Essential and current methods for a practical approach to comparative neuropathology

The understanding of mechanisms that provoke neurological diseases in humans and in animals has progressed rapidly in recent years, mainly due to the advent of new research instruments and our increasing liability to assemble large, complex data sets acquired across several approaches into an integrated representation of neural function at the molecular, cellular, and systemic levels. Nevertheless, morphology always represents the essential approaches that are crucial for any kind of interpretation of the lesions or to explain new molecular pathways in the diseases. This mini-review has been designed to illustrate the newest and also well-established principal methods for the nervous tissue collection and processing as well as to describe the histochemical and immunohistochemical staining tools that are currently most suitable for a neuropathological assessment of the central nervous system. We also present the results of our neuropathological studies covering material from 170 cases belonging to 10 different species of mammals. Specific topics briefly addressed in this paper provide a technical and practical guide not only for researchers that daily focus their effort on neuropathology studies, but also to pathologists who occasionally have to approach to nervous tissue evaluation to answer questions about neuropathology issues

Cerebral venous hemodynamic abnormalities in episodic and chronic migraine

Alterations of cerebral venous drainage have been demonstrated in chronic migraine (CM), suggesting that cerebral venous hemodynamic abnormalities (CVHAs) play a role in this condition. The aim of the present study was to look for a correlation between CM and CVHAs. We recruited 33 subjects suffering from CM with or without analgesic overuse, 29 episodic migraine (EM) patients with or without aura, and 21 healthy subjects as controls (HCs). CVHAs were evaluated by transcranial and extracranial echo-color Doppler evaluation of five venous hemodynamic parameters. CVHAs were significantly more frequent in the CM and EM patients than in the HCs. In the migraine patients, CVHAs were not correlated with clinical features. Cerebral venous hemodynamic abnormalities in episodic and chronic migraine The significantly greater frequency of CVHAs observed in the migraineurs may reflect a possible relationship between migraine and these abnormalities. Prospective longitudinal studies are needed to investigate whether CVHAs have a role in the processes of migraine chronification

Molecular diagnosis of carcinomas of the thyroid gland.

Our understanding of the molecular pathology of thyroid cancer has progressed significantly. It is now apparent that thyroid tumors show a very good correlation between genotype and phenotype, a correlation that is much stronger than that observed in tumors of many other organs. Activation of classic oncogenes (BRAF, RAS, RET) activate MAPK signalling. Other pathways like the PI3K/PTEN/AKT cascade are also active in many thyroid tumors. The analysis of molecular profiles is generating data that can be applied to improve patient management. The common occurrence of thyroid nodules in the general population and the widespread use of fine needle aspiration for the preoperative diagnosis of thyroid nodules creates an unprecedented opportunity to apply what we have learnt from the molecular alterations of thyroid cancer to the clinical arena

Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS).Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function

Induced expression of the Fragaria 7 ananassa Rapid alkalinization factor-33-like gene decreases anthracnose ontogenic resistance of unripe strawberry fruit stages

Rapid alkalinization factor (RALF) genes encode for ubiquitous small peptides that stimulate apoplastic alkalinization through interaction with malectin-like receptor kinase. RALF peptides may act as negative regulators of plant immune response, inhibiting the formation of the signal receptor complex for immune activation. Recently RALF homologues were identified in different fungal pathogen genomes contributing to host infection ability. Here, FaRALF-33-like gene expression was evaluated in strawberry fruits inoculated with Colletotrichum acutatum, Botrytis cinerea, or Penicillium expansum after 24 and 48 h post-infection. To investigate the role of FaRALF-33-like in strawberry susceptibility, transient transformation was used to overexpress it in white unripe fruits and silence it in red ripe fruits. Agroinfiltrated fruits were inoculated with C. acutatum and expression, and histological analysis of infection were performed. Silencing of FaRALF-33-like expression in C. acutatum-inoculated red fruits led to a delay in fruit colonization by the fungal pathogen, and infected tissues showed less penetrated infective hyphae than in wild-type fruits. In contrast, C. acutatum-inoculated white unripe fruits overexpressing the FaRALF-33-like gene decreased the ontogenic resistance of these fruits, leading to the appearance of disease symptoms and penetrated subcuticular hyphae, normally absent in white unripe fruits. The different response of transfected strawberry fruits to C. acutatum supports the hypothesis that the FaRALF-33-like gene plays an important role in the susceptibility of fruits to the fungal pathogen C. acutatum

Desogestrel down-regulates PHOX2B and its target genes in progesterone responsive neuroblastoma cells

The paired-like homeobox 2B gene (PHOX2B) encodes a key transcription factor that plays a role in the development of the autonomic nervous system and the neural structures involved in controlling breathing. In humans, PHOX2B over-expression plays a role in the pathogenesis of tumours arising from the sympathetic nervous system such as neuroblastomas, and heterozygous PHOX2B mutations cause Congenital Central Hypoventilation Syndrome (CCHS), a life-threatening neurocristopathy characterised by the defective autonomic control of breathing and involving altered CO2/H+ chemosensitivity. The recovery of CO2/H+ chemosensitivity and increased ventilation have been observed in two CCHS patients using the potent contraceptive progestin desogestrel. Given the central role of PHOX2B in the pathogenesis of CCHS, and the progesterone-mediated effects observed in the disease, we generated progesterone-responsive neuroblastoma cells, and evaluated the effects of 3-Ketodesogestrel (3-KDG), the biologically active metabolite of desogestrel, on the expression of PHOX2B and its target genes. Our findings demonstrate that, through progesterone nuclear receptor PR-B, 3-KDG down-regulates PHOX2B gene expression, by a post-transcriptional mechanism, and its target genes and open up the possibility that this mechanism may contribute to the positive effects observed in some CCHS patients

Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity

MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC's consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours

Endometrial carcinoma: Past, present, and future

N

Polyphase folding at upper structural levels in the Borbera valley (Northern Apennines, Italy): implications for the tectonic evolution of the linkage area between Alps and Apennines

The Borbera Valley (northwestern Italy) is located in a complex geological area where the linkage between Alps and Apennines occurs. In this area the Antola Unit (Late Cretaceous–Palaeocene) is unconformably overlain by the Upper Eocene–Miocene succession of the Tertiary Piedmont Basin. The structural analysis indicates the occurrence of a folding phase of Late Oligocene–Early Miocene age, characterised by recumbent F2 folds. These folds are superposed onto D1 structures related to an early folding phase of Middle Eocene, affecting only the Antola Unit. The occurrence of map-scale D2 folding phase structures that affect the Tertiary Piedmont Basin succession suggests that the linkage area between Alps and Apennines was reactivated during the Late Oligocene–Early Miocene