The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Topological and Variational Properties of a Model for the Reconstruction of Three-Dimensional Transparent Images with Self-Occlusions

We introduce and study a two-dimensional variational model for the reconstruction of a smooth generic solid shape E, which may handle the self-occlusions and that can be considered as an improvement of the 2.1D sketch of Nitzberg and Mumford (Proceedings of the Third International Conference on Computer Vision, Osaka, 1990). We characterize from the topological viewpoint the apparent contour of E, namely, we characterize those planar graphs that are apparent contours of some shape E. This is the classical problem of recovering a three-dimensional layered shape from its apparent contour, which is of interest in theoretical computer vision. We make use of the so-called Huffman labeling (Machine Intelligence, vol. 6, Am. Elsevier, New York, 1971), see also the papers of Williams (Ph.D. Dissertation, 1994 and Int. J. Comput. Vis. 23:93–108, 1997) and the paper of Karpenko and Hughes (Preprint, 2006) for related results. Moreover, we show that if E and F are two shapes having the same apparent contour, then E and F differ by a global homeomorphism which is strictly increasing on each fiber along the direction of the eye of the observer. These two topological theorems allow to find the domain of the functional ℱ describing the model. Compactness, semicontinuity and relaxation properties of ℱ are then studied, as well as connections of our model with the problem of completion of hidden contours.

Photonic-aware neural networks

Neural Computing and Applications - Photonics-based neural networks promise to outperform electronic counterparts, accelerating neural network computations while reducing power consumption and...     

Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model

The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.     

PDGF/PDGFR: A Possible Molecular Target in Scleroderma Fibrosis

Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFRα autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF/PDGFR targeting therapies.     

In vitro antifungal activity and chemical composition of Warionia saharae essential oil against 3 apple phytopathogenic fungi

Essential oil of aerial parts of Warionia saharae was obtained by hydrodistillation and analyzed by GC and GC-MS. Thirty-nine compounds were identified, accounting for 93.2% of the total oil. β-Eudesmol (34.9%), nerolidol-E (23%), and linalool (15.2%) were the most abundant components. The antifungal activity of the W. saharae oil was tested by poisoned food (PF) technique and the volatile activity (VA) assay against 3 phytopathogenic causing the deterioration for apple. The results indicated that the W. saharae oil inhibited significantly the mycelial growth of all strains tested (p<0.05). The minimum inhibitory concentration against Alternaria sp. was 2 μL/mL air in VA assay, whereas >2 μL/mL in PF technique for all strains. Fungal spore production was completely inhibited at 1 μL/mL air for Alternaria sp. and at 2 μL/mL air for Penicillium expansum and Rhizopus stolonifer.     

Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice

It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were down-regulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.     

Performance analysis of parallel Schwarz preconditioners in the LES of turbulent channel flows

We present a comparative study of parallel Schwarz preconditioners in the solution of linear systems arising in a Large Eddy Simulation (LES) procedure for turbulent plane channel flows. This procedure applies a time-splitting technique to suitably filtered Navier–Stokes equations, in order to decouple the continuity and momentum equations, and uses a semi-implicit scheme for time integration and finite volumes for space discretisation. This approach requires the solution of four sparse linear systems at each time step, accounting for a large part of the overall simulation; hence the linear system solvers are a crucial component in the whole procedure. Several preconditioners are applied in the simulation of a reference test case for the LES community, using discretisation grids of different sizes, with the aim of analysing the effects of different algorithmic choices defining the preconditioners, and identifying the most effective ones for the selected problem. The preconditioners, coupled with the GMRES method, are run within SParC-LES, a recently developed LES code based on the PSBLAS and MLD2P4 libraries for parallel sparse matrix computations and preconditioning.