University of Milan

About: University of Milan is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Transplantation. The organization has 58413 authors who have published 139784 publications receiving 4636354 citations. The organization is also known as: Università degli Studi di Milano & Statale.

Activation of microglial cells by beta-amyloid protein and interferon-gamma

Abstract: Alzheimer's disease is the most common cause of progressive intellectual failure. The lesions that develop, called senile plaques, are extracellular deposits principally composed of insoluble aggregates of beta-amyloid protein (A beta), infiltrated by reactive microglia and astrocytes. Although A beta, and a portion of it, the fragment 25-35 (A beta (25-35)), have been shown to exert a direct toxic effect on neurons, the role of microglia in such neuronal injury remains unclear. Here we report a synergistic effect between A beta and interferon-gamma (IFN-gamma) in triggering the production of reactive nitrogen intermediates and tumour-necrosis factor-alpha (TNF-alpha) from microglia. Furthermore, using co-culture experiments, we show that activation of microglia with IFN-gamma and A beta leads to neuronal cell injury in vitro. These findings suggest that A beta and IFN-gamma activate microglia to produce reactive nitrogen intermediates and TNF-alpha, and this may have a role in the pathogenesis of neuronal degeneration observed in ageing and Alzheimer's disease.

Breakdown of cortical effective connectivity during sleep.

Abstract: When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premotor area) is transmitted to the rest of the brain. During quiet wakefulness, an initial response (approximately 15 milliseconds) at the stimulation site was followed by a sequence of waves that moved to connected cortical areas several centimeters away. During non-rapid eye movement sleep, the initial response was stronger but was rapidly extinguished and did not propagate beyond the stimulation site. Thus, the fading of consciousness during certain stages of sleep may be related to a breakdown in cortical effective connectivity.

Reference to Kinds across Language

Abstract: This paper is devoted to the study of bare nominal arguments (i.e., determinerless NPs occurring in canonical argumental positions) from a crosslinguistic point of view. It is proposed that languages may vary in what they let their NPs denote. In some languages (like Chinese), NPs are argumental (names of kinds) and can thus occur freely without determiner in argument position; in others they are predicates (Romance), and this prevents NPs from occurring as arguments, unless the category D(eterminer) is projected. Finally, there are languages (like Germanic or Slavic) which allow both predicative and argumental NPs; these languages, being the ‘union’ of the previous two types, are expected to behave like Romance for certain aspects of their nominal system (the singular count portion) and like Chinese for others (the mass and plural portions). This hypothesis (the ‘Nominal Mapping Parameter’) is investigated not just through typological considerations, but also through a detailed contrastive analysis of bare arguments in Germanic (English) vs. Romance (Italian). Some general consequences of this view, which posits a limited variation in the mapping from syntax into semantics, for current theories of Universal Grammar and acquisition are considered.

Assessing computational tools for the discovery of transcription factor binding sites.

Abstract: The prediction of regulatory elements is a problem where computational methods offer great hope. Over the past few years, numerous tools have become available for this task. The purpose of the current assessment is twofold: to provide some guidance to users regarding the accuracy of currently available tools in various settings, and to provide a benchmark of data sets for assessing future tools.

Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease

Abstract: Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, loss of a beneficial activity of wild-type huntingtin may also cause the death of striatal neurons. Here we demonstrate that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. We show that this beneficial activity of huntingtin is lost when the protein becomes mutated, resulting in decreased production of cortical BDNF. This leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD.