Structural diversity of neuronal calcium sensor proteins and insights for activation of retinal guanylyl cyclase by GCAP1.

Neuronal calcium sensor (NCS) proteins, a sub-branch of the calmodulin superfamily, are expressed in the brain and retina where they transduce calcium signals and are genetically linked to degenerative diseases. The amino acid sequences of NCS proteins are highly conserved but their physiological functions are quite different. Retinal recoverin controls Ca(2) (+)-dependent inactivation of light-excited rhodopsin during phototransduction, guanylyl cyclase activating proteins 1 and 2 (GCAP1 and GCAP2) promote Ca(2) (+)-dependent activation of retinal guanylyl cyclases, and neuronal frequenin (NCS-1) modulates synaptic activity and neuronal secretion. Here we review the molecular structures of myristoylated forms of NCS-1, recoverin, and GCAP1 that all look very different, suggesting that the attached myristoyl group helps to refold these highly homologous proteins into different three-dimensional folds. Ca(2) (+)-binding to both recoverin and NCS-1 cause large protein conformational changes that ejects the covalently attached myristoyl group into the solvent exterior and promotes membrane targeting (Ca(2) (+)-myristoyl switch). The GCAP proteins undergo much smaller Ca(2) (+)-induced conformational changes and do not possess a Ca(2) (+)-myristoyl switch. Recent structures of GCAP1 in both its activator and Ca(2) (+)-bound inhibitory states will be discussed to understand structural determinants that control their Ca(2) (+)-dependent activation of retinal guanylyl cyclases

The genus Sipha Passerini (Hemiptera: Aphididae) in North America

Five species of the aphid genus Sipha Passerini (Hemiptera: Aphididae) are reported in North America and are reviewed herein. Of these species, three are adventive species and include: Sipha elegans del Guercio, Sipha glyceriae (Kaltenbach), and Sipha maydis Passerini. Sipha maydis was discovered in California in 2007 and now has been found in Georgia. The genus also includes two native species: Sipha agropyronensis (Gillette) and Sipha flava (Forbes). Sipha maydis can be distinguished easily from all the other species in the genus that occur in North America because it is black. All the species except S. agropyronensis have been implicated in damage to crop plants. A key to the apterae and alatae of Sipha found in North America is included

Comments on the Emergence and Persistence of Inequality in Premodern Societies

The author discusses the development and persistence of permanent inequality in human societies. He comments on an article which undertakes inequality in premodern societies and proposed that intergenerational wealth transmission is the reason for the evolution and persistence of inequality, mentioning the three categories of wealth including material, relational, and embodied

A marine reservoir effect ΔR value for Kitandach, in Prince Rupert Harbour, British Columbia, Canada

Prince Rupert Harbour (PRH), on the north Pacific Coast of British Columbia, contains at least 157 shell middens, of which 66 are known villages, in an area of approximately 180 km. These sites span the last 9500 yr and in some cases are immense, exceeding 20,000 m surface area and several meters in depth. Recent archaeological research in PRH has become increasingly reliant on radiocarbon dates from marine shell for developing chronologies. However, this is problematic as the local marine reservoir effect (MRE) remains poorly understood in the region. To account for the MRE and to better date the Harbour’s sites, we propose a ΔR of 273 ± 38 for the PRH area, based on our work at the site of Kitandach (GbTo-34), a massive shell midden-village centrally located within the Harbour. We followed the multiple paired sample approach for samples from speci fic contexts and ensured contemporaneity within the groups of marine and terrestrial materials by statistically assessing for outliers using the χ2 test. Taking together, the results for this and previous studies, it appears the MRE was fairly constant over the past 5000 yr

Depression and Empathy Predict Emotion-Modulated Startle Reactivity

Research supports varied patterns of emotion-modulated startle (EMS) reactivity among depressed individuals. The purpose of this study was to examine whether these varied patterns can be explained by depression, empathic tendencies, and emotional stimuli. The EMS paradigm is a well-validated measure of emotion-modulated reactivity in which the magnitude of startle reflexes in reaction to acoustic stimuli are recorded while participants view pleasant, neutral, and negative images (Lang, Bradley, & Cuthbert, 1990). Young adults (N = 120; Mage = 19.54, SD = 1.41; 75% female) completed self-report rating scales of depression symptoms and cognitive and affective empathic tendencies and the EMS paradigm. Individuals with low depression, regardless of their cognitive (hp2 = .44 and .47) and affective empathic tendencies (hp2 = .49 and .36), and individuals with high depression and high cognitive and affective empathic tendencies (hp2 = .23, .46, respectively) exhibited the typical linear EMS reactivity pattern of increasing startle reflex magnitude from pleasant to neutral to unpleasant images. In contrast, individuals with high depression along with low cognitive and affective empathic tendencies exhibited blunted EMS reactivity patterns (hp2 = .000, .04, respectively). These findings indicate blunted EMS reactivity patterns only in depressed individuals who have low cognitive and affective empathic tendencies and are likely disengaged from emotional stimuli, thus suggesting variability among depressed individuals in motivational states that prime or inhibit the startle reflex

Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.info:eu-repo/semantics/publishedVersio

Episodic Learning with Control Lyapunov Functions for Uncertain Robotic Systems

Many modern nonlinear control methods aim to endow systems with guaranteed properties, such as stability or safety, and have been successfully applied to the domain of robotics. However, model uncertainty remains a persistent challenge, weakening theoretical guarantees and causing implementation failures on physical systems. This paper develops a machine learning framework centered around Control Lyapunov Functions (CLFs) to adapt to parametric uncertainty and unmodeled dynamics in general robotic systems. Our proposed method proceeds by iteratively updating estimates of Lyapunov function derivatives and improving controllers, ultimately yielding a stabilizing quadratic program model-based controller. We validate our approach on a planar Segway simulation, demonstrating substantial performance improvements by iteratively refining on a base model-free controller