(Table S1) Age determination of ODP Site 202-1240

Interannual-decadal variability in the equatorial Pacific El Niño-Southern Oscillation (ENSO) induces climate changes at global scale, but its potential influence during past global climate change is not yet well constrained. New high-resolution eastern equatorial Pacific proxy records of thermocline conditions present new evidence of strong orbital control in ENSO-like variability over the last 275,000 years. Recurrent intervals of saltier thermocline waters are associated with the dominance of La Niña-like conditions during glacial terminations, coinciding with periods of low precession and high obliquity. The parallel dominance of d13C-depleted waters supports the advection of Antarctic origin waters toward the tropical thermocline. This "oceanic tunneling" is proposed to have reinforced orbitally induced changes in ENSO-like variability, composing a complex high- and low-latitude feedback during glacial terminations.

Operational characterisation of a Micro-SME producing farmhouse cheese in the south of Venezuela

A piece of research is presented that was conducted on the Guayanes Farmhouse Telita Cheese Producers Network located in the Piar and Padre Chien rural municipalities of Bolivar state in Venezuela. Guayanes telita cheese is a regional dairy product. The producers are to be found in a rural area with a high potential for marketing the label in the Southern Common Market (MERCOSUR). This market is the focal point of the strategic importance of this study for the Region and the Country. The research is of a descriptive scope conducted in the field. A questionnaire based on good food production practice was used as a data gathering technique. The final sample comprised 30 production units. Statistical processing was performed with version 15.2 of the STATGRAPHICS Centurion computational tool. The results would appear to confirm previous studies that point to the existence of factors that prevent these Micro-SMEs from guaranteeing the food safety of the product. The results indicate that new lines of research need to be opened up. These are oriented towards formulating strategies for the continuous improvement of these micro-SMEs, including quality control indicators.

Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice

Heart failure is accompanied by severely impaired β-adrenergic receptor (βAR) function, which includes loss of βAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of βAR function is agonist-stimulated receptor phosphorylation by the βAR kinase (βARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in βAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of βARK1 or the β2AR were mated into a genetic model of murine heart failure (MLP−/−). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP−/− and MLP−/−/β2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP−/−/βARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP−/−/βARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP−/− mice but less than controls. Importantly, heightened βAR desensitization in the MLP−/− mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the βARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal βAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit βARK1 as a novel mode of therapy.

Be Careful Where You Smile : Culture Shapes Judgments of Intelligence and Honesty of Smiling Individuals

We thank all the supporting team-members involved in the translation procedures and data collections. Research was supported by the Polish NCN Grant 2011/03/N/HS6/05112 (K.K.) and Chinese NNSF Grant 31200788 (C.X).

Domain-specific gene disruption reveals critical regulation of neuregulin signaling by its cytoplasmic tail

Neuregulins are a multi-isoform family of growth factors that activate members of the erbB family of receptor tyrosine kinases. The membrane-anchored isoforms contain the receptor-activating ligand in their extracellular domain, a single membrane-spanning region, and a long cytoplasmic tail. To evaluate the potential biological role of the intracellular domain of the membrane-anchored neuregulin isoforms, we used a domain-specific gene disruption approach to produce a mouse line in which only the region of the neuregulin gene encoding almost the entire intracellular domain was disrupted. Consistent with previous reports in which all neuregulin isoforms were disrupted, the resulting homozygous neuregulin mutants died at E10.5 of circulatory failure and displayed defects in neural and cardiac development. To further understand these in vivo observations, we evaluated a similarly truncated neuregulin construct after transient expression in COS-7 cells. This cytoplasmic tail-deleted mutant, unlike wild-type neuregulin isoforms, was resistant to proteolytic release of its extracellular-domain ligand, a process required for erbB receptor activation. Thus, proteolytic processing of the membrane-bound neuregulin isoforms involved in cranial ganglia and heart embryogenesis is likely developmentally regulated and is critically controlled by their intracellular domain. This observation indicates that erbB receptor activation by membrane-bound neuregulins most likely involves a unique temporally and spatially regulated “inside-out” signaling process that is critical for processing and release of the extracellular-domain ligand.