Growth Hormone Secretagogues Protect Mouse Cardiomyocytes from in vitro Ischemia/Reperfusion Injury through Regulation of Intracellular Calcium

Background: Ischemic heart disease is a leading cause of mortality. To study this disease, ischemia/reperfusion (I/R) models are widely used to mimic the process of transient blockage and subsequent recovery of cardiac coronary blood supply. We aimed to determine whether the presence of the growth hormone secretagogues, ghrelin and hexarelin, would protect/improve the function of heart from I/R injury and to examine the underlying mechanisms. Methodology/Principal Findings: Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus. Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments. In freshly isolated cardiomyocytes from these hearts, single cell shortening, intracellular calcium ([Ca ] ) transients and caffeine-releasable sarcoplasmic reticulum (SR) Ca were measured. In addition, RT-PCR and Western blots were used to examine the expression level of GHS receptor type 1a (GHS-R1a), and phosphorylated phospholamban (p-PLB), respectively. Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca ] transient amplitude and caffeine-releasable SR Ca content after I/R through recovery of p-PLB. GHS-R1a antagonists, [D-Lys3]-GHRP-6 (200 nM) and BIM28163 (100 nM), completely blocked the effects of GHS on both cell shortening and [Ca ] transients. Conclusion/Significance: Through activation of GHS-R1a, ghrelin and hexarelin produced a positive inotropic effect on ischemic cardiomyocytes and protected them from I/R injury probably by protecting or recovering p-PLB (and therefore SR Ca content) to allow the maintenance or recovery of normal cardiac contractility. These observations provide supporting evidence for the potential therapeutic application of ghrelin and hexarelin in patients with cardiac I/R injury

Integrated parentheticals in quotations and free indirect discourse

Free Indirect Discourse and Quotations are introduced by a special kind of parentheticals, minimally constituted by a subject and a predicate of saying, thinking etc. I propose that these parentheticals are represented in a syntactic structure integrated with that of the reported sentence. The phrases hosting the parentheticals are projected by prosody oriented heads, i.e., heads which do not express a lexical content, but are read at the syntax-phonology interface as special instructions for realizing the peculiar intonation associated to parentheticals, the so-called comma intonation. I show that this approach offers several advantages, contributing in solving some long standing problems connected with the syntactic status of parentheticals in general.In this chapter I consider the syntactic properties of a particular kind of parentheticals, those introducing Quotations – henceforth, QU – and Free Indirect Discourse – henceforth, FID. Consider the following examples: (1) I will leave tomorrow, said John (2) The new ration did not start till tomorrow and he had only four cigarettes left, thought Winston (adapted, from Orwell 1984). Example (1) is a QU structure and the parenthetical in question is said John. Example (2) is a FID construction and the parenthetical is thought Winston. As already well known, they have special properties from an interpretive, syntactic and phonological point of view. QU and FID parentheticals are alike under many points of view, even if the two constructions must be kept separate, especially with respect to the interpretation of pronouns and verbal forms. For the purposes of this work, I will in general consider them alike. Observe now the following paradigm: (3) John said that Mary left (4) John said: “Mary left” (5) Maria, said John, left. It seems to me that the most important goal for a syntactic analysis is to provide a coherent analysis of the similarities and differences among the constructions in (3)- (5). At first sight, these structures seem very much alike, both from the point of view of their meaning and their syntax – to the extent that some scholars have proposed a direct syntactic derivation (Emonds 1973; Ross 1973), for instance of (5) starting from (3). I will show here that the situation is indeed much more complex than that. In particular, in this paper I show that example (5) is closer to (4) than to (3). The approach I will develop here is an integrated view of parentheticals, complying with Kayne’s (1994) Linear Correspondence Axiom (LCA)

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Towards a Fine-Grained Theory of Focus

This paper investigates the roles of focus, arguing that such a notion is too wide and can be applied to several phenomena. I show that focus needs to be further specified for (at least) another feature and is therefore made of smaller primitive traits. These can combine to create bundles of features, which give rise to the several types of foci we know. Moreover, these features are subject to parametrization and can thus account for cross-linguistic differences

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person