288 research outputs found
Recensione di C. Lucifora, C.M. Vicario, Il cervello morale. Dalle scienze cognitive all'intelligenza artificiale
No full textReview of the book l cervello morale. Dalle scienze cognitive all’intelligenza artificiale by Chiara Lucifora e Carmelo Mario Vicari
Palermo 1860. Stereoscopie di Eugène Sevaistre
No full textLo studio analizza la figura del fotografo francese, attivo in sicilia, nella metà del XIX secolo
In Defense of the Central Role of Consciousness versus the Prevalence of the Unconscious in Bargh’s and Kahneman’s Models of Mind.
No full textone of the most common dichotomies in psychology is that of consciousness and unconscious- ness. Various theoretical proposals dealing with this dichotomy are available and this diversity re ects a certain elusiveness of these concepts. Such a situation turns out to be problematic, in that critical analyses of this dichotomy rarely progress towards a speci c theory or position but, instead, refer to a wide class of theories which in essence deal to the dichotomy in the same manner. In order to avoid this problem, this paper addresses Bargh’s and Kahneman’s pro- posals on the conscious-unconsciousness distinction and their relations. on the basis of such an analysis, our aim is to assess how conscious processes are in uential in explaining human behaviour, despite the emphasis placed on the unconscious dimension. this paper proposes to closely examine consciousness and subjectivity, in that they are fundamental dimensions for explaining the unitary nature of human behaviour
The multifaceted role of cma in glioma: Enemy or ally?
No full textChaperone‐mediated autophagy (CMA) is a catabolic pathway fundamental for cell homeostasis, by which specific damaged or non‐essential proteins are degraded. CMA activity has three main levels of regulation. The first regulatory level is based on the targetability of specific proteins possessing a KFERQ‐like domain, which can be recognized by specific chaperones and delivered to the lysosomes. Target protein unfolding and translocation into the lysosomal lumen constitutes the second level of CMA regulation and is based on the modulation of Lamp2A multimerization. Finally, the activity of some accessory proteins represents the third regulatory level of CMA activity. CMA’s role in oncology has not been fully clarified covering both pro-survival and pro‐death roles in different contexts. Taking all this into account, it is possible to comprehend the actual complexity of both CMA regulation and the cellular consequences of its activity allowing it to be elected as a modulatory and not only catabolic machinery. In this review, the role covered by CMA in oncology is discussed with a focus on its relevance in glioma. Molecular correlates of CMA importance in glioma responsiveness to treatment are described to identify new early efficacy biomarkers and new therapeutic targets to overcome resistance
PET biomarkers and probes for treatment response assessment in glioblastoma : a work in progress
No full textAims: Several pharmacological approaches are used for glioblastoma (GBM) treatment, each hinging on the triggering of different biochemical or functional processes; the development of specific and sensitive PET procedures for monitoring their efficacy proceeds with the identification of such new treatments. This paper presents an overview of the available “tumour biomarker”–“PET probe” pairs (i.e. the combination of a tumour target and a selective PET radiopharmaceutical) for monitoring the different treatments for GBM tested in human subjects. Methods: A bibliographic search for papers on PET imaging for assessing treatment response in GBM was performed in PubMed and Web of science databases using the following string: (PET or positron) and (glioblastoma) and (treatment) and (monitoring); papers dealing with studies in human subjects published over the last 10 years were reviewed. Further papers were extracted from the bibliography of the reviewed papers. Results: In this review, we highlight through a detailed table that in spite of the current use in GBM patients of a large variety of PET radiopharmaceuticals, very few papers have specifically addressed the issue of the optimization and use of imaging biomarker–probe pairs for the assessment of treatment response in GBM. While new PET probes are being developed for assessing old and new GBM biomarkers, very few clinical trials have been performed to this end. Conclusion: Whereas it appears that the use of old and new PET radiopharmaceuticals can advance the non-invasive assessment of treatment response in GBM, the optimal match of biomarker–probe pairs although highly needed is still being sought in particular with the active development of new highly specific treatments characterized by novel antitumoral targeting strategies
Indagine sierologia riguardante la diffusione del virus Visna/Maedi (MVV) in allevamenti ovini in Italia
No full textSUMMARY - In order to gel a generai indication of thè extent of maedi-visna infection in
dairy and meat sheep flocks in Italy, a wide serological survey covering flocks in several
provinces was carried out in 1998.
Blood samples were obtained through thè courtesy of veterinary surgeons involved in testing
flocks for brucellosis. The recommendation given was to obtain blood samples from thè older
ewes in thè flocks, though on a few occasions blood samples were received from sheep under
two years old. On most farms about 10% of thè flock was bled. However if in thè sample of
ewes tested no serological positive sheep were discovered, then a further group was bled until
at least 75% of thè flock had been sampled or altematively at least one sheep had been
detected with antibodies to MV virus.
On receipt of thè blood samples sera were removed and store at -20°C lili tested. The test
used was thè agar gel immunodiffusion test (AGID). The method adopted was that described
by thè Ministry of Agriculture and Fisheries Central Veterinary Laboratory, Weybridge, UK.
The survey covered flocks in 7 of thè 21 regions in Italy and from 1 ,to 27 farms according to
thè region. Evidence of thè infection with MV virus was found in ali regions and thè number
of farms with antibody positive sheep was from 1 to 20 (44-100%).
A total of 1735 sheep were tested in 7 regions. The number tested on each farm varied from 1
to 100% partly according to thè size of thè flock. Antibodies were found in thè sera of 347
(20%)
sheep
CMA mediates resistance in breast cancer models
No full textAbstract Background Breast cancer (BC) is the most common malignancy in women and the second leading cause of cancer-related death; chemoresistance is still a clinical challenge mainly because of the different molecular features of this kind of tumour. Doxorubicin (Doxo) is widely used despite its adverse effects and the common onset of resistance. Chaperone-Mediated Autophagy (CMA) has been identified as an important mechanism through which chemotherapeutics can exert their cytotoxic effects and, in this context, LAMP-2A, the key player of CMA, can be a useful biomarker. Methods A cohort of patients and breast cancer cells have been screened for Doxo effect and CMA activation by analysing the LAMP-2A level. Molecular silencing has been used to clarify CMA role in BC responsiveness to treatments. Low Doxo doses were combined with other drugs (TMZ or PX-478, a HIF-1α inhibitor) to evaluate their cytotoxic ability and their role in modulating CMA. Results In this paper, we showed that CMA is an important mechanism mediating the responsiveness of breast cancer cell to different treatments (Doxo and TMZ, as suggested by triple negative cells that are TMZ-resistant and fails to activate CMA). The LAMP-2A expression level was specific for different cell lines and patient-derived tumour subtypes, and was also useful in discriminating patients for their survival rates. Moreover, molecular silencing or pharmacological blockage of HIF-1α activity reverted BC resistance to TMZ. The combination of low-dose Doxo with TMZ or PX-478 showed that the drug associations have synergistic behaviours. Conclusion Here, we demonstrated that CMA activity exerts a fundamental role in the responsiveness to different treatments, and LAMP-2A can be proposed as a reliable prognostic biomarker in breast cancer. In this context, HIF-1α, a potential target of CMA, can also be assessed as a valuable therapeutic target in BC in view of identifying new, more efficient and less toxic therapeutic drug combinations. Moreover, the possibility to combine Doxo with other drugs acting on different but coherent molecular targets could help overcome resistance and open the way to a decrease in the dose of the single drugs
Optical imaging probes in oncology
No full textCancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management.Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation.The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed
Hypoxia-inducible factor-1α activity as a switch for glioblastoma responsiveness to temozolomide
No full textRationale: The activity of the transcription factor, hypoxia-inducible factor (HIF)-1α, is a common driver of a number of the pathways involved in the aggressiveness of glioblastomas (GBMs), and it has been suggested that the reduction in this activity observed, soon after the administration of temozolomide (TMZ), can be a biomarker of an early response in GBM models. As HIF-1α is a tightly regulated protein, studying the processes involved in its downregulation could shed new light on the mechanisms underlying GBM sensitivity or resistance to TMZ. Methods: The effect of HIF-1α silencing on cell responsiveness to TMZ was assessed in four genetically different human GBM cell lines by evaluating cell viability and apoptosis-related gene balance. LAMP-2A silencing was used to evaluate the contribution of chaperone-mediated autophagy (CMA) to the modulation of HIF-1α activity in TMZ-sensitive and TMZ-resistant cells. Results: The results showed that HIF-1α but not HIF-2α activity is associated with GBM responsiveness to TMZ: its downregulation improves the response of TMZ-resistant cells, while blocking CMA-mediated HIF-1α degradation induces resistance to TMZ in TMZ-sensitive cells. These findings are in line with the modulation of crucial apoptosis-related genes. Conclusion: Our results demonstrate the central role played by HIF-1α activity in determining the sensitivity or resistance of GBMs to TMZ, and we suggest that CMA is the cellular mechanism responsible for modulating this activity after TMZ treatment
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