Humor as a Reward Mechanism: Event-Related Potentials in the Healthy and Diseased Brain

Humor processing involves distinct processing stages including incongruity detection, emotional response, and engagement of mesolimbic reward regions. Dysfunctional reward processing and clinical symptoms in response to humor have been previously described in both hypocretin deficient narcolepsy-cataplexy (NC) and in idiopathic Parkinson disease (PD). For NC patients, humor is the strongest trigger for cataplexy, a transient loss of muscle tone, whereas dopamine-deficient PD-patients show blunted emotional responses to humor. To better understand the role of reward system and the various contributions of hypocretinergic and dopaminergic mechanisms to different stages of humor processing we examined the electrophysiological response to humorous and neutral pictures when given as reward feedback in PD, NC and healthy controls. Humor compared to neutral feedback demonstrated modulation of early ERP amplitudes likely corresponding to visual processing stages, with no group differences. At 270 ms post-feedback, conditions showed topographical and amplitudinal differences for frontal and left posterior electrodes, in that humor feedback was absent in PD patients but increased in NC patients. We suggest that this effect relates to a relatively early affective response, reminiscent of increased amygdala response reported in NC patients. Later ERP differences, corresponding to the late positive potential, revealed a lack of sustained activation in PD, likely due to altered dopamine regulation in reward structures in these patients. This research provides new insights into the temporal dynamics and underlying mechanisms of humor detection and appreciation in health and disease.     

Increased or decreased levels of Caenorhabditis elegans lon-3, a gene encoding a collagen,cause reciprocal changes in body length

Body length in C. elegans is regulated by a member of the TGFbeta family, DBL-1. Loss-of-function mutations in dbl-1, or in genes encoding components of the signaling pathway it activates, cause worms to be shorter than wild type and slightly thinner (Sma). Overexpression of dbl-1 confers the Lon phenotype characterized by an increase in body length. We show here that loss-of-function mutations in dbl-1 and lon-1, respectively, cause a decrease or increase in the ploidy of nuclei in the hypodermal syncytial cell, hyp7. To learn more about the regulation of body length in C. elegans we carried out a genetic screen for new mutations causing a Lon phenotype. We report here the cloning and characterization of lon-3. lon-3 is shown to encode a putative cuticle collagen that is expressed in hypodermal cells. We show that, whereas putative null mutations in lon-3 (or reduction of lon-3 activity by RNAi) causes a Lon phenotype, increasing lon-3 gene copy number causes a marked reduction in body length. Morphometric analyses indicate that the lon-3 loss-of-function phenotype resembles that caused by overexpression of dbl-1. Furthermore, phenotypes caused by defects in dbl-1 or lon-3 expression are in both cases suppressed by a null mutation in sqt-1, a second cuticle collagen gene. However, whereas loss of dbl-1 activity causes a reduction in hypodermal endoreduplication, the reduction in body length associated with overexpression of lon-3 occurs in the absence of defects in hypodermal ploidy.     

Sampling a diverse flora for novel biochemicals: An analysis of NCI collections from Madagascar

An analysis of the taxonomic composition of 6,496 samples of plants collected for the National Cancer Institute is conducted and the results are presented. The results show that collecting has been highly biased towards woody plant families, as these species are often abundant, they yield samples of multiple parts, and it is often easy to collect sufficient material for isolation of chemicals present in low concentration. Conversely, herbaceous plants that are small or grow in sparse populations are underrepresented in collections. Three of the ten generically most diverse families in Madagascar have not been sampled, and of these ten families, only Rubiaceae and Euphorbiaceae have had greater numbers of samples collected than predicted if collecting was random. The causes of this bias are discussed, and solutions to ensure that bioprospecting efforts gather samples reflective of the diversity present are presented.

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Echantillonage d’une flore diverse pour des nouveaux composes biochimiques: Une Analyze des Collections de NCI Recoltees a Madagascar

Zusammenfassung  Une analyze de la composition taxonomique de 6496 échantillons recoltés pour le National Cancer Institute est conduite et les resultants obtenus montrent que la récolte a été foretment biaisée, tendant pour une forte proportion des families des plantes ligneuses don’t les espèces sont souvent abondantes, peuvent fournir plusieurs sortes d’échantillon et souvent permettent facilement de collecter suffisament des matérielles pour l’isolation des composes chimiques presents à faible concentration. Contrairement, les plantes herbacées que sont de petites tailles our qui poussent avec des populations clairsemées sont sous representées dans les collections. Trois parmi les dix families génériquement les plus diversifies n’ont pas été recoltées, et de ces dix families, seules les Rubiaceae el les Euphorbiaceae ont eu les plus grands nombres d’échantillons que prévus si la récolte a été fait au hazard. Les cause de cette disproportion sont discutées et les solutions pour assurer que les efforts de bioprospection rassemblent des échantillons reflétant la diversité présente sont presentées.

     

Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype

Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. Given that the aif hypomorphic harlequin (Hq) mutant mouse model displays severe sarcopenia, we examined skeletal muscle from the aif hypomorphic mice in more detail. Adult AIF-deficient skeletal myofibers display oxidative stress and a severe form of atrophy, associated with a loss of myonuclei and a fast to slow fiber type switch, both in "slow" muscles such as soleus, as well as in "fast" muscles such as extensor digitorum longus, most likely resulting from an increase of MEF2 activity. This fiber type switch was conserved in regenerated soleus and EDL muscles of Hq mice subjected to cardiotoxin injection. In addition, muscle regeneration in soleus and EDL muscles of Hq mice was severely delayed. Freshly cultured myofibers, soleus and EDL muscle sections from Hq mice displayed a decreased satellite cell pool, which could be rescued by pretreating aif hypomorphic mice with the manganese-salen free radical scavenger EUK-8. Satellite cell activation seems to be abnormally long in Hq primary culture compared to controls. However, AIF deficiency did not affect myoblast cell proliferation and differentiation. Thus, AIF protects skeletal muscles against oxidative stress-induced damage probably by protecting satellite cells against oxidative stress and maintaining skeletal muscle stem cell number and activation.     

Evolution of prehistoric lithic industries of the Philippines during the Pleistocene

During the past ten years, our knowledge of Paleolithic industries in the Philippines has grown thanks to new excavations and discoveries of stone implements, but also thanks to new studies on older collections. The study of knapped stones in the Philippines dates back to the 1920s. At this time, stone tools were used as type fossils to propose an initial chronology of prehistoric cultures. Later, taxonomies and functional analyses were used to assess lithic assemblages until the end of the 1990s. Current functional technology and traceological methods allow us to propose new hypotheses about prehistoric behavior during the Pleistocene, and also technological developments across the archipelago during the Paleolithic.     

Human B-cell differentiation by Fc fragment of IgG. I. Fc fragment from human IgG induces plasma cell generation but cannot induce lymphocyte proliferation

Circulating mononuclear cells (MNC) from normal donors were examined for lymphocyte proliferation and plasma cell differentiation following stimulation by Fc and Fab fragments or by intact IgG. Lymphocyte differentiation and DNA synthesis were examined as a function of culture duration and concentration of Fc, Fab fragments, and IgG. Plasma cells containing intracytoplasmic Ig were demonstrated by immunofluorescence with a polyvalent antiserum to human immunoglobulin and with specific antisera (anti-mu, -gamma, -alpha, -delta, -kappa, and -lambda chains). DNA synthesis of mononuclear cells cultures was analyzed by measuring [3H]thymidine incorporation. The results indicated that only the Fc fragments are able to induce the differentiation of B cells. The polyclonal plasma cell response to Fc fragments was dose dependent, peaked on the sixth day of culture, and was isotypically diverse (IgM greater than IgA greater than IgG). This activity requires the presence of T helper cells and monocytes. In contrast, the Fc fragments were unable to induce a proliferative response.     

Regulation of a presynaptic adenylate cyclase from bovine cerebellum by β-adrenergic receptors

Intact crude synaptosomes from bovine cerebellum contain, in addition to an externally accessible (postsynaptic) adenylate cyclase, an enzyme with its catalytic center oriented towards the inside of the synaptosome (presynaptic adenylate cyclase). This is demonstrated by the unmasking of latent adenylate cyclase activity by Triton X-100. Furthermore, intact crude synaptosomes can synthesize cyclic AMP from adenine. This synthesis takes place inside the synaptosome as the postsynaptic adenylate cyclase is inactive in the Krebs-Ringer buffer. Presynaptic adenylate cyclase activity is not influenced by depolarization, as shown by [³H]adenine pulse-labeling, but is stimulated by (?)-norepinephrine and (?)-isoproterenol. (±)-Propranolol inhibits this stimulation whereas phentolamine has no effect, suggesting the presence of a β-adrenergic receptor-coupled presynaptic adenylate cyclase.