1,721,423 research outputs found
Projective mechanisms subtending real world phenomena wipe away cause effect relationships
No full textCausal relationships lie at the very core of scientific description of biophysical phenomena. Nevertheless, observable facts involving changes in system shape, dimension and symmetry may elude simple cause and effect inductive explanations. Here we argue that numerous physical and biological phenomena such as chaotic dynamics, symmetry breaking, long-range collisionless neural interactions, zero-valued energy singularities, and particle/wave duality can be accounted for in terms of purely topological mechanisms devoid of causality. We illustrate how simple topological claims, seemingly far away from scientific inquiry (e.g., “given at least some wind on Earth, there must at all times be a cyclone or anticyclone somewhere”; “if one stirs to dissolve a lump of sugar in a cup of coffee, it appears there is always a point without motion”; “at any moment, there is always a pair of antipodal points on the Earth's surface with equal temperatures and barometric pressures”) reflect the action of non-causal topological rules. To do so, we introduce some fundamental topological tools and illustrate how phenomena such as double slit experiments, cellular mechanisms and some aspects of brain function can be explained in terms of geometric projections and mappings, rather than local physical effects. We conclude that unavoidable, passive, spontaneous topological modifications may lead to novel functional biophysical features, independent of exerted physical forces, thermodynamic constraints, temporal correlations and probabilistic a priori knowledge of previous cases
Mitochondrial targeting in LRRK2-associated parkinsonism (PARK8)
No full textAmong monogenic forms of Parkinson's disease (PD), the most frequent is associated with the leucine-rich repeat kinase2 (LRRK2) mutation, named PARK8 and the most common G2019S mutation. LRRK2 is expressed in the dopamine (DA) neurons of the substantia nigra compacta, suggesting a role in PD degeneration. In PD, mitochondrial complex I is impaired thus inhibitors of this complex and 6-OHDA are used to lesion the DA nigrostriatal system and induce experimental parkisonism. To study the role of LRRK2, models carrying LRRK2 pathogenic mutations have been developed. LRRK2 mutants cause neurodegeneration impairing mitochondrial activity indicating a prominent role of this structure in LRRK2-mediated death signals. Kinase regulation of mitochondrial dynamics are pivotal in these processes in relation to PD onset and expression of G2019S mutation alters the homeostasis of mitochondrial Ca2+. Drugs able to correct LRRK2-associated mitochondrial dysfunction may attenuate parkinsonism in mice. Aim 1.
We will investigate whether the G2019S mutation renders dopamine (DA) neurons more prone to death over aging or following exposure to parkinsonian toxins, ultimately making mice more susceptible to develop parkinsonism. Therefore, our first main goal is to provide behavioral, electrophysiological (striatal slices), biochemical (cell lines and mesencephalic/cerebrocortical neurons) and neurochemical (microdyalisis/synaptosomes) characterization of i) mice over-expressing human LRRK2 carrying the G2019S mutation; ii) LRRK2 Knock-Out (KO) mice; iii) LRKK2 G2019S Knock-In (KI) mice and iv) mice expressing a LRRK2 mutation (D1994S) associated with null kinase activity (Kinase Dead; KD mice). Aim 2. We will take advantage of these multiple genetic models and expertises available, to evaluate: i) the relation between mouse phenotype and age (3, 6 and 12 months); ii) the effect of exposure to various parkinsonian toxins such as MPTP, 6-OHDA and rotenone. Aim 3. In addition, mitochondrial drugs will be administered to correct behavioral and biochemical deficits in LRKK2 mice in vivo and ex vivo, as well as in cell lines. In particular, drugs specific for mitochondrial targets (permeability transition pore, radical oxygen production, dynamin-related GTPases) will be used in order to protect from in vitro and in vivo degeneration DA neurons carrying the characterized LRRK2 mutations
Epidemiologia Facile
No full textCome si pianifica uno studio epidemiologico? Quale relazione esiste fra prevalenza, incidenza e durata di una malattia? Come si dimostra l’associazione statistica fra due eventi? Cos’è il valore di cut-off di un test? Come si valuta l’efficacia di un intervento preventivo?
Frutto dell’esperienza maturata nel corso di perfezionamento a distanza in Metodologia Epidemiologica dell’Università di Bari, il materiale didattico è stato opportunamente ampliato, riorganizzato e raccolto al fine di creare un testo agile, ma al contempo completo ed efficace per il supporto alla didattica di base.Grazie alla presenza di esercitazioni con test di autovalutazione (su CD-ROM) e al forte orientamento alla pratica, il manuale si propone come lo strumento essenziale per chi voglia avviarsi allo studio e alla pratica dell’epidemiologia
Epidemiologia Facile
No full textCome si pianifica uno studio epidemiologico? Quale relazione esiste fra prevalenza, incidenza e durata di una malattia? Come si dimostra l’associazione statistica fra due eventi? Cos’è il valore di cut-off di un test? Come si valuta l’efficacia di un intervento preventivo?
Frutto dell’esperienza maturata nel corso di perfezionamento a distanza in Metodologia Epidemiologica dell’Università di Bari, il materiale didattico è stato opportunamente ampliato, riorganizzato e raccolto al fine di creare un testo agile, ma al contempo completo ed efficace per il supporto alla didattica di base.Grazie alla presenza di esercitazioni con test di autovalutazione (su CD-ROM) e al forte orientamento alla pratica, il manuale si propone come lo strumento essenziale per chi voglia avviarsi allo studio e alla pratica dell’epidemiologia
Federigo Tozzi e Ada Negri: il carteggio inedito (con un articolo ritrovato)
No full textPubblicazione integrale del carteggio tra Federigo Tozzi e Ada Negri, con ampia introduzione e in appendice La recensione di Tozzi a Le solitarie (L'Idea Nazionale)
- …
