The Role of Gender Information in Pronoun Resolution: Evidence from Chinese

Although previous studies have consistently demonstrated that gender information is used to resolve pronouns, the mechanisms underlying the use of gender information continue to be controversial. The present study used event-related potentials (ERPs) to investigate whether working memory modulates the effect of gender information on pronoun resolution. The critical pronoun agreed or disagreed with its antecedent in gender. Moreover, the distance between a pronoun and its antecedent was varied to assess the influence of working memory. Compared with the congruent pronouns, the incongruent pronouns elicited an N400 effect in the short distance condition and a P600 effect in the long distance condition. The results suggest that the effect of gender information on pronoun comprehension is modulated by working memory

Right hemisphere has the last laugh: neural dynamics of joke appreciation

Understanding a joke relies on semantic, mnemonic, inferential, and emotional contributions from multiple brain areas. Anatomically constrained magnetoencephalography (aMEG) combining high-density whole-head MEG with anatomical magnetic resonance imaging allowed us to estimate where the humor-specific brain activations occur and to understand their temporal sequence. Punch lines provided either funny, not funny (semantically congruent), or nonsensical (incongruent) replies to joke questions. Healthy subjects rated them as being funny or not funny. As expected, incongruous endings evoke the largest N400m in left-dominant temporo-prefrontal areas, due to integration difficulty. In contrast, funny punch lines evoke the smallest N400m during this initial lexical–semantic stage, consistent with their primed “surface congruity” with the setup question. In line with its sensitivity to ambiguity, the anteromedial prefrontal cortex may contribute to the subsequent “second take” processing, which, for jokes, presumably reflects detection of a clever “twist” contained in the funny punch lines. Joke-selective activity simultaneously emerges in the right prefrontal cortex, which may lead an extended bilateral temporo-frontal network in establishing the distant unexpected creative coherence between the punch line and the setup. This progression from an initially promising but misleading integration from left frontotemporal associations, to medial prefrontal ambiguity evaluation and right prefrontal reprocessing, may reflect the essential tension and resolution underlying humor

Association between Protective and Deleterious HLA Alleles with Multiple Sclerosis in Central East Sardinia

The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13–0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26–2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS

A Role for Thrombospondin-1 Deficits in Astrocyte-Mediated Spine and Synaptic Pathology in Down's Syndrome

Down's syndrome (DS) is the most common genetic cause of mental retardation. Reduced number and aberrant architecture of dendritic spines are common features of DS neuropathology. However, the mechanisms involved in DS spine alterations are not known. In addition to a relevant role in synapse formation and maintenance, astrocytes can regulate spine dynamics by releasing soluble factors or by physical contact with neurons. We have previously shown impaired mitochondrial function in DS astrocytes leading to metabolic alterations in protein processing and secretion. In this study, we investigated whether deficits in astrocyte function contribute to DS spine pathology.Using a human astrocyte/rat hippocampal neuron coculture, we found that DS astrocytes are directly involved in the development of spine malformations and reduced synaptic density. We also show that thrombospondin 1 (TSP-1), an astrocyte-secreted protein, possesses a potent modulatory effect on spine number and morphology, and that both DS brains and DS astrocytes exhibit marked deficits in TSP-1 protein expression. Depletion of TSP-1 from normal astrocytes resulted in dramatic changes in spine morphology, while restoration of TSP-1 levels prevented DS astrocyte-mediated spine and synaptic alterations. Astrocyte cultures derived from TSP-1 KO mice exhibited similar deficits to support spine formation and structure than DS astrocytes.These results indicate that human astrocytes promote spine and synapse formation, identify astrocyte dysfunction as a significant factor of spine and synaptic pathology in the DS brain, and provide a mechanistic rationale for the exploration of TSP-1-based therapies to treat spine and synaptic pathology in DS and other neurological conditions

A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils.

We report here that a monomeric de novo designed alpha-helix-turn-alpha-helix peptide, alpha t alpha, when incubated at 37 degrees C in an aqueous buffer at neutral pH, forms nonbranching, protease resistant fibrils that are 6-10 nm in diameter. These fibrils are rich in beta-sheet and bind the amyloidophilic dye Congo red. alpha t alpha fibrils thus display the morphologic, structural, and tinctorial properties of authentic amyloid fibrils. Surprisingly, unlike fibrils formed by peptides such as the amyloid beta-protein or the islet amyloid polypeptide, alpha t alpha fibrils were not toxic to cultured rat primary cortical neurons or PC12 cells. These results suggest that the potential to form fibrils under physiologic conditions is not limited to those proteins associated with amyloidoses and that fibril formation alone is not predictive of cytotoxic activity