Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS

Gao Xingjian, Lun chuangzuo 《论创作》

Gao Xingjian,Lun chuangzuo 《论创作》(Hong Kong, Mingpao yuekan chubanshe 明报月刊出版社, 2008,426 pp. ISBN 978-988-7576-2-3)di Simona Gall

Gao Xingjian – Entre le chinois et le français

Gao Xingjian 高行健 (Ganzhou, 1940) – déclaré persona non grata en Chine continentale depuis 1990 et citoyen français à partir de 1998 – est écrivain et artiste peintre. Après avoir abandonné la Chine, il s’est installé en France et il a choisi de se consacrer totalement à la quête d’une liberté dans la création ; son œuvre littéraire a été couronnée par le prix Nobel de littérature en 2000. Gao Xingjian a toujours revendiqué une position « à la marge », qui se situe au-delà de l’identité nation..

MET Oncogene Controls Invasive Growth by Coupling with NMDA Receptor

SIMPLE SUMMARY: The MET oncogene, encoding the tyrosine kinase receptor for a hepatocyte growth factor (HGF), plays a key role in the onset and progression of aggressive forms of breast cancer. Recently, it was found that the glutamate receptor, which has a well-known role in the nervous system, is expressed in many types of tumors outside the nervous system and contributes to metastatic behavior in breast cancer cells. Here, we highlight that MET protein physically interacts with glutamate receptors in two highly metastatic breast cancer cell lines. HGF, which creates a supportive proinvasive microenvironment for the tumor cells, stabilizes this interaction. Pharmacological inhibition of glutamate receptors blunts the migration and invasion elicited by HGF, suggesting drug repurposing of glutamate receptor antagonists for anticancer therapy. ABSTRACT: The N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel involved in excitatory synaptic transmission. Outside the nervous system, the NMDAR is expressed in a variety of tissues and in cancers, notably in the highly invasive and metastatic triple-negative breast carcinoma. MET encodes the tyrosine kinase receptor for HGF and is a master regulator gene for “invasive growth”. In silico analysis shows that high expression of the NMDAR2B subunit is a negative prognostic factor in human invasive breast carcinoma. Here, we show that in triple-negative breast cancer cell lines NMDAR2B and MET proteins are coexpressed. HGF stimulation of these cells is followed by autophosphorylation of the MET kinase and phosphorylation of the NMDAR2B subunit at tyrosines 1252 and 1474. MET and phosphorylated NMDAR2B are physically associated, as demonstrated by co-immunoprecipitation, confocal immunofluorescence, and proximity ligation assays. Notably, pharmacological inhibition of NMDAR by MK801 and ifenprodil blunts the biological response to HGF. These results demonstrate the existence of a MET-NMDAR crosstalk driving the invasive program, paving the way for a new combinatorial therapy

DUSP26 (dual specificity phosphatase 26)

The DUSP26 gene encodes for an atypical dual specificity phosphatase commonly referred to as Dusp26 or MPK8. Although its physiological role is poorly understood, different substrates have been reported to be dephosphorylated by Dusp26, including p53, Kif3, Erk and p38. In this report we summarize the current knowledge on DUSP26 gene, its transcripts, the encoded protein and its function in normal and tumorous tissues. Notably, the phosphatase is overexpressed in neuroblastoma and ATC cells, where it promotes chemoresistance by inhibiting the p53 and the p38 proteins, respectively. Dusp26 represents a promising novel therapeutic target to be integrated with others and with conventional medicine, to improve survival outcome in patients and to reduce toxicity

HGF/Met axis has anti-apoptotic and anti-autophagic function in hypoxic cardiac injury

Ischaemic heart disease is the main cause of death in western countries. Cardiac tissue is primarily damaged by cardiomyocyte cell death triggered by low oxygen supply to the heart (hypoxia). The current therapeutic approach is coronary angioplastic intervention or thrombolytic treatments to resume blood flow in the ischaemic heart. Unfortunately, reperfusion itself causes a burst of ROS production responsible for cardiomyocyte death and myocardial dysfunction. Indeed, the majority of patients surviving to acute myocardial infarction undergoes progressive heart failure, with 50% mortality at five years from diagnosis. Apoptosis of cardiomyocytes is dangerous both during ischaemia and reperfusion. In line with this concept, we have shown that treatment of H9c2 cardiomyoblasts with cobalt chloride (CoCl2), a chemical mimetic of hypoxia, induces caspase-dependent apoptosis. Unexpectedly, we found that 3-methyladenine, an inhibitor of autophagy initiation, partially prevents CoCl2-mediated cell death, indicating that also autophagy contributes to cardiomyoblast death. Consistently, we found an increase in the autophagic flux in dying cells. Mechanistically, we have shown that CoCl2 upregulates Redd1, Bnip3 and phospho-AMPK proteins and causes inhibition of mTOR, the main negative regulator of autophagy.  In light of these observations, it is important to discover new therapeutic tools displaying a dual prosurvival mechanism. To this aim, we have analyzed the cardioprotective action of HGF/Met axis in hypoxic injury. To activate Met signaling we have used either the HGF ligand or two different monoclonal antibodies (mAbs) directed against the extracellular moiety of Met receptor. Owing a divalent structure, the two mAbs can dimerize and activate Met receptor, thus displaying agonist activity. Hypoxic injury was fully prevented by either HGF or Met agonist mAbs through both anti-apoptotic and anti-autophagic functions. By pharmacological inhibition we showed that activation of mTOR is the protective signaling downstream to Met, being involved in the anti-autophagic effect. In conclusion, HGF or Met agonist mAbs promote cell survival by negative dual regulation of apoptotic and autophagic cell death and represent promising new therapeutic tools to manage cardiac diseases

Survey on the role of brown hares (Lepus europaeus, Pallas 1778) as carriers of zoonotic dermatophytes

The occurrence of dermatophytes and keratinophilic fungi was investigated by hair-brush technique on the coat of 986 apparently healthy brown hares (Lepus europaeus, Pallas 1778) caught in 9 restocking and capture zones in Central Italy. Overall, 7.5% hair samples gave positive results. Trichophyton terrestre (2.1%), Chrysosporium sp, Chrysosporium keratinophilum, Microsporum gypseum, Trichophyton gloriae and Trichophyton mentagrophytes (0.6% each), Trichophyton erinacei and Scopulariopsis brevicaulis (0.4% each), Chrysosporium asperatum (0.3%), Arthroderma sp and Microsporum canis (0.1% each) were identified in cultures with single isolates, whereas Chrysosporium sp/T. mentagrophytes (0.3%), Chrysosporium sp/T. terrestre and M. gypseum/T. terrestre (0.2% each), Chrysosporium tropicum/T. terrestre, M. canis/T. terrestre and T. ajelloi/T. terrestre (0.1% each) were identified in cultures with mixed isolates. T. erinacei and M. canis have not previously been isolated from hares. M. canis, T. erinacei and T. mentagrophytes were the most clinically important dermatophytes found. Altogether, they were isolated only from 1.5% hair samples. Thus, it is concluded that brown hares may play a limited epidemiological role as carriers of zoonotic dermatophytes. Nevertheless, this should be taken into consideration as many people may be exposed to zoonotic agents from brown hares during hunting and trapping activities