Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 mu M epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion protein to laminin gamma 1 chain

The prion protein (PrP(C)) is highly expressed in the nervous system, and its abnormal conformer is associated with prion diseases. PrP(C) is anchored to cell membranes by glycosylphosphatidylinositol, and transmembrane proteins are likely required for PrP(C)-mediated intracellular signaling. Binding of laminin (Ln) to PrP(C) modulates neuronal plasticity and memory. We addressed signaling pathways triggered by PrP(C)-Ln interaction in order to identify transmembrane proteins involved in the transduction of PrP(C)-Ln signals. The Ln gamma 1-chain peptide, which contains the Ln binding site for PrP(C), induced neuritogenesis through activation of phospholipase C (PLC), Ca(2+) mobilization from intracellular stores, and protein kinase C and extracellular signal-regulated kinase (ERK1/2) activation in primary cultures of neurons from wild-type, but not PrP(C)-null mice. Phage display, coimmunoprecipitation, and colocalization experiments showed that group I metabotropic glutamate receptors (mGluR1/5) associate with PrP(C). Expression of either mGluR1 or mGluR5 in HEK293 cells reconstituted the signaling pathways mediated by PrP(C)-Ln gamma 1 peptide interaction. Specific inhibitors of these receptors impaired PrP(C)-Ln gamma 1 peptide-induced signaling and neuritogenesis. These data show that group I mGluRs are involved in the transduction of cellular signals triggered by PrP(C)-Ln, and they support the notion that PrP(C) participates in the assembly of multiprotein complexes with physiological functions on neurons.-Beraldo, F. H., Arantes, C. P., Santos, T. G., Machado, C. F., Roffe, M., Hajj, G. N., Lee, K. S., Magalhaes, A. C., Caetano, F. A., Mancini, G. L., Lopes, M. H., Americo, T. A., Magdesian, M. H., Ferguson, S. S. G., Linden, R., Prado, M. A. M., Martins, V. R. Metabotropic glutamate receptors trans-duce signals for neurite outgrowth after binding of the prion protein to laminin gamma 1 chain. FASEB J. 25, 265-279 (2011). www.fasebj.org

Can't Get No Satisfaction: Lessons Learned while Developing an Assessment of Faculty Awareness and Attitudes towards Library Services

The presentation was offered as part of the CUNY Library Assessment Conference, Reinventing Libraries: Reinventing Assessment, held at the City University of New York in June 2014.

På gott och ont : En kvalitativ studie om ungdomars upplevelser av vistelsen på HVB-hemmet Närsjögläntan

Syftet med denna uppsats är att undersöka hur ungdomar som varit placerade på Närsjögläntans HVB-hem har upplevt sin vistelse och vilka implikationer som vistelsen medfört. Våra frågeställningar berör hur ungdomar ha upplevt tiden på Närsjögläntan, hur livet efter placeringen ser ut och hur de lyckats att anpassa sig till livet utanför institutionen samt hur ungdomarnas liv såg ut innan placeringen på Närsjögläntan i förhållande till livet efteråt.Den empiriska undersökningen har utförts genom ostrukturerade kvalitativa intervjuer med fem respondenter. Vår forskningsansats grundar sig i hermeneutiken och vår undersöknings- och analysmetod influeras av grounded theory. Våra teoretiska perspektiv utgår från E. Goffmans teori om totala institutioner och G. H. Meads socialisationsteori.De slutsatser vi drar utifrån denna studie är att ungdomarna upplever att Närsjögläntan i allmänhet och personalen i synnerhet har haft en stor betydelse för deras förbättrade livssituation och självbild efter placeringen. Dock framgår att livssituationen efter vistelsen innefattar viss kvarvarande problematik som till viss del är beroende av negativa konsekvenser som institutionsvistelsen fört med sig.

Konsekvenser av rollövertagandet : ”I”, ”me” och individualiteten

Consequences of role taking: the ”I”, the ”me” and individuality This paper analyzes the tendency of taking the ”I” and the ”me” in G. H. Meads theory of role taking as two separate, qualitatively different parts of human personality, the ”I” being of individual origin, the ”me” of social. In the original Meadian sense role taking gives rise to both the ”I” and the ”me”. They are dialectically united rather than dualistically separated aspects. They refer to the joint functional power of the subject, finding itself as an object, mediated by the Other. As a consequence, the link between body and the social world becomes theoretically more stringent, as the body is given its place as a cognitive social object among others, this by contrast to interpretations where the body is left as an object mainly outside the human social experience and as a source of agency sui generis, a conception which is in opposition to Meads. The stress on the ”I”-phase, as related to body and concrete action in combination with its direct relation to the ”me”-phase, actualizes Mead as a forerunner in modern biologic/neurologic research on human perceptual, motivational and intentional capacity.Swedish Mead interpreters are critically analyzed. Interpretations of Charon, Giddens, Joas and Habermas are partly scrutinized. The author defines the conceptual pair in terms of activity, subjectivity, temporal relativity and distance.

Motståndets betydelse : Ett bidrag till aktör-strukturdebatten

The significance of inhibition: a contribution to the agency-structure debate A central problem in social theory today is how to integrate agency and structure. The vital question is how to explain social reality by proceeding from both the notion of people doing things which affect the social relationships in which they are embedded (agency) and the idea of the social context moulding social activity (structure). Sociologists as Pierre Bourdieu, Anthony Giddens and Jürgen Habermas call attention to social practices as the ”missing link” between agency and structure. In accentuating social practices, the aim is to explain how people in their daily encounters actively contribute to the production and reproduction of social structures. This article puts forth the posthumous contribution of George Herbert Mead to the agency-structure debate. I argue that his social pragmatist theory gives us a compound and thorough– but not fully recognized – explanation of the dynamics and the course of events in structurally framed encounters. By especially emphasizing the importance Mead ascribes to the inhibited social act, I examine how his theory deepens the understanding of social practices as a bridge between agency and structure.

Självet, rollerna och pågående koordinationer av mänskliga handlingar : Om att försöka se ’samhället’ som något annat än fängelse eller marionetteater

The self, roles and the ongoing coordination of human action. Trying to see ‘society’ as neither prison nor puppet theatre In the article it is argued that structural North-American role-sociology may be integrated with theories emphasizing ‘society’ as ongoing processes (f. ex. Giddens’ theory of structuration). This is possible if the concept of role is defined as a recurrence oriented to the action of others standing out as a regularity in a societal process. But this definition makes it necessary to in a fundamental way understand what kind of social being the role-actor is. This is done with the help of Hans Joas’ theory of creativity and Merleau-Pontys concept of ‘flesh’ arguing that Meads concept of the ‘I’ maybe understood as an embodied self-asserting I, which at least in reflexive modernity has the creative power to split Meads ‘me’ into a self-voiced subject-me and an other voiced object-me. The embodied I communicating with the subject-me may be viewed as that role-actor which is something else than the role played. But this kind of role-actor is making for new troubles because it is hard to understand how this kind of self is creating self-coherence by using Meads concept of ‘the generalized other’. This trouble is handled by using Alain Touraines concept of the ‘subject’ and arguing that the generalized other is dissolving in de-modernized modernity. In split modernity self-coherence may instead be created by what in the article is called the generalized subject. This concept means a kind of communicative future based evaluation, which has its base in the ‘subject’ opposing the split powers of both the instrumentality of markets and of life-worlds trying to create ‘fundamentalistic’ self-identities. This kind of self is communicative because it also must respect the other as ‘subject’. It exists only in the battle against the forces of the market or a community. It never constructs an ideal city or a higher type of individual. It creates and protects a clearing that is constantly being invaded, to use the words of the old Frenchman himself. Asa kind of test-case it is by the way in the article shown how Becks concept of individualization may be understood in a deeply social and role-sociological way.

Upregulation of Sadness During Films

Testing the relative effectiveness of reappraisal and exaggeration in upregulating sadness.

An Injection-locked Diode Laser for Cold Rydberg Atom Experiments

A free-running, temperature stabilized diode laser has been injection-locked to an external cavity diode laser for use in cold Rydberg atom experiments. Cold rubidium atoms in a magneto-optical trap (MOT) are excited to Rydberg states using a 10 ns laser pulse. The Rydberg atoms spontaneously ionize due to dipole forces, and the collisional ionization dynamics are observed as a function of atom density and principal quantum number of the Rydberg state, n. The injection-locked diode laser will be used as a repumper in conjunction with a dark spontaneous-force optical trap (SPOT) to increase the Rydberg state density. We report on the design of the injection-locked laser system.