NASA's current activities in free space optical communications

NASA Astrophysics Data System (ADS)

Edwards, Bernard L.

2017-11-01

NASA and other space agencies around the world are currently developing free space optical communication systems for both space-to-ground links and space-to-space links. This paper provides an overview of NASA's current activities in free space optical communications with a focus on Near Earth applications. Activities to be discussed include the Lunar Laser Communication Demonstration, the Laser Communications Relay Demonstration, and the commercialization of the underlying technology. The paper will also briefly discuss ongoing efforts and studies for Deep Space optical communications. Finally the paper will discuss the development of international optical communication standards within the Consultative Committee for Space Data Systems.

Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

PubMed

Endendijk, Joyce J; Beltz, Adriene M; McHale, Susan M; Bryk, Kristina; Berenbaum, Sheri A

2016-10-01

Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.

Comparison of FDMA and CDMA for second generation land-mobile satellite communications

NASA Technical Reports Server (NTRS)

Yongacoglu, A.; Lyons, R. G.; Mazur, B. A.

1990-01-01

Code Division Multiple Access (CDMA) and Frequency Division Multiple Access (FDMA) (both analog and digital) systems capacities are compared on the basis of identical link availabilities and physical propagation models. Parameters are optimized for a bandwidth limited, multibeam environment. For CDMA, the benefits of voice activated carriers, antenna discrimination, polarization reuse, return link power control and multipath suppression are included in the analysis. For FDMA, the advantages of bandwidth efficient modulation/coding combinations, voice activated carriers, polarization reuse, beam placement, and frequency staggering were taken into account.

Neurobiological correlates of cognitions in fear and anxiety: a cognitive-neurobiological information-processing model.

PubMed

Hofmann, Stefan G; Ellard, Kristen K; Siegle, Greg J

2012-01-01

We review likely neurobiological substrates of cognitions related to fear and anxiety. Cognitive processes are linked to abnormal early activity reflecting hypervigilance in subcortical networks involving the amygdala, hippocampus, and insular cortex, and later recruitment of cortical regulatory resources, including activation of the anterior cingulate cortex and prefrontal cortex to implement avoidant response strategies. Based on this evidence, we present a cognitive-neurobiological information-processing model of fear and anxiety, linking distinct brain structures to specific stages of information processing of perceived threat.

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

PubMed Central

Beurel, E; Jope, R S

2014-01-01

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

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

PubMed

Beurel, E; Jope, R S

2014-12-16

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

Brokering Adult and Continuing Education through Unions and Small Businesses in the Lehigh Valley. "The Link Program".

ERIC Educational Resources Information Center

Schuehler, Susan S.; And Others

A project entitled the LINK Program was undertaken to develop a model program of educational brokering through union locals and small businesses in the Lehigh Valley in Pennsylvania. Included among the major project activities were the following: contacting unions, presenting a model program to them, and soliciting support from union officials;…

Outcome measurement of hand function following mirror therapy for stroke rehabilitation: A systematic review.

PubMed

Cantero-Téllez, Raquel; Naughton, Nancy; Algar, Lori; Valdes, Kristin

2018-02-28

Systematic review. Mirror therapy is a treatment used to address hand function following a stroke. Measurement of outcomes using appropriate assessment tools is crucial; however, many assessment options exist. The purpose of this study is to systematically review outcome measures that are used to assess hand function following mirror therapy after stroke and, in addition, to identify the psychometric and descriptive properties of the included measures and through the linking process determine if the outcome measures are representative of the International Classification of Functioning, Disability and Health (ICF). Following a comprehensive literature search, outcome measures used in the included studies were linked to the ICF and analyzed based on descriptive information and psychometric properties. Eleven studies met inclusion criteria and included 24 different assessment tools to measure hand or upper limb function. Most outcome measures used in the selected studies (63%) were rated by the evaluating therapist. Thirteen outcome measures (54%) linked to the ICF body function category and 10 measures (42%) linked to activities and participation. One outcome measure was linked to not defined, and all other ICF categories were not represented. A majority of outcome measures have been assessed for validity, reliability, and responsiveness, but responsiveness was the least investigated psychometric property. Current studies on mirror therapy after stroke are not consistent in the assessment tools used to determine hand function. Understanding of study outcomes requires analysis of the assessment tools. The outcome measures used in the included studies are not representative of personal and environmental factors, but tools linking to body functions and activities and participations provide important information on functional outcome. Integrating a combination of measures that are psychometrically sound and reflective of the ICF should be considered for assessment of hand function after mirror therapy after stroke. Copyright © 2018 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Escape from harm: linking affective vision and motor responses during active avoidance

PubMed Central

Keil, Andreas

2014-01-01

When organisms confront unpleasant objects in their natural environments, they engage in behaviors that allow them to avoid aversive outcomes. Here, we linked visual processing of threat to its behavioral consequences by including a motor response that terminated exposure to an aversive event. Dense-array steady-state visual evoked potentials were recorded in response to conditioned threat and safety signals viewed in active or passive behavioral contexts. The amplitude of neuronal responses in visual cortex increased additively, as a function of emotional value and action relevance. The gain in local cortical population activity for threat relative to safety cues persisted when aversive reinforcement was behaviorally terminated, suggesting a lingering emotionally based response amplification within the visual system. Distinct patterns of long-range neural synchrony emerged between the visual cortex and extravisual regions. Increased coupling between visual and higher-order structures was observed specifically during active perception of threat, consistent with a reorganization of neuronal populations involved in linking sensory processing to action preparation. PMID:24493849

Roller Coaster Science.

ERIC Educational Resources Information Center

Sumners, Carolyn; Jones, Howard L.

1983-01-01

Discusses the science of roller coasters, relating gravity, potential/kinetic energy, inertia, and centripetal force to the various parts of the ride, providing tips on linking classroom discussions to field trips. Includes sample student activity sheet and source for additional units using amusement park rides/playground activities to teach…

Linking Complexity with Cultural Historical Activity Theory

ERIC Educational Resources Information Center

McMurtry, Angus

2006-01-01

This paper explores the similarities and differences between complexity science's and cultural-historical activity theory's understandings of human learning. Notable similarities include their emphasis on the importance of social systems or collectives in understanding human knowledge and practices, as well as their characterization of systems'…

Linking JNK Activity to the DNA Damage Response

PubMed Central

Picco, Vincent

2013-01-01

The activity of c-Jun N-terminal kinase (JNK) was initially described as ultraviolet- and oncogene-induced kinase activity on c-Jun. Shortly after this initial discovery, JNK activation was reported for a wider variety of DNA-damaging agents, including γ-irradiation and chemotherapeutic compounds. As the DNA damage response mechanisms were progressively uncovered, the mechanisms governing the activation of JNK upon genotoxic stresses became better understood. In particular, a recent set of papers links the physical breakage in DNA, the activation of the transcription factor NF-κB, the secretion of TNF-α, and an autocrine activation of the JNK pathway. In this review, we will focus on the pathway that is initiated by a physical break in the DNA helix, leading to JNK activation and the resultant cellular consequences. The implications of these findings will be discussed in the context of cancer therapy with DNA-damaging agents. PMID:24349633

Melanogenesis inhibitory activity of a 7-O-9'-linked neolignan from Alpinia galanga fruit.

PubMed

Manse, Yoshiaki; Ninomiya, Kiyofumi; Nishi, Ryosuke; Kamei, Iyori; Katsuyama, Yushi; Imagawa, Takahito; Chaipech, Saowanee; Muraoka, Osamu; Morikawa, Toshio

2016-12-01

An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC 50 =7.3μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9'-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 phenylpropanoids (2-15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC 50 =2.5μM), 1'S-1'-acetoxychavicol acetate (2, 5.0μM), and 1'S-1'-acetoxyeugenol acetate (3, 5.6μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1'-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9'-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1' (IC 50 =1.9μM) and 2' (4.5μM)] and racemic mixtures [(±)-1 (2.2μM) and (±)-2 (4.4μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1-3 inhibited tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathways from Religion to Health: Mediation by Psychosocial and Lifestyle Mechanisms

PubMed Central

Morton, Kelly R.; Lee, Jerry W.; Martin, Leslie R.

2016-01-01

Religiosity, often measured as attendance at religious services, is linked to better physical health and longevity though the mechanisms linking the two are debated. Potential explanations include: a healthier lifestyle, increased social support from congregational members, and/or more positive emotions. Thus far, these mechanisms have not been tested simultaneously in a single model though they likely operate synergistically. We test this model predicting all-cause mortality in Seventh-day Adventists, a denomination that explicitly promotes a healthy lifestyle. This allows the more explicit health behaviors linked to the religious doctrine (e.g., healthy diet) to be compared with other mechanisms not specific to religious doctrine (e.g., social support and positive emotions). Finally, this study examines both Church Activity (including worship attendance and church responsibilities) and Religious Engagement (coping, importance, and intrinsic beliefs). Religious Engagement is more is more inner-process focused (vs. activity-based) and less likely to be confounded with age and its associated functional status limitations, although it should be noted that age is controlled in the present study. The findings suggest that Religious Engagement and Church Activity operate through the mediators of health behavior, emotion, and social support to decrease mortality risk. All links between Religious Engagement and mortality are positive but indirect through positive Religious Support, Emotionality, and lifestyle mediators. However, Church Activity has a direct positive effect on mortality as well as indirect effects through, Religious Support, Emotionality, and lifestyle mediators (diet and exercise). The models were invariant by gender and for both Blacks and Whites. PMID:28435513

Pathways from Religion to Health: Mediation by Psychosocial and Lifestyle Mechanisms.

PubMed

Morton, Kelly R; Lee, Jerry W; Martin, Leslie R

2017-02-01

Religiosity, often measured as attendance at religious services, is linked to better physical health and longevity though the mechanisms linking the two are debated. Potential explanations include: a healthier lifestyle, increased social support from congregational members, and/or more positive emotions. Thus far, these mechanisms have not been tested simultaneously in a single model though they likely operate synergistically. We test this model predicting all-cause mortality in Seventh-day Adventists, a denomination that explicitly promotes a healthy lifestyle. This allows the more explicit health behaviors linked to the religious doctrine (e.g., healthy diet) to be compared with other mechanisms not specific to religious doctrine (e.g., social support and positive emotions). Finally, this study examines both Church Activity (including worship attendance and church responsibilities) and Religious Engagement (coping, importance, and intrinsic beliefs). Religious Engagement is more is more inner-process focused (vs. activity-based) and less likely to be confounded with age and its associated functional status limitations, although it should be noted that age is controlled in the present study. The findings suggest that Religious Engagement and Church Activity operate through the mediators of health behavior, emotion, and social support to decrease mortality risk. All links between Religious Engagement and mortality are positive but indirect through positive Religious Support, Emotionality, and lifestyle mediators. However, Church Activity has a direct positive effect on mortality as well as indirect effects through, Religious Support, Emotionality, and lifestyle mediators (diet and exercise). The models were invariant by gender and for both Blacks and Whites.

Physics of magnetospheric boundary layers

NASA Technical Reports Server (NTRS)

Cairns, Iver H.

1995-01-01

This final report was concerned with the ideas that: (1) magnetospheric boundary layers link disparate regions of the magnetosphere-solar wind system together; and (2) global behavior of the magnetosphere can be understood only by understanding its internal linking mechanisms and those with the solar wind. The research project involved simultaneous research on the global-, meso-, and micro-scale physics of the magnetosphere and its boundary layers, which included the bow shock, the magnetosheath, the plasma sheet boundary layer, and the ionosphere. Analytic, numerical, and simulation projects were performed on these subjects, as well as comparisons of theoretical results with observational data. Other related activity included in the research included: (1) prediction of geomagnetic activity; (2) global MHD (magnetohydrodynamic) simulations; (3) Alfven resonance heating; and (4) Critical Ionization Velocity (CIV) effect. In the appendixes are list of personnel involved, list of papers published; and reprints or photocopies of papers produced for this report.

Recycled Art: Create Puppets Using Recycled Objects.

ERIC Educational Resources Information Center

Clearing, 2003

2003-01-01

Presents an activity from "Healthy Foods from Healthy Soils" for making puppets using recycled food packaging materials. Includes background information, materials, instructions, literature links, resources, and benchmarks. (NB)

Understanding Threshold Effects of Organized Activity Involvement in Adolescents: Sex and Family Income as Moderators

ERIC Educational Resources Information Center

Randall, Edin T.; Bohnert, Amy M.

2012-01-01

The current study examined the curvilinear links between involvement in organized activities (OA) and sport activities specifically and various indicators of psychological and social development. Participants included 150 9th and 10th graders (57% females) from an urban, selective-enrollment high school. Eligibility for admission is based on city…

Activities to Grow On: Friendship Links.

ERIC Educational Resources Information Center

Newman, Joan; And Others

1992-01-01

Presents a collection of Valentine's Day-related kindergarten activities designed to help friendships grow. They include making personalized place mats as a group, creating decorated mail pouches, building heart shaped bird feeders, reading a book about friendly secrets and surprises, and decorating hearts with compliments about each student. (SM)

Intergenerational Service Learning with Elders: Multidisciplinary Activities and Outcomes

ERIC Educational Resources Information Center

Krout, John A.; Bergman, Elizabeth; Bianconi, Penny; Caldwell, Kathryn; Dorsey, Julie; Durnford, Susan; Erickson, Mary Ann; Lapp, Julia; Monroe, Janice Elich; Pogorzala, Christine; Taves, Jessica Valdez

2010-01-01

This article provides an overview of the activities included in a 3-year, multidisciplinary, intergenerational service-learning project conducted as part of a Foundation for Long-Term Care Service Learning: Linking Three Generations grant. Courses from four departments (gerontology, psychology, occupational therapy, and health promotion and…

Intergenerational Pathways Linking Childhood Sexual Abuse to HIV Risk Among Women

PubMed Central

Cavanaugh, Courtenay E.; Classen, Catherine C.

2009-01-01

Childhood sexual abuse is prevalent among women and it has been linked to a number of problems affecting women's health and functioning including women's parenting practices. Another body of literature has linked specific maternal parenting practices to daughters’ HIV risk, including mother-daughter sex communication, monitoring/knowledge about daughters’ activities, mother-daughter relationship quality, attitudes towards sex, and modeling of sexual values. This paper reviews and links these two bodies of literature to indicate how maternal histories of childhood sexual abuse may compromise mothers’ parenting practices, which may in turn impact daughters’ HIV risk. We also build upon Malow and colleagues’ model (2006) of the associations between childhood sexual abuse and HIV risk to present a model indicating potential intergenerational pathways between childhood sexual abuse and HIV risk among women. The literature supporting this model and gaps in the literature are described. PMID:19333846

Tools to investigate how interprofessional education activities link to competencies.

PubMed

West, Courtney; Veronin, Michael; Landry, Karen; Kurz, Terri; Watzak, Bree; Quiram, Barbara; Graham, Lori

2015-01-01

Integrating interprofessional education (IPE) activities and curricular components in health professions education has been emphasized recently by the inclusion of accreditation standards across disciplines. The Interprofessional Education Collaborative (IPEC) established IPE competencies in 2009, but evaluating how activities link to competencies has not been investigated in depth. The purpose of this project is to investigate how well two IPE activities align with IPEC competencies. To evaluate how our IPE activities met IPEC competencies, we developed a checklist and an observation instrument. A brief description of each is included as well as the outcomes. We analyzed Disaster Day, a simulation exercise that includes participants from Nursing, Medicine, and Pharmacy, and Interprofessional Healthcare Ethics (IPHCE), a course that introduced medical, nursing, and pharmacy students to ethical issues using didactic sessions and case discussions. While both activities appeared to facilitate the development of IPE competencies, Disaster Day aligned more with IPEC competencies than the IPHCE course and appears to be a more comprehensive way of addressing IPEC competencies. However, offering one IPE activity or curricular element is not sufficient. Having several IPE options available, utilizing the tools we developed to map the IPE curriculum and evaluating competency coverage is recommended.

Chemoprevention activity of 25-hydroxyvitamin D in the MMTV-PyMT mouse model of breast cancer

USDA-ARS?s Scientific Manuscript database

Development of oncologic conditions is often linked to inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Current effective vitamin D analogs including the naturally occurring active metabol...

The Ideological Basis of Teacher Organization or Why We Do What We Do.

ERIC Educational Resources Information Center

Sutton, James H.

An attempt to explain the behavior of local, state and national teacher organizations by reference to the ideological basis for their activities, this paper links professionalism and excellence to previous organizational activity and demonstrates their continuity. Significant topics include the professionalization of teaching amid societal…

Curriculum Counselor.

ERIC Educational Resources Information Center

Doty, Robert

1995-01-01

Features Internet sites that are sources for lesson plans, materials, group discussion topics, activities, test questions, computer software, and videos for K-12 education. Resources highlighted include CNN Newsroom, KidLink, and AskERIC. (AEF)

Magnetic Evolution Linked to the Interrelated Activity Complexes Involving Transequatorial Coronal Holes

NASA Astrophysics Data System (ADS)

Gutiérrez, Heidy; Taliashvili, Lela; Lazarian, Alexandre

2018-06-01

We studied a magnetic evolution linked to a cadence of interrelated activities developed in a large solar region during Carrington rotations, CRs 2119 - 2121, based on multi-wavelength and multi-spacecraft observations. Three coronal holes (CHs), two transequatorial and one isolated, eight filaments and some active regions were distributed closely in the region. Every of these filaments partial and/or complete eruption was linked to a Coronal Mass Ejection (CME) or coronal jet. We found different types of interrelated activities: eruptions of three pairs of interrelated filaments close to a CH and eruptions of two filaments close to the active region and CH. Some indicators of the magnetic reconnection were observed frequently during the pre- as well as post-filament eruptions. Additionally, post-filament eruption and/or post-CME processes show their implication in the evolution of nearby CHs and newly formed transient CHs or dimming regions, including a new CH formation. We discussed the small- and large-scale magnetic reconfigurations associated with these interrelated activity complexes, the ones involving long-lived transequatorial CHs, and their possible implication in the evolution of the global solar magnetic field, especially with the starting processes of quadruple configuration and polarity reversal of the solar cycle 24.

On the link between media coverage of anorexia and pro-anorexic practices on the web.

PubMed

Yom-Tov, Elad; Boyd, Danah M

2014-03-01

Links between media portrayals of celebrities and participation in activities related to anorexia are of interest to both researchers and practitioners but are difficult to study over long time periods and in large populations. Here we aim to determine the links between media portrayals of celebrities and online practices related to anorexia. We examined the Internet searching activities of 9.2 million people, focusing on searches related to known celebrities, especially those perceived by the public as suffering from anorexia, and on searches indicative of anorexic practices. Additionally, we tracked media attention of individual celebrities by monitoring all messages from Twitter related to those celebrities. We found that a subset of users focus their browsing activities on celebrities perceived as anorexic. There was an increase of 14% in the hazard of performing anorexia-related searches after searching for information on the celebrities most perceived as anorexic. Media attention of a celebrity was a trigger for search activity, and when focused on a celebrity perceived as anorexic, resulted in a 33% increase in hazard for carrying out anorexic searches. Strikingly, when media attention included a reference to anorexia, the hazard decreased by 22%. Our findings suggest that it would be beneficial for media, when reporting on those celebrities who are known to suffer from anorexia, to include this information in their reporting. Copyright © 2013 Wiley Periodicals, Inc.

Membrane-To-Nucleus Signaling Links Insulin-Like Growth Factor-1- and Stem Cell Factor-Activated Pathways

PubMed Central

Hayashi, Yujiro; Asuzu, David T.; Gibbons, Simon J.; Aarsvold, Kirsten H.; Bardsley, Michael R.; Lomberk, Gwen A.; Mathison, Angela J.; Kendrick, Michael L.; Shen, K. Robert; Taguchi, Takahiro; Gupta, Anu; Rubin, Brian P.; Fletcher, Jonathan A.; Farrugia, Gianrico; Urrutia, Raul A.; Ordog, Tamas

2013-01-01

Stem cell factor (mouse: Kitl, human: KITLG) and insulin-like growth factor-1 (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST), the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC), the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2), a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i). GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K) 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes. PMID:24116170

Physical Activity and Quality of Life Experienced by Highly Active Individuals with Physical Disabilities

ERIC Educational Resources Information Center

Giacobbi, Peter R., Jr.; Stancil, Michael; Hardin, Brent; Bryant, Lance

2008-01-01

The present study examined links between physical activity and quality of life experienced by individuals with physical disabilities recruited from a wheelchair user's basketball tournament. The participants included 12 male and 14 female adults between the ages of 18-54 (M = 31.12, SD = 10.75) who all reported one or more condition(s) that…

Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities

PubMed Central

2011-01-01

Background Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element. Results This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called Gene expression and Transcription factor activity based Relevance Network (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to E. coli data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of E. coli during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by using our reconstructed network. Conclusions The GTRNetwork algorithm introduces the hidden layer TFA into classic relevance score-based gene regulatory network reconstruction processes. Integrating the TFA biological information with regulatory network reconstruction algorithms significantly improves both detection of new links and reduces that rate of false positives. The application of GTRNetwork on E. coli gene transcriptome data gives a set of potential regulatory links with promising biological significance for isobutanol stress and other conditions. PMID:21668997

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation

PubMed Central

Webber, Emily S.; Mankin, David E.

2016-01-01

Abstract The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility. PMID:27822506

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

PubMed

Webber, Emily S; Mankin, David E; Cromwell, Howard C

2016-01-01

The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

The Confidentiality of Library Users' Records.

ERIC Educational Resources Information Center

Drobnicki, John A.

Many activities that take place in the library, including circulation and interlibrary loan and reserve requests, result in the creation of records linking clients to specific kinds of information. Several groups, including law enforcement officials, have attempted on various occasions to gain access to these records. This research paper provides…

Linking Major Depression and The Neural Substrates of Associative Processing

PubMed Central

Harel, Eiran Vadim; Tennyson, Robert Langley; Fava, Maurizio; Bar, Moshe

2016-01-01

It has been proposed that mood correlates with the breadth of associative thinking. Here we set to test this hypothesis in healthy and depressed individuals. Generating contextual associations engages a network of cortical regions including the parahippocampal cortex (PHC), retrosplenial complex, and medial prefrontal cortex. The link between mood, associative processing, and its underlying cortical infrastructure provides a promising avenue for elucidating the mechanisms underlying cognitive impairments in Major Depressive Disorder (MDD). Participants included fifteen non-medicated individuals with acute Major Depressive Episode and fifteen healthy matched controls. In an fMRI experiment, participants viewed images of objects that are either strongly or weakly associated with a specific context (e.g., a beach chair vs. a water bottle), while rating the commonality of each object. Analyses were performed to examine brain activation and structural differences between groups. Consistent with our hypothesis, controls showed greater activation of the contextual associations network compared with depressed participants. In addition, PHC structural volume was correlated with ruminative tendency and, volumes of the hippocampal subfields were significantly smaller in depressed participants. Surprisingly, depressed participants showed increased activity in the entorhinal cortex (ERC) compared with controls. We integrate these findings within a mechanistic account linking mood and associative thinking, and suggest directions for the future. PMID:27553369

OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids.

PubMed

Hornung, Veit; Hartmann, Rune; Ablasser, Andrea; Hopfner, Karl-Peter

2014-08-01

Recent discoveries in the field of innate immunity have highlighted the existence of a family of nucleic acid-sensing proteins that have similar structural and functional properties. These include the well-known oligoadenylate synthase (OAS) family proteins and the recently identified OAS homologue cyclic GMP-AMP (cGAMP) synthase (cGAS). The OAS proteins and cGAS are template-independent nucleotidyltransferases that, once activated by double-stranded nucleic acids in the cytosol, produce unique classes of 2'-5'-linked second messenger molecules, which - through distinct mechanisms - have crucial antiviral functions. 2'-5'-linked oligoadenylates limit viral propagation through the activation of the enzyme RNase L, which degrades host and viral RNA, and 2'-5'-linked cGAMP activates downstream signalling pathways to induce de novo antiviral gene expression. In this Progress article, we describe the striking functional and structural similarities between OAS proteins and cGAS, and highlight their roles in antiviral immunity.

Autonomous Motion Learning for Intra-Vehicular Activity Space Robot

NASA Astrophysics Data System (ADS)

Watanabe, Yutaka; Yairi, Takehisa; Machida, Kazuo

Space robots will be needed in the future space missions. So far, many types of space robots have been developed, but in particular, Intra-Vehicular Activity (IVA) space robots that support human activities should be developed to reduce human-risks in space. In this paper, we study the motion learning method of an IVA space robot with the multi-link mechanism. The advantage point is that this space robot moves using reaction force of the multi-link mechanism and contact forces from the wall as space walking of an astronaut, not to use a propulsion. The control approach is determined based on a reinforcement learning with the actor-critic algorithm. We demonstrate to clear effectiveness of this approach using a 5-link space robot model by simulation. First, we simulate that a space robot learn the motion control including contact phase in two dimensional case. Next, we simulate that a space robot learn the motion control changing base attitude in three dimensional case.

Spacer conformation in biologically active molecules. Part 2. Structure and conformation of 4-[2-(diphenylmethylamino)ethyl]-1-(2-methoxyphenyl) piperazine and its diphenylmethoxy analog—potential 5-HT 1A receptor ligands

NASA Astrophysics Data System (ADS)

Karolak-Wojciechowska, J.; Fruziński, A.; Czylkowski, R.; Paluchowska, M. H.; Mokrosz, M. J.

2003-09-01

As a part of studies on biologically active molecule structures with aliphatic linking chain, the structures of 4-[2-diphenylmethylamino)ethyl]-1-(2-methoxyphenyl)piperazine dihydrochloride ( 1) and 4-[2-diphenylmethoxy)ethyl]-1-(2-methoxyphenyl)piperazine fumarate ( 2) have been reported. In both compounds, four atomic non-all-carbons linking chains (N)C-C-X-C are present. The conformation of that linking spacer depends on the nature of the X-atom. The preferred conformation for chain with XNH has been found to be fully extended while for that with XO—the bend one. It was confirmed by conformational calculations (strain energy distribution and random search) and crystallographic data, including statistics from CCDC.

Structural characterization and macrophage immunomodulatory activity of a novel polysaccharide from Smilax glabra Roxb.

PubMed

Wang, Min; Yang, Xiao-Bo; Zhao, Jing-Wen; Lu, Chuan-Jian; Zhu, Wei

2017-01-20

A novel heteropolysaccharide (SGRP1) with great immunomodulatory activity was isolated from the root of Smilax glabra Roxb. by hot water extraction. Physical and chemical analyses showed that SGRP1 had an average molecular weight of 1.26×10 4 Da and was composed of mannose, fucose and glucose in molar ratio of 1.00:3.09:39.41. The glycosidic linkage types of SGRP1 were proven to be (1→3)-linked -α-l-Fuc, (1→3)-linked-α-l-Man, (1→)-linked-α-d-Glc, and (1→6)-linked-α-d-Glc. The in vitro immunomodulatory assays demonstrated that SGRP1 could evidently promote the phagocytosis and increase macrophage-derived biological factors including nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion via JNK and ERK signaling pathways and NLRP3 inflammasome signaling pathway. The data supported that SGRP1 had immunomodulatory potential through activating macrophages and enhancing host immune system function, which enabled it to be a novel immunomodulator for application in immunological diseases or functional food. Copyright © 2016 Elsevier Ltd. All rights reserved.

Links to Literature--Huge Trees, Small Drawings: Ideas of Relative Sizes.

ERIC Educational Resources Information Center

Burton, Gail

1996-01-01

Discusses a unit integrating science, mathematics, and environmental education centered around "The Great Kapok Tree," by Lynne Cherry (1990). Ratios are used to make scale drawings of trees in a rain forest. Other activities include a terrarium and problem-solving activities based on eating habits of rain forest animals. (KMC)

Identifying Diverse Means for Assessing Physical Activity

ERIC Educational Resources Information Center

Perlman, Dana J.; Pearson, Phil

2012-01-01

Physical inactivity is of concern for the majority of age groups within the United States. Limited engagement in physical activity (PA) has been linked with an increased risk for a host of health problems, including but not limited to heart disease, diabetes and cancer. Benefits of PA are widely documented and accepted yet many people, especially…

Recombinant human erythropoietin (rHuEPO): cross-linking with disuccinimidyl esters and identification of the interfacing domains in EPO.

PubMed Central

Haniu, M.; Narhi, L. O.; Arakawa, T.; Elliott, S.; Rohde, M. F.

1993-01-01

Several amino groups of recombinant human erythropoietin are selectively cross-linked by specific cross-linkers including disuccinimidyl suberate or dithiobis(succinimidyl propionate). Intramolecular cross-linkings are obtained without significant change of the protein conformation using appropriate concentrations (0.2 mM) of the cross-linkers, which possess an 11-12-A length of a spacer between two reacting groups. Intramolecularly cross-linked peptides obtained suggest that several amino groups in erythropoietin (EPO) are positioned at a distance of near 12 A in the solution state. These interfacing amino groups include Lys 20-Lys 154, Lys 45-Lys 140, Lys 52-Lys 154, Lys 52-Lys 140, and Ala 1-Lys 116. A comparison of the cross-linking results between nonglycosylated EPO and glycosylated EPO suggests that both proteins retain high similarity regarding protein conformation. These results fit a structural model similar to that of human growth hormone, in which four alpha-helical bundles and a long stretch of beta-sheet structure are involved in the active protein. PMID:8401229

Sensitive detection of proteasomal activation using the Deg-On mammalian synthetic gene circuit.

PubMed

Zhao, Wenting; Bonem, Matthew; McWhite, Claire; Silberg, Jonathan J; Segatori, Laura

2014-04-08

The ubiquitin proteasome system (UPS) has emerged as a drug target for diverse diseases characterized by altered proteostasis, but pharmacological agents that enhance UPS activity have been challenging to establish. Here we report the Deg-On system, a genetic inverter that translates proteasomal degradation of the transcriptional regulator TetR into a fluorescent signal, thereby linking UPS activity to an easily detectable output, which can be tuned using tetracycline. We demonstrate that this circuit responds to modulation of UPS activity in cell culture arising from the inhibitor MG-132 and activator PA28γ. Guided by predictive modelling, we enhanced the circuit's signal sensitivity and dynamic range by introducing a feedback loop that enables self-amplification of TetR. By linking UPS activity to a simple and tunable fluorescence output, these genetic inverters will enable a variety of applications, including screening for UPS activating molecules and selecting for mammalian cells with different levels of proteasome activity.

Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants

PubMed Central

Janjua, Naveed Zafar; Kuo, Margot; Chong, Mei; Yu, Amanda; Alvarez, Maria; Cook, Darrel; Armour, Rosemary; Aiken, Ciaran; Li, Karen; Mussavi Rizi, Seyed Ali; Woods, Ryan; Godfrey, David; Wong, Jason; Gilbert, Mark; Tyndall, Mark W.; Krajden, Mel

2016-01-01

Background The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. Methods The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Results Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90–100%). Conclusion Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV. PMID:26954020

Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants.

PubMed

Janjua, Naveed Zafar; Kuo, Margot; Chong, Mei; Yu, Amanda; Alvarez, Maria; Cook, Darrel; Armour, Rosemary; Aiken, Ciaran; Li, Karen; Mussavi Rizi, Seyed Ali; Woods, Ryan; Godfrey, David; Wong, Jason; Gilbert, Mark; Tyndall, Mark W; Krajden, Mel

2016-01-01

The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90-100%). Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

Criteria for Evaluating Alternative Network and Link Layer Protocols for the NASA Constellation Program Communication Architecture

NASA Technical Reports Server (NTRS)

Benbenek, Daniel; Soloff, Jason; Lieb, Erica

2010-01-01

Selecting a communications and network architecture for future manned space flight requires an evaluation of the varying goals and objectives of the program, development of communications and network architecture evaluation criteria, and assessment of critical architecture trades. This paper uses Cx Program proposed exploration activities as a guideline; lunar sortie, outpost, Mars, and flexible path options are described. A set of proposed communications network architecture criteria are proposed and described. They include: interoperability, security, reliability, and ease of automating topology changes. Finally a key set of architecture options are traded including (1) multiplexing data at a common network layer vs. at the data link layer, (2) implementing multiple network layers vs. a single network layer, and (3) the use of a particular network layer protocol, primarily IPv6 vs. Delay Tolerant Networking (DTN). In summary, the protocol options are evaluated against the proposed exploration activities and their relative performance with respect to the criteria are assessed. An architectural approach which includes (a) the capability of multiplexing at both the network layer and the data link layer and (b) a single network layer for operations at each program phase, as these solutions are best suited to respond to the widest array of program needs and meet each of the evaluation criteria.

Drought Resilience and Water Conservation Technical Brief

EPA Pesticide Factsheets

In many areas of the US, the frequency, intensity, and duration of drought events are increasing, this brief highlights EPA drought and conservation activities across the nation and includes links to additional materials and reference documents.

Dual control active superconductive devices

DOEpatents

Martens, Jon S.; Beyer, James B.; Nordman, James E.; Hohenwarter, Gert K. G.

1993-07-20

A superconducting active device has dual control inputs and is constructed such that the output of the device is effectively a linear mix of the two input signals. The device is formed of a film of superconducting material on a substrate and has two main conduction channels, each of which includes a weak link region. A first control line extends adjacent to the weak link region in the first channel and a second control line extends adjacent to the weak link region in the second channel. The current flowing from the first channel flows through an internal control line which is also adjacent to the weak link region of the second channel. The weak link regions comprise small links of superconductor, separated by voids, through which the current flows in each channel. Current passed through the control lines causes magnetic flux vortices which propagate across the weak link regions and control the resistance of these regions. The output of the device taken across the input to the main channels and the output of the second main channel and the internal control line will constitute essentially a linear mix of the two input signals imposed on the two control lines. The device is especially suited to microwave applications since it has very low input capacitance, and is well suited to being formed of high temperature superconducting materials since all of the structures may be formed coplanar with one another on a substrate.

CNN Newsroom Classroom Guides. April 1999.

ERIC Educational Resources Information Center

Turner Educational Services, Inc., Newtown, PA.

These classroom guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of April, provide program rundowns, suggestions for class activities and discussion, links to related World Wide Web sites, and lists of related news terms. Top stories include: NATO includes Belgrade in its targets, three U.S.…

The Privilege of Ease: Social Class and Campus Life at Highly Selective, Private Universities

ERIC Educational Resources Information Center

Martin, Nathan D.

2012-01-01

Active involvement in college activities is linked to a host of student development outcomes, including personal growth, achievement and satisfaction. Yet, to date there has been too little attention to how social class shapes campus involvement. Through an analysis of survey data of students attending a single elite university and a national…

Linking structure and activity in nonlinear spiking networks

PubMed Central

Josić, Krešimir; Shea-Brown, Eric

2017-01-01

Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks’ spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities—including those of different cell types—combine with connectivity to shape population activity and function. PMID:28644840

Transfer and Cross‐Collateralization of Clean Water State Revolving Funds and Drinking Water State Revolving Funds

EPA Pesticide Factsheets

Link containing Federal laws and Executive Orders, including cross-cutting federal authorities, apply to projects and activities receiving assistance under the Clean Water State Revolving Fund (CWSRF) program.

Structure-activity relationship of carbamate-linked cationic lipids bearing hydroxyethyl headgroup for gene delivery.

PubMed

Zhi, Defu; Zhang, Shubiao; Qureshi, Farooq; Zhao, Yinan; Cui, Shaohui; Wang, Bing; Chen, Huiying; Yang, Baoling; Zhao, Defeng

2013-12-01

A novel series of carbamate-linked cationic lipids containing hydroxyl headgroup were synthesized and included in formulations for transfection assays. The DNA-lipid complexes were characterized for their ability to bind DNA, their size, ζ-potential and cytotoxicity. Compared with our previously reported cationic transfection lipid DDCDMA lacking the hydroxyl group and the commercially available, these cationic liposomes exhibited relatively higher transfection efficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Climatic change by cloudiness linked to the spatial variability of sea surface temperatures

NASA Technical Reports Server (NTRS)

Otterman, J.

1975-01-01

An active role in modifying the earth's climate is suggested for low cloudiness over the circumarctic oceans. Such cloudiness, linked to the spatial differences in ocean surface temperatures, was studied. The temporal variations from year to year of ocean temperature patterns can be pronounced and therefore, the low cloudiness over this region should also show strong temporal variations, affecting the albedo of the earth and therefore the climate. Photographs are included.

Data on the association of the nuclear envelope protein Sun1 with nucleoli.

PubMed

Moujaber, Ossama; Omran, Nawal; Kodiha, Mohamed; Pié, Brigitte; Cooper, Ellis; Presley, John F; Stochaj, Ursula

2017-08-01

SUN proteins participate in diverse cellular activities, many of which are connected to the nuclear envelope. Recently, the family member SUN1 has been linked to novel biological activities. These include the regulation of nucleoli, intranuclear compartments that assemble ribosomal subunits. We show that SUN1 associates with nucleoli in several mammalian epithelial cell lines. This nucleolar localization is not shared by all cell types, as SUN1 concentrates at the nuclear envelope in ganglionic neurons and non-neuronal satellite cells. Database analyses and Western blotting emphasize the complexity of SUN1 protein profiles in different mammalian cells. We constructed a STRING network which identifies SUN1-related proteins as part of a larger network that includes several nucleolar proteins. Taken together, the current data highlight the diversity of SUN1 proteins and emphasize the possible links between SUN1 and nucleoli.

Controlling under-actuated robot arms using a high speed dynamics process

NASA Technical Reports Server (NTRS)

Jain, Abhinandan (Inventor); Rodriguez, Guillermo (Inventor)

1994-01-01

The invention controls an under-actuated manipulator by first obtaining predetermined active joint accelerations of the active joints and the passive joint friction forces of the passive joints, then computing articulated body qualities for each of the joints from the current positions of the links, and finally computing from the articulated body qualities and from the active joint accelerations and the passive joint forces, active joint forces of the active joints. Ultimately, the invention transmits servo commands to the active joint forces thus computed to the respective ones of the joint servos. The computation of the active joint forces is accomplished using a recursive dynamics algorithm. In this computation, an inward recursion is first carried out for each link, beginning with the outermost link in order to compute the residual link force of each link from the active joint acceleration if the corresponding joint is active, or from the known passive joint force if the corresponding joint is passive. Then, an outward recursion is carried out for each link in which the active joint force is computed from the residual link force if the corresponding joint is active or the passive joint acceleration is computed from the residual link force if the corresponding joint is passive.

Love Hurts (in More Ways Than One): Specificity of Psychological Symptoms as Predictors and Consequences of Romantic Activity Among Early Adolescent Girls*

PubMed Central

Starr, Lisa R.; Davila, Joanne; Stroud, Catherine B.; Li, Po Ching Clara; Yoneda, Athena; Hershenberg, Rachel; Miller, Melissa Ramsay

2012-01-01

Objective Research has linked adolescent romantic and sexual activities to depressive symptoms. The current study examines whether such activities are uniquely linked to depressive symptoms versus symptoms of other disorders (including anxiety, externalizing, and eating disorders), and whether co-occurring symptoms more precisely account for the association between depressive symptoms and romantic involvement. Method Early adolescent girls (N = 83; mean age = 13.45) participated in baseline and 1-year follow up data collection. Results Romantic (i.e., dating and sexual) activities were longitudinally related to numerous types of symptoms. The association between depressive symptoms and romantic variables remained when considering co-occurring symptoms. Girls with more comorbid disorders reported more romantic activities. Conclusions Results suggest that the maladaptive consequences and precipitants of adolescent romantic activities extend beyond depression, but also imply that this association is not secondary to comorbid symptoms. Future work should clarify causal pathways. PMID:22307747

Love hurts (in more ways than one): specificity of psychological symptoms as predictors and consequences of romantic activity among early adolescent girls.

PubMed

Starr, Lisa R; Davila, Joanne; Stroud, Catherine B; Clara Li, Po Ching; Yoneda, Athena; Hershenberg, Rachel; Ramsay Miller, Melissa

2012-04-01

Research has linked adolescent romantic and sexual activities to depressive symptoms. The current study examines whether such activities are uniquely linked to depressive symptoms versus symptoms of other disorders (including anxiety, externalizing, and eating disorders), and whether co-occurring symptoms more precisely account for the association between depressive symptoms and romantic involvement. Early adolescent girls (N = 83; mean age = 13.45) participated in baseline and 1-year follow up data collection. Romantic (i.e., dating and sexual) activities were longitudinally related to numerous types of symptoms. The association between depressive symptoms and romantic variables remained when considering co-occurring symptoms. Girls with more comorbid disorders reported more romantic activities. Results suggest that the maladaptive consequences and precipitants of adolescent romantic activities extend beyond depression, but also imply that this association is not secondary to comorbid symptoms. Future work should clarify causal pathways. © 2012 Wiley Periodicals, Inc.

Detection of eQTL modules mediated by activity levels of transcription factors.

PubMed

Sun, Wei; Yu, Tianwei; Li, Ker-Chau

2007-09-01

Studies of gene expression quantitative trait loci (eQTL) in different organisms have shown the existence of eQTL hot spots: each being a small segment of DNA sequence that harbors the eQTL of a large number of genes. Two questions of great interest about eQTL hot spots arise: (1) which gene within the hot spot is responsible for the linkages, i.e. which gene is the quantitative trait gene (QTG)? (2) How does a QTG affect the expression levels of many genes linked to it? Answers to the first question can be offered by available biological evidence or by statistical methods. The second question is harder to address. One simple situation is that the QTG encodes a transcription factor (TF), which regulates the expression of genes linked to it. However, previous results have shown that TFs are not overrepresented in the eQTL hot spots. In this article, we consider the scenario that the propagation of genetic perturbation from a QTG to other linked genes is mediated by the TF activity. We develop a procedure to detect the eQTL modules (eQTL hot spots together with linked genes) that are compatible with this scenario. We first detect 27 eQTL modules from a yeast eQTL data, and estimate TF activity profiles using the method of Yu and Li (2005). Then likelihood ratio tests (LRTs) are conducted to find 760 relationships supporting the scenario of TF activity mediation: (DNA polymorphism --> cis-linked gene --> TF activity --> downstream linked gene). They are organized into 4 eQTL modules: an amino acid synthesis module featuring a cis-linked gene LEU2 and the mediating TF Leu3; a pheromone response module featuring a cis-linked gene GPA1 and the mediating TF Ste12; an energy-source control module featuring two cis-linked genes, GSY2 and HAP1, and the mediating TF Hap1; a mitotic exit module featuring four cis-linked genes, AMN1, CSH1, DEM1 and TOS1, and the mediating TF complex Ace2/Swi5. Gene Ontology is utilized to reveal interesting functional groups of the downstream genes in each module. Our methods are implemented in an R package: eqtl.TF, which includes source codes and relevant data. It can be freely downloaded at http://www.stat.ucla.edu/~sunwei/software.htm. http://www.stat.ucla.edu/~sunwei/yeast_eQTL_TF/supplementary.pdf.

Affective traits link to reliable neural markers of incentive anticipation.

PubMed

Wu, Charlene C; Samanez-Larkin, Gregory R; Katovich, Kiefer; Knutson, Brian

2014-01-01

While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n=52) as they played a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and trait Negative Arousal. In a subsample (n=14) retested over 2.5years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (-$5.00) showed significant test-retest reliability (intraclass correlations>0.50, p's<0.01). In the full sample (n=52), trait Positive Arousal correlated with individual differences in left NAcc activity during anticipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms. © 2013. Published by Elsevier Inc. All rights reserved.

Affective traits link to reliable neural markers of incentive anticipation

PubMed Central

Wu, Charlene C.; Samanez-Larkin, Gregory R.; Katovich, Kiefer; Knutson, Brian

2013-01-01

While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n = 52) as they played a Monetary Incentive Delay Task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and Negative Arousal. In a subsample (n = 14) retested over 2.5 years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (−$5.00) showed significant test-retest reliability (intraclass correlations > 0.50, p’s < 0.01). In the full sample (n = 52), trait Positive Arousal correlated with individual differences in left NAcc activity during anticipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms. PMID:24001457

Deficiency of the Arabidopsis Helicase RTEL1 Triggers a SOG1-Dependent Replication Checkpoint in Response to DNA Cross-Links

PubMed Central

Hu, Zhubing; Cools, Toon; Kalhorzadeh, Pooneh; Heyman, Jefri; De Veylder, Lieven

2015-01-01

To maintain genome integrity, DNA replication is executed and regulated by a complex molecular network of numerous proteins, including helicases and cell cycle checkpoint regulators. Through a systematic screening for putative replication mutants, we identified an Arabidopsis thaliana homolog of human Regulator of Telomere Length 1 (RTEL1), which functions in DNA replication, DNA repair, and recombination. RTEL1 deficiency retards plant growth, a phenotype including a prolonged S-phase duration and decreased cell proliferation. Genetic analysis revealed that rtel1 mutant plants show activated cell cycle checkpoints, specific sensitivity to DNA cross-linking agents, and increased homologous recombination, but a lack of progressive shortening of telomeres, indicating that RTEL1 functions have only been partially conserved between mammals and plants. Surprisingly, RTEL1 deficiency induces tolerance to the deoxynucleotide-depleting drug hydroxyurea, which could be mimicked by DNA cross-linking agents. This resistance does not rely on the essential replication checkpoint regulator WEE1 but could be blocked by a mutation in the SOG1 transcription factor. Taken together, our data indicate that RTEL1 is required for DNA replication and that its deficiency activates a SOG1-dependent replication checkpoint. PMID:25595823

The core structure of ginsenan PA, a phagocytosis-activating polysaccharide from the root of Panax ginseng.

PubMed

Tomoda, M; Hirabayashi, K; Shimizu, N; Gonda, R; Ohara, N

1994-09-01

Controlled Smith degradation and limited hydrolysis of ginsenan PA, the main phagocytosis-activating polysaccharide isolated from the root of Panax ginseng C. A. Meyer, were performed. The reticuloendothelial system-potentiating and anti-complementary activities of the degradation products were investigated. Methylation analysis of the primary and secondary Smith degradation products indicated that the core structural features of ginsenan PA include a backbone chain mainly composed of beta-1,3-linked D-galactose. Almost half of the galactose units in the backbone carry side-chains composed of beta-1,6-linked D-galactosyl residues at position 6. Further 3,6-branching of D-galactose units was observed in a part of the side-chains. alpha-L-Arabinose units are connected mainly to the core galactose moieties via position 6. Removal of most of the arabinose units had a considerable effect on immunological activity.

Examining the Link Between Public Transit Use and Active Commuting

PubMed Central

Bopp, Melissa; Gayah, Vikash V.; Campbell, Matthew E.

2015-01-01

Background: An established relationship exists between public transportation (PT) use and physical activity. However, there is limited literature that examines the link between PT use and active commuting (AC) behavior. This study examines this link to determine if PT users commute more by active modes. Methods: A volunteer, convenience sample of adults (n = 748) completed an online survey about AC/PT patterns, demographic, psychosocial, community and environmental factors. t-test compared differences between PT riders and non-PT riders. Binary logistic regression analyses examined the effect of multiple factors on AC and a full logistic regression model was conducted to examine AC. Results: Non-PT riders (n = 596) reported less AC than PT riders. There were several significant relationships with AC for demographic, interpersonal, worksite, community and environmental factors when considering PT use. The logistic multivariate analysis for included age, number of children and perceived distance to work as negative predictors and PT use, feelings of bad weather and lack of on-street bike lanes as a barrier to AC, perceived behavioral control and spouse AC were positive predictors. Conclusions: This study revealed the complex relationship between AC and PT use. Further research should investigate how AC and public transit use are related. PMID:25898405

Examining the link between public transit use and active commuting.

PubMed

Bopp, Melissa; Gayah, Vikash V; Campbell, Matthew E

2015-04-17

An established relationship exists between public transportation (PT) use and physical activity. However, there is limited literature that examines the link between PT use and active commuting (AC) behavior. This study examines this link to determine if PT users commute more by active modes. A volunteer, convenience sample of adults (n = 748) completed an online survey about AC/PT patterns, demographic, psychosocial, community and environmental factors. t-test compared differences between PT riders and non-PT riders. Binary logistic regression analyses examined the effect of multiple factors on AC and a full logistic regression model was conducted to examine AC. Non-PT riders (n = 596) reported less AC than PT riders. There were several significant relationships with AC for demographic, interpersonal, worksite, community and environmental factors when considering PT use. The logistic multivariate analysis for included age, number of children and perceived distance to work as negative predictors and PT use, feelings of bad weather and lack of on-street bike lanes as a barrier to AC, perceived behavioral control and spouse AC were positive predictors. This study revealed the complex relationship between AC and PT use. Further research should investigate how AC and public transit use are related.

Fund Raising and Public College Trustees.

ERIC Educational Resources Information Center

Farley, Eileen

1986-01-01

Public college trustees' responsibilities in fund raising include ensuring that private fund-raising takes place, setting policies and priorities, linking private philanthropy and public funding authorities, assuring college support of alumni and public relations activities, furthering public confidence, and giving. (MSE)

Anticonvulsant activity of artificial sweeteners: a structural link between sweet-taste receptor T1R3 and brain glutamate receptors.

PubMed

Talevi, Alan; Enrique, Andrea V; Bruno-Blanch, Luis E

2012-06-15

A virtual screening campaign based on application of a topological discriminant function capable of identifying novel anticonvulsant agents indicated several widely-used artificial sweeteners as potential anticonvulsant candidates. Acesulfame potassium, cyclamate and saccharin were tested in the Maximal Electroshock Seizure model (mice, ip), showing moderate anticonvulsant activity. We hypothesized a probable structural link between the receptor responsible of sweet taste and anticonvulsant molecular targets. Bioinformatic tools confirmed a highly significant sequence-similarity between taste-related protein T1R3 and several metabotropic glutamate receptors from different species, including glutamate receptors upregulated in epileptogenesis and certain types of epilepsy. Copyright © 2012 Elsevier Ltd. All rights reserved.

A novel series of N-acyl substituted indole-linked benzimidazoles and naphthoimidazoles as potential anti inflammatory, anti biofilm and anti microbial agents.

PubMed

Abraham, Rajan; Prakash, Periakaruppan; Mahendran, Karthikeyan; Ramanathan, Murugappan

2018-01-01

A novel N-acyl substituted indole-linked benzimidazoles and naphthoimidazoles were synthesized. Their chemical structures were confirmed using spectroscopic tools including 1 H NMR, 13 C NMR and CHN-elemental analyses. Anti inflammatory activity for all target compounds was evaluated in-vitro. The synthesized compounds hinder the biofilm formation and control the growth of the pathogen, Staphylococcus epidermis. Anti microbial activity of the compounds was evaluated against both Gram negative and Gram positive bacteria such as Staphylococcus aureus (MTCC 2940), Pseudomonas aeruginosa (MTCC424), Escherchia coli (MTCC 443) and Enterococcus fecalis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Constrained Active Learning for Anchor Link Prediction Across Multiple Heterogeneous Social Networks

PubMed Central

Zhu, Junxing; Zhang, Jiawei; Wu, Quanyuan; Jia, Yan; Zhou, Bin; Wei, Xiaokai; Yu, Philip S.

2017-01-01

Nowadays, people are usually involved in multiple heterogeneous social networks simultaneously. Discovering the anchor links between the accounts owned by the same users across different social networks is crucial for many important inter-network applications, e.g., cross-network link transfer and cross-network recommendation. Many different supervised models have been proposed to predict anchor links so far, but they are effective only when the labeled anchor links are abundant. However, in real scenarios, such a requirement can hardly be met and most anchor links are unlabeled, since manually labeling the inter-network anchor links is quite costly and tedious. To overcome such a problem and utilize the numerous unlabeled anchor links in model building, in this paper, we introduce the active learning based anchor link prediction problem. Different from the traditional active learning problems, due to the one-to-one constraint on anchor links, if an unlabeled anchor link a=(u,v) is identified as positive (i.e., existing), all the other unlabeled anchor links incident to account u or account v will be negative (i.e., non-existing) automatically. Viewed in such a perspective, asking for the labels of potential positive anchor links in the unlabeled set will be rewarding in the active anchor link prediction problem. Various novel anchor link information gain measures are defined in this paper, based on which several constraint active anchor link prediction methods are introduced. Extensive experiments have been done on real-world social network datasets to compare the performance of these methods with state-of-art anchor link prediction methods. The experimental results show that the proposed Mean-entropy-based Constrained Active Learning (MC) method can outperform other methods with significant advantages. PMID:28771201

Constrained Active Learning for Anchor Link Prediction Across Multiple Heterogeneous Social Networks.

PubMed

Zhu, Junxing; Zhang, Jiawei; Wu, Quanyuan; Jia, Yan; Zhou, Bin; Wei, Xiaokai; Yu, Philip S

2017-08-03

Nowadays, people are usually involved in multiple heterogeneous social networks simultaneously. Discovering the anchor links between the accounts owned by the same users across different social networks is crucial for many important inter-network applications, e.g., cross-network link transfer and cross-network recommendation. Many different supervised models have been proposed to predict anchor links so far, but they are effective only when the labeled anchor links are abundant. However, in real scenarios, such a requirement can hardly be met and most anchor links are unlabeled, since manually labeling the inter-network anchor links is quite costly and tedious. To overcome such a problem and utilize the numerous unlabeled anchor links in model building, in this paper, we introduce the active learning based anchor link prediction problem. Different from the traditional active learning problems, due to the one-to-one constraint on anchor links, if an unlabeled anchor link a = ( u , v ) is identified as positive (i.e., existing), all the other unlabeled anchor links incident to account u or account v will be negative (i.e., non-existing) automatically. Viewed in such a perspective, asking for the labels of potential positive anchor links in the unlabeled set will be rewarding in the active anchor link prediction problem. Various novel anchor link information gain measures are defined in this paper, based on which several constraint active anchor link prediction methods are introduced. Extensive experiments have been done on real-world social network datasets to compare the performance of these methods with state-of-art anchor link prediction methods. The experimental results show that the proposed Mean-entropy-based Constrained Active Learning (MC) method can outperform other methods with significant advantages.

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

PubMed

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms leading to the development of these cancers.

Modulation of type II TGF-β receptor degradation by integrin-linked kinase.

PubMed

Vi, Linda; Boo, Stellar; Sayedyahossein, Samar; Singh, Randeep K; McLean, Sarah; Di Guglielmo, Gianni M; Dagnino, Lina

2015-03-01

Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-β (TGF-β) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-β and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-β receptor stimulation. We now show that ILK associates with type II TGF-β receptors (TβRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TβRII are decreased, through mechanisms that involve enhanced ubiquitination and proteasomal degradation. Partitioning of TGF-β receptors into membrane has been linked to proteasome-dependent receptor degradation. We found that interfering with membrane raft formation in ILK-deficient cells restored TβRII levels and signaling. These observations support a model whereby ILK functions in fibroblasts to direct TβRII away from degradative pathways during their differentiation into myofibroblasts.

Enterocin F4-9, a Novel O-Linked Glycosylated Bacteriocin

PubMed Central

Maky, Mohamed Abdelfattah; Ishibashi, Naoki; Zendo, Takeshi; Perez, Rodney Honrada; Doud, Jehan Ragab; Karmi, Mohamed

2015-01-01

Enterococcus faecalis F4-9 isolated from Egyptian salted-fermented fish produces a novel bacteriocin, termed enterocin F4-9. Enterocin F4-9 was purified from the culture supernatant by three steps, and its molecular mass was determined to be 5,516.6 Da by mass spectrometry. Amino acid and DNA sequencing showed that the propeptide consists of 67 amino acid residues, with a leader peptide containing a double glycine cleavage site to produce a 47-amino-acid mature peptide. Enterocin F4-9 is modified by two molecules of N-acetylglucosamine β-O-linked to Ser37 and Thr46. The O-linked N-acetylglucosamine moieties are essential for the antimicrobial activity of enterocin F4-9. Further analysis of the enterocin F4-9 gene cluster identified enfC, which has high sequence similarity to a glycosyltransferase. The antimicrobial activity of enterocin F4-9 covered a limited range of bacteria, including, interestingly, a Gram-negative strain, Escherichia coli JM109. Enterocin F4-9 is sensitive to protease, active at a wide pH range, and moderately resistant to heat. PMID:25956765

Hispanics in U.S. History. Volume 1: Through 1865. Volume 2: 1865 to the Present. The Newcomers Series.

ERIC Educational Resources Information Center

de Varona, Frank; And Others

Each of these two textbooks on Hispanic-American history contains 4 units divided into 20 chapters. Each chapter includes an overarching question; text; reading comprehension questions; study tips; an activity involving geography skills, links between past and present, or daily life; an activity involving arts and technology or using primary…

Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation

PubMed Central

2014-01-01

Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension. PMID:25349818

Cognitive Jointly Optimal Code-Division Channelization and Routing Over Cooperative Links

DTIC Science & Technology

2014-04-01

i List of Figures Fig. 1: Comparison between code-division channelization and FDM. Fig. 2: Secondary receiver SINR as a function of the iteration step...transmission percentage as a function of the number of active links under Cases rank(X′′) = 1 and > 1 (the study includes also the random code assignment...scheme); (b) Instantaneous output SINR of a primary signal against primary SINR-QoS threshold SINRthPU (thick line) and instanta- neous output SINR of

Transcription map of Xq27: candidates for several X-linked diseases.

PubMed

Zucchi, I; Jones, J; Affer, M; Montagna, C; Redolfi, E; Susani, L; Vezzoni, P; Parvari, R; Schlessinger, D; Whyte, M P; Mumm, S

1999-04-15

Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found. Copyright 1999 Academic Press.

Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney

PubMed Central

Toma, Ildikó; Kang, Jung Julie; Sipos, Arnold; Vargas, Sarah; Bansal, Eric; Hanner, Fiona; Meer, Elliott; Peti-Peterdi, János

2008-01-01

Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein–coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury. PMID:18535668

77 FR 59410 - Agency Information Collection Activities: National Interest Waivers, Supplemental Evidence to I...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... to add [Insert OMB Control Number] in the subject box. All submissions received must include the... Act notice that is available via the link in the footer of http://www.regulations.gov . Note: The...

The CEIC Review, 2001.

ERIC Educational Resources Information Center

Page, Stephen, Ed.

2001-01-01

These six issues examine education in the inner cities. Titles include: "Pathways to School/Community/Family Partnership Results: Measures of Success and Student Learning" (e.g., promoting community partnerships and active learning through federal policy and linking child development knowledge with partnership evaluation); "Emerging…

Active Travel Behavior in a Border Region of Texas and New Mexico: Motivators, Deterrents, and Characteristics.

PubMed

Sener, Ipek N; Lee, Richard J

2017-08-01

Active travel has been linked with improved transportation and health outcomes, such as reduced traffic congestion and air pollution, improved mobility, accessibility, and equity, and increased physical and mental health. The purpose of this study was to better understand active travel characteristics, motivators, and deterrents in the El Paso, TX, region. A multimodal transportation survey brought together elements of transportation and health, with a focus on attitudinal characteristics. The analysis consisted of an initial descriptive analysis, spatial analysis, and multivariate binary and ordered-response models of walking and bicycling behavior. The motivators and deterrents of active travel differed for walkers, bicyclists, and noncyclists interested in bicycling. The link between active travel and life satisfaction was moderated by age, with a negative association for older travelers. This effect was stronger for bicycling than it was for walking. Based on the findings, several interventions to encourage walking and bicycling were suggested. These included infrastructure and built environment enhancements, workplace programs, and interventions targeting specific subpopulations.

Ontology Design Patterns: Bridging the Gap Between Local Semantic Use Cases and Large-Scale, Long-Term Data Integration

NASA Astrophysics Data System (ADS)

Shepherd, Adam; Arko, Robert; Krisnadhi, Adila; Hitzler, Pascal; Janowicz, Krzysztof; Chandler, Cyndy; Narock, Tom; Cheatham, Michelle; Schildhauer, Mark; Jones, Matt; Raymond, Lisa; Mickle, Audrey; Finin, Tim; Fils, Doug; Carbotte, Suzanne; Lehnert, Kerstin

2015-04-01

Integrating datasets for new use cases is one of the common drivers for adopting semantic web technologies. Even though linked data principles enables this type of activity over time, the task of reconciling new ontological commitments for newer use cases can be daunting. This situation was faced by the Biological and Chemical Oceanography Data Management Office (BCO-DMO) as it sought to integrate its existing linked data with other data repositories to address newer scientific use cases as a partner in the GeoLink Project. To achieve a successful integration with other GeoLink partners, BCO-DMO's metadata would need to be described using the new ontologies developed by the GeoLink partners - a situation that could impact semantic inferencing, pre-existing software and external users of BCO-DMO's linked data. This presentation describes the process of how GeoLink is bridging the gap between local, pre-existing ontologies to achieve scientific metadata integration for all its partners through the use of ontology design patterns. GeoLink, an NSF EarthCube Building Block, brings together experts from the geosciences, computer science, and library science in an effort to improve discovery and reuse of data and knowledge. Its participating repositories include content from field expeditions, laboratory analyses, journal publications, conference presentations, theses/reports, and funding awards that span scientific studies from marine geology to marine ecology and biogeochemistry to paleoclimatology. GeoLink's outcomes include a set of reusable ontology design patterns (ODPs) that describe core geoscience concepts, a network of Linked Data published by participating repositories using those ODPs, and tools to facilitate discovery of related content in multiple repositories.

To trade or not to trade: Link prediction in the virtual water network

NASA Astrophysics Data System (ADS)

Tuninetti, Marta; Tamea, Stefania; Laio, Francesco; Ridolfi, Luca

2017-12-01

In the international trade network, links express the (temporary) presence of a commercial exchange of goods between any two countries. Given the dynamical behaviour of the trade network, where links are created and dismissed every year, predicting the link activation/deactivation is an open research question. Through the international trade network of agricultural goods, water resources are 'virtually' transferred from the country of production to the country of consumption. We propose a novel methodology for link prediction applied to the network of virtual water trade. Starting from the assumption of having links between any two countries, we estimate the associated virtual water flows by means of a gravity-law model using country and link characteristics as drivers. We consider the links with estimated flows higher than 1000 m3/year as active links, while the others as non-active links. Flows traded along estimated active links are then re-estimated using a similar but differently-calibrated gravity-law model. We were able to correctly model 84% of the existing links and 93% of the non-existing links in year 2011. It is worth to note that the predicted active links carry 99% of the global virtual water flow; hence, missed links are mainly those where a minimum volume of virtual water is exchanged. Results indicate that, over the period from 1986 to 2011, population, geographical distances between countries, and agricultural efficiency (through fertilizers use) are the major factors driving the link activation and deactivation. As opposed to other (network-based) models for link prediction, the proposed method is able to reconstruct the network architecture without any prior knowledge of the network topology, using only the nodes and links attributes; it thus represents a general method that can be applied to other networks such as food or value trade networks.

Parallel language activation and cognitive control during spoken word recognition in bilinguals

PubMed Central

Blumenfeld, Henrike K.; Marian, Viorica

2013-01-01

Accounts of bilingual cognitive advantages suggest an associative link between cross-linguistic competition and inhibitory control. We investigate this link by examining English-Spanish bilinguals’ parallel language activation during auditory word recognition and nonlinguistic Stroop performance. Thirty-one English-Spanish bilinguals and 30 English monolinguals participated in an eye-tracking study. Participants heard words in English (e.g., comb) and identified corresponding pictures from a display that included pictures of a Spanish competitor (e.g., conejo, English rabbit). Bilinguals with higher Spanish proficiency showed more parallel language activation and smaller Stroop effects than bilinguals with lower Spanish proficiency. Across all bilinguals, stronger parallel language activation between 300–500ms after word onset was associated with smaller Stroop effects; between 633–767ms, reduced parallel language activation was associated with smaller Stroop effects. Results suggest that bilinguals who perform well on the Stroop task show increased cross-linguistic competitor activation during early stages of word recognition and decreased competitor activation during later stages of word recognition. Findings support the hypothesis that cross-linguistic competition impacts domain-general inhibition. PMID:24244842

Biofeedback With Implanted Blood-Pressure Device

NASA Technical Reports Server (NTRS)

Rischell, Robert E.

1988-01-01

Additional uses found for equipment described in "Implanted Blood-Pressure-Measuring Device" (GSC-13042). Implanted with device electronic circuitry that measures, interprets, and transmits data via inductive link through patient's skin to external receiver. Receiver includes audible alarm generator activated when patient's blood pressure exceeds predetermined threshold. Also included in receiver a blood-pressure display, recorder, or both, for use by patient or physician.

Characterization of the Neutralizing Antibody Response in a Case of Genetically Linked HIV Superinfection.

PubMed

Ssemwanga, Deogratius; Doria-Rose, Nicole A; Redd, Andrew D; Shiakolas, Andrea R; Longosz, Andrew F; Nsubuga, Rebecca N; Mayanja, Billy N; Asiki, Gershim; Seeley, Janet; Kamali, Anatoli; Ransier, Amy; Darko, Samuel; Walker, Michael P; Bruno, Daniel; Martens, Craig; Douek, Daniel; Porcella, Stephen F; Quinn, Thomas C; Mascola, John R; Kaleebu, Pontiano

2018-04-23

This report describes the identification of a genetically confirmed linked heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a woman with chronic HIV infection who acquired a second strain of the virus from her husband. Serum neutralizing antibody (NAb) responses against their homologous and heterologous viruses, including the superinfecting strain, in the woman and her husband were examined before and after onset of HIV-SI. The woman displayed a moderately potent and broad anti-HIV NAb response prior to superinfection but did not possess NAb activity against the superinfecting strain. This case highlights the unique potential of linked HIV-SI studies to examine natural protection from HIV infection.

Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase.

PubMed

Selak, Mary A; Armour, Sean M; MacKenzie, Elaine D; Boulahbel, Houda; Watson, David G; Mansfield, Kyle D; Pan, Yi; Simon, M Celeste; Thompson, Craig B; Gottlieb, Eyal

2005-01-01

Several mitochondrial proteins are tumor suppressors. These include succinate dehydrogenase (SDH) and fumarate hydratase, both enzymes of the tricarboxylic acid (TCA) cycle. However, to date, the mechanisms by which defects in the TCA cycle contribute to tumor formation have not been elucidated. Here we describe a mitochondrion-to-cytosol signaling pathway that links mitochondrial dysfunction to oncogenic events: succinate, which accumulates as a result of SDH inhibition, inhibits HIF-alpha prolyl hydroxylases in the cytosol, leading to stabilization and activation of HIF-1alpha. These results suggest a mechanistic link between SDH mutations and HIF-1alpha induction, providing an explanation for the highly vascular tumors that develop in the absence of VHL mutations.

A Longitudinal Assessment of the Links Between Physical Activity and Self-Esteem in Early Adolescent Non-Hispanic Females

PubMed Central

Schmalz, Dorothy L.; Deane, Glenn D.; Birch, Leann L.; Davison, Kirsten Krahnstoever

2008-01-01

Purpose: For decades, researchers have proclaimed the positive psychosocial benefits of participation in physical activity. However, recent meta-analyses of the literature have found infrequent and inconclusive empirical support for the link between physical activity and psychosocial well-being. In this study, we use data from a longitudinal study to explore the links between participation in physical activity and global self-esteem among girls from childhood into early adolescence and the direction of this relationship. Methods: Participants included 197 non-Hispanic white girls. Girls' participation in physical activity and their global self-esteem were assessed when they were 9, 11, and 13 years old. Panel regression was used to assess the lagged effect of physical activity on self-esteem and the lagged effect of self-esteem on physical activity, controlling for family socioeconomic status (SES) and girls' body mass index (BMI). Results: A significant lagged effect of physical activity on self-esteem was identified. Specifically, higher physical activity at ages 9 and 11 years predicted higher self-esteem at ages 11 and 13 years respectively, controlling for covariates. Positive effects of physical activity on self-esteem were most apparent at age 11 and for girls with higher BMI. No support was gained for the lagged effect of self-esteem on physical activity. Conclusions: Results suggest that participating in physical activity can lead to positive self-esteem among adolescent girls, particularly for younger girls and those at greatest risk of overweight. These findings highlight the necessity of promoting physical activity among adolescent girls as a method of fostering positive self-worth. PMID:18023784

Algal toxins in Upper Klamath Lake, Oregon: Linking water quality to juvenile sucker health

USGS Publications Warehouse

VanderKooi, S.P.; Burdick, S.M.; Echols, K.R.; Ottinger, C.A.; Rosen, B.H.; Wood, T.M.

2010-01-01

As the lead science agency for the Department of Interior, the U.S. Geological Survey is actively involved in resource issues in the Klamath River basin. Activities include research projects on endangered Lost River and shortnose suckers, threatened coho salmon, groundwater resources, seasonal runoff forecasting, water quality in Upper Klamath Lake and the Klamath River, nutrient cycling in wetlands, and assessment of land idling programs to reduce water consumption. Many of these studies are collaborations with various partners including Department of Interior agencies, Indian Tribes, and State agencies.

MayaQuest: A Student-Directed Expedition.

ERIC Educational Resources Information Center

Hefte, Rachel

1995-01-01

Describes an educational project linking classrooms using telecommunications with a four-person bicycling team exploring Mayan ruins in Central America. Provides a historical overview of the Mayan civilization. Includes suggested activities and provides information on how to obtain lesson plans on the project. (CFR)

Curcumin, inflammation, and chronic diseases: how are they linked?

PubMed

He, Yan; Yue, Yuan; Zheng, Xi; Zhang, Kun; Chen, Shaohua; Du, Zhiyun

2015-05-20

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

Functional analysis of the Helicobacter pullorum N-linked protein glycosylation system.

PubMed

Jervis, Adrian J; Wood, Alison G; Cain, Joel A; Butler, Jonathan A; Frost, Helen; Lord, Elizabeth; Langdon, Rebecca; Cordwell, Stuart J; Wren, Brendan W; Linton, Dennis

2018-04-01

N-linked protein glycosylation systems operate in species from all three domains of life. The model bacterial N-linked glycosylation system from Campylobacter jejuni is encoded by pgl genes present at a single chromosomal locus. This gene cluster includes the pglB oligosaccharyltransferase responsible for transfer of glycan from lipid carrier to protein. Although all genomes from species of the Campylobacter genus contain a pgl locus, among the related Helicobacter genus only three evolutionarily related species (H. pullorum, H. canadensis and H. winghamensis) potentially encode N-linked protein glycosylation systems. Helicobacter putative pgl genes are scattered in five chromosomal loci and include two putative oligosaccharyltransferase-encoding pglB genes per genome. We have previously demonstrated the in vitro N-linked glycosylation activity of H. pullorum resulting in transfer of a pentasaccharide to a peptide at asparagine within the sequon (D/E)XNXS/T. In this study, we identified the first H. pullorum N-linked glycoprotein, termed HgpA. Production of histidine-tagged HgpA in the background of insertional knockout mutants of H. pullorum pgl/wbp genes followed by analysis of HgpA glycan structures demonstrated the role of individual gene products in the PglB1-dependent N-linked protein glycosylation pathway. Glycopeptide purification by zwitterionic-hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry identified six glycosites from five H. pullorum proteins, which was consistent with proteins reactive with a polyclonal antiserum generated against glycosylated HgpA. This study demonstrates functioning of a H. pullorum N-linked general protein glycosylation system.

DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice.

PubMed

Shi, Sally Yu; Lu, Shun-Yan; Sivasubramaniyam, Tharini; Revelo, Xavier S; Cai, Erica P; Luk, Cynthia T; Schroer, Stephanie A; Patel, Prital; Kim, Raymond H; Bombardier, Eric; Quadrilatero, Joe; Tupling, A Russell; Mak, Tak W; Winer, Daniel A; Woo, Minna

2015-06-16

Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one of the most evolutionarily conserved proteins across species, and mutations in DJ-1 have been linked to some cases of Parkinson's disease. Here we show that DJ-1 maintains cellular metabolic homeostasis via modulating ROS levels in murine skeletal muscles, revealing a role of DJ-1 in maintaining efficient fuel utilization. We demonstrate that, in the absence of DJ-1, ROS uncouple mitochondrial respiration and activate AMP-activated protein kinase, which triggers Warburg-like metabolic reprogramming in muscle cells. Accordingly, DJ-1 knockout mice exhibit higher energy expenditure and are protected from obesity, insulin resistance and diabetes in the setting of fuel surplus. Our data suggest that promoting mitochondrial uncoupling may be a potential strategy for the treatment of obesity-associated metabolic disorders.

[An integrative model of the psychological benefits of gardening in older adults].

PubMed

Tournier, Isabelle; Postal, Virginie

2014-12-01

This review of the literature tackles the question of the psychological benefits linked to gardening in older adults. First, the current data on these benefits are reviewed, and the findings reveal that gardening is linked to feelings of accomplishment, well-being and peace, a decrease of depressive symptoms, a protective effect on cognitive functions as well as to the development of social links for community living older adults. In institutionalized older adults, gardening promotes internal locus of control and well-being, and is related to a decrease of sadness and anxiety. Second, several explanatory theories are discussed. All of them postulate an action on the cognitive and/or emotional spheres, which were included into a integrated model that must be tested in future research. In conclusion, gardening appears to be a beneficial activity for promoting older adults' functioning but the current knowledge still has to be extended to understand the specific mechanisms of action. This deeper understanding is necessary in order to improve the future actions depending on this activity.

Improving community development by linking agriculture, nutrition and education: design of a randomised trial of "home-grown" school feeding in Mali.

PubMed

Masset, Edoardo; Gelli, Aulo

2013-02-21

Providing food through schools has well documented effects in terms of the education, health and nutrition of school children. However, there is limited evidence in terms of the benefits of providing a reliable market for small-holder farmers through "home-grown" school feeding approaches. This study aims to evaluate the impact of school feeding programmes sourced from small-holder farmers on small-holder food security, as well as on school children's education, health and nutrition in Mali. In addition, this study will examine the links between social accountability and programme performance. This is a field experiment planned around the scale-up of the national school feeding programme, involving 116 primary schools in 58 communities in food insecure areas of Mali. The randomly assigned interventions are: 1) a school feeding programme group, including schools and villages where the standard government programme is implemented; 2) a "home-grown" school feeding and social accountability group, including schools and villages where the programme is implemented in addition to training of community based organisations and local government; and 3) the control group, including schools and household from villages where the intervention will be delayed by at least two years, preferably without informing schools and households. Primary outcomes include small-holder farmer income, school participation and learning, and community involvement in the programme. Other outcomes include nutritional status and diet-diversity. The evaluation will follow a mixed method approach, including household, school and village level surveys as well as focus group discussions with small-holder farmers, school children, parents and community members. The impact evaluation will be incorporated within the national monitoring and evaluation (M&E) system strengthening activities that are currently underway in Mali. Baselines surveys are planned for 2012. A monthly process monitoring visits, spot checks and quarterly reporting will be undertaken as part of the regular programme monitoring activities. Evaluation surveys are planned for 2014. National governments in sub-Saharan Africa have demonstrated strong leadership in the response to the recent food and financial crises by scaling-up school feeding programmes. "Home-grown" school feeding programmes have the potential to link the increased demand for school feeding goods and services to community-based stakeholders, including small-holder farmers and women's groups. Alongside assessing the more traditional benefits to school children, this evaluation will be the first to examine the impact of linking school food service provision to small-holder farmer income, as well as the link between community level engagement and programme performance. ISRCTN76705891.

Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory.

PubMed

Fazio, Leonardo; Pergola, Giulio; Papalino, Marco; Di Carlo, Pasquale; Monda, Anna; Gelao, Barbara; Amoroso, Nicola; Tangaro, Sabina; Rampino, Antonio; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2018-05-22

Dopamine D 1 receptor (D 1 R) signaling shapes prefrontal cortex (PFC) activity during working memory (WM). Previous reports found higher WM performance associated with alleles linked to greater expression of the gene coding for D 1 Rs ( DRD1 ). However, there is no evidence on the relationship between genetic modulation of DRD1 expression in PFC and patterns of prefrontal activity during WM. Furthermore, previous studies have not considered that D 1 Rs are part of a coregulated molecular environment, which may contribute to D 1 R-related prefrontal WM processing. Thus, we hypothesized a reciprocal link between a coregulated (i.e., coexpressed) molecular network including DRD1 and PFC activity. To explore this relationship, we used three independent postmortem prefrontal mRNA datasets (total n = 404) to characterize a coexpression network including DRD1 Then, we indexed network coexpression using a measure (polygenic coexpression index- DRD1 -PCI) combining the effect of single nucleotide polymorphisms (SNPs) on coexpression. Finally, we associated the DRD1 -PCI with WM performance and related brain activity in independent samples of healthy participants (total n = 371). We identified and replicated a coexpression network including DRD1 , whose coexpression was correlated with DRD1 -PCI. We also found that DRD1 -PCI was associated with lower PFC activity and higher WM performance. Behavioral and imaging results were replicated in independent samples. These findings suggest that genetically predicted expression of DRD1 and of its coexpression partners stratifies healthy individuals in terms of WM performance and related prefrontal activity. They also highlight genes and SNPs potentially relevant to pharmacological trials aimed to test cognitive enhancers modulating DRD1 signaling.

HTLV-1 Tax Stabilizes MCL-1 via TRAF6-Dependent K63-Linked Polyubiquitination to Promote Cell Survival and Transformation

PubMed Central

Choi, Young Bong; Harhaj, Edward William

2014-01-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein hijacks the host ubiquitin machinery to activate IκB kinases (IKKs) and NF-κB and promote cell survival; however, the key ubiquitinated factors downstream of Tax involved in cell transformation are unknown. Using mass spectrometry, we undertook an unbiased proteome-wide quantitative survey of cellular proteins modified by ubiquitin in the presence of Tax or a Tax mutant impaired in IKK activation. Tax induced the ubiquitination of 22 cellular proteins, including the anti-apoptotic BCL-2 family member MCL-1, in an IKK-dependent manner. Tax was found to promote the nondegradative lysine 63 (K63)-linked polyubiquitination of MCL-1 that was dependent on the E3 ubiquitin ligase TRAF6 and the IKK complex. Tax interacted with and activated TRAF6, and triggered its mitochondrial localization, where it conjugated four carboxyl-terminal lysine residues of MCL-1 with K63-linked polyubiquitin chains, which stabilized and protected MCL-1 from genotoxic stress-induced degradation. TRAF6 and MCL-1 played essential roles in the survival of HTLV-1 transformed cells and the immortalization of primary T cells by HTLV-1. Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation. PMID:25340740

Novel magnetic cross-linked lipase aggregates for improving the resolution of (R, S)-2-octanol.

PubMed

Liu, Ying; Guo, Chen; Liu, Chun-Zhao

2015-03-01

Novel magnetic cross-linked lipase aggregates were fabricated by immobilizing the cross-linked lipase aggregates onto magnetic particles with a high number of -NH2 terminal groups using p-benzoquinone as the cross-linking agent. At the optimal fabrication conditions, 100% of immobilization efficiency and 139% of activity recovery of the magnetic cross-linked lipase aggregates were achieved. The magnetic cross-linked lipase aggregates were able to efficiently resolve (R, S)-2-octanol, and retained 100% activity and 100% enantioselectivity after 10 cycles of reuse, whereas the cross-linked lipase aggregates only retained about 50% activity and 70% enantioselectivity due to insufficient cross-linking. These results provide a great potential for industrial applications of the magnetic cross-linked lipase aggregates. © 2014 Wiley Periodicals, Inc.

Physical activity and telomere biology: exploring the link with aging-related disease prevention.

PubMed

Ludlow, Andrew T; Roth, Stephen M

2011-02-21

Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling

PubMed Central

Chakraborty, Atanu; Diefenbacher, Markus E.; Mylona, Anastasia; Kassel, Olivier; Behrens, Axel

2015-01-01

The c-Jun/AP-1 transcription factor controls key cellular behaviours, including proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While the JNK pathway has been well characterised, the mechanism of activation by Ras was elusive. Here we identify the uncharacterised ubiquitin ligase Trim7 as a critical component of AP-1 activation via Ras. We found that MSK1 directly phosphorylates Trim7 in response to direct activation by the Ras–Raf–MEK–ERK pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity. Trim7 mediates Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilisation. Consequently, Trim7 depletion reduces RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer model, and knockdown of Trim7 in established xenografts reduces tumour growth. Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1 completes the long sought-after mechanism linking growth factor signalling and AP-1 activation. PMID:25851810

Deficiency of the Arabidopsis helicase RTEL1 triggers a SOG1-dependent replication checkpoint in response to DNA cross-links.

PubMed

Hu, Zhubing; Cools, Toon; Kalhorzadeh, Pooneh; Heyman, Jefri; De Veylder, Lieven

2015-01-01

To maintain genome integrity, DNA replication is executed and regulated by a complex molecular network of numerous proteins, including helicases and cell cycle checkpoint regulators. Through a systematic screening for putative replication mutants, we identified an Arabidopsis thaliana homolog of human Regulator of Telomere Length 1 (RTEL1), which functions in DNA replication, DNA repair, and recombination. RTEL1 deficiency retards plant growth, a phenotype including a prolonged S-phase duration and decreased cell proliferation. Genetic analysis revealed that rtel1 mutant plants show activated cell cycle checkpoints, specific sensitivity to DNA cross-linking agents, and increased homologous recombination, but a lack of progressive shortening of telomeres, indicating that RTEL1 functions have only been partially conserved between mammals and plants. Surprisingly, RTEL1 deficiency induces tolerance to the deoxynucleotide-depleting drug hydroxyurea, which could be mimicked by DNA cross-linking agents. This resistance does not rely on the essential replication checkpoint regulator WEE1 but could be blocked by a mutation in the SOG1 transcription factor. Taken together, our data indicate that RTEL1 is required for DNA replication and that its deficiency activates a SOG1-dependent replication checkpoint. © 2015 American Society of Plant Biologists. All rights reserved.

Changes in Your Watershed.

ERIC Educational Resources Information Center

Hill, Mindy

1995-01-01

Encourages educators to teach with concepts so that students may then proceed individually to link important information into a larger context. The lessons are particularly applicable to environmental education and are centered around the concept of change. The activities include information about geologic, climatic, and cultural change. (AIM)

How to Motivate Your Students

ERIC Educational Resources Information Center

Girmus, Ronald L.

2012-01-01

Student motivation is critical for learning. Psychological and neuroscientific evidence demonstrate that motivation and cognition are inextricably linked. In field research, 660 k-12 teachers were surveyed to self-identify the most successful strategies and activities they used to motivate students. A literature review that included 190 education…

The Montessori Farm School: Erdkinder Beginnings 2000.

ERIC Educational Resources Information Center

Kahn, David

2001-01-01

Discusses the development of the Montessori Farm School in Huntsburg, Ohio, summarizing prototype activities of the Erdkinder project and discussing psychological and pedagogical outcomes. Considers areas of struggle in how the school opened and includes diagrams for linking pedagogical and work experiences. Describes community transformations…

Pain in autoimmune disorders.

PubMed

Mifflin, Katherine A; Kerr, Bradley J

2017-06-01

Most autoimmune diseases are associated with pathological pain development. Autoimmune diseases with pathological pain include complex regional pain syndrome, rheumatoid arthritis, and Guillian-Barré syndrome to name a few. The present Review explores research linking the immune system to the development of pathological pain in autoimmune diseases. Pathological pain has been linked to T-cell activation and the release of cytokines from activated microglia in the dorsal horn of the spinal cord. New research on the role of autoantibodies in autoimmunity has generated insights into potential mechanisms of pain associated with autoimmune disease. Autoantibodies may act through various mechanisms in autoimmune disorders. These include the alteration of neuronal excitability via specific antigens such as the voltage-gated potassium channel complexes or by mediating bone destruction in rheumatoid arthritis. Although more research must be done to understand better the role of autoantibodies in autoimmune disease related pain, this may be a promising area of research for new analgesic therapeutic targets. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Children's patterns of emotional reactivity to conflict as explanatory mechanisms in links between interpartner aggression and child physiological functioning.

PubMed

Davies, Patrick T; Sturge-Apple, Melissa L; Cicchetti, Dante; Manning, Liviah G; Zale, Emily

2009-11-01

This paper examined children's fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children's emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. The results are interpreted within conceptualizations of how exposure and reactivity to family risk organize individual differences in physiological functioning.

Chemical properties and biological activity of a polysaccharide from Melocactus depressus.

PubMed

da Silva, Bernadete P; Parente, José P

2002-01-01

An arabinogalactan with mean Mr of 6.85 x 10(4), was isolated from the pulps of Melocactus depressus Hook by fractionation on Sephacryl S-300 HR. Chemical and spectroscopic studies indicated that it has a branched arabinogalactan type structure composed of beta-(1-->4) linked D-galactopyranose residues with beta-(1-->3) and beta-(1-->6) branching points. Its structural features include also alpha-(1-->2), alpha-(1-->3) and alpha-(1-->5) linked L-arabinofuranose residues. The polysaccharide demonstrated a phagocytosis stimulating property.

Bombesin-dependent pro-MMP-9 activation in prostatic cancer cells requires beta1 integrin engagement.

PubMed

Festuccia, Claudio; Angelucci, Adriano; Gravina, Giovanni; Eleuterio, Enrica; Vicentini, Carlo; Bologna, Mauro

2002-10-15

Bombesin-like peptides, including the mammalian homologue gastrin-releasing peptide, are highly expressed and secreted by neuroendocrine cells in prostate carcinoma tissues and are likely to be related to the progression of this neoplastic disease. Previously, we demonstrated that bombesin increased migration and protease expression in androgen-independent cells. In this work we show that bombesin is able to activate pro-MMP-9 through a mechanism involving the beta1 integrin subunit. In fact, MMP-9 processing was evident only when beta1 integrin was engaged with specific adhesive substrates, such as type I collagen, or when cells were seeded on dishes coated with antibodies against beta1 integrin, resulting in activation of the surface ligand. When exogenous pro-MMP-9 was added to PC3 cells, MMP-9 active forms were produced within 30 min by bombesin-treated cultures while control cultures expressed activated forms only after a longer time and at lower levels. MMP-9 activation required cytoskeleton integrity since this effect was abolished by cytochalasin D. Engagement of beta1 integrin caused an increased membrane-linked uPA activity which was required for MMP-9 activation. The cross talk between bombesin- and beta1-integrin-engaged signals seems to be crucial for the modulation of both membrane-linked uPA activity and MMP-9 activation and triggers complex intracellular signaling pathways requiring activation of tyrosine kinase activity, including that of src and PI3K. The beta1 integrin may be considered an important mechanism by which bombesin induces MMP-9 activation. This finding supports the idea that cellular responses to growth factors may be driven by cell-matrix interactions and stresses the role of neuroendocrine factors in prostate carcinoma progression.

Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5).

PubMed

Singh, Sheo B; Kaelin, David E; Meinke, Peter T; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Olsen, David B; Lagrutta, Armando; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Takeuchi, Tomoko; Takano, Hisashi; Ohata, Kohei; Kurasaki, Haruaki; Nishimura, Akinori; Shibata, Takeshi; Fukuda, Yasumichi

2015-09-01

Oxabicyclooctane linked novel bacterial topoisomerase inhibitors (NBTIs) are new class of recently reported broad-spectrum antibacterial agents. They target bacterial DNA gyrase and topoisomerase IV and bind to a site different than quinolones. They show no cross-resistance to known antibiotics and provide opportunity to combat drug-resistant bacteria. A structure activity relationship of the C-2 substituted ether analogs of 1,5-naphthyridine oxabicyclooctane-linked NBTIs are described. Synthesis and antibacterial activities of a total of 63 analogs have been summarized representing alkyl, cyclo alkyl, fluoro alkyl, hydroxy alkyl, amino alkyl, and carboxyl alkyl ethers. All compounds were tested against three key strains each of Gram-positive and Gram-negative bacteria as well as for hERG binding activities. Many key compounds were also tested for the functional hERG activity. Six compounds were evaluated for efficacy in a murine bacteremia model of Staphylococcus aureus infection. Significant tolerance for the ether substitution (including polar groups such as amino and carboxyl) at C-2 was observed for S. aureus activity however the same was not true for Enterococcus faecium and Gram-negative strains. Reduced clogD generally showed reduced hERG activity and improved in vivo efficacy but was generally associated with decreased overall potency. One of the best compounds was hydroxy propyl ether (16), which mainly retained the potency, spectrum and in vivo efficacy of AM8085 associated with the decreased hERG activity and improved physical property. Copyright © 2015 Elsevier Ltd. All rights reserved.

Research in Biological and Medical Sciences, Including Biochemistry, Communicable Disease and Immunology Internal Medicine, Nuclear Medicine, Physiology, Psychiatry, Surgery, and Veterinary Medicine

DTIC Science & Technology

1976-07-01

aversive stimuli, and activity in a variety of physiological systems implicated in psychosomatic dis- orders. The focus is on arrangement of consequences... activity are held to be linked cen- trally under most conditions. Changes in response to the pre-food stimulus in these DRL animals were less pronounced...individual differences both in autonomic activity and lever-pressing behavior. The to bolst increasi some of the latt the capa with the blood pr

Urban environment interventions linked to the promotion of physical activity. A mixed methods study applied to the urban context of Latin America

PubMed Central

Gomez, Luis F; Sarmiento, Rodrigo; Ordoñez, Maria Fernanda; Pardo, Carlos Felipe; de Sá, Thiago Hérick; Mallarino, Christina H; Miranda, J Jaime; Mosquera, Janeth; Parra, Diana Celmira; Reis, Rodrigo; Quistberg, Alex

2015-01-01

This study summarizes the evidence from quantitative systematic reviews that assessed the association between urban environment attributes and physical activity. It also documents sociopolitical barriers and facilitators involved in urban interventions linked with active living in the ten most populated urban settings of Latin America. The synthesis of evidence indicates that several attributes of urban environments are associated with physical activity, including land-use mix and cycling infrastructure. The documentary analysis indicated that despite the benefits and opportunities provided by the programs and existing infrastructure in the examined cities, an overall concern is the rising inequality in the coverage and distribution of the initiatives in the region. If these programs and initiatives are to achieve a real population level effect that helps to reduce health disparities, they need to examine their social and spatial distribution within the cities so they can reach underserved populations and develop to their full potential. PMID:25748111

Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes

PubMed Central

2017-01-01

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that display a wide variety of biological activities, from antimicrobial to antiallodynic. Lanthipeptides that display antimicrobial activity are called lantibiotics. The post-translational modification reactions of lanthipeptides include dehydration of Ser and Thr residues to dehydroalanine and dehydrobutyrine, a transformation that is carried out in three unique ways in different classes of lanthipeptides. In a cyclization process, Cys residues then attack the dehydrated residues to generate the lanthionine and methyllanthionine thioether cross-linked amino acids from which lanthipeptides derive their name. The resulting polycyclic peptides have constrained conformations that confer their biological activities. After installation of the characteristic thioether cross-links, tailoring enzymes introduce additional post-translational modifications that are unique to each lanthipeptide and that fine-tune their activities and/or stability. This review focuses on studies published over the past decade that have provided much insight into the mechanisms of the enzymes that carry out the post-translational modifications. PMID:28135077

Urban environment interventions linked to the promotion of physical activity: a mixed methods study applied to the urban context of Latin America.

PubMed

Gomez, Luis F; Sarmiento, Rodrigo; Ordoñez, Maria Fernanda; Pardo, Carlos Felipe; de Sá, Thiago Hérick; Mallarino, Christina H; Miranda, J Jaime; Mosquera, Janeth; Parra, Diana C; Reis, Rodrigo; Quistberg, D Alex

2015-04-01

This study summarizes the evidence from quantitative systematic reviews that assessed the association between urban environment attributes and physical activity. It also documents sociopolitical barriers and facilitators involved in urban interventions linked with active living in the ten most populated urban settings of Latin America. The synthesis of evidence indicates that several attributes of urban environments are associated with physical activity, including land-use mix and cycling infrastructure. The documentary analysis indicated that despite the benefits and opportunities provided by the programs and existing infrastructure in the examined cities, an overall concern is the rising inequality in the coverage and distribution of the initiatives in the region. If these programs and initiatives are to achieve a real population level effect that helps to reduce health disparities, they need to examine their social and spatial distribution within the cities so they can reach underserved populations and develop to their full potential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enterocin F4-9, a Novel O-Linked Glycosylated Bacteriocin.

PubMed

Maky, Mohamed Abdelfattah; Ishibashi, Naoki; Zendo, Takeshi; Perez, Rodney Honrada; Doud, Jehan Ragab; Karmi, Mohamed; Sonomoto, Kenji

2015-07-01

Enterococcus faecalis F4-9 isolated from Egyptian salted-fermented fish produces a novel bacteriocin, termed enterocin F4-9. Enterocin F4-9 was purified from the culture supernatant by three steps, and its molecular mass was determined to be 5,516.6 Da by mass spectrometry. Amino acid and DNA sequencing showed that the propeptide consists of 67 amino acid residues, with a leader peptide containing a double glycine cleavage site to produce a 47-amino-acid mature peptide. Enterocin F4-9 is modified by two molecules of N-acetylglucosamine β-O-linked to Ser37 and Thr46. The O-linked N-acetylglucosamine moieties are essential for the antimicrobial activity of enterocin F4-9. Further analysis of the enterocin F4-9 gene cluster identified enfC, which has high sequence similarity to a glycosyltransferase. The antimicrobial activity of enterocin F4-9 covered a limited range of bacteria, including, interestingly, a Gram-negative strain, Escherichia coli JM109. Enterocin F4-9 is sensitive to protease, active at a wide pH range, and moderately resistant to heat. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals.

PubMed

Arbulo-Echevarria, Mikel M; Muñoz-Miranda, Juan Pedro; Caballero-García, Andrés; Poveda-Díaz, José L; Fernández-Ponce, Cecilia; Durán-Ruiz, M Carmen; Miazek, Arkadiusz; García-Cózar, Francisco; Aguado, Enrique

2016-08-01

Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins. We have previously found that the adaptor linker for activation of T cells, evolutionarily related to non-T cell activation linker, is cleaved upon proapoptotic stimuli in T lymphocytes and thymocytes, in a tyrosine phosphorylation-dependent fashion. Here, we describe non-T cell activation linker proteolytic cleavage triggered in human B cells and monocytes by Fas cross-linking and staurosporine treatment. Non-T cell activation linker is cleaved, producing an N-terminal fragment of ∼22 kDa, and such cleavage is abrogated in the presence of caspase 8/granzyme B and caspase 3 inhibitors. Moreover, we have identified an aspartic acid residue at which non-T cell activation linker is cleaved, which similar to linker for activation of T cells, this aspartic acid residue is located close to tyrosine and serine residues, suggesting an interdependence of phosphorylation and proteolytic cleavage. Consistently, induction of non-T cell activation linker phosphorylation by pervanadate inhibits its cleavage. Interestingly, the truncated isoform of non-T cell activation linker, generated after cleavage, has a decreased signaling ability when compared with the full-length molecule. Altogether, our results suggest that cleavage of transmembrane adaptors constitutes a general mechanism for signal termination of immune receptors. © Society for Leukocyte Biology.

Creative Uses for Calculator-based Laboratory (CBL) Technology in Chemistry.

ERIC Educational Resources Information Center

Sales, Cynthia L.; Ragan, Nicole M.; Murphy, Maureen Kendrick

1999-01-01

Reviews three projects that use a graphing calculator linked to a calculator-based laboratory device as a portable data-collection system for students in chemistry classes. Projects include Isolation, Purification and Quantification of Buckminsterfullerene from Woodstove Ashes; Determination of the Activation Energy Associated with the…

Identification and Characterization of Tumor Antigens Associated with Breast Cancer

DTIC Science & Technology

2000-08-01

syndrome (ATR-X syndrome) which effective antitumoral immunity is currently an area of includes a- thalassemia , urogenital abnormalities, and a active...major histocompatibility complex class I-re- linked mental retardation with a- thalassemia (ATR-X stricted antigen of a murine colon tumor derives from

Ventral striatal activity links adversity and reward processing in children.

PubMed

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

2017-08-01

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

Qualitative Twitter analysis of participants, tweet strategies, and tweet content at a major urologic conference.

PubMed

Borgmann, Hendrik; Woelm, Jan-Henning; Merseburger, Axel; Nestler, Tim; Salem, Johannes; Brandt, Maximilian P; Haferkamp, Axel; Loeb, Stacy

2016-01-01

The microblogging social media platform Twitter is increasingly being adopted in the urologic field. We aimed to analyze participants, tweet strategies, and tweet content of the Twitter discussion at a urologic conference. A comprehensive analysis of the Twitter activity at the European Association of Urology Congress 2013 (#eau2013) was performed, including characteristics of user profiles, engagement and popularity measurements, characteristics and timing of tweets, and content analysis. Of 218 Twitter contributors, doctors (45%) were the most frequent, ahead of associations (15%), companies (10%), and journals (3%). However, journals had the highest tweet/participant rate (22 tweets/participant), profile activity (median: 1177, total tweets, 1805 followers, 979 following), and profile popularity (follower/following ratio: 2.1; retweet rank percentile: 96%). Links in a profile were associated with higher engagement (p<0.0001) and popularity (p<0.0001). Of 1572 tweets, 57% were original tweets, 71% contained mentions, 20% contained links, and 25% included pictures. The majority of tweets (88%) were during conference hours, with an average of 24.7 tweets/hour and a peak activity of 71 tweets/hour. Overall, 59% of tweets were informative, led by the topics uro-oncology (21%), urologic research (21%), and urotechnology (12%). Limitations include the analysis of a single conference analysis, assessment of global profile and not domain-specific activity, and the rapid evolution in Twitter-using habits. Results of this single conference qualitative analysis are promising for an enrichment of the scientific discussions at urologic conferences through the use of Twitter.

Drilling Deep Into STEM Education with JOIDES Resolution Education and Outreach Officers

NASA Astrophysics Data System (ADS)

Christiansen, E. A.

2015-12-01

During International Ocean Discovery Program (IODP) expeditions, IODP scientists and Education/Outreach (E/O) Officers enter classrooms and informal science venues via live Internet video links between the JOIDES Resolution (JR) and land-based learning centers. Post-expedition, E/O Officers, serving as JR Ambassadors, deepen and broaden the learning experience by bringing STEM from the JR to the general public through targeted outreach events at those land-based sites. Youth and adult learners participate in scientific inquiry through interactive activities linked directly to the video broadcast experience. Outreach venues include museums, summer camps, and after-school programs; classroom visits from E/O Officers encompass kindergarten to undergraduate school groups and often include professional development for educators. Events are hands-on with simulations, expedition samples, core models, and equipment available for interaction. This program can serve as a model for linking virtual and real experiences; deepening the educational value of virtual field trip events; and bringing cutting edge science into both classrooms and informal science venues.

Linking Sexual and Reproductive Health and Rights and HIV Services for Young People: The Link Up Project.

PubMed

Stackpool-Moore, Lucy; Bajpai, Divya; Caswell, Georgina; Crone, Tyler; Dewar, Fleur; Gray, Greg; Kyendikuwa, Allen; Mellin, Julie; Miller, Andrew; Morgan, Felicity; Orza, Luisa; Stevenson, Jacqui; Westerhof, Nienke; Wong, Felicia; Yam, Eileen; Zieman, Brady

2017-02-01

Sexual health and access to services are a pressing need for young people. This article introduces Link Up, a 3-year project in three African and two Asian countries, to enable and scale up access to integrated HIV services and sexual and reproductive health and rights for marginalized young people. The young people we worked with in this project included young men who have sex with men, young sex workers, young people who use drugs, young transgender people, young homeless people, and other vulnerable young people. The research and programmatic activities of Link Up, as illustrated in this Supplement, have highlighted the importance of recognizing and engaging with diversity among young people to improve access to services and outcomes protecting their health and human rights. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review

PubMed Central

Dinas, Petros C.; Lahart, Ian M.; Timmons, James A.; Svensson, Per-Arne; Koutedakis, Yiannis; Flouris, Andreas D.; Metsios, George S.

2017-01-01

Background: Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Methods: Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. Results: We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. Conclusions: The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews. PMID:28620456

A network dedicated to sciences dissemination : Scité

NASA Astrophysics Data System (ADS)

Botman, M.; Scité Network

2005-11-01

The activities of the network Scité are destined for the schools and the general public and include laboratories visits, training periods, seminars, conferences, adult courses specially designed for teachers, etc. Since 2002, collaborations between universities and enterprises are enhanced and developed to bring to light the variety of jobs linked to science and the multi-disciplinary process leading to industrial application of scientific findings. Activities will include, enterprises visits preparation of CD and video support presenting "passionate" jobs, and the set up of interactive workshops for students. Systematic relations and interactions with scientific as well as global media are established and formalised. Activities enhancing such interactions include the development of media-universities interface assuring the quality and the adequacy of scientific information transfer and vulgarisation. Based on the wide expertise accumulated through recent projects, Scité Network develop innovative activities involving a wide range of actors: universities, enterprises, media, schools, general public.

SAR studies directed toward the pyridine moiety of the sap-feeding insecticide sulfoxaflor (Isoclast™ active).

PubMed

Loso, Michael R; Benko, Zoltan; Buysse, Ann; Johnson, Timothy C; Nugent, Benjamin M; Rogers, Richard B; Sparks, Thomas C; Wang, Nick X; Watson, Gerald B; Zhu, Yuanming

2016-02-01

Sap-feeding insect pests constitute a major insect pest complex that includes a range of aphids, whiteflies, planthoppers and other insect species. Sulfoxaflor (Isoclast™ active), a new sulfoximine class insecticide, targets sap-feeding insect pests including those resistant to many other classes of insecticides. A structure activity relationship (SAR) investigation of the sulfoximine insecticides revealed the importance of a 3-pyridyl ring and a methyl substituent on the methylene bridge linking the pyridine and the sulfoximine moiety to achieving strong Myzus persicae activity. A more in depth QSAR investigation of pyridine ring substituents revealed a strong correlation with the calculated logoctanol/water partition coefficient (SlogP). Model development resulted in a highly predictive model for a set of 18 sulfoximines including sulfoxaflor. The model is consistent with and helps explain the highly optimized pyridine substitution pattern for sulfoxaflor. Copyright © 2015 Elsevier Ltd. All rights reserved.

HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains.

PubMed

Shibata, Yuri; Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Gohda, Jin; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro; Inoue, Jun-Ichiro

2017-01-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation.

HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains

PubMed Central

Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro

2017-01-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation. PMID:28103322

Policy Issues for Integrating Parenting Interventions and Addiction Treatment for Women.

ERIC Educational Resources Information Center

VanBremen, Jane R.; Chasnoff, Ira J.

1994-01-01

This article addresses the rationale for linking addiction treatment programs and parenting education interventions in substance-abusing families. Specific components of a parenting program for women in recovery are detailed, including parenting classes and support groups, mother-child play groups, and family literacy activities. Program…

CNN Newsroom Classroom Guides. September 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for September 1-30, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: Venezuela constitutional crisis, Panama's first female…

CNN Newsroom Classroom Guides. August 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These classroom guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for August 2-31, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: the drought and heatwave in the northeastern United…

Latina Mothers' School Preparation Activities and Their Relation to Children's Literacy Skills

ERIC Educational Resources Information Center

Durand, Tina M.

2010-01-01

Few studies have examined the link between children's early school achievement and parents' at-home practices exclusively among Latino groups. This study examined the relation between Latina mothers' reported at-home practices regarding school preparation and their children's literacy skills. Participants included 56 kindergarten children and…

Peace--Iowa's Link.

ERIC Educational Resources Information Center

Gore, Deborah, Ed.

1991-01-01

This theme journal issue is devoted to an exploration of peace and its history in Iowa. The features and activities include: Iowa's Peace Tradition; A Global View; World Map; A Mesquakie Tale; Swords into Plowshares; Make a Peace Crane; Student Protest; Goldfinch Patriotism Debate; Peace Meal; A Short Story; and Work It Out. (DB)

Ah-choo! Increased Risk of Pollen Allergies in the Northern Hemisphere

ERIC Educational Resources Information Center

Constible, Juanita; Sandro, Luke

2008-01-01

In this problem-based learning activity designed for nonscience majors, students assume the roles of scientists working for a public relations firm. Teams of students design communication products illustrating links between climate change and pollen allergies. Students develop a variety of process skills critical to scientists, including working…

A Thermodynamics Course Package in Onenote

ERIC Educational Resources Information Center

Falconer, John L.; Nicodemus, Garret D.; Medlin, J. Will; deGrazia, Janet; McDanel, Katherine P.

2014-01-01

A ready-to-use package of active-learning materials for a semester-long chemical engineering thermodynamics course was prepared for instructors, and similar materials are being prepared for a material and energy balance course. The course package includes ConcepTests, explanations of the ConcepTests for instructors, links to screencasts, chapter…

CNN Newsroom Classroom Guides. August 1998.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These Classroom Guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of August, provide program rundowns, suggestions for class activities and discussion, links to pertinent World Wide Web sites, and lists of related news terms. Topics include: meetings over weapons inspections in Iraq could either…

Active Cooperation Between Primary Users and Cognitive Radio Users in Heterogeneous Ad-Hoc Networks

DTIC Science & Technology

2012-04-01

processing to wireless communications and networking, including space-time coding and modulation for MIMO wireless communications, MIMO - OFDM systems, and...multiinput-multioutput ( MIMO ) system that can significantly increase the link capacity and realize a new form of spatial diversity which has been termed

CNN Newsroom Classroom Guides. May 1999.

ERIC Educational Resources Information Center

Turner Educational Services, Inc., Newtown, PA.

These classroom guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of May, provide program rundowns, suggestions for class activities and discussion, links to related World Wide Web sites, and lists of related news terms. Top stories include: Reverend Jesse Jackson secures release of U.S. soldiers…

Communication Apprehension Levels of Student Governance Leaders

ERIC Educational Resources Information Center

Miller, Michael T.; Nadler, Daniel P.

2009-01-01

A major component of the college student experience is the engagement with out-of-class activities. This involvement has been linked to a variety of success indicators, including higher levels of academic achievement, high retention and matriculation, and overall collegiate satisfaction. One of the key areas for student engagement is college…

OCCURRENCE OF VIRULENCE FACTOR ACTIVITY RELATIONSHIP (VFAR) IN ESCHERICHIA COLI ISOLATED FROM MUNICIPAL WASTEWATER EFFLUENTS

EPA Science Inventory

Escherichia coli O157:H7 has been linked to waterborne outbreaks in the United States and abroad. Methods employed to detect this pathogen typically are cultural based and take advantage of phenotypic traits that are specific for this serotype, including slow sorbitol fermentati...

CNN Newsroom Classroom Guides. February 1999.

ERIC Educational Resources Information Center

Turner Educational Services, Inc., Newtown, PA.

These classroom guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of February, provide program rundowns, suggestions for class activities and discussion, links to related World Wide Web sites, and lists of related news terms. Topics include: Monica Lewinsky scheduled to be deposed for the Senate,…

Linking Online Sexual Activities to Health Outcomes among Teens

ERIC Educational Resources Information Center

O'Sullivan, Lucia F.

2014-01-01

New digital technologies are highly responsive to many of the developmental needs of adolescents, including their need for intimate connection and social identity. This chapter explores adolescents' use of web-based sexual information, texting and "sexting," online dating sites, role-playing games, and sexually explicit media, and…

Characterization of breakpoint cluster region kinase and SH2-binding activities.

PubMed

Afar, D E; Witte, O N

1995-01-01

BCR is an interesting signaling protein, whose cellular function is currently unknown. Its biochemical properties include serine kinase activity, SH2-binding activity, and a GTPase-activating activity. The SH2-binding activity is particularly interesting because it may link BCR to signaling pathways involving SH2-containing molecules. Since tyrosine phosphorylation of BCR has been detected in CML-derived cell lines and since tyrosine-phosphorylated BCR shows increased affinity toward certain SH2 domains, it seems particularly important to further characterize this activity. This chapter described a simple purification scheme for partial purification of BCR, which can be used to assess in vitro kinase and SH2-binding activities.

Strategies, linkers and coordination polymers for high-performance sorbents

DOEpatents

Matzger, Adam J.; Wong-Foy, Antek G.; Lebel, Oliver

2015-09-15

A linking ligand compound includes three bidentate chemical moieties distributed about a central chemical moiety. Another linking ligand compound includes a bidentate linking ligand and a monodentate chemical moiety. Coordination polymers include a plurality of metal clusters linked together by residues of the linking ligand compounds.

Comparison of physical activity questionnaires for the elderly with the International Classification of Functioning, Disability and Health (ICF)--an analysis of content.

PubMed

Eckert, Katharina G; Lange, Martin A

2015-03-14

Physical activity questionnaires (PAQ) have been extensively used to determine physical activity (PA) levels. Most PAQ are derived from an energy expenditure-based perspective and assess activities with a certain intensity level. Activities with a moderate or vigorous intensity level are predominantly used to determine a person's PA level in terms of quantity. Studies show that the time spent engaging in moderate and vigorous intensity PA does not appropriately reflect the actual PA behavior of older people because they perform more functional, everyday activities. Those functional activities are more likely to be considered low-intense and represent an important qualitative health-promoting activity. For the elderly, functional, light intensity activities are of special interest but are assessed differently in terms of quantity and quality. The aim was to analyze the content of PAQ for the elderly. N = 18 sufficiently validated PAQ applicable to adults (60+) were included. Each item (N = 414) was linked to the corresponding code of the International Classification of Functioning, Disability and Health (ICF) using established linking rules. Kappa statistics were calculated to determine rater agreement. Items were linked to 598 ICF codes and 62 different ICF categories. A total of 43.72% of the codes were for sports-related activities and 14.25% for walking-related activities. Only 9.18% of all codes were related to household tasks. Light intensity, functional activities are emphasized differently and are underrepresented in most cases. Additionally, sedentary activities are underrepresented (5.55%). κ coefficients were acceptable for n = 16 questionnaires (0.48-1.00). There is a large inconsistency in the understandings of PA in elderly. Further research should focus (1) on a conceptual understanding of PA in terms of the behavior of the elderly and (2) on developing questionnaires that inquire functional, light intensity PA, as well as sedentary activities more explicitly.

Functional overlap between regions involved in speech perception and in monitoring one's own voice during speech production.

PubMed

Zheng, Zane Z; Munhall, Kevin G; Johnsrude, Ingrid S

2010-08-01

The fluency and the reliability of speech production suggest a mechanism that links motor commands and sensory feedback. Here, we examined the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or not and by examining the overlap with the network recruited during passive listening to speech sounds. We used real-time signal processing to compare brain activity when participants whispered a consonant-vowel-consonant word ("Ted") and either heard this clearly or heard voice-gated masking noise. We compared this to when they listened to yoked stimuli (identical recordings of "Ted" or noise) without speaking. Activity along the STS and superior temporal gyrus bilaterally was significantly greater if the auditory stimulus was (a) processed as the auditory concomitant of speaking and (b) did not match the predicted outcome (noise). The network exhibiting this Feedback Type x Production/Perception interaction includes a superior temporal gyrus/middle temporal gyrus region that is activated more when listening to speech than to noise. This is consistent with speech production and speech perception being linked in a control system that predicts the sensory outcome of speech acts and that processes an error signal in speech-sensitive regions when this and the sensory data do not match.

Functional overlap between regions involved in speech perception and in monitoring one’s own voice during speech production

PubMed Central

Zheng, Zane Z.; Munhall, Kevin G; Johnsrude, Ingrid S

2009-01-01

The fluency and reliability of speech production suggests a mechanism that links motor commands and sensory feedback. Here, we examine the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or not, and examining the overlap with the network recruited during passive listening to speech sounds. We use real-time signal processing to compare brain activity when participants whispered a consonant-vowel-consonant word (‘Ted’) and either heard this clearly, or heard voice-gated masking noise. We compare this to when they listened to yoked stimuli (identical recordings of ‘Ted’ or noise) without speaking. Activity along the superior temporal sulcus (STS) and superior temporal gyrus (STG) bilaterally was significantly greater if the auditory stimulus was a) processed as the auditory concomitant of speaking and b) did not match the predicted outcome (noise). The network exhibiting this Feedback type by Production/Perception interaction includes an STG/MTG region that is activated more when listening to speech than to noise. This is consistent with speech production and speech perception being linked in a control system that predicts the sensory outcome of speech acts, and that processes an error signal in speech-sensitive regions when this and the sensory data do not match. PMID:19642886

Promoting active transportation as a partnership between urban planning and public health: the columbus healthy places program.

PubMed

Green, Christine Godward; Klein, Elizabeth G

2011-01-01

Active transportation has been considered as one method to address the American obesity epidemic. To address obesity prevention through built-environment change, the local public health department in Columbus, Ohio, established the Columbus Healthy Places (CHP) program to formally promote active transportation in numerous aspects of community design for the city. In this article, we present a case study of the CHP program and discuss the review of city development rezoning applications as a successful strategy to link public health to urban planning. Prior to the CHP review, 7% of development applications in Columbus included active transportation components; in 2009, 64% of development applications adopted active transportation components specifically recommended by the CHP review. Active transportation recommendations generally included adding bike racks, widening or adding sidewalks, and providing sidewalk connectivity. Recommendations and lessons learned from CHP are provided.

Increased premotor cortex activation in high functioning autism during action observation.

PubMed

Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

2015-04-01

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Promoting Active Transportation as a Partnership Between Urban Planning and Public Health: The Columbus Healthy Places Program

PubMed Central

Green, Christine Godward; Klein, Elizabeth G.

2011-01-01

Active transportation has been considered as one method to address the American obesity epidemic. To address obesity prevention through built-environment change, the local public health department in Columbus, Ohio, established the Columbus Healthy Places (CHP) program to formally promote active transportation in numerous aspects of community design for the city. In this article, we present a case study of the CHP program and discuss the review of city development rezoning applications as a successful strategy to link public health to urban planning. Prior to the CHP review, 7% of development applications in Columbus included active transportation components; in 2009, 64% of development applications adopted active transportation components specifically recommended by the CHP review. Active transportation recommendations generally included adding bike racks, widening or adding sidewalks, and providing sidewalk connectivity. Recommendations and lessons learned from CHP are provided. PMID:21563711

Transforming Growth Factor-β-Activated Kinase 1 Is Required for Human FcγRIIIb-Induced Neutrophil Extracellular Trap Formation.

PubMed

Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

2016-01-01

Neutrophils (PMNs) are the most abundant leukocytes in the blood. PMN migrates from the circulation to sites of infection where they are responsible for antimicrobial functions. PMN uses phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. Several stimuli, including bacteria, fungi, and parasites, and some pharmacological compounds, such as Phorbol 12-myristate 13-acetate (PMA), are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. Recently, it was reported that FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. Direct cross-linking of FcγRIIA or integrins did not promote NET formation. FcγRIIIb-induced NET formation presented different kinetics from PMA-induced NET formation, suggesting differences in signaling. Because FcγRIIIb also induces a strong activation of extracellular signal-regulated kinase (ERK) and nuclear factor Elk-1, and the transforming growth factor-β-activated kinase 1 (TAK1) has recently been implicated in ERK signaling, in the present report, we explored the role of TAK1 in the signaling pathway activated by FcγRIIIb leading to NET formation. FcγRIIIb was stimulated by specific monoclonal antibodies, and NET formation was evaluated in the presence or absence of pharmacological inhibitors. The antibiotic LL Z1640-2, a selective inhibitor of TAK1 prevented FcγRIIIb-induced, but not PMA-induced NET formation. Both PMA and FcγRIIIb cross-linking induced phosphorylation of ERK. But, LL Z1640-2 only inhibited the FcγRIIIb-mediated activation of ERK. Also, only FcγRIIIb, similarly to transforming growth factor-β-induced TAK1 phosphorylation. A MEK (ERK kinase)-specific inhibitor was able to prevent ERK phosphorylation induced by both PMA and FcγRIIIb. These data show for the first time that FcγRIIIb cross-linking activates TAK1, and that this kinase is required for triggering the MEK/ERK signaling pathway to NETosis.

Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines?

PubMed Central

Freitag, Caroline M.; Miller, Richard J.

2014-01-01

Chronic pain presents a widespread and intractable medical problem. While numerous pharmaceuticals are used to treat chronic pain, drugs that are safe for extended use and highly effective at treating the most severe pain do not yet exist. Chronic pain resulting from nervous system injury (neuropathic pain) is common in conditions ranging from multiple sclerosis to HIV-1 infection to type II diabetes. Inflammation caused by neuropathy is believed to contribute to the generation and maintenance of neuropathic pain. Chemokines are key inflammatory mediators, several of which (MCP-1, RANTES, MIP-1α, fractalkine, SDF-1 among others) have been linked to chronic, neuropathic pain in both human conditions and animal models. The important roles chemokines play in inflammation and pain make them an attractive therapeutic target. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors known for their roles in metabolism. Recent research has revealed that PPARs also play a role in inflammatory gene repression. PPAR agonists have wide-ranging effects including inhibition of chemokine expression and pain behavior reduction in animal models. Experimental evidence suggests a connection between the pain ameliorating effects of PPAR agonists and suppression of inflammatory gene expression, including chemokines. In early clinical research, one PPARα agonist, palmitoylethanolamide (PEA), shows promise in relieving chronic pain. If this link can be better established, PPAR agonists may represent a new drug therapy for neuropathic pain. PMID:25191225

Improving community development by linking agriculture, nutrition and education: design of a randomised trial of “home-grown” school feeding in Mali

PubMed Central

2013-01-01

Background Providing food through schools has well documented effects in terms of the education, health and nutrition of school children. However, there is limited evidence in terms of the benefits of providing a reliable market for small-holder farmers through “home-grown” school feeding approaches. This study aims to evaluate the impact of school feeding programmes sourced from small-holder farmers on small-holder food security, as well as on school children’s education, health and nutrition in Mali. In addition, this study will examine the links between social accountability and programme performance. Design This is a field experiment planned around the scale-up of the national school feeding programme, involving 116 primary schools in 58 communities in food insecure areas of Mali. The randomly assigned interventions are: 1) a school feeding programme group, including schools and villages where the standard government programme is implemented; 2) a “home-grown” school feeding and social accountability group, including schools and villages where the programme is implemented in addition to training of community based organisations and local government; and 3) the control group, including schools and household from villages where the intervention will be delayed by at least two years, preferably without informing schools and households. Primary outcomes include small-holder farmer income, school participation and learning, and community involvement in the programme. Other outcomes include nutritional status and diet-diversity. The evaluation will follow a mixed method approach, including household, school and village level surveys as well as focus group discussions with small-holder farmers, school children, parents and community members. The impact evaluation will be incorporated within the national monitoring and evaluation (M&E) system strengthening activities that are currently underway in Mali. Baselines surveys are planned for 2012. A monthly process monitoring visits, spot checks and quarterly reporting will be undertaken as part of the regular programme monitoring activities. Evaluation surveys are planned for 2014. Discussion National governments in sub-Saharan Africa have demonstrated strong leadership in the response to the recent food and financial crises by scaling-up school feeding programmes. “Home-grown” school feeding programmes have the potential to link the increased demand for school feeding goods and services to community-based stakeholders, including small-holder farmers and women’s groups. Alongside assessing the more traditional benefits to school children, this evaluation will be the first to examine the impact of linking school food service provision to small-holder farmer income, as well as the link between community level engagement and programme performance. Trial registration ISRCTN76705891 PMID:23433395

The Transcription Factor EB Links Cellular Stress to the Immune Response



PubMed Central

Nabar, Neel R.; Kehrl, John H.

2017-01-01

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB’s function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation. PMID:28656016

The role of serotonin in personality inference: tryptophan depletion impairs the identification of neuroticism in the face.

PubMed

Ward, Robert; Sreenivas, Shubha; Read, Judi; Saunders, Kate E A; Rogers, Robert D

2017-07-01

Serotonergic mechanisms mediate the expression of personality traits (such as impulsivity, aggression and anxiety) that are linked to vulnerability to psychological illnesses, and modulate the identification of emotional expressions in the face as well as learning about broader classes of appetitive and aversive signals. Faces with neutral expressions signal a variety of socially relevant information, such that inferences about the big five personality traits, including Neuroticism, Extraversion and Agreeableness, can be accurately made on the basis of emotionally neutral facial photographs. Given the close link between Neuroticism and psychological distress, we investigated the effects of diminished central serotonin activity (achieved by tryptophan depletion) upon the accuracy of 52 healthy (non-clinical) adults' discriminations of personality from facial characteristics. All participants were able to discriminate reliably four of the big five traits. However, the tryptophan-depleted participants were specifically less accurate in discriminating Neuroticism than the matched non-depleted participants. These data suggest that central serotonin activity modulates the identification of not only negative facial emotional expression but also a broader class of signals about personality characteristics linked to psychological distress.

The Transcription Factor EB Links Cellular Stress to the Immune Response

.

PubMed

Nabar, Neel R; Kehrl, John H

2017-06-01

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB's function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation.

Social Relationships, Leisure Activity, and Health in Older Adults

PubMed Central

Chang, Po-Ju; Wray, Linda; Lin, Yeqiang

2015-01-01

Objective Although the link between enhanced social relationships and better health has generally been well established, few studies have examined the role of leisure activity in this link. This study examined how leisure influences the link between social relationships and health in older age. Methods Using data from the 2006 and 2010 waves of the nationally representative U.S. Health and Retirement Study and structural equation modelling analyses, we examined data on 2,965 older participants to determine if leisure activities mediated the link between social relationships and health in 2010, controlling for race, education level, and health in 2006. Results The results demonstrated that leisure activities mediate the link between social relationships and health in these age groups. Perceptions of positive social relationships were associated with greater involvement in leisure activities, and greater involvement in leisure activities was associated with better health in older age. Discussion & Conclusions The contribution of leisure to health in these age groups is receiving increasing attention, and the results of this study add to the literature on this topic, by identifying the mediating effect of leisure activity on the link between social relationships and health. Future studies aimed at increasing leisure activity may contribute to improved health outcomes in older adults. PMID:24884905

Social relationships, leisure activity, and health in older adults.

PubMed

Chang, Po-Ju; Wray, Linda; Lin, Yeqiang

2014-06-01

Although the link between enhanced social relationships and better health has generally been well established, few studies have examined the role of leisure activity in this link. This study examined how leisure influences the link between social relationships and health in older age. Using data from the 2006 and 2010 waves of the nationally representative U.S. Health and Retirement Study and structural equation modeling analyses, we examined data on 2,965 older participants to determine if leisure activities mediated the link between social relationships and health in 2010, controlling for race, education level, and health in 2006. The results demonstrated that leisure activities mediate the link between social relationships and health in these age groups. Perceptions of positive social relationships were associated with greater involvement in leisure activities, and greater involvement in leisure activities was associated with better health in older age. The contribution of leisure to health in these age groups is receiving increasing attention, and the results of this study add to the literature on this topic, by identifying the mediating effect of leisure activity on the link between social relationships and health. Future studies aimed at increasing leisure activity may contribute to improved health outcomes in older adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Distributed Cognition (DCOG): Foundations for a Computational Associative Memory Model

DTIC Science & Technology

2006-08-01

retrieved through context and attention . Instead of looking up an old exemplar in memory, we simulate it by activating the same (or almost the same) set of...association, regardless of current activation. We restrict our attention here to immediate links; although the algorithm can be generalized to include...recognition. A shift in attention may, by creating a new context, trigger the recognition of a concept. A detailed example of the use of attention in

Unit: Digging Up Evidence, Inspection Set, National Trial Print.

ERIC Educational Resources Information Center

Australian Science Education Project, Toorak, Victoria.

The teachers' guide to this trial version of a unit prepared by the Australian Science Education Project is an overprinted copy of the students' manual, including comments on the teaching techniques suggested for each activity, lists of recommended references and visual aids, and indications of links with other units produced by the Project. There…

CNN Newsroom Classroom Guides. October 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for October 1-29, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: nuclear accident in Japan (October 1); debate over the nuclear…

CNN Newsroom Classroom Guides. December 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for December 1-17, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: World AIDS Day, World Trade Organization protests in Seattle,…

CNN Newsroom Classroom Guides. November 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for November 1-30, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: EgyptAir Flight 990 crash, Oslo summit, India cyclone,…

Are Alcohol Expectancies Associations? Comment on Moss and Albery (2009)

ERIC Educational Resources Information Center

Wiers, Reinout W.; Stacy, Alan W.

2010-01-01

Moss and Albery (2009) presented a dual-process model of the alcohol-behavior link, integrating alcohol expectancy and alcohol myopia theory. Their integrative theory rests on a number of assumptions including, first, that alcohol expectancies are associations that can be activated automatically by an alcohol-relevant context, and second, that…

An Exploration of Note-Taking in an Online Calculus Course

ERIC Educational Resources Information Center

van de Sande, Carla; Abramson, Jay; Judson-Garcia, Julia

2017-01-01

Taking notes is a popular activity for students attending instructional lectures and has been linked to achievement. Research on note-taking has shown that the contents and usefulness of student notes depends on several factors, including the pace of the lecture and the presence of organizational and selection cues. However, this research has…

CNN Newsroom Classroom Guides. January 2000.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for January 3-28, 2000, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: issues of the Millennium, 100 hours of the Millennium, Mideast…

CNN Newsroom Classroom Guides. July 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for July 1-30, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related new terms. Top stories include: Kosovo after the strikes, and saving the Everglades (July 1-2);…

The Now Frontier. Linking Earth and Planets. Issue No. 1-4.

ERIC Educational Resources Information Center

Jet Propulsion Lab., Pasadena, CA.

This publication includes four pamphlets providing background material for understanding the NASA program of planetary flights. Each issue presents student involvement activities as well as suggested reading lists. Issue 1 describes the innermost planets of the solar system. Issue 2 gives information about the evolution of the planetary system as…

Low cost bioluminescence imaging as an alternative to in vivo bioassays for quantifying biologically active staphylococcal enterotoxin type E

USDA-ARS?s Scientific Manuscript database

Staphylococcus aureus is a major causative agent implicated in outbreaks of food poisoning, acting through the production of a range of toxins including staphylococcal enterotoxin type E (SEE). While tests such as enzyme-linked immunosorbent (ELISA) exist to detect the toxin molecules, existing meth...

CNN Newsroom Classroom Guides. February 2000.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for February 1-29, 2000, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: significance of the New Hampshire Primary, victors in the New…

CNN Newsroom Classroom Guides, March 2000.

ERIC Educational Resources Information Center

Turner Educational Services, Inc., Newtown, PA.

These classroom guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of March, provide program rundowns, suggestions for class activities and discussion, Web links, and a list of related news terms. Top stories include: primary victories in the Bush campaign and preparations by Gore and Bradley for the…

CNN Newsroom Classroom Guides. June 1999.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These guides, designed to accompany the daily Cable News Network (CNN) Newsroom broadcasts for June 1-30, 1999, provide program rundowns, suggestions for class activities and discussion, links to relevant World Wide Web sites, and a list of related news terms. Top stories include: NATO bombings in Belgrade amid peace negotiations, people of South…

Exploring the Links between Mentoring and Work-Integrated Learning

ERIC Educational Resources Information Center

Smith-Ruig, Theresa

2014-01-01

The role of work-integrated learning (WIL) is a popular focus at many universities, including among academics in the business disciplines in Australia. This article explores whether a mentoring programme provided for female business and law students results in similar benefits as those reported for WIL activities and, hence, provides career- and…

Rugby and Mathematics: A Surprising Link among Geometry, the Conics, and Calculus.

ERIC Educational Resources Information Center

Jones, Troy; Jackson, Steven

2001-01-01

Describes a rugby problem designed to help students understand the maximum-minimum situation. Presents a series of explorations that locate an optimal place for kicking the ball to maximize the angle at the goalposts. Uses interactive geometry software to construct a model of the situation. Includes a sample student activity. (KHR)

Food and mood.

PubMed

Ottley, C

A number of specific nutrients and other active substances in foods are thought to have a direct impact on mood. Carol Ottley explores the evidence linking food with aspects of mood and behaviour. Areas covered include premenstrual syndrome, chocolate craving, mood swings, and how we eat in relation to specific mood states such as fear, happiness and anxiety.

A Missing Link To Understanding Evolution.

ERIC Educational Resources Information Center

Chandler, Pauline

1997-01-01

Describes an activity in which students assume the roles of scientists living in the year 2,001,997 and make their own fossil record discoveries of animals that have undergone evolutionary changes since 1997. Students choose the animals as well as create the adaptations that have taken place. Includes a sample scoring rubric. (DKM)

Therapists' causal attributions of clients' problems and selection of intervention strategies.

PubMed

Royce, W S; Muehlke, C V

1991-04-01

Therapists' choices of intervention strategies are influenced by many factors, including judgments about the bases of clients' problems. To assess the relationships between such causal attributions and the selection of intervention strategies, 196 counselors, psychologists, and social workers responded to the written transcript of a client's interview by answering two questionnaires, a 1982 scale (Causal Dimension Scale by Russell) which measured causal attribution of the client's problem, and another which measured preference for emotional, rational, and active intervention strategies in dealing with the client, based on the 1979 E-R-A taxonomy of Frey and Raming. A significant relationship was found between the two sets of variables, with internal attributions linked to rational intervention strategies and stable attributions linked to active strategies. The results support Halleck's 1978 hypothesis that theories of psychotherapy tie interventions to etiological considerations.

Modulation of integrin-linked kinase nucleo-cytoplasmic shuttling by ILKAP and CRM1.

PubMed

Nakrieko, Kerry-Ann; Vespa, Alisa; Mason, David; Irvine, Timothy S; D'Souza, Sudhir J A; Dagnino, Lina

2008-07-15

Integrin-linked kinase (ILK) plays key roles in a variety of cell functions, including cell proliferation, adhesion and migration. Within the cell, ILK localizes to multiple sites, including the cytoplasm, focal adhesion complexes that mediate cell adhesion to extracellular substrates, as well as cell-cell junctions in epidermal keratinocytes. Central to understanding ILK function is the elucidation of the mechanisms that regulate its subcellular localization. We now demonstrate that ILK is imported into the nucleus through sequences in its N-terminus, via active transport mechanisms that involve nuclear pore complexes. In addition, nuclear ILK can be rapidly exported into the cytoplasm through a CRM1-dependent pathway, and its export is enhanced by the type 2C protein phosphatase ILKAP. Nuclear localization of ILK in epidermal keratinocytes is associated with increased DNA synthesis, which is sensitive to inhibition by ILKAP. Our studies demonstrate the importance for keratinocyte proliferation of ILK regulation through changes in its subcellular localization, and establish ILKAP and CRM1 as pivotal modulators of ILK subcellular distribution and activity in these cells.

Environmental surveillance and monitoring. The next frontiers ...

EPA Pesticide Factsheets

High throughput toxicity testing (HTT) technologies along with the world-wide web are revolutionizing both generation and access to data regarding the bioactivities that chemicals can elicit when they interact with specific proteins, genes, or other targets in the body of an organism. However, to date, most of the focus has been on the application of such data to assessment of individual chemicals. We suggest that environmental surveillance and monitoring represent the next frontiers for HTT. Resources already exist in curated databases of chemical-biological interactions, including highly standardized quantitative dose-response data generated from nascent HTT programs like ToxCast and Tox21, to link chemicals detected through environmental analytical chemistry to known biological activities. The emergence of the adverse outcome pathway framework and associated knowledgebase for linking molecular or pathway-level perturbations of biological systems to adverse outcomes traditionally considered in risk assessment and regulatory decision-making through a series of measureable biological changes provides a critical link between activity and hazard. Furthermore, environmental samples can be directly analyzed via HTT platforms to provide an unprecedented breadth of biological activity characterization that integrates the effects of all compounds present in a mixture, whether known or not. Novel application of these chemical-biological interaction data provide an oppor

A global view of undergraduate education in pharmacovigilance.

PubMed

Hartman, Jenny; Härmark, Linda; van Puijenbroek, Eugène

2017-07-01

The aim of this study was to gain insight in current pharmacovigilance educational activities and to gather information on which topics should be included in the undergraduate pharmacovigilance core curriculum. A web-based questionnaire was carried out containing 45 questions divided over four sections between 28 October 2014 and 31 January 2015. Potential participants working in pharmacovigilance and/or providing training in this field were invited via email and a widespread web link and snowball sampling was used to recruit additional participants. The questionnaire was filled out by 307 respondents from 88 different countries with a response rate of 29.3% for the email invitation and an unknown rate for the web link. Respondents were mainly pharmacists and physicians. Currently, lectures are the largest proportion of educational activities and all healthcare profession curricula have a mode of 2 h as number of contact hours per course. Respondents rated clinical aspects as the most important subdomain to be included in the core curriculum with prevention of adverse drug reactions as the most important subtopic. This was followed by communication aspects between parties, with communication between regulatory authorities and healthcare professionals, methodological aspects with causality assessment, and regulatory aspects with benefit-risk assessment. This is similar to subjects addressed in current educational activities with little difference between medical and pharmacy curricula. This study gave a good general impression in current educational activities and the respondents' needs and wishes for future activities worldwide, which both will be used for the development of the undergraduate pharmacovigilance core curriculum.

RGS16 inhibits breast cancer cell growth by mitigating phosphatidylinositol 3-kinase signaling.

PubMed

Liang, Genqing; Bansal, Geetanjali; Xie, Zhihui; Druey, Kirk M

2009-08-07

Aberrant activity of the phosphatidylinositol 3-kinase (PI3K) pathway supports growth of many tumors including those of breast, lung, and prostate. Resistance of breast cancer cells to targeted chemotherapies including tyrosine kinase inhibitors (TKI) has been linked to persistent PI3K activity, which may in part be due to increased membrane expression of epidermal growth factor (EGF) receptors (HER2 and HER3). Recently we found that proteins of the RGS (regulator of G protein signaling) family suppress PI3K activity downstream of the receptor by sequestering its p85alpha subunit from signaling complexes. Because a substantial percentage of breast tumors have RGS16 mutations and reduced RGS16 protein expression, we investigated the link between regulation of PI3K activity by RGS16 and breast cancer cell growth. RGS16 overexpression in MCF7 breast cancer cells inhibited EGF-induced proliferation and Akt phosphorylation, whereas shRNA-mediated extinction of RGS16 augmented cell growth and resistance to TKI treatment. Exposure to TKI also reduced RGS16 expression in MCF7 and BT474 cell lines. RGS16 bound the amino-terminal SH2 and inter-SH2 domains of p85alpha and inhibited its interaction with the EGF receptor-associated adapter protein Gab1. These results suggest that the loss of RGS16 in some breast tumors enhances PI3K signaling elicited by growth factors and thereby promotes proliferation and TKI evasion downstream of HER activation.

Serum Amyloid P Is a Sialylated Glycoprotein Inhibitor of Influenza A Viruses

PubMed Central

Job, Emma R.; Bottazzi, Barbara; Gilbertson, Brad; Edenborough, Kathryn M.; Brown, Lorena E.; Mantovani, Alberto; Brooks, Andrew G.; Reading, Patrick C.

2013-01-01

Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells. PMID:23544079

Children’s Patterns of Emotional Reactivity to Conflict as Explanatory Mechanisms in Links Between Interpartner Aggression and Child Physiological Functioning

PubMed Central

Davies, Patrick T.; Sturge-Apple, Melissa L.; Cicchetti, Dante; Manning, Liviah G.; Zale, Emily

2009-01-01

Background This paper examined children’s fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Methods Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children’s emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. Conclusions The results are interpreted within conceptualizations of how exposure and reactivity to family risk organizing individual differences in physiological functioning. PMID:19744183

Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

PubMed Central

Zourdos, Michael C.; Jo, Edward; Ormsbee, Michael J.

2013-01-01

Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation. PMID:24324381

Citric-Acid-Derived Photo-cross-Linked Biodegradable Elastomers

PubMed Central

Gyawali, Dipendra; Tran, Richard T.; Guleserian, Kristine J.; Tang, Liping; Yang, Jian

2010-01-01

Citric-acid-derived thermally cross-linked biodegradable elastomers (CABEs) have recently received significant attention in various biomedical applications, including tissue-engineering orthopedic devices, bioimaging and implant coatings. However, citric-acid-derived photo-cross-linked biodegradable elastomers are rarely reported. Herein, we report a novel photo-cross-linked biodegradable elastomer, referred to as poly(octamethylene maleate citrate) (POMC), which preserves pendant hydroxyl and carboxylic functionalities after cross-linking for the potential conjugation of biologically active molecules. POMC is a low-molecular-mass pre-polymer with a molecular mass average between 701 and 1291 Da. POMC networks are soft and elastic with an initial modulus of 0.07 to 1.3 MPa and an elongation at break between 38 and 382%. FT-IR–ATR results confirmed the successful surface immobilization of type-I collagen onto POMC films, which enhanced in vitro cellular attachment and proliferation. Photo-polymerized POMC films implanted subcutaneously into Sprague–Dawley rats demonstrated minimal in vivo inflammatory responses. The development of POMC enriches the family of citric-acid-derived biodegradable elastomers and expands the available biodegradable polymers for versatile needs in biomedical applications. PMID:20557687

Triphasic spike-timing-dependent plasticity organizes networks to produce robust sequences of neural activity

PubMed Central

Waddington, Amelia; Appleby, Peter A.; De Kamps, Marc; Cohen, Netta

2012-01-01

Synfire chains have long been proposed to generate precisely timed sequences of neural activity. Such activity has been linked to numerous neural functions including sensory encoding, cognitive and motor responses. In particular, it has been argued that synfire chains underlie the precise spatiotemporal firing patterns that control song production in a variety of songbirds. Previous studies have suggested that the development of synfire chains requires either initial sparse connectivity or strong topological constraints, in addition to any synaptic learning rules. Here, we show that this necessity can be removed by using a previously reported but hitherto unconsidered spike-timing-dependent plasticity (STDP) rule and activity-dependent excitability. Under this rule the network develops stable synfire chains that possess a non-trivial, scalable multi-layer structure, in which relative layer sizes appear to follow a universal function. Using computational modeling and a coarse grained random walk model, we demonstrate the role of the STDP rule in growing, molding and stabilizing the chain, and link model parameters to the resulting structure. PMID:23162457

Link prediction in the network of global virtual water trade

NASA Astrophysics Data System (ADS)

Tuninetti, Marta; Tamea, Stefania; Laio, Francesco; Ridolfi, Luca

2016-04-01

Through the international food-trade, water resources are 'virtually' transferred from the country of production to the country of consumption. The international food-trade, thus, implies a network of virtual water flows from exporting to importing countries (i.e., nodes). Given the dynamical behavior of the network, where food-trade relations (i.e., links) are created and dismissed every year, link prediction becomes a challenge. In this study, we propose a novel methodology for link prediction in the virtual water network. The model aims at identifying the main factors (among 17 different variables) driving the creation of a food-trade relation between any two countries, along the period between 1986 and 2011. Furthermore, the model can be exploited to investigate the network configuration in the future, under different possible (climatic and demographic) scenarios. The model grounds the existence of a link between any two nodes on the link weight (i.e., the virtual water flow): a link exists when the nodes exchange a minimum (fixed) volume of virtual water. Starting from a set of potential links between any two nodes, we fit the associated virtual water flows (both the real and the null ones) by means of multivariate linear regressions. Then, links with estimated flows higher than a minimum value (i.e., threshold) are considered active-links, while the others are non-active ones. The discrimination between active and non-active links through the threshold introduces an error (called link-prediction error) because some real links are lost (i.e., missed links) and some non-existing links (i.e., spurious links) are inevitably introduced in the network. The major drivers are those significantly minimizing the link-prediction error. Once the structure of the unweighted virtual water network is known, we apply, again, linear regressions to assess the major factors driving the fluxes traded along (modelled) active-links. Results indicate that, on the one hand, population and fertilizer use, together with link properties (such as the distance between nodes), are the major factors driving the links creation; on the other hand, population, distance, and gross domestic product are essential to model the flux entity. The results are promising since the model is able to correctly predict the 85% of the 16422 food-trade links (15% are missed), by spuriously adding to the real network only the 5% of non-existing links. The link-prediction error, evaluated as the sum of the percentage of missed and spurious links, is around 20% and it is constant over the study period. Only the 0.01% of the global virtual water flow is traded along missed links and an even lower flow is added by the spurious links (0.003%).

Role of mTOR Complexes in Neurogenesis.

PubMed

LiCausi, Francesca; Hartman, Nathaniel W

2018-05-22

Dysregulation of neural stem cells (NSCs) is associated with several neurodevelopmental disorders, including epilepsy and autism spectrum disorder. The mammalian target of rapamycin (mTOR) integrates the intracellular signals to control cell growth, nutrient metabolism, and protein translation. mTOR regulates many functions in the development of the brain, such as proliferation, differentiation, migration, and dendrite formation. In addition, mTOR is important in synaptic formation and plasticity. Abnormalities in mTOR activity is linked with severe deficits in nervous system development, including tumors, autism, and seizures. Dissecting the wide-ranging roles of mTOR activity during critical periods in development will greatly expand our understanding of neurogenesis.

Physical activity and cognitive-health content in top-circulating magazines, 2006-2008.

PubMed

Price, Anna E; Corwin, Sara J; Friedman, Daniela B; Laditka, Sarah B; Colabianchi, Natalie; Montgomery, Kara M

2011-04-01

Physical activity may promote cognitive health in older adults. Popular media play an important role in preventive health communication. This study examined articles discussing associations between physical activity and cognitive health in top-circulating magazines targeting older adults. 42,753 pages of magazines published from 2006 to 2008 were reviewed; 26 articles met inclusion criteria. Explanations regarding the link between physical activity and cognitive health were provided in 57.7% of articles. These explanations were generally consistent with empirical evidence; however, few articles included empirical evidence. Physical activity recommendations were presented in 80.8% of articles; a wide range was recommended (90-300 min of physical activity per wk). Socioeconomic status and education level were not mentioned in the text. Results suggest an opportunity for greater coverage regarding the role of physical activity in promoting cognitive health in popular media. Magazine content would benefit from including more empirical evidence, culturally sensitive content, and physical activity recommendations that are consistent with U.S. guidelines.

Chemical characteristics and anticoagulant activities of two sulfated polysaccharides from Enteromorpha linza (Chlorophyta)

NASA Astrophysics Data System (ADS)

Qi, Xiaohui; Mao, Wenjun; Chen, Yin; Chen, Yanli; Zhao, Chunqi; Li, Na; Wang, Chunyan

2013-03-01

Two sulfated polysaccharides, designated MP and SP, were extracted from the marine green alga Enteromorpha linza using hot water and then purified using ion-exchange and size-exclusion chromatography. The anticoagulant activities of MP and SP were examined by determination of their activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) using human plasma. Results showed that MP and SP were composed of abundant rhamnose with small amounts of xylose and glucuronic acid, whereas SP also contained a small amount of galactose. Approximate molecular weights of MP and SP were 535 and 502 kDa, respectively. As compared with SP, MP had higher contents of sulfate ester (19.0%) and uronic acid (14.9%). The MP mainly consisted of (1→4)-linked rhamnose residues with partially sulfated groups at the C-3 position, and small amounts of (1→3, 4)-linked rhamnose, (1→2, 4)-linked rhamnose, (1→4)-linked glucuronic acid and (1→4)-linked xylose residues. The SP contained abundant (1→4)-linked rhamnose with minor amounts of (1→3)-linked rhamnose, (1→3, 4)-linked rhamnose, (1→2, 4)-linked rhamnose, (1→4)-linked glucuronic acid, (1→4)-linked xylose, and (1→3)-linked galactose residues. The sulfate groups were mainly located at C-3 of (1→4)-linked rhamnose residues. Both MP and SP, in particular the former, effectively prolonged APTT and TT. This work demonstrates that MP and SP have unique structural characteristics distinct from those of other sulfated polysaccharides from Enteromorpha. The MP is a potential source of anticoagulant, and the difference in anticoagulant activities of the two sulfated polysaccharides is directly linked to the discrepancy of their chemical features.

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

PubMed

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

1996-07-01

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

Does the Neighborhood Context Alter the Link between Youth's After-School Time Activities and Developmental Outcomes? A Multilevel Analysis

ERIC Educational Resources Information Center

Fauth, Rebecca C.; Roth, Jodie L.; Brooks-Gunn, Jeanne

2007-01-01

This article examines links between different measures of after-school time activity participation (5 specific activities and breadth) on youth's developmental outcomes (anxiety/depression, delinquency, and substance use) over 6 years and whether these links are moderated by neighborhood-level variables. The sample (N = 1,315) of 9- and…

Active Semi-Supervised Community Detection Based on Must-Link and Cannot-Link Constraints

PubMed Central

Cheng, Jianjun; Leng, Mingwei; Li, Longjie; Zhou, Hanhai; Chen, Xiaoyun

2014-01-01

Community structure detection is of great importance because it can help in discovering the relationship between the function and the topology structure of a network. Many community detection algorithms have been proposed, but how to incorporate the prior knowledge in the detection process remains a challenging problem. In this paper, we propose a semi-supervised community detection algorithm, which makes full utilization of the must-link and cannot-link constraints to guide the process of community detection and thereby extracts high-quality community structures from networks. To acquire the high-quality must-link and cannot-link constraints, we also propose a semi-supervised component generation algorithm based on active learning, which actively selects nodes with maximum utility for the proposed semi-supervised community detection algorithm step by step, and then generates the must-link and cannot-link constraints by accessing a noiseless oracle. Extensive experiments were carried out, and the experimental results show that the introduction of active learning into the problem of community detection makes a success. Our proposed method can extract high-quality community structures from networks, and significantly outperforms other comparison methods. PMID:25329660

Extracurricular Activities in Multiethnic Middle Schools: Ideal Context for Positive Intergroup Attitudes?

PubMed

Knifsend, Casey A; Juvonen, Jaana

2017-06-01

This study examined processes by which extracurricular participation is linked with positive ethnic intergroup attitudes in multiethnic middle schools in California. Specifically, the mediating roles of activity-related cross-ethnic friendships and social identities including alliances with multiple groups were examined in a sample including African American or Black, East or South-East Asian, White, and Latino youth (N = 1,446; M age  = 11.60 in sixth grade). Results of multilevel modeling suggested that in addition to activity-related cross-ethnic friendships, complex social identities mediated the association between availability of cross-ethnic peers in activities and ethnic intergroup attitudes. Results are discussed in terms of how activities can be structured to promote cross-ethnic relationships and complex social identities, as well as positive ethnic intergroup attitudes. © 2016 The Authors. Journal of Research on Adolescence © 2016 Society for Research on Adolescence.

Temporo-parietal dysfunction in Tourette syndrome: Insights from an fMRI study of Theory of Mind.

PubMed

Eddy, Clare M; Cavanna, Andrea E; Rickards, Hugh E; Hansen, Peter C

2016-10-01

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics, repetitive movements and vocalizations which are prompted by a sensory-cognitive premonitory urge. Complex tics include environmentally dependent social behaviors such as echoing of other people's speech and actions. Recent studies have suggested that adults with TS can show differences to controls in Theory of Mind (ToM): reasoning about mental states (e.g. beliefs, emotions). In this study, twenty-five adults with uncomplicated TS (no co-morbid disorders, moderate tic severity), and twenty-five healthy age and gender matched controls were scanned with fMRI during an established ToM task. Neural activity was contrasted across ToM trials involving reasoning about false-belief, and matched trials requiring judgments about physical states rather than mental states. Contrasting task conditions uncovered differential fMRI activation in TS during ToM involving the right temporo-parietal junction (TPJ), right amygdala and posterior cingulate. Further analysis revealed that activity within the right TPJ as localised by this task covaried with the severity of symptoms including echophenomena, impulse control problems and premonitory urges in TS. Amygdala activation was also linked to premonitory urges, while activity in the left TPJ during ToM was linked to ratings of non-obscene socially inappropriate symptoms. These findings indicate that patients with TS exhibit atypical functional activation within key neural substrates involved in ToM. More generally, our data could highlight an important role for TPJ dysfunction in driving compulsive behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

New derivatives of 11-methyl-6-[2-(dimethylamino)ethyl]-6H-indolo[2,3-b]quinoline as cytotoxic DNA topoisomerase II inhibitors.

PubMed

Luniewski, Wojciech; Wietrzyk, Joanna; Godlewska, Joanna; Switalska, Marta; Piskozub, Malgorzata; Peczynska-Czoch, Wanda; Kaczmarek, Lukasz

2012-10-01

Novel indolo[2,3-b]quinoline derivatives substituted at N-6 and C-2 or C-9 positions with (dimethylamino)ethyl chains linked to heteroaromatic core by ether, amide or amine bonds, were manufactured and evaluated in vitro for their cytotoxic activity against several cell lines of different origin including multidrug resistant sublines and tested for their ability to influence the cell cycle and inhibit topoisomerase II activity. It was found, that all compounds show cytotoxic activity against cell lines tested, including multidrug resistant LoVo/DX, MES-SA/DX5 and HL-60 sublines. The tested compounds induce the G(2)M phase cell cycle arrest in Jurkat cells, and inhibit topoisomerase II activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Spirituality and the International Classification of Functioning, Disability and Health: content comparison of questionnaires measuring mindfulness based on the International Classification of Functioning.

PubMed

Offenbächer, Martin; Sauer, Sebastian; Hieblinger, Robin; Hufford, David J; Walach, Harald; Kohls, Niko

2011-01-01

To identify and compare the concepts contained in questionnaires measuring mindfulness using the International Classification of Functioning (ICF) as external reference. Questionnaires which are published in peer-reviewed journals and listed in Pubmed or PsycInfo were included. The questionnaires were analysed and, using a content-analytical approach, the respective items were categorised and linked to the ICF. Ten questionnaires were included. Ninety-four per cent (N = 341) of the concepts could be linked to 37 different ICF categories. One hundred and seventy-one (50.1%) concepts were linked to ICF categories of the component Body Function, 74 (21.7%) to categories of the component Activity and Participation and none to categories of the component Environmental Factors. In total, 28.2% of the linked concepts belonged to Personal factors, which are not yet classified in the ICF. The questionnaires exhibited considerable differences regarding content density (i.e. the average number of concepts per item) and content diversity (i.e. the number of ICF categories per concept). The ICF provides an useful external reference to identify and compare the concepts contained in mindfulness questionnaires. Also, mindfulness questionnaire concepts suggest potentially useful factors for classification within the ICF.

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Structural Characteristics and Anticancer Activity of Fucoidan from the Brown Alga Sargassum mcclurei

PubMed Central

Duc Thinh, Pham; Menshova, Roza V.; Ermakova, Svetlana P.; Anastyuk, Stanislav D.; Ly, Bui Minh; Zvyagintseva, Tatiana N.

2013-01-01

Three different fucoidan fractions were isolated and purified from the brown alga, Sargassum mcclurei. The SmF1 and SmF2 fucoidans are sulfated heteropolysaccharides that contain fucose, galactose, mannose, xylose and glucose. The SmF3 fucoidan is highly sulfated (35%) galactofucan, and the main chain of the polysaccharide contains a →3)-α-l-Fucp(2,4SO3−)-(1→3)-α-l-Fucp(2,4SO3−)-(1→ motif with 1,4-linked 3-sulfated α-l-Fucp inserts and 6-linked galactose on reducing end. Possible branching points include the 1,2,6- or 1,3,6-linked galactose and/or 1,3,4-linked fucose residues that could be glycosylated with terminal β-d-Galp residues or chains of alternating sulfated 1,3-linked α-l-Fucp and 1,4-linked β-d-Galp residues, which have been identified in galactofucans for the first time. Both α-l-Fucp and β-d-Galp residues are sulfated at C-2 and/or C-4 (and some C-6 of β-d-Galp) and potentially the C-3 of terminal β-d-Galp, 1,4-linked β-d-Galp and 1,4-linked α-l-Fucp residues. All fucoidans fractions were less cytotoxic and displayed colony formation inhibition in colon cancer DLD-1 cells. Therefore, these fucoidan fractions are potential antitumor agents. PMID:23648551

The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease.

PubMed

Gouweleeuw, L; Naudé, P J W; Rots, M; DeJongste, M J L; Eisel, U L M; Schoemaker, R G

2015-05-01

Depression is more common in patients with cardiovascular disease than in the general population. Conversely, depression is a risk factor for developing cardiovascular disease. Comorbidity of these two pathologies worsens prognosis. Several mechanisms have been indicated in the link between cardiovascular disease and depression, including inflammation. Systemic inflammation can have long-lasting effects on the central nervous system, which could be associated with depression. NGAL is an inflammatory marker and elevated plasma levels are associated with both cardiovascular disease and depression. While patients with depression show elevated NGAL levels, in patients with comorbid heart failure, NGAL levels are significantly higher and associated with depression scores. Systemic inflammation evokes NGAL expression in the brain. This is considered a proinflammatory effect as it is involved in microglia activation and reactive astrocytosis. Animal studies support a direct link between NGAL and depression/anxiety associated behavior. In this review we focus on the role of NGAL in linking depression and cardiovascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiology and social media: are private practice radiology groups more social than academic radiology departments?

PubMed

Glover, McKinley; Choy, Garry; Boland, Giles W; Saini, Sanjay; Prabhakar, Anand M

2015-05-01

This study assesses the prevalence of use of the most commonly used social media sites among private radiology groups (PRGs) and academic radiology departments (ARDs). The 50 largest PRGs and the 50 ARDs with the highest level of funding from the National Institutes of Health were assessed for presence of a radiology-specific social media account on Facebook, Twitter, Instagram, Pinterest, YouTube, and LinkedIn. Measures of organizational activity and end-user activity were collected, including the number of posts and followers, as appropriate; between-group comparisons were performed. PRGs adopted Facebook 12 months earlier (P = .02) and Twitter 18 months earlier (P = .02) than did ARDs. A total of 76% of PRGs maintained ≥1 account on the social media sites included in the study, compared with 28% of ARDs (P < .0001). The prevalence of having an account on the social media sites for PRGs was: Facebook, 66%; LinkedIn, 56%; Twitter, 42%; YouTube, 20%; Pinterest, 4%; and Instagram, 2%. The prevalence of radiology-specific social media accounts for ARDs was: Facebook, 18%; LinkedIn, 0%; Twitter, 24%; YouTube, 6%; Pinterest, 0%; and Instagram, 0%. There was no significant difference between ARDs and PRGs in measures of end-user or organizational activity on Facebook or Twitter. Use of social media in health care is emerging as mainstream, with PRGs being early adopters of Facebook and Twitter in comparison with ARDs. Competitive environments and institutional policies may be strong factors that influence how social media is used by radiologists at the group and department levels. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

PubMed Central

Polverino, Francesca; Celli, Bartolome R.

2018-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients. PMID:29468936

Deletion of nfnAB in Thermoanaerobacterium saccharolyticum and Its Effect on Metabolism

DOE PAGES

Lo, Jonathan; Zheng, Tianyong; Olson, Daniel G.; ...

2015-06-29

NfnAB catalyzes the reversible transfer of electrons from reduced ferredoxin and NADH to 2 NADP +. The NfnAB complex has been hypothesized to be the main enzyme for ferredoxin oxidization in strains of Thermoanaerobacterium saccharolyticum engineered for increased ethanol production. NfnAB complex activity was detectable in crude cell extracts of T. saccharolyticum. In this paper, activity was also detected using activity staining of native PAGE gels. The nfnAB gene was deleted in different strains of T. saccharolyticum to determine its effect on end product formation. In wild-type T. saccharolyticum, deletion of nfnAB resulted in a 46% increase in H 2more » formation but otherwise little change in other fermentation products. In two engineered strains with 80% theoretical ethanol yield, loss of nfnAB caused two different responses: in one strain, ethanol yield decreased to about 30% of the theoretical value, while another strain had no change in ethanol yield. Biochemical analysis of cell extracts showed that the ΔnfnAB strain with decreased ethanol yield had NADPH-linked alcohol dehydrogenase (ADH) activity, while the ΔnfnAB strain with unchanged ethanol yield had NADH-linked ADH activity. Deletion of nfnAB caused loss of NADPH-linked ferredoxin oxidoreductase activity in all cell extracts. Significant NADH-linked ferredoxin oxidoreductase activity was seen in all cell extracts, including those that had lost nfnAB. This suggests that there is an unidentified NADH:ferredoxin oxidoreductase (distinct from nfnAB) playing a role in ethanol formation. The NfnAB complex plays a key role in generating NADPH in a strain that had become reliant on NADPH-ADH activity. Importance: Thermophilic anaerobes that can convert biomass-derived sugars into ethanol have been investigated as candidates for biofuel formation. Many anaerobes have been genetically engineered to increase biofuel formation; however, key aspects of metabolism remain unknown and poorly understood. One example is the mechanism for ferredoxin oxidation and transfer of electrons to NAD(P) +. The electron-bifurcating enzyme complex NfnAB is known to catalyze the reversible transfer of electrons from reduced ferredoxin and NADH to 2 NADP + and is thought to play key roles linking NAD(P)(H) metabolism with ferredoxin metabolism. Finally, we report the first deletion of nfnAB and demonstrate a role for NfnAB in metabolism and ethanol formation in Thermoanaerobacterium saccharolyticum and show that this may be an important feature among other thermophilic ethanologenic anaerobes.« less

WheatGenome.info: A Resource for Wheat Genomics Resource.

PubMed

Lai, Kaitao

2016-01-01

An integrated database with a variety of Web-based systems named WheatGenome.info hosting wheat genome and genomic data has been developed to support wheat research and crop improvement. The resource includes multiple Web-based applications, which are implemented as a variety of Web-based systems. These include a GBrowse2-based wheat genome viewer with BLAST search portal, TAGdb for searching wheat second generation genome sequence data, wheat autoSNPdb, links to wheat genetic maps using CMap and CMap3D, and a wheat genome Wiki to allow interaction between diverse wheat genome sequencing activities. This portal provides links to a variety of wheat genome resources hosted at other research organizations. This integrated database aims to accelerate wheat genome research and is freely accessible via the web interface at http://www.wheatgenome.info/ .

An emerging link between LIM domain proteins and nuclear receptors.

PubMed

Sala, Stefano; Ampe, Christophe

2018-06-01

Nuclear receptors are ligand-activated transcription factors that partake in several biological processes including development, reproduction and metabolism. Over the last decade, evidence has accumulated that group 2, 3 and 4 LIM domain proteins, primarily known for their roles in actin cytoskeleton organization, also partake in gene transcription regulation. They shuttle between the cytoplasm and the nucleus, amongst other as a consequence of triggering cells with ligands of nuclear receptors. LIM domain proteins act as important coregulators of nuclear receptor-mediated gene transcription, in which they can either function as coactivators or corepressors. In establishing interactions with nuclear receptors, the LIM domains are important, yet pleiotropy of LIM domain proteins and nuclear receptors frequently occurs. LIM domain protein-nuclear receptor complexes function in diverse physiological processes. Their association is, however, often linked to diseases including cancer.

Wear Measurement of Highly Cross-linked UHMWPE using a 7Be Tracer Implantation Technique

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

Wimmer, Markus A.; Laurent, Michael P.; Dwivedi, Yasha

2013-01-01

The very low wear rates achieved with the current highly cross-linked ultrahigh molecular weight polyethylenes (UHMWPE) used in joint prostheses have proven to be difficult to measure accurately by gravimetry. Tracer methods are there- fore being explored. The purpose of this study was to perform a proof-of-concept experiment on the use of the radioactive tracer beryllium-7 (7Be) for the determination of in vitro wear in a highly cross-linked orthopedic UHMWPE. Three cross-linked and four conventional UHMWPE pins made from compression- molded GUR 1050, were activated with 109 to 1010 7Be nuclei using a new implantation setup that produced a homogenousmore » distribution of implanted nuclei up to 8.5 lm below the surface. The pins were tested for wear in a six-station pin-on-flat appara- tus for up to 7.1 million cycles (178 km). A Germanium gamma detector was employed to determine activity loss of the UHMWPE pins at preset intervals during the wear test. The wear of the cross-linked UHMWPE pins was readily detected and esti- mated to be 17 6 3 lg per million cycles. The conventional-to- cross-linked ratio of the wear rates was 13.1 6 0.8, in the expected range for these materials. Oxidative degradation dam- age from implantation was negligible; however, a weak depend- ence of wear on implantation dose was observed limiting the number of radioactive tracer atoms that can be introduced. Future applications of this tracer technology may include the analysis of location-specific wear, such as loss of material in the post or backside of a tibial insert.« less

A New Remote Communications Link to Reduce Residential PV Solar Costs

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

King, Randy; Sugiyama, Rod

Monitoring of PV/DER site production is expensive to install and unreliable. Among third party systems providers, lost communications links are a growing concern. Nearly 20% of links are failing, provisioning is complex, recovery is expensive, production data is lost, and access is fragmented. FleetLink is a new concept in DER system communications, purpose built for lowering the cost of maintaining active contact with residential end user sites and ensuring that production data is reliably available to third party systems providers. Systems providers require accurate, secure system monitoring and reporting of production data and system faults while driving down overall costsmore » to compete effectively. This plug and play, independently operating communications solution lowers the cost of fleet contact from typically .08 dollars-$.12/W down to .02 dollars -.03/W including installation and maintenance expenses. FleetLink establishes a breakthrough in simplicity that facilitates rapid expansion of residential solar by reducing initial capital outlay and lowering installation labor time and skill levels. The solution also facilitates higher DER installation growth rates by driving down maintenance costs and eliminating communications trouble calls. This is accomplished by the FleetLink’s unique network technology that enables dynamic network configuration for fast changes, and active, self-healing DER site contact for uptime assurance. Using an open source network framework with proprietary, application specific enhancements, FleetLink independently manages connectivity, security, recovery, grid control communications, and fleet expansion while presenting a compliant SunSpec interface to the third party operations centers. The net system cost savings of at least .05 dollars/W supports the SunShot cost goals and the flexibility and scalability of the solution accelerates the velocity and ubiquitous adoption of solar.« less

Applying activity-based costing in long-term care.

PubMed

Wodchis, W P

1998-01-01

As greater numbers of the elderly use health services, and as health care costs climb, effective financial tracking is essential. Cost management in health care can benefit if costs are linked to the care activities where they are incurred. Activity-based costing (ABC) provides a useful approach. The framework aligns costs (inputs), through activities (process), to outputs and outcomes. It allocates costs based on client care needs rather than management structure. The ABC framework was tested in a residential care facility and in supportive housing apartments. The results demonstrate the feasibility and advantages of ABC for long term care agencies, including community-based care.

Secondary science teachers' use of laboratory activities: Linking epistemological beliefs, goals, and practices

NASA Astrophysics Data System (ADS)

Kang, Nam-Hwa; Wallace, Carolyn S.

2005-01-01

The purpose of this study was to explore how science teachers' epistemological beliefs and teaching goals are related to their use of lab activities. Research questions include (a) What are the teachers' epistemological beliefs pertaining to lab activities? (b) Why do the science teachers use lab activities? (c) How are the teachers' epistemological beliefs and instructional goals related to teaching actions? Two major aspects of epistemologies guided this study: ontological aspect (certainty/diversity of truth) and relational aspect (relationship between the knower and the known). The ontological aspect addresses whether one views knowledge as one certain truth or as tentative multiple truths. The relational aspect addresses whether one views him/herself as a receiver of prescribed knowledge separating self from knowledge construction or as an active meaning maker connecting self to the knowledge construction processes. More sophisticated epistemological beliefs include the acknowledgement of multiple interpretations of the same phenomena and active role of the knower in knowledge construction. Three experienced secondary science teachers were interviewed and observed throughout an academic course. The findings illustrate that a teacher's naïve epistemological beliefs are clearly reflected in the teacher's teaching practices. However, a teacher's sophisticated epistemological beliefs are not always clearly connected to the practice. This seems to be related to the necessary negotiation among their epistemological beliefs, teaching contexts, and instructional goals. Ontological and relational beliefs seem to be connected to different facets of teaching practices. Findings indicate that various syntheses of different aspects of epistemological beliefs and instructional goals are linked to teachers' diverse ways of using lab activities. Implications for research and teacher education are discussed.

Linking hydrolytic activities to variables influencing a submerged membrane bioreactor (MBR) treating urban wastewater under real operating conditions.

PubMed

Gómez-Silván, C; Arévalo, J; Pérez, J; González-López, J; Rodelas, B

2013-01-01

The seasonal variation of the hydrolytic activities acid and alkaline phosphatase, α-glucosidase and protease, was studied in both the aerated and anoxic phases of a full-scale membrane bioreactor (MBR) (total operational volume = 28.2 m(3)), operated in pre-denitrification mode and fed real urban wastewater. Non-metric multidimensional scaling (MDS) and BIO-ENV analysis were used to study the distribution of enzyme activities in different seasons of the year (spring, summer and autumn) and unveil their relationships with changes in variables influencing the system (composition of influent wastewater, activated sludge temperature and biomass concentration in the bioreactors). The activities of all the tested hydrolases were remarkably dynamic, and each enzyme showed complex and diverse patterns of variation. Except in the summer season, the variables included in this study gave a good explanation of those patterns and displayed high and consistent correlations with them; however, markedly different correlation trends were found in each season, indicating dissimilar adaptation responses of the community to the influence of changing conditions. A consistent and highly negative correlation between protease and α-glucosidase was revealed in all the experiments. The variables included in this study showed contrary influences on these activities, suggesting an alternation of the major groups of carbon-degrading hydrolases in connection to changes in temperature and the availability and composition of nutrients in the different seasons. Sampling over a long period of time was required to adequately lay down the links between hydrolytic activities and the variables influencing the MBR system. These results highlight the complexity of the regulation of substrate degradation by the mixed microbial sludge communities under real operating conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

21 CFR 201.319 - Water-soluble gums, hydrophilic gums, and hydrophilic mucilloids (including, but not limited to...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Water-soluble gums, hydrophilic gums, and..., carboxymethylcellulose sodium, carrageenan, chondrus, glucomannan ((B-1,4 linked) polymannose acetate), guar gum, karaya... active ingredients; required warnings and directions. 201.319 Section 201.319 Food and Drugs FOOD AND...

Energy. Stop Faking It! Finally Understanding Science So You Can Teach It.

ERIC Educational Resources Information Center

Robertson, William C.

This book explains science concepts in a manner in which non-science teachers and parents can understand and learn science through activities. The concepts covered in this book include energy, simple machines, temperature, and heat transfer. Each chapter is supported with internet resources available at SciLinks and ends with a summary and…

Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants

USDA-ARS?s Scientific Manuscript database

High levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA(2) has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM...

Nitrogen-induced terrestrial eutrophication: cascading effects and impacts on ecosystem services

Treesearch

Christopher M. Clark; Michael D. Bell; James W. Boyd; Jana E. Compton; Eric A. Davidson; Christine Davis; Mark E. Fenn; Linda Geiser; Laurence Jones; Tamara F. Blett

2017-01-01

Human activity has significantly increased the deposition of nitrogen (N) on terrestrial ecosystems over pre-industrial levels leading to a multitude of effects including losses of biodiversity, changes in ecosystem functioning, and impacts on human well-being. It is challenging to explicitly link the level of deposition on an ecosystem to the cascade of...

STEM Education in the United States: Selected Web Resources

ERIC Educational Resources Information Center

Harrington, Eileen G.

2015-01-01

The purpose of this webliography is to provide an overview of STEM education in the U.S. It provides easy access to research and best practices in the field, as well as specific programs, activities, and lesson plans that formal and informal educators can implement. The webliography also includes links to advocacy programs and resources for…

Explaining Why Early-Maturing Girls Are More Exposed to Sexual Harassment in Early Adolescence

ERIC Educational Resources Information Center

Skoog, Therése; Bayram Özdemir, Sevgi

2016-01-01

In this study, we tested two competing explanations of the previously established link between early female puberty and sexual harassment in early adolescence. The sample included 680 seventh-grade Swedish girls (M[subscript age] = 13.40, SD = 0.53). Findings revealed that looking more sexually mature and being sexually active mediated the link…

Serving-Maids and Literacy: An Approach to Teaching Literacy through History and Music.

ERIC Educational Resources Information Center

Turner-Bisset, R.

2001-01-01

Presents a case study of an integrated approach to teaching history, literacy and music, in a Year 6 class. Suggests success was due to use of varied teaching approaches including storytelling, drama, singing and discussion. Emphasizes links between genuine historical tasks, and activities in the National Literacy Strategy. Suggests how music…

The College Connection: A Handbook for High School Students. Links to Success.

ERIC Educational Resources Information Center

Houston Independent School District, TX.

This handbook is a year-by-year planning guide to college preparatory activities for high school students and it begins with the 9th grade. These topics are included: (1) introduction to planning and the decision-making process; (2) educational and occupational alternatives; (3) considerations in choosing a college; (4) types of academic…

NSAID-activated gene 1 mediates pro-inflammatory signaling activation and paclitaxel chemoresistance in type I human epithelial ovarian cancer stem-like cells.

PubMed

Kim, Ki-Hyung; Park, Seong-Hwan; Do, Kee Hun; Kim, Juil; Choi, Kyung Un; Moon, Yuseok

2016-11-01

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in developed countries. Chronic endogenous sterile pro-inflammatory responses are strongly linked to EOC progression and chemoresistance to anti-cancer therapeutics. In the present study, the activity of epithelial NF-κB, a key pro-inflammatory transcription factor, was enhanced with the progress of EOC. This result was mechanistically linked with an increased expression of NSAID-Activated Gene 1 (NAG-1) in MyD88-positive type I EOC stem-like cells, compared with that in MyD88-negative type II EOC cells. Elevated NAG-1 as a potent biomarker of poor prognosis in the ovarian cancer was positively associated with the levels of NF-κB activation, chemokines and stemness markers in type I EOC cells. In terms of signal transduction, NAG-1-activated SMAD-linked and non-canonical TGFβ-activated kinase 1 (TAK-1)-activated pathways contributed to NF-κB activation and the subsequent induction of some chemokines and cancer stemness markers. In addition to effects on NF-κB-dependent gene regulation, NAG-1 was involved in expression of EGF receptor and subsequent activation of EGF receptor-linked signaling. The present study also provided evidences for links between NAG-1-linked signaling and chemoresistance in ovarian cancer cells. NAG-1 and pro-inflammatory NF-κB were positively associated with resistance to paclitaxel in MyD88-positive type I EOC cells. Mechanistically, this chemoresistance occurred due to enhanced activation of the SMAD-4- and non-SMAD-TAK-1-linked pathways. All of the present data suggested NAG-1 protein as a crucial mediator of EOC progression and resistance to the standard first-line chemotherapy against EOC, particularly in MyD88-positive ovarian cancer stem-like cells.

Retweets as a Predictor of Relationships among Users on Social Media.

PubMed

Tsugawa, Sho; Kito, Kosuke

2017-01-01

Link prediction is the problem of detecting missing links or predicting future link formation in a network. Application of link prediction to social media, such as Twitter and Facebook, is useful both for developing novel services and for sociological analyses. While most existing research on link prediction uses only the social network topology for the prediction, in social media, records of user activities such as posting, replying, and reposting are available. These records are expected to reflect user interest, and so incorporating them should improve link prediction. However, research into link prediction using the records of user activities is still in its infancy, and the effectiveness of such records for link prediction has not been fully explored. In this study, we focus in particular on records of reposting as a promising source that could be useful for link prediction, and investigate their effectiveness for link prediction on the popular social media platform Twitter. Our results show that (1) the prediction accuracy of techniques using reposting records is higher than that of popular topology-based techniques such as common neighbors and resource allocation for actively retweeting users, (2) the accuracy of link prediction techniques that use network topology alone can be improved by incorporating reposting records.

Retweets as a Predictor of Relationships among Users on Social Media

PubMed Central

Kito, Kosuke

2017-01-01

Link prediction is the problem of detecting missing links or predicting future link formation in a network. Application of link prediction to social media, such as Twitter and Facebook, is useful both for developing novel services and for sociological analyses. While most existing research on link prediction uses only the social network topology for the prediction, in social media, records of user activities such as posting, replying, and reposting are available. These records are expected to reflect user interest, and so incorporating them should improve link prediction. However, research into link prediction using the records of user activities is still in its infancy, and the effectiveness of such records for link prediction has not been fully explored. In this study, we focus in particular on records of reposting as a promising source that could be useful for link prediction, and investigate their effectiveness for link prediction on the popular social media platform Twitter. Our results show that (1) the prediction accuracy of techniques using reposting records is higher than that of popular topology-based techniques such as common neighbors and resource allocation for actively retweeting users, (2) the accuracy of link prediction techniques that use network topology alone can be improved by incorporating reposting records. PMID:28107489

Controlling self-sustained spiking activity by adding or removing one network link

NASA Astrophysics Data System (ADS)

Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

2013-06-01

Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

Chronic inflammation is etiology of extrinsic aging.

PubMed

Thornfeldt, Carl R

2008-03-01

Skin care regimens using active ingredients that are recommended by physicians who treat mucocutaneous conditions including aging should become more focused on reversing and preventing chronic inflammation. This adjustment of therapeutic and preventive strategies is necessary because chronic inflammation appears strongly linked to many preventable and treatable skin diseases and conditions such as visible skin aging. Mucocutaneous inflammation as the final common pathway of many systemic and mucocutaneous diseases including extrinsic aging has been established at the molecular and cellular levels. The corollary to this strategy includes inhibition of primary activators of mucocutaneous inflammation such as stratum corneum permeability barrier disruption, blocking any pro-inflammatory environmental insult such as ultraviolet radiation, and quenching tissue responses to these insults. This review will present the scientific rationale substantiating the conclusion that chronic inflammation is the common denominator in many mucocutaneous pathophysiologic processes including extrinsic skin aging.

Gamma Oscillations and Visual Binding

NASA Astrophysics Data System (ADS)

Robinson, Peter A.; Kim, Jong Won

2006-03-01

At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

PubMed

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S; Jain, Shalini; Lowell, Bradford B; Krashes, Michael J; Wess, Jürgen

2016-01-08

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

Impact of drought on crime in California: A synthetic control approach.

PubMed

Goin, Dana E; Rudolph, Kara E; Ahern, Jennifer

2017-01-01

Climate and weather have been linked to criminal activity. The connection between climatological conditions and crime is of growing importance as we seek to understand the societal implications of climate change. This study describes the mechanisms theorized to link annual variations in climate to crime in California and examines the effect of drought on statewide crime rates from 2011-2015. California has suffered severe drought since 2011, resulting in intensely dry winters and several of the hottest days on record. It is likely that the drought increased economic stress and shifted routine activities of the population, potentially increasing the likelihood of crime. We used a synthetic control method to estimate the impact of California's drought on both property and violent crimes. We found a significant increase in property crimes during the drought, but no effect on violent crimes. This result was robust to several sensitivity analyses, including a negative control.

Impact of drought on crime in California: A synthetic control approach

PubMed Central

Rudolph, Kara E.; Ahern, Jennifer

2017-01-01

Climate and weather have been linked to criminal activity. The connection between climatological conditions and crime is of growing importance as we seek to understand the societal implications of climate change. This study describes the mechanisms theorized to link annual variations in climate to crime in California and examines the effect of drought on statewide crime rates from 2011–2015. California has suffered severe drought since 2011, resulting in intensely dry winters and several of the hottest days on record. It is likely that the drought increased economic stress and shifted routine activities of the population, potentially increasing the likelihood of crime. We used a synthetic control method to estimate the impact of California’s drought on both property and violent crimes. We found a significant increase in property crimes during the drought, but no effect on violent crimes. This result was robust to several sensitivity analyses, including a negative control. PMID:28977002

An integrated user-oriented laboratory for verification of digital flight control systems: Features and capabilities

NASA Technical Reports Server (NTRS)

Defeo, P.; Doane, D.; Saito, J.

1982-01-01

A Digital Flight Control Systems Verification Laboratory (DFCSVL) has been established at NASA Ames Research Center. This report describes the major elements of the laboratory, the research activities that can be supported in the area of verification and validation of digital flight control systems (DFCS), and the operating scenarios within which these activities can be carried out. The DFCSVL consists of a palletized dual-dual flight-control system linked to a dedicated PDP-11/60 processor. Major software support programs are hosted in a remotely located UNIVAC 1100 accessible from the PDP-11/60 through a modem link. Important features of the DFCSVL include extensive hardware and software fault insertion capabilities, a real-time closed loop environment to exercise the DFCS, an integrated set of software verification tools, and a user-oriented interface to all the resources and capabilities.

Telomeres and Mitochondria in the Aging Heart

PubMed Central

Moslehi, Javid; DePinho, Ronald A.; Sahin, Ergün

2013-01-01

Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. PMID:22539756

A Mobile Satellite Experiment (MSAT-X) network definition

NASA Technical Reports Server (NTRS)

Wang, Charles C.; Yan, Tsun-Yee

1990-01-01

The network architecture development of the Mobile Satellite Experiment (MSAT-X) project for the past few years is described. The results and findings of the network research activities carried out under the MSAT-X project are summarized. A framework is presented upon which the Mobile Satellite Systems (MSSs) operator can design a commercial network. A sample network configuration and its capability are also included under the projected scenario. The Communication Interconnection aspect of the MSAT-X network is discussed. In the MSAT-X network structure two basic protocols are presented: the channel access protocol, and the link connection protocol. The error-control techniques used in the MSAT-X project and the packet structure are also discussed. A description of two testbeds developed for experimentally simulating the channel access protocol and link control protocol, respectively, is presented. A sample network configuration and some future network activities of the MSAT-X project are also presented.

Cellular-based modeling of oscillatory dynamics in brain networks.

PubMed

Skinner, Frances K

2012-08-01

Oscillatory, population activities have long been known to occur in our brains during different behavioral states. We know that many different cell types exist and that they contribute in distinct ways to the generation of these activities. I review recent papers that involve cellular-based models of brain networks, most of which include theta, gamma and sharp wave-ripple activities. To help organize the modeling work, I present it from a perspective of three different types of cellular-based modeling: 'Generic', 'Biophysical' and 'Linking'. Cellular-based modeling is taken to encompass the four features of experiment, model development, theory/analyses, and model usage/computation. The three modeling types are shown to include these features and interactions in different ways. Copyright © 2012 Elsevier Ltd. All rights reserved.

TSPO Expression and Brain Structure in the Psychosis Spectrum.

PubMed

Hafizi, Sina; Guma, Elisa; Koppel, Alex; Da Silva, Tania; Kiang, Michael; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Chakravarty, M Mallar; Mizrahi, Romina

2018-06-12

Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [ 18 F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [ 18 F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [ 18 F]FEPPA V T (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [ 18 F]FEPPA V T and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis. Copyright © 2018. Published by Elsevier Inc.

The relation between sexual behavior and religiosity subtypes: a test of the secularization hypothesis.

PubMed

Farmer, Melissa A; Trapnell, Paul D; Meston, Cindy M

2009-10-01

Previous literature on religion and sexual behavior has focused on narrow definitions of religiosity, including religious affiliation, religious participation, or forms of religiousness (e.g., intrinsic religiosity). Trends toward more permissive premarital sexual activity in the North American Christian-Judeo religion support the secularization hypothesis of religion, which posits an increasing gap between religious doctrine and behavior. However, the recent rise of fundamentalist and new age religious movements calls for a reexamination of the current link between religion and sexual behavior. The use of dual definitions of religiosity, including religious affiliation and dimensional subtypes, may further characterize this link. The present cross-sectional study evaluated patterns of sexual behavior in a young adult sample (N = 1302, M age = 18.77 years) in the context of the secularization hypothesis using religious affiliation and a liberal-conservative continuum of religious subtypes: paranormal belief, spirituality, intrinsic religiosity, and fundamentalism. Results indicated few affiliation differences in sexual behavior in men or women. Sexual behaviors were statistically predicted by spirituality, fundamentalism, and paranormal belief, and the endorsement of fundamentalism in particular was correlated with lower levels of female sexual behavior. The secularization hypothesis was supported by consistent levels of sexual activity across affiliations and is contradicted by the differential impact of religiosity subtypes on sexual behavior. Findings suggested that the use of religious subtypes to evaluate religious differences, rather than solely affiliation, may yield useful insights into the link between religion and sexual behavior.

Dissociating retrieval success from incidental encoding activity during emotional memory retrieval, in the medial temporal lobe

PubMed Central

Shafer, Andrea T.; Dolcos, Florin

2014-01-01

The memory-enhancing effect of emotion has been linked to the engagement of emotion- and memory-related medial temporal lobe (MTL) regions (amygdala-AMY; hippocampus-HC; parahippocampus-PHC), during both encoding and retrieval. However, recognition tasks used to investigate the neural correlates of retrieval make it difficult to distinguish MTL engagement linked to retrieval success (RS) from that linked to incidental encoding success (ES) during retrieval. This issue has been investigated for retrieval of non-emotional memories, but not for emotional memory retrieval. To address this, we used event-related functional MRI in conjunction with an emotional distraction and two episodic memory tasks (one testing memory for distracter items and the other testing memory for new/lure items presented in the first memory task). This paradigm allowed for dissociation of MTL activity specifically linked to RS from that linked to both RS and incidental ES during retrieval. There were two novel findings regarding the neural correlates of emotional memory retrieval. First, greater emotional RS was identified bilaterally in AMY, HC, and PHC. However, AMY activity was most impacted when accounting for ES activity, as only RS activity in left AMY was dissociated from ES activity during retrieval, whereas portions of HC and PHC showing greater emotional RS were largely uninvolved in ES. Second, an earlier and more anteriorly spread response (left AMY and bilateral HC, PHC) was linked to greater emotional RS activity, whereas a later and more posteriorly localized response (right posterior PHC) was linked to greater neutral RS activity. These findings shed light on MTL mechanisms subserving the memory-enhancing effect of emotion at retrieval. PMID:24917798

Potential effects of vildagliptin on biomarkers associated with prothrombosis in diabetes mellitus.

PubMed

Khan, Sana; Khan, Saba; Panda, Bibhu Prasad; Akhtar, Mohd; Najmi, Abul Kalam

2015-01-01

Diabetes mellitus (DM) is one of the risks linked with susceptibility of thrombosis. We tried to inspect the effect of a novel oral antidiabetic agent, vildagliptin, in preventing prothrombosis associated with DM. DM was produced by a dose of streptozotocin (STZ) or in albino wistar rats. Rats were treated orally with pioglitazone, standard treatment and vildagliptin alone and in combination for 3 weeks. Finally, the varied levels of coagulation biomarkers, including activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen and inflammatory parameters, nitric oxide (NO), C-reactive protein (CRP) and TNF-α and lipid profile were estimated along with platelet count and total leukocyte count (TLC). In vitro fibrinolytic activity of both the drugs was also determined. Vildagliptin significantly reduced cholesterol, triglycerides, TLC, CRP and TNF-α and increased aPTT and NO levels in STZ diabetic rats. However, pioglitazone was more successful in reducing fibrinogen and platelet count. Nevertheless, combination of the drugs was also effective than pioglitazone or vildagliptin alone in improvising hypercoagulation and inflammatory biomarkers. It is evident from the present study that vildagliptin has an influence on the biomarkers linked to the progression of thrombosis and may delay thrombogenesis linked to DM. Hence, vildagliptin alone and in combination might prove as an encouraging therapy for DM-linked thrombosis marked by inflammation and hypercoagulation.

Activation of duck RIG-I by TRIM25 is independent of anchored ubiquitin.

PubMed

Miranzo-Navarro, Domingo; Magor, Katharine E

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25 activation of duck RIG-I.

Twelve Years of Education and Public Outreach with the Fermi Gamma-ray Space Telescope

NASA Astrophysics Data System (ADS)

Cominsky, Lynn R.; McLin, K. M.; Simonnet, A.; Fermi E/PO Team

2013-04-01

During the past twelve years, NASA's Fermi Gamma-ray Space Telescope has supported a wide range of Education and Public Outreach (E/PO) activities, targeting K-14 students and the general public. The purpose of the Fermi E/PO program is to increase student and public understanding of the science of the high-energy Universe, through inspiring, engaging and educational activities linked to the mission’s science objectives. The E/PO program has additional more general goals, including increasing the diversity of students in the Science, Technology, Engineering and Mathematics (STEM) pipeline, and increasing public awareness and understanding of Fermi science and technology. Fermi's multi-faceted E/PO program includes elements in each major outcome category: ● Higher Education: Fermi E/PO promotes STEM careers through the use of NASA data including research experiences for students and teachers (Global Telescope Network), education through STEM curriculum development projects (Cosmology curriculum) and through enrichment activities (Large Area Telescope simulator). ● Elementary and Secondary education: Fermi E/PO links the science objectives of the Fermi mission to well-tested, customer-focused and NASA-approved standards-aligned classroom materials (Black Hole Resources, Active Galaxy Education Unit and Pop-up book, TOPS guides, Supernova Education Unit). These materials have been distributed through (Educator Ambassador and on-line) teacher training workshops and through programs involving under-represented students (after-school clubs and Astro 4 Girls). ● Informal education and public outreach: Fermi E/PO engages the public in sharing the experience of exploration and discovery through high-leverage multi-media experiences (Black Holes planetarium and PBS NOVA shows), through popular websites (Gamma-ray Burst Skymap, Epo's Chronicles), social media (Facebook, MySpace), interactive web-based activities (Space Mysteries, Einstein@Home) and activities by amateur astronomers nation-wide (Supernova! Toolkit). This poster highlights various facets of the Fermi E/PO program.

WheatGenome.info: an integrated database and portal for wheat genome information.

PubMed

Lai, Kaitao; Berkman, Paul J; Lorenc, Michal Tadeusz; Duran, Chris; Smits, Lars; Manoli, Sahana; Stiller, Jiri; Edwards, David

2012-02-01

Bread wheat (Triticum aestivum) is one of the most important crop plants, globally providing staple food for a large proportion of the human population. However, improvement of this crop has been limited due to its large and complex genome. Advances in genomics are supporting wheat crop improvement. We provide a variety of web-based systems hosting wheat genome and genomic data to support wheat research and crop improvement. WheatGenome.info is an integrated database resource which includes multiple web-based applications. These include a GBrowse2-based wheat genome viewer with BLAST search portal, TAGdb for searching wheat second-generation genome sequence data, wheat autoSNPdb, links to wheat genetic maps using CMap and CMap3D, and a wheat genome Wiki to allow interaction between diverse wheat genome sequencing activities. This system includes links to a variety of wheat genome resources hosted at other research organizations. This integrated database aims to accelerate wheat genome research and is freely accessible via the web interface at http://www.wheatgenome.info/.

Cross-Linked Enzyme Aggregates for Applications in Aqueous and Nonaqueous Media.

PubMed

Roy, Ipsita; Mukherjee, Joyeeta; Gupta, Munishwar N

2017-01-01

Extensive cross-linking of a precipitate of a protein by a cross-linking reagent (glutaraldehyde has been most commonly used) creates an insoluble enzyme preparation called cross-linked enzyme aggregates (CLEAs). CLEAs show high stability and performance in conventional aqueous as well as nonaqueous media. These are also stable at fairly high temperatures. CLEAs with more than one kind of enzyme activity can be prepared, and such CLEAs are called combi-CLEAs or multipurpose CLEAs. Extent of cross-linking often influences their morphology, stability, activity, and enantioselectivity.

Instructor-Created Activities to Engage Undergraduate Nursing Research Students.

PubMed

Pierce, Linda L; Reuille, Kristina M

2018-03-01

In flipped or blended classrooms, instruction intentionally shifts to a student-centered model for a problem-based learning approach, where class time explores topics in greater depth, creating meaningful learning opportunities. This article describes instructor-created activities focused on research processes linked to evidence-based practice that engage undergraduate nursing research students. In the classroom, these activities include individual and team work to foster critical thinking and stimulate student discussion of topic material. Six activities for small and large student groups are related to quantitative, qualitative, and both research processes, as well as applying research evidence to practice. Positive student outcomes included quantitative success on assignments and robust student topic discussions, along with instructor-noted overall group engagement and interest. Using these activities can result in class time for the construction of meaning, rather than primarily information transmission. Instructors may adopt these activities to involve and stimulate students' critical thinking about research and evidence-based practice. [J Nurs Educ. 2018;57(3):174-177.]. Copyright 2018, SLACK Incorporated.

O-GlcNAc transferase regulates transcriptional activity of human Oct4.

PubMed

Constable, Sandii; Lim, Jae-Min; Vaidyanathan, Krithika; Wells, Lance

2017-10-01

O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc. Octamer-binding protein 4 (Oct4) is one of the key transcription factors required for pluripotency of ES cells and more recently, the generation of induced pluripotent stem (iPS) cells. The action of Oct4 is modulated by the addition of several post-translational modifications, including O-GlcNAc. Previous studies in mice found a single site of O-GlcNAc addition responsible for transcriptional regulation. This study was designed to determine if this mechanism is conserved in humans. We mapped 10 novel sites of O-GlcNAc attachment on human Oct4, and confirmed a role for OGT in transcriptional activation of Oct4 at a site distinct from that found in mouse that allows distinction between different Oct4 target promoters. Additionally, we uncovered a potential new role for OGT that does not include its catalytic function. These results confirm that human Oct4 activity is being regulated by OGT by a mechanism that is distinct from mouse Oct4. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polyimides with attached chromophores for improved performance in electro-optical devices

NASA Astrophysics Data System (ADS)

Guenthner, Andrew J.; Wright, Michael E.; Fallis, Stephen; Lindsay, Geoffrey A.; Petteys, Brian J.; Yandek, Gregory R.; Zang, De-Yu; Sanghadasa, Mohan; Ashley, Paul R.

2006-08-01

A method of chemical synthesis that allows for the facile attachment of a wide variety of chemical compounds, including highly active nonlinear optical chromophores, to polyimides has been developed recently at the Naval Air Warfare Center, Weapons Division. The synthesis of these compounds is presented, along with a discussion of their relevant physical and chemical properties, alone and in comparison to equivalent guest/host materials. Examples of attached chromophores include the well-known Disperse Red 1, along with high-activity chromophores of more recent interest such as FTC and CLD. The synthesis of structures that contain both attached chromophores and chemical functionalities that enable thermal cross-linking of the polyimides is also discussed.

Characterization of member of DUF1888 protein family, self-cleaving and self-assembling endopeptidase.

PubMed

Osipiuk, Jerzy; Mulligan, Rory; Bargassa, Monireh; Hamilton, John E; Cunningham, Mark A; Joachimiak, Andrzej

2012-06-01

The crystal structure of SO1698 protein from Shewanella oneidensis was determined by a SAD method and refined to 1.57 Å. The structure is a β sandwich that unexpectedly consists of two polypeptides; the N-terminal fragment includes residues 1-116, and the C-terminal one includes residues 117-125. Electron density also displayed the Lys-98 side chain covalently linked to Asp-116. The putative active site residues involved in self-cleavage were identified; point mutants were produced and characterized structurally and in a biochemical assay. Numerical simulations utilizing molecular dynamics and hybrid quantum/classical calculations suggest a mechanism involving activation of a water molecule coordinated by a catalytic aspartic acid.

Wear Measurement of Highly Cross-Linked UHMWPE Using a 7Be Tracer Implantation Technique

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

Wimmer, Markus; Laurent, Michael P.; Dwivedi, Yash

2013-01-29

The very low wear rates achieved with the current highly cross-linked ultra-high molecular weight polyethylenes (UHMWPE) used in joint prostheses have proven to be difficult to measure accurately by gravimetry. Tracer methods are therefore being explored. The purpose of this study was to effect a proof-of-concept on the use of the radioactive tracer beryllium-7 (7Be) for the determination of wear in a highly cross-linked orthopedic UHMWPE. Three crosslinked and four conventional UHMWPE pins made from compression-molded GUR 1050, were activated with 109 to 1010 7Be nuclei using a new implantation setup that produced a homogenous distribution of implanted nuclei upmore » to 8.5 μm below the surface. The pins were tested for wear in a six-station pin-on-flat apparatus for up to 7.1 million cycles (178 km). A Germanium gamma detector was employed to determine activity loss of the UHMWPE pins at preset intervals during the wear test. The wear of the cross-linked UHMWPE pins was readily detected and estimated to be 17 ± 3 μg/Mc. The conventional-to-cross-linked ratio of the wear rates was 13.1 ± 0.8, in the expected range for these materials. It was estimated that implantation reduced the average wear rate by approximately 20%, and the oxidative degradation damage from implantation was negligible. Future applications of this tracer technology may include the analysis of location-specific wear, such as loss of material in the post or backside of a tibial insert.« less

View From Camera Not Used During Curiosity's First Six Months on Mars

NASA Image and Video Library

2017-12-08

This view of Curiosity's left-front and left-center wheels and of marks made by wheels on the ground in the "Yellowknife Bay" area comes from one of six cameras used on Mars for the first time more than six months after the rover landed. The left Navigation Camera (Navcam) linked to Curiosity's B-side computer took this image during the 223rd Martian day, or sol, of Curiosity's work on Mars (March 22, 2013). The wheels are 20 inches (50 centimeters) in diameter. Curiosity carries a pair of main computers, redundant to each other, in order to have a backup available if one fails. Each of the computers, A-side and B-side, also has other redundant subsystems linked to just that computer. Curiosity operated on its A-side from before the August 2012 landing until Feb. 28, when engineers commanded a switch to the B-side in response to a memory glitch on the A-side. One set of activities after switching to the B-side computer has been to check the six engineering cameras that are hard-linked to that computer. The rover's science instruments, including five science cameras, can each be operated by either the A-side or B-side computer, whichever is active. However, each of Curiosity's 12 engineering cameras is linked to just one of the computers. The engineering cameras are the Navigation Camera (Navcam), the Front Hazard-Avoidance Camera (Front Hazcam) and Rear Hazard-Avoidance Camera (Rear Hazcam). Each of those three named cameras has four cameras as part of it: two stereo pairs of cameras, with one pair linked to each computer. Only the pairs linked to the active computer can be used, and the A-side computer was active from before landing, in August, until Feb. 28. All six of the B-side engineering cameras have been used during March 2013 and checked out OK. Image Credit: NASA/JPL-Caltech NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

PubMed

Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

2018-03-01

Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

Immunomodulatory Activity of Dietary Fiber: Arabinoxylan and Mixed-Linked Beta-Glucan Isolated from Barley Show Modest Activities in Vitro

PubMed Central

Samuelsen, Anne Berit; Rieder, Anne; Grimmer, Stine; Michaelsen, Terje E.; Knutsen, Svein H.

2011-01-01

High intake of dietary fiber is claimed to protect against development of colorectal cancer. Barley is a rich source of dietary fiber, and possible immunomodulatory effects of barley polysaccharides might explain a potential protective effect. Dietary fiber was isolated by extraction and enzyme treatment. A mixed-linked β-glucan (WSM-TPX, 96.5% β-glucan, Mw 886 kDa), an arabinoxylan (WUM-BS-LA, 96.4% arabinoxylan, Mw 156 kDa), a mixed-linked β-glucan rich fraction containing 10% arabinoxylan (WSM-TP) and an arabinoxylan rich fraction containing 30% mixed-linked β-glucan (WUM-BS) showed no significant effect on IL-8 secretion and proliferation of two intestinal epithelial cell lines, Caco-2 and HT-29, and had no significant effect on the NF-κB activity in the monocytic cell line U937-3κB-LUC. Further enriched arabinoxylan fractions (WUM-BS-LA) from different barley varieties (Tyra, NK96300, SB94897 and CDCGainer) were less active than the mixed-linked β-glucan rich fractions (WSM-TP and WSM-TPX) in the complement-fixing test. The mixed-linked β-glucan rich fraction from NK96300 and CDCGainer showed similar activities as the positive control while mixed-linked β-glucan rich fractions from Tyra and SB94897 were less active. From these results it is concluded that the isolated high molecular weight mixed-linked β-glucans and arabinoxylans from barley show low immunological responses in selected in vitro test systems and thus possible anti-colon cancer effects of barley dietary fiber cannot be explained by our observations. PMID:21340001

A non-heme iron-mediated chemical demethylation in DNA and RNA.

PubMed

Yi, Chengqi; Yang, Cai-Guang; He, Chuan

2009-04-21

DNA methylation is arguably one of the most important chemical signals in biology. However, aberrant DNA methylation can lead to cytotoxic or mutagenic consequences. A DNA repair protein in Escherichia coli, AlkB, corrects some of the unwanted methylations of DNA bases by a unique oxidative demethylation in which the methyl carbon is liberated as formaldehyde. The enzyme also repairs exocyclic DNA lesions--that is, derivatives in which the base is augmented with an additional heterocyclic subunit--by a similar mechanism. Two proteins in humans that are homologous to AlkB, ABH2 and ABH3, repair the same spectrum of lesions; another human homologue of AlkB, FTO, is linked to obesity. In this Account, we describe our studies of AlkB, ABH2, and ABH3, including our development of a general strategy to trap homogeneous protein-DNA complexes through active-site disulfide cross-linking. AlkB uses a non-heme mononuclear iron(II) and the cofactors 2-ketoglutarate (2KG) and dioxygen to effect oxidative demethylation of the DNA base lesions 1-methyladenine (1-meA), 3-methylcytosine (3-meC), 1-methylguanine (1-meG), and 3-methylthymine (3-meT). ABH3, like AlkB, works better on single-stranded DNA (ssDNA) and is capable of repairing damaged bases in RNA. Conversely, ABH2 primarily repairs lesions in double-stranded DNA (dsDNA); it is the main housekeeping enzyme that protects the mammalian genome from 1-meA base damage. The AlkB-family proteins have moderate affinities for their substrates and bind DNA in a non-sequence-specific manner. Knowing that these proteins flip the damaged base out from the duplex DNA and insert it into the active site for further processing, we first engineered a disulfide cross-link in the active site to stabilize the Michaelis complex. Based on the detailed structural information afforded by the active-site cross-linked structures, we can readily install a cross-link away from the active site to obtain the native-like structures of these complexes. The crystal structures show a distinct base-flipping feature in AlkB and establish ABH2 as a dsDNA repair protein. They also provide a molecular framework for understanding the demethylation reaction catalyzed by these proteins and help to explain their substrate preferences. The chemical cross-linking method demonstrated here can be applied to trap other labile protein-DNA interactions and can serve as a general strategy for exploring the structural and functional aspects of base-flipping proteins.

Extracurricular Activity Participation in High School: Mechanisms Linking Participation to Math Achievement and 4-Year College Attendance

ERIC Educational Resources Information Center

Morris, David S.

2016-01-01

Extracurricular activity participation (EAP) has been positively linked with increased academic achievement and college attendance. However, the mechanisms linking EAP to educational outcomes are poorly understood. Using the Education Longitudinal Study of 2002 (ELS), this study contributes to our understanding of the relationship between EAP and…

Do parents' exercise habits predict 13-18-year-old adolescents' involvement in sport?

PubMed

Sukys, Saulius; Majauskienė, Daiva; Cesnaitiene, Vida J; Karanauskiene, Diana

2014-09-01

This study examined links between parents' exercise habits and adolescents' participation in sports activities, considering the aspects of gender and age. It was hypothesized that regular exercise by both parents would be related to children's involvement in sport regardless of their gender and age. Moreover, it was hypothesized that children's sports activities would be more strongly related to their father's exercise activities. The study also examined the links between parents' exercise habits and children's motivation for sports. It was hypothesized that competition motives would be more important for children whose parents exercised regularly. The research sample included 2335 students from the seventh (n = 857), ninth (n = 960) and eleventh (n = 518) grades of various Lithuanian schools. The study used a questionnaire survey method, which revealed the links between parents' exercise habits and their children's participation in sport. Assessment of data for girls and boys showed that daughters' participation in sport could be predicted by both their fathers' and mothers' exercise habits, but sons' sports activities could be predicted only by the regular physical activities of their fathers. The assessment of children's sporting activities according to age revealed links between parental exercising and the engagement of older (15-16 years old), but not younger adolescents (13-14 years old). Analysis of sports motivation showed that competition motives were more important for boys than for girls. Fitness, well-being and appearance motives were more important for older adolescents (15-18 years old), while competition motives were more important for younger adolescents (13-14 years old). Research revealed the relationship between children's sport motives and fathers' exercise habits, while examination of mothers' exercise revealed no difference. Key pointsParental exercising significantly predicts adolescents' engagement in sport. Daughter's engagement in sport is related to both parents whereas son's involvement in sport is related only to father's exercise habits.Regular exercising of both mother and father predicts 13 - 14-year-old adolescents' engagement in sport. However, mother exercising is not related to older adolescents' involvement in sport.Research revealed the relation of adolescents' sport motives and father's exercising, and no differences were established depending on mother's exercise habits.

The association between sexual satisfaction and body image in women.

PubMed

Pujols, Yasisca; Seal, Brooke N; Meston, Cindy M

2010-02-01

Although sexual functioning has been linked to sexual satisfaction, it only partially explains the degree to which women report being sexually satisfied. Other factors include quality of life, relational variables, and individual factors such as body image. Of the few studies that have investigated the link between body image and sexual satisfaction, most have considered body image to be a single construct and have shown mixed results. The present study assessed multiple body image variables in order to better understand which aspects of body image influence multiple domains of sexual satisfaction, including sexual communication, compatibility, contentment, personal concern, and relational concern in a community sample of women. Women between the ages of 18 and 49 years in sexual relationships (N = 154) participated in an Internet survey that assessed sexual functioning, five domains of sexual satisfaction, and several body image variables. Body image variables included the sexual attractiveness, weight concern, and physical condition subscales of the Body Esteem Scale, the appearance-based subscale of the Cognitive Distractions During Sexual Activity Scale, and body mass index. Total score of the Sexual Satisfaction Scale for Women was the main outcome measure. Sexual functioning was measured by a modified Female Sexual Function Index. Consistent with expectations, correlations indicated significant positive relationships between sexual functioning, sexual satisfaction, and all body image variables. A multiple regression analysis revealed that sexual satisfaction was predicted by high body esteem and low frequency of appearance-based distracting thoughts during sexual activity, even after controlling for sexual functioning status. Several aspects of body image, including weight concern, physical condition, sexual attractiveness, and thoughts about the body during sexual activity predict sexual satisfaction in women. The findings suggest that women who experience low sexual satisfaction may benefit from treatments that target these specific aspects of body image.

Communications for UAS Integration in the NAS Phase 2 Satellite Communications and Terrestrial Extension

NASA Technical Reports Server (NTRS)

Griner, Jim; Kerczewski, Bob

2017-01-01

In order to provide for the safe integration of unmanned aircraft systems (UAS) into the National Airspace System, the command and control communications link connecting the ground-based pilot with the unmanned aircraft must be highly reliable and robust, with national and international standards to enable interoperability and certification. Both line-of-sight (LOS) links using terrestrial-based communications and beyond-line-of-sight (BLOS) links using satellite communications, supported by national and international standards, are required for integrated UAS operations. The National Aeronautics and Space Administration (NASA) has undertaken an extensive technology development and test program in order to provide the required technical data needed to enable C2 standards development. NASAs UAS Integration in the National Airspace System (NAS), or UAS in the NAS Project, included as a major element the Command and Control Communications (C2) Subproject, based at NASAs Glenn Research Center. The successful first phase of the C2 Subproject, completed during 2012-2016, focused primarily on line-of-sight communications. Accomplishments included air-ground channel propagation characterization and modeling; CNPC prototype radio development; CNPC radio flight testing; satellite communications spectrum study and interference analysis; and development of C2 LOS communications standards development. The second phase of the C2 Subproject will focus primarily on beyond-line-of-sight communications, although a follow-on activity for terrestrial LOS communications, known as Terrestrial Extension, is also included. In addition to the terrestrial element, Phase 2 also includes technology development and testing activities for Ka-Band BLOS C2 Satellite Communications; Ku-Band BLOS C2 Satellite Communications; Ku-Band Interference and Propagation; and C-Band Satellite Communications. This paper will provide brief overviews of the C2 Subproject and its Phase I accomplishments, followed by a description of the plans for the C2 Subproject Phase 2.

Communications for UAS Integration in the NAS Phase 2 - Satellite Communications and Terrestrial Extension

NASA Technical Reports Server (NTRS)

Griner, James H.; Kerczewski, Robert J.

2017-01-01

In order to provide for the safe integration of unmanned aircraft systems (UAS) into the National Airspace System, the command and control communications link connecting the ground-based pilot with the unmanned aircraft must be highly reliable and robust, with national and international standards to enable interoperability and certification. Both line-of-sight (LOS) links using terrestrial-based communications and beyond-line-of-sight (BLOS) links using satellite communications, supported by national and international standards, are required for integrated UAS operations. The National Aeronautics and Space Administration (NASA) has undertaken an extensive technology development and test program in order to provide the required technical data needed to enable C2 standards development. NASAs UAS Integration in the National Airspace System (NAS), or UAS in the NAS Project, included as a major element the Command and Control Communications (C2) Subproject, based at NASAs Glenn Research Center. The successful first phase of the C2 Subproject, completed during 2012-2016, focused primarily on line-of-sight communications. Accomplishments included air-ground channel propagation characterization and modeling; CNPC prototype radio development; CNPC radio flight testing; satellite communications spectrum study and interference analysis; and development of C2 LOS communications standards development. The second phase of the C2 Subproject will focus primarily on beyond-line-of-sight communications, although a follow-on activity for terrestrial LOS communications, known as Terrestrial Extension, is also included. In addition to the terrestrial element, Phase 2 also includes technology development and testing activities for Ka-Band BLOS C2 Satellite Communications; Ku-Band BLOS C2 Satellite Communications; Ku-Band Interference and Propagation; and C-Band Satellite Communications. This paper will provide brief overviews of the C2 Subproject and its Phase I accomplishments, followed by a description of the plans for the C2 Subproject Phase 2.

ChemTechLinks: Alliances for Chemical Technician Education

NASA Astrophysics Data System (ADS)

Nameroff, Tamara

2003-09-01

ChemTechLinks (CTL) is a project of the American Chemical Society (ACS) Educational and International Activities Division and funded by the National Science Foundation to support and advance chemistry-based technician education. The project aims to help improve technician education programs, foster academic-industry alliances, provide professional development opportunities for faculty, and increase student recruitment into chemical technology. The CTL Web site serves as an information clearinghouse and link to other ACS resources and programs, including a Web-based, Voluntary Industry Standards (VIS) database, the Chemistry Technician Program Approval Service, the College Chemistry Consultants Service, summer workshops for high school teachers and two-year college faculty that emphasize a technology-oriented curriculum, scholarships for two-year college faculty to attend ACS Short Courses, a self-study instructional guide for faculty to use in preparing for classroom instruction, and information and free recruitment materials about career opportunities in chemistry technology.

Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways

PubMed Central

Seki, Ekihiro; Schwabe, Robert F.

2014-01-01

Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty and autoimmune origin. Inflammation is typically present in all disease stages, and associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression. We will summarize the contributions of different inflammatory cells, including hepatic macrophages, T- and B-lymphocytes, NK cells and platelets, as well as key effectors such as cytokines, chemokines, and damage-associated molecular patterns. Furthermore, we will discuss the relevance of inflammatory signaling pathways for clinical liver disease and for the development of anti-fibrogenic strategies. PMID:25066777

The Venus Transit, the Mayan Calendar and Astronomy Education in Guanajuato, Mexico

NASA Astrophysics Data System (ADS)

Bravo-Alfaro, H.; Caretta, C. A.; Brito, E. M. S.; Campos, P.; Macias, F.

2015-03-01

In this work we present two aspects of the Astronomy education activities carried out in 2012 by a multidisciplinary group at Universidad de Guanajuato, including specialists in Astronomy, Social Sciences and Environmental Engineering. The first program linked the Venus Transit, occurred in June 2012, with a national campaign of vulgarization of both modern and ancient (Mayan) Astronomy. Professional astronomers all around the country took advantage of the recent myth linked to the end of a large Mayan calendar cycle (13 baktuns, or some 5125 years) happening, after certain authors, in December 2012. In Guanajuato, the Astronomy Department organized live observations of the Venus Transit at two different locations, and complemented with conferences about astronomical events and the fake predictions of disasters linked to the ``end`` of the Mayan calendar. This program was very successful not only in Guanajuato but throughout the country, with several thousands of people attending live observations, conferences, expositions, etc.

Factors associated with delay in trauma team activation and impact on patient outcomes.

PubMed

Connolly, Rory; Woo, Michael Y; Lampron, Jacinthe; Perry, Jeffrey J

2017-09-05

Trauma code activation is initiated by emergency physicians using physiological and anatomical criteria, mechanism of injury, and patient demographic factors. Our objective was to identify factors associated with delayed trauma team activation. We assessed consecutive cases from a regional trauma database from January 2008 to March 2014. We defined a delay in trauma code activation as a time greater than 30 minutes from the time of arrival. We conducted univariate analysis for factors potentially influencing trauma team activation, and we subsequently used multiple logistic regression analysis models for delayed activation in relation to mortality, length of stay, and time to operative management. Patients totalling 846 were included for our analysis; 4.1% (35/846) of trauma codes were activated after 30 minutes. Mean age was 40.8 years in the early group versus 49.2 in the delayed group (p=0.01). Patients were over age 70 years in 7.6% in the early activation group versus 17.1% in the delayed group (p=0.04). There was no significant difference in sex, type of injury, injury severity, or time from injury between the two groups. There was no significant difference in mortality, median length of stay, or median time to operative management. Delayed activation is linked with increasing age with no clear link to increased mortality. Given the severe injuries in the delayed cohort that required activation of the trauma team, further emphasis on the older trauma patient and interventions to recognize this vulnerable population should be made.

Maternal Exposure to Occupational Asthmagens during Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development

ERIC Educational Resources Information Center

Singer, Alison B.; Windham, Gayle C.; Croen, Lisa A.; Daniels, Julie L.; Lee, Brian K.; Qian, Yinge; Schendel, Diana E.; Fallin, M. Daniele; Burstyn, Igor

2016-01-01

Maternal immune activity has been linked to children with autism spectrum disorder (ASD). We examined maternal occupational exposure to asthma-causing agents during pregnancy in relation to ASD risk. Our sample included 463 ASD cases and 710 general population controls from the Study to Explore Early Development whose mothers reported at least one…

Propensity Scoring and the Relationship between Sexual Media and Adolescent Sexual Behavior: Comment on Steinberg and Monahan (2011)

ERIC Educational Resources Information Center

Collins, Rebecca L.; Martino, Steven C.; Elliott, Marc N.

2011-01-01

Longitudinal research has demonstrated a link between exposure to sexual content in media and subsequent changes in adolescent sexual behavior, including initiation of intercourse and various noncoital sexual activities. Based on a reanalysis of one of the data sets involved, Steinberg and Monahan (2011) have challenged these findings. However,…

Linking Minority and Disadvantaged High School Students with Health Professions Training: A Win-Win Situation for Students and Older Adults.

ERIC Educational Resources Information Center

Padula, Cynthia A.; Leinhaas, Marie M.; Dodge, Kathleen A.

2002-01-01

Minority high school students (n=19) attended a health care career exploration program that included classroom sessions, group and individual activities, field trips, lectures, job shadowing, and a final report. On completion, most were considering careers in geriatrics or gerontology and had more positive attitudes toward older adults. (SK)

Lactate: link between glycolytic and oxidative metabolism.

PubMed

Brooks, George A

2007-01-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

Humoral immunity and autism spectrum disorders.

PubMed

Fluegge, Keith

2017-05-01

Abnormal immune activation, particularly of a humoral nature, has consistently been described in the etiopathogenesis of autism spectrum disorders (ASD). In this journal, Mead and Ashwood (2015) reviewed immune abnormalities in autism and linked them to severity of classic autistic symptoms. However, there remains a lack of clarity as to how environmental risk factors in ASD may contribute to such immunophenotypes. The evidence presented herein highlights these immune deficits of a humoral nature in ASD. Moreover, aligned with prior research showing a link between chronic air pollution and suppression of humoral immunity, the author of this commentary has proposed that environmental exposure to pervasive air pollutants, particularly nitrous oxide (N 2 O), may target several anti-inflammatory biomarkers, including alpha 7 nicotinic acetylcholine receptor (α7nAChR) inhibition and stimulation of kappa opioid receptor (KOR) activity. Given that these physiological targets, in particular, may promote the oft-noted humoral immunophenotypes in ASD, including B cell survival and muted antibody responses, this correspondence supports an existing line of evidence that air pollution, and particularly exposure to environmental N 2 O, may be an important etiological risk factor in ASD. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

LDRD 2013 Annual Report: Laboratory Directed Research and Development Program Activities

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

Bookless, W.

This LDRD project establishes a research program led by Jingguang Chen, who has started a new position as a Joint Appointee between BNL and Columbia University as of FY2013. Under this project, Dr. Chen will establish a new program in catalysis science at BNL and Columbia University. The LDRD program will provide initial research funding to start research at both BNL and Columbia. At BNL, Dr. Chen will initiate laboratory research, including hiring research staff, and will collaborate with the existing BNL catalysis and electrocatalysis research groups. At Columbia, a subcontract to Dr. Chen will provide startup funding for hismore » laboratory research, including initial graduate student costs. The research efforts will be linked under a common Catalysis Program in Sustainable Fuels. The overall impact of this project will be to strengthen the BNL catalysis science program through new linked research thrusts and the addition of an internationally distinguished catalysis scientist.« less

Odors regulate Arc expression in neuronal ensembles engaged in odor processing.

PubMed

Guthrie, K; Rayhanabad, J; Kuhl, D; Gall, C

2000-06-26

Synaptic activity is critical to developmental and plastic processes that produce long-term changes in neuronal connectivity and function. Genes expressed by neurons in an activity-dependent fashion are of particular interest since the proteins they encode may mediate neuronal plasticity. One such gene encodes the activity-regulated cytoskeleton-associated protein, Arc. The present study evaluated the effects of odor stimulation on Arc expression in rat olfactory bulb. Arc mRNA was rapidly increased in functionally linked cohorts of neurons topographically activated by odor stimuli. These included neurons surrounding individual glomeruli, mitral cells and transynaptically activated granule cells. Dendritic Arc immunoreactivity was also increased in odor-activated glomeruli. Our results suggest that odor regulation of Arc expression may contribute to activity-dependent structural changes associated with olfactory experience.

Greenshell™ Mussels: A Review of Veterinary Trials and Future Research Directions.

PubMed

Eason, Charles T; Adams, Serean L; Puddick, Jonathan; Romanazzi, Donato; Miller, Matthew R; King, Nick; Johns, Sarah; Forbes-Blom, Elizabeth; Hessian, Paul A; Stamp, Lisa K; Packer, Michael A

2018-03-27

The therapeutic benefits of Greenshell™ mussel (GSM; Perna canaliculus ) preparations have been studied using in vitro test systems, animal models, and human clinical trials focusing mainly on anti-inflammatory and anti-arthritic effects. Activity is thought to be linked to key active ingredients that include omega-3 polyunsaturated fatty acids, a variety of carotenoids and other bioactive compounds. In this paper, we review the studies that have been undertaken in dogs, cats, and horses, and outline new research directions in shellfish breeding and high-value nutrition research programmes targeted at enhancing the efficacy of mussel and algal extracts. The addition of GSM to animal diets has alleviated feline degenerative joint disease and arthritis symptoms, and chronic orthopaedic pain in dogs. In horses, GSM extracts decreased the severity of lameness and joint pain and provided improved joint flexion in limbs with lameness attributed to osteoarthritis. Future research in this area should focus on elucidating the key active ingredients in order to link concentrations of these active ingredients with their pharmacokinetics and therapeutic effects. This would enable consistent and improved efficacy from GSM-based products for the purpose of improved animal health.

Spatial dynamics of SIRT1 and the subnuclear distribution of NADH species

PubMed Central

Aguilar-Arnal, Lorena; Ranjit, Suman; Stringari, Chiara; Orozco-Solis, Ricardo; Gratton, Enrico; Sassone-Corsi, Paolo

2016-01-01

Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that functions as metabolic sensor of cellular energy and modulates biochemical pathways in the adaptation to changes in the environment. SIRT1 substrates include histones and proteins related to enhancement of mitochondrial function as well as antioxidant protection. Fluctuations in intracellular NAD+ levels regulate SIRT1 activity, but how SIRT1 enzymatic activity impacts on NAD+ levels and its intracellular distribution remains unclear. Here, we show that SIRT1 determines the nuclear organization of protein-bound NADH. Using multiphoton microscopy in live cells, we show that free and bound NADH are compartmentalized inside of the nucleus, and its subnuclear distribution depends on SIRT1. Importantly, SIRT6, a chromatin-bound deacetylase of the same class, does not influence NADH nuclear localization. In addition, using fluorescence fluctuation spectroscopy in single living cells, we reveal that NAD+ metabolism in the nucleus is linked to subnuclear dynamics of active SIRT1. These results reveal a connection between NAD+ metabolism, NADH distribution, and SIRT1 activity in the nucleus of live cells and pave the way to decipher links between nuclear organization and metabolism. PMID:27791113

Glucose, epithelium, and enteric nervous system: dialogue in the dark.

PubMed

Pfannkuche, H; Gäbel, G

2009-06-01

The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

A biopsychological review of gambling disorder

PubMed Central

Quintero, Gabriel C

2017-01-01

The present review is an overview of previous experimental work on biopsychological aspects of gambling disorder. It includes the topics 1) gambling disorder from the neuroimaging and electroencephalography (EEG) perspective, 2) cognitive, executive functioning, and neuropsychological aspects of gambling disorder, and 3) rodent models of gambling disorder. Penalties and losses in gambling can differ in terms of brain activity. Also, specific patterns of brain activity, brain anatomical traits, EEG responses, and cognitive and executive performance can discriminate pathological gamblers from nonpathological gamblers. Also, pathological gamblers can display dysfunction in such brain areas as the insula, frontal lobe, and orbitofrontal cortex. Pathological gambling is a heterogeneous disorder that can vary depending on the severity of cognition, the style of gambling (strategic or not), the prospect of recovery, proneness to relapse, and proneness to treatment withdrawal. Finally, based on rodent models of gambling, the appropriateness of gambling decision is influenced by the presence of cues, the activity of dopamine receptors, and the activity of some brain areas (infralimbic, prelimbic, or rostral agranular insular cortex). Pathological gamblers differed in terms of frontoparietal brain activation compared to nonpathological gamblers (if winning or losing a game). Pathological gamblers had dysfunctional EEG activity. The severity of gambling was linked to the magnification and content of cognitive distortions. The insula was fundamental in the distortion of cognitions linked to result analysis during gambling activity. PMID:28096672

Processing Semblances Induced through Inter-Postsynaptic Functional LINKs, Presumed Biological Parallels of K-Lines Proposed for Building Artificial Intelligence

PubMed Central

Vadakkan, Kunjumon I.

2011-01-01

The internal sensation of memory, which is available only to the owner of an individual nervous system, is difficult to analyze for its basic elements of operation. We hypothesize that associative learning induces the formation of functional LINK between the postsynapses. During memory retrieval, the activation of either postsynapse re-activates the functional LINK evoking a semblance of sensory activity arriving at its opposite postsynapse, nature of which defines the basic unit of internal sensation – namely, the semblion. In neuronal networks that undergo continuous oscillatory activity at certain levels of their organization re-activation of functional LINKs is expected to induce semblions, enabling the system to continuously learn, self-organize, and demonstrate instantiation, features that can be utilized for developing artificial intelligence (AI). This paper also explains suitability of the inter-postsynaptic functional LINKs to meet the expectations of Minsky’s K-lines, basic elements of a memory theory generated to develop AI and methods to replicate semblances outside the nervous system. PMID:21845180

Neural correlates of metacognitive ability and of feeling confident: a large-scale fMRI study.

PubMed

Molenberghs, Pascal; Trautwein, Fynn-Mathis; Böckler, Anne; Singer, Tania; Kanske, Philipp

2016-12-01

One important aspect of metacognition is the ability to accurately evaluate one's performance. People vary widely in their metacognitive ability and in general are too confident when evaluating their performance. This often leads to poor decision making with potentially disastrous consequences. To further our understanding of the neural underpinnings of these processes, this fMRI study investigated inter-individual differences in metacognitive ability and effects of trial-by-trial variation in subjective feelings of confidence when making metacognitive assessments. Participants (N = 308) evaluated their performance in a high-level social and cognitive reasoning task. The results showed that higher metacognitive accuracy was associated with a decrease in activation in the anterior medial prefrontal cortex, an area previously linked to metacognition on perception and memory. Moreover, the feeling of confidence about one's choices was associated with an increase of activation in reward, memory and motor related areas including bilateral striatum and hippocampus, while less confidence was associated with activation in areas linked with negative affect and uncertainty, including dorsomedial prefrontal and bilateral orbitofrontal cortex. This might indicate that positive affect is related to higher confidence thereby biasing metacognitive decisions towards overconfidence. In support, behavioural analyses revealed that increased confidence was associated with lower metacognitive accuracy. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Members of the DAN family are BMP antagonists that form highly stable noncovalent dimers.

PubMed

Kattamuri, Chandramohan; Luedeke, David M; Nolan, Kristof; Rankin, Scott A; Greis, Kenneth D; Zorn, Aaron M; Thompson, Thomas B

2012-12-14

Signaling of bone morphogenetic protein (BMP) ligands is antagonized by a number of extracellular proteins, including noggin, follistatin and members of the DAN (differential screening selected gene abberative in neuroblastoma) family. Structural studies on the DAN family member sclerostin (a weak BMP antagonist) have previously revealed that the protein is monomeric and consists of an eight-membered cystine knot motif with a fold similar to transforming growth factor-β ligands. In contrast to sclerostin, certain DAN family antagonists, including protein related to DAN and cerberus (PRDC), have an unpaired cysteine that is thought to function in covalent dimer assembly (analogous to transforming growth factor-β ligands). Through a combination of biophysical and biochemical studies, we determined that PRDC forms biologically active dimers that potently inhibit BMP ligands. Furthermore, we showed that PRDC dimers, surprisingly, are not covalently linked, as mutation of the unpaired cysteine does not inhibit dimer formation or biological activity. We further demonstrated that the noncovalent PRDC dimers are highly stable under both denaturing and reducing conditions. This study was extended to the founding family member DAN, which also forms noncovalent dimers that are highly stable. These results demonstrate that certain DAN family members can form both monomers and noncovalent dimers, implying that biological activity of DAN family members might be linked to their oligomeric state. Published by Elsevier Ltd.

Adverse Effects of Common Sports and Recreational Activities on Male Reproduction.

PubMed

Panara, Kush; Masterson, John M; Savio, Luis F; Ramasamy, Ranjith

2018-05-03

Male factor infertility plays a significant role in infertility. Many factors have been associated with male infertility; however, the link between many sports and recreational factors and male reproduction remains poorly characterized. To evaluate the current literature regarding the impact of many common sports and recreational factors on male reproduction. A comprehensive PubMed and Embase search for relevant articles published between 1970 and 2017 was performed by combining the following search terms: male, sports (including individual sports), traumatic brain injury, sauna, hot tub, fertility, erectile dysfunction, varicocele, environment, cell phone, and laptop computer. Hypogonadism and erectile dysfunction can be associated with sports with high rates of head injuries, such as American football. Although early reports linked other sports, such as bicycling, to erectile dysfunction, subsequent studies isolated these associations to sports cycling rather than recreational cycling. Certain sports (football, basketball, handball, and volleyball) were linked to increasing prevalence and severity of varicocele, offering a potential link to male infertility. In addition, recreational activities such as sauna, hot tubs, Jacuzzis, heated car seats, and laptop use were associated with high testicular temperature, which can impair spermatogenesis. Radio frequency electromagnetic waves from cell phones and laptops have also been shown to have deleterious effects on sperm viability and motility. Many common sports and daily activities represent potential sources of male infertility. Clinicians should be aware of these associations in explaining idiopathic infertility in males. Male infertility is an often overlooked component of a couple's inability to conceive. We outline many common and often overlooked sports and recreational exposures that have been associated with male infertility. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Engagement of Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Induces Transforming Growth Factor β (TGF-β) Production by Murine CD4+ T Cells

PubMed Central

Chen, Wanjun; Jin, Wenwen; Wahl, Sharon M.

1998-01-01

Evidence indicates that cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) may negatively regulate T cell activation, but the basis for the inhibitory effect remains unknown. We report here that cross-linking of CTLA-4 induces transforming growth factor β (TGF-β) production by murine CD4+ T cells. CD4+ T helper type 1 (Th1), Th2, and Th0 clones all secrete TGF-β after antibody cross-linking of CTLA-4, indicating that induction of TGF-β by CTLA-4 signaling represents a ubiquitous feature of murine CD4+ T cells. Stimulation of the CD3–T cell antigen receptor complex does not independently induce TGF-β, but is required for optimal CTLA-4–mediated TGF-β production. The consequences of cross-linking of CTLA-4, together with CD3 and CD28, include inhibition of T cell proliferation and interleukin (IL)-2 secretion, as well as suppression of both interferon γ (Th1) and IL-4 (Th2). Moreover, addition of anti–TGF-β partially reverses this T cell suppression. When CTLA-4 was cross-linked in T cell populations from TGF-β1 gene–deleted (TGF-β1−/−) mice, the T cell responses were only suppressed 38% compared with 95% in wild-type mice. Our data demonstrate that engagement of CTLA-4 leads to CD4+ T cell production of TGF-β, which, in part, contributes to the downregulation of T cell activation. CTLA-4, through TGF-β, may serve as a counterbalance for CD28 costimulation of IL-2 and CD4+ T cell activation. PMID:9815262

KinD is a checkpoint protein linking spore formation to extracellular-matrix production in Bacillus subtilis biofilms.

PubMed

Aguilar, Claudio; Vlamakis, Hera; Guzman, Alejandra; Losick, Richard; Kolter, Roberto

2010-05-18

Bacillus subtilis cells form multicellular biofilm communities in which spatiotemporal regulation of gene expression occurs, leading to differentiation of multiple coexisting cell types. These cell types include matrix-producing and sporulating cells. Extracellular matrix production and sporulation are linked in that a mutant unable to produce matrix is delayed for sporulation. Here, we show that the delay in sporulation is not due to a growth advantage of the matrix-deficient mutant under these conditions. Instead, we show that the link between matrix production and sporulation is through the Spo0A signaling pathway. Both processes are regulated by the phosphorylated form of the master transcriptional regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P), matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation commences. We have found that Spo0A~P levels are maintained at low levels in the matrix-deficient mutant, thereby delaying expression of sporulation-specific genes. This is due to the activity of one of the components of the Spo0A phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation defect of matrix mutants, while its overproduction delays sporulation. Our data indicate that KinD displays a dual role as a phosphatase or a kinase and that its activity is linked to the presence of extracellular matrix in the biofilms. We propose a novel role for KinD in biofilms as a checkpoint protein that regulates the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a component therein, is sensed.

KinD Is a Checkpoint Protein Linking Spore Formation to Extracellular-Matrix Production in Bacillus subtilis Biofilms

PubMed Central

Aguilar, Claudio; Vlamakis, Hera; Guzman, Alejandra; Losick, Richard; Kolter, Roberto

2010-01-01

ABSTRACT Bacillus subtilis cells form multicellular biofilm communities in which spatiotemporal regulation of gene expression occurs, leading to differentiation of multiple coexisting cell types. These cell types include matrix-producing and sporulating cells. Extracellular matrix production and sporulation are linked in that a mutant unable to produce matrix is delayed for sporulation. Here, we show that the delay in sporulation is not due to a growth advantage of the matrix-deficient mutant under these conditions. Instead, we show that the link between matrix production and sporulation is through the Spo0A signaling pathway. Both processes are regulated by the phosphorylated form of the master transcriptional regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P), matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation commences. We have found that Spo0A~P levels are maintained at low levels in the matrix-deficient mutant, thereby delaying expression of sporulation-specific genes. This is due to the activity of one of the components of the Spo0A phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation defect of matrix mutants, while its overproduction delays sporulation. Our data indicate that KinD displays a dual role as a phosphatase or a kinase and that its activity is linked to the presence of extracellular matrix in the biofilms. We propose a novel role for KinD in biofilms as a checkpoint protein that regulates the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a component therein, is sensed. PMID:20689749

Space activities and global popular music culture

NASA Astrophysics Data System (ADS)

Wessels, Allison Rae; Collins, Patrick

During the "space age" era, space activities appear increasingly as a theme in Western popular music, as they do in popular culture generally. In combination with the electronics and tele-communications revolution, "pop/rock" music has grown explosively during the space age to become an effectively global culture. From this base a number of trends are emerging in the pattern of influences that space activities have on pop music. The paper looks at the use of themes and imagery in pop music; the role of space technology in the modern "globalization" of pop music; and current and future links between space activities and pop music culture, including how public space programmes are affected by its influence on popular attitudes.

Endoplasmic reticulum stress in obesity and obesity-related disorders: An expanded view.

PubMed

Pagliassotti, Michael J; Kim, Paul Y; Estrada, Andrea L; Stewart, Claire M; Gentile, Christopher L

2016-09-01

The endoplasmic reticulum (ER) is most notable for its central roles in calcium ion storage, lipid biosynthesis, and protein sorting and processing. By virtue of its extensive membrane contact sites that connect the ER to most other organelles and to the plasma membrane, the ER can also regulate diverse cellular processes including inflammatory and insulin signaling, nutrient metabolism, and cell proliferation and death via a signaling pathway called the unfolded protein response (UPR). Chronic UPR activation has been observed in liver and/or adipose tissue of dietary and genetic murine models of obesity, and in human obesity and non-alcoholic fatty liver disease (NAFLD). Activation of the UPR in obesity and obesity-related disorders likely has two origins. One linked to classic ER stress involving the ER lumen and one linked to alterations to the ER membrane environment. This review discusses both of these origins and also considers the role of post-translational protein modifications, such as acetylation and palmitoylation, and ER-mitochondrial interactions to obesity-mediated impairments in the ER and activation of the UPR. Copyright © 2016 Elsevier Inc. All rights reserved.

Isohelical DNA-Binding Oligomers: Antiviral Activity and Application for the Design of Nanostructured Devices

NASA Astrophysics Data System (ADS)

Gursky, Georgy; Nikitin, Alexei; Surovaya, Anna; Grokhovsky, Sergey; Andronova, Valeria; Galegov, Georgy

We performed a systematic search for new structural motifs isohelical to double-stranded DNA and found five motifs that can be used for the design and synthesis of new DNA-binding oligomers. Some of the DNA-binding oligomers can be equipped with fluorescence chromophores and metal-chelating groups and may serve as conductive wires in nano-scaled electric circuits. A series of new DNA-binding ligands were synthesized by a modular assembly of pyrrole carboxamides and novel pseudopeptides of the form (XY)n. Here, Y is a glycine residue; n is the degree of polymerization. X is an unusual amino acid residue containing a five-membered aromatic ring. Antiviral activity of bis-linked netropsin derivatives is studied. Bis-netropsins containing 15 and 31 lysine residues at the N-termini inhibit most effectively reproduction of the herpes virus type 1 in the Vero cell culture, including virus variants resistant to acyclovir and its analogues. Antiviral activity of bis-linked netropsin derivatives is correlated with their ability to interact with long clusters of AT-base pairs in the origin of replication of the viral DNA.

Agm1/Pgm3-Mediated Sugar Nucleotide Synthesis Is Essential for Hematopoiesis and Development▿

PubMed Central

Greig, Kylie T.; Antonchuk, Jennifer; Metcalf, Donald; Morgan, Phillip O.; Krebs, Danielle L.; Zhang, Jian-Guo; Hacking, Douglas F.; Bode, Lars; Robb, Lorraine; Kranz, Christian; de Graaf, Carolyn; Bahlo, Melanie; Nicola, Nicos A.; Nutt, Stephen L.; Freeze, Hudson H.; Alexander, Warren S.; Hilton, Douglas J.; Kile, Benjamin T.

2007-01-01

Carbohydrate modification of proteins includes N-linked and O-linked glycosylation, proteoglycan formation, glycosylphosphatidylinositol anchor synthesis, and O-GlcNAc modification. Each of these modifications requires the sugar nucleotide UDP-GlcNAc, which is produced via the hexosamine biosynthesis pathway. A key step in this pathway is the interconversion of GlcNAc-6-phosphate (GlcNAc-6-P) and GlcNAc-1-P, catalyzed by phosphoglucomutase 3 (Pgm3). In this paper, we describe two hypomorphic alleles of mouse Pgm3 and show there are specific physiological consequences of a graded reduction in Pgm3 activity and global UDP-GlcNAc levels. Whereas mice lacking Pgm3 die prior to implantation, animals with less severe reductions in enzyme activity are sterile, exhibit changes in pancreatic architecture, and are anemic, leukopenic, and thrombocytopenic. These phenotypes are accompanied by specific rather than wholesale changes in protein glycosylation, suggesting that while universally required, the functions of certain proteins and, as a consequence, certain cell types are especially sensitive to reductions in Pgm3 activity. PMID:17548465

T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic programming

PubMed Central

Yang, Kai; Shrestha, Sharad; Zeng, Hu; Karmaus, Peer W.F.; Neale, Geoffrey; Vogel, Peter; Guertin, David A.; Lamb, Richard F.; Chi, Hongbo

2014-01-01

SUMMARY Naïve T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic programming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and Th2 cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 co-stimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity. PMID:24315998

Structural and Functional Analyses of the Severe Acute Respiratory Syndrome Coronavirus Endoribonuclease Nsp15

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

Bhardwaj, Kanchan; Palaninathan, Satheesh; Alcantara, Joanna Maria Ortiz

2008-03-31

The severe acute respiratory syndrome (SARS) coronavirus encodes several RNA-processing enzymes that are unusual for RNA viruses, including Nsp15 (nonstructural protein 15), a hexameric endoribonuclease that preferentially cleaves 3' of uridines. We solved the structure of a catalytically inactive mutant version of Nsp15, which was crystallized as a hexamer. The structure contains unreported flexibility in the active site of each subunit. Substitutions in the active site residues serine 293 and proline 343 allowed Nsp15 to cleave at cytidylate, whereas mutation of leucine 345 rendered Nsp15 able to cleave at purines as well as pyrimidines. Mutations that targeted the residues involvedmore » in subunit interactions generally resulted in the formation of catalytically inactive monomers. The RNA-binding residues were mapped by a method linking reversible cross-linking, RNA affinity purification, and peptide fingerprinting. Alanine substitution of several residues in the RNA-contacting portion of Nsp15 did not affect hexamer formation but decreased the affinity of RNA binding and reduced endonuclease activity. This suggests a model for Nsp15 hexamer interaction with RNA.« less

Endoplasmic Reticulum Stress in Obesity and Obesity-Related Disorders: An Expanded View

PubMed Central

Pagliassotti, M.J.; Kim, P. Y.; Estrada, A.L.; Stewart, C.M.; Gentile, C.L.

2016-01-01

The Endoplasmic Reticulum (ER) is most notable for its central roles in calcium ion storage, lipid biosynthesis, and protein sorting and processing. By virtue of its extensive membrane contact sites that connect the ER to most other organelles and to the plasma membrane, the ER can also regulate diverse cellular processes including inflammatory and insulin signaling, nutrient metabolism, and cell proliferation and death via a signaling pathway called the unfolded protein response (UPR). Chronic UPR activation has been observed in liver and/or adipose tissue of dietary and genetic murine models of obesity, and in human obesity and non-alcoholic fatty liver disease (NAFLD). Activation of the UPR in obesity and obesity-related disorders likely has two origins. One linked to classic ER stress involving the ER lumen and one linked to alterations to the ER membrane environment. This review discusses both of these origins and also considers the role of post-translational protein modifications, such as acetylation and palmitoylation, and ER-mitochondrial interactions to obesity-mediated impairments in the ER and activation of the UPR. PMID:27506731

System data communication structures for active-control transport aircraft, volume 1

NASA Technical Reports Server (NTRS)

Hopkins, A. L.; Martin, J. H.; Brock, L. D.; Jansson, D. G.; Serben, S.; Smith, T. B.; Hanley, L. D.

1981-01-01

Candidate data communication techniques are identified, including dedicated links, local buses, broadcast buses, multiplex buses, and mesh networks. The design methodology for mesh networks is then discussed, including network topology and node architecture. Several concepts of power distribution are reviewed, including current limiting and mesh networks for power. The technology issues of packaging, transmission media, and lightning are addressed, and, finally, the analysis tools developed to aid in the communication design process are described. There are special tools to analyze the reliability and connectivity of networks and more general reliability analysis tools for all types of systems.

Enriched Audience Engagement Through Twitter: Should More Academic Radiology Departments Seize the Opportunity?

PubMed

Prabhu, Vinay; Rosenkrantz, Andrew B

2015-07-01

The aim of this study was to evaluate use of the microblogging social network Twitter by academic radiology departments (ARDs) in the United States. Twitter was searched to identify all accounts corresponding with United States ARDs. All original tweets from identified accounts over a recent 3-month period (August to October 2014) were archived. Measures of account activity, as well as tweet and link content, were summarized. Fifteen ARDs (8.2%) had Twitter accounts. Ten (5.5%) had "active" accounts, with ≥1 tweet over the 3-month period. Active accounts averaged 711 ± 925 followers (maximum, 2,885) and 61 ± 93 tweets (maximum, 260) during the period. Among 612 tweets from active accounts, content most commonly related to radiology-related education (138), dissemination of departmental research (102), general departmental or hospital promotional material (62), departmental awards or accomplishments (60), upcoming departmental lectures (59), other hospital-related news (55), medical advice or information for patients (38), local community events or news (29), social media and medicine (27), and new departmental or hospital hires or expansion (19). Eighty percent of tweets (490 of 612) included 315 unique external links. Most frequent categories of link sources were picture-, video-, and music-sharing websites (89); the ARD's website or blog (83); peer-reviewed journal articles (40); the hospital's or university's website (34), the lay press (28), and Facebook (14). Twitter provides ARDs the opportunity to engage their own staff members, the radiology community, the department's hospital, and patients, through a broad array of content. ARDs frequently used Twitter for promotional and educational purposes. Because only a small fraction of ARDs actively use Twitter, more departments are encouraged to take advantage of this emerging communication tool. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders*

PubMed Central

Li, Min; Quan, Chao; Toth, Rachel; Campbell, David G.; MacKintosh, Carol; Wang, Hong Yu; Chen, Shuai

2015-01-01

Diabetes is strongly associated with cognitive decline, but the molecular reasons are unknown. We found that fasting and peripheral insulin promote phosphorylation and dephosphorylation, respectively, of specific residues on brain proteins including cytoskeletal regulators such as slit-robo GTPase-activating protein 3 (srGAP3) and microtubule affinity-regulating protein kinases (MARKs), in which deficiency or dysregulation is linked to neurological disorders. Fasting activates protein kinase A (PKA) but not PKB/Akt signaling in the brain, and PKA can phosphorylate the purified srGAP3. The phosphorylation of srGAP3 and MARKs were increased when PKA signaling was activated in primary neurons. Knockdown of PKA decreased the phosphorylation of srGAP3. Furthermore, WAVE1, a protein kinase A-anchoring protein, formed a complex with srGAP3 and PKA in the brain of fasted mice to facilitate the phosphorylation of srGAP3 by PKA. Although brain cells have insulin receptors, our findings are inconsistent with the down-regulation of phosphorylation of target proteins being mediated by insulin signaling within the brain. Rather, our findings infer that systemic insulin, through a yet unknown mechanism, inhibits PKA or protein kinase(s) with similar specificity and/or activates an unknown phosphatase in the brain. Ser858 of srGAP3 was identified as a key regulatory residue in which phosphorylation by PKA enhanced the GAP activity of srGAP3 toward its substrate, Rac1, in cells, thereby inhibiting the action of this GTPase in cytoskeletal regulation. Our findings reveal novel mechanisms linking peripheral insulin sensitivity with cytoskeletal remodeling in neurons, which may help to explain the association of diabetes with neurological disorders such as Alzheimer disease. PMID:26499801

Physical activity, sleep duration and metabolic health in children fluctuate with the lunar cycle: science behind the myth

PubMed Central

Sjödin, A; Hjorth, M F; Damsgaard, C T; Ritz, C; Astrup, A; Michaelsen, K F

2015-01-01

Behaviours of several animal species have been linked to lunar periodicity. Evidence for such links in humans is weak; however, recently, shorter sleep duration was reported around full moon in two small samples of adults. As restrictions in sleep duration have been shown to adversely affect glucose regulation and physical activity to improve glucose regulation, one could speculate that cardiometabolic risk factors might also be affected by the lunar phase. We retrospectively examined 795 Danish children, aged 8–11 years, with more than 13 000 24-h accelerometer recordings of activity and sleep as well as 2000 measurements of different cardiometabolic risk factors, including insulin sensitivity, appetite hormones and blood pressure, during nine lunar phases. During the period around full moon, children were 5.0 and 3.2 min per day less active, slept 2.4 and 4.1 min per night longer, had 0.03 and 0.05 higher homeostatic model assessment of insulin resistance and 0.6 and 0.8 mmHg higher mean arterial blood pressure compared with days around half moon and new moon, respectively (all P ≤ 0.02). Furthermore, ghrelin was lower and leptin was higher during the period around full moon compared with days around half moon (both P < 0.001). The results suggest that physical activity rather than sleep is responsible for the metabolic alterations observed around full moon. However, we have no understanding of potential mechanisms that may mediate a potential true link between childhood behaviour and the lunar cycle or confounders that may explain this, apparently leading to fluctuation in a number of cardiometabolic risk markers conjointly with lunar phases. PMID:25808903

Physical activity, sleep duration and metabolic health in children fluctuate with the lunar cycle: science behind the myth.

PubMed

Sjödin, A; Hjorth, M F; Damsgaard, C T; Ritz, C; Astrup, A; Michaelsen, K F

2015-04-01

Behaviours of several animal species have been linked to lunar periodicity. Evidence for such links in humans is weak; however, recently, shorter sleep duration was reported around full moon in two small samples of adults. As restrictions in sleep duration have been shown to adversely affect glucose regulation and physical activity to improve glucose regulation, one could speculate that cardiometabolic risk factors might also be affected by the lunar phase. We retrospectively examined 795 Danish children, aged 8-11 years, with more than 13,000 24-h accelerometer recordings of activity and sleep as well as 2000 measurements of different cardiometabolic risk factors, including insulin sensitivity, appetite hormones and blood pressure, during nine lunar phases. During the period around full moon, children were 5.0 and 3.2 min per day less active, slept 2.4 and 4.1 min per night longer, had 0.03 and 0.05 higher homeostatic model assessment of insulin resistance and 0.6 and 0.8 mmHg higher mean arterial blood pressure compared with days around half moon and new moon, respectively (all P ≤ 0.02). Furthermore, ghrelin was lower and leptin was higher during the period around full moon compared with days around half moon (both P < 0.001). The results suggest that physical activity rather than sleep is responsible for the metabolic alterations observed around full moon. However, we have no understanding of potential mechanisms that may mediate a potential true link between childhood behaviour and the lunar cycle or confounders that may explain this, apparently leading to fluctuation in a number of cardiometabolic risk markers conjointly with lunar phases. © 2015 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity.

Stress--the battle for hearts and minds: links between depression, stress and ischemic heart disease.

PubMed

Korszun, Ania; Frenneaux, Michael P

2006-09-01

Depression and ischemic heart disease (IHD) are strongly related common disorders. Depression itself is an independent cardiac risk factor and is associated with a two- to threefold increase in IHD mortality. Attention has now shifted to identifying the common underlying mechanisms that could make individuals susceptible to both disorders. Abnormalities that have been implicated in this relationship include abnormal platelet activation, decreased baroreceptor sensitivity and endothelial dysfunction. Depression and IHD both have a high association with environmental stress, and depression is characterized by abnormalities of the stress-hormone axis. This review provides a brief overview of some recent developments in our understanding of the pathophysiological links between stress, depression and IHD.

Macroenvironmental factors including GDP per capita and physical activity in Europe.

PubMed

Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

2013-02-01

Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across leisure-time, occupational, and transport-related domains) is warranted.

Magnetic Resonance Imaging Features as Surrogate Markers of X-Linked Hypophosphatemic Rickets Activity.

PubMed

Lempicki, Marta; Rothenbuhler, Anya; Merzoug, Valérie; Franchi-Abella, Stéphanie; Chaussain, Catherine; Adamsbaum, Catherine; Linglart, Agnès

2017-01-01

X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal <1.5), being >1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity. © 2017 S. Karger AG, Basel.

Bioactive polyphenols and cardiovascular disease: chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response?

PubMed Central

Goszcz, Katarzyna; Duthie, Garry G; Stewart, Derek; Leslie, Stephen J

2017-01-01

Polyphenols are widely regarded to have a wide range of health‐promoting qualities, including beneficial effects on cardiovascular disease. Historically, the benefits have been linked to their well‐recognized powerful antioxidant activity. However, the concept that the beneficial effects are attributable to direct antioxidant activity in vivo does not pay sufficient heed to the fact that polyphenols degrade rapidly, are poorly absorbed and rapidly metabolized, resulting in very low bioavailability. This review explores alternative mechanisms by which polyphenols, or their metabolites, exert biological activity via mechanisms that can be activated by physiologically relevant concentrations. Evidence is presented to support the action of phenolic derivatives on receptors and signalling pathways to induce adaptive responses that drive changes in endogenous antioxidant, antiplatelet, vasodilatory and anti‐inflammatory effects. The implications are that in vitro antioxidant measures as predictors of polyphenol protective activity in vivo hold little relevance and that closer attention needs to be paid to bioavailable metabolites to understand the mode of action of these diet‐derived components. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:28071785

Are physical activity levels linked to nutrient adequacy? Implications for cancer risk.

PubMed

Csizmadi, Ilona; Kelemen, Linda E; Speidel, Thomas; Yuan, Yan; Dale, Laura C; Friedenreich, Christine M; Robson, Paula J

2014-01-01

Cancer prevention guidelines recommend a healthy body mass index, physical activity, and nutrient intake from food rather than supplements. Sedentary individuals may restrict energy intake to prevent weight gain and in so doing may compromise nutritional intake. We conducted a cross-sectional analysis to determine if adequacy of micronutrients is linked to physical activity levels (PALs) in healthy-weight adults. Tomorrow Project participants in Alberta, Canada (n = 5333), completed past-year diet and physical activity questionnaires. The percent meeting Dietary Reference Intakes (DRIs) was reported across low and high PAL groups, and the relation between PAL and percent achieved DRI was determined using multiple linear regression analyses. Overall, <50% of healthy-weight participants met DRIs for folate, calcium, and vitamin D. Percent achieved DRI increased linearly with increasing PAL in both genders (P < 0.01). A hypothetical increase in PAL from 1.4 to 1.9 was associated with a DRI that was 8%-13% higher for folate and vitamin C (men) and 5%-15% higher for calcium and iron (women). Healthy-weight adults at higher PALs appear more likely to meet DRIs for potential cancer-preventing nutrients. The benefits of higher PALs may extend beyond the usual benefits attributed to physical activity to include having a more favorable impact on nutrient adequacy.

Observing the work of the Clinical Nurse Specialist: a pilot study.

PubMed

Darmody, Julie V

2005-01-01

The Clinical Nurse Specialist (CNS) is an advanced practice nurse (APN) with graduate preparation as a clinical expert within a specialty area of nursing practice. There is a need for information about the work of the CNS in order to link CNS activities to outcomes and costs of care. To describe the work of the CNS in the acute care setting using the National Association of Clinical Nurse Specialists (NACNS) model as an organizing framework. Descriptive pilot study of the work of the CNS in acute care. A 500-bed academic medical center located in the Midwestern United States. Five masters-prepared APNs in a unit-based CNS role. Direct observation and time study were used to record activities and time for 4 hours with each CNS (n = 5) for a total of 20 hours of observation. CNS activity and time within each practice domain included patient/client (30%), nursing (44%), organization/system (10%), and other activities (16%). Specific activities observed were linked to possible outcomes in the NACNS framework. The NACNS model provided a useful framework for developing a data collection tool that can be used in a larger study that analyzes the work of the acute care CNS. Describing the work of the CNS is an important preliminary step to measuring outcomes and costs of care.

Polyelectrolyte complexes between (cross-linked) N-carboxyethylchitosan and (quaternized) poly[2-(dimethylamino)ethyl methacrylate]: preparation, characterization, and antibacterial properties.

PubMed

Yancheva, Elena; Paneva, Dilyana; Maximova, Vera; Mespouille, Laetitia; Dubois, Philippe; Manolova, Nevena; Rashkov, Iliya

2007-03-01

Novel polyelectrolyte complexes (PECs) between N-carboxyethylchitosan (CECh) and well-defined (quaternized) poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) have been obtained. The modification of chitosan into CECh allows the preparation of PECs in a pH range in which chitosan cannot form complexes. The CECh/PDMAEMA complex is formed in a narrow pH range around 7. The quaternization of the tertiary amino groups of PDMAEMA enables complex formation with CECh both in neutral and in alkaline medium. Cross-linked CECh is also capable of forming complexes with (quaternized) PDMAEMA. The antibacterial activity of (cross-linked) CECh, (quaternized) PDMAEMA, and their complexes against Escherichia coli has been evaluated. In contrast to (quaternized) PDMAEMA, (cross-linked) CECh exhibits no antibacterial activity. The complex formation between cross-linked CECh and (quaternized) PDMAEMA results in a loss of the inherent antibacterial activity of the latter in neutral medium. In acidic medium, the complexes exhibit strong antibacterial activity due to complex disintegration and release of (quaternized) PDMAEMA.

The Laser Communications Relay Demonstration Experiment Program

NASA Technical Reports Server (NTRS)

Israel, Dave

2017-01-01

This paper elaborates on the Laser Communications Relay Demonstration (LCRD) Experiment Program, which will engage in a number of pre-determined experiments and also call upon a wide variety of experimenters to test new laser communications technology and techniques, and to gather valuable data. LCRD is a joint project between NASAs Goddard Space Flight Center (GSFC), the Jet Propulsion Laboratory (JPL), and the Massachusetts Institute of Technology Lincoln Laboratory (MIT LL). LCRD will test the functionality in various settings and scenarios of optical communications links from a GEO payload to ground stations in Southern California and Hawaii over a two-year period following launch in 2019. The LCRD investigator team will execute numerous experiments to test critical aspects of laser communications activities over real links and systems, collecting data on the effects of atmospheric turbulence and weather on performance and communications availability. LCRD will also incorporate emulations of target scenarios, including direct-to-Earth (DTE) links from user spacecraft and optical relay providers supporting user spacecraft. To supplement and expand upon the results of these experiments, the project also includes a Guest Experimenters Program, which encourages individuals and groups from government agencies, academia and industry to propose diverse experiment ideas.

The Laser Communications Relay Demonstration Experiment Program

NASA Technical Reports Server (NTRS)

Israel, David J.; Edwards, Bernard L.; Moores, John D.; Piazzolla, Sabino; Merritt, Scott

2017-01-01

This paper elaborates on the Laser Communications Relay Demonstration (LCRD) Experiment Program, which will engage in a number of pre-determined experiments and also call upon a wide variety of experimenters to test new laser communications technology and techniques, and to gather valuable data. LCRD is a joint project between NASA's Goddard Space Flight Center (GSFC), the Jet Propulsion Laboratory (JPL), and the Massachusetts Institute of Technology Lincoln Laboratory (MIT LL). LCRD will test the functionality in various settings and scenarios of optical communications links from a GEO (Geosynchronous Earth Orbit) payload to ground stations in Southern California and Hawaii over a two-year period following launch in 2019. The LCRD investigator team will execute numerous experiments to test critical aspects of laser communications activities over real links and systems, collecting data on the effects of atmospheric turbulence and weather on performance and communications availability. LCRD will also incorporate emulations of target scenarios, including direct-to-Earth (DTE) links from user spacecraft and optical relay providers supporting user spacecraft. To supplement and expand upon the results of these experiments, the project also includes a Guest Experimenters Program, which encourages individuals and groups from government agencies, academia and industry to propose diverse experiment ideas.

BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

PubMed

Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

2014-05-01

Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

Associations among social capital, parenting for active lifestyles, and youth physical activity in rural families living in upstate New York.

PubMed

Davison, Kirsten K; Nishi, Akihiro; Kranz, Sibylle; Wyckoff, Lynae; May, John J; Earle-Richardson, Giulia B; Strogatz, David S; Jenkins, Paul L

2012-10-01

While emerging research supports a positive relationship between social capital and youth physical activity (PA), few studies have examined possible mechanisms explaining this relationship and no studies have focused on rural youth. In this study, we examined parents' support of children's PA as an intermediary factor linking social capital and youth PA in a largely rural cross sectional sample of American children aged 6- to 19-years and their parents/guardians (N=767 families) living in upstate New York. Parents completed a self-administered survey assessing demographic factors, perceived social capital, support for children's PA, and children's PA including time spent outdoors and days per week of sufficient PA. Structural equation modeling was used to test the hypothesis that higher social capital is linked with higher parental support for PA and, in turn, higher PA in children. Analyses were conducted separately for younger (6-12 years) and older (13-19 years) children and controlled for demographic factors (child age, household education, participation in a food assistance program) and perceived neighborhood safety. Anticipated relationships among social capital, parents' activity-related support, and children's PA were identified for older, but not younger children. Findings suggest that parent support for children's PA is one possible mechanism linking social capital and youth PA and the parents of adolescents may rely more heavily on cues from their social environment to shape their approaches to supporting their children's PA than parents of younger children. Copyright © 2012 Elsevier Ltd. All rights reserved.

A palliative care link nurse programme in Mulago Hospital, Uganda: an evaluation using mixed methods.

PubMed

Downing, Julia; Batuli, Mwazi; Kivumbi, Grace; Kabahweza, Josephine; Grant, Liz; Murray, Scott A; Namukwaya, Elizabeth; Leng, Mhoira

2016-04-08

Integrating palliative care (PC) and empowering the health care workforce is essential to achieve universal access to PC services. In 2010, 46% of patients in Mulago Hospital, Uganda had a life limiting illness, of whom 96% had PC needs. The university/hospital specialist PC unit (Makerere/Mulago Palliative Care Unit -MPCU) implemented a link-nurse model to empower hospital nurses to provide generalist PC. Over two years, 27 link nurses were trained and mentored and 11 clinical protocols developed. The aim of the study was to evaluate the impact of the palliative care link nurse programme at Mulago Hospital An evaluation approach utilising mixed methods was used integrating qualitative and quantitative data including: pre and post course assessment confidence ratings; course evaluation forms; audit of clinical guidelines availability; review of link-nurse activity sheets/action plans; review of MPCU patient documentation; Most Significant Change (MSC); individual and focus group interviews. A significant difference was seen in nurses' confidence after the training (p < 0.001). From July 2012 to December 2013, link nurses identified 2447 patients needing PC, of whom they cared for 2113 (86%) and referred 334 (14%) to MPCU. Clinical guidelines/protocols were utilised in 50% of wards. Main themes identified include: change in attitude; developing new skills and knowledge; change in relationships; improved outcomes of care, along with the challenges that they experienced in integrating PC. Since the start of the programme there has been an increase in PC patients seen at the hospital (611 in 2011 to 1788 in 2013). The link-nurse programme is a practical model for integrating PC into generalist services. Recommendations have been made for ongoing development and expansion of the programme as an effective health systems strengthening approach in similar healthcare contexts, as well as the improvement in medical and nursing education.

2 Gbit/s 0.5 μm complementary metal-oxide semiconductor optical transceiver with event-driven dynamic power-on capability

NASA Astrophysics Data System (ADS)

Wang, Xingle; Kiamilev, Fouad; Gui, Ping; Wang, Xiaoqing; Ekman, Jeremy; Zuo, Yongrong; Blankenberg, Jason; Haney, Michael

2006-06-01

A 2 Gb/s0.5 μm complementary metal-oxide semiconductor optical transceiver designed for board- or backplane level power-efficient interconnections is presented. The transceiver supports optical wake-on-link (OWL), an event-driven dynamic power-on technique. Depending on external events, the transceiver resides in either the active mode or the sleep mode and switches accordingly. The active-to-sleep transition shuts off the normal, gigabit link and turns on dedicated circuits to establish a low-power (~1.8 mW), low data rate (less than 100 Mbits/s) link. In contrast the normal, gigabit link consumes over 100 mW. Similarly the sleep-to-active transition shuts off the low-power link and turns on the normal, gigabit link. The low-power link, sharing the same optical channel with the normal, gigabit link, is used to achieve transmitter/receiver pair power-on synchronization and greatly reduces the power consumption of the transceiver. A free-space optical platform was built to evaluate the transceiver performance. The experiment successfully demonstrated the event-driven dynamic power-on operation. To our knowledge, this is the first time a dynamic power-on scheme has been implemented for optical interconnects. The areas of the circuits that implement the low-power link are approximately one-tenth of the areas of the gigabit link circuits.

All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.

PubMed

Karmali, Reem; Dalovisio, Andrew; Borgia, Jeffrey A; Venugopal, Parameswaran; Kim, Brian W; Grant-Szymanski, Kelly; Hari, Parameswaran; Lazarus, Hillard

2015-03-01

Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management and monitoring of the endangered Shenandoah salamander under climate change: Workshop report 10-12 April 2012

USGS Publications Warehouse

Grant, Evan H. Campbell; Wofford, John E.B.; Smith, D.R.; Dennis, J.; Hawkins-Hoffman, C.; Schaberl, J.; Foley, M.; Bogle, M.

2014-01-01

Here we report on a structured decision making (SDM) process to identify management strategies to ensure persistence of the federally endangered Shenandoah salamander (Plethodon shenandoah), given that it may be at increased extinction risk under projected climate change. The focus of this report is the second of two SDM workshops; in the first workshop, participants developed a prototype of the decision, including problem frame, management objectives and a suite of potential management strategies, predictive models to inform the decision and link alternatives with the objectives to identify potential solutions, and identified data needs to reduce key uncertainties in the decision. Participants in this second workshop included experts in National Park Service policy at multiple administrative levels, who refined objectives, further evaluated the initial management alternatives, and discussed policy constraints on implementing active management for the species and its high-elevation habitat. The conclusion of the second workshop was similar to that of the first: the current state of information and objectives suggest that there is some value in considering active management to reduce the long-term extinction risk for the species, though there are institutional conservative policies to implementing active management at range-wide scales. The workshop participants also emphasized a conservative NPS management philosophy, including caution in implementing management actions that may ultimately harm the system, a stated assumption that ecosystem changes were “natural” unless demonstrated otherwise (therefore not warranting active management to mitigate), and a need to demonstrate that extinction risk is tied to anthropogenic influence prior to taking active management to mitigate specific anthropogenic influences. Even within a protected area having minimal human disturbance, intertwined environmental variables and interspecific relationships that drive population trends challenge our ability to demonstrate direct links with (anthropogenically influenced) climate change and the decline of a species. Thus while this policy may reduce the potential for injurious management, it may also necessitate extraordinary resources to reduce uncertainty regarding fundamental drivers of species decline prior to taking action.

KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules.

PubMed

Miah, S M Shahjahan; Hughes, Tracey L; Campbell, Kerry S

2008-03-01

KIR2DL4 (2DL4) is a member of the killer cell Ig-like receptor (KIR) family in human NK cells. It can stimulate potent cytokine production and weak cytolytic activity in resting NK cells, but the mechanism for 2DL4-mediated signaling remains unclear. In this study we characterized the signaling pathways stimulated by 2DL4 engagement. In a human NK-like cell line, KHYG-1, cross-linking of 2DL4 activated MAPKs including JNK, ERK, and p38. Furthermore, 2DL4 cross-linking resulted in phosphorylation of IkappaB kinase beta (IKKbeta) and the phosphorylation and degradation of IkappaBalpha, which indicate activation of the classical NF-kappaB pathway. Engagement of 2DL4 was also shown to activate the transcription and translation of a variety of cytokine genes, including TNF-alpha, IFN-gamma, MIP1alpha, MIP1beta, and IL-8. Pharmacological inhibitors of JNK, MEK1/2 and p38, blocked IFN-gamma, IL-8, and MIP1alpha production, suggesting that MAPKs are regulating 2DL4-mediated cytokine production in a nonredundant manner. Activation of both p38 and ERK appear to be upstream of the stimulation of NF-kappaB. Mutation of a transmembrane arginine in 2DL4 to glycine (R/G mutant) abrogated FcepsilonRI-gamma association, as well as receptor-mediated cytolytic activity and calcium responses. Surprisingly, the R/G mutant still activated MAPKs and the NF-kappaB pathway and selectively stimulated the production of MIP1alpha, but not that of IFN-gamma or IL-8. In conclusion, we provide evidence that the activating functions of 2DL4 can be compartmentalized into two distinct structural modules: 1) through transmembrane association with FcepsilonRI-gamma; and 2) through another receptor domain independent of the transmembrane arginine.

Get the Facts: Drinking Water and Intake

MedlinePlus

... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Related Links CDC Food ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Related Links CDC Food ...

Antimicrobial Substances for Food Packaging Products: The Current Situation.

PubMed

Pellerito, Alessandra; Ameen, Sara M; Micali, Maria; Caruso, Giorgia

2018-04-04

Antimicrobial substances are widely used in many anthropic activities, including sanitary and military services for the human population. These compounds are also known to be used in food production, agricultural activities, and partially correlated industrial sectors. However, there are concerns regarding the link between the abuse of antimicrobial agents in these ambits and the possible detection of antibiotic-resistant microorganisms. Modern food and beverage products are generally found on the market as prepackaged units, with several exceptions. Consequently, positive and negative features of a specific food or beverage should be considered as the result of the synergic action of different components, including the container (or the assembled sum of packaging materials). At present, the meaning of food container also includes the creation and development of new packaging materials that are potentially able to interact with the contained food. "Active" packaging systems can be realized with antimicrobial substances. On the other hand, a careful evaluation of risks and advantages correlated with antimicrobial agents is needed because of possible negative and/or unexpected failures.

Characterization of Member of DUF1888 Protein Family, Self-cleaving and Self-assembling Endopeptidase*

PubMed Central

Osipiuk, Jerzy; Mulligan, Rory; Bargassa, Monireh; Hamilton, John E.; Cunningham, Mark A.; Joachimiak, Andrzej

2012-01-01

The crystal structure of SO1698 protein from Shewanella oneidensis was determined by a SAD method and refined to 1.57 Å. The structure is a β sandwich that unexpectedly consists of two polypeptides; the N-terminal fragment includes residues 1–116, and the C-terminal one includes residues 117–125. Electron density also displayed the Lys-98 side chain covalently linked to Asp-116. The putative active site residues involved in self-cleavage were identified; point mutants were produced and characterized structurally and in a biochemical assay. Numerical simulations utilizing molecular dynamics and hybrid quantum/classical calculations suggest a mechanism involving activation of a water molecule coordinated by a catalytic aspartic acid. PMID:22493430

Learning About Wisconsin: Activities, Historical Documents, and Resources Linked to Wisconsin's Model Academic Standards for Social Studies in Grades 4-12. Bulletin No. 99238.

ERIC Educational Resources Information Center

Fortier, John D.; Grady, Susan M.; Prickette, Karen R.

Wisconsin's Model Academic Standards for Social Studies provide direction for curriculum, instruction, assessment, and professional development. The standards identify eras and themes in Wisconsin history. Many of these standards can be taught using content related to the study of Wisconsin. The sample lessons included in this document identify…

What Strategy Should Bulgaria Pursue to Track and Disrupt Terror Networks in the Balkans?

DTIC Science & Technology

2014-03-01

important function of law enforcement is to “disrupt terrorist financing that includes by uncovering links between terrorists and organized criminal groups... money laundering , black market activity, and drug trade.”119 C. SUMMARY International terrorism is constantly evolving in its tactics and...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited WHAT STRATEGY SHOULD

*Combining regional - and local-scale air quality models with exposure models for use in environmental health studies - Title changed from Linking air quality and exposure models for use in environmental health studies

EPA Science Inventory

Population-based human exposure models predict the distribution of personal exposures to pollutants of outdoor origin using a variety of inputs, including air pollution concentrations; human activity patterns, such as the amount of time spent outdoors versus indoors, commuting, w...

The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network.

PubMed

Palhano-Fontes, Fernanda; Andrade, Katia C; Tofoli, Luis F; Santos, Antonio C; Crippa, Jose Alexandre S; Hallak, Jaime E C; Ribeiro, Sidarta; de Araujo, Draulio B

2015-01-01

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

Spatial and Temporal Variability and Trends in 2001-2016 Global Fire Activity

NASA Astrophysics Data System (ADS)

Earl, Nick; Simmonds, Ian

2018-03-01

Fire regimes across the globe have great spatial and temporal variability, and these are influence by many factors including anthropogenic management, climate, and vegetation types. Here we utilize the satellite-based "active fire" product, from Moderate Resolution Imaging Spectroradiometer (MODIS) sensors, to statistically analyze variability and trends in fire activity from the global to regional scales. We split up the regions by economic development, region/geographical land use, clusters of fire-abundant areas, or by religious/cultural influence. Weekly cycle tests are conducted to highlight and quantify part of the anthropogenic influence on fire regime across the world. We find that there is a strong statistically significant decline in 2001-2016 active fires globally linked to an increase in net primary productivity observed in northern Africa, along with global agricultural expansion and intensification, which generally reduces fire activity. There are high levels of variability, however. The large-scale regions exhibit either little change or decreasing in fire activity except for strong increasing trends in India and China, where rapid population increase is occurring, leading to agricultural intensification and increased crop residue burning. Variability in Canada has been linked to a warming global climate leading to a longer growing season and higher fuel loads. Areas with a strong weekly cycle give a good indication of where fire management is being applied most extensively, for example, the United States, where few areas retain a natural fire regime.

A cannabinoid link between mitochondria and memory.

PubMed

Hebert-Chatelain, Etienne; Desprez, Tifany; Serrat, Román; Bellocchio, Luigi; Soria-Gomez, Edgar; Busquets-Garcia, Arnau; Pagano Zottola, Antonio Christian; Delamarre, Anna; Cannich, Astrid; Vincent, Peggy; Varilh, Marjorie; Robin, Laurie M; Terral, Geoffrey; García-Fernández, M Dolores; Colavita, Michelangelo; Mazier, Wilfrid; Drago, Filippo; Puente, Nagore; Reguero, Leire; Elezgarai, Izaskun; Dupuy, Jean-William; Cota, Daniela; Lopez-Rodriguez, Maria-Luz; Barreda-Gómez, Gabriel; Massa, Federico; Grandes, Pedro; Bénard, Giovanni; Marsicano, Giovanni

2016-11-24

Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB 1 ) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB 1 receptors. Genetic exclusion of CB 1 receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB 1 receptors signal through intra-mitochondrial Gα i protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB 1 receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.

Differences in extracellular matrix proteins between Friesian horses with aortic rupture, unaffected Friesians and Warmblood horses.

PubMed

Ploeg, M; Gröne, A; van de Lest, C H A; Saey, V; Duchateau, L; Wolsein, P; Chiers, K; Ducatelle, R; van Weeren, P R; de Bruijn, M; Delesalle, C

2017-09-01

Unlike in Warmblood horses, aortic rupture is quite common in Friesian horses, in which a hereditary trait is suspected. The aortic connective tissue in affected Friesians shows histological changes such as medial necrosis, elastic fibre fragmentation, mucoid material accumulation and fibrosis with aberrant collagen morphology. However, ultrastructural examination of the collagen fibres of the mid-thoracic aorta has been inconclusive in further elucidating the pathogenesis of the disease. To assess several extracellular matrix (ECM) components biochemically in order to explore a possible underlying breed-related systemic ECM defect in Friesians with aortic rupture. Cadaver study. Tissues from affected Friesians (n = 18), unaffected Friesians (n = 10) and Warmblood horses (n = 30) were compared. Samples were taken from the thoracic aorta at the level of the rupture site, from two locations caudal to the rupture and from the deep digital flexor tendon. Total collagen content, post-translational modifications of collagen formation including lysine hydroxylation, and hydroxylysylpyridinoline (HP), lysylpyridinoline (LP) and pyrrole cross-links were analysed. Additionally, elastin cross-links, glycosaminoglycan content and matrix metalloproteinase (MMP) activity were assessed. Significantly increased MMP activity and increased LP and HP cross-linking, lysine hydroxylation and elastin cross-linking were found at the site of rupture in affected Friesians. These changes may reflect processes involved in healing and aneurysm formation. Unaffected Friesians had less lysine hydroxylation and pyrrole cross-linking within the tendons compared with Warmblood horses. No differences in the matrix of the aorta were found between normal Warmbloods and Friesian horses. Small sample size. The differences in collagen parameters in tendon tissue may reflect differences in connective tissue metabolism between Friesians and Warmblood horses. © 2017 EVJ Ltd.

Recent Geological and Hydrological Activity in Amazonis and Elysium Basins and Their Link, Marte Valles (AME): Prime Target for Future Reconnaissance

NASA Astrophysics Data System (ADS)

Dohm, J. M.; Robbins, S. J.; Hynek, B. M.

2012-03-01

Amazonis and Elysium basins and their link, Marte Vallis (AME), uniquely point to a geologically and hydrologically active Mars. We will present evidence for why AME reconnaissance can help address whether Mars is geologically, hydrologically, and biologically active.

Links Between Watershed Activities and the Degradation of Coastal, Tidal Salt Marshes in Southern New England USA

EPA Science Inventory

Human activities (e.g., land development, wastewater) in coastal watersheds in New England USA are linked with community- and system-level changes in tidal, organic-rich salt marshes. Significant relationships between various indicators of watershed activities and ecosystem stru...

Developmental Experiences during Extracurricular Activities and Australian Adolescents' Self-Concept: Particularly Important for Youth from Disadvantaged Schools

ERIC Educational Resources Information Center

Blomfield, Corey J.; Barber, Bonnie L.

2011-01-01

Extracurricular activities provide adolescents with a number of positive personal and interpersonal developmental experiences. This study investigated whether developmental experiences that occurred during extracurricular activities were linked to a more positive self-concept for Australian adolescents, and whether this link was particularly…

Diurnal, seasonal, and interannual differences in the links of probabilities of derivation of different types Es with solar activity

NASA Astrophysics Data System (ADS)

Petrukhin, Venedict F.; Poddubnaya, I. V.; Ponomarev, Evgenij A.; Sutyrin, Nicolaj A.

2004-12-01

The analysis of the ionospheric data on Irkutsk obtained from 1960 to 1996 was made. Was shown, that the link of probabilities of observation of the sporadic derivations in E-region of ionosphere with solar activity (SA) essentially depends on time of day, season and correlation between solar and geophysical parameters. For different types of sporadic derivations this link has different character and with a different image varies with current of time. It is necessary to mark, that the link of night sporadic derivations (Es such as "f") with solar activity in the summer very high and practically does not vary in time (r=-0.897-/+0.04). The temporary course of coefficients of correlation between solar activity and probability of observation of sporadic stratums (r) of a different type varies depending on the season. Further, for stratums of a type "cl" and "l" the change r happens within increase of SA. At the same time, there is an abnormal behavior of height so f sporadic stratums such as "cl". There is an impression that in a considered time frame there is competition of two factors. One of them - solar activity, which in the norm supports the negative correlation link with frequency of observation and second - a factor of an unknown nature, which has caused evocative anomaly of altitude, becomes dominant above natural negative link.

Tandem UIMs confer Lys48 ubiquitin chain substrate preference to deubiquitinase USP25

PubMed Central

Kawaguchi, Kohei; Uo, Kazune; Tanaka, Toshiaki; Komada, Masayuki

2017-01-01

Ubiquitin-specific protease (USP) 25, belonging to the USP family of deubiquitinases, harbors two tandem ubiquitin-interacting motifs (UIMs), a ~20-amino-acid α-helical stretch that binds to ubiquitin. However, the role of the UIMs in USP25 remains unclear. Here we show that the tandem UIM region binds to Lys48-, but not Lys63-, linked ubiquitin chains, where the two UIMs played a critical and cooperative role. Purified USP25 exhibited higher ubiquitin isopeptidase activity to Lys48-, than to Lys63-, linked ubiquitin chains. Mutations that disrupted the ubiquitin-binding ability of the tandem UIMs resulted in a reduced ubiquitin isopeptidase activity of USP25, suggesting a role for the UIMs in exerting the full catalytic activity of USP25. Moreover, when mutations that convert the binding preference from Lys48- to Lys63-linked ubiquitin chains were introduced into the tandem UIM region, the USP25 mutants acquired elevated and reduced isopeptidase activity toward Lys63- and Lys48-linked ubiquitin chains, respectively. These results suggested that the binding preference of the tandem UIMs toward Lys48-linked ubiquitin chains contributes not only to the full catalytic activity but also to the ubiquitin chain substrate preference of USP25, possibly by selectively holding the Lys48-linked ubiquitin chain substrates in the proximity of the catalytic core. PMID:28327663

The contribution of human agricultural activities to increasing evapotranspiration is significantly greater than climate change effect over Heihe agricultural region.

PubMed

Zou, Minzhong; Niu, Jun; Kang, Shaozhong; Li, Xiaolin; Lu, Hongna

2017-08-18

Evapotranspiration (ET) is a major component linking the water, energy, and carbon cycles. Understanding changes in ET and the relative contribution rates of human activity and of climate change at the basin scale is important for sound water resources management. In this study, changes in ET in the Heihe agricultural region in northwest China during 1984-2014 were examined using remotely-sensed ET data with the Soil and Water Assessment Tool (SWAT). Correlation analysis identified the dominant factors that influence change in ET per unit area and those that influence change in total ET. Factor analysis identified the relative contribution rates of the dominant factors in each case. The results show that human activity, which includes factors for agronomy and irrigation, and climate change, including factors for precipitation and relative humidity, both contribute to increases in ET per unit area at rates of 60.93% and 28.01%, respectively. Human activity, including the same factors, and climate change, including factors for relative humidity and wind speed, contribute to increases in total ET at rates of 53.86% and 35.68%, respectively. Overall, in the Heihe agricultural region, the contribution of human agricultural activities to increased ET was significantly greater than that of climate change.

Rethinking the solar flare paradigm

NASA Astrophysics Data System (ADS)

D, B. MELROSE

2018-07-01

It is widely accepted that solar flares involve release of magnetic energy stored in the solar corona above an active region, but existing models do not include the explicitly time-dependent electrodynamics needed to describe such energy release. A flare paradigm is discussed that includes the electromotive force (EMF) as the driver of the flare, and the flare-associated current that links different regions where magnetic reconnection, electron acceleration, the acceleration of mass motions and current closure occur. The EMF becomes localized across regions where energy conversion occurs, and is involved in energy propagation between these regions.

Orbiter CIU/IUS communications hardware evaluation

NASA Technical Reports Server (NTRS)

Huth, G. K.

1979-01-01

The DOD and NASA inertial upper stage communication system design, hardware specifications and interfaces were analyzed to determine their compatibility with the Orbiter payload communications equipment (Payload Interrogator, Payload Signal Processors, Communications Interface Unit, and the Orbiter operational communications equipment (the S-Band and Ku-band systems). Topics covered include (1) IUS/shuttle Orbiter communications interface definition; (2) Orbiter avionics equipment serving the IUS; (3) IUS communication equipment; (4) IUS/shuttle Orbiter RF links; (5) STDN/TDRS S-band related activities; and (6) communication interface unit/Orbiter interface issues. A test requirement plan overview is included.

Suggested Planting Guidelines - Best Management Practices for Revegetation of Actively Used Training Lands in the Northeastern United States

DTIC Science & Technology

2012-09-01

Indiana Crane Naval Warfare Center Jefferson Proving Ground Camp Atterbury 62,473 1,033 33,484 ERDC/CRREL TR-12-10 4 State and Facility Land...2012). They include seeding wildflowers and forbs as well as planting woody materials. Equipment used in the planting process is not included in...on invasive weeds by state can be found at http://www.fs.fed.us/rm/boise/research/ shrub /links.shtml ERDC/CRREL TR-12-10 18 3 Selecting the Seed

Stretchy Proteins on Stretchy Substrates: The Important Elements of Integrin-Mediated Rigidity Sensing

PubMed Central

Moore, Simon W.; Roca-Cusachs, Pere; Sheetz, Michael P.

2013-01-01

Matrix and tissue rigidity guides many cellular processes, including the differentiation of stem cells and the migration of cells in health and disease. Cells actively and transiently test rigidity using mechanisms limited by inherent physical parameters that include the strength of extracellular attachments, the pulling capacity on these attachments, and the sensitivity of the mechanotransduction system. Here we focus on rigidity sensing mediated through the integrin family of extracellular matrix receptors and linked proteins, and discuss the evidence supporting these proteins as mechanosensors. PMID:20708583

Living long and ageing well: is epigenomics the missing link between nature and nurture?

PubMed

Rea, Irene Maeve; Dellet, Margaret; Mills, Ken I

2016-02-01

Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

Cultural orientations, daily activities, and adjustment in Mexican American youth.

PubMed

McHale, Susan M; Updegraff, Kimberly A; Kim, Ji-Yeon; Cansler, Emily

2009-05-01

The links between youth's daily activities and adjustment and the role of cultural practices and values in these links were studied in 469 youth from 237 Mexican American families. In home interviews, data on mothers', fathers', and two adolescent-age siblings' cultural practices (language use, social contacts) and values (for familism, for education achievement) were collected, along with data on youth risky behavior and depressive symptoms. In 7 nightly phone calls, youth reported on their day's free time activities (i.e., sports, academics, religious activities, television viewing, and hanging out). Analyses revealed that youth who spent more time in unsupervised hanging out reported more depressive symptoms and risky behavior, and those who spent more time in academic activities reported less risky behavior. Results also indicated that more Anglo-oriented youth spent more time in sports, that more Mexican-oriented youth spent more time watching television, that fathers' familism values were related to youth's time in religious activities, and that parents' educational values were linked to youth's time in academic activities. Some evidence indicated that parents' cultural practices and values, particularly fathers', moderated the links between daily activities and youth adjustment.

A top-down perspective on dopamine, motivation and memory.

PubMed

Phillips, Anthony G; Vacca, Giada; Ahn, Soyon

2008-08-01

Dopamine (DA) activity, in the form of increased neural firing or enhanced release of transmitter from nerve terminals and varicosities, is linked to a number of important psychological processes including: movement; hedonic reactions to positive reward; provision of an error detection signal during the acquisition of new learning; response to novel stimuli; provision of reinforcement signals essential for acquisition of new action patterns; and incentive motivation. This review focuses primarily on our research linking dynamic changes in DA efflux on the timescale of minutes, with incentive motivation, as revealed by brain dialysis experiments in behaving animals. Recent experiments on sensory-specific satiety and successive positive and negative contrast are discussed along with the distinction between preparatory behaviors that precede contact with biologically significant stimuli and subsequent consummatory behaviors. The relationship between DA efflux in the medial prefrontal cortex (mPFC) and foraging for food based on working memory is also discussed in support of the conjecture that DA may serve as a link between motivation and memory functions. Evidence in support of 'top-down' regulation of dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to introduce a mechanism by which activation of ascending DA projections in this manner might optimize dopaminergic modulation of executive function within regions such as the mPFC. Collectively, these processes could ensure coordination between cognitive processes that assess current opportunities and the motivational systems that select and engage patterns of approach behavior that bring organisms into contact with the essentials for survival.

Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis.

PubMed

Nutku, Esra; Aizawa, Hideyuki; Hudson, Sherry A; Bochner, Bruce S

2003-06-15

Sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), which exists in 2 isoforms including one possessing cytoplasmic tyrosine motifs, is expressed only on human eosinophils, basophils, and mast cells. Until now, its function was unknown. Here we define a novel function of Siglec-8 on eosinophils. Siglec-8 cross-linking with antibodies rapidly generated caspase-3-like activity and reduced eosinophil viability through induction of apoptosis. The pancaspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp-(Ome)-fluoromethyl ketone (zVAD-FMK) completely blocked this response, implicating caspases in Siglec-8 cross-linking-induced apoptosis. Eosinophil survival-promoting cytokines such as interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) failed to block apoptosis and instead enhanced the sensitivity of eosinophils to undergo apoptosis in response to Siglec-8 antibody. Siglec-8 activation may provide a useful therapeutic approach to reduce numbers of eosinophils (and perhaps basophils and mast cells) in disease states where these cells are important.

Linking departmental priorities to knowledge management: the experiences of Santa Cruz County's Human Services Department.

PubMed

Lindberg, Arley

2012-01-01

Federal welfare reform, local service collaborations, and the evolution of statewide information systems inspired agency interest in evidence-informed practice and knowledge sharing systems. Four agency leaders, including the Director, Deputy Director, Director of Planning and Evaluation, and Staff Development Program Manager championed the development of a learning organization based on knowledge management throughout the agency. Internal department restructuring helped to strengthen the Planning and Evaluation, Staff Development, and Personnel units, which have become central to supporting knowledge sharing activities. The Four Pillars of Knowledge framework was designed to capture agency directions in relationship to future knowledge management goals. Featuring People, Practice, Technology and Budget, the framework links the agency's services, mission and goals to the process of becoming a learning organization. Built through an iterative process, the framework was created by observing existing activities in each department rather than being designed from the top down. Knowledge management can help the department to fulfill its mission despite reduced resources. Copyright © Taylor & Francis Group, LLC

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

PubMed Central

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S.; Jain, Shalini; Lowell, Bradford B.; Krashes, Michael J.; Wess, Jürgen

2016-01-01

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity. PMID:26743492

Strong mechanically induced effects in DC current-biased suspended Josephson junctions

NASA Astrophysics Data System (ADS)

McDermott, Thomas; Deng, Hai-Yao; Isacsson, Andreas; Mariani, Eros

2018-01-01

Superconductivity is a result of quantum coherence at macroscopic scales. Two superconductors separated by a metallic or insulating weak link exhibit the AC Josephson effect: the conversion of a DC voltage bias into an AC supercurrent. This current may be used to activate mechanical oscillations in a suspended weak link. As the DC-voltage bias condition is remarkably difficult to achieve in experiments, here we analyze theoretically how the Josephson effect can be exploited to activate and detect mechanical oscillations in the experimentally relevant condition with purely DC current bias. We unveil how changing the strength of the electromechanical coupling results in two qualitatively different regimes showing dramatic effects of the oscillations on the DC-voltage characteristic of the device. These include the appearance of Shapiro-type plateaus for weak coupling and a sudden mechanically induced retrapping for strong coupling. Our predictions, measurable in state-of-the-art experimental setups, allow the determination of the frequency and quality factor of the resonator using DC only techniques.

Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

PubMed

Mody, Nimesh

2017-11-01

Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

The GENCODE exome: sequencing the complete human exome

PubMed Central

Coffey, Alison J; Kokocinski, Felix; Calafato, Maria S; Scott, Carol E; Palta, Priit; Drury, Eleanor; Joyce, Christopher J; LeProust, Emily M; Harrow, Jen; Hunt, Sarah; Lehesjoki, Anna-Elina; Turner, Daniel J; Hubbard, Tim J; Palotie, Aarno

2011-01-01

Sequencing the coding regions, the exome, of the human genome is one of the major current strategies to identify low frequency and rare variants associated with human disease traits. So far, the most widely used commercial exome capture reagents have mainly targeted the consensus coding sequence (CCDS) database. We report the design of an extended set of targets for capturing the complete human exome, based on annotation from the GENCODE consortium. The extended set covers an additional 5594 genes and 10.3 Mb compared with the current CCDS-based sets. The additional regions include potential disease genes previously inaccessible to exome resequencing studies, such as 43 genes linked to ion channel activity and 70 genes linked to protein kinase activity. In total, the new GENCODE exome set developed here covers 47.9 Mb and performed well in sequence capture experiments. In the sample set used in this study, we identified over 5000 SNP variants more in the GENCODE exome target (24%) than in the CCDS-based exome sequencing. PMID:21364695

Antibacterial activity of synthetic curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA).

PubMed

Vilekar, Prachi; King, Catherine; Lagisetty, Pallavi; Awasthi, Vibhudutta; Awasthi, Shanjana

2014-04-01

Curcumin is well known for its antimicrobial and anti-inflammatory properties. However, since systemic absorption and bioavailability of curcumin from gastrointestinal tract is considerably poor, synthetic curcuminoids are being developed as better alternatives. Two curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA), were included in this study. We investigated the antibacterial activity of EF24 and EF2DTPA against Gram-negative (Escherichia coli) and Gram-positive (Enterococcus faecalis, Staphylococcus aureus) bacteria. We also studied the effects of EF24 and EF2DTPA on uptake and localization of pHrodo-labeled E. coli in the acidic compartments (phagolysosomes) of dendritic cells (DCs) under in vitro conditions. Our results demonstrate that treatment with EF24 and EF2DTPA directly suppresses the bacterial growth. However, these compounds do not affect the bacterial uptake or localization in the DCs.

Tribology of alternative bearings.

PubMed

Fisher, John; Jin, Zhongmin; Tipper, Joanne; Stone, Martin; Ingham, Eileen

2006-12-01

The tribological performance and biological activity of the wear debris produced has been compared for highly cross-linked polyethylene, ceramic-on-ceramic, metal-on-metal, and modified metal bearings in a series of in vitro studies from a single laboratory. The functional lifetime demand of young and active patients is 10-fold greater than the estimated functional lifetime of traditional polyethylene. There is considerable interest in using larger diameter heads in these high demand patients. Highly cross-linked polyethylene show a four-fold reduction in functional biological activity. Ceramic-on-ceramic bearings have the lowest wear rates and least reactive wear debris. The functional biological activity is 20-fold lower than with highly cross-linked polyethylene. Hence, ceramic-on-ceramic bearings address the tribological lifetime demand of highly active patients. Metal-on-metal bearings have substantially lower wear rates than highly cross-linked polyethylene and wear decreases with head diameter. Bedding in wear is also lower with reduced radial clearance. Differential hardness ceramic-on-metal bearings and the application of ceramic-like coatings reduce metal wear and ion levels.

A Role for the Motor System in Binding Abstract Emotional Meaning

PubMed Central

Carota, Francesca; Hauk, Olaf; Mohr, Bettina; Pulvermüller, Friedemann

2012-01-01

Sensorimotor areas activate to action- and object-related words, but their role in abstract meaning processing is still debated. Abstract emotion words denoting body internal states are a critical test case because they lack referential links to objects. If actions expressing emotion are crucial for learning correspondences between word forms and emotions, emotion word–evoked activity should emerge in motor brain systems controlling the face and arms, which typically express emotions. To test this hypothesis, we recruited 18 native speakers and used event-related functional magnetic resonance imaging to compare brain activation evoked by abstract emotion words to that by face- and arm-related action words. In addition to limbic regions, emotion words indeed sparked precentral cortex, including body-part–specific areas activated somatotopically by face words or arm words. Control items, including hash mark strings and animal words, failed to activate precentral areas. We conclude that, similar to their role in action word processing, activation of frontocentral motor systems in the dorsal stream reflects the semantic binding of sign and meaning of abstract words denoting emotions and possibly other body internal states. PMID:21914634

Measurement of activity limitations and participation restrictions: examination of ICF-linked content and scale properties of the FIM and PC-PART instruments.

PubMed

Darzins, Susan W; Imms, Christine; Di Stefano, Marilyn

2017-05-01

To explore the operationalization of activity and participation-related measurement constructs through comparison of item phrasing, item response categories and scoring (scale properties) for two separate instruments targeting activities of daily living. Personal Care Participation Assessment and Resource Tool (PC-PART) item content was linked to ICF categories using established linking rules. Previously reported ICF-linked FIM content categories and ICF-linked PC-PART content categories were compared to identify common ICF categories between the instruments. Scale properties of both instruments were compared using a patient scenario to explore the instruments' separate measurement constructs. The PC-PART and FIM shared 15 of the 53 level two ICF-linked categories identified across both instruments. Examination of the instruments' scale properties for items with overlapping ICF content, and exploration through a patient scenario, provided supportive evidence that the instruments measure different constructs. While the PC-PART and FIM share common ICF-linked content, they measure separate constructs. Measurement construct was influenced by the instruments' scale properties. The FIM was observed to measure activity limitations and the PC-PART measured participation restrictions. Scrutiny of instruments' scale properties in addition to item content is critical in the operationalization of activity and participation-related measurement constructs. Implications for Rehabilitation When selecting outcome measures for use in rehabilitation it is necessary to examine both the content of the instruments' items and item phrasing, response categories and scoring, to clarify the construct being measured. Measurement of activity limitations as well as participation restrictions in activities of daily living required for community life provides a more comprehensive measurement of rehabilitation outcomes than measurement of either construct alone. To measure the effects of interventions used in rehabilitation, it is necessary to select measures with relevant content and scale properties that enable evaluation of change in the constructs that are expected to change, as a result of the rehabilitation intervention.

Sensitive kinase assay linked with phosphoproteomics for identifying direct kinase substrates

PubMed Central

Xue, Liang; Wang, Wen-Horng; Iliuk, Anton; Hu, Lianghai; Galan, Jacob A.; Yu, Shuai; Hans, Michael; Geahlen, Robert L.; Tao, W. Andy

2012-01-01

Our understanding of the molecular control of many disease pathologies requires the identification of direct substrates targeted by specific protein kinases. Here we describe an integrated proteomic strategy, termed kinase assay linked with phosphoproteomics, which combines a sensitive kinase reaction with endogenous kinase-dependent phosphoproteomics to identify direct substrates of protein kinases. The unique in vitro kinase reaction is carried out in a highly efficient manner using a pool of peptides derived directly from cellular kinase substrates and then dephosphorylated as substrate candidates. The resulting newly phosphorylated peptides are then isolated and identified by mass spectrometry. A further comparison of these in vitro phosphorylated peptides with phosphopeptides derived from endogenous proteins isolated from cells in which the kinase is either active or inhibited reveals new candidate protein substrates. The kinase assay linked with phosphoproteomics strategy was applied to identify unique substrates of spleen tyrosine kinase (Syk), a protein-tyrosine kinase with duel properties of an oncogene and a tumor suppressor in distinctive cell types. We identified 64 and 23 direct substrates of Syk specific to B cells and breast cancer cells, respectively. Both known and unique substrates, including multiple centrosomal substrates for Syk, were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity. PMID:22451900

The Saccharomyces cerevisiae DPM1 gene encoding dolichol-phosphate-mannose synthase is able to complement a glycosylation-defective mammalian cell line.

PubMed Central

Beck, P J; Orlean, P; Albright, C; Robbins, P W; Gething, M J; Sambrook, J F

1990-01-01

The Saccharomyces cerevisiae DPM1 gene product, dolichol-phosphate-mannose (Dol-P-Man) synthase, is involved in the coupled processes of synthesis and membrane translocation of Dol-P-Man. Dol-P-Man is the lipid-linked sugar donor of the last four mannose residues that are added to the core oligosaccharide transferred to protein during N-linked glycosylation in the endoplasmic reticulum. We present evidence that the S. cerevisiae gene DPM1, when stably transfected into a mutant Chinese hamster ovary cell line, B4-2-1, is able to correct the glycosylation defect of the cells. Evidence for complementation includes (i) fluorescence-activated cell sorter analysis of differential lectin binding to cell surface glycoproteins, (ii) restoration of Dol-P-Man synthase enzymatic activity in crude cell lysates, (iii) isolation and high-performance liquid chromatography fractionation of the lipid-linked oligosaccharides synthesized in the transfected and control cell lines, and (iv) the restoration of endoglycosidase H sensitivity to the oligosaccharides transferred to a specific glycoprotein synthesized in the DPM1 CHO transfectants. Indirect immunofluorescence with a primary antibody directed against the DPM1 protein shows a reticular staining pattern of protein localization in transfected hamster and monkey cell lines. Images PMID:2201896

Deriving Leaf Area Index (LAI) from multiple lidar remote sensing systems

NASA Astrophysics Data System (ADS)

Tang, H.; Dubayah, R.; Zhao, F.

2012-12-01

LAI is an important biophysical variable linking biogeochemical cycles of earth systems. Observations with passive optical remote sensing are plagued by saturation and results from different passive and active sensors are often inconsistent. Recently lidar remote sensing has been applied to derive vertical canopy structure including LAI and its vertical profile. In this research we compare LAI retrievals from three different types of lidar sensors. The study areas include the La Selva Biological Station in Costa Rica and Sierra Nevada Forest in California. We first obtain independent LAI estimates from different lidar systems including airborne lidar (LVIS), spaceborne lidar (GLAS) and ground lidar (Echidna). LAI retrievals are then evaluated between sensors as a function of scale, land cover type and sensor characteristics. We also assess the accuracy of these LAI products against ground measurements. By providing a link between ground observations, ground lidar, aircraft and space-based lidar we hope to demonstrate a path for deriving more accurate estimates of LAI on a global basis, and to provide a more robust means of validating passive optical estimates of this important variable.

IKKε-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex

PubMed Central

Zhou, Alicia Y.; Shen, Rhine R.; Kim, Eejung; Lock, Ying J.; Xu, Ming; Chen, Zhijian J.; Hahn, William C.

2014-01-01

SUMMARY IκB kinase ε (IKKε, IKBKE) is a key regulator of innate immunity and a breast cancer oncogene, amplified in ~30% of breast cancers, that promotes malignant transformation through NF-κB activation. Here we show that IKKε is modified and regulated by K63-linked polyubiquitination at Lysine 30 and Lysine 401. TNFα and IL-1β stimulation induces IKKε K63-linked polyubiquitination over baseline levels in both macrophages and breast cancer cell lines, and this modification is essential for IKKε kinase activity, IKKε-mediated NF-κB activation and IKKε-induced malignant transformation. Disruption of K63-linked ubiquitination of IKKε does not affect its overall structure but impairs the recruitment of canonical NF-κB proteins. A cIAP1/cIAP2/TRAF2 E3 ligase complex binds to and ubiquitinates IKKε. Together, these observations demonstrate that K63-linked polyubiquitination regulates IKKε activity in both inflammatory and oncogenic contexts and suggests an alterative approach to target this breast cancer oncogene. PMID:23453969

The role of protein O-linked beta-N-acetylglucosamine in mediating cardiac stress responses.

PubMed

Chatham, John C; Marchase, Richard B

2010-02-01

The modification of serine and threonine residues of nuclear and cytoplasmic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) has emerged as a highly dynamic post-translational modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O-GlcNAc on cellular function has been in the context of its adverse effects in mediating a range of chronic disease processes, including diabetes, cancer and neurodegenerative diseases. However, at the cellular level it has been shown that O-GlcNAc levels are increased in response to stress; augmentation of this response improved cell survival while attenuation decreased cell viability. Thus, it has become apparent that strategies that augment O-GlcNAc levels are pro-survival, whereas those that reduce O-GlcNAc levels decrease cell survival. There is a long history demonstrating the effectiveness of acute glucose-insulin-potassium (GIK) treatment and to a lesser extent glutamine in protecting against a range of stresses, including myocardial ischemia. A common feature of these approaches for metabolic cardioprotection is that they both have the potential to stimulate O-GlcNAc synthesis. Consequently, here we examine the links between metabolic cardioprotection with the ischemic cardioprotection associated with acute increases in O-GlcNAc levels. Some of the protective mechanisms associated with activation of O-GlcNAcylation appear to be transcriptionally mediated; however, there is also strong evidence to suggest that transcriptionally independent mechanisms also play a critical role. In this context we discuss the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis including the role of non-voltage gated, capacitative calcium entry as a potential mechanism contributing to this protection. Copyright 2009 Elsevier B.V. All rights reserved.

A three-way parallel ICA approach to analyze links among genetics, brain structure and brain function.

PubMed

Vergara, Victor M; Ulloa, Alvaro; Calhoun, Vince D; Boutte, David; Chen, Jiayu; Liu, Jingyu

2014-09-01

Multi-modal data analysis techniques, such as the Parallel Independent Component Analysis (pICA), are essential in neuroscience, medical imaging and genetic studies. The pICA algorithm allows the simultaneous decomposition of up to two data modalities achieving better performance than separate ICA decompositions and enabling the discovery of links between modalities. However, advances in data acquisition techniques facilitate the collection of more than two data modalities from each subject. Examples of commonly measured modalities include genetic information, structural magnetic resonance imaging (MRI) and functional MRI. In order to take full advantage of the available data, this work extends the pICA approach to incorporate three modalities in one comprehensive analysis. Simulations demonstrate the three-way pICA performance in identifying pairwise links between modalities and estimating independent components which more closely resemble the true sources than components found by pICA or separate ICA analyses. In addition, the three-way pICA algorithm is applied to real experimental data obtained from a study that investigate genetic effects on alcohol dependence. Considered data modalities include functional MRI (contrast images during alcohol exposure paradigm), gray matter concentration images from structural MRI and genetic single nucleotide polymorphism (SNP). The three-way pICA approach identified links between a SNP component (pointing to brain function and mental disorder associated genes, including BDNF, GRIN2B and NRG1), a functional component related to increased activation in the precuneus area, and a gray matter component comprising part of the default mode network and the caudate. Although such findings need further verification, the simulation and in-vivo results validate the three-way pICA algorithm presented here as a useful tool in biomedical data fusion applications. Copyright © 2014 Elsevier Inc. All rights reserved.

An ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na+-Activated K+ Channels in Aplysia Neurons.

PubMed

Zhang, Yalan; Ni, Weiming; Horwich, Arthur L; Kaczmarek, Leonard K

2017-02-22

Mutations that alter levels of Slack (KCNT1) Na + -activated K + current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica , a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp. In contrast, outward potassium currents were significantly reduced by microinjection of mutant G85R SOD1YFP that had been preincubated at 37°C or of cross-linked dimers of G85R SOD1YFP. Reduction of potassium current was also seen with multimeric G85R SOD1YFP of ∼300 kDa or >300 kDa that had been cross-linked. In current clamp recordings, microinjection of cross-linked 300 kDa increased excitability by depolarizing the resting membrane potential, and decreasing the latency of action potentials triggered by depolarization. The effect of cross-linked 300 kDa on potassium current was reduced by removing Na + from the bath solution, or by knocking down levels of Slack using siRNA. It was also prevented by pharmacological inhibition of ASK1 (apoptosis signal-regulating kinase 1) or of c-Jun N-terminal kinase, but not by an inhibitor of p38 mitogen-activated protein kinase. These results suggest that soluble mutant SOD1 oligomers rapidly trigger a kinase pathway that regulates the activity of Na + -activated K + channels in neurons. SIGNIFICANCE STATEMENT Slack Na + -activated K + channels (KCNT1, K Na 1.1) regulate neuronal excitability but are also linked to cytoplasmic signaling pathways that control neuronal protein translation. Mutations that alter the amplitude of these currents have devastating effects on neuronal development and function. We find that injection of oligomers of mutant superoxide dismutase 1 (SOD1) into the cytoplasm of invertebrate neurons rapidly suppresses these Na + -activated K + currents and that this effect is mediated by a MAP kinase cascade, including ASK1 and c-Jun N-terminal kinase. Because amyotrophic lateral sclerosis is a fatal adult-onset neurodegenerative disease produced by mutations in SOD1 that cause the enzyme to form toxic oligomers, our findings suggest that suppression of Slack channels may be an early step in the progression of the disease. Copyright © 2017 the authors 0270-6474/17/372258-08$15.00/0.

Connecting Family Learning and Active Citizenship

ERIC Educational Resources Information Center

Flanagan, Mary

2009-01-01

In Ireland family learning and active citizenship has not been linked together until 2006. It was while the Clare Family Learning Project was involved in a family learning EU learning network project, that a suggestion to create a new partnership project linking both areas was made and FACE IT! was born (Families and Active Citizenship…

The multicenter benchmarking study of burn injury: A content analysis of the outcome measures using the international classification of functioning, disability and health.

PubMed

Osborne, Candice L; Petersson, Christina; Graham, James E; Meyer, Walter J; Simeonsson, Rune J; Suman, Oscar E; Ottenbacher, Kenneth J

2016-11-01

To link, classify and describe the content of the Multicenter Benchmarking Study Burn Outcomes Questionnaires (BOQ) using the International Classification of Functioning, Disability and Health (ICF) to determine if the information garnered provides researchers with the data necessary to develop a comprehensive understanding of life after burns. Two ICF linking experts used a standardized linking technique endorsed by the World Health Organization to link all BOQ concepts to the ICF. Linking results were analyzed to determine the comprehensiveness of each of the five measures. The activities and participation component was most frequently addressed followed by the body functions component. Environmental factors are not extensively covered and body structures are not addressed. ICF chapter and category distribution were skewed and varied between assessments. The majority of BOQ items are of the health status perspective. BOQ item composition could be improved with a more even distribution of pertinent ICF topics. Assessment authors may consider addressing the impact of environmental factors on participation. Including body structure concepts would allow investigators to track structural deformation and/or developmental delay. Generally speaking, this data should not be used to examine quality of life outcomes. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Track with overlapping links for dry coal extrusion pumps

DOEpatents

Saunders, Timothy; Brady, John D

2014-01-21

A chain for a particulate material extrusion pump includes a plurality of links, each of the plurality of links having a link body and a link ledge, wherein each link ledge of the plurality of links at least partially overlaps the link body of an adjacent one of the plurality of links.

Inability of keratinocytes lacking their specific transglutaminase to form cross-linked envelopes: absence of envelopes as a simple diagnostic test for lamellar ichthyosis.

PubMed

Jeon, S; Djian, P; Green, H

1998-01-20

Epidermal keratinocytes, late in their terminal differentiation, form cross-linked envelopes resistant to ionic detergent and reducing agent. Because the cross-linking process is catalyzed by the keratinocyte transglutaminase, the absence of active transglutaminase should result in failure of the keratinocyte to form a cross-linked envelope. Three keratinocyte strains bearing mutations in the keratinocyte transglutaminase were examined: two contained no detectable transglutaminase mRNA and none contained active enzyme. All three were unable to form cross-linked envelopes, either spontaneously in stratified cultures or upon induction with Ca2+. Although stratum corneum of normal humans and scales from patients with different ichthyotic diseases contain cross-linked envelopes, those from patients with transglutaminase-negative lamellar ichthyosis do not. Therefore, the disease due to the absence of transglutaminase may be readily distinguished from other ichthyotic disease by a simple test for cross-linked envelopes.

Protein-linked Ubiquitin Chain Structure Restricts Activity of Deubiquitinating Enzymes*

PubMed Central

Schaefer, Jonathan B.; Morgan, David O.

2011-01-01

The attachment of lysine 48 (Lys48)-linked polyubiquitin chains to proteins is a universal signal for degradation by the proteasome. Here, we report that long Lys48-linked chains are resistant to many deubiquitinating enzymes (DUBs). Representative enzymes from this group, Ubp15 from yeast and its human ortholog USP7, rapidly remove mono- and diubiquitin from substrates but are slow to remove longer Lys48-linked chains. This resistance is lost if the structure of Lys48-linked chains is disrupted by mutation of ubiquitin or if chains are linked through Lys63. In contrast to Ubp15 and USP7, Ubp12 readily cleaves the ends of long chains, regardless of chain structure. We propose that the resistance to many DUBs of long, substrate-attached Lys48-linked chains helps ensure that proteins are maintained free from ubiquitin until a threshold of ubiquitin ligase activity enables degradation. PMID:22072716

Activation of Duck RIG-I by TRIM25 Is Independent of Anchored Ubiquitin

PubMed Central

Miranzo-Navarro, Domingo; Magor, Katharine E.

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25 activation of duck RIG-I. PMID:24466302

Exercising the hepatobiliary-gut axis. The impact of physical activity performance.

PubMed

Molina-Molina, Emilio; Lunardi Baccetto, Raquel; Wang, David Q-H; de Bari, Ornella; Krawczyk, Marcin; Portincasa, Piero

2018-05-24

Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation and intestinal microbiota. Several metabolic abnormalities, including nonalcoholic fatty liver as well as cholesterol cholelithiasis, represent two conditions explained by changes of the aforementioned pathways. This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, that is nonalcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory status. A full definition of physical activity includes the knowledge of aerobic and endurance exercise, metabolic equivalent tasks, duration, frequency and intensity, beneficial and harmful effects. Physical activity influences the hepatobiliary-gut axis at different levels and brings benefits to fat distribution, liver fat and gallbladder disease while interacting with bile acids as signalling molecules, intestinal microbiota and inflammatory changes in the body. Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit.

PubMed Central

Lusky, M; Berg, L; Weiher, H; Botchan, M

1983-01-01

Bovine papilloma virus (BPV) contains a cis-acting DNA element which can enhance transcription of distal promoters. Utilizing both direct and indirect transient transfection assays, we showed that a 59-base-pair DNA sequence from the BPV genome could activate the simian virus 40 promoter from distances exceeding 2.5 kilobases and in an orientation-independent manner. In contrast to the promoter 5'-proximal localization of other known viral activators, this element was located immediately 3' to the early polyadenylation signal in the BPV genome. Deletion of these sequences from the BPV genome inactivated the transforming ability of BPV recombinant plasmids. Orientation-independent reinsertion of this 59-base-pair sequence, or alternatively of activator DNA sequences from simian virus 40 or polyoma virus, restored the transforming activity of the BPV recombinant plasmids. Furthermore, the stable transformation frequency of the herpes simplex virus type 1 thymidine kinase gene was enhanced when linked to restriction fragments of BPV DNA which included the defined activator element. This enhancement was orientation independent with respect to the thymidine kinase promoter. The enhancement also appeared to be unrelated to the establishment of the recombinant plasmids as episomes, since in transformed cells these sequences are found linked to high-molecular-weight DNA. We propose that the enhancement of stable transformation frequencies and the activation of transcription units are in this case alternate manifestations of the same biochemical events. Images PMID:6308425

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

PubMed

Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Innate immunity, insulin resistance and type 2 diabetes.

PubMed

Fernández-Real, José Manuel; Pickup, John C

2008-01-01

Recent evidence has disclosed previously unrecognized links among insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to altered production or function of circulating innate immune proteins, cellular pattern-recognition receptors and inflammatory cytokines have been linked with insulin resistance, type 2 diabetes, obesity and atherosclerosis. Cellular innate immune associations with obesity and insulin resistance include increased white blood cell count and adipose tissue macrophage numbers. The innate immune response is modulated possibly by both predisposition (genetic or fetal programming), perhaps owing to evolutionary pressures caused by acute infections at the population level (pandemics), and chronic low exposure to environmental products or infectious agents. The common characteristics shared among innate immunity activation, obesity and insulin resistance are summarized.

On Cuteness: Unlocking the Parental Brain and Beyond.

PubMed

Kringelbach, Morten L; Stark, Eloise A; Alexander, Catherine; Bornstein, Marc H; Stein, Alan

2016-07-01

Cuteness in offspring is a potent protective mechanism that ensures survival for otherwise completely dependent infants. Previous research has linked cuteness to early ethological ideas of a 'Kindchenschema' (infant schema) where infant facial features serve as 'innate releasing mechanisms' for instinctual caregiving behaviours. We propose extending the concept of cuteness beyond visual features to include positive infant sounds and smells. Evidence from behavioural and neuroimaging studies links this extended concept of cuteness to simple 'instinctual' behaviours and to caregiving, protection, and complex emotions. We review how cuteness supports key parental capacities by igniting fast privileged neural activity followed by slower processing in large brain networks also involved in play, empathy, and perhaps even higher-order moral emotions. Copyright © 2016 Elsevier Ltd. All rights reserved.

On cuteness: unlocking the parental brain and beyond

PubMed Central

Kringelbach, M.L.; Stark, E.A.; Alexander, C.; Bornstein, M.H.; Stein, A.

2016-01-01

Cuteness in offspring is a potent protective mechanism that ensures survival for otherwise completely dependent infants. Previous research has linked cuteness to early ethological ideas of a “kindchenschema” (infant schema) where infant facial features serve as “innate releasing mechanisms” for instinctual caregiving behaviours. We propose extending the concept of cuteness beyond visual features to include positive infant sounds and smells. Evidence from behavioural and neuroimaging studies links this extended concept of cuteness to simple “instinctual” behaviours and to caregiving, protection and complex emotions. We review how cuteness supports key parental capacities by igniting fast privileged neural activity followed by slower processing in large brain networks also involved in play, empathy, and perhaps even higher-order moral emotions. PMID:27211583

A structural and kinetic study on myofibrils prevented from shortening by chemical cross-linking.

PubMed

Herrmann, C; Sleep, J; Chaussepied, P; Travers, F; Barman, T

1993-07-20

In previous work, we studied the early steps of the Mg(2+)-ATPase activity of Ca(2+)-activated myofibrils [Houadjeto, M., Travers, F., & Barman, T. (1992) Biochemistry 31, 1564-1569]. The myofibrils were free to contract, and the results obtained refer to the ATPase cycle of myofibrils contracting with no external load. Here we studied the ATPase of myofibrils contracting isometrically. To prevent shortening, we cross-linked them with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC). SDS-PAGE and Western blot analyses showed that the myosin rods were extensively cross-linked and that 8% of the myosin heads were cross-linked to the thin filament. The transient kinetics of the cross-linked myofibrils were studied in 0.1 M potassium acetate, pH 7.4 and 4 degrees C, by the rapid-flow quench method. The ATP binding steps were studied by the cold ATP chase and the cleavage and release of products steps by the Pi burst method. In Pi burst experiments, the sizes of the bursts were equal within experimental error to the ATPase site concentrations (as determined by the cold ATP chase methods) for both cross-linked (isometric) and un-cross-linked (isotonic) myofibrils. This shows that in both cases the rate-limiting step is after the cleavage of ATP. When cross-linked, the kcat of Ca(2+)-activated myofibrils was reduced from 1.7 to 0.8 s-1. This is consistent with the observation that fibers shortening at moderate velocity have a higher ATPase activity than isometric fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Which characteristics of planning matter? Individual and dyadic physical activity plans and their effects on plan enactment.

PubMed

Keller, Jan; Fleig, Lena; Hohl, Diana Hilda; Wiedemann, Amelie U; Burkert, Silke; Luszczynska, Aleksandra; Knoll, Nina

2017-09-01

Past research supports individual planning as an effective intervention strategy to increase physical activity in individuals. A similar strategy, dyadic planning, adds a planning partner who supports an individual's planning processes. Whether the two planning formats differ in terms of participants' entered plan content and whether and how different content characteristics are linked to plan enactment remains unknown. By investigating the content of generated plans, this study aimed at distinguishing plan characteristics of the two planning formats and examining their role as predictors of later plan enactment. Secondary analyses of a three-arm RCT with German couples (data collection between 2013 and 2015). Couples were assigned to an individual (IPC, n = 114) or dyadic planning condition (DPC, n = 111) and formulated up to 5 physical activity plans for a target person. Couples assigned to a control condition were not included as they did not generate plans. The following characteristics were distinguished and coded for each plan: number of planned opportunities, presence of a planned routine, planned cue- or activity-related specificity, activity-related intensity, and chronological plan rank. One week before (T0) and two weeks following (T2) the intervention (T1), increase vs. no increase of the planned activity was coded as a dichotomous plan enactment variable. Multilevel logistic regressions were fit. Plan enactment was higher in dyadic than in individual planners. Findings indicated that routines (e.g., after work) were positively related to plan enactment, whereas a high specificity of when-cues (e.g., Friday at 6.30 p.m.) showed a negative relationship. None of the examined plan characteristics could explain differences in enactment between IPC and DPC. Linking health behaviours to other behavioural routines seems beneficial for subsequent plan enactment. Dyadic planning was linked with higher enactment rates than individual planning. However, as mechanisms underlying this effect remain unclear, they should be investigated further. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of chebulic acid on advanced glycation endproducts-induced collagen cross-links.

PubMed

Lee, Ji-Young; Oh, Jun-Gu; Kim, Jin Sook; Lee, Kwang-Won

2014-01-01

Advanced glycation end-products (AGEs) have been implicated in the development of diabetic complications. We report the antiglycating activity of chebulic acid (CA), isolated from Terminalia chebula on breaking the cross-links of proteins induced by AGEs and inhibiting the formation of AGEs. Aminoguanidine (AG) reduced 50% of glycated bovine serum albumin (BSA) with glycolaldehyde (glycol-BSA)-induced cross-links of collagen at a concentration of 67.8 ± 2.5 mM, the level of CA required for exerting a similar antiglycating activity was 38.8 ± 0.5 µM. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC50=1.46 ± 0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC50=72.2 ± 2.4 mM). IC50 values of DPPH· scavenging activity for CA and ascorbic acid (AA) were 39.2 ± 4.9 and 19.0 ± 1.2 µg dry matter (DM) mL(-1), respectively, and ferric reducing and antioxidant power (FRAP) activities for CA and AA were 4.70 ± 0.06 and 11.4 ± 0.1 mmol/FeSO4·7H2O/g DM, respectively. The chelating activities of CA, AG and ALT711 on copper-catalyzed oxidation of AA were compared, and in increasing order, ALT-711 (IC50 of 1.92 ± 0.20 mM)

The brain’s conversation with itself: neural substrates of dialogic inner speech

PubMed Central

Weis, Susanne; McCarthy-Jones, Simon; Moseley, Peter; Smailes, David; Fernyhough, Charles

2016-01-01

Inner speech has been implicated in important aspects of normal and atypical cognition, including the development of auditory hallucinations. Studies to date have focused on covert speech elicited by simple word or sentence repetition, while ignoring richer and arguably more psychologically significant varieties of inner speech. This study compared neural activation for inner speech involving conversations (‘dialogic inner speech’) with single-speaker scenarios (‘monologic inner speech’). Inner speech-related activation differences were then compared with activations relating to Theory-of-Mind (ToM) reasoning and visual perspective-taking in a conjunction design. Generation of dialogic (compared with monologic) scenarios was associated with a widespread bilateral network including left and right superior temporal gyri, precuneus, posterior cingulate and left inferior and medial frontal gyri. Activation associated with dialogic scenarios and ToM reasoning overlapped in areas of right posterior temporal cortex previously linked to mental state representation. Implications for understanding verbal cognition in typical and atypical populations are discussed. PMID:26197805

The Rheumatoid Arthritis-Associated Citrullinome.

PubMed

Tilvawala, Ronak; Nguyen, Son Hong; Maurais, Aaron J; Nemmara, Venkatesh V; Nagar, Mitesh; Salinger, Ari J; Nagpal, Sunil; Weerapana, Eranthie; Thompson, Paul R

2018-03-21

Increased protein citrullination is linked to various diseases including rheumatoid arthritis (RA), lupus, and cancer. Citrullinated autoantigens, a hallmark of RA, are recognized by anti-citrullinated protein antibodies (ACPAs) which are used to diagnose RA. ACPA-recognizing citrullinated enolase, vimentin, keratin, and filaggrin are also pathogenic. Here, we used a chemoproteomic approach to define the RA-associated citrullinome. The identified proteins include numerous serine protease inhibitors (Serpins), proteases and metabolic enzymes. We demonstrate that citrullination of antiplasmin, antithrombin, t-PAI, and C1 inhibitor (P1-Arg-containing Serpins) abolishes their ability to inhibit their cognate proteases. Citrullination of nicotinamide N-methyl transferase (NNMT) also abolished its methyltransferase activity. Overall, these data advance our understanding of the roles of citrullination in RA and suggest that extracellular protein arginine deiminase (PAD) activity can modulate protease activity with consequent effects on Serpin-regulated pathways. Moreover, our data suggest that inhibition of extracellular PAD activity will be therapeutically relevant. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis, Characterization, and Antibacterial Activity of Cross-Linked Chitosan-Glutaraldehyde

PubMed Central

Li, Bin; Shan, Chang-Lin; Zhou, Qing; Fang, Yuan; Wang, Yang-Li; Xu, Fei; Han, Li-Rong; Ibrahim, Muhammad; Guo, Long-Biao; Xie, Guan-Lin; Sun, Guo-Chang

2013-01-01

This present study deals with synthesis, characterization and antibacterial activity of cross-linked chitosan-glutaraldehyde. Results from this study indicated that cross-linked chitosan-glutaraldehyde markedly inhibited the growth of antibiotic-resistant Burkholderia cepacia complex regardless of bacterial species and incubation time while bacterial growth was unaffected by solid chitosan. Furthermore, high temperature treated cross-linked chitosan-glutaraldehyde showed strong antibacterial activity against the selected strain 0901 although the inhibitory effects varied with different temperatures. In addition, physical-chemical and structural characterization revealed that the cross-linking of chitosan with glutaraldehyde resulted in a rougher surface morphology, a characteristic Fourier transform infrared (FTIR) band at 1559 cm−1, a specific X-ray diffraction peak centered at 2θ = 15°, a lower contents of carbon, hydrogen and nitrogen, and a higher stability of glucose units compared to chitosan based on scanning electron microscopic observation, FTIR spectra, X-ray diffraction pattern, as well as elemental and thermo gravimetric analysis. Overall, this study indicated that cross-linked chitosan-glutaraldehyde is promising to be developed as a new antibacterial drug. PMID:23670533

Link Prediction in Evolving Networks Based on Popularity of Nodes.

PubMed

Wang, Tong; He, Xing-Sheng; Zhou, Ming-Yang; Fu, Zhong-Qian

2017-08-02

Link prediction aims to uncover the underlying relationship behind networks, which could be utilized to predict missing edges or identify the spurious edges. The key issue of link prediction is to estimate the likelihood of potential links in networks. Most classical static-structure based methods ignore the temporal aspects of networks, limited by the time-varying features, such approaches perform poorly in evolving networks. In this paper, we propose a hypothesis that the ability of each node to attract links depends not only on its structural importance, but also on its current popularity (activeness), since active nodes have much more probability to attract future links. Then a novel approach named popularity based structural perturbation method (PBSPM) and its fast algorithm are proposed to characterize the likelihood of an edge from both existing connectivity structure and current popularity of its two endpoints. Experiments on six evolving networks show that the proposed methods outperform state-of-the-art methods in accuracy and robustness. Besides, visual results and statistical analysis reveal that the proposed methods are inclined to predict future edges between active nodes, rather than edges between inactive nodes.

Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta.

PubMed

Dobrowolny, Gabriella; Martini, Martina; Scicchitano, Bianca Maria; Romanello, Vanina; Boncompagni, Simona; Nicoletti, Carmine; Pietrangelo, Laura; De Panfilis, Simone; Catizone, Angela; Bouchè, Marina; Sandri, Marco; Rudolf, Rüdiger; Protasi, Feliciano; Musarò, Antonio

2018-04-20

Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1 G93A in transgenic MLC/SOD1 G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1 G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration. The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1 G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity. Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 28, 1105-1119.

Radical-scavenging-linked antioxidant activities of extracts from black chokeberry and blueberry cultivated in Korea.

PubMed

Hwang, Seok Joon; Yoon, Won Byong; Lee, Ok-Hwan; Cha, Seung Ju; Kim, Jong Dai

2014-03-01

The objective of this study was to investigate the radical-scavenging-linked antioxidant properties of the extracts from black chokeberry and blueberry cultivated in Korea. The 70% ethanol extracts were prepared from black chokeberry and blueberry, and evaluated for total phenolic content, total flavonoid content, total proanthocyanidin content, and antioxidative activities, using various in vitro assays, such as DPPH(2,2-diphenyl-1-picrylhydrazyl), ABTS(2,2-azino-bis-(3-ethylenebenzothiozoline-6-sulphonic acid)) radical-scavenging activity, FRAP(ferric-reducing antioxidant power) and reducing power. The major phenolic compounds, including cyanidin-3-galactoside, cyanidin-3-arabinoside, neochlorogenic acid, procyanidin B1, were analysed by HPLC with a photodiode array detector. Results showed that total phenol, flavonoid and proanthocyanidin contents of black chokeberry extract were higher than those of blueberry extract. In addition, black chokeberry extract exhibited higher free radical-scavenging activity and reducing power than did blueberry extract. Cyanidin-3-galactoside was identified as a major phenolic compound, with considerable content in black chokeberry, that correlated with its higher antioxidant and radical-scavenging effects. These results suggest that black chokeberry extracts could be considered as a good source of natural antioxidants and functional food ingredients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibition of homologous phosphorolytic ribonucleases by citrate may represent an evolutionarily conserved communicative link between RNA degradation and central metabolism

PubMed Central

Stone, Carlanne M.; Butt, Louise E.; Bufton, Joshua C.; Lourenco, Daniel C.; Gowers, Darren M.; Pickford, Andrew R.; Cox, Paul A.

2017-01-01

Abstract Ribonucleases play essential roles in all aspects of RNA metabolism, including the coordination of post-transcriptional gene regulation that allows organisms to respond to internal changes and environmental stimuli. However, as inherently destructive enzymes, their activity must be carefully controlled. Recent research exemplifies the repertoire of regulatory strategies employed by ribonucleases. The activity of the phosphorolytic exoribonuclease, polynucleotide phosphorylase (PNPase), has previously been shown to be modulated by the Krebs cycle metabolite citrate in Escherichia coli. Here, we provide evidence for the existence of citrate-mediated inhibition of ribonucleases in all three domains of life. In silico molecular docking studies predict that citrate will bind not only to bacterial PNPases from E. coli and Streptomyces antibioticus, but also PNPase from human mitochondria and the structurally and functionally related archaeal exosome complex from Sulfolobus solfataricus. Critically, we show experimentally that citrate also inhibits the exoribonuclease activity of bacterial, eukaryotic and archaeal PNPase homologues in vitro. Furthermore, bioinformatics data, showing key citrate-binding motifs conserved across a broad range of PNPase homologues, suggests that this regulatory mechanism may be widespread. Overall, our data highlight a communicative link between ribonuclease activity and central metabolism that may have been conserved through the course of evolution. PMID:28334892

Genetic causal beliefs about obesity, self-efficacy for weight control, and obesity-related behaviours in a middle-aged female cohort.

PubMed

Knerr, Sarah; Bowen, Deborah J; Beresford, Shirley A A; Wang, Catharine

2016-01-01

Obesity is a heritable condition with well-established risk-reducing behaviours. Studies have shown that beliefs about the causes of obesity are associated with diet and exercise behaviour. Identifying mechanisms linking causal beliefs and behaviours is important for obesity prevention and control. Cross-sectional multi-level regression analyses of self-efficacy for weight control as a possible mediator of obesity attributions (diet, physical activity, genetic) and preventive behaviours in 487 non-Hispanic White women from South King County, Washington. Self-reported daily fruit and vegetable intake and weekly leisure-time physical activity. Diet causal beliefs were positively associated with fruit and vegetable intake, with self-efficacy for weight control partially accounting for this association. Self-efficacy for weight control also indirectly linked physical activity attributions and physical activity behaviour. Relationships between genetic causal beliefs, self-efficacy for weight control, and obesity-related behaviours differed by obesity status. Self-efficacy for weight control contributed to negative associations between genetic causal attributions and obesity-related behaviours in non-obese, but not obese, women. Self-efficacy is an important construct to include in studies of genetic causal beliefs and behavioural self-regulation. Theoretical and longitudinal work is needed to clarify the causal nature of these relationships and other mediating and moderating factors.

Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8.

PubMed

Toosi, Siavash; Orlow, Seth J; Manga, Prashiela

2012-11-01

Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.

Search for a clinical cookbook: understanding the recipe for heat applications in surgical procedures

NASA Astrophysics Data System (ADS)

Verdaasdonck, Rudolf M.; van Swol, Christiaan F. P.

1997-06-01

In this proceeding a summary is given of the slides presented at the meeting. For a detailed description of the research and clinical applications, references are included. An update of current research and clinical activities can be found on the web page of the medical laser center: www.cv.ruu.nl/LaserCenter. Links to other laser sites. At this site reprints can be requested.

To Grow or Not to Grow? A Post-Great Recession Synopsis of the Political, Financial, and Social Contract Challenges Facing the University of California. Research & Occasional Paper Series: CSHE.15.13

ERIC Educational Resources Information Center

Douglass, John Aubrey

2013-01-01

After more than two decades of state disinvestment, the University of California faces significant challenges and misunderstandings regarding its operating costs, its wide array of activities, and its mission. Reduced funding from the state for public higher education, including UC, has essentially severed the historic link between state…

Project CHOICE: #170. A Career Education Unit for Grades 1 and 2. We Work with Animals. (Agriculture and Ecological Studies Career Cluster).

ERIC Educational Resources Information Center

Kern County Superintendent of Schools, Bakersfield, CA.

This teaching unit on working with animals is part of the Agriculture and Biological Studies Career Cluster included in a series of career guidebooks developed by Project CHOICE (Children Have Options in Career Education). The units are designed to provide the classroom teacher with a source of career-related activities linking first and second…

Development of Compositionally Graded Metallic Glass Alloys with Desirable Properties

DTIC Science & Technology

2016-06-01

individual study . Include participation in conferences, workshops, and seminars not listed under major activities. At OSU, one graduate student ...best glass former in a fraction of the experimental time of previous study , which identified similar compositions of Cu57.6Zr32.4Ti10,13 and...years, several experimental and computational studies have suggested a direct link between the population of shear transformation zones (STZs

The Sun as a star

NASA Technical Reports Server (NTRS)

Jordan, S. D. (Editor)

1981-01-01

Solar physics was reviewed in the context of the solar atmoshere. The understanding of the solar atmosphere is linked to stellar atmospheric research. Topics covered include: the existence of the chromosphere, the corona, and the solar wind; the interactive complex of convection, differential rotation, magnetic field generation and concentration, and the activity cycle; phenomena such as granulation, supergranulation, the 5 minute oscillation, filigree, faculae, sunspots, spicules, prominences, surges, and the spectacular flares.

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

PubMed

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action.

Improving Science Communication and Engaging the Public in Astronomy and Nature

NASA Astrophysics Data System (ADS)

Arion, Douglas N.

2016-01-01

A partnershipship between Carthage College and the Appalachian Mountain Club has delivered a successful public education and outreach program that merges natural environment topics and astronomy. Over the four years of activity, over 25,000 people have received programming. The effort has trained nature educators, permanent and seasonal AMC staff, and undergraduate physics and astronomy students to integrate diverse topical material and deliver high quality programming to the lay public. Unique to the program is the holistic nature of the material delivered - an 'atypical' astronomy program. Linking observable characteristics of the natural world with astronomical history and phenomena, and emphasizing the unique sequence of events that have led to human life on Earth, the program has changed attitudes and behaviors among the public participants. Successful interventions have included hands-on observing programs (day and night) that link nature content to the observed objects; table-talk presentations on nature/astronomy topics; dark skies preservation workshops; and hands-on activities developed for younger audiences, including schools, camps, and family groups. An extensive evaluation and assessment effort managed by a leading sociologist has demonstrated the effectiveness of the approach, and contributed to continuous improvement in the program content and methods. This work was supported in part by NSF Grant 1432662.

An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders.

PubMed

Masten, Carrie L; Colich, Natalie L; Rudie, Jeffrey D; Bookheimer, Susan Y; Eisenberger, Naomi I; Dapretto, Mirella

2011-07-01

Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.

Eicosanoids in Metabolic Syndrome

PubMed Central

Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

2013-01-01

Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders

PubMed Central

Masten, Carrie L.; Colich, Natalie L.; Rudie, Jeffrey D.; Bookheimer, Susan Y.; Eisenberger, Naomi I.; Dapretto, Mirella

2011-01-01

Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives. PMID:22318914

Evaluation and Utilization as a Public Health Tool of a National Molecular Epidemiological Tuberculosis Outbreak Database within the United Kingdom from 1997 to 2001

PubMed Central

Drobniewski, F. A.; Gibson, A.; Ruddy, M.; Yates, M. D.

2003-01-01

The aim of this study was to develop a national model and analyze the value of a molecular epidemiological Mycobacterium tuberculosis DNA fingerprint-outbreak database. Incidents were investigated by the United Kingdom PHLS Mycobacterium Reference Unit (MRU) from June 1997 to December 2001, inclusive. A total of 124 incidents involving 972 tuberculosis cases, including 520 patient cultures from referred incidents and 452 patient cultures related to two population studies, were examined by using restriction fragment length polymorphism IS6110 fingerprinting and rapid epidemiological typing. Investigations were divided into the following three categories, reflecting different operational strategies: retrospective passive analysis, retrospective active analysis, and retrospective prospective analysis. The majority of incidents were in the retrospective passive analysis category, i.e., the individual submitting isolates has a suspicion they may be linked. Outbreaks were examined in schools, hospitals, farms, prisons, and public houses, and laboratory cross-contamination events and unusual clinical presentations were investigated. Retrospective active analysis involved a major outbreak centered on a high school. Contact tracing of a teenager with smear-positive pulmonary tuberculosis matched 14 individuals, including members of his class, and another 60 cases were identified in schools clinically and radiologically and by skin testing. Retrospective prospective analysis involved an outbreak of 94 isoniazid-resistant tuberculosis cases in London, United Kingdom, that began after cases were identified at one hospital in January 2000. Contact tracing and comparison with MRU databases indicated that the earliest matched case had occurred in 1995. Subsequently, the MRU changed to an active prospective analysis targeting linked isoniazid-monoresistant isolates for follow up. The patients were multiethnic, born mainly in the United Kingdom, and included professionals, individuals from the music industry, intravenous drug abusers, and prisoners. PMID:12734218

Evaluation and utilization as a public health tool of a national molecular epidemiological tuberculosis outbreak database within the United Kingdom from 1997 to 2001.

PubMed

Drobniewski, F A; Gibson, A; Ruddy, M; Yates, M D

2003-05-01

The aim of this study was to develop a national model and analyze the value of a molecular epidemiological Mycobacterium tuberculosis DNA fingerprint-outbreak database. Incidents were investigated by the United Kingdom PHLS Mycobacterium Reference Unit (MRU) from June 1997 to December 2001, inclusive. A total of 124 incidents involving 972 tuberculosis cases, including 520 patient cultures from referred incidents and 452 patient cultures related to two population studies, were examined by using restriction fragment length polymorphism IS6110 fingerprinting and rapid epidemiological typing. Investigations were divided into the following three categories, reflecting different operational strategies: retrospective passive analysis, retrospective active analysis, and retrospective prospective analysis. The majority of incidents were in the retrospective passive analysis category, i.e., the individual submitting isolates has a suspicion they may be linked. Outbreaks were examined in schools, hospitals, farms, prisons, and public houses, and laboratory cross-contamination events and unusual clinical presentations were investigated. Retrospective active analysis involved a major outbreak centered on a high school. Contact tracing of a teenager with smear-positive pulmonary tuberculosis matched 14 individuals, including members of his class, and another 60 cases were identified in schools clinically and radiologically and by skin testing. Retrospective prospective analysis involved an outbreak of 94 isoniazid-resistant tuberculosis cases in London, United Kingdom, that began after cases were identified at one hospital in January 2000. Contact tracing and comparison with MRU databases indicated that the earliest matched case had occurred in 1995. Subsequently, the MRU changed to an active prospective analysis targeting linked isoniazid-monoresistant isolates for follow up. The patients were multiethnic, born mainly in the United Kingdom, and included professionals, individuals from the music industry, intravenous drug abusers, and prisoners.

Student and Community Engagement in Earth, Space, and Environmental Sciences Through Experiential Learning and Citizen Science as Part of Research Broader Impact

NASA Astrophysics Data System (ADS)

Ibrahim, Alaa; Ahmed, Yasmin

2015-04-01

Fulfilling the broader impact of a research project in Earth and environmental sciences is an excellent opportunity for educational and outreach activities that connect scientists and society and enhance students and community engagement in STEM fields in general and in Earth, space, and environmental sciences in particular. Here we present the experience developed in this endeavor as part of our Partnerships for Enhanced Engagement in Research (PEER) project sponsored by USAID/NSF/NAS. The project introduced educational and outreach activities that included core curriculum course development for university students from all majors, community-based learning projects, citizen science and outreach programs to school students and community members. Through these activities, students worked with the project scientists on a variety of activities that ranged from citizen science and undergraduate research to run mass experiments that measure the quality of air, drinking water, and ultraviolet level in greater Cairo, Egypt, to community awareness campaigns through the production of short documentaries and communicating them with stakeholders and target groups, including schools and TV stations. The activities enhanced students learning and the public awareness on climate change and the underlying role of human activities. It also connected effectively the project scientists with college and university students a well as the wider segments of the society, which resulted in a host of benefits including better scientific literacy and appreciation to the role of scientists, promoting scientists as role models, sharing the values of science, and motivating future generations to puruse a career in science This work is part of the PEER research project 2-239 sponsored by USAID/NSF/NAS Project Link (at National Academies website): http://sites.nationalacademies.org/PGA/dsc/peerscience/PGA_084046.htm website: http://CleanAirEgypt.org Links to cited work: Core Curriculum Course: http://bit.ly/FutureLife Citizen Science Project: Quality of Air, Drinking Water, and U.V. Level in Greater Cairo: Map 1: http://bit.ly/AirWaterLightMap1 Map 2: http://bit.ly/AirWaterLightMap2 Short Documentaries Student Projects: https://vimeo.com/science2society/videos Project video: https://vimeo.com/100427525

Student and Community Engagement in Earth, Space, and Environmental Sciences Through Experiential Learning and Citizen Science as Part of Research Broader Impact

NASA Astrophysics Data System (ADS)

Ibrahim, A. I.; Tutwiler, R.; Zakey, A.; Shokr, M. E.; Ahmed, Y.; Jereidini, D.; Eid, M.

2014-12-01

Fulfilling the broader impact of a research project in Earth and environmental sciences is an excellent opportunity for educational and outreach activities that connect scientists and society and enhance students and community engagement in STEM fields in general and in Earth, space, and environmental sciences in particular. Here we present the experience developed in this endeavor as part of our Partnerships for Enhanced Engagement in Research (PEER) project sponsored by USAID/NSF/NAS. The project introduced educational and outreach activities that included core curriculum course development for university students from all majors, community-based learning projects, citizen science and outreach programs to school students and community members. Through these activities, students worked with the project scientists on a variety of activities that ranged from citizen science and undergraduate research to run mass experiments that measure the quality of air, drinking water, and ultraviolet level in greater Cairo, Egypt, to community awareness campaigns through the production of short documentaries and communicating them with stakeholders and target groups, including schools and TV stations. The activities enhanced students learning and the public awareness on climate change and the underlying role of human activities. It also connected effectively the project scientists with college and university students a well as the wider segments of the society, which resulted in a host of benefits including better scientific literacy and appreciation to the role of scientists, promoting scientists as role models, sharing the values of science, and motivating future generations to puruse a career in science Note: This presentation is a PEER project sponsored by USAID/NSF/NAS Project Link (at National Academies website): http://sites.nationalacademies.org/PGA/dsc/peerscience/PGA_084046.htmwebsite: http://CleanAirEgypt.orgLinks to cited work: Core Curriculum Course: http://bit.ly/FutureLife Citizen Science Project: Quality of Air, Drinking Water, and U.V. Level in Greater Cairo: Map 1: http://bit.ly/AirWaterLightMap1 Map 2: http://bit.ly/AirWaterLightMap2 Short Documentaries Student Projects: https://vimeo.com/science2society/videos Project video: http://CleanAirEgypt.org

Hanny and the Mystery of the Voorwerp: Citizen Science in the Classroom

NASA Astrophysics Data System (ADS)

Costello, K.; Reilly, E.; Bracey, G.; Gay, P.

2012-08-01

The highly engaging graphic comic Hanny and the Mystery of the Voorwerp is the focus of an eight-day educational unit geared to middle level students. Activities in the unit link national astronomy standards to the citizen science Zooniverse website through tutorials that lead to analysis of real data online. NASA resources are also included in the unit. The content of the session focused on the terminology and concepts - galaxy formation, types and characteristics of galaxies, use of spectral analysis - needed to classify galaxies. Use of citizen science projects as tools to teach inquiry in the classroom was the primary focus of the workshop. The session included a hands-on experiment taken from the unit, including a NASA spectral analysis activity called "What's the Frequency, Roy G Biv?" In addition, presenters demonstrated the galaxy classification tools found in the "Galaxy Zoo" project at the Zooniverse citizen science website.

Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.

PubMed

Robinson, Antwon D; Ramanathan, Kodangudi B; McGee, Jesse E; Newman, Kevin P; Weber, Karl T

2011-08-01

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

Anti-inflammatory and immunomodulatory properties of Carica papaya.

PubMed

Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

2016-07-01

Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

Multiple biological pathways link cognitive lifestyle to protection from dementia.

PubMed

Valenzuela, Michael J; Matthews, Fiona E; Brayne, Carol; Ince, Paul; Halliday, Glenda; Kril, Jillian J; Dalton, Marshall A; Richardson, Kathryn; Forster, Gill; Sachdev, Perminder S

2012-05-01

An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population-based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans. Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 individuals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinically matched individuals with high and low CLS. CLS groups did not differ on several Alzheimer disease neuropathologic measures; however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness. An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Protein microspheres for controlled drug delivery and related analysis of biopolymers

NASA Astrophysics Data System (ADS)

Kirk, James Forrest

Rheumatoid arthritis (RA) is a systemic disorder which manifests itself most notably in the synovial joints. In recent years, methotrexate (MTX), a foliate antagonist, has been used with some success for treatment of RA. MTX has a maximum cumulative dose beyond which it becomes dangerous to administer due primarily to liver toxicity. This unfortunate side effect has prompted research into means of delivering MTX to the synovial joint in hopes of making more efficient use of the drug. Both MTX and its sodium salt (Na-MTX) were loaded into microspheres (MS) composed of bovine serum albumin (BSA) stabilized by cross linking with dialdehydes or ferric ion. MS were prepared with two levels of drug loading at two different levels of cross linking. MTX loading densities as high as 46.8% w/w were achieved in the aldehyde cross linking system and as high as 46.3% w/w were achieved with ferric ion cross linking. Using Na-MTX, the values were 37.2% w/w and 31.7% w/w respectively. Both MTX and Na-MTX were elutable from the MS into phosphate buffered saline at 37sp°C. MTX elution from aldehyde cross linked microspheres was load dependent with ca. 60% eluted by 9 hours at low loading and ca. 60% eluted by 24 hours at high loading. In the ferric ion cross link system, the elution was independent of loading with 50% elution occurring between 20 and 48 hours. Na-MTX elution was independent of drug loading or cross link system with 50% elution occurring in less than two hours in all cases. Other investigations included the loading of mitoxantrone (NOV) and of enzyme. NOV was loaded onto BSA microspheres to a concentration of 19.3% w/w and was used successfully in the treatment of murine ovarian tumors. Acid phosphatase was successfully loaded onto and into BSA microspheres. This enzyme retained its initial activity up to four months on post-loaded spheres. The enzyme also remained active inside the microsphere as demonstrated by a substrate cleavage assay.

Alpha Oscillations Are Causally Linked to Inhibitory Abilities in Ageing.

PubMed

Borghini, Giulia; Candini, Michela; Filannino, Cristina; Hussain, Masud; Walsh, Vincent; Romei, Vincenzo; Zokaei, Nahid; Cappelletti, Marinella

2018-05-02

Aging adults typically show reduced ability to ignore task-irrelevant information, an essential skill for optimal performance in many cognitive operations, including those requiring working memory (WM) resources. In a first experiment, young and elderly human participants of both genders performed an established WM paradigm probing inhibitory abilities by means of valid, invalid, and neutral retro-cues. Elderly participants showed an overall cost, especially in performing invalid trials, whereas younger participants' general performance was comparatively higher, as expected.Inhibitory abilities have been linked to alpha brain oscillations but it is yet unknown whether in aging these oscillations (also typically impoverished) and inhibitory abilities are causally linked. To probe this possible causal link in aging, we compared in a second experiment parietal alpha-transcranial alternating current stimulation (tACS) with either no stimulation (Sham) or with two control stimulation frequencies (theta- and gamma-tACS) in the elderly group while performing the same WM paradigm. Alpha- (but not theta- or gamma-) tACS selectively and significantly improved performance (now comparable to younger adults' performance in the first experiment), particularly for invalid cues where initially elderly showed the highest costs. Alpha oscillations are therefore causally linked to inhibitory abilities and frequency-tuned alpha-tACS interventions can selectively change these abilities in the elderly. SIGNIFICANCE STATEMENT Ignoring task-irrelevant information, an ability associated to rhythmic brain activity in the alpha frequency band, is fundamental for optimal performance. Indeed, impoverished inhibitory abilities contribute to age-related decline in cognitive functions like working memory (WM), the capacity to briefly hold information in mind. Whether in aging adults alpha oscillations and inhibitory abilities are causally linked is yet unknown. We experimentally manipulated frequency-tuned brain activity using transcranial alternating current stimulation (tACS), combined with a retro-cue paradigm assessing WM and inhibition. We found that alpha-tACS induced a significant improvement in target responses and misbinding errors, two indexes of inhibition. We concluded that in aging alpha oscillations are causally linked to inhibitory abilities, and that despite being impoverished, these abilities are still malleable. Copyright © 2018 the authors 0270-6474/18/384419-12$15.00/0.

Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

PubMed

Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

2017-08-01

Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

Pharmacological and structure-activity relationship evaluation of 4-aryl-1-diphenylacetyl(thio)semicarbazides.

PubMed

Wujec, Monika; Kędzierska, Ewa; Kuśmierz, Edyta; Plech, Tomasz; Wróbel, Andrzej; Paneth, Agata; Orzelska, Jolanta; Fidecka, Sylwia; Paneth, Piotr

2014-04-16

This article describes the synthesis of six 4-aryl-(thio)semicarbazides (series a and b) linked with diphenylacetyl moiety along with their pharmacological evaluation on the central nervous system in mice and computational studies, including conformational analysis and electrostatic properties. All thiosemicarbazides (series b) were found to exhibit strong antinociceptive activity in the behavioural model. Among them, compound 1-diphenylacetyl-4-(4-methylphenyl)thiosemicarbazide 1b was found to be the most potent analgesic agent, whose activity is connected with the opioid system. For compounds from series a significant anti-serotonergic effect, especially for compound 1-diphenylacetyl-4-(4-methoxyphenyl)semicarbazide 2b was observed. The computational studies strongly support the obtained results.

Nano-swimmers in biological membranes and propulsion hydrodynamics in two dimensions.

PubMed

Huang, Mu-Jie; Chen, Hsuan-Yi; Mikhailov, Alexander S

2012-11-01

Active protein inclusions in biological membranes can represent nano-swimmers and propel themselves in lipid bilayers. A simple model of an active inclusion with three particles (domains) connected by variable elastic links is considered. First, the membrane is modeled as a two-dimensional viscous fluid and propulsion behavior in two dimensions is examined. After that, an example of a microscopic dynamical simulation is presented, where the lipid bilayer structure of the membrane is resolved and the solvent effects are included by multiparticle collision dynamics. Statistical analysis of data reveals ballistic motion of the swimmer, in contrast to the classical diffusion behavior found in the absence of active transitions between the states.

Nutrition, metabolic factors and cancer risk.

PubMed

Dossus, Laure; Kaaks, Rudolf

2008-08-01

Excess body weight (adiposity) and physical inactivity are increasingly being recognized as major nutritional risk factors for cancer, and especially for many of those cancer types that have increased incidence rates in affluent, industrialized parts of the world. In this review, an overview is presented of some key biological mechanisms that may provide important metabolic links between nutrition, physical activity and cancer, including insulin resistance and reduced glucose tolerance, increased activation of the growth hormone/IGF-I axis, alterations in sex-steroid synthesis and/or bioavailability, and low-grade chronic inflammation through the effects of adipokines and cytokines.

AMS Prototyping Activities

NASA Technical Reports Server (NTRS)

Burleigh, Scott

2008-01-01

This slide presentation reviews the activity around the Asynchronous Message Service (AMS) prototype. An AMS reference implementation has been available since late 2005. It is aimed at supporting message exchange both in on-board environments and over space links. The implementation incoroporates all mandatory elements of the draft recommendation from July 2007: (1) MAMS, AMS, and RAMS protocols. (2) Failover, heartbeats, resync. (3) "Hooks" for security, but no cipher suites included in the distribution. The performance is reviewed, and a Benchmark latency test over VxWorks Message Queues is shown as histograms of a count vs microseconds per 1000-byte message

The pituitary - Aging and spaceflown rats

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Grindeland, R. E.

1991-01-01

Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

Do Parents’ Exercise Habits Predict 13–18-Year-Old Adolescents’ Involvement in Sport?

PubMed Central

Sukys, Saulius; Majauskienė, Daiva; Cesnaitiene, Vida J.; Karanauskiene, Diana

2014-01-01

This study examined links between parents’ exercise habits and adolescents’ participation in sports activities, considering the aspects of gender and age. It was hypothesized that regular exercise by both parents would be related to children’s involvement in sport regardless of their gender and age. Moreover, it was hypothesized that children’s sports activities would be more strongly related to their father’s exercise activities. The study also examined the links between parents’ exercise habits and children’s motivation for sports. It was hypothesized that competition motives would be more important for children whose parents exercised regularly. The research sample included 2335 students from the seventh (n = 857), ninth (n = 960) and eleventh (n = 518) grades of various Lithuanian schools. The study used a questionnaire survey method, which revealed the links between parents’ exercise habits and their children’s participation in sport. Assessment of data for girls and boys showed that daughters’ participation in sport could be predicted by both their fathers’ and mothers’ exercise habits, but sons’ sports activities could be predicted only by the regular physical activities of their fathers. The assessment of children’s sporting activities according to age revealed links between parental exercising and the engagement of older (15–16 years old), but not younger adolescents (13–14 years old). Analysis of sports motivation showed that competition motives were more important for boys than for girls. Fitness, well-being and appearance motives were more important for older adolescents (15–18 years old), while competition motives were more important for younger adolescents (13–14 years old). Research revealed the relationship between children’s sport motives and fathers’ exercise habits, while examination of mothers’ exercise revealed no difference. Key points Parental exercising significantly predicts adolescents’ engagement in sport. Daughter’s engagement in sport is related to both parents whereas son’s involvement in sport is related only to father’s exercise habits. Regular exercising of both mother and father predicts 13 - 14-year-old adolescents’ engagement in sport. However, mother exercising is not related to older adolescents’ involvement in sport. Research revealed the relation of adolescents’ sport motives and father’s exercising, and no differences were established depending on mother’s exercise habits. PMID:25177177

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

PubMed

Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

2016-07-01

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.

PubMed

Aggarwal, Bharat B; Yuan, Wei; Li, Shiyou; Gupta, Subash C

2013-09-01

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of arts activities in developing resilience and mental wellbeing in children and young people a rapid review of the literature.

PubMed

Zarobe, Leyre; Bungay, Hilary

2017-11-01

This rapid review explores the role of arts activities in promoting the mental wellbeing and resilience of children and young people aged between 11 and 18 years. A systematic search of the literature was undertaken across 18 databases; no date limit was set on publication. Search terms included a range of creative activities: music, dance, singing, drama and visual arts; these were combined with terms linked to aspects of mental health, emotional wellbeing and resilience. Only studies related to activities that took place within community settings and those related to extracurricular activities based within schools were included. Following the application of inclusion and exclusion criteria, eight papers were included in the review. The interventions used in the studies were diverse and the research was heterogeneous; therefore, narrative synthesis of the results was conducted. The findings from the studies are considered in terms of the contribution the activities make to building resilience of children and young people. It was found that participating in arts activities can have a positive effect on self-confidence, self-esteem, relationship building and a sense of belonging, qualities which have been associated with resilience and mental wellbeing. Although the research evidence is limited, there is some support for providing structured group arts activities to help build resilience and contribute to positive mental wellbeing of children and young people.

Active transfer fault zone linking a segmented extensional system (Betics, southern Spain): Insight into heterogeneous extension driven by edge delamination

NASA Astrophysics Data System (ADS)

Martínez-Martínez, José Miguel; Booth-Rea, Guillermo; Azañón, José Miguel; Torcal, Federico

2006-08-01

Pliocene and Quaternary tectonic structures mainly consisting of segmented northwest-southeast normal faults, and associated seismicity in the central Betics do not agree with the transpressive tectonic nature of the Africa-Eurasia plate boundary in the Ibero-Maghrebian region. Active extensional deformation here is heterogeneous, individual segmented normal faults being linked by relay ramps and transfer faults, including oblique-slip and both dextral and sinistral strike-slip faults. Normal faults extend the hanging wall of an extensional detachment that is the active segment of a complex system of successive WSW-directed extensional detachments which have thinned the Betic upper crust since middle Miocene. Two areas, which are connected by an active 40-km long dextral strike-slip transfer fault zone, concentrate present-day extension. Both the seismicity distribution and focal mechanisms agree with the position and regime of the observed faults. The activity of the transfer zone during middle Miocene to present implies a mode of extension which must have remained substantially the same over the entire period. Thus, the mechanisms driving extension should still be operating. Both the westward migration of the extensional loci and the high asymmetry of the extensional systems can be related to edge delamination below the south Iberian margin coupled with roll-back under the Alborán Sea; involving the asymmetric westward inflow of asthenospheric material under the margins.

Phase space representation of neutron monitor count rate and atmospheric electric field in relation to solar activity in cycles 21 and 22.

PubMed

Silva, H G; Lopes, I

Heliospheric modulation of galactic cosmic rays links solar cycle activity with neutron monitor count rate on earth. A less direct relation holds between neutron monitor count rate and atmospheric electric field because different atmospheric processes, including fluctuations in the ionosphere, are involved. Although a full quantitative model is still lacking, this link is supported by solid statistical evidence. Thus, a connection between the solar cycle activity and atmospheric electric field is expected. To gain a deeper insight into these relations, sunspot area (NOAA, USA), neutron monitor count rate (Climax, Colorado, USA), and atmospheric electric field (Lisbon, Portugal) are presented here in a phase space representation. The period considered covers two solar cycles (21, 22) and extends from 1978 to 1990. Two solar maxima were observed in this dataset, one in 1979 and another in 1989, as well as one solar minimum in 1986. Two main observations of the present study were: (1) similar short-term topological features of the phase space representations of the three variables, (2) a long-term phase space radius synchronization between the solar cycle activity, neutron monitor count rate, and potential gradient (confirmed by absolute correlation values above ~0.8). Finally, the methodology proposed here can be used for obtaining the relations between other atmospheric parameters (e.g., solar radiation) and solar cycle activity.

Exosome platform for diagnosis and monitoring of traumatic brain injury

PubMed Central

Taylor, Douglas D.; Gercel-Taylor, Cicek

2014-01-01

We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. PMID:25135964

Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B.

PubMed

Rivera, G M; Antoku, S; Gelkop, S; Shin, N Y; Hanks, S K; Pawson, T; Mayer, B J

2006-06-20

The Nck family of Src homology (SH) 2/SH3 domain adaptors functions to link tyrosine phosphorylation induced by extracellular signals with downstream regulators of actin dynamics. We investigated the role of mammalian Nck adaptors in signaling from the activated platelet-derived growth factor (PDGF) receptor (PDGFbetaR) to the actin cytoskeleton. We report here that Nck adaptors are required for cytoskeletal reorganization and chemotaxis stimulated by PDGF-B. Analysis of tyrosine-phosphorylated proteins demonstrated that Crk-associated substrate (p130(Cas)), not the activated PDGFbetaR itself, is the major Nck SH2 domain-binding protein in PDGF-B-stimulated cells. Both Nck- and p130(Cas)-deficient cells fail to display cytoskeletal rearrangements, including the formation of membrane ruffles and the disassembly of actin bundles, typically shown by their WT counterparts in response to PDGF-B. Furthermore, Nck and p130(Cas) colocalize in phosphotyrosine-enriched membrane ruffles induced by PDGF-B in NIH 3T3 cells. These results suggest that Nck adaptors play an essential role in linking the activated PDGFbetaR with actin dynamics through a pathway that involves p130(Cas).

Immunostimulatory activity of sulfated galactans isolated from the red seaweed Gracilaria fisheri and development of resistance against white spot syndrome virus (WSSV) in shrimp.

PubMed

Wongprasert, Kanokpan; Rudtanatip, Tawut; Praiboon, Jantana

2014-01-01

Sulfated galactans (SG) were isolated from the red seaweed Gracilaria fisheri (G. fisheri). Chemical analysis revealed SG contains sulfate (12.7%) and total carbohydrate (42.2%) with an estimated molecular mass of 100 kDa. Structure analysis by NMR and FT-IR spectroscopy revealed that SG is a complex structure with a linear backbone of alternating 3-linked β-D-galactopyranose and 4-linked 3,6-anhydrogalactose units with partial 6-O-methylate-β-D-galactopyranose and with sulfation occurring on C4 of D-galactopyranose and C6 of L-galactopyranose units. SG treatment enhanced immune parameters including total haemocytes, phenoloxidase activity, superoxide anions and superoxide dismutase in shrimp Penaeus monodon. Shrimp fed with Artemia salina enriched with SG (100 and 200 μg ml(-1)) and inoculated with white spot syndrome virus (WSSV) showed a significantly lower mortality rate and lower viral VP 28 amplification and expression than control. The results suggest that SG from G. fisheri exhibits immune stimulatory and antiviral activities that could protect P. monodon from WSSV infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Mack, Hildegard I.D.; Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu

Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in knownmore » LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. - Highlights: • LKB1 is a tumor suppressor that is linked to Peutz-Jeghers syndrome. • Peutz-Jeghers syndrome patients have a high incidence of cervical cancer. • Cervical cancer is caused by HPV infections. • This study investigates LKB1 tumor suppressor activity in cervical cancer.« less

Effects of Aging on the Neural Correlates of Successful Item and Source Memory Encoding

PubMed Central

Dennis, Nancy A.; Hayes, Scott M.; Prince, Steven E.; Madden, David J.; Huettel, Scott A.; Cabeza, Roberto

2009-01-01

To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding activity in hippocampal and prefrontal regions were more pronounced for SM (pairs) compared to item memory (faces and scenes). Age-related reductions were also found in regions specialized in processing faces (fusiform face area) and scenes (parahippocampal place area), but these reductions were similar for item and SM. Functional connectivity between the hippocampus and the rest of the brain was also affected by aging; whereas connections with posterior cortices were weaker in older adults, connections with anterior cortices including prefrontal regions were stronger in older adults. Taken together, the results provide a link between SM deficits in older adults and reduced recruitment of hippocampal and prefrontal regions during encoding. The functional connectivity findings are consistent with a posterior-anterior shift with aging (PASA), previously reported in several cognitive domains and linked to functional compensation. PMID:18605869

Transcription regulation by the Mediator complex.

PubMed

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

Peroxiredoxin 2 and peroxide metabolism in the erythrocyte.

PubMed

Low, Felicia M; Hampton, Mark B; Winterbourn, Christine C

2008-09-01

Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides. Prx2 is the third most abundant protein in erythrocytes, and competes effectively with catalase and glutathione peroxidase to scavenge low levels of hydrogen peroxide, including that derived from hemoglobin autoxidation. Low thioredoxin reductase activity in the erythrocyte is able to keep up with this basal oxidation and maintain the Prx2 in its reduced form, but exposure to exogenous hydrogen peroxide causes accumulation of the disulfide-linked dimer. The high cellular concentration means that although turnover is slow, erythrocyte Prx2 can act as a noncatalytic scavenger of hydrogen peroxide and a sink for hydrogen peroxide before turnover becomes limiting. The consequences of Prx2 oxidation for the erythrocyte are not well characterized, but mice deficient in this protein develop severe hemolytic anemia associated with Heinz body formation. Prx2, also known as calpromotin, regulates ion transport by associating with the membrane and activating the Gárdos channel. How Prx2 redox transformations are linked to membrane association and channel activation is yet to be established. In this review, we discuss the functional properties of Prx2 and its role as a major component of the erythrocyte antioxidant system.

Discovery and structure-guided fragment-linking of 4-(2,3-dichlorobenzoyl)-1-methyl-pyrrole-2-carboxamide as a pyruvate kinase M2 activator.

PubMed

Matsui, Yumi; Yasumatsu, Isao; Asahi, Takashi; Kitamura, Takahiro; Kanai, Kazuo; Ubukata, Osamu; Hayasaka, Hitoshi; Takaishi, Sachiko; Hanzawa, Hiroyuki; Katakura, Shinichi

2017-07-01

Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic intermediates as building blocks for biosynthetic processes, and thereby supporting cell proliferation. Activation of PKM2 should invert aerobic glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has gained attention as a promising cancer therapy target. To obtain novel PKM2 activators, we conducted a high-throughput screening (HTS). Among several hit compounds, a fragment-like hit compound with low potency but high ligand efficiency was identified. Two molecules of the hit compound bound at one activator binding site, and the molecules were linked based on the crystal structure. Since this linkage succeeded in maintaining the original position of the hit compound, the obtained compound exhibited highly improved potency in an in vitro assay. The linked compound also showed PKM2 activating activity in a cell based assay, and cellular growth inhibition of the A549 cancer cell line. Discovery of this novel scaffold and binding mode of the linked compound provides a valuable platform for the structure-guided design of PKM2 activators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transnational organizational considerations for sociocultural differences in ethics and virtual team functioning in laboratory animal science.

PubMed

Pritt, Stacy L; Mackta, Jayne

2010-05-01

Business models for transnational organizations include linking different geographies through common codes of conduct, policies, and virtual teams. Global companies with laboratory animal science activities (whether outsourced or performed inhouse) often see the need for these business activities in relation to animal-based research and benefit from them. Global biomedical research organizations can learn how to better foster worldwide cooperation and teamwork by understanding and working with sociocultural differences in ethics and by knowing how to facilitate appropriate virtual team actions. Associated practices include implementing codes and policies transcend cultural, ethnic, or other boundaries and equipping virtual teams with the needed technology, support, and rewards to ensure timely and productive work that ultimately promotes good science and patient safety in drug development.

The Online GVP/USGS Weekly Volcanic Activity Report: Providing Timely Information About Worldwide Volcanism

NASA Astrophysics Data System (ADS)

Mayberry, G. C.; Guffanti, M. C.; Luhr, J. F.; Venzke, E. A.; Wunderman, R. L.

2001-12-01

The awesome power and intricate inner workings of volcanoes have made them a popular subject with scientists and the general public alike. About 1500 known volcanoes have been active on Earth during the Holocene, approximately 50 of which erupt per year. With so much activity occurring around the world, often in remote locations, it can be difficult to find up-to-date information about current volcanism from a reliable source. To satisfy the desire for timely volcano-related information the Smithsonian Institution and US Geological Survey combined their strengths to create the Weekly Volcanic Activity Report. The Smithsonian's Global Volcanism Program (GVP) has developed a network of correspondents while reporting worldwide volcanism for over 30 years in their monthly Bulletin of the Global Volcanism Network. The US Geological Survey's Volcano Hazards Program studies and monitors volcanoes in the United States and responds (upon invitation) to selected volcanic crises in other countries. The Weekly Volcanic Activity Report is one of the most popular sites on both organization's websites. The core of the Weekly Volcanic Activity Report is the brief summaries of current volcanic activity around the world. In addition to discussing various types of volcanism, the summaries also describe precursory activity (e.g. volcanic seismicity, deformation, and gas emissions), secondary activity (e.g. debris flows, mass wasting, and rockfalls), volcanic ash hazards to aviation, and preventative measures. The summaries are supplemented by links to definitions of technical terms found in the USGS photoglossary of volcano terms, links to information sources, and background information about reported volcanoes. The site also includes maps that highlight the location of reported volcanoes, an archive of weekly reports sorted by volcano and date, and links to commonly used acronyms. Since the Weekly Volcanic Activity Report's inception in November 2000, activity has been reported at over 60 volcanoes, with an average of 10 volcanoes discussed each week. Notable volcanic activity during November 2000-November 2001 included an eruption beginning on 6 February at Nyamuragira in the Democratic Republic of the Congo; it issued low-viscosity lava flows that traveled towards inhabited towns, and also produced ash clouds that adversely effected the health of residents and livestock near the volcano. Eruptions at Mayon in the Philippines on 24 June and 25 July caused local authorities to raise the alert to the highest level, close area airports, and evacuate thousands of residents near the volcano. Most recently a large flank eruption at Etna in Italy began on 17 July and gained worldwide attention as extensive lava flows threatened a small town and a tourist complex. While the information found in the Weekly Volcanic Activity Report, ranging from large eruptions to small precursory events, is of interest to the general public, it has also proven to be a valuable resource to volcano observatory staff, universities, researchers, secondary schools, and the aviation community.

Orbital debris and near-Earth environmental management: A chronology

NASA Technical Reports Server (NTRS)

Portree, David S. F.; Loftus, Joseph P., Jr.

1993-01-01

This chronology covers the 32-year history of orbital debris and near-Earth environmental concerns. It tracks near-Earth environmental hazard creation, research, observation, experimentation, management, mitigation, protection, and policy-making, with emphasis on the orbital debris problem. Included are the Project West Ford experiments; Soviet ASAT tests and U.S. Delta upper stage explosions; the Ariane V16 explosion, U.N. treaties pertinent to near-Earth environmental problems, the PARCS tests; space nuclear power issues, the SPS/orbital debris link; Space Shuttle and space station orbital debris issues; the Solwind ASAT test; milestones in theory and modeling the Cosmos 954, Salyut 7, and Skylab reentries; the orbital debris/meteoroid research link; detection system development; orbital debris shielding development; popular culture and orbital debris; Solar Max results; LDEF results; orbital debris issues peculiar to geosynchronous orbit, including reboost policies and the stable plane; seminal papers, reports, and studies; the increasing effects of space activities on astronomy; and growing international awareness of the near-Earth environment.

Role of TGF-β signaling in inherited and acquired myopathies

PubMed Central

2011-01-01

The transforming growth factor-beta (TGF-β) superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs), and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders. PMID:21798096

Brain mast cells link the immune system to anxiety-like behavior

PubMed Central

Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

2008-01-01

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

Brain mast cells link the immune system to anxiety-like behavior.

PubMed

Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

2008-11-18

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

A Performance Evaluation of NACK-Oriented Protocols as the Foundation of Reliable Delay- Tolerant Networking Convergence Layers

NASA Technical Reports Server (NTRS)

Iannicca, Dennis; Hylton, Alan; Ishac, Joseph

2012-01-01

Delay-Tolerant Networking (DTN) is an active area of research in the space communications community. DTN uses a standard layered approach with the Bundle Protocol operating on top of transport layer protocols known as convergence layers that actually transmit the data between nodes. Several different common transport layer protocols have been implemented as convergence layers in DTN implementations including User Datagram Protocol (UDP), Transmission Control Protocol (TCP), and Licklider Transmission Protocol (LTP). The purpose of this paper is to evaluate several stand-alone implementations of negative-acknowledgment based transport layer protocols to determine how they perform in a variety of different link conditions. The transport protocols chosen for this evaluation include Consultative Committee for Space Data Systems (CCSDS) File Delivery Protocol (CFDP), Licklider Transmission Protocol (LTP), NACK-Oriented Reliable Multicast (NORM), and Saratoga. The test parameters that the protocols were subjected to are characteristic of common communications links ranging from terrestrial to cis-lunar and apply different levels of delay, line rate, and error.

Telecommunications and navigation systems design for manned Mars exploration missions

NASA Astrophysics Data System (ADS)

Hall, Justin R.; Hastrup, Rolf C.

1989-06-01

This paper discusses typical manned Mars exploration needs for telecommunications, including preliminary navigation support functions. It is a brief progress report on an ongoing study program within the current NASA JPL Deep Space Network (DSN) activities. A typical Mars exploration case is defined, and support approaches comparing microwave and optical frequency performance for both local in situ and Mars-earth links are described. Optical telecommunication and navigation technology development opportunities in a Mars exploration program are also identified. A local Mars system telecommunication relay and navigation capability for service support of all Mars missions has been proposed as part of an overall solar system communications network. The effects of light-time delay and occultations on real-time mission decision-making are discussed; the availability of increased local mass data storage may be more important than increasing peak data rates to earth. The long-term frequency use plan will most likely include a mix of microwave, millimeter-wave and optical link capabilities to meet a variety of deep space mission needs.

Telecommunications and navigation systems design for manned Mars exploration missions

NASA Technical Reports Server (NTRS)

Hall, Justin R.; Hastrup, Rolf C.

1989-01-01

This paper discusses typical manned Mars exploration needs for telecommunications, including preliminary navigation support functions. It is a brief progress report on an ongoing study program within the current NASA JPL Deep Space Network (DSN) activities. A typical Mars exploration case is defined, and support approaches comparing microwave and optical frequency performance for both local in situ and Mars-earth links are described. Optical telecommunication and navigation technology development opportunities in a Mars exploration program are also identified. A local Mars system telecommunication relay and navigation capability for service support of all Mars missions has been proposed as part of an overall solar system communications network. The effects of light-time delay and occultations on real-time mission decision-making are discussed; the availability of increased local mass data storage may be more important than increasing peak data rates to earth. The long-term frequency use plan will most likely include a mix of microwave, millimeter-wave and optical link capabilities to meet a variety of deep space mission needs.

A new model of exercise referral scheme in primary care: is the effect on adherence to physical activity sustainable in the long term? A 15-month randomised controlled trial.

PubMed

Martín-Borràs, Carme; Giné-Garriga, Maria; Puig-Ribera, Anna; Martín, Carlos; Solà, Mercè; Cuesta-Vargas, Antonio I

2018-03-03

Studies had not yet overcome the most relevant barriers to physical activity (PA) adherence. An exercise referral scheme (ERS) with mechanisms to promote social support might enhance adherence to PA in the long term. A randomised controlled trial in 10 primary care centres in Spain. To assess the effectiveness of a primary care-based ERS linked to municipal resources and enhancing social support and social participation in establishing adherence to PA among adults over a 15-month period. 422 insufficiently active participants suffering from at least one chronic condition were included. 220 patients (69.5 (8.4) years; 136 women) were randomly allocated to the intervention group (IG) and 202 (68.2 (8.9) years; 121 women) to the control group (CG). The IG went through a 12-week standardised ERS linked to community resources and with inclusion of mechanisms to enhance social support. The CG received usual care from their primary care practice. The main outcome measure was self-report PA with the International Physical Activity Questionnaire and secondary outcomes included stages of change and social support to PA practice. Participant-level data were collected via questionnaires at baseline, and at months 3, 9 and 15. The study statistician and research assessors were blinded to group allocation. Compared with usual care, follow-up data at month 15 for the ERS group showed a significant increase of self-reported PA (IG: 1373±1845 metabolic equivalents (MET) min/week, n=195; CG: 919±1454 MET min/week, n=144; P=0.009). Higher adherence (in terms of a more active stage of change) was associated with higher PA level at baseline and with social support. Prescription from ordinary primary care centres staff yielded adherence to PA practice in the long term. An innovative ERS linked to community resources and enhancing social support had shown to be sustainable in the long term. NCT00714831; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Disability, participation, and subjective wellbeing among older couples

PubMed Central

Freedman, Vicki A.; Stafford, Frank; Schwarz, Norbert; Conrad, Frederick; Cornman, Jennifer C.

2012-01-01

This paper investigates the link between disability and subjective wellbeing, using data from the 2009 Disability and Use of Time supplement to the Panel Study of Income Dynamics, the longest running national panel study in the United States. Disability is construed broadly to include both the presence of any physical, cognitive, or sensory impairment or activity limitation and also the severity of underlying impairments. Subjective wellbeing is measured using two distinct approaches: reports of life satisfaction and of moment-to-moment wellbeing—both positive and negative—on the previous day. The latter, collected through 24-h time diaries, also offers for the first time the ability to explore the role of participation in particular kinds of activities linking disability to subjective wellbeing. The analytic sample included married persons ages 60 and older and their spouses (n = 751 married individuals) who completed 1498 diaries. Several new findings emerged: no matter what the measure of wellbeing, older married adults with disability report worse subjective wellbeing than those without, and neither different demographic and socioeconomic profiles nor differences in participation fully account for these disparities. Influences of disability on global life satisfaction and episodic reports of happiness were relatively small and of comparable size. However, notably sizeable differences were identified in the cumulative number of pleasant minutes experienced yesterday by disability status - on the order of 71 fewer minutes on average for those with a disability of average severity. Differences appear to be more strongly linked to somatic symptoms of pain and feeling tired than to differential intensity of experiencing happiness, sadness, frustration, or worry. We also found limited support for the notion that participation partially mediates the relationship between disability and global, but not episodic, subjective wellbeing. PMID:22226156

Control of a community outbreak of hepatitis A in an area of low endemicity, Wales, 2016.

PubMed

Vaz, J; Floyd, C; Mason, B; Shankar, A G; Lewis, H

2017-10-03

Incidence of hepatitis A in Wales is low (average of 0.48/100,000 inhabitants from 2004-2015). We describe a community outbreak of hepatitis A involving 3 schools (primary and secondary) in South Wales between March and June 2016 and reflect on the adequacy of the control measures used. Anyone in South Wales epidemiologically linked to a serological and/or RNA positive confirmed case of hepatitis A during the 15-50 d before onset of symptoms (diarrhea, vomiting, fever, nausea, AND jaundice, or jaundice-associated symptom) was defined as a case. Case identification was based on laboratory or GP suspicion notification, changing to active surveillance toward the end. As per national guidance, household contacts were identified and offered immunisation while in schools vaccination followed evidence of transmission. We went beyond guidance by vaccinating street play mates and in secondary schools. Mass vaccination uptake was calculated. There were 17 cases, mostly in children under 16 y of age. All cases had an epidemiological link to either a school or a household case (except primary) and no travel history. Street playing was the only epidemiological link between 2 cases in different schools. A total of 139 household contacts were identified. All schools, including secondary one, had a transmission event preceding mass vaccination (overall uptake 85%, reaching 1,574 individuals) and no tertiary cases emerged after the campaigns. We recommend extending guidance to include actions taken that helped curb this outbreak: 1) vaccinating in secondary school and 2) broadening the household contact definition. Based on our learning we further suggest 3) vaccinating upon identification of a single case who attended school while infectious regardless of source and 4) active case finding by serologically testing contacts.

Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain

PubMed Central

Puglia, Meghan H.; Lillard, Travis S.; Morris, James P.; Connelly, Jessica J.

2015-01-01

In humans, the neuropeptide oxytocin plays a critical role in social and emotional behavior. The actions of this molecule are dependent on a protein that acts as its receptor, which is encoded by the oxytocin receptor gene (OXTR). DNA methylation of OXTR, an epigenetic modification, directly influences gene transcription and is variable in humans. However, the impact of this variability on specific social behaviors is unknown. We hypothesized that variability in OXTR methylation impacts social perceptual processes often linked with oxytocin, such as perception of facial emotions. Using an imaging epigenetic approach, we established a relationship between OXTR methylation and neural activity in response to emotional face processing. Specifically, high levels of OXTR methylation were associated with greater amounts of activity in regions associated with face and emotion processing including amygdala, fusiform, and insula. Importantly, we found that these higher levels of OXTR methylation were also associated with decreased functional coupling of amygdala with regions involved in affect appraisal and emotion regulation. These data indicate that the human endogenous oxytocin system is involved in attenuation of the fear response, corroborating research implicating intranasal oxytocin in the same processes. Our findings highlight the importance of including epigenetic mechanisms in the description of the endogenous oxytocin system and further support a central role for oxytocin in social cognition. This approach linking epigenetic variability with neural endophenotypes may broadly explain individual differences in phenotype including susceptibility or resilience to disease. PMID:25675509

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

Zheng, Tianyong; Olson, Daniel G.; Tian, Liang

Clostridium thermocellum and Thermoanaerobacterium saccharolyticumare thermophilic bacteria that have been engineered to produce ethanol from the cellulose and hemicellulose fractions of biomass, respectively. Although engineered strains of T. saccharolyticumproduce ethanol with a yield of 90% of the theoretical maximum, engineered strains ofC. thermocellumproduce ethanol at lower yields (~50% of the theoretical maximum). In the course of engineering these strains, a number of mutations have been discovered in theiradhEgenes, which encode both alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes. To understand the effects of these mutations, theadhEgenes from six strains ofC. thermocellumandT. saccharolyticumwere cloned and expressed inEscherichia coli, the enzymesmore » produced were purified by affinity chromatography, and enzyme activity was measured. In wild-type strains of both organisms, NADH was the preferred cofactor for both ALDH and ADH activities. In high-ethanol-producing (ethanologen) strains ofT. saccharolyticum, both ALDH and ADH activities showed increased NADPH-linked activity. Interestingly, the AdhE protein of the ethanologenic strain ofC. thermocellumhas acquired high NADPH-linked ADH activity while maintaining NADH-linked ALDH and ADH activities at wild-type levels. When single amino acid mutations in AdhE that caused increased NADPH-linked ADH activity were introduced intoC. thermocellumandT. saccharolyticum, ethanol production increased in both organisms. Structural analysis of the wild-type and mutant AdhE proteins was performed to provide explanations for the cofactor specificity change on a molecular level. This work describes the characterization of the AdhE enzyme from different strains ofC. thermocellumandT. saccharolyticum.C. thermocellumandT. saccharolyticumare thermophilic anaerobes that have been engineered to make high yields of ethanol and can solubilize components of plant biomass and ferment the sugars to ethanol. In the course of engineering these strains, several mutations arose in the bifunctional ADH/ALDH protein AdhE, changing both enzyme activity and cofactor specificity. We show that changing AdhE cofactor specificity from mostly NADH linked to mostly NADPH linked resulted in higher ethanol production byC. thermocellumandT. saccharolyticum.« less

Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair.

PubMed

Leung, Justin Wai Chung; Wang, Yucai; Fong, Ka Wing; Huen, Michael Shing Yan; Li, Lei; Chen, Junjie

2012-03-20

The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of cross-linked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway.

Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair

PubMed Central

Leung, Justin Wai Chung; Wang, Yucai; Fong, Ka Wing; Huen, Michael Shing Yan; Li, Lei; Chen, Junjie

2012-01-01

The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of cross-linked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway. PMID:22396592

Synthesis and antitumor activity evaluation of a novel combi-nitrosourea prodrug: Designed to release a DNA cross-linking agent and an inhibitor of O(6)-alkylguanine-DNA alkyltransferase.

PubMed

Sun, Guohui; Zhang, Na; Zhao, Lijiao; Fan, Tengjiao; Zhang, Shufen; Zhong, Rugang

2016-05-01

The drug resistance of CENUs induced by O(6)-alkylguanine-DNA alkyltransferase (AGT), which repairs the O(6)-alkylated guanine and subsequently inhibits the formation of dG-dC cross-links, hinders the application of CENU chemotherapies. Therefore, the discovery of CENU analogs with AGT inhibiting activity is a promising approach leading to novel CENU chemotherapies with high therapeutic index. In this study, a new combi-nitrosourea prodrug 3-(3-(((2-amino-9H-purin-6-yl)oxy)methyl)benzyl)-1-(2-chloroethyl)-1-nitrosourea (6), designed to release a DNA cross-linking agent and an inhibitor of AGT, was synthesized and evaluated for its antitumor activity and ability to induce DNA interstrand cross-links (ICLs). The results indicated that 6 exhibited higher cytotoxicity against mer(+) glioma cells compared with ACNU, BCNU, and their respective combinations with O(6)-benzylguanine (O(6)-BG). Quantifications of dG-dC cross-links induced by 6 were performed using HPLC-ESI-MS/MS. Higher levels of dG-dC cross-link were observed in 6-treated human glioma SF763 cells (mer(+)), whereas lower levels of dG-dC cross-link were observed in 6-treated calf thymus DNA, when compared with the groups treated with BCNU and ACNU. The results suggested that the superiority of 6 might result from the AGT inhibitory moiety, which specifically functions in cells with AGT activity. Molecular docking studies indicated that five hydrogen bonds were formed between the O(6)-BG analogs released from 6 and the five residues in the active pocket of AGT, which provided a reasonable explanation for the higher AGT-inhibitory activity of 6 than O(6)-BG. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modified carbohydrate-chitosan compounds, methods of making the same and methods of using the same

DOEpatents

Venditti, Richard A; Pawlak, Joel J; Salam, Abdus; El-Tahlawy, Khaled Fathy

2015-03-10

Compositions of matter are provided that include chitosan and a modified carbohydrate. The modified carbohydrate includes a carbohydrate component and a cross linking agent. The modified carbohydrate has increased carboxyl content as compared to an unmodified counterpart carbohydrate. A carboxyl group of the modified carbohydrate is covalently bonded with an amino group of chitosan. The compositions of matter provided herein may include cross linked starch citrate-chitosan and cross linked hemicellulose citrate-chitosan, including foams thereof. These compositions yield excellent absorbency and metal chelation properties. Methods of making cross linked modified carbohydrate-chitosan compounds are also provided.

Electromyography of 3 scapular muscles: a comparative analysis of the cuff link device and a standard push-up.

PubMed

Tucker, W Steven; Campbell, Brian M; Swartz, Erik E; Armstrong, Charles W

2008-01-01

The Cuff Link is a closed kinetic chain rehabilitation apparatus for the upper extremity. Limited research has established its effectiveness to elicit muscle activation of the scapular muscles. To determine if scapular muscle activation differs in response to 2 upper extremity closed kinetic chain exercises: Cuff Link and standard push-up. A single-group, repeated-measures design. Controlled laboratory. Twenty-eight healthy individuals (13 women: age = 19.69 +/- 1.55 years, height = 167.44 +/- 9.52 cm, mass = 61.00 +/- 8.79 kg; 15 men: age = 22.00 +/- 3.91 years, height = 181.44 +/- 6.60 cm, mass = 82.36 +/- 13.23 kg) with no history of shoulder or low back injury volunteered to participate in this study. Participants performed 10 trials of complete revolutions on the Cuff Link and 10 full-weight-bearing push-ups. We controlled trial velocity and randomized order. Trunk and shoulder positions were normalized to the participant's height. Using surface electromyography, we recorded muscle activity of the serratus anterior, middle trapezius, and lower trapezius. Rectified and smoothed electromyography data for the serratus anterior, middle trapezius, and lower trapezius were normalized as a percentage of the maximal voluntary isometric contractions (%MVIC). Mean muscle activity of the serratus anterior, middle trapezius, and lower trapezius. We used paired-samples t tests to analyze the mean data for each condition. The alpha level was adjusted to .016 to avoid a type I error. Middle trapezius %MVIC was greater during push-ups (27.01 +/- 20.40%) than during use of the Cuff Link (11.49 +/- 9.46%) (P = .001). Lower trapezius %MVIC was greater during push-ups (36.07 +/- 18.99%) than during use of the Cuff Link (16.29 +/- 8.64%) (P = .001). There was no difference in %MVIC for the serratus anterior between conditions. The push-up demonstrated greater middle trapezius and lower trapezius activation levels compared with the Cuff Link. However, the push-up had a high participant failure rate. Because serratus anterior activation levels were similar, the Cuff Link may be an appropriate alternative for individuals lacking the upper body strength to perform a push-up.

Studying Activity Series of Metals.

ERIC Educational Resources Information Center

Hoon, Tien-Ghun; And Others

1995-01-01

Presents teaching strategies that illustrate the linking together of numerous chemical concepts involving the activity of metals (quantitative analysis, corrosion, and electrolysis) through the use of deep-level processing strategies. Concludes that making explicit links in the process of teaching chemistry can lead effectively to meaningful…

Structural Analysis and Immuno-Stimulating Activity of an Acidic Polysaccharide from the Stems of Dendrobium nobile Lindl.

PubMed

Wang, Jun-Hui; Zuo, Shu-Rong; Luo, Jian-Ping

2017-04-10

Dendrobium nobile Lindl., an epiphytic herb distributed in the Southeast Asia, is used as a tonic and antipyretic herbal medicine in China. In this study, a water-soluble acidic heteropolysaccharide, DNP-W4, containing mannose, glucose, galactose, xylose, rhamnose, and galacturonic acid, in the molar ratios of 1.0:4.9:2.5:0.5:1.0:0.9, was obtained from the stems of Dendrobium nobile Lindl. Using methylation analysis, partial acid hydrolysis, pectolyase treatment, NMR, and ESI-MS, the structure of DNP-W4 was elucidated. The obtained data indicated that DNP-W4 was a complex heteropolysaccharide and possessed a backbone composed of (1→4)-linked β-d-Glcp, (1→6)-linked β-d-Glcp, and (1→6)-linked β-d-Galp, with substitutes at O-4/6 of Glcp residues and O-3 of Galp. The branches of DNP-W4 were composed of terminal Manp, (1→6)-linked β-d-Manp, (1→3)-linked β-d-Glcp, β-d-Glcp, β-d-Galp, (1→4)-linked α-d-GalAp, (1→2)-linked α-L-Rhap, and Xylp. DNP-W4 had little immunological activities, but its derivatives had immuno-stimulating activities to some extent.

Protective link for superconducting coil

DOEpatents

Umans, Stephen D [Belmont, MA

2009-12-08

A superconducting coil system includes a superconducting coil and a protective link of superconducting material coupled to the superconducting coil. A rotating machine includes first and second coils and a protective link of superconducting material. The second coil is operable to rotate with respect to the first coil. One of the first and second coils is a superconducting coil. The protective link is coupled to the superconducting coil.

The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

PubMed Central

Palhano-Fontes, Fernanda; Andrade, Katia C.; Tofoli, Luis F.; Santos, Antonio C.; Crippa, Jose Alexandre S.; Hallak, Jaime E. C.; Ribeiro, Sidarta; de Araujo, Draulio B.

2015-01-01

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN. PMID:25693169

Linked Ocean Data

NASA Astrophysics Data System (ADS)

Leadbetter, Adam; Arko, Robert; Chandler, Cynthia; Shepherd, Adam

2014-05-01

"Linked Data" is a term used in Computer Science to encapsulate a methodology for publishing data and metadata in a structured format so that links may be created and exploited between objects. Berners-Lee (2006) outlines the following four design principles of a Linked Data system: Use Uniform Resource Identifiers (URIs) as names for things. Use HyperText Transfer Protocol (HTTP) URIs so that people can look up those names. When someone looks up a URI, provide useful information, using the standards (Resource Description Framework [RDF] and the RDF query language [SPARQL]). Include links to other URIs so that they can discover more things. In 2010, Berners-Lee revisited his original design plan for Linked Data to encourage data owners along a path to "good Linked Data". This revision involved the creation of a five star rating system for Linked Data outlined below. One star: Available on the web (in any format). Two stars: Available as machine-readable structured data (e.g. An Excel spreadsheet instead of an image scan of a table). Three stars: As two stars plus the use of a non-proprietary format (e.g. Comma Separated Values instead of Excel). Four stars: As three stars plus the use of open standards from the World Wide Web Commission (W3C) (i.e. RDF and SPARQL) to identify things, so that people can point to your data and metadata. Five stars: All the above plus link your data to other people's data to provide context Here we present work building on the SeaDataNet common vocabularies served by the NERC Vocabulary Server, connecting projects such as the Rolling Deck to Repository (R2R) and the Biological and Chemical Oceanography Data Management Office (BCO-DMO) and other vocabularies such as the Marine Metadata Interoperability Ontology Register and Repository and the NASA Global Change Master Directory to create a Linked Ocean Data cloud. Publishing the vocabularies and metadata in standard RDF XML and exposing SPARQL endpoints renders them five-star Linked Data repositories. The benefits of this approach include: increased interoperability between the metadata created by projects; improved data discovery as users of SeaDataNet, R2R and BCO-DMO terms can find data using labels with which they are familiar both standard tools and newly developed custom tools may be used to explore the data; and using standards means the custom tools are easier to develop Linked Data is a concept which has been in existence for nearly a decade, and has a simple set of formal best practices associated with it. Linked Data is increasingly being seen as a driver of the next generation of "community science" activities. While many data providers in the oceanographic domain may be unaware of Linked Data, they may also be providing it at one of its lower levels. Here we have shown that it is possible to deliver the highest standard of Linked Oceanographic Data, and some of the benefits of the approach.

Macromolecular cross-linked enzyme aggregates (M-CLEAs) of α-amylase.

PubMed

Nadar, Shamraja S; Muley, Abhijeet B; Ladole, Mayur R; Joshi, Pranoti U

2016-03-01

Macromolecular cross-linked enzyme aggregates (M-CLEAs) of α-amylase were prepared by precipitation and subsequent cross-linking. The non-toxic, biodegradable, biocompatible, renewable polysaccharide based macromolecular cross-linkers viz. agar, chitosan, dextran, and gum arabic were used as a substitute for traditional glutaraldehyde to augment activity recovery toward macromolecular substrate. Macromolecular cross-linkers were prepared by periodate mediated controlled oxidation of polysaccharides. The effects of precipitating agent, concentration and different cross-linkers on activity recovery of α-amylase CLEAs were investigated. α-Amylase aggregated with ammonium sulphate and cross-linked by dextran showed 91% activity recovery, whereas glutaraldehyde CLEAs (G-CLEAs) exhibited 42% activity recovery. M-CLEAs exhibited higher thermal stability in correlation with α-amylase and G-CLEAs. Moreover, dextran and chitosan M-CLEAs showed same affinity for starch hydrolysis as of free α-amylase. The changes in secondary structures revealed the enhancements in structural and conformational rigidity attributed by cross-linkers. Finally, after five consecutive cycles dextran M-CLEAs retained 1.25 times higher initial activity than G-CLEAs. Copyright © 2015 Elsevier B.V. All rights reserved.

A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs.

PubMed

Eniade, Adewale; Purushotham, Madhusudhan; Ben, Robert N; Wang, J B; Horwath, Kathleen

2003-01-01

Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.

Demonstration of 3 alpha(17 beta)-hydroxysteroid dehydrogenase distinct from 3 alpha-hydroxysteroid dehydrogenase in hamster liver.

PubMed Central

Ohmura, M; Hara, A; Nakagawa, M; Sawada, H

1990-01-01

NAD(+)-linked and NADP(+)-linked 3 alpha-hydroxysteroid dehydrogenases were purified to homogeneity from hamster liver cytosol. The two monomeric enzymes, although having similar molecular masses of 38,000, differed from each other in pI values, activation energy and heat stability. The two proteins also gave different fragmentation patterns by gel electrophoresis after digestion with protease. The NADP(+)-linked enzyme catalysed the oxidoreduction of various 3 alpha-hydroxysteroids, whereas the NAD(+)-linked enzyme oxidized the 3 alpha-hydroxy group of pregnanes and some bile acids, and the 17 beta-hydroxy group of testosterone and androstanes. The thermal stabilities of the 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the NAD(+)-linked enzyme were identical, and the two enzyme activities were inhibited by mixing 17 beta- and 3 alpha-hydroxysteroid substrates, respectively. Medroxyprogesterone acetate, hexoestrol and 3 beta-hydroxysteroids competitively inhibited 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the enzyme. These results show that hamster liver contains a 3 alpha(17 beta)-hydroxysteroid dehydrogenase structurally and functionally distinct from 3 alpha-hydroxysteroid dehydrogenase. Images Fig. 1. Fig. 2. PMID:2317205

CISN ShakeAlert Earthquake Early Warning System Monitoring Tools

NASA Astrophysics Data System (ADS)

Henson, I. H.; Allen, R. M.; Neuhauser, D. S.

2015-12-01

CISN ShakeAlert is a prototype earthquake early warning system being developed and tested by the California Integrated Seismic Network. The system has recently been expanded to support redundant data processing and communications. It now runs on six machines at three locations with ten Apache ActiveMQ message brokers linking together 18 waveform processors, 12 event association processes and 4 Decision Module alert processes. The system ingests waveform data from about 500 stations and generates many thousands of triggers per day, from which a small portion produce earthquake alerts. We have developed interactive web browser system-monitoring tools that display near real time state-of-health and performance information. This includes station availability, trigger statistics, communication and alert latencies. Connections to regional earthquake catalogs provide a rapid assessment of the Decision Module hypocenter accuracy. Historical performance can be evaluated, including statistics for hypocenter and origin time accuracy and alert time latencies for different time periods, magnitude ranges and geographic regions. For the ElarmS event associator, individual earthquake processing histories can be examined, including details of the transmission and processing latencies associated with individual P-wave triggers. Individual station trigger and latency statistics are available. Detailed information about the ElarmS trigger association process for both alerted events and rejected events is also available. The Google Web Toolkit and Map API have been used to develop interactive web pages that link tabular and geographic information. Statistical analysis is provided by the R-Statistics System linked to a PostgreSQL database.

Nutrition and Physical Activity Strategies for Cancer Prevention in Current National Comprehensive Cancer Control Program Plans

PubMed Central

Puckett, Mary; Neri, Antonio; Underwood, J. Michael; Stewart, Sherri L.

2016-01-01

Obesity, diet and physical inactivity are risk factors for some cancers. Grantees of the National Comprehensive Cancer Control Program (NCCCP) in US states, tribes, and territories develop plans to coordinate funding and activities for cancer prevention and control. Including information and goals related to nutrition and physical activity (NPA) is a key opportunity for primary cancer prevention, but it is currently unclear to what extent NCCCP plans address these issues. We reviewed 69 NCCCP plans and searched for terms related to NPA. Plans were coded as (1) knowledge of NPA and cancer link; (2) goals to improve NPA behaviors; and (3) strategies to increase healthy NPA activities, environments, or systems changes. NPA content was consistently included in all cancer plans examined across all years. Only 4 (6 %) outlined only the relationship between NPA and cancer without goals or strategies. Fifty-nine plans (89 %) contained goals or strategies related to NPA, with 53 (82 %) including both. However, numbers of goals, strategies, and detail provided varied widely. All programs recognized the importance of NPA in cancer prevention. Most plans included NPA goals and strategies. Increasing the presence of NPA strategies that can be modified or adapted appropriately locally could help with more widespread implementation and measurement of NPA interventions. PMID:26994988

Chromatin looping and eRNA transcription precede the transcriptional activation of gene in the β-globin locus

PubMed Central

Kim, Yea Woon; Lee, Sungkung; Yun, Jangmi; Kim, AeRi

2015-01-01

Enhancers are closely positioned with actively transcribed target genes by chromatin looping. Non-coding RNAs are often transcribed on active enhancers, referred to as eRNAs (enhancer RNAs). To explore the kinetics of enhancer–promoter looping and eRNA transcription during transcriptional activation, we induced the β-globin locus by chemical treatment and analysed cross-linking frequency between the β-globin gene and locus control region (LCR) and the amount of eRNAs transcribed on the LCR in a time course manner. The cross-linking frequency was increased after chemical induction but before the transcriptional activation of gene in the β-globin locus. Transcription of eRNAs was increased in concomitant with the increase in cross-linking frequency. These results show that chromatin looping and eRNA transcription precedes the transcriptional activation of gene. Concomitant occurrence of the two events suggests functional relationship between them. PMID:25588787

The Non-catalytic B Subunit of Coagulation Factor XIII Accelerates Fibrin Cross-linking*

PubMed Central

Souri, Masayoshi; Osaki, Tsukasa; Ichinose, Akitada

2015-01-01

Covalent cross-linking of fibrin chains is required for stable blood clot formation, which is catalyzed by coagulation factor XIII (FXIII), a proenzyme of plasma transglutaminase consisting of catalytic A (FXIII-A) and non-catalytic B subunits (FXIII-B). Herein, we demonstrate that FXIII-B accelerates fibrin cross-linking. Depletion of FXIII-B from normal plasma supplemented with a physiological level of recombinant FXIII-A resulted in delayed fibrin cross-linking, reduced incorporation of FXIII-A into fibrin clots, and impaired activation peptide cleavage by thrombin; the addition of recombinant FXIII-B restored normal fibrin cross-linking, FXIII-A incorporation into fibrin clots, and activation peptide cleavage by thrombin. Immunoprecipitation with an anti-fibrinogen antibody revealed an interaction between the FXIII heterotetramer and fibrinogen mediated by FXIII-B and not FXIII-A. FXIII-B probably binds the γ-chain of fibrinogen with its D-domain, which is near the fibrin polymerization pockets, and dissociates from fibrin during or after cross-linking between γ-chains. Thus, FXIII-B plays important roles in the formation of a ternary complex between proenzyme FXIII, prosubstrate fibrinogen, and activator thrombin. Accordingly, congenital or acquired FXIII-B deficiency may result in increased bleeding tendency through impaired fibrin stabilization due to decreased FXIII-A activation by thrombin and secondary FXIII-A deficiency arising from enhanced circulatory clearance. PMID:25809477

An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat.

PubMed

Kenney, S; Kamine, J; Markovitz, D; Fenrick, R; Pagano, J

1988-03-01

Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, we demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses.

Exercise and academic performance among nursing and kinesiology students at US colleges.

PubMed

Bellar, David; Judge, Lawrence W; Petersen, Jeffrey; Bellar, Ann; Bryan, Charity L

2014-01-01

Lack of physical activity is a contributor to the obesity epidemic and is speculated to relate to reduced academic performance; however, this link has yet to be examined within the college population. The purpose of this study in a group of undergraduate students, was to determine if aerobic exercise activity was related to academic performance. The participants for this study included 740 students at multiple universities enrolled in nursing and kinesiology studies. The participants completed the Leisure and Physical Activity Questionnaire. Pearson's χ(2) analysis revealed differences in grade point average with aerobic activity (χ(2) = 44.29, P ≤ 0.001) as well as a trend toward differences in grade point average with weightlifting activity (χ(2) = 22.69, P = 0.61). Based on these findings it can be suggested that college students engage in greater aerobic exercise.

The Association Between Sexual Satisfaction and Body Image in Women

PubMed Central

Pujols, Yasisca; Meston, Cindy M.; Seal, Brooke N.

2010-01-01

Introduction Although sexual functioning has been linked to sexual satisfaction, it only partially explains the degree to which women report being sexually satisfied. Other factors include quality of life, relational variables, and individual factors such as body image. Of the few studies that have investigated the link between body image and sexual satisfaction, most have considered body image to be a single construct and have shown mixed results. Aim The present study assessed multiple body image variables in order to better understand which aspects of body image influence multiple domains of sexual satisfaction, including sexual communication, compatibility, contentment, personal concern, and relational concern in a community sample of women. Methods Women between the ages of 18 and 49 years in sexual relationships (N = 154) participated in an Internet survey that assessed sexual functioning, five domains of sexual satisfaction, and several body image variables. Main Outcome Measures Body image variables included the sexual attractiveness, weight concern, and physical condition subscales of the Body Esteem Scale, the appearance-based subscale of the Cognitive Distractions During Sexual Activity Scale, and body mass index. Total score of the Sexual Satisfaction Scale for Women was the main outcome measure. Sexual functioning was measured by a modified Female Sexual Function Index. Results Consistent with expectations, correlations indicated significant positive relationships between sexual functioning, sexual satisfaction, and all body image variables. A multiple regression analysis revealed that sexual satisfaction was predicted by high body esteem and low frequency of appearance-based distracting thoughts during sexual activity, even after controlling for sexual functioning status. Conclusion Several aspects of body image, including weight concern, physical condition, sexual attractiveness, and thoughts about the body during sexual activity predict sexual satisfaction in women. The findings suggest that women who experience low sexual satisfaction may benefit from treatments that target these specific aspects of body image. PMID:19968771

Promoting Physical Activity in Middle School Girls: Trial of Activity for Adolescent Girls

PubMed Central

Webber, Larry S.; Catellier, Diane J.; Lytle, Leslie A.; Murray, David M.; Pratt, Charlotte A.; Young, Deborah R.; Elder, John P.; Lohman, Timothy G.; Stevens, June; Jobe, Jared B.; Pate, Russell R.

2008-01-01

Background Physical activity is important for weight control and good health; however, activity levels decline in the adolescent years, particularly in girls. Design Group randomized controlled trial Setting/participants Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States. Random, cross-sectional samples were drawn within schools: 6th graders in 2003 (n=1721) and 8th graders in 2005 (n=3504) and 2006 (n=3502). Intervention A 2-year study-directed intervention (fall 2003 to spring 2005) targeted schools, community agencies, and girls to increase opportunities, support, and incentives for increased physical activity. Components included programs linking schools and community agencies, physical education, health education, and social marketing. A third-year intervention used school and community personnel to direct intervention activities. Main outcome measures The primary outcome, daily MET-weighted minutes of moderate-to-vigorous physical activity (MET-weighted MVPA), was assessed using accelerometry. Percent body fat was assessed using anthropometry. Results After the staff-directed intervention (pre-stated primary outcome), there were no differences (mean= −0.4, 95% CI= CI= −8.2 to 7.4) in adjusted MET-weighted MVPA between 8th-grade girls in schools assigned to intervention or control. Following the Program Champion–directed intervention, girls in intervention schools were more physically active than girls in control schools (mean difference 10.9 MET-weighted minutes of MVPA, 95% CI=0.52–21.2). This difference is about 1.6 minutes of daily MVPA or 80 kcal per week. There were no differences in fitness or percent body fat at either 8th-grade timepoint. Conclusion A school-based, community-linked intervention modestly improved physical activity in girls. PMID:18312804

The Mechanisms Linking Health Literacy to Behavior and Health Status

PubMed Central

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

2011-01-01

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

Kinetics versus thermodynamics in materials modeling: The case of the di-vacancy in iron

NASA Astrophysics Data System (ADS)

Djurabekova, F.; Malerba, L.; Pasianot, R. C.; Olsson, P.; Nordlund, K.

2010-07-01

Monte Carlo models are widely used for the study of microstructural and microchemical evolution of materials under irradiation. However, they often link explicitly the relevant activation energies to the energy difference between local equilibrium states. We provide a simple example (di-vacancy migration in iron) in which a rigorous activation energy calculation, by means of both empirical interatomic potentials and density functional theory methods, clearly shows that such a link is not granted, revealing a migration mechanism that a thermodynamics-linked activation energy model cannot predict. Such a mechanism is, however, fully consistent with thermodynamics. This example emphasizes the importance of basing Monte Carlo methods on models where the activation energies are rigorously calculated, rather than deduced from widespread heuristic equations.

Reading, Writing, and Reserve: Literacy Activities are linked to Hippocampal Volume and Memory in Multiple Sclerosis

PubMed Central

Sumowski, James F.; Rocca, Maria A.; Leavitt, Victoria M.; Riccitelli, Gianna; Meani, Alessandro; Comi, Giancarlo; Filippi, Massimo

2016-01-01

Consistent with basic research on enriched environments and the cognitive reserve literature, greater engagement in cognitive leisure activities during early adulthood has been linked to preserved memory and larger hippocampal volume in persons with multiple sclerosis (MS). Herein we investigated which specific types of cognitive leisure activities contribute to reserve. Reading-writing activities were positively linked to (a) hippocampal volume within independent samples of Italian (n=187) and American (n=55) MS patients, and (b) memory in subsamples of Italian (n=97) and American (n=53) patients with memory data. Art-music and games-hobbies did not contribute. Findings directly inform the development of targeted evidence-based enrichment programs aiming to bolster reserve against memory decline. PMID:26920377

Time Use as Cause and Consequence of Youth Development

PubMed Central

Lam, Chun Bun; McHale, Susan M.

2014-01-01

From an ecological perspective, daily activities are both causes and consequences of youth development. As causes, daily activities represent distinct sets of socialization experiences that afford opportunities to acquire new competencies and behavioral patterns. As consequences, daily activities reflect youth’s force and resource characteristics, including developmental status, temperament and motivation, and pre-existing levels of adjustment. An ecological perspective also highlights the role of the larger sociocultural context in shaping and conditioning the links between daily activities and youth development. In this article, we draw on research with children and adolescents to consider how an ecological perspective can provide a flexible framework for studying time use as a developmental phenomenon. We also discuss methodological issues and suggest research that should be conducted in this broad area. PMID:25821514

Inability of keratinocytes lacking their specific transglutaminase to form cross-linked envelopes: Absence of envelopes as a simple diagnostic test for lamellar ichthyosis

PubMed Central

Jeon, Saewha; Djian, Philippe; Green, Howard

1998-01-01

Epidermal keratinocytes, late in their terminal differentiation, form cross-linked envelopes resistant to ionic detergent and reducing agent. Because the cross-linking process is catalyzed by the keratinocyte transglutaminase, the absence of active transglutaminase should result in failure of the keratinocyte to form a cross-linked envelope. Three keratinocyte strains bearing mutations in the keratinocyte transglutaminase were examined: two contained no detectable transglutaminase mRNA and none contained active enzyme. All three were unable to form cross-linked envelopes, either spontaneously in stratified cultures or upon induction with Ca2+. Although stratum corneum of normal humans and scales from patients with different ichthyotic diseases contain cross-linked envelopes, those from patients with transglutaminase-negative lamellar ichthyosis do not. Therefore, the disease due to the absence of transglutaminase may be readily distinguished from other ichthyotic diseases by a simple test for cross-linked envelopes. PMID:9435253

Behavior Change with Fitness Technology in Sedentary Adults: A Review of the Evidence for Increasing Physical Activity

PubMed Central

Sullivan, Alycia N.; Lachman, Margie E.

2017-01-01

Physical activity is closely linked with health and well-being; however, many Americans do not engage in regular exercise. Older adults and those with low socioeconomic status are especially at risk for poor health, largely due to their sedentary lifestyles. Fitness technology, including trackers and smartphone applications (apps), has become increasingly popular for measuring and encouraging physical activity in recent years. However, many questions remain regarding the effectiveness of this technology for promoting behavior change. Behavior change techniques such as goal setting, feedback, rewards, and social factors are often included in fitness technology. However, it is not clear which components are most effective and which are actually being used by consumers. We discuss additional strategies not typically included in fitness technology devices or apps that are promising for engaging inactive, vulnerable populations. These include action planning, restructuring negative attitudes, enhancing environmental conditions, and identifying other barriers to regular physical activity. We consider which strategies are most conducive to motivating behavior change among sedentary adults. Overall, fitness technology has the potential to significantly impact public health, research, and policies. We suggest ways in which app developers and behavior change experts can collaborate to develop successful apps. Advances are still needed to help inactive individuals determine how, when, where, and with whom they can increase their physical activity. PMID:28123997

Standard Local Operating Procedures for Endangered Species (SLOPES) for Selected Nationwide Permit Activities Affecting Bull Trout in Western Montana and Northern Idaho. Endangered Species Act Section 7 Consultation: Biological Opinion

DTIC Science & Technology

2013-05-17

include, in order of importance, non-native species, water withdrawals, angling and poaching , forestry practices management and legacy mining impacts ...Dunham et al. 2007, Isaak et al. 2010). A growing body of literature has linked these hydrologic trends with impacts to aquatic 31 ecosystems and...7 Impact Category 1 – Short-term Disturbance

America's Hero to the World, George C. Marshall. Teacher's Guide. Second Edition [and] Resource Packet [and] George C. Marshall: An American Leader. A Teacher's Notebook.

ERIC Educational Resources Information Center

Thompson, Rachel Yarnell; Sittig, Linda H.

This teaching unit about George C. Marshall contains a teacher's guide, a resource packet, and a teacher's notebook. The teacher's guide includes ten introductory, overarching, and culminating activities: (1) About this Guide; (2) Getting to Know Him; (3) Marshal on Video; (4) Share a Space with a Hero; (5) On a Global Stage--Links; (6) A Picture…

Que La Tortilla Se Vuelvai A History of U.S. Agribusiness Companies in Mexico. (May the Tortilla Return! A History of U.S. Agribusiness Companies in Mexico.)

ERIC Educational Resources Information Center

Murdy, Jack

1978-01-01

There is a direct link, today and historically, between Mexico's underdevelopment and maldistribution of wealth, and U.S. domination of Mexico's economy, including the current penetration by U.S. transnationals. Activity in the food production and processing industries is just one facet of the total picture, but one of the most important.…

Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

DTIC Science & Technology

2016-09-01

Denatured collagen was detec- ted with anticollagen antibody (1:1000). For integrin-blocking enzyme -linked immunosorbent assay, wells were coated with...migration on denatured collagen; it failed to reduce cell adhesion. Moreover a peptide antagonist of alpha 10 beta 1 may inhibit ovarian tumor growth in...stromal cell adhesion, migration and proliferation on distinct ECM substrates including native and denatured collagen. 4   D). As outlined in aim 2

Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

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

Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable andmore » stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.« less

Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

DOE PAGES

Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; ...

2015-04-21

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable andmore » stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.« less

Late Holocene and recent rainforest cultural landscapes of North Queensland, Australia

NASA Astrophysics Data System (ADS)

Steinberger, L. M.; Moss, P. T.; Haberle, S.; Cosgrove, R.; Ferrier

2011-12-01

The tropical rainforests of North Queensland, Australia, have been environments of significant human activity for several thousand years. Palaeoecological research has highlighted the long-term effects of Quaternary climate change on these environments at a broad spatial scale, including the expansion of tropical rainforest across the region following the termination of the Last Glacial Maximum. However, identifying the effects of a hunter-gatherer Aboriginal population has been more difficult. Palaeoecological suggestions of Pleistocene Aboriginal burning, based on pollen and charcoal records, have relied on coincident timing with a general narrative of colonisation rather than direct links with archaeological evidence. Current research is explicitly examining the environmental consequences of human activity in North Queensland rainforests by producing local palaeoecological data directly linked to sites and periods of human occupation. Pollen, macrocharcoal and phytolith records have been produced from sites of human activity within the rainforest. Late Holocene Aboriginal occupation of the rainforest is demonstrated to have had significant cultural links to patches of open vegetation that existed within the rainforest. While these patches are likely to have originated as edaphically controlled remnants of Pleistocene vegetation, their expansion and maintenance in the late Holocene is associated with increasing intensity of Aboriginal occupation of the rainforest. Late Holocene Aboriginal rainforest occupation is also contrasted with the historical European colonisation of the rainforest in the late 19th century, which resulted in the most significant environmental changes in the region since the early Holocene. Historical and ethnographic records provide important cultural context for understanding the transition between Aboriginal and European cultural landscapes of the rainforest.

Medicinal plant activity on Helicobacter pylori related diseases

PubMed Central

Wang, Yuan-Chuen

2014-01-01

More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention. PMID:25132753

Medicinal plant activity on Helicobacter pylori related diseases.

PubMed

Wang, Yuan-Chuen

2014-08-14

More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention.

Linking Formal and Informal Science Education: A Successful Model using Libraries, Volunteers and NASA Resources

NASA Astrophysics Data System (ADS)

Race, M. S.; Lafayette Library; Learning Center Foundation (Lllcf)

2011-12-01

In these times of budget cuts, tight school schedules, and limited opportunities for student field trips and teacher professional development, it is especially difficult to expose elementary and middle school students to the latest STEM information-particularly in the space sciences. Using our library as a facilitator and catalyst, we built a volunteer-based, multi-faceted, curriculum-linked program for students and teachers in local middle schools (Grade 8) and showcased new astronomical and planetary science information using mainly NASA resources and volunteer effort. The project began with the idea of bringing free NASA photo exhibits (FETTU) to the Lafayette and Antioch Libraries for public display. Subsequently, the effort expanded by adding layers of activities that brought space and science information to teachers, students and the pubic at 5 libraries and schools in the 2 cities, one of which serves a diverse, underserved community. Overall, the effort (supported by a pilot grant from the Bechtel Foundation) included school and library based teacher workshops with resource materials; travelling space museum visits with hands-on activities (Chabot-to-Go); separate powerpoint presentations for students and adults at the library; and concurrent ancillary space-related themes for young children's programs at the library. This pilot project, based largely on the use of free government resources and online materials, demonstrated that volunteer-based, standards-linked STEM efforts can enhance curriculum at the middle school, with libraries serving a special role. Using this model, we subsequently also obtained a small NASA-Space Grant award to bring star parties and hand-on science activities to three libraries this Fall, linking with numerous Grade 5 teachers and students in two additional underserved areas of our county. It's not necessary to reinvent the wheel, you just collect the pieces and build on what you already have.

Social networking sites: emerging and essential tools for communication in dermatology.

PubMed

Amir, Mahsa; Sampson, Blake P; Endly, Dawnielle; Tamai, Jennifer M; Henley, Jill; Brewer, Ann Chang; Dunn, Jeffrey H; Dunnick, Cory A; Dellavalle, Robert P

2014-01-01

The use of social media by dermatology journals and professional and patient-centered dermatology organizations remains largely unknown and, to our knowledge, has yet to be fully evaluated. To evaluate and quantify the extent of involvement of dermatology journals, professional dermatology organizations, and dermatology-related patient advocate groups on social networking sites. We obtained an archived list of 102 current dermatology journals from SCImago on the World Wide Web and used the list to investigate Facebook, Twitter, and individual journal websites for the presence of social media accounts. We identified professional and patient-centered dermatology organization activity on social networks through queries of predetermined search terms on Google, Facebook, Twitter, and LinkedIn. The activity of each entity was documented by recording the following metrics of popularity: the numbers of Facebook "likes," Twitter "followers," and LinkedIn "members." The numbers of Facebook likes, Twitter followers, and LinkedIn members corresponding to each dermatology journal and each professional and patient-related dermatology organization. On July 17, 2012, of the 102 dermatology journals ranked by SCImago, 12.7% were present on Facebook and 13.7% on Twitter. We identified popular dermatology journals based on Facebook likes and Twitter followers, led by the Journal of the American Academy of Dermatology and Dermatology Times, respectively. Popular professional dermatology organizations included dermRounds Dermatology Network (11 251 likes on Facebook and 2900 followers on Twitter). The most popular dermatology patient-centered organizations were the Skin Cancer Foundation (20 119 likes on Facebook), DermaTalk (21 542 followers on Twitter), and the National Psoriasis Foundation (200 members on LinkedIn). Patient-centered and professional dermatology organizations use social networking sites; however, academic journals tend to lag behind significantly. Although some journals are active in social media, most have yet to recognize the potential benefits of fully embracing popular social networks.

Characterization of a water-soluble polysaccharide from Boletus edulis and its antitumor and immunomodulatory activities on renal cancer in mice.

PubMed

Wang, Dong; Sun, Shu-Qing; Wu, Wei-Zhen; Yang, Shun-Liang; Tan, Jian-Ming

2014-05-25

A polysaccharide (BEP, Mw=113,432Da) was purified from Boletus edulis, which had a backbone consisting of (1→6)-linked-α-d-glucopyranosyl, (1→2,6)-linked-α-d-galactopyranosyl, (1→6)-linked-α-d-galactopyranosyl, and (1→3)-linked-α-d-rhamnopyranosyl residues, which were branched at O-2 position of (1→2,6)-linked-α-d-galactopyranosyl residue with a single terminal (1→)-linked-α-l-arabinofuranosyl residue. After 32 days' BEP administration to Renca tumor bearing mice, the tumor mass of Renca transplanted in mice was significantly repressed. Furthermore, BEP could significantly increase the spleen and thymus indices, stimulate splenocytes proliferation, augment NK cell and CTL activities in spleen, and promote the secretion of the cytokines IL-2 and TNF-α in Renca tumor bearing mice. Meanwhile oral administration of BEP (100 and 400mg/kg) restored all the altered hematological and biochemical parameters of tumor-bearing mice to normal levels. Thus, these data demonstrate that BEP possesses potential immunomodulatory activity and might be employed as effective therapeutic agents for the prevention of renal caner. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch

PubMed Central

Morales-Lázaro, Sara L.; Llorente, Itzel; Sierra-Ramírez, Félix; López-Romero, Ana E.; Ortíz-Rentería, Miguel; Serrano-Flores, Barbara; Simon, Sidney A.; Islas, León D.; Rosenbaum, Tamara

2016-01-01

The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation. PMID:27721373

Linking Microbial Community Structure, Activity and Carbon Cycling in Biological Soil Crust

NASA Astrophysics Data System (ADS)

Swenson, T.; Karaoz, U.; Swenson, J.; Bowen, B.; Northen, T.

2016-12-01

Soils play a key role in the global carbon cycle, but the relationships between soil microbial communities and metabolic pathways are poorly understood. In this study, biological soil crusts (biocrusts) from the Colorado Plateau are being used to develop soil metabolomics methods and statistical models to link active microbes to the abundance and turnover of soil metabolites and to examine the detailed substrate and product profiles of individual soil bacteria isolated from biocrust. To simulate a pulsed activity (wetting) event and to analyze the subsequent correlations between soil metabolite dynamics, community structure and activity, biocrusts were wetup with water and samples (porewater and DNA) were taken at various timepoints up to 49.5 hours post-wetup. DNA samples were sequenced using the HiSeq sequencing platform and porewater metabolites were analyzed using untargeted liquid chromatography/ mass spectrometry. Exometabolite analysis revealed the release of a breadth of metabolites including sugars, amino acids, fatty acids, dicarboxylic acids, nucleobases and osmolytes. In general, many metabolites (e.g. amino acids and nucleobases) immediately increased in abundance following wetup and then steadily decreased. However, a few continued to increase over time (e.g. xanthine). Interestingly, in a previous study exploring utilization of soil metabolites by sympatric bacterial isolates from biocrust, we observed xanthine to be released by some Bacilli sp. Furthermore, our current metagenomics data show that members of the Paenibacillaceae family increase in abundance in late wetup samples. Previous 16S amplicon data also show a "Firmicutes bloom" following wetup with the new metagenomic data resolving this at genome-level. Our continued metagenome and exometabolome analyses are allowing us to examine complex pulsed-activity events in biocrust microbial communities specifically by correlating the abundance of microbes to the release of soil metabolites. Ultimately, these approaches will provide an important complement to sequencing efforts linking soil microbes and soil metabolites to enable genomic sciences approaches for understanding and modeling soil carbon cycling.

Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8/19.

PubMed

Park, Min Ju; Shen, Hailian; Spaeth, Jason M; Tolvanen, Jaana H; Failor, Courtney; Knudtson, Jennifer F; McLaughlin, Jessica; Halder, Sunil K; Yang, Qiwei; Bulun, Serdar E; Al-Hendy, Ayman; Schenken, Robert S; Aaltonen, Lauri A; Boyer, Thomas G

2018-03-30

Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at high frequency in uterine fibroids (UFs) and breast fibroepithelial tumors as well as recurrently, albeit less frequently, in malignant uterine leimyosarcomas, chronic lymphocytic leukemias, and colorectal cancers. Previously, we reported that UF-linked mutations in MED12 disrupt its ability to activate cyclin C (CycC)-dependent kinase 8 (CDK8) in Mediator, implicating impaired Mediator-associated CDK8 activity in the molecular pathogenesis of these clinically significant lesions. Notably, the CDK8 paralog CDK19 is also expressed in myometrium, and both CDK8 and CDK19 assemble into Mediator in a mutually exclusive manner, suggesting that CDK19 activity may also be germane to the pathogenesis of MED12 mutation-induced UFs. However, whether and how UF-linked mutations in MED12 affect CDK19 activation is unknown. Herein, we show that MED12 allosterically activates CDK19 and that UF-linked exon 2 mutations in MED12 disrupt its CDK19 stimulatory activity. Furthermore, we find that within the Mediator kinase module, MED13 directly binds to the MED12 C terminus, thereby suppressing an apparent UF mutation-induced conformational change in MED12 that otherwise disrupts its association with CycC-CDK8/19. Thus, in the presence of MED13, mutant MED12 can bind, but cannot activate, CycC-CDK8/19. These findings indicate that MED12 binding is necessary but not sufficient for CycC-CDK8/19 activation and reveal an additional step in the MED12-dependent activation process, one critically dependent on MED12 residues altered by UF-linked exon 2 mutations. These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in UFs. © 2018 Park et al.

Environmental influences on food choice, physical activity and energy balance.

PubMed

Popkin, Barry M; Duffey, Kiyah; Gordon-Larsen, Penny

2005-12-15

In this paper, the environment is defined as the macro- and community-level factors, including physical, legal and policy factors, that influence household and individual decisions. Thus, environment is conceived as the external context in which household and individual decisions are made. This paper reviews the literature on the ways the environment affects diet, physical activity, and obesity. Other key environmental factors discussed include economic, legal, and policy factors. Behind the major changes in diet and physical activity in the US and globally lie large shifts in food production, processing, and distribution systems as well as food shopping and eating options, resulting in the increase in availability of energy-dense foods. Similarly, the ways we move at home, work, leisure, and travel have shifted markedly, resulting in substantial reductions in energy expenditure. Many small area studies have linked environmental shifts with diet and activity changes. This paper begins with a review of environmental influences on diet and physical activity, and includes the discussion of two case studies on environmental influences on physical activity in a nationally representative sample of US adolescents. The case studies illustrate the important role of physical activity resources and the inequitable distribution of such activity-related facilities and resources, with high minority, low educated populations at strong disadvantage. Further, the research shows a significant association of such facilities with individual-level health behavior. The inequity in environmental supports for physical activity may underlie health disparities in the US population.

Mental Well-Being and Sport-Related Identities in College Students

PubMed Central

Miller, Kathleen E.; Hoffman, Joseph H.

2010-01-01

Past research has linked physical activity and sports participation with improved mental and social well-being, including reduced risk of depression and suicidality. In this study we examined relationships among several dimensions of athletic involvement (team sport participation, individual sport participation, athlete identity, and jock identity), gender, and depression and suicidal behavior in a sample of 791 undergraduate students. Both participation in a team sport and athlete identity were associated with lower depression scores. Athlete identity was also associated with lower odds of a past-year suicide attempt, whereas jock identity was associated with elevated odds of a suicide attempt. The findings are discussed in light of the relationship between mental well-being and a larger constellation of health-risk behaviors linked to a “toxic jock” identity. PMID:20661467

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

PubMed Central

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

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

PubMed

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

2004-01-01

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

Typologies of sexually explicit media use among MSM: An application of latent class analysis

PubMed Central

Erickson, Darin J.; Galos, Dylan L; Smolenski, Derek, J.; Iantaffi, Alex; Rosser, B.R. Simon

2014-01-01

The viewing of sexually explicit media (SEM) is widespread, especially among men, and research linking SEM viewing and sexual behavior has shown a variety of results, some positive (e.g., sexuality education) and some negative (e.g., poorer body image). These results might be due to limitations in measuring SEM consumption, particularly around typology. The goal of the current study was to examine potential patterns of SEM viewing activities. Using data from an online survey of men who have sex with men (MSM), we conducted latent class analyses of 15 SEM activities. Results suggested a three-class solution. The most prevalent class included over 60% of men and was characterized by viewing primarily safer-sex or conventional behaviors. The second class included 32% of men and had a similar albeit amplified pattern of viewing. The final class included just 7% of men and was marked by high levels of viewing of all activities, including fetish and kink. Compared to the conventional or safer-sex class, the other classes had lower internalized homonegativity, lower condom use self-efficacy, and higher SEM consumption or dose. Implications for HIV prevention, sexuality research and the SEM industry are discussed. PMID:25642301

Towards Improved Linkage of Disaster Risk Reduction and Climate Change Adaptation in Health: A Review.

PubMed

Banwell, Nicola; Rutherford, Shannon; Mackey, Brendan; Chu, Cordia

2018-04-18

Climate change and climate-sensitive disasters significantly impact health. Linking Disaster Risk Reduction (DRR) and Climate Change Adaptation (CCA) is essential for addressing these ever present, complex and increasing risks. Recent calls have been made to build these links in health. However, there is a need to clearly articulate why linking DRR and CCA is important in health. Furthermore, little is known about how DRR and CCA should be linked in health. By extensively examining relevant literature, this review presents the current state of knowledge of linking DRR and CCA in health. This includes the potential for maximising conceptual synergies such as building resilience, and reducing vulnerability and risk. Additionally, technical and operational synergies are identified to link DRR and CCA in health, including: policy, Early Warning Systems, vulnerability and risk assessment, health systems strengthening, infrastructure resilience, disaster preparedness and response, and health impact pathways. Public health actors have a central role in building these links due to their expertise, work functions, and experience in addressing complex health risks. The review concludes with recommendations for future research, including how to better link DRR and CCA in health; and the opportunities, challenges and enablers to build and sustain these links.

FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch.

PubMed

Chen, Yulong; Terajima, Masahiko; Banerjee, Priyam; Guo, Houfu; Liu, Xin; Yu, Jiang; Yamauchi, Mitsuo; Kurie, Jonathan M

2017-04-05

Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and -wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde-derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities.

FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch

PubMed Central

Chen, Yulong; Terajima, Masahiko; Banerjee, Priyam; Guo, Houfu; Liu, Xin; Yu, Jiang; Yamauchi, Mitsuo; Kurie, Jonathan M.

2017-01-01

Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and –wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde–derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities. PMID:28378777

Links between personality, time perspective, and intention to practice physical activity during cancer treatment: an exploratory study.

PubMed

Villaron, Charlène; Marqueste, Tanguy; Eisinger, François; Cappiello, Maria-Antonietta; Therme, Pierre; Cury, François

2017-04-01

The purpose of the study was to analyze links between personality, time perspective, and intention to practice physical activity during cancer treatment. One hundred forty-three patients participated in survey by questionnaire. Intention to practice physical activity, time perspective using Zimbardo Time Perspective Inventory, and personality with the Big Five Inventory were measured. Structural equation models using Lisrel were developed to examine hypothetical links between the variables. The adjusted model evidenced an excellent fit (comparative fit index = 0.92; root-mean-square error of approximation = 0.076; P = .014). Results showed that intention to practice exercise was positively linked with openness to experience and negatively with present fatalist time perspective. Moreover, conscientiousness and neuroticism were found to be linked with future time perspective, which was positively related with intention to practice physical activity. The present exploratory study with patients suffering from cancer underlined the importance of considering jointly time perspective dimensions and personality factors for health behavior recommendations. Based on our results, we propose some reflections on practice to help nurses and physicians increase patient's motivation to be physically active. Taking into account patients' personality and time perspective, we would be able to propose specific awareness messages and offer short interventions to have an impact on patients' motivation to practice. Copyright © 2016 John Wiley & Sons, Ltd.

Diarylsulfonamides and their bioisosteres as dual inhibitors of alkaline phosphatase and carbonic anhydrase: Structure activity relationship and molecular modelling studies.

PubMed

Al-Rashida, Mariya; Ejaz, Syeda Abida; Ali, Sharafat; Shaukat, Aisha; Hamayoun, Mehwish; Ahmed, Maqsood; Iqbal, Jamshed

2015-05-15

The effect of bioisosteric replacement of carboxamide linking group with sulfonamide linking group, on alkaline phosphatase (AP) and carbonic anhydrase (CA) inhibition activity of aromatic benzenesulfonamides was investigated. A series of carboxamide linked aromatic benzenesulfonamides 1a-1c, 2a-2d and their sulfonamide linked bioisosteres 3a-3d, 4a-4d was synthesized and evaluated for inhibitory activity against bovine tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase (IAP) and bCA II. A significant increase in CA inhibition activity was observed upon bioisosteric replacement of carboxamide linking group with a sulfonamide group. Some of these compounds were identified as highly potent and selective AP inhibitors. Compounds 1b, 2b, 3d, 4d 5b and 5c were found to be selective bTNAP inhibitors, whereas compounds 1a, 1c, 2a, 2c, 2d, 3a, 3c, 4a, 4b, 4c, 5a were found to be selective bIAP inhibitors. For most active AP inhibitor 3b, detailed kinetic studies indicated a competitive mode of inhibition against tissue non-specific alkaline phosphatase (TNAP) and non-competitive mode of inhibition against intestinal alkaline phosphatase (IAP). Molecular docking studies were carried out to rationalize important binding site interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20.

PubMed

Lin, Su-Chang; Chung, Jee Y; Lamothe, Betty; Rajashankar, Kanagalaghatta; Lu, Miao; Lo, Yu-Chih; Lam, Amy Y; Darnay, Bryant G; Wu, Hao

2008-02-15

Nuclear factor kappaB (NF-kappaB) activation in tumor necrosis factor, interleukin-1, and Toll-like receptor pathways requires Lys63-linked nondegradative polyubiquitination. A20 is a specific feedback inhibitor of NF-kappaB activation in these pathways that possesses dual ubiquitin-editing functions. While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. To elucidate the molecular basis for the DUB activity of A20, we determined its crystal structure and performed a series of biochemical and cell biological studies. The structure reveals the potential catalytic mechanism of A20, which may be significantly different from papain-like cysteine proteases. Ubiquitin can be docked onto a conserved A20 surface; this interaction exhibits charge complementarity and no steric clash. Surprisingly, A20 does not have specificity for Lys63-linked polyubiquitin chains. Instead, it effectively removes Lys63-linked polyubiquitin chains from TRAF6 without dissembling the chains themselves. Our studies suggest that A20 does not act as a general DUB but has the specificity for particular polyubiquitinated substrates to assure its fidelity in regulating NF-kappaB activation in the tumor necrosis factor, interleukin-1, and Toll-like receptor pathways.

Suppressed epidemics in multirelational networks

NASA Astrophysics Data System (ADS)

Xu, Elvis H. W.; Wang, Wei; Xu, C.; Tang, Ming; Do, Younghae; Hui, P. M.

2015-08-01

A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1 -p , respectively. The fraction of infected nodes ρ (p ) shows a nonmonotonic behavior, with ρ drops with p for small p and increases for large p . For small to moderate w1/w0 ratios, ρ (p ) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range pL≤p ≤pR , and an active phase with mixed infected and healthy nodes for p pR . A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clusters. A theory that uses the possible local environments of a node as variables is formulated. The theory gives results in good agreement with simulation results, thereby showing the necessity of including longer spatial correlations.

Intrinsic brain subsystem associated with dietary restraint, disinhibition and hunger: an fMRI study.

PubMed

Zhao, Jizheng; Li, Mintong; Zhang, Yi; Song, Huaibo; von Deneen, Karen M; Shi, Yinggang; Liu, Yijun; He, Dongjian

2017-02-01

Eating behaviors are closely related to body weight, and eating traits are depicted in three dimensions: dietary restraint, disinhibition, and hunger. The current study aims to explore whether these aspects of eating behaviors are related to intrinsic brain activation, and to further investigate the relationship between the brain activation relating to these eating traits and body weight, as well as the link between function connectivity (FC) of the correlative brain regions and body weight. Our results demonstrated positive associations between dietary restraint and baseline activation of the frontal and the temporal regions (i.e., food reward encoding) and the limbic regions (i.e., homeostatic control, including the hypothalamus). Disinhibition was positively associated with the activation of the frontal motivational system (i.e., OFC) and the premotor cortex. Hunger was positively related to extensive activations in the prefrontal, temporal, and limbic, as well as in the cerebellum. Within the brain regions relating to dietary restraint, weight status was negatively correlated with FC of the left middle temporal gyrus and left inferior temporal gyrus, and was positively associated with the FC of regions in the anterior temporal gyrus and fusiform visual cortex. Weight status was positively associated with the FC within regions in the prefrontal motor cortex and the right ACC serving inhibition, and was negatively related with the FC of regions in the frontal cortical-basal ganglia-thalamic circuits responding to hunger control. Our data depicted an association between intrinsic brain activation and dietary restraint, disinhibition, and hunger, and presented the links of their activations and FCs with weight status.

Daily Rhythmic Behaviors and Thermoregulatory Patterns Are Disrupted in Adult Female MeCP2-Deficient Mice

PubMed Central

Wu, Chiping; Bardakjian, Berj L.; Zhang, Liang; Eubanks, James H.

2012-01-01

Mutations in the X-linked gene encoding Methyl-CpG-binding protein 2 (MECP2) have been associated with neurodevelopmental and neuropsychiatric disorders including Rett Syndrome, X-linked mental retardation syndrome, severe neonatal encephalopathy, and Angelman syndrome. Although alterations in the performance of MeCP2-deficient mice in specific behavioral tasks have been documented, it remains unclear whether or not MeCP2 dysfunction affects patterns of periodic behavioral and electroencephalographic (EEG) activity. The aim of the current study was therefore to determine whether a deficiency in MeCP2 is sufficient to alter the normal daily rhythmic patterns of core body temperature, gross motor activity and cortical delta power. To address this, we monitored individual wild-type and MeCP2-deficient mice in their home cage environment via telemetric recording over 24 hour cycles. Our results show that the normal daily rhythmic behavioral patterning of cortical delta wave activity, core body temperature and mobility are disrupted in one-year old female MeCP2-deficient mice. Moreover, female MeCP2-deficient mice display diminished overall motor activity, lower average core body temperature, and significantly greater body temperature fluctuation than wild-type mice in their home-cage environment. Finally, we show that the epileptiform discharge activity in female MeCP2-deficient mice is more predominant during times of behavioral activity compared to inactivity. Collectively, these results indicate that MeCP2 deficiency is sufficient to disrupt the normal patterning of daily biological rhythmic activities. PMID:22523589

PTB’S Time and Frequency Activities in 2006: New DCF77 Electronics, New NTP Servers, and Calibration Activities

DTIC Science & Technology

2007-01-01

PTTI) Meeting ( TWSTFT ) is being routinely performed with several European and US stations. On the initiative of NICT, a TWSTFT link was...During the last 2 years, PTB has upgraded its TWSTFT and GPS capabilities in order to achieve better reliability and robustness against system failures...NTP-server, and, briefly, the calibration of the international time links, i.e. the result of the latest calibration of the TWSTFT links to the USNO

P-glycoprotein ATPase activity requires lipids to activate a switch at the first transmission interface.

PubMed

Loo, Tip W; Clarke, David M

2016-04-01

P-glycoprotein (P-gp) is an ABC (ATP-Binding Cassette) drug pump. A common feature of ABC proteins is that they are organized into two wings. Each wing contains a transmembrane domain (TMD) and a nucleotide-binding domain (NBD). Drug substrates and ATP bind at the interface between the TMDs and NBDs, respectively. Drug transport involves ATP-dependent conformational changes between inward- (open, NBDs far apart) and outward-facing (closed, NBDs close together) conformations. P-gps crystallized in the presence of detergent show an open structure. Human P-gp is inactive in detergent but basal ATPase activity is restored upon addition of lipids. The lipids might cause closure of the wings to bring the NBDs close together to allow ATP hydrolysis. We show however, that cross-linking the wings together did not activate ATPase activity when lipids were absent suggesting that lipids may induce other structural changes required for ATPase activity. We then tested the effect of lipids on disulfide cross-linking of mutants at the first transmission interface between intracellular loop 4 (TMD2) and NBD1. Mutants L443C/S909C and L443C/R905C but not G471C/S909C and V472C/S909C were cross-linked with oxidant when in membranes. The mutants were then purified and cross-linked with or without lipids. Mutants G471C/S909C and V472C/S909C cross-linked only in the absence of lipids whereas mutants L443C/S909C and L443C/R905C were cross-linked only in the presence of lipids. The results suggest that lipids activate a switch at the first transmission interface and that the structure of P-gp is different in detergents and lipids. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Tunable Enzymatic Activity and Enhanced Stability of Cellulase Immobilized in Biohybrid Nanogels.

PubMed

Peng, Huan; Rübsam, Kristin; Jakob, Felix; Schwaneberg, Ulrich; Pich, Andrij

2016-11-14

This paper reports a facile approach for encapsulation of enzymes in nanogels. Our approach is based on the use of reactive copolymers able to get conjugated with enzyme and build 3D colloidal networks or biohybrid nanogels. In a systematic study, we address the following question: how the chemical structure of nanogel network influences the biocatalytic activity of entrapped enzyme? The developed method allows precise control of the enzyme activity and improvement of enzyme resistance against harsh store conditions, chaotropic agents, and organic solvents. The nanogels were constructed via direct chemical cross-linking of water-soluble reactive copolymers poly(N-vinylpyrrolidone-co-N-methacryloxysuccinimide) with proteins such as enhanced green fluorescent protein (EGFP) and cellulase in water-in-oil emulsion. The water-soluble reactive copolymers with controlled amount of reactive succinimide groups and narrow dispersity were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Poly(ethylene glycol) bis(3-aminopropyl) and branched polyethylenimine were utilized as model cross-linkers to optimize synthesis of nanogels with different architectures in the preliminary experiments. Biofluorescent nanogels with different loading amount of EGFP and varying cross-linking densities were obtained. We demonstrate that the biocatalytic activity of cellulase-conjugated nanogels (CNG) can be elegantly tuned by control of their cross-linking degrees. Circular dichroism (CD) spectra demonstrated that the secondary structures of the immobilized cellulase were changed in the aspect of α-helix contents. The secondary structures of cellulase in highly cross-linked nanogels were strongly altered compared with loosely cross-linked nanogels. The fluorescence resonance energy transfer (FRET) based study further revealed that nanogels with lower cross-linking degree enable higher substrate transport rate, providing easier access to the active site of the enzyme. The biohybrid nanogels demonstrated significantly improved stability in preserving enzymatic activity compared with free cellulase. The functional biohybrid nanogels with tunable enzymatic activity and improved stability are promising candidates for applications in biocatalysis, biomass conversion, or energy utilization fields.

Supporting awareness through collaborative brushing and linking of tabular data.

PubMed

Hajizadeh, Amir Hossein; Tory, Melanie; Leung, Rock

2013-12-01

Maintaining an awareness of collaborators' actions is critical during collaborative work, including during collaborative visualization activities. Particularly when collaborators are located at a distance, it is important to know what everyone is working on in order to avoid duplication of effort, share relevant results in a timely manner and build upon each other's results. Can a person's brushing actions provide an indication of their queries and interests in a data set? Can these actions be revealed to a collaborator without substantially disrupting their own independent work? We designed a study to answer these questions in the context of distributed collaborative visualization of tabular data. Participants in our study worked independently to answer questions about a tabular data set, while simultaneously viewing brushing actions of a fictitious collaborator, shown directly within a shared workspace. We compared three methods of presenting the collaborator's actions: brushing & linking (i.e. highlighting exactly what the collaborator would see), selection (i.e. showing only a selected item), and persistent selection (i.e. showing only selected items but having them persist for some time). Our results demonstrated that persistent selection enabled some awareness of the collaborator's activities while causing minimal interference with independent work. Other techniques were less effective at providing awareness, and brushing & linking caused substantial interference. These findings suggest promise for the idea of exploiting natural brushing actions to provide awareness in collaborative work.