Nuclear mRNA retention and aberrant doppel protein expression in human astrocytic tumor cells

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Future perspectives in melanoma research. Meeting report from the “Melanoma Bridge. Napoli, December 2nd-4th 2012”

Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third “Melanoma Research: “A bridge from Naples to the World” meeting, shortened as “Bridge Melanoma Meeting” took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients

Demência com corpos de lewy: considerações fisiopatológicas e terapêuticas

Introduction: Dementia with Lewy bodies (DLB) is a neurodegenerative condition characterized by the presence of Lewy bodies, intracellular aggregates composed mainly of alpha-synuclein. Clinically, DLB is manifested by cognitive symptoms, such as cognitive fluctuations, impaired attention and memory, as well as neuropsychiatric symptoms and parkinsonian symptoms, such as muscle rigidity and tremors. Objective: To evaluate the pathophysiology, pathogenesis and management of dementia with Lewy bodies. Methodology: This is a bibliographic review that included original articles and systematic reviews in English and Portuguese, which addressed the pathogenic, pathophysiological and treatment implications of DLB, published between 2012 and 2024, selected from the PubMed, Scopus and SciELO databases. After careful selection, 15 articles were chosen to compose this bibliographic review. Results: DCL has genetic aspects, including the SNCA, GBA and APOE genes, which play an important role in this process. Furthermore, there are significant immunological implications in DLB, with an increase in CD3+ and CD4+ T cells in some regions of the brain. The treatment of MCI is challenging, focusing on symptom management, with an emphasis on cholinesterase inhibitors for cognitive and neuropsychiatric symptoms. Considerations: DLB is characterized by a complex pathophysiology, marked by genetic aspects and immunopathogenic components relevant to the course of the disease. Clinical management of DLB mainly aims to control symptoms, especially cognitive, neuropsychiatric and sleep-related symptoms. Such therapeutic interventions are crucial to improving patients' comfort and quality of life.Introdução: A demência com corpos de Lewy (DCL) é uma condição neurodegenerativa caracterizada pela presença de corpos de Lewy, agregados intracelulares compostos principalmente de alfa-sinucleína. Clinicamente, a DCL se manifesta por sintomas cognitivos, como flutuações cognitivas, comprometimento da atenção e da memória, além de sintomas neuropsiquiátricos e sintomas parkinsonianos, como rigidez muscular e tremores. Objetivo: Avaliar a fisiopatologia, a patogênese e o manejo da demência com corpos de Lewy. Metodologia: Trata-se de uma revisão bibliográfica que incluiu artigos originais e revisões sistemáticas em inglês e português, que abordaram as implicações patogências, fisiopatológicas e tratamento da DCL, publicados entre 2012 e 2024, selecionados nas bases de dados PubMed, Scopus e SciELO. Após a seleção criteriosa, foram escolhidos 15 artigos para compor esta revisão bibliográfica. Resultados: A DCL é apresenta aspectos genéticos, incluindo os genes SNCA, GBA e APOE, desempenham um papel importante nesse processo. Além disso, há implicações imunológicas significativas na DCL, com aumento de células T CD3+ e CD4+ em algumas regiões do encéfalo. O tratamento da DCL é desafiador, focando na gestão dos sintomas, com destaque para inibidores da colinesterase para sintomas cognitivos e neuropsiquiátricos. Considerações: A DCL é caracterizada por uma fisiopatologia complexa, marcada por aspectos genéticos e componentes imunopatogênicos relevantes no curso da doença. O manejo clínico da DCL visa principalmente controlar os sintomas, especialmente os cognitivos, neuropsiquiátricos e relacionados ao sono. Tais intervenções terapêuticas são cruciais para melhorar o conforto e a qualidade de vida dos pacientes

T-REX OU4 HIRES: the high resolution spectrograph for the E-ELT

The goal of this unit was to consolidate the project for the construction of the high resolution spectrometer of the E-ELT (HIRES). The task included the development of scientific cases and tools to predict the instrumental performances. From the technical point of view it included several R&D activities in collaboration with highly specialized Italian companies; it culminated with the detailed design of a highly modular instrument based on well established technologies. From the management point of view it lead to the consolidation of a large international consortium that spans over 12 countries and includes most of the European and ESO-related institutes interested in high resolution spectroscopy. This consortium is led by INAF; its formal creation is awaiting the official call by ESO for the phase-A study for the HIRES instrument of the E-ELT

The doppel gene biology: a scientific journey from brain to testis, and return.

Doppel is a newly recognized prion-like molecule encoded by a novel gene locus, PRND, located on the same chromosomal region of the prion (PRNP) coding gene. Doppel was considered a paralogue and the first member of the prion-gene family, possibly originated through an ancestral gene duplication event. Prion and doppel have different expression patterns, suggesting that the gene products exhibit different biological functions. Actually, doppel is not involved in the aetiology of the Transmissible Spongiform Encephalopathies (TSEs) or “prion diseases” and is highly expressed only within the testicular tissue, suggesting an important physiological role in the process of spermatogenesis. The restricted spatial and temporal expression profile of doppel has suggested its investigation within particular pathological contexts, such as cancers, showing that it might represent a novel and attractive diagnostic molecular marker and that might provide insights into the regulatory pathways of tumor-cell transformation

COGNITION ENHANCERS BETWEEN TREATING AND DOPING THE MIND

Memory, attention and creativity represent three different cognitive domains, which are interconnected and contribute the “mental performance” of an individual. Modern neuroscience has investigated some of the neuronal circuits and of the neurotransmitters and molecular events underlying the above-mentioned cognitive functions. Within this renewed reference context, some of the properties of the components of the remedies to increase mental performance have been studied and validated in experimental models and, to date, these substances are named “smart drugs”, “memory enhancing drugs” or “nootropic drugs” (from the Greek root noos for mind and tropein for toward). Recently pharmaceutical industries are increasingly focusing on the research for potential substances in this field: several “smart drugs” are in clinical trials and could be on the market in few years. Furthermore, a quick survey from Internet highlights the presence of a great variety of both approved and non-approved drugs, with some of them addressing to only medical and others to performance-oriented use, opening room to some reflections or speculations from scientific and ethical points of view. In order to point out the effect of nootropic drugs on cognition of healthy people, we reviewed the literature on drug enhancement of various cognitive functions, including memory, attention and creativity. As their simplest, memory is regarded as the ability to remember events or learned material, attention is the cognitive process of selectively concentrating on one aspect while ignoring distracters and creativity could be described as the ability to create products or ideas which are original and which possess a social usefulness. Reports from literature reveal that some medications currently available to patients with memory disorders may also increase performances in healthy people and that drugs designed for psychiatric disorders can also be used to enhance certain mental functions. However, the long-term effects of these drugs are unknown, but their apparent effectiveness allows room to their use and misuse. At variance with these literature data showing scientific, even if poor, evidence of the effect of smart drugs in the field of memory and attention, only indirect information on creativity can be obtained by studies of the effects of diseases and drugs on the artistic productivity of classic painters and famous authors, offering a link to understand the neuronal basis of this cognitive function and a cue to understand how drugs (used to correct the illness) may affect the function. On the basis of these cues, in this review we will discuss some critical aspects of the different cerebral circuits and molecular events regulating memory, attention and creativity in order to outline the neurobiological bases of the effects of “smart drugs” on cognitive functions, and to evaluate their putative pharmaceutical development