Transglutaminase 2 null macrophages respond to lipopolysaccharide stimulation by elevated proinflammatory cytokine production due to an enhanced αvβ3 integrin-induced Src tyrosine kinase signaling

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with several additional biochemical functions. Loss of TG2 in vivo results in impaired phagocytosis of apoptotic cells and altered proinflammatory cytokine production by macrophages engulfing apoptotic cells leading to autoimmunity. It has been proposed that TG2 acts as an integrin ß(3) coreceptor in the engulfment process, while altered proinflammatory cytokine production is related to the lack of latent TGFß activation by TG2 null macrophages. Here we report that TG2 null macrophages respond to lipopolysaccharide treatment by elevated IL-6 and TNFa production. Though TGFß has been proposed to act as a feed back regulator of proinflammatory cytokine production in LPS-stimulated macrophages, this phenomenon is not related to the lack of active TGFß production. Instead, in the absence of TG2 integrin ß(3) maintains an elevated basal Src family kinase activity in macrophages, which leads to enhanced phosphorylation and degradation of the I?Ba. Low basal levels of I?Ba explain the enhanced sensitivity of TG2 null macrophages to signals that regulate NF-?B. Our data suggest that TG2 null macrophages bear a proinflammatory phenotype, which might contribute to the enhanced susceptibility of these mice to develop autoimmunity and atherosclerosis.

Total factor productivity and the spillover hypothesis: some new evidence

In this paper I test the spillover hypothesis of the endogenous growth literature on a sample of manufacturing firms in Italy, 1989–1994, using a new approach based on the Malmquist index. First, I measure the productivity growth registered by the high- and non-high-tech firms computing the Malmquist index with DEA. I decompose it into technical change and technical efficiency change. Then I test whether the technical change registered by high-tech firms affects productivity growth of non-high-tech firms, after controlling for factors which can potentially affect productivity growth.

The temporal binding deficit hypothesis of autism

Frith has argued that people with autism show “weak central coherence,” an unusual bias toward piecemeal rather than configurational processing and a reduction in the normal tendency to process information in context. However, the precise cognitive and neurological mechanisms underlying weak central coherence are still unknown. We propose the hypothesis that the features of autism associated with weak central coherence result from a reduction in the integration of specialized local neural networks in the brain caused by a deficit in temporal binding. The visuoperceptual anomalies associated with weak central coherence may be attributed to a reduction in synchronization of high-frequency gamma activity between local networks processing local features. The failure to utilize context in language processing in autism can be explained in similar terms. Temporal binding deficits could also contribute to executive dysfunction in autism and to some of the deficits in socialization and communication.

Language against the odds, or rather not:the weak central coherence hypothesis and language

EV is a child with a talent for learning language combined with Asperger syndrome. EV’s talent is evident in the unusual circumstances of her acquisition of both her first (Bulgarian) and second (German) languages and the unique patterns of both receptive and expressive language (in both the L1 and L2), in which she shows subtle dissociations in competence and performance consistent with an uneven cognitive profile of skills and abilities. We argue that this case provides support for theories of language learning and usage that require more general underlying cognitive mechanisms and skills. One such account, the Weak Central Coherence (WCC) hypothesis of autism, provides a plausible framework for the interpretation of the simultaneous co-occurrence of EV’s particular pattern of cognitive strengths and weaknesses. Furthermore, we show that specific features of the uneven cognitive profile of Asperger syndrome can help explain the observed language talent displayed by EV. Thus, rather than demonstrating a case where language learning takes place despite the presence of deficits, EV’s case illustrates how a pattern of strengths within this profile can specifically promote language learning.

Beyond the aspect hypothesis:tense-aspect development in advanced L2 French

The Aspect Hypothesis (AH) claims that the association of any verb category (lexical aspect) with any grammatical aspect (perfective or imperfective) constitutes the endpoint of acquisition. The present book evaluates the explanatory power of the Aspect Hypothesis for the acquisition of French past tenses, which constitutes a serious stumbling block for foreign learners, even at the highest levels of proficiency. The present research applies the Aspect Hypothesis to the production of 61 Anglophone 'advanced learners' in a tutored environment. In so doing, it tests concurrent explanations, including the influence of the input, the influence of chunking, and the hypothesis of cyclic development. It discusses the cotextual and contextual factors that still provoke «non-native glitches» at the final stage of the Aspect Hypothesis. The book shows that the AH fails to account for the complex phenomenon of past tense development, as it adopts a local and linear approach.

Color categories: confirmation of the relativity hypothesis

The question of whether language affects our categorization of perceptual continua is of particular interest for the domain of color where constraints on categorization have been proposed both within the visual system and in the visual environment. Recent research (Roberson, Davies, & Davidoff, 2000; Roberson et al., in press) found substantial evidence of cognitive color differences between different language communities, but concerns remained as to how representative might be a tiny, extremely remote community. The present study replicates and extends previous findings using additional paradigms among a larger community in a different visual environment. Adult semi-nomadic tribesmen in Southern Africa carried out similarity judgments, short-term memory and long-term learning tasks. They showed different cognitive organization of color to both English and another language with the five color terms. Moreover, Categorical Perception effects were found to differ even between languages with broadly similar color categories. The results provide further evidence of the tight relationship between language and cognition.

Hypothesis: is Alzheimer's disease a metal-induced immune disorder?

A hypothesis that a metal-induced immune disorder may be involved in the pathogenesis of some forms of Alzheimer's disease (AD) is presented. The classical complement pathway is activated in AD and T cells and reactive microglia appear in the brain. Studies of metal induced autoimmunity and the use of compounds containing aluminium as vaccine adjuvants suggest that metals can activate complement and can be taken up by antigen presenting cells. The consequent immune response could contribute to neuronal damage, beta-amyloid deposition and cell death. The strengths and weaknesses of this hypothesis are discussed and tests of some aspects are proposed.

The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis"

The most influential theory to explain the pathogenesis of Alzheimer's disease (AD) has been the "Amyloid Cascade Hypothesis" (ACH) first formulated in 1992. The ACH proposes that the deposition of ß-amyloid (Aß) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.

La politique linguistique et l'avenir du Francais au Mexique:etude du cas de l'universite de Veracruz

In a linguistic context where it seems the entire world is only interested in learning English, it is worth considering the idea of whether French still has a place in Mexico. In spite of the predominance of English, there is nevertheless a feeling that French remains alive in Mexico, and indeed in certain areas has retained its strength and appeal. This hypothesis was to put to the test by exploring the current linguistic environment prevalent in the state of Veracruz. An investigation in the form of questionnaires and interviews of all those connected to the teaching of French (including students, teachers and employees and directors of language schools) shows that the desire of the Mexican government of promoting English for everyone is not necessarily consistent with the desire and expectations of the general populace. This in turn suggest the need of adopting a policy that enables us not only to take into consideration what people seem to be telling us regarding the learning of foreign learning but also of what they are not telling us. If the teaching and learning of French as a foreign language remains strong in Veracruz, it is explained much more by the long and friendly relationship that people in the state have had with French people (and their culture) than it is by any instrumental needs of learning their language. This is seen in the fact that students here consistently describe their motivation for learning French from an emotional or affective standpoint rather than from professional one. It seems that the ties between the Mexican and French people remain solid. Another interesting characteristic of students of French in Veracruz is the positive attitude they seem to have regarding languages in general, which in turn enables them to take further advantage of the benefits made available from globalization. In reality, there exists no rivalry between French and English and therefore it is unnecessary to adopt measures that would address such struggle. It is however a matter of great urgency that authorities in the arenas of politics and academia take a closer look at the policies they design regarding the study of foreign languages in general, and that they consider, specifically, a wholly alternative to the one language model of teaching and learning of foreign language – in this case English-, a model that for all intents and purposes has failed. In the midst of a globalized world, and during this current period of increased linguistic activity, the aforementioned assertions serve not only to support my initial hypothesis, but also to help shake off the dust of some out-dated belief systems and lay down the framework for a new, better informed and well thought-out policy of foreign languages planning.

Self-assembly of trehalose molecules on a lysozyme surface: the broken glass hypothesis

To help understand how sugar interactions with proteins stabilise biomolecular structures, we compare the three main hypotheses for the phenomenon with the results of long molecular dynamics simulations on lysozyme in aqueous trehalose solution (0.75 M). We show that the water replacement and water entrapment hypotheses need not be mutually exclusive, because the trehalose molecules assemble in distinctive clusters on the surface of the protein. The flexibility of the protein backbone is reduced under the sugar patches supporting earlier findings that link reduced flexibility of the protein with its higher stability. The results explain the apparent contradiction between different experimental and theoretical results for trehalose effects on proteins.

Further studies on the patterns of senile plaques in senile dementia of the Alzheimer type (SDAT) with a hypothesis on the colonization of the cortex

The pattern of senile plaques was investigated in various brain regions of six SDAT brains. In 91 pattern analyses, the regularly spaced clump was the most common pattern found in 64.8% of analyses. Clumping due to large aggregations of uncored plaques in sulci was also common. Regularly spaced clumps were equally common in the hippocampus and neocortex. The pattern of plaques varied in different tissue sections from the same brain region. Cored and uncored plaques presented a similar range of patterns but their pattern varied when they were both present in the same tissue section. Both clump diameter and the intensity of clumping were positively correlated with cored but unrelated to uncored plaque density. Plaques may develop in regular clumps on subcortical afferents and during development of the disease the clumps may spread laterally and ultimately coalesce.

The spatial patterns of plaques and tangles in Alzheimer's disease do not support the 'cascade hypothesis'

In Alzheimer's disease (AD), the 'Cascade hypothesis' proposes that the formation of paired helical filaments (PHF) may be casually linked to the deposition of beta/A4 protein. Hence, there should be a close spatial relationship between senile plaques and cellular neurofibrillary tangles in a local region of the brain. In tissue from 6 AD patients, plaques and tangles occurred in clusters and individual clusters were often regularly spaced along the cortical strip. However, the clusters of plaques and tangles were in phase in only 4/32 cortical tissues examined. Hence, the data were not consistent with the 'Cascade hypothesis' that beta/A4 and PHF are directly linked in AD.