities related to patient encounters to better understand what aspects of self-regulated learning contribute to…

Chinese Parenting Styles and Children's Self-Regulated Learning

ERIC Educational Resources Information Center

Huang, Juan; Prochner, Larry

2004-01-01

Self-regulated learning is an important aspect of student learning and academic achievement. Certain parenting styles help children develop self-regulated learning and encourage them to exert control over their own learning. The purpose of this study was to examine the relationship between Chinese parenting style and children's involvement in…

A Pivotal Role of DELLAs in Regulating Multiple Hormone Signals.

PubMed

Davière, Jean-Michel; Achard, Patrick

2016-01-04

Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey information from multiple developmental and environmental signals. Moreover, in plants many processes such as growth, development, and defense are regulated in similar ways by multiple hormones. Among them, gibberellins (GAs) are phytohormones with pleiotropic actions, regulating various growth processes throughout the plant life cycle. Previous work has revealed extensive interplay between GAs and other hormones, but the molecular mechanism became apparent only recently. Molecular and physiological studies have demonstrated that DELLA proteins, considered as master negative regulators of GA signaling, integrate multiple hormone signaling pathways through physical interactions with transcription factors or regulatory proteins from different families. In this review, we summarize the latest progress in GA signaling and its direct crosstalk with the main phytohormone signaling, emphasizing the multifaceted role of DELLA proteins with key components of major hormone signaling pathways. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Multiple Risks, Emotion Regulation Skill, and Cortisol in Low-Income African American Youth: A Prospective Study

ERIC Educational Resources Information Center

Kliewer, Wendy; Reid-Quinones, Kathryn; Shields, Brian J.; Foutz, Lauren

2009-01-01

Associations between multiple risks, emotion regulation skill, and basal cortisol levels were examined in a community sample of 69 African American youth (mean age = 11.30 years; 49% male) living in an urban setting. Multiple risks were assessed at Time 1 and consisted of 10 demographic and psychosocial risk factors including parent, child, and…

Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with Borderline Personality Disorder

PubMed Central

Silvers, Jennifer A.; Hubbard, Alexa D.; Biggs, Emily; Shu, Jocelyn; Fertuck, Eric; Chaudhury, Sadia; Grunebaum, Michael F.; Weber, Jochen; Kober, Hedy; Chesin, Megan; Brodsky, Beth S.; Koenigsberg, Harold; Ochsner, Kevin N.; Stanley, Barbara

2016-01-01

The present neuroimaging study investigated two aspects of difficulties with emotion associated with Borderline Personality Disorder (BPD1): affective lability and difficulty regulating emotion. While these two characteristics have been previously linked to BPD symptomology, it remains unknown whether individual differences in affective lability and emotion regulation difficulties are subserved by distinct neural substrates within a BPD sample. To address this issue, sixty women diagnosed with BPD were scanned while completing a task that assessed baseline emotional reactivity as well as top-down emotion regulation. More affective instability, as measured by the Affective Lability Scale (ALS2), positively correlated with greater amygdala responses on trials assessing emotional reactivity. Greater difficulties with regulating emotion, as measured by the Difficulties with Emotion Regulation Scale (DERS3), was negatively correlated with left inferior frontal gyrus (IFG4) recruitment on trials assessing regulatory ability. These findings suggest that, within a sample of individuals with BPD, greater bottom-up amygdala activity is associated with heightened affective lability. By contrast, difficulties with emotion regulation are related to reduced IFG recruitment during emotion regulation. These results point to distinct neural mechanisms for different aspects of BPD symptomology. PMID:27379614

Multiple Aspects of Self-Regulation Uniquely Predict Mathematics but Not Letter–Word Knowledge in the Early Elementary Grades

PubMed Central

Blair, Clancy; Ursache, Alexandra; Greenberg, Mark; Vernon-Feagans, Lynne

2017-01-01

The relation of self-regulation measured prior to school entry to developing math and reading ability in prekindergarten through the second grade was examined in a prospective longitudinal sample of 1,292 children and families in predominantly rural and low-income communities in 2 regions of high poverty in the United States. Direct assessments of executive function, effortful control, and stress response physiology (indexed by resting levels of cortisol and alpha amylase obtained from saliva) were measured at child age 48 months and parents and teachers reported on children’s effortful control using temperament rating scales at child age approximately 60 months. Math and reading ability, as measured by the Woodcock-Johnson III applied problems and letter–word subtests, respectively, were measured at prekindergarten through the second grade. Effects for self-regulation measures were seen primarily for initial level and to some extent growth in both mathematics and reading, even when controlling for family demographic characteristics that represent relevant selection factors into higher levels of both self-regulation and academic achievement. These effects persisted for mathematics but not for reading with the inclusion of child cognitive abilities, vocabulary, and speed of processing measured in prekindergarten, concurrent with the first time point for the academic measures. Results are interpreted as indicating a role for self-regulation in learning ability generally, likely through support for attention and reasoning abilities that are most specific to the assessment of mathematics in this analysis. Implications for instruction and for assessment and the best ways to support the development of early math and reading ability for children at risk for school failure are discussed. PMID:25688999

MicroRNA-7a regulates Müller glia differentiation by attenuating Notch3 expression.

PubMed

Baba, Yukihiro; Aihara, Yuko; Watanabe, Sumiko

2015-09-01

miRNA-7a plays critical roles in various biological aspects in health and disease. We aimed to reveal roles of miR-7a in mouse retinal development by loss- and gain-of-function analyses of miR-7a. Plasmids encoding miR-7a or miR-7a-decoy (anti-sense miR-7a) were introduced into mouse retina at P0, and the retina was cultured as explant. Then, proliferation of retinal progenitors and differentiation of retinal subtypes were examined by immunostaining. miR-7a had no apparent effect on the proliferation of retinal progenitor cells. However, the expression of Müller glia marker, cyclin D3, was reduced by miR-7a overexpression and up-regulated by miR-7a decoy, suggesting that miR-7a negatively regulates differentiation of Müller glia. Targets of miR-7a, which were predicted by using a public program miRNA.org, and Notch3 was suggested to be one of candidate genes of miR-7a target. Notch3 3' UTR appeared to contain complementary sequence to the seed sequence of miR-7a. A reporter assay in NIH3T3 cells using a plasmid containing multiple repeats of potential target sequence of 3' Notch UTR showed that miR-7a suppress expression of reporter EGFP through 3'UTR region. Expression of sh-Notch3 and over-expression of NICD3 in retina suggested that miR-7a regulates Müller glia differentiation through attenuation of Notch3 expression. Taken together, we revealed that the miR-7a regulates the differentiation of Müller glia through the suppression of Notch3 expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple aspects of self-regulation uniquely predict mathematics but not letter-word knowledge in the early elementary grades.

PubMed

Blair, Clancy; Ursache, Alexandra; Greenberg, Mark; Vernon-Feagans, Lynne

2015-04-01

The relation of self-regulation measured prior to school entry to developing math and reading ability in prekindergarten through the second grade was examined in a prospective longitudinal sample of 1,292 children and families in predominantly rural and low-income communities in 2 regions of high poverty in the United States. Direct assessments of executive function, effortful control, and stress response physiology (indexed by resting levels of cortisol and alpha amylase obtained from saliva) were measured at child age 48 months and parents and teachers reported on children's effortful control using temperament rating scales at child age approximately 60 months. Math and reading ability, as measured by the Woodcock-Johnson III applied problems and letter-word subtests, respectively, were measured at prekindergarten through the second grade. Effects for self-regulation measures were seen primarily for initial level and to some extent growth in both mathematics and reading, even when controlling for family demographic characteristics that represent relevant selection factors into higher levels of both self-regulation and academic achievement. These effects persisted for mathematics but not for reading with the inclusion of child cognitive abilities, vocabulary, and speed of processing measured in prekindergarten, concurrent with the first time point for the academic measures. Results are interpreted as indicating a role for self-regulation in learning ability generally, likely through support for attention and reasoning abilities that are most specific to the assessment of mathematics in this analysis. Implications for instruction and for assessment and the best ways to support the development of early math and reading ability for children at risk for school failure are discussed. (c) 2015 APA, all rights reserved).

Resilience thinking: integrating resilience, adaptability and transformability

Treesearch

Carl Folke; Stephen R. Carpenter; Brian Walker; Marten Scheffer; Terry Chapin; Johan Rockstrom

2010-01-01

Resilience thinking addresses the dynamics and development of complex social-ecological systems (SES). Three aspects are central: resilience, adaptability and transformability. These aspects interrelate across multiple scales. Resilience in this context is the capacity of a SES to continually change and adapt yet remain within critical thresholds. Adaptability is part...

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism.

PubMed

Shi, Yuguang; Cheng, Dong

2009-07-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications.

Expression of voltage-activated calcium channels in the early zebrafish embryo.

PubMed

Sanhueza, Dayán; Montoya, Andro; Sierralta, Jimena; Kukuljan, Manuel

2009-05-01

Increases in cytosolic calcium concentrations regulate many cellular processes, including aspects of early development. Calcium release from intracellular stores and calcium entry through non-voltage-gated channels account for signalling in non-excitable cells, whereas voltage-gated calcium channels (CaV) are important in excitable cells. We report the expression of multiple transcripts of CaV, identified by its homology to other species, in the early embryo of the zebrafish, Danio rerio, at stages prior to the differentiation of excitable cells. CaV mRNAs and proteins were detected as early as the 2-cell stages, which indicate that they arise from both maternal and zygotic transcription. Exposure of embryos to pharmacological blockers of CaV does not perturb early development significantly, although late effects are appreciable. These results suggest that CaV may have a role in calcium homeostasis and control of cellular process during early embryonic development.

HITS-CLIP yields genome-wide insights into brain alternative RNA processing

NASA Astrophysics Data System (ADS)

Licatalosi, Donny D.; Mele, Aldo; Fak, John J.; Ule, Jernej; Kayikci, Melis; Chi, Sung Wook; Clark, Tyson A.; Schweitzer, Anthony C.; Blume, John E.; Wang, Xuning; Darnell, Jennifer C.; Darnell, Robert B.

2008-11-01

Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.

Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons

PubMed Central

Yao, Pamela J.; Manor, Uri; Petralia, Ronald S.; Brose, Rebecca D.; Wu, Ryan T. Y.; Ott, Carolyn; Wang, Ya-Xian; Charnoff, Ari; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

2017-01-01

Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense, as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid β-peptide, hydrogen peroxide, and high levels of glutamate. Collectively our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons. PMID:27932496

Documenting the doable and doing the documented: bridging strategies at the UK Stem Cell Bank.

PubMed

Stephens, Neil; Atkinson, Paul; Glasner, Peter

2011-12-01

We explore the local negotiation of regulatory practice at the UK Stem Cell Bank, the first Bank of its type in the world. Basing our empirical work on a detailed analysis of one aspect of the Bank's regulatory commitment--the completion of the Cell Line Information form--we make visible the necessary judgements and labour involved in interpreting and operationalizing externally imposed regulation. The discussion opens by detailing the problems encountered when the Bank completes the form: reconciling a bureaucratic system of accountability with craft-like laboratory skills involving multiple kinds of tacit knowledge. We follow this by explicating the emergent 'bridging strategies' pursued by the Bank to address these issues, highlighting their reliance upon the formation of trust and social networks. The closing discussion emphasizes the contingent assembly of regulatory practices that emerge in the local setting.

Milk as a medium for pediatric formulations: Experimental findings and regulatory aspects.

PubMed

Soulele, Konstantina; Macheras, Panos

2015-08-15

In the case of pediatric medicinal products the selection of an appropriate and palatable liquid dosage form can make the difference between treatment success and failure. Since the recent adoption of Pediatric Regulations in the U.S. and E.U., there is a greater demand for age-appropriate medicines for children. Extended research on the use of milk on drug administration in pediatric population has shown the multiple benefits of its use. Milk exhibits great solubilizing, gastroprotective and taste masking properties, which are very important characteristics in the case of insoluble, irritating and bitter-tasting active compounds. Milk-based formulations rely on a novel, simple and user-friendly approach for the delivery of ionized and unionized lipophilic drugs. In parallel they can provide critical nutritive elements and a wide range of biologically active peptides, very important elements especially for pediatric patients. Copyright © 2015. Published by Elsevier B.V.

Towards the social analysis of twinship.

PubMed

Stewart, E A

2000-12-01

The article examines the proposition that twinship is an irreducibly social phenomenon. Gender, age, birth order, socio-economic status and other variables are considered, along with the role of different patterns of socialization as these affect twinship. It is argued that, to a very large extent, from conception. through gestation, childbirth and subsequently childhood and adolescence, the social processing and regulation of social members take place in unitary terms and that therefore twins (and higher multiples) are an anomaly in relation to such processes. Twins' reactions to stigma, stereotyping and labelling are explored as an integral aspect of the social structuring of twinship. The role of the twin, as distinct from the role of the non-twin, is examined in the context of cultural expectations of twinship regarding similarity of identity and similarity of behaviour. Subsequent or concurrent processes of differentiation between twins are also examined. The article concludes with suggestions for further analyses of twinship.

RNA mobility in parasitic plant – host interactions

PubMed Central

Kim, Gunjune

2017-01-01

ABSTRACT The parasitic plant Cuscuta exchanges mRNAs with its hosts. Systemic mobility of mRNAs within plants is well documented, and has gained increasing attention as studies using grafted plant systems have revealed new aspects of mobile mRNA regulation and function. But parasitic plants take this phenomenon to a new level by forming seamless connections to a wide range of host species, and raising questions about how mRNAs might function after transfer to a different species. Cuscuta and other parasitic plant species also take siRNAs from their hosts, indicating that multiple types of RNA are capable of trans-specific movement. Parasitic plants are intriguing systems for studying RNA mobility, in part because such exchange opens new possibilities for control of parasitic weeds, but also because they provide a fresh perspective into understanding roles of RNAs in inter-organismal communication. PMID:28277936

Longitudinal relations between parental media monitoring and adolescent aggression, prosocial behavior, and externalizing problems.

PubMed

Padilla-Walker, Laura M; Coyne, Sarah M; Collier, Kevin M

2016-01-01

The current study examined longitudinal relations between parental media monitoring and adolescent behavior, and explored indirect effects via sympathy and self-regulation. A sample of adolescents and their mothers from Northwestern and Mountain West cities in the USA participated in a study at three time points, approximately one year apart (N = 681; M age of child at Time 3 = 13.33, SD = 1.06; 51% female; 73% European American, 9% African American, 17% Multi-ethnic). Though findings varied by reporter, results suggested that restrictive and active media monitoring were indirectly associated with adolescents' prosocial behavior, aggression, and externalizing behavior, with restrictive monitoring being somewhat maladaptive and active monitoring adaptive. The discussion focuses on the need to examine multiple aspects of media monitoring, and highlights implications of findings for parents. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Sensitivity, child regulatory processes, and naturally occurring declines in antisocial behavior across childhood.

PubMed

Buck, Katharine Ann

2014-12-01

Despite considerable research on why antisocial behavior develops and interventions that reduce it, aspects of everyday family processes that may promote naturally occurring declines in antisocial behavior or that may result from such declines in most children without intervention are poorly understood. The current study explored family processes that may enable children to replace antisocial tendencies and the effects that declines in antisocial behavior may have on parenting and child regulatory processes. Longitudinal data from 1,022 children (54 months-6th grade) from the NICHD Study of Early Child Care and Youth Development were examined. Findings demonstrated that naturally occurring declines in antisocial behavior both predicted and were predicted by maternal sensitivity, emotion regulation, and social skills. These declines predicted but were not predicted by declines in hostile attributions. The data revealed multiple indirect paths, which highlight the complex nature of these variables across development.

Nuclear envelope and genome interactions in cell fate

PubMed Central

Talamas, Jessica A.; Capelson, Maya

2015-01-01

The eukaryotic cell nucleus houses an organism’s genome and is the location within the cell where all signaling induced and development-driven gene expression programs are ultimately specified. The genome is enclosed and separated from the cytoplasm by the nuclear envelope (NE), a double-lipid membrane bilayer, which contains a large variety of trans-membrane and associated protein complexes. In recent years, research regarding multiple aspects of the cell nucleus points to a highly dynamic and coordinated concert of efforts between chromatin and the NE in regulation of gene expression. Details of how this concert is orchestrated and how it directs cell differentiation and disease are coming to light at a rapid pace. Here we review existing and emerging concepts of how interactions between the genome and the NE may contribute to tissue specific gene expression programs to determine cell fate. PMID:25852741

Poly(A)-binding proteins and mRNA localization: who rules the roost?

PubMed

Gray, Nicola K; Hrabálková, Lenka; Scanlon, Jessica P; Smith, Richard W P

2015-12-01

RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals. © 2015 Authors; published by Portland Press Limited.

Deciphering the associations between gene expression and copy number alteration using a sparse double Laplacian shrinkage approach

PubMed Central

Shi, Xingjie; Zhao, Qing; Huang, Jian; Xie, Yang; Ma, Shuangge

2015-01-01

Motivation: Both gene expression levels (GEs) and copy number alterations (CNAs) have important biological implications. GEs are partly regulated by CNAs, and much effort has been devoted to understanding their relations. The regulation analysis is challenging with one gene expression possibly regulated by multiple CNAs and one CNA potentially regulating the expressions of multiple genes. The correlations among GEs and among CNAs make the analysis even more complicated. The existing methods have limitations and cannot comprehensively describe the regulation. Results: A sparse double Laplacian shrinkage method is developed. It jointly models the effects of multiple CNAs on multiple GEs. Penalization is adopted to achieve sparsity and identify the regulation relationships. Network adjacency is computed to describe the interconnections among GEs and among CNAs. Two Laplacian shrinkage penalties are imposed to accommodate the network adjacency measures. Simulation shows that the proposed method outperforms the competing alternatives with more accurate marker identification. The Cancer Genome Atlas data are analysed to further demonstrate advantages of the proposed method. Availability and implementation: R code is available at http://works.bepress.com/shuangge/49/ Contact: shuangge.ma@yale.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26342102

The Impacts of Information-Sharing Mechanisms on Spatial Market Formation Based on Agent-Based Modeling

PubMed Central

Li, Qianqian; Yang, Tao; Zhao, Erbo; Xia, Xing’ang; Han, Zhangang

2013-01-01

There has been an increasing interest in the geographic aspects of economic development, exemplified by P. Krugman’s logical analysis. We show in this paper that the geographic aspects of economic development can be modeled using multi-agent systems that incorporate multiple underlying factors. The extent of information sharing is assumed to be a driving force that leads to economic geographic heterogeneity across locations without geographic advantages or disadvantages. We propose an agent-based market model that considers a spectrum of different information-sharing mechanisms: no information sharing, information sharing among friends and pheromone-like information sharing. Finally, we build a unified model that accommodates all three of these information-sharing mechanisms based on the number of friends who can share information. We find that the no information-sharing model does not yield large economic zones, and more information sharing can give rise to a power-law distribution of market size that corresponds to the stylized fact of city size and firm size distributions. The simulations show that this model is robust. This paper provides an alternative approach to studying economic geographic development, and this model could be used as a test bed to validate the detailed assumptions that regulate real economic agglomeration. PMID:23484007

Interventional procedures and future drug therapy for hypertension.

PubMed

Lobo, Melvin D; Sobotka, Paul A; Pathak, Atul

2017-04-14

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Regulation of Animal Use: Voluntary and Involuntary.

ERIC Educational Resources Information Center

Clark, J. Derrell

1979-01-01

The regulation (voluntary and involuntary) of animal care and use throughout history in research and teaching is reviewed. The role of several organizations concerned with various aspects of animal quality, care, and use is discussed. (BH)

Journal entries facilitating preprofessional scientific literacy and mutualistic symbiotic relationships

NASA Astrophysics Data System (ADS)

Vander Vliet, Valerie J.

This study explored journal writing as an alternative assessment to promote the development of pre-professional scientific literacy and mutualistic symbiotic relationships between teaching and learning, instruction and assessment, and students and teachers. The larger context of this study is an action reaction project of the attempted transformation of a traditional first year undergraduate pre-professional biology class to sociocultural constructivist principles. The participants were commuter and residential, full and part-time students ranging in age from 18 to 27 and 18/21 were female. The backgrounds of the students varied considerably, ranging from low to upper middle income, including students of Black and Asian heritage. The setting was a medium-sized Midwestern university. The instructor has twenty years of experience teaching Biology at the college level. The data were analyzed using the constant comparative method and the development of grounded theory. The journal entries were analyzed as to their function and form in relationship to the development of multiple aspects of pre-professional scientific literacy. The perceptions of the students as to the significance of the use of journal entries were also determined through the analysis of their use of journal entries in their portfolios and statements in surveys and portfolios. The analysis revealed that journal entries promoted multiple aspects of pre-professional scientific literacy in both students and the instructor and facilitated the development of mutualistic symbiotic relationships between teaching and learning, instruction and assessment, and students and teachers. The function analysis revealed that the journal entries fulfilled the functions intended for the development of multiple aspects of pre-professional scientific literacy. The complexity of journal writing emerged from the form analysis, which revealed the multiple form elements inherent in journal entries. Students perceived journal entries to act as cognitive, affective, and social catalysts of pre-professional scientific literacy. This study has shown that journal entries facilitate the development of multiple aspects of scientific literacy and mutualistic symbiotic relationships between teaching and learning, instruction and assessment, and students and teachers.

Number of Repetitions Required to Retain Single-Digit Multiplication Math Facts for Elementary Students

ERIC Educational Resources Information Center

Burns, Matthew K.; Ysseldyke, Jim; Nelson, Peter M.; Kanive, Rebecca

2015-01-01

Computational fluency is an important aspect of math proficiency. Despite widely held beliefs about the differential difficulty of single-digit multiplication math facts, little empirical work has examined this issue. The current study analyzed the number of repetitions needed to master multiplication math facts. Data from 15,402 3rd, 4th, and 5th…

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

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

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

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

PubMed

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

2013-01-01

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

Environmental permitting in Thailand

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

Byers, A.C.

Thailand's 1992 enhancement and Conservation of Environmental Quality Act and regulations require any entry proposing to construct a thermal power plant with a capacity greater that 10 MW to perform various environmental studies and prepare an environmental Impact Assessment (EIA) report in accordance with the guidelines issued by the office of Environmental Policy and Planning (OEPP). Approval of the EIA is a prerequisite to the issuance of most other construction permits. Applicable environmental standards and regulation are promulgated by the Pollution Control Department (PCD), a wholly separate agency for the OEPP. The PCD is a fairly new organization and, asmore » a result, their staff is still gaining understanding of the multiple environmental aspects of power generation. Accordingly, the PCD is still in process of drafting key regulations applicable to the power industry. This paper examines the current guidelines, practices, procedures and legal requirements regarding environmental licensing of a thermal power plant in Thailand. The requisite scope and content of the EIA report will be identified, as well as the current procedure for its official review and approval by the OEPP. The paper will address the challenges of working with local consultants and identify potential pitfalls in the report preparation process. Areas of particular interest in the EIA review will be identified based on recent examples of OEPP comments on previous SPP and IPP projects. Additionally, the development of applicable environmental standards by the PCD will be identified along with their plans for implementing these standards. The paper will also examine the relationship of the OEPP and PCD, and reflect upon trends for environmental regulation in Thailand in the near future.« less

Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning

PubMed Central

Vempati, Prakash; Popel, Aleksander S.; Mac Gabhann, Feilim

2014-01-01

The regulation of vascular endothelial growth factor A (VEGF) is critical to neovascularization in numerous tissues under physiological and pathological conditions. VEGF has multiple isoforms, created by alternative splicing or proteolytic cleavage, and characterized by different receptor-binding and matrix-binding properties. These isoforms are known to give rise to a spectrum of angiogenesis patterns marked by differences in branching, which has functional implications for tissues. In this review, we detail the extensive extracellular regulation of VEGF and the ability of VEGF to dictate the vascular phenotype. We explore the role of VEGF-releasing proteases and soluble carrier molecules on VEGF activity. While proteases such as MMP9 can ‘release’ matrix-bound VEGF and promote angiogenesis, for example as a key step in carcinogenesis, proteases can also suppress VEGF’s angiogenic effects. We explore what dictates pro- or anti-angiogenic behavior. We also seek to understand the phenomenon of VEGF gradient formation. Strong VEGF gradients are thought to be due to decreased rates of diffusion from reversible matrix binding, however theoretical studies show that this scenario cannot give rise to lasting VEGF gradients in vivo. We propose that gradients are formed through degradation of sequestered VEGF. Finally, we review how different aspects of the VEGF signal, such as its concentration, gradient, matrix-binding, and NRP1-binding can differentially affect angiogenesis. We explore how this allows VEGF to regulate the formation of vascular networks across a spectrum of high to low branching densities, and from normal to pathological angiogenesis. A better understanding of the control of angiogenesis is necessary to improve upon limitations of current angiogenic therapies. PMID:24332926

Screening of differentially expressed genes between multiple trauma patients with and without sepsis.

PubMed

Ji, S C; Pan, Y T; Lu, Q Y; Sun, Z Y; Liu, Y Z

2014-03-17

The purpose of this study was to identify critical genes associated with septic multiple trauma by comparing peripheral whole blood samples from multiple trauma patients with and without sepsis. A microarray data set was downloaded from the Gene Expression Omnibus (GEO) database. This data set included 70 samples, 36 from multiple trauma patients with sepsis and 34 from multiple trauma patients without sepsis (as a control set). The data were preprocessed, and differentially expressed genes (DEGs) were then screened for using packages of the R language. Functional analysis of DEGs was performed with DAVID. Interaction networks were then established for the most up- and down-regulated genes using HitPredict. Pathway-enrichment analysis was conducted for genes in the networks using WebGestalt. Fifty-eight DEGs were identified. The expression levels of PLAU (down-regulated) and MMP8 (up-regulated) presented the largest fold-changes, and interaction networks were established for these genes. Further analysis revealed that PLAT (plasminogen activator, tissue) and SERPINF2 (serpin peptidase inhibitor, clade F, member 2), which interact with PLAU, play important roles in the pathway of the component and coagulation cascade. We hypothesize that PLAU is a major regulator of the component and coagulation cascade, and down-regulation of PLAU results in dysfunction of the pathway, causing sepsis.

Process Mining Techniques for Analysing Patterns and Strategies in Students' Self-Regulated Learning

ERIC Educational Resources Information Center

Bannert, Maria; Reimann, Peter; Sonnenberg, Christoph

2014-01-01

Referring to current research on self-regulated learning, we analyse individual regulation in terms of a set of specific sequences of regulatory activities. Successful students perform regulatory activities such as analysing, planning, monitoring and evaluating cognitive and motivational aspects during learning not only with a higher frequency…

Anger Regulation and Social Acceptance in Early Adolescence: Associations with Gender and Ethnicity

ERIC Educational Resources Information Center

Perry-Parrish, Carisa; Webb, Lindsey; Zeman, Janice; Spencer, Sarah; Malone, Celeste; Borowski, Sarah; Reynolds, Elizabeth; Hankinson, Jessica; Specht, Matt; Ostrander, Rick

2017-01-01

Anger regulation among adolescents is important to investigate given theoretical and empirical support for its critical association with peer relationships. This study examined two aspects of anger regulation (i.e., inhibition, dysregulation) using self-report and peer-nominations and their associations with social acceptance among 163 Black and…

Genomics and evolutionary aspect of calcium signaling event in calmodulin and calmodulin-like proteins in plants.

PubMed

Mohanta, Tapan Kumar; Kumar, Pradeep; Bae, Hanhong

2017-02-03

Ca 2+ ion is a versatile second messenger that operate in a wide ranges of cellular processes that impact nearly every aspect of life. Ca 2+ regulates gene expression and biotic and abiotic stress responses in organisms ranging from unicellular algae to multi-cellular higher plants through the cascades of calcium signaling processes. In this study, we deciphered the genomics and evolutionary aspects of calcium signaling event of calmodulin (CaM) and calmodulin like- (CML) proteins. We studied the CaM and CML gene family of 41 different species across the plant lineages. Genomic analysis showed that plant encodes more calmodulin like-protein than calmodulins. Further analyses showed, the majority of CMLs were intronless, while CaMs were intron rich. Multiple sequence alignment showed, the EF-hand domain of CaM contains four conserved D-x-D motifs, one in each EF-hand while CMLs contain only one D-x-D-x-D motif in the fourth EF-hand. Phylogenetic analysis revealed that, the CMLs were evolved earlier than CaM and later diversified. Gene expression analysis demonstrated that different CaM and CMLs genes were express differentially in different tissues in a spatio-temporal manner. In this study we provided in detailed genome-wide identifications and characterization of CaM and CML protein family, phylogenetic relationships, and domain structure. Expression study of CaM and CML genes were conducted in Glycine max and Phaseolus vulgaris. Our study provides a strong foundation for future functional research in CaM and CML gene family in plant kingdom.

Content Analysis of Diet-Related Mobile Apps: A Self-Regulation Perspective.

PubMed

Zahry, Nagwan R; Cheng, Ying; Peng, Wei

2016-10-01

Diet-related mobile apps hold promise in helping individuals self-regulate their eating behaviors. Nevertheless, little is known about the extent to which diet-related mobile apps incorporate the established behavior change theories and evidence-based practices that promote dietary self-regulation. Guided by the self-regulation aspect of Bandura's social cognitive theory and the Dietary Guidelines for Americans 2010 of the U.S. Department of Agriculture, this study conducts a content analysis of diet-related mobile apps for iPhone (N = 400). In terms of the adherence to the self-regulation aspect of the social cognitive theory, results show that although 72.5% of the apps incorporate at least one theoretical construct, few apps tap all three processes of self-regulation (i.e., self-observation/monitoring, judgment process, and self-reaction). Additionally, outcome expectation is manifested in a majority of the diet-related apps. In terms of the Dietary Guidelines for Americans 2010, while the diet-related apps equally emphasize setting goals for calorie intake or nutrient consumption, more apps feature nutrient tracking than calorie tracking. Implications and limitations are discussed.

Heart rate variability indices as bio-markers of top-down self-regulatory mechanisms: A meta-analytic review.

PubMed

Holzman, Jacob B; Bridgett, David J

2017-03-01

Theoretical perspectives posit that heart-rate variability (HRV) reflects self-regulatory capacity and therefore can be employed as a bio-marker of top-down self-regulation (the ability to regulate behavioral, cognitive, and emotional processes). However, existing findings of relations between self-regulation and HRV indices are mixed. To clarify the nature of such relations, we conducted a meta-analysis of 123 studies (N=14,347) reporting relations between HRV indices and aspects of top-down self-regulation (e.g., executive functioning, emotion regulation, effortful control). A significant, albeit small, effect was observed (r=0.09) such that greater HRV was related to better top-down self-regulation. Differences in relations were negligible across aspects of self-regulation, self-regulation measurement methods, HRV computational techniques, at-risk compared with healthy samples, and the context of HRV measurement. Stronger relations were observed in older relative to younger samples and in published compared to unpublished studies. These findings generally support the notion that HRV indices can tentatively be employed as bio-markers of top-down self-regulation. Conceptual and theoretical implications, and critical gaps in current knowledge to be addressed by future work, are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

7 CFR 3406.28 - Confidential aspects of proposals and awards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Confidential aspects of proposals and awards. 3406.28 Section 3406.28 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE 1890 INSTITUTION CAPACITY BUILDING...

7 CFR 3405.21 - Confidential aspects of proposals and awards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Confidential aspects of proposals and awards. 3405.21 Section 3405.21 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE HIGHER EDUCATION CHALLENGE GRANTS...

An Investigation into the Capacity of Student Motivation and Emotion Regulation Strategies to Predict Engagement and Resilience in the Middle School Classroom

ERIC Educational Resources Information Center

Fried, Leanne; Chapman, Elaine

2012-01-01

Although most of the initial research on self-regulated learning focused on cognitive and meta-cognitive aspects, there has been a growing interest in the emotion and motivation domains of self-regulation. This article reports on research undertaken to investigate specific motivation and emotion regulation strategies used by middle school students…

A letter of intent for an experiment to study strong electromagnetic fields at RHIC via multiple electromagnetic processes

NASA Technical Reports Server (NTRS)

Fatyga, M.; Norbury, John W.

1992-01-01

An experimental program at the Relativistic Heavy Ion Collider (RHIC) which is designed to study nonperturbative aspects of electrodynamics is outlined. Additional possibilities for new studies of electrodynamics via multiple electromagnetic processes are also described.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

PubMed

García Merino, A; Ramón Ara Callizo, J; Fernández Fernández, O; Landete Pascual, L; Moral Torres, E; Rodríguez-Antigüedad Zarrantz, A

2017-03-01

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Using a Multiobjective Approach to Balance Mission and Network Goals within a Delay Tolerant Network Topology

DTIC Science & Technology

2009-03-01

incorporating autonomous actions, but none appear to incorporate a cognitive aspect used to balance multiple objectives as is the focus of this work. There...routing algorithm) and/or mission type decision (orbit path change). In this component, the pseudo- cognitive aspect is implemented within the...orbit change behavior doesn’t know which orbit to choose. This is where the cognitive aspect takes over. Since the orbit change behavior doesn’t

Sociological aspects of permanent manned occupancy of space.

PubMed

Bluth, B J

1981-01-01

The author examines human experiences with isolation and confined groups to determine the sociological aspects of social isolation in space. Precedent experiences include Antarctic stations, oceanographic research vessels, submarines, undersea laboratories, and space simulators. The Soviet experience with multiple-person crews on the Salyut 6 space station is explored. Sociological aspects of isolation and confinement aboard a space station include physiological stress, social and psychological stress, group size and composition, group organization, architectural programming, privacy, and work/rest scheduling.

16 CFR 1500.127 - Substances with multiple hazards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Substances with multiple hazards. 1500.127 Section 1500.127 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS § 1500.127...

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

PubMed

Iparraguirre, Leire; Muñoz-Culla, Maider; Prada-Luengo, Iñigo; Castillo-Triviño, Tamara; Olascoaga, Javier; Otaegui, David

2017-09-15

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice. Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a 'sponge system' and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers. Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered. Therefore, we carried out expression profiling of 13.617 circular RNAs in peripheral blood leucocytes from multiple sclerosis patients and healthy controls finding 406 differentially expressed (P-value < 0.05, Fold change > 1.5) and demonstrate after validation that, circ_0005402 and circ_0035560 are underexpressed in multiple sclerosis patients and could be used as biomarkers of the disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Broadband piezoelectric energy harvesting devices using multiple bimorphs with different operating frequencies.

PubMed

Xue, Huan; Hu, Yuantai; Wang, Qing-Ming

2008-09-01

This paper presents a novel approach for designing broadband piezoelectric harvesters by integrating multiple piezoelectric bimorphs (PBs) with different aspect ratios into a system. The effect of 2 connecting patterns among PBs, in series and in parallel, on improving energy harvesting performance is discussed. It is found for multifrequency spectra ambient vibrations: 1) the operating frequency band (OFB) of a harvesting structure can be widened by connecting multiple PBs with different aspect ratios in series; 2) the OFB of a harvesting structure can be shifted to the dominant frequency domain of the ambient vibrations by increasing or decreasing the number of PBs in parallel. Numerical results show that the OFB of the piezoelectric energy harvesting devices can be tailored by the connection patterns (i.e., in series and in parallel) among PBs.

Self-regulated compliance in preschoolers with autism spectrum disorder: The role of temperament and parental disciplinary style.

PubMed

Ostfeld-Etzion, Sharon; Feldman, Ruth; Hirschler-Guttenberg, Yael; Laor, Nathaniel; Golan, Ofer

2016-10-01

Regulatory difficulties are common in children with autism spectrum disorder. This study focused on an important aspect of self-regulation-the ability to willingly comply with frustrating demands of socialization agents, termed "self-regulated compliance." We studied compliance to parental demands in 40 preschoolers with autism spectrum disorder and 40 matched typically developing preschoolers, during separate interactions with mother and father, while engaging in two paradigms: toy pick-up and delayed gratification, which tap the "do" and "don't" aspects of self-regulated socialization at this age. Parents' disciplinary style was micro-coded from the two paradigms and child temperament was parent reported. Compared to their typically developing peers, children with autism spectrum disorder showed more noncompliance and less self-regulated compliance to parental demands and prohibitions and greater temperamental difficulties across several domains. No group differences were found in parental disciplinary style. Child self-regulated compliance was associated with parental supportive disciplinary style and with child attention focusing. Findings highlight the importance of parental supportive presence in structuring the development of socialization in children with autism spectrum disorder. Implications for parent-child emotion regulation interventions are discussed. © The Author(s) 2015.

Compliance and Cognitive Function: A Methodological Approach to Measuring Unintentional Errors in Medication Compliance in the Elderly.

ERIC Educational Resources Information Center

Isaac, Lisa M.; And Others

1993-01-01

Assessed multiple aspects of cognitive performance, medication planning ability, and medication compliance in 20 elderly outpatients. Findings suggest that aspects of attention/concentration, visual and verbal memory, and motor function which are untapped by simple mental status assessment are related to medication access, planning, and compliance…

Integrated Testlets: A New Form of Expert-Student Collaborative Testing

ERIC Educational Resources Information Center

Shiell, Ralph C.; Slepkov, Aaron D.

2015-01-01

Integrated testlets are a new assessment tool that encompass the procedural benefits of multiple-choice testing, the pedagogical advantages of free-response-based tests, and the collaborative aspects of a viva voce or defence examination format. The result is a robust assessment tool that provides a significant formative aspect for students.…

Satisfaction with Individualized Education Programs among Parents of Young Children with ASD

ERIC Educational Resources Information Center

Slade, Nicole; Eisenhower, Abbey; Carter, Alice S.; Blacher, Jan

2018-01-01

We examined parents' satisfaction with multiple aspects of their children's individualized education programs (IEPs). Parents (n = 142) raising children ages 4 to 8 years old with autism spectrum disorder (ASD) reported their satisfaction with four aspects of their children's IEPs: (a) content of the IEP document, (b) services provided, (c)…

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

PubMed

Miller, Jonathan; Watrous, Andrew J; Tsitsiklis, Melina; Lee, Sang Ah; Sheth, Sameer A; Schevon, Catherine A; Smith, Elliot H; Sperling, Michael R; Sharan, Ashwini; Asadi-Pooya, Ali Akbar; Worrell, Gregory A; Meisenhelter, Stephen; Inman, Cory S; Davis, Kathryn A; Lega, Bradley; Wanda, Paul A; Das, Sandhitsu R; Stein, Joel M; Gorniak, Richard; Jacobs, Joshua

2018-06-21

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

7 CFR 3402.21 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Confidential aspects of applications and awards. 3402.21 Section 3402.21 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE...

7 CFR 3402.21 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Confidential aspects of applications and awards. 3402.21 Section 3402.21 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE...

7 CFR 2903.22 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Confidential aspects of applications and awards. 2903.22 Section 2903.22 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

7 CFR 2903.22 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Confidential aspects of applications and awards. 2903.22 Section 2903.22 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

7 CFR 2903.22 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Confidential aspects of applications and awards. 2903.22 Section 2903.22 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

7 CFR 2903.22 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Confidential aspects of applications and awards. 2903.22 Section 2903.22 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

7 CFR 2903.22 - Confidential aspects of applications and awards.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Confidential aspects of applications and awards. 2903.22 Section 2903.22 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE BIODIESEL FUEL EDUCATION PROGRAM Supplementary...

Professional Competence of Teachers: Effects on Instructional Quality and Student Development

ERIC Educational Resources Information Center

Kunter, Mareike; Klusmann, Uta; Baumert, Jürgen; Richter, Dirk; Voss, Thamar; Hachfeld, Axinja

2013-01-01

This study investigates teachers' pedagogical content knowledge, professional beliefs, work-related motivation, and self-regulation as aspects of their professional competence. Specifically, it examines how these aspects impact instruction and, in turn, student outcomes. In a nationally representative sample of 194 German secondary school…

7 CFR 3405.21 - Confidential aspects of proposals and awards.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Confidential aspects of proposals and awards. 3405.21 Section 3405.21 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE HIGHER EDUCATION CHALLENGE GRANTS PROGRAM Supplementary Information § 3405.21...

7 CFR 3405.21 - Confidential aspects of proposals and awards.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Confidential aspects of proposals and awards. 3405.21 Section 3405.21 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE HIGHER EDUCATION CHALLENGE GRANTS PROGRAM Supplementary Information § 3405.21...

7 CFR 3405.21 - Confidential aspects of proposals and awards.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Confidential aspects of proposals and awards. 3405.21 Section 3405.21 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE HIGHER EDUCATION CHALLENGE GRANTS PROGRAM Supplementary Information § 3405.21...

7 CFR 3405.21 - Confidential aspects of proposals and awards.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Confidential aspects of proposals and awards. 3405.21 Section 3405.21 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE HIGHER EDUCATION CHALLENGE GRANTS PROGRAM Supplementary Information § 3405.21...

Relationships between gross- and fine motor functions, cognitive abilities, and self-regulatory aspects of students with physical disabilities.

PubMed

Varsamis, Panagiotis; Agaliotis, Ioannis

2015-12-01

This article reports research on self-regulatory aspects (i.e., goal-setting, self-efficacy and self-evaluation) of secondary and post-secondary students with congenital motor disabilities, who performed a ball-throwing-at-a-target task. Participants were divided into four subgroups presenting distinct combinations of motor and cognitive abilities (i.e., normal cognitive development and mild physical disabilities, normal cognitive development and severe physical disabilities, mild-to-moderate intellectual disability and mild physical disabilities, and mild-to-moderate intellectual disability and severe physical disabilities). Results showed that students presenting mild motor disabilities exhibited a positive self-concept and self-regulation profile, irrespective of their cognitive functioning. Students with considerable motor disabilities, but without cognitive challenges, presented a negative, though realistic self-concept and self-regulation profile. Finally, students with considerable motor disabilities and mild-to-moderate cognitive disabilities showed a positive, though unrealistic, self-regulation profile. The nature of the diverse relationship of motor and cognitive (dis)abilities to specific self-regulatory aspects are discussed, and important instructional implications are mentioned. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fast concurrent array-based stacks, queues and deques using fetch-and-increment-bounded, fetch-and-decrement-bounded and store-on-twin synchronization primitives

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

Chen, Dong; Gara, Alana; Heidelberger, Philip

Implementation primitives for concurrent array-based stacks, queues, double-ended queues (deques) and wrapped deques are provided. In one aspect, each element of the stack, queue, deque or wrapped deque data structure has its own ticket lock, allowing multiple threads to concurrently use multiple elements of the data structure and thus achieving high performance. In another aspect, new synchronization primitives FetchAndIncrementBounded (Counter, Bound) and FetchAndDecrementBounded (Counter, Bound) are implemented. These primitives can be implemented in hardware and thus promise a very fast throughput for queues, stacks and double-ended queues.

Aspect ratio dependence of auger recombination and carrier multiplication in PbSe nanorods.

PubMed

Padilha, Lazaro A; Stewart, John T; Sandberg, Richard L; Bae, Wan Ki; Koh, Weon-Kyu; Pietryga, Jeffrey M; Klimov, Victor I

2013-03-13

Nanomaterials with efficient carrier multiplication (CM), that is, generation of multiple electron-hole pairs by single photons, have been the object of intense scientific interest as potential enablers of high efficiency generation-III photovoltaics. In this work, we explore nanocrystal shape control as a means for enhancing CM. Specifically, we investigate the influence of aspect ratio (ρ) of PbSe nanorods (NRs) on both CM and the inverse of this process, Auger recombination. We observe that Auger lifetimes in NRs increase with increasing particle volume and for a fixed cross-sectional size follow a linear dependence on the NR length. For a given band gap energy, the CM efficiency in NRs shows a significant dependence on aspect ratio and exhibits a maximum at ρ ∼ 6-7 for which the multiexciton yields are a factor of ca. 2 higher than those in quantum dots with a similar bandgap energy. To rationalize our experimental observations, we analyze the influence of dimensionality on both CM and non-CM energy-loss mechanisms and offer possible explanations for the seemingly divergent effects the transition from zero- to one-dimensional confinement has on the closely related processes of Auger recombination and CM.

Role of Multiple Representations in Physics Problem Solving

ERIC Educational Resources Information Center

Maries, Alexandru

2013-01-01

This thesis explores the role of multiple representations in introductory physics students' problem solving performance through several investigations. Representations can help students focus on the conceptual aspects of physics and play a major role in effective problem solving. Diagrammatic representations can play a particularly important role…

Endocrine hormones and local signals during the development of the mouse mammary gland.

PubMed

Brisken, Cathrin; Ataca, Dalya

2015-01-01

Most of mammary gland development occurs postnatally under the control of female reproductive hormones, which in turn interact with other endocrine factors. While hormones impinge on many tissues and trigger very complex biological responses, tissue recombination experiments with hormone receptor-deficient mammary epithelia revealed eminent roles for estrogens, progesterone, and prolactin receptor (PrlR) signaling that are intrinsic to the mammary epithelium. A subset of the luminal mammary epithelial cells expresses the estrogen receptor α (ERα), the progesterone receptor (PR), and the PrlR and act as sensor cells. These cells convert the detected systemic signals into local signals that are developmental stage-dependent and may be direct, juxtacrine, or paracrine. This setup ensures that the original input is amplified and that the biological responses of multiple cell types can be coordinated. Some key mediators of hormone action have been identified such as Wnt, EGFR, IGFR, and RANK signaling. Multiple signaling pathways such as FGF, Hedgehog, and Notch signaling participate in driving different aspects of mammary gland development locally but how they link to the hormonal control remains to be elucidated. An increasing number of endocrine factors are appearing to have a role in mammary gland development, the adipose tissue is increasingly recognized to play a role in endocrine regulation, and a complex role of the immune system with multiple different cell types is being revealed. For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

Self-Regulation and Math Attitudes: Effects on Academic Performance in Developmental Math Courses at a Community College

ERIC Educational Resources Information Center

Otts, Cynthia D.

2010-01-01

The purpose of the study was to investigate the relationship among math attitudes, self-regulated learning, and course outcomes in developmental math. Math attitudes involved perceived usefulness of math and math anxiety. Self-regulated learning represented the ability of students to control cognitive, metacognitive, and behavioral aspects of…

Using Self-Regulation as a Framework for Implementing Strategy Instruction to Foster Reading Comprehension

ERIC Educational Resources Information Center

Souvignier, Elmar; Mokhlesgerami, Judith

2006-01-01

Research on the implementation of reading strategies suggests that self-regulated learning might be a powerful framework to optimize effects on reading comprehension. Models of self-regulation emphasize that the teaching of strategy knowledge (Strat) has to be complemented by offering skills of cognitive (CSR) and motivational (MSR) aspects of…

Cognitive Modeling and Self-Regulation of Learning in Instructional Settings

ERIC Educational Resources Information Center

White, Marie C.

2017-01-01

Self-regulation of cognition and behavior is an important aspect of student learning and academic performance in the 21st-century classroom. The purpose of the chapter is to present how an integrated framework of cyclical phases and developmental levels of self-regulated learning play a significant role in modeling and self-regulatory learning as…

Learner Self-Regulation and Web 2.0 Tools Management in Personal Learning Environment

ERIC Educational Resources Information Center

Yen, Cherng-Jyh; Tu, Chih-Hsiung; Sujo-Montes, Laura E.; Armfield, Shadow W. J.; Chan, Junn-Yih

2013-01-01

Web 2.0 technology integration requires a higher level of self-regulated learning skills to create a Personal Learning Environment (PLE). This study examined each of the four aspects of learner self-regulation in online learning (i.e., environment structuring, goal setting, time management, & task strategies) as the predictor for level of…

Self-Regulated Compliance in Preschoolers with Autism Spectrum Disorder: The Role of Temperament and Parental Disciplinary Style

ERIC Educational Resources Information Center

Ostfeld-Etzion, Sharon; Feldman, Ruth; Hirschler-Guttenberg, Yael; Laor, Nathaniel; Golan, Ofer

2016-01-01

Regulatory difficulties are common in children with autism spectrum disorder. This study focused on an important aspect of self-regulation--the ability to willingly comply with frustrating demands of socialization agents, termed "self-regulated compliance." We studied compliance to parental demands in 40 preschoolers with autism spectrum…

Single-Cell and Single-Molecule Analysis of Gene Expression Regulation.

PubMed

Vera, Maria; Biswas, Jeetayu; Senecal, Adrien; Singer, Robert H; Park, Hye Yoon

2016-11-23

Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells. Definition of heterogeneity has revealed stochastic processes, determined characteristics of under-represented cell types or transitional states, and integrated cellular behaviors in the context of multicellular organisms. In this review, we discuss novel aspects of gene expression of eukaryotic cells and multicellular organisms revealed by the latest advances in single-cell and single-molecule imaging technology.

A Study on the Metacognitive Awareness of Secondary School Students

ERIC Educational Resources Information Center

Jaleel, Sajna; Premachandran. P

2016-01-01

Metacognition means "thinking about one's own thinking". There are two aspects of metacognition:--reflection--thinking about what we know and self-regulation-managing how we go about learning. Taking together, these processes make up an important aspect of learning and development. Developing these metacognitive abilities is not simply…

Innovative applications of food-related emulsions.

PubMed

Kiokias, S; Varzakas, T

2017-10-13

Research on oxidative stability of multiple emulsions is very scarce. Given that this is a relevant topic that must be ascertained before the successful application of multiple emulsions in foods (especially when a combination of highly unsaturated oils is used as a lipid phase), this review mainly focuses on various aspects of the multiple emulsions. Fat replacement in meat products using emulsions is critically discussed along with innovative applications of natural antioxidants in food-based emulsions and multiple emulsions based on bioactive compounds/encapsulation as well as confectionery products.

Progenitors of Secondary Crest Myofibroblasts are Developmentally Committed in Early Lung Mesoderm

PubMed Central

Li, Changgong; Li, Min; Li, Sha; Xing, Yiming; Yang, Chang-Yo; Li, Aimin; Borok, Zea; De Langhe, Stijn; Minoo, Parviz

2015-01-01

Development of the mammalian lung is predicated on cross-communications between two highly interactive tissues, the endodermally-derived epithelium and the mesodermally-derived pulmonary mesenchyme. While much attention has been paid the lung epithelium, the pulmonary mesenchyme, partly due to lack of specific tractable markers remains under-investigated. The lung mesenchyme is derived from the lateral plate mesoderm and is the principal recipient of Hedgehog (Hh) signaling, a morphogenetic network that regulates multiple aspects of embryonic development. Using the Hh-responsive Gli1-creERT2 mouse line, we identified the mesodermal targets of Hh signaling at various time points during embryonic and postnatal lung development. Cell lineage analysis showed these cells serve as progenitors to contribute to multiple lineages of mesodermally-derived differentiated cell types that include parenchymal or interstitial myofibroblasts, parabronchial and perivascular smooth muscle as well as rare populations of cells within the mesothelium. Most importantly, Gli1-creERT2 identified the progenitors of secondary crest myofibroblasts, a hitherto intractable cell type that plays a key role in alveolar formation, a vital process about which little is currently known. Transcriptome analysis of Hh-targeted progenitor cells transitioning from the pseudoglandular to the saccular phase of lung development revealed important modulations of key signaling pathways. Amongst these, there was significant down-regulation of canonical WNT signaling. Ectopic stabilization of β-Catenin via inactivation of Apc by Gli1-creERT2 expanded the Hh-targeted progenitor pools, which caused the formation of fibroblastic masses within the lung parenchyma. The Gli1-creERT2 mouse line represents a novel tool in the analysis of mesenchymal cell biology and alveolar formation during lung development. PMID:25448080

48 CFR 16.402-4 - Structuring multiple-incentive contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Structuring multiple-incentive contracts. 16.402-4 Section 16.402-4 Federal Acquisition Regulations System FEDERAL ACQUISITION... include a cost incentive (or constraint) that operates to preclude rewarding a contractor for superior...

A framework for multi-criteria assessment of model enhancements

NASA Astrophysics Data System (ADS)

Francke, Till; Foerster, Saskia; Brosinsky, Arlena; Delgado, José; Güntner, Andreas; López-Tarazón, José A.; Bronstert, Axel

2016-04-01

Modellers are often faced with unsatisfactory model performance for a specific setup of a hydrological model. In these cases, the modeller may try to improve the setup by addressing selected causes for the model errors (i.e. data errors, structural errors). This leads to adding certain "model enhancements" (MEs), e.g. climate data based on more monitoring stations, improved calibration data, modifications in process formulations. However, deciding on which MEs to implement remains a matter of expert knowledge, guided by some sensitivity analysis at best. When multiple MEs have been implemented, a resulting improvement in model performance is not easily attributed, especially when considering different aspects of this improvement (e.g. better performance dynamics vs. reduced bias). In this study we present an approach for comparing the effect of multiple MEs in the face of multiple improvement aspects. A stepwise selection approach and structured plots help in addressing the multidimensionality of the problem. The approach is applied to a case study, which employs the meso-scale hydrosedimentological model WASA-SED for a sub-humid catchment. The results suggest that the effect of the MEs is quite diverse, with some MEs (e.g. augmented rainfall data) cause improvements for almost all aspects, while the effect of other MEs is restricted to few aspects or even deteriorate some. These specific results may not be generalizable. However, we suggest that based on studies like this, identifying the most promising MEs to implement may be facilitated.

Electromagnetic decay of Monopole-Antimonopole pair

NASA Astrophysics Data System (ADS)

Calucci, Giorgio

2018-04-01

A Monopole-Antimonopole pair could annihilate producing a photon shower: Some aspects of the shower like the multiplicity distribution and angular correlations are investigated within a model suitable for processes with high multiplicities and therefore difficult to deal with standard perturbative treatment. The possible production of electron-positron pairs is also considered.

Configurations of Multiple Disparities in Reading Performance: Longitudinal Observations across France, Germany, Sweden and the United Kingdom

ERIC Educational Resources Information Center

Lenkeit, Jenny; Schwippert, Knut; Knigge, Michel

2018-01-01

Research provides evidence that gender, immigrant background and socio-economic characteristics present multiple disadvantaging characteristics that change their relative importance and configurations over time. When evaluating inequalities researchers tend to focus on one particular aspect and often use composite measures when evaluating…

Biography of George Eastman: A Multiple Intelligences Profile.

ERIC Educational Resources Information Center

Hogle, Jan G.

This paper describes the life and achievements of businessman, philanthropist, and photographic innovator, George Eastman. Aspects of multiple intelligences theory with regard to Eastman's life are discussed. The paper details Eastman's many and varied successes after a poor childhood and notes that, although he left school at 13 to help support…

Exploring Elementary Teachers' Perceptions about the Developmental Appropriateness and Importance of Nature of Science Aspects

ERIC Educational Resources Information Center

Sahin, Elif Adibelli; Deniz, Hasan

2016-01-01

This study explored how four elementary teachers assessed the developmental appropriateness and importance of nine nature of science (NOS) aspects after participating in a yearlong professional development program. A multiple-embedded case study design was employed. The primary data sources included (a) Views of Nature of Science Elementary School…

Direct molecular regulation of the myogenic determination gene Myf5 by Pax3, with modulation by Six1/4 factors, is exemplified by the -111 kb-Myf5 enhancer.

PubMed

Daubas, Philippe; Buckingham, Margaret E

2013-04-15

The Myf5 gene plays an important role in myogenic determination during mouse embryo development. Multiple genomic regions of the Mrf4-Myf5 locus have been characterised as enhancer sequences responsible for the complex spatiotemporal expression of the Myf5 gene at the onset of myogenesis. These include an enhancer sequence, located at -111 kb upstream of the Myf5 transcription start site, which is responsible of Myf5 activation in ventral somitic domains (Ribas et al., 2011. Dev. Biol. 355, 372-380). We show that the -111 kb-Myf5 enhancer also directs transgene expression in some limb muscles, and is active at foetal as well as embryonic stages. We have carried out further characterisation of the regulation of this enhancer and show that the paired-box Pax3 transcription factor binds to it in vitro as in vivo, and that Pax binding sites are essential for its activity. This requirement is independent of the previously reported regulation by TEAD transcription factors. Six1/4 which, like Pax3, are important upstream regulators of myogenesis, also bind in vivo to sites in the -111 kb-Myf5 enhancer and modulate its activity. The -111 kb-Myf5 enhancer therefore shares common functional characteristics with another Myf5 regulatory sequence, the hypaxial and limb 145 bp-Myf5 enhancer, both being directly regulated in vivo by Pax3 and Six1/4 proteins. However, in the case of the -111 kb-Myf5 enhancer, Six has less effect and we conclude that Pax regulation plays a major role in controlling this aspect of the Myf5 gene expression at the onset of myogenesis in the embryo. Copyright © 2013 Elsevier Inc. All rights reserved.

Ironing out the role of the cyclin-dependent kinase inhibitor, p21 in cancer: Novel iron chelating agents to target p21 expression and activity.

PubMed

Moussa, Rayan S; Park, Kyung Chan; Kovacevic, Zaklina; Richardson, Des R

2018-03-20

Iron (Fe) has become an important target for the development of anti-cancer therapeutics with a number of Fe chelators entering human clinical trials for advanced and resistant cancer. An important aspect of the activity of these compounds is their multiple molecular targets, including those that play roles in arresting the cell cycle, such as the cyclin-dependent kinase inhibitor, p21. At present, the exact mechanism by which Fe chelators regulate p21 expression remains unclear. However, recent studies indicate the ability of chelators to up-regulate p21 at the mRNA level was dependent on the chelator and cell-type investigated. Analysis of the p21 promoter identified that the Sp1-3-binding site played a significant role in the activation of p21 transcription by Fe chelators. Furthermore, there was increased Sp1/ER-α and Sp1/c-Jun complex formation in melanoma cells, suggesting these complexes were involved in p21 promoter activation. Elucidating the mechanisms involved in the regulation of p21 expression in response to Fe chelator treatment in neoplastic cells will further clarify how these agents achieve their anti-tumor activity. It will also enhance our understanding of the complex roles p21 may play in neoplastic cells and lead to the development of more effective and specific anti-cancer therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

Mitogen-Activated Protein Kinase Cascade MKK7-MPK6 Plays Important Roles in Plant Development and Regulates Shoot Branching by Phosphorylating PIN1 in Arabidopsis

PubMed Central

Liang, Yan; Wu, Xiaowei; Cai, Yueyue; Zhang, Yuanya; Wang, Yingchun; Li, Jiayang; Wang, Yonghong

2016-01-01

Emerging evidences exhibit that mitogen-activated protein kinase (MAPK/MPK) signaling pathways are connected with many aspects of plant development. The complexity of MAPK cascades raises challenges not only to identify the MAPK module in planta but also to define the specific role of an individual module. So far, our knowledge of MAPK signaling has been largely restricted to a small subset of MAPK cascades. Our previous study has characterized an Arabidopsis bushy and dwarf1 (bud1) mutant, in which the MAP Kinase Kinase 7 (MKK7) was constitutively activated, resulting in multiple phenotypic alterations. In this study, we found that MPK3 and MPK6 are the substrates for phosphorylation by MKK7 in planta. Genetic analysis showed that MKK7-MPK6 cascade is specifically responsible for the regulation of shoot branching, hypocotyl gravitropism, filament elongation, and lateral root formation, while MKK7-MPK3 cascade is mainly involved in leaf morphology. We further demonstrated that the MKK7-MPK6 cascade controls shoot branching by phosphorylating Ser 337 on PIN1, which affects the basal localization of PIN1 in xylem parenchyma cells and polar auxin transport in the primary stem. Our results not only specify the functions of the MKK7-MPK6 cascade but also reveal a novel mechanism for PIN1 phosphorylation, establishing a molecular link between the MAPK cascade and auxin-regulated plant development. PMID:27618482

Structural and Functional Characterization of Nrf2 Degradation by the Glycogen Synthase Kinase 3/β-TrCP Axis

PubMed Central

Rada, Patricia; Rojo, Ana I.; Evrard-Todeschi, Nathalie; Innamorato, Nadia G.; Cotte, Axelle; Jaworski, Tomasz; Tobón-Velasco, Julio C.; Devijver, Herman; García-Mayoral, María Flor; Van Leuven, Fred; Hayes, John D.

2012-01-01

The transcription factor NF-E2-related factor 2 (Nrf2) is a master regulator of a genetic program, termed the phase 2 response, that controls redox homeostasis and participates in multiple aspects of physiology and pathology. Nrf2 protein stability is regulated by two E3 ubiquitin ligase adaptors, Keap1 and β-TrCP, the latter of which was only recently reported. Here, two-dimensional (2D) gel electrophoresis and site-directed mutagenesis allowed us to identify two serines of Nrf2 that are phosphorylated by glycogen synthase kinase 3β (GSK-3β) in the sequence DSGISL. Nuclear magnetic resonance studies defined key residues of this phosphosequence involved in docking to the WD40 propeller of β-TrCP, through electrostatic and hydrophobic interactions. We also identified three arginine residues of β-TrCP that participate in Nrf2 docking. Intraperitoneal injection of the GSK-3 inhibitor SB216763 led to increased Nrf2 and heme oxygenase-1 levels in liver and hippocampus. Moreover, mice with hippocampal absence of GSK-3β exhibited increased levels of Nrf2 and phase 2 gene products, reduced glutathione, and decreased levels of carbonylated proteins and malondialdehyde. This study establishes the structural parameters of the interaction of Nrf2 with the GSK-3/β-TrCP axis and its functional relevance in the regulation of Nrf2 by the signaling pathways that impinge on GSK-3. PMID:22751928

Dynamic landscape of the local translation at activated synapses.

PubMed

Khlebodarova, T M; Kogai, V V; Trifonova, E A; Likhoshvai, V A

2018-01-01

The mammalian target of rapamycin (mTOR) signaling pathway is the central regulator of cap-dependent translation at the synapse. Disturbances in mTOR pathway have been associated with several neurological diseases, such as autism and epilepsy. RNA-binding protein FMRP, a negative regulator of translation initiation, is one of the key components of the local translation system. Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and dephosphorylation by PP2A phosphatase, respectively. S6 kinase and PP2A phosphatase are activated in response to mGluR receptor stimulation through different signaling pathways and at different rates. The dynamic aspects of this system are poorly understood. We developed a mathematical model of FMRP-dependent regulation of postsynaptic density (PSD) protein synthesis in response to mGluR receptor stimulation and conducted in silico experiments to study the regulatory circuit functioning. The modeling results revealed the possibility of generating oscillatory (cyclic and quasi-cyclic), chaotic and even hyperchaotic dynamics of postsynaptic protein synthesis as well as the presence of multiple attractors in a wide range of parameters of the local translation system. The results suggest that autistic disorders associated with mTOR pathway hyperactivation may be due to impaired proteome stability associated with the formation of complex dynamic regimes of PSD protein synthesis in response to stimulation of mGluR receptors on the postsynaptic membrane of excitatory synapses on pyramidal hippocampal cells.

Phosphatidic acid - a simple phospholipid with multiple faces.

PubMed

Zegarlińska, Jolanta; Piaścik, Magda; Sikorski, Aleksander F; Czogalla, Aleksander

2018-01-01

Phosphatidic acid (PA) is the simplest glycerophospholipid naturally occurring in living organisms, and even though its content among other cellular lipids is minor, it is drawing more and more attention due to its multiple biological functions. PA is a precursor for other phospholipids, acts as a lipid second messenger and, due to its structural properties, is also a modulator of membrane shape. Although much is known about interaction of PA with its effectors, the molecular mechanisms remain unresolved to a large degree. Throughout many of the well-characterized PA cellular sensors, no conserved binding domain can be recognized. Moreover, not much is known about the cellular dynamics of PA and how it is distributed among subcellular compartments. Remarkably, PA can play distinct roles within each of these compartments. For example, in the nucleus it behaves as a mitogen, influencing gene expression regulation, and in the Golgi membrane it plays a role in membrane trafficking. Here, we discuss how a biophysical experimental approach enabled PA behavior to be described in the context of a lipid bilayer and to what extent various physicochemical conditions may modulate the functional properties of this lipid. Understanding these aspects would help to unravel specific mechanisms of PA-driven membrane transformations and protein recruitment and thus would lead to a clearer picture of the biological role of PA.

Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia.

PubMed

Majumdar, A; Lun, K; Brand, M; Drummond, I A

2000-05-01

Pax genes are important developmental regulators and function at multiple stages of vertebrate kidney organogenesis. In this report, we have used the zebrafish pax2.1 mutant no isthmus to investigate the role for pax2.1 in development of the pronephros. We demonstrate a requirement for pax2.1 in multiple aspects of pronephric development including tubule and duct epithelial differentiation and cloaca morphogenesis. Morphological analysis demonstrates that noi(- )larvae specifically lack pronephric tubules while glomerular cell differentiation is unaffected. In addition, pax2.1 expression in the lateral cells of the pronephric primordium is required to restrict the domains of Wilms' tumor suppressor (wt1) and vascular endothelial growth factor (VEGF) gene expression to medial podocyte progenitors. Ectopic podocyte-specific marker expression in pronephric duct cells correlates with loss of expression of the pronephric tubule and duct-specific markers mAb 3G8 and a Na(+)/K(+) ATPase (&agr;)1 subunit. The results suggest that the failure in pronephric tubule differentiation in noi arises from a patterning defect during differentiation of the pronephric primordium and that mutually inhibitory regulatory interactions play an important role in defining the boundary between glomerular and tubule progenitors in the forming nephron.

Role of vitamin D in regulating the neural stem cells of mouse model with multiple sclerosis.

PubMed

Gu, S-G; Wang, C-J; Zhao, G; Li, G-Y

2015-11-01

Multiple sclerosis (MS) is an autoimmune disease that results with a damaged myelin sheath as a result, there is an impairment of nerve impulse conduction. The medication for MS is able to delay its progression, but complete recovery is impossible. Recent studies with neural stem cells have promising results in treating as well as to recover the damaged nerves, but research on in vivo model system is limited in this aspect. Here we are able to successfully establish an MS mice model by injecting with myelin basic protein and we studied the neural stem cell response in supplement with vitamin D. Through histology we provide strong evidence that the MS pathogenesis is reverted on response to vitamin D. We also identified through immunohistochemistry and western blotting that the vitamin D has the ability to trigger neural stem cells, and thereby it assist in recovery from MS. Further, their roles in preventing as well as delaying the MS development are also proven. The role of vitamin D has also cross checked with the help of tunnel assay. Overall, our results conclude that the lesion associated apoptotic signals are reduced on administrated with vitamin D. The present data help to design a new therapeutic intervention to cure MS.

Innate and adaptive immunity at Mucosal Surfaces of the Female Reproductive Tract: Stratification and Integration of Immune Protection against the Transmission of Sexually Transmitted Infections

PubMed Central

Hickey, DK; Patel, MV; Fahey, JV; Wira, CR

2011-01-01

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract. PMID:21353708

Diffractive centrosymmetric 3D-transmission phase gratings positioned at the image plane of optical systems transform lightlike 4D-WORLD as tunable resonators into spectral metrics...

NASA Astrophysics Data System (ADS)

Lauinger, Norbert

1999-08-01

Diffractive 3D phase gratings of spherical scatterers dense in hexagonal packing geometry represent adaptively tunable 4D-spatiotemporal filters with trichromatic resonance in visible spectrum. They are described in the (lambda) - chromatic and the reciprocal (nu) -aspects by reciprocal geometric translations of the lightlike Pythagoras theorem, and by the direction cosine for double cones. The most elementary resonance condition in the lightlike Pythagoras theorem is given by the transformation of the grating constants gx, gy, gz of the hexagonal 3D grating to (lambda) h1h2h3 equals (lambda) 111 with cos (alpha) equals 0.5. Through normalization of the chromaticity in the von Laue-interferences to (lambda) 111, the (nu) (lambda) equals (lambda) h1h2h3/(lambda) 111-factor of phase velocity becomes the crucial resonance factor, the 'regulating device' of the spatiotemporal interaction between 3D grating and light, space and time. In the reciprocal space equal/unequal weights and times in spectral metrics result at positions of interference maxima defined by hyperbolas and circles. A database becomes built up by optical interference for trichromatic image preprocessing, motion detection in vector space, multiple range data analysis, patchwide multiple correlations in the spatial frequency spectrum, etc.

Broadcast Services. Information Bulletin No. 3.

ERIC Educational Resources Information Center

Federal Communications Commission, Washington, DC.

Radio and television broadcasting is authorized and regulated by the Federal Communications Commission (FCC). Following a brief description of the development of broadcasting, broadcast regulations, and the Commission, this report examines various aspects of the subject pertaining to the fairness doctrine, political broadcasting, advertising, sale…

75 FR 62069 - Federal Acquisition Regulation; Sudan Waiver Process

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

... regarding the offeror's past performance and integrity (see the Past Performance Information Retrieval... aspects of the waiver request for consultations. This information will be provided, in a waiver request....regulations.gov , including any personal and/or business confidential information provided. FOR FURTHER...

48 CFR 2101.301 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. 2101.301 Section... Acquisition Regulations 2101.301 Policy. (a) Procedures, contract clauses, and other aspects of the... the policies and procedures contained in this chapter as implemented and supplemented from time to...

48 CFR 2101.301 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. 2101.301 Section... Acquisition Regulations 2101.301 Policy. (a) Procedures, contract clauses, and other aspects of the... the policies and procedures contained in this chapter as implemented and supplemented from time to...

48 CFR 2101.301 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. 2101.301 Section... Acquisition Regulations 2101.301 Policy. (a) Procedures, contract clauses, and other aspects of the... the policies and procedures contained in this chapter as implemented and supplemented from time to...

48 CFR 36.209 - Construction contracts with architect-engineer firms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... with architect-engineer firms. 36.209 Section 36.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 36.209 Construction contracts with architect-engineer firms. No...

48 CFR 36.209 - Construction contracts with architect-engineer firms.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with architect-engineer firms. 36.209 Section 36.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 36.209 Construction contracts with architect-engineer firms. No...

48 CFR 36.209 - Construction contracts with architect-engineer firms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... with architect-engineer firms. 36.209 Section 36.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 36.209 Construction contracts with architect-engineer firms. No...

48 CFR 36.209 - Construction contracts with architect-engineer firms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... with architect-engineer firms. 36.209 Section 36.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 36.209 Construction contracts with architect-engineer firms. No...

48 CFR 36.209 - Construction contracts with architect-engineer firms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... with architect-engineer firms. 36.209 Section 36.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 36.209 Construction contracts with architect-engineer firms. No...

22 CFR 120.25 - Empowered Official.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... liability and administrative penalties for violating the Arms Export Control Act and the International Traffic in Arms Regulations; and (4) Has the independent authority to: (i) Enquire into any aspect of a...

22 CFR 120.25 - Empowered Official.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... liability and administrative penalties for violating the Arms Export Control Act and the International Traffic in Arms Regulations; and (4) Has the independent authority to: (i) Inquire into any aspect of a...

22 CFR 120.25 - Empowered Official.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... liability and administrative penalties for violating the Arms Export Control Act and the International Traffic in Arms Regulations; and (4) Has the independent authority to: (i) Enquire into any aspect of a...

22 CFR 120.25 - Empowered Official.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... liability and administrative penalties for violating the Arms Export Control Act and the International Traffic in Arms Regulations; and (4) Has the independent authority to: (i) Enquire into any aspect of a...

22 CFR 120.25 - Empowered Official.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS... liability and administrative penalties for violating the Arms Export Control Act and the International Traffic in Arms Regulations; and (4) Has the independent authority to: (i) Enquire into any aspect of a...

Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

PubMed

Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

2017-10-01

The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Photomorphogenic responses to ultraviolet-B light.

PubMed

Jenkins, Gareth I

2017-11-01

Exposure to ultraviolet B (UV-B) light regulates numerous aspects of plant metabolism, morphology and physiology through the differential expression of hundreds of genes. Photomorphogenic responses to UV-B are mediated by the photoreceptor UV RESISTANCE LOCUS8 (UVR8). Considerable progress has been made in understanding UVR8 action: the structural basis of photoreceptor function, how interaction with CONSTITUTIVELY PHOTOMORPHOGENIC 1 initiates signaling and how REPRESSOR OF UV-B PHOTOMORPHOGENESIS proteins negatively regulate UVR8 action. In addition, recent research shows that UVR8 mediates several responses through interaction with other signaling pathways, in particular auxin signaling. Nevertheless, many aspects of UVR8 action remain poorly understood. Most research to date has been undertaken with Arabidopsis, and it is important to explore the functions and regulation of UVR8 in diverse plant species. Furthermore, it is essential to understand how UVR8, and UV-B signaling in general, regulates processes under natural growth conditions. Ultraviolet B regulates the expression of many genes through UVR8-independent pathways, but the activity and importance of these pathways in plants growing in sunlight are poorly understood. © 2017 John Wiley & Sons Ltd.

Preschoolers' Cognitive and Emotional Self-Regulation in Pretend Play: Relations with Executive Functions and Quality of Play

ERIC Educational Resources Information Center

Slot, Pauline Louise; Mulder, Hanna; Verhagen, Josje; Leseman, Paul P. M.

2017-01-01

The preschool period is marked by rapid growth of children's self-regulation and related executive functions. Self-regulation is considered an important aspect of school readiness and is related to academic and social--emotional outcomes in childhood. Pretend play, as part of the early childhood curriculum, is hypothesized to support…

How Cognitive, Metacognitive, Motivational and Emotional Self-Regulation Influence School Performance in Adolescence and Early Adulthood

ERIC Educational Resources Information Center

Bakracevic Vukman, Karin; Licardo, Marta

2010-01-01

This contribution aims to examine how different areas of self-regulation are related to academic achievement in adolescents and young adults. The study involved participants, drawn from following age groups: 14-15, 17-18 and 22-23. In order to get information about cognitive, metacognitive, motivational and emotional aspects of self-regulation,…

Biodiversity simultaneously enhances the production and stability of community biomass, but the effects are independent.

PubMed

Cardinale, Bradley J; Gross, Kevin; Fritschie, Keith; Flombaum, Pedro; Fox, Jeremy W; Rixen, Christian; van Ruijven, Jasper; Reich, Peter B; Scherer-Lorenzen, Michael; Wilsey, Brian J

2013-08-01

To predict the ecological consequences of biodiversity loss, researchers have spent much time and effort quantifying how biological variation affects the magnitude and stability of ecological processes that underlie the functioning of ecosystems. Here we add to this work by looking at how biodiversity jointly impacts two aspects of ecosystem functioning at once: (1) the production of biomass at any single point in time (biomass/area or biomass/ volume), and (2) the stability of biomass production through time (the CV of changes in total community biomass through time). While it is often assumed that biodiversity simultaneously enhances both of these aspects of ecosystem functioning, the joint distribution of data describing how species richness regulates productivity and stability has yet to be quantified. Furthermore, analyses have yet to examine how diversity effects on production covary with diversity effects on stability. To overcome these two gaps, we reanalyzed the data from 34 experiments that have manipulated the richness of terrestrial plants or aquatic algae and measured how this aspect of biodiversity affects community biomass at multiple time points. Our reanalysis confirms that biodiversity does indeed simultaneously enhance both the production and stability of biomass in experimental systems, and this is broadly true for terrestrial and aquatic primary producers. However, the strength of diversity effects on biomass production is independent of diversity effects on temporal stability. The independence of effect sizes leads to two important conclusions. First, while it may be generally true that biodiversity enhances both productivity and stability, it is also true that the highest levels of productivity in a diverse community are not associated with the highest levels of stability. Thus, on average, diversity does not maximize the various aspects of ecosystem functioning we might wish to achieve in conservation and management. Second, knowing how biodiversity affects productivity gives no information about how diversity affects stability (or vice versa). Therefore, to predict the ecological changes that occur in ecosystems after extinction, we will need to develop separate mechanistic models for each independent aspect of ecosystem functioning.

Self-regulated learning of basic arithmetic skills: a longitudinal study.

PubMed

Throndsen, Inger

2011-12-01

Several studies have examined young primary school children's use of strategies when solving simple addition and subtraction problems. Most of these studies have investigated students' strategy use as if they were isolated processes. To date, we have little knowledge about how math strategies in young students are related to other important aspects in self-regulated learning. The main purpose of this study was to examine relations between young primary school children's basic mathematical skills and their use of math strategies, their metacognitive competence and motivational beliefs, and to investigate how students with basic mathematics skills at various levels differ in respect to the different self-regulation components. The participants were comprised of 27 Year 2 students, all from the same class. The data were collected in three stages (autumn Year 2, spring Year 2, and autumn Year 3). The children's arithmetic skills were measured by age relevant tests, while strategy use, metacognitive competence, and motivational beliefs were assessed through individual interviews. The participants were divided into three performance groups; very good students, good students, and not-so-good students. Analyses revealed that young primary school children at different levels of basic mathematics skill may differ in several important aspects of self-regulated learning. Analyses revealed that a good performance in addition and subtraction was related not only to the children's use of advanced mathematics strategies, but also to domain-specific metacognitive competence, ability attribution for success, effort attribution for failure, and high perceived self-efficacy when using specific strategies. The results indicate that instructional efforts to facilitate self-regulated learning of basic arithmetic skills should address cognitive, metacognitive, and motivational aspects of self-regulation. This is particularly important for low-performing students. ©2010 The British Psychological Society.

Recognition of aspect-dependent three-dimensional objects by an echolocating Atlantic bottlenose dolphin.

PubMed

Helweg, D A; Roitblat, H L; Nachtigall, P E; Hautus, M J

1996-01-01

We examined the ability of a bottlenose dolphin (Tursiops truncatus) to recognize aspect-dependent objects using echolocation. An aspect-dependent object such as a cube produces acoustically different echoes at different angles relative to the echolocation signal. The dolphin recognized the objects even though the objects were free to rotate and sway. A linear discriminant analysis and nearest centroid classifier could classify the objects using average amplitude, center frequency, and bandwidth of object echoes. The results show that dolphins can use varying acoustic properties to recognize constant objects and suggest that aspect-independent representations may be formed by combining information gleaned from multiple echoes.

Protein function prediction--the power of multiplicity.

PubMed

Rentzsch, Robert; Orengo, Christine A

2009-04-01

Advances in experimental and computational methods have quietly ushered in a new era in protein function annotation. This 'age of multiplicity' is marked by the notion that only the use of multiple tools, multiple evidence and considering the multiple aspects of function can give us the broad picture that 21st century biology will need to link and alter micro- and macroscopic phenotypes. It might also help us to undo past mistakes by removing errors from our databases and prevent us from producing more. On the downside, multiplicity is often confusing. We therefore systematically review methods and resources for automated protein function prediction, looking at individual (biochemical) and contextual (network) functions, respectively.

Medicolegal issues in multiple pregnancy.

PubMed

Gersell, Deborah J

2007-02-01

Any discussion of multiple pregnancy figures prominently in the consideration of the medicolegal aspects of placental pathology. Multiple gestations are common and becoming more so with assisted reproductive techniques, and multiples are associated with a disproportionate share of complications that may result in disputes over quality of care. Higher rates of intrauterine growth retardation, prematurity, stillbirth, morbidity, mortality, cerebral palsy, anomalous development, and malformation as compared with singletons are well documented in multiple pregnancy and should be anticipated. Monochorionic placentation and complications of vascular anastomosis are important factors contributing to poor outcome. Other factors, although occurring in all gestations, are relevant because they are more common in multiple gestations.

Exploring Metaskills of Knowledge-Creating Inquiry in Higher Education

ERIC Educational Resources Information Center

Muukkonen, Hanni; Lakkala, Minna

2009-01-01

The skills of knowledge-creating inquiry are explored as a challenge for higher education. The knowledge-creation approach to learning provides a theoretical tool for addressing them: In addition to the individual and social aspects in regulation of inquiry, the knowledge-creation approach focuses on aspects related to advancing shared objects of…

41 CFR 302-2.8 - When must I complete all aspects my relocation?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 4 2013-07-01 2012-07-01 true When must I complete all aspects my relocation? 302-2.8 Section 302-2.8 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time...

41 CFR 302-2.8 - When must I complete all aspects my relocation?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 41 Public Contracts and Property Management 4 2014-07-01 2014-07-01 false When must I complete all aspects my relocation? 302-2.8 Section 302-2.8 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time...

41 CFR 302-2.8 - When must I complete all aspects my relocation?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false When must I complete all aspects my relocation? 302-2.8 Section 302-2.8 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time...

41 CFR 302-2.8 - When must I complete all aspects my relocation?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 41 Public Contracts and Property Management 4 2011-07-01 2011-07-01 false When must I complete all aspects my relocation? 302-2.8 Section 302-2.8 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time...

41 CFR 302-2.8 - When must I complete all aspects my relocation?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false When must I complete all aspects my relocation? 302-2.8 Section 302-2.8 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time...

Small RNA biology is systems biology.

PubMed

Jost, Daniel; Nowojewski, Andrzej; Levine, Erel

2011-01-01

During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.

DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. G.

2016-01-01

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., ‘correct’ (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes. PMID:27672359

DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees.

PubMed

Biergans, Stephanie D; Claudianos, Charles; Reinhard, Judith; Galizia, C G

2016-01-01

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes.

The targets of curcumin.

PubMed

Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

2011-03-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

Borrelia burgdorferi infection induces lipid mediator production during Lyme arthritis.

PubMed

Brown, Charles R; Dennis, Edward A

2017-10-01

Experimental Lyme arthritis provides a mouse model for exploring the development of pathology following infection of C3H mice with Borrelia burgdorferi. Infected mice develop a reliable inflammatory arthritis of the ankle joint with severity that typically peaks around two to three weeks post-infection and then undergoes spontaneous resolution. This makes experimental Lyme arthritis an excellent model for investigating the mechanisms that drive both the development and resolution phases of inflammatory disease. Eicosanoids are powerful lipid mediators of inflammation and are known to regulate multiple aspects of inflammatory processes. While much is known about the role of eicosanoids in regulating immune responses during autoimmune disease and cancer, relatively little is known about their role during bacterial infection. In this review, we discuss the role of eicosanoid biosynthetic pathways in mediating inflammatory responses during bacterial infection using experimental Lyme arthritis as a model system. We point out the critical role eicosanoids play in disease development and highlight surprising differences between sterile autoimmune responses and those occurring in response to bacterial infection. These differences should be kept in mind when designing therapies and treatments for inflammatory diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Effects of bisphenol A, an environmental endocrine disruptor, on the endogenous hormones of plants.

PubMed

Wang, Shengman; Wang, Lihong; Hua, Weiqi; Zhou, Min; Wang, Qingqing; Zhou, Qing; Huang, Xiaohua

2015-11-01

Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical in the environment that exerts potential harm to plants. Phytohormones play important roles both in regulating multiple aspects of plant growth and in plants' responses to environmental stresses. But how BPA affects plant growth by regulating endogenous hormones remains poorly understood. Here, we found that treatment with 1.5 mg L(-1) BPA improved the growth of soybean seedlings, companied by increases in the contents of indole-3-acetic acid (IAA) and zeatin (ZT), and decreases in the ratios of abscisic acid (ABA)/IAA, ABA/gibberellic acid (GA), ABA/ZT, ethylene (ETH)/GA, ETH/IAA, and ETH/ZT. Treatment with higher concentrations of BPA (from 3 to 96 mg L(-1)) inhibited the growth of soybean seedlings, meanwhile, decreased the contents of IAA, GA, ZT, and ETH, and increased the content of ABA and the ratios of ABA/IAA, ABA/GA, ABA/ZT, ETH/GA, ETH/IAA, and ETH/ZT. The increases in the ratios of growth and stress hormones were correlated with the increase in the BPA content of the roots. Thus, BPA could affect plant growth through changing the levels of single endogenous hormone and the ratios of growth and stress hormones in the roots because of BPA absorption by the roots.

Queen pheromones: The chemical crown governing insect social life.

PubMed

Holman, Luke

2010-11-01

Group-living species produce signals that alter the behavior and even the physiology of their social partners. Social insects possess especially sophisticated chemical communication systems that govern every aspect of colony life, including the defining feature of eusociality: reproductive division of labor. Current evidence hints at the central importance of queen pheromones, but progress has been hindered by the fact that such pheromones have only been isolated in honeybees. In a pair of papers on the ant Lasius niger, we identified and investigated a queen pheromone regulating worker sterility. The cuticular hydrocarbon 3-methylhentriacontane (3-MeC(31)) is correlated with queen maturity and fecundity and workers are also more likely to execute surplus queens that have low amounts of this chemical. Experiments with synthetic 3-MeC(31) found that it inhibits ovarian development in queenless workers and lowers worker aggression towards objects coated with it. Production of 3-MeC(31) by queens was depressed by an experimental immune challenge, and the same chemical was abundant on queenlaid eggs, suggesting that the workers' responses to the queen are conditional on her health and fecundity. Together with other studies, these results indicate that queen pheromones are honest signals of quality that simultaneously regulate multiple social behaviors.

Metastasis Suppressor Genes: At the Interface Between the Environment and Tumor Cell Growth

PubMed Central

Hurst, Douglas R.; Welch, Danny R.

2013-01-01

The molecular mechanisms and genetic programs required for cancer metastasis are sometimes overlapping, but components are clearly distinct from those promoting growth of a primary tumor. Every sequential, rate-limiting step in the sequence of events leading to metastasis requires coordinated expression of multiple genes, necessary signaling events, and favorable environmental conditions or the ability to escape negative selection pressures. Metastasis suppressors are molecules that inhibit the process of metastasis without preventing growth of the primary tumor. The cellular processes regulated by metastasis suppressors are diverse and function at every step in the metastatic cascade. As we gain knowledge into the molecular mechanisms of metastasis suppressors and cofactors with which they interact, we learn more about the process, including appreciation that some are potential targets for therapy of metastasis, the most lethal aspect of cancer. Until now, metastasis suppressors have been described largely by their function. With greater appreciation of their biochemical mechanisms of action, the importance of context is increasingly recognized especially since tumor cells exist in myriad microenvironments. In this review, we assemble the evidence that selected molecules are indeed suppressors of metastasis, collate the data defining the biochemical mechanisms of action, and glean insights regarding how metastasis suppressors regulate tumor cell communication to–from microenvironments. PMID:21199781

Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid-Activated Receptor

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

Kruse, Schoen W; Suino-Powell, Kelly; Zhou, X Edward

2010-01-12

The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 {angstrom} crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix {alpha}10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site,more » thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation.« less

Targets of curcumin

PubMed Central

Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

2010-01-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

Suppressor of gamma response 1 (SOG1) encodes a putative transcription factor governing multiple responses to DNA damage

PubMed Central

Yoshiyama, Kaoru; Conklin, Phillip A.; Huefner, Neil D.; Britt, Anne B.

2009-01-01

The Arabidopsis sog1-1 (suppressor of gamma response) mutant was originally isolated as a second-site suppressor of the radiosensitive phenotype of seeds defective in the repair endonuclease XPF. Here, we report that SOG1 encodes a putative transcription factor. This gene is a member of the NAC domain [petunia NAM (no apical meristem) and Arabidopsis ATAF1, 2 and CUC2] family (a family of proteins unique to land plants). Hundreds of genes are normally up-regulated in Arabidopsis within an hour of treatment with ionizing radiation; the induction of these genes requires the damage response protein kinase ATM, but not the related kinase ATR. Here, we find that SOG1 is also required for this transcriptional up-regulation. In contrast, the SOG1-dependent checkpoint response observed in xpf mutant seeds requires ATR, but does not require ATM. Thus, phenotype of the sog1-1 mutant mimics aspects of the phenotypes of both atr and atm mutants in Arabidopsis, suggesting that SOG1 participates in pathways governed by both of these sensor kinases. We propose that, in plants, signals related to genomic stress are processed through a single, central transcription factor, SOG1. PMID:19549833

Genetics of Vitiligo

PubMed Central

Spritz, Richard; Andersen, Genevieve

2016-01-01

Synopsis Vitiligo is “complex disorder” (also termed polygenic and multifactorial), reflecting simultaneous contributions of multiple genetic risk factors and environmental triggers. Large-scale genome-wide association studies, principally in European-derived whites and in Chinese, have discovered approximately 50 different genetic loci that contribute to vitiligo risk, some of which also contribute to other autoimmune diseases that are epidemiologically associated with vitiligo. At many of these vitiligo susceptibility loci the corresponding relevant genes have now been identified, and for some of these genes the specific DNA sequence variants that contribute to vitiligo risk are also now known. A large fraction of these genes encode proteins involved in immune regulation, a number of others play roles in cellular apoptosis, and still others are involved in regulating functions of melanocytes. For this last group, there appears to be an opposite relationship between susceptibility to vitiligo and susceptibility to melanoma, suggesting that vitiligo may engage a normal mechanism of immune surveillance for melanoma. While many of the specific biologic mechanisms through which these genetic factors operate to cause vitiligo remain to be elucidated, it is now clear that vitiligo is an autoimmune disease involving a complex relationship between programming and function of the immune system, aspects of the melanocyte autoimmune target, and dysregulation of the immune response. PMID:28317533

Developing mechanisms of self-regulation.

PubMed

Posne, M I; Rothbart, M K

2000-01-01

Child development involves both reactive and self-regulatory mechanisms that children develop in conjunction with social norms. A half-century of research has uncovered aspects of the physical basis of attentional networks that produce regulation, and has given us some knowledge of how the social environment may alter them. In this paper, we discuss six forms of developmental plasticity related to aspects of attention. We then focus on effortful or executive aspects of attention, reviewing research on temperamental individual differences and important pathways to normal and pathological development. Pathologies of development may arise when regulatory and reactive systems fail to reach the balance that allows for both self-expression and socially acceptable behavior. It remains a challenge for our society during the next millennium to obtain the information necessary to design systems that allow a successful balance to be realized by the largest possible number of children.

Self-Regulated Learning Strategies in Relation with Statistics Anxiety

ERIC Educational Resources Information Center

Kesici, Sahin; Baloglu, Mustafa; Deniz, M. Engin

2011-01-01

Dealing with students' attitudinal problems related to statistics is an important aspect of statistics instruction. Employing the appropriate learning strategies may have a relationship with anxiety during the process of statistics learning. Thus, the present study investigated multivariate relationships between self-regulated learning strategies…

Linguistic Aspects of Legal Language.

ERIC Educational Resources Information Center

Crandall, JoAnn; Charrow, Veda R.

Efforts to simplify language used in consumer documents come from the consumer movement and a public disillusioned with big business and government. Even before President Carter's 1978 executive order mandating simplification in government regulations, some agencies were revising regulations for clarity. However, these efforts were based on too…

77 FR 60660 - Proposed Establishment Class E Airspace; Kasigluk, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... your comments. You may also submit comments through the Internet at http://www.regulations.gov . FOR..., aeronautical, economic, environmental, and energy-related aspects of the proposal. Communications should...). You may also submit comments through the Internet at http://www.regulations.gov . Commenters wishing...

Wellbeing: causes and consequences of emotion regulation in work settings.

PubMed

Zammuner, V L; Galli, C

2005-10-01

Emotion regulation processes are a crucial aspect of the working role in jobs which require employee-customer interactions: What kinds of regulation processes are activated, with what frequency, and what are their correlates and consequences are important aspects to consider because of their potential implications for the well-being of individuals. To investigate these issues, a set of studies was carried out with Italian workers (N=769) performing service jobs in different sectors. Job-related, socio-demographic, and individual psychological variables were taken into account. The results confirmed the hypothesis that in service job-roles emotional labour (EL) is a component whose negative and positive implications for employees' well-being need to be considered. Emotional labour, embedded in a net of relationships with such job variables as frequency and duration of client-interaction, can result in high psychological costs for service workers. In particular, surface acting regulation was found to have a personal cost, indexed by the burnout dimensions of emotional exhaustion and depersonalization.

Wait-Time and Multiple Representation Levels in Chemistry Lessons

ERIC Educational Resources Information Center

Li, Winnie Sim Siew; Arshad, Mohammad Yusof

2014-01-01

Wait-time is an important aspect in a teaching and learning process, especially after the teacher has posed questions to students, as it is one of the factors in determining quality of students' responses. This article describes the practices of wait-time one after teacher's questions at multiple representation levels among twenty three chemistry…

Multiple evanescent white dot syndrome (MEWDS).

PubMed

Leys, A; Leys, M; Jonckheere, P; De Laey, J J

1990-01-01

We describe the course of MEWDS (multiple evanescent white dot syndrome) in 2 young females. The first patient presented with a very pronounced macular edema. The second patient had merely optic disc edema. Both had an enlargement of the blind spot, which normalized later. Only the granular aspect of the fovea persisted in the involved eye.

Using focused plenoptic cameras for rich image capture.

PubMed

Georgiev, T; Lumsdaine, A; Chunev, G

2011-01-01

This approach uses a focused plenoptic camera to capture the plenoptic function's rich "non 3D" structure. It employs two techniques. The first simultaneously captures multiple exposures (or other aspects) based on a microlens array having an interleaved set of different filters. The second places multiple filters at the main lens aperture.

Insidious Incentives: A Critical Exercise to Explore Knowing, Context, and Multiple Views

ERIC Educational Resources Information Center

Stepanovich, Paul L.; Hopkins, Pamela J.; Stark, Ernest

2017-01-01

Critical thinking requires that we dig beneath the surface of organizational issues to explore multiple views, context, and aspects of knowing. In this exercise, students explore these deeper issues with the question: Are incentives effective? A hypothetical case unfolds to show how two consulting groups can arrive at very different…

Children's Comprehension Monitoring of Multiple Situational Dimensions of a Narrative

ERIC Educational Resources Information Center

Wassenburg, Stephanie I.; Beker, Katinka; van den Broek, Paul; van der Schoot, Menno

2015-01-01

Narratives typically consist of information on multiple aspects of a situation. In order to successfully create a coherent representation of the described situation, readers are required to monitor all these situational dimensions during reading. However, little is known about whether these dimensions differ in the ease with which they can be…

Using Multiple Representations to Promote Grade 11 Students' Scientific Understanding of the Particle Theory of Matter

ERIC Educational Resources Information Center

Adadan, Emine

2013-01-01

This study explored two groups of Grade 11 (age 16-17) students' conceptual understandings about aspects of particle theory before, immediately after, and 3 months after instruction with multiple representations (IMR) and instruction with verbal representations (IVR). Data sources included open-ended questionnaires, interviews, and student…