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The transitioning of nanotechnology from laboratory to industrial-scale manufacturing poses various challenges in nanoparticle realization. From this perspective, beside the conventional synthetic procedure, based on the seed-mediated growth approach, a reshaping thermal strategy has been investigated to improve the control on gold nanorods aspect ratio, with the aim to point out a potential and encouraging way to better manage the scalability and reproducibility of nanoparticles. For this purpose, nanorods covered with CTAB and nanorods enclosed within a silica shell of tuned thickness have been synthesized and submitted to a post-thermal treatment at various temperatures, up to 300 °C for CTAB recovered gold nanorods (AuNR@CTAB), and up to 500 °C for silica-shell embedded gold nanorods (AuNR@SiO2). For AuNR@CTAB, through accurate temperature control, the longitudinal plasmonic band can be moved very close to the transversal one upon slight reduction of their length. Instead, for AuNR@SiO2, owing to the fully inorganic shell, a higher temperature of treatment can be reached leading to the possibility of reshaping the nanorods into spheres without the observation of any by-products.

International audience; Three room-temperature metallomesogens based on Zn(II) cations pentacoordinated by different chelating N^N^N terpyridines and two monodentate gallate co-ligands were designed and synthesized. Depending on the terpyridine ligand's tip functionality, the complexes self-assemble into either a 3D hexagonal mesophase or into a columnar hexagonal mesophase. A systematic study between the structure (molecular architecture, arrangement of the molecules and columns, and chains in both types of mesophases) and photophysical properties (emission maxima and yields, lifetimes of the excited states in the mesophase), correlated with investigations of single molecules in solution, was conducted. Remarkably, one complex exhibited a record quantum yield of 95.0% in solution, while in the mesophase, despite quenching due to the radiative deactivation from the ILCT state, still retained a considerable emission yield of ϕ = 20.2%. The polarized emission of an oriented film, determined for the first time in columnar metallomesogens, shows a dichroic emission ratio (I||/I⊥) of 1.30. DFT and TDDFT computational studies confirmed the origin of the observed fluorescence anisotropy from the transition dipole moment oriented along the C2 symmetry axis of the molecule combined with a high level of order in the 3D mesophase.

Four new Pt(ii) ionic complexes assembled from N-donor ligands and curcumin display interesting antioxidant and antimicrobial properties.

Gold nanospheres, coated with luminescent molecules (1-pyrenemethylamine hydrochloride, fluorescein isothiocyanate or cresyl violet perchlorate), have been synthesized and purified by a fast one-step procedure. Luminescent nanoparticles have been obtained, in which the match of the plasmonic and emissive properties gives nanosized fluorophores useful in different application fields.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD.

International audience; Blue-green luminescent terpyridine-containing Pt II and Zn II complexes are reported. Equipped with lipophilic gallate units, which act as monodentate ancillary coordinating ligands and/or as anions, they display low-temperature mesomorphic properties (lamello-columnar and hexagonal mesophases for Pt II and Zn II complexes, respectively). The mesomorphic properties were investigated by polarised optical microscopy, differential scanning calorimetry, thermogravimetric analysis and X-ray scattering of bulk materials and oriented thin films. The model of self-assembly into the lamello-columnar phase of the Pt II complex has been described in detail. The optical properties of the complexes were investigated in the liquid and condensed liquid crystalline states, highlighting the delicate balance between the role of the metal in determining the type of excited state responsible for the emission, and the role of the ancillary ligand in driving intermolecular interactions for proper mesophase formation.

Recently, several papers on weaker forms of classical covering properties of Menger, Hurewicz and Rothberger have been published. We complement this investigation studying new weak versions of these properties. Our study is related to selective versions of the quasi-Lindelof property introduced in 1979 by A.V. Arhangel'skii. For example, we define quasi-Menger spaces and show that they are different from other weak versions of Menger's property.

Given metric spaces ( X , d ) and ( Y , ρ ) , a partial map between X and Y is a pair ( D , u ) , where D is a closed subset of X and u : D → Y is a function. We introduce a general convergence notion for nets of such partial functions. While our initial description is variational in nature, we show that this description amounts to bornological convergence of the associated net of graphs as defined by Lechicki, Levi and Spakowski [26] with respect to a natural bornology on X × Y , and which places the work on continuous partial functions of Brandi, Ceppitelli, and Hola [12] , [13] , [20] , [21] in a general framework.

We study various variations on selective separability in non-regular topological spaces. We use the notions of θ -closure and θ -density to define selective versions of θ -separability. These properties are also related to topological games.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular dementia caused by mutations in NOTCH3 gene. Pathology is manifested in small- and middle-sized arteries throughout the body, though primarily in cerebral white matter. Hemodynamics is altered in CADASIL and NOTCH3 is suggested to regulate actin filament polymerization and thereby vascular tone. We analyzed NOTCH3 expression and morphology of actin cytoskeleton in genetically genuine cultured human CADASIL vascular smooth muscle cells (VSMCs) (including a cell line homozygous for p. Arg133Cys mutation) derived from different organs, and in control VSMCs with short hairpin RNA (shRNA)-silenced NOTCH3. NOTCH3 protein level was higher in VSMCs derived from adult than newborn arteries in both CADASIL and control VSMCs. CADASIL VSMCs showed altered actin cytoskeleton including increased branching and node formation, and more numerous and smaller adhesion sites than control VSMCs. Alterations in actin cytoskeleton in shRNA-silenced VSMCs were similar as in CADASIL VSMCs. Severity of the alterations in actin filaments corresponded to NOTCH3 expression level being most severe in VSMCs derived from adult cerebral arteries. These observations suggest that hypomorphic NOTCH3 activity causes alterations in actin organization in CADASIL. Furthermore, arteries from different organs have specific characteristics, which modify the effects of the NOTCH3 mutation and which is one explanation for the exceptional susceptibility of cerebral white matter arteries.

Notch3 is a single pass transmembrane protein belonging to the Notch receptor family. Notch proteins are involved in a very conserved signaling system (Notch signaling) with a broad spectrum of functions, from cell proliferation and differentiation to apoptosis. Mutations in Notch3 gene are linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a disorder characterized by stroke and dementia in young adults. Studies evaluating Notch3 expression in human differentiated cells and adult tissues have shown high Notch3 levels only in vascular smooth muscle cells (VSMC). However, it has been hypothesized that Notch3 is ubiquitously expressed in adult human tissues. Our aim was to evaluate Notch3 expression in human peripheral blood lymphocytes (PBLs) and fibroblasts from normal healthy subjects. In both cell types, we examined the expression of Notch3 by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, we assessed Notch3 protein expression by Western blot analysis. RT-PCR and qRT-PCR analysis showed the presence of Notch3 mRNA in both cell types. Western blot analysis confirmed Notch3 protein expression in PBLs and fibroblasts though showing different profiles. Our data support the expression of Notch3 in adult human cell types, and suggests that PBLs and fibroblasts could provide readily available cells for the study of the role of Notch3 expression in the pathogenetic mechanisms leading to different human disease. J. Cell. Physiol. 227: 1771–1775, 2012. © 2011 Wiley Periodicals, Inc.

Cofinal completeness of a metric space, which is a property between completeness and compactness, can be characterized in terms of a measure of local compactness functional [7]. Using this functional, we introduce and then study the variational notion of cofinally complete subset of a metric space.

Alagille syndrome (AGS) is an autosomal dominant disorder characterized by cholestasis, cardiac, skeletal and ocular abnormalities. Increasing importance is being given to vascular and central nervous system impairment. AGS is in most cases caused by heterozygous mutations in the Jagged-1 (JAG1) gene encoding a cell-surface ligand of the Notch receptors. The interaction between Notch1 and JAG1 induces proliferation and inhibits apoptosis. We evaluated the role of apoptosis in AGS patients carrying a truncating mutation in exon 7 of JAG1. Peripheral blood lymphocytes (PBLs) from two patients were exposed to 2-deoxy-d-ribose (dRib). Apoptosis was analyzed by flow cytometry, fluorescence microscopy and Western blotting. PBLs from patients showed a significantly higher percentage of apoptosis than controls both in standard culture conditions and after dRib treatment, however we demonstrated a lack of caspase-8 activation in those cells. Our results confirm that JAG1 may play a role in apoptosis regulation. In particular, truncating mutations in JAG1 could lead to Notch signaling inhibition and determine a deregulation of survival and proliferation, favoring apoptosis. Moreover, the lack of caspase-8 activation in AGS patients indicates a possible selective impairment of caspase-8 cleavage suggesting that JAG1 plays a specific role in the regulation of caspase-8 activation.

We study statistical versions of several classical kinds of convergence of sequences of functions between metric spaces (Dini, Arzelà, and Alexandroff) in different function spaces. Also, we discuss a statistical approach to recently introduced notions of strong uniform convergence and exhaustiveness.

In 1883 Arzela (1983/1984) [2] gave a necessary and sufficient condition via quasi-uniform convergence for the pointwise limit of a sequence of real-valued continuous functions on a compact interval to be continuous. Arzela's work paved the way for several outstanding papers. A milestone was the P.S. Alexandroff convergence introduced in 1948 to tackle the question for a sequence of continuous functions from a topological space (not necessarily compact) to a metric space. In 2009, in the realm of metric spaces, Beer and Levi (2009) [10] found another necessary and sufficient condition through the novel notion of strong uniform convergence on finite sets. We offer a direct proof of the equivalence of Arzela, Alexandroff and Beer–Levi conditions. The proof reveals the internal gear of these important convergences and sheds more light on the problem. We also study the main properties of the topology of strong uniform convergence of functions on bornologies, initiated in Beer and Levi (2009) [10] .

We introduce and investigate statistical convergence in topological and uniform spaces and show how this convergence can be applied to selection principles theory, function spaces and hyperspaces.

In this paper we investigate relationships between closure-type and convergence-type properties of hyperspaces over a space X and covering properties of X.

In this paper we use Bartle’s technique to study duality between a topological space and a function space. Normally such a duality forms an essential part of Functional Analysis. We introduce several new topologies such as the topology of even convergenceTe, the closed-cocompact topologyTk ′, the (strong) local proximal convergence.

A SEPARATION AXIOM WEAKER THAN R0

LetC(X,Y) be the space of continuous functions from a metric space (X,d) to a metric space (Y, e).C(X, Y) can be thought as subset of the hyperspaceCL(X×Y) of closed and nonempty subsets ofX×Y by identifying each element ofC(X,Y) with its graph. We considerC(X,Y) with the topology inherited from the Wijsman topology induced onCL(X×Y) by the box metric ofd ande. We study the relationships between the Wijsman topology and the compact-open topology onC(X,Y) and also conditions under which the Wijsman topology coincide with the Fell topology. Sufficient conditions under which the compactopen topology onC(X,Y) is weaker than the Wijsman topology are given (IfY is totally bounded, then for every metric spaceX the compactopen topology onC(X,Y) is weaker than the Wijsman topology and the same is true forX locally connected andY rim-totally bounded). We prove that a metric spaceX is boundedly compact iff the Wijsman topology onC(X, ℝ) is weaker than the compact-open topology. We show that ifX is a σ-compact complete metric space andY a compact metric space, then the Wijsman topology onC(X,Y) is Polish.

Cerebrolysin is the only drug available for clinical use containing active fragments of some important neurotrophic factors obtained from purified porcine brain proteins, which has long been used for the treatment of dementia and stroke sequels. Cerebrolysin has growth factor-like activities and promotes neuronal survival and sprouting, however, its molecular mechanism still needs to be determined. It has been shown that Cerebrolysin may interact with proteolytic pathways linked to apoptosis. Administration of Cerebrolysin significantly reduces the number of apoptotic neurons after glutamate exposure. Furthermore, it has been reported that Cerebrolysin inhibits free radicals formation and lipid peroxidation. In vitro we evaluated the protective effects of Cerebrolysin towards spontaneous and induced apoptotic death in cells from healthy individuals. Peripheral blood lymphocytes (PBLs) from 10 individuals were used as cell model; 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analysed using flow cytometry and fluorescence microscopy. Our results showed that Cerebrolysin significantly reduced the number of apoptotic PBLs after dRib treatment, although it had no significative effects on cells cultured in standard conditions. Our work showed a protective effect of Cerebrolysin on oxidative stress-induced apoptosis and suggested that PBLs can be used as an easy obtainable and handy cell model to verify Cerebrolysin effects in neurodegenerative pathologies.

Cerebrolysin (Cere) is a peptidergic nootropic drug with neurotrophic properties which has been used to treat dementia and sequelae of stroke. Use of Cere prevents nuclear structural changes typical of apoptosis and significantly reduces the number of apoptotic cells after several apoptotic stimuli. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis. The aim of this study was to evaluate the in vitro protective effects of Cere against oxidative stress-induced apoptosis in cells from CADASIL patients. We used peripheral blood lymphocytes (PBLs) from 15 CADASIL patients (age range 34-70 years); 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analyzed by flow cytometry and fluorescence microscopy. Administration of Cere to PBLs from CADASIL patients cultured under standard conditions had no effect on the percentage of apoptotic cells. Administration of Cere to PBLs cultured with dRib caused a significant decrease in apoptosis after 48 h of culture in only 5 patients, whereas in the other 10 patients, Cere treatment was not associated with any significant difference in the percentage of apoptosis. This result showed a protective effect of Cere against oxidative stress-induced apoptosis only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably does not influence the anti-apoptotic properties of Cere in vitro.

ATP13A2 gene encodes for a protein of the group 5 P-type ATPase family. ATP13A2 mutations are responsible for Kufor–Rakeb syndrome (KRS), a rare autosomal recessive juvenile parkinsonism characterized by the subacute onset of extrapyramidal, pyramidal and cognitive dysfunction with secondary nonresponsiveness to levodopa. FBXO7 protein is an F-box-containing protein. Recessive FBXO7 mutations are responsible for PARK15, a rare juvenile parkinsonism characterized by progressive neurodegeneration with extrapyramidal and pyramidal system involvement. Our aim was to evaluate apoptosis in cells from two KRS siblings carrying a homozygous ATP13A2 mutation and a heterozygous FBXO7 mutation. We also analysed apoptosis in the patients’ healthy parents. Peripheral blood lymphocytes from the KRS patients and parents were exposed to 2-deoxy-D-ribose; apoptosis was analysed by flow cytometry and fluorescence microscopy. Apoptosis was much higher in lymphocytes from the KRS patients and parents than in controls, both in standard conditions and after induction with a pro-apoptotic stimulus. The lack of correlation between increased apoptosis and the presence of the mutated FBXO7 gene rules out the involvement of FBXO7 in apoptosis regulation. The altered apoptotic pattern of subjects with mutated ATP13A2 suggests a correlation between apoptosis alteration and the mutated ATP13A2 protein. We hypothesize that ATP13A2 mutations may compromise protein function, disrupting cell cation balance and rendering cells prone to apoptosis. However, the deregulation of apoptosis in KRS patients displaying different disease severity suggested that the altered apoptotic pathway probably does not have a pathogenetic role in KRS by itself.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease affecting vascular smooth muscle cells of nearly all tissues. Clinical manifestations mainly concern the central nervous system with repeated TIA/stroke, migraine, psychiatric disturbances, and cognitive decline. Minor findings have been reported in muscle, nerve, and skin. CADASIL is due to NOTCH3 gene mutations. This gene has been identified as an up-regulator of c-FLIP, an inhibitor of Fas-ligand-induced apoptosis. The aim of this study was to assess the involvement of oxidative stress-induced apoptosis in cells from 16 Italian CADASIL patients. Peripheral blood lymphocytes (PBLs) and fibroblasts from CADASIL patients were exposed to 2-deoxy-D-ribose (dRib), which induces apoptosis by oxidative stress. Apoptosis was analyzed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy for caspase-3 activation, phosphatidylserine exposure and mitochondrial membrane depolarization. PBLs and fibroblasts from CADASIL patients showed a significantly higher response to dRib-induced apoptosis than those of controls. PBLs from CADASIL patients also showed a significantly higher percentage of apoptotic cells than PBLs from controls, even when cultured without dRib. The greater susceptibility of PBLs and fibroblasts from CADASIL patients to dRib-induced apoptosis suggests that NOTCH3 mutations are an important apoptotic trigger. Since PBLs from patients showed higher levels of apoptosis even in the absence of an apoptotic stimulus, cells from CADASIL patients appear to be physiologically prone to apoptotic cell death.

[EN] The subject of hyperspace topologies on closed or closed and compact subsets of a topological space X began in the early part of the last century with the discoveries of Hausdorff metric and Vietoris hit-and-miss topology. In course of time, several hyperspace topologies were discovered either for solving some problems in Applied or Pure Mathematics or as natural generalizations of the existing ones. Each hyperspace topology can be split into a lower and an upper part. In the upper part the original set inclusion of Vietoris was generalized to proximal set inclusion. Then the topologization of the Wijsman topology led to the upper Bombay topology which involves two proximities. In all these developments the lower topology, involving intersection of finitely many open sets, was generalized to locally finite families but intersection was left unchanged. Recently the authors studied symmetric proximal topology in which proximity was used for the first time in the lower part replacing intersection with its generalization: nearness. In this paper we use two proximities also in the lower part and we obtain the lower Bombay hypertopology. Consequently, a new hypertopology arises in a natural way: the symmetric Bombay topology which is the join of a lower and an upper Bombay topology.

To further investigate the mechanisms which regulate sympathetic vascular tone, we studied the effects of the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, thapsigargin, on the vasoconstriction induced by transmural nerve stimulation and noradrenaline in superfused human saphenous vein rings. The contractions induced by both transmural nerve stimulation and noradrenaline were potentiated by thapsigargin in endothelium-intact, but not in endothelium-denuded vessels. This potentiation was unaffected by the non-selective endothelin ET(A/B) receptor antagonist, Ro 47-0203 (4-tert-Butyyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin-4yl]benzene sulfonamide), or by the nitric oxide (NO) synthase inhibitor, L-NNA (N(omega)-nitro-L-arginine), but was inhibited by the thromboxane A(2) receptor antagonist, Bay u3405 (3(R)-[[(4-flurophenyl) sulphonyl]amino-1,2,3,4-tetrahydro-9H-carbazole-9-propanoic acid]) or by the thromboxane A(2) synthase inhibitor, UK 38485 (3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indole-1-propanoic acid). Moreover, the thapsigargin-induced noradrenergic hyperresponsiveness, as well as that produced by subthreshold concentrations of the thromboxane A(2) mimetic, U 46619, were blocked by the Ca(2+) channel antagonist, verapamil. In conclusion, our results indicate that thapsigargin enhances the contractions produced by sympathetic nerve stimulation in human saphenous vein rings through the endothelial release of thromboxane A(2) that potentiates the vasoconstriction induced by the noradrenergic mediator with a verapamil-sensitive mechanism.

In this paper we study function space topologies on closed multifunctions, i.e. closed relations on X x Y using various hypertopologies. The hypertopologies are in essence, graph topologies i.e topologies on functions considered as graphs which are subsets of X x Y . We also study several topologies, including one that is derived from the Attouch-Wets filter on the range. We state embedding theorems which enable us to generalize and prove some recent results in the literature with the use of known results in the hyperspace of the range space and in the function space topologies of ordinary functions.

[EN] Recently it was shown that the lower Hausdorff metric (uniform) topology is generated by families of uniformly discrete sets as hit sets. This result leads to a new hypertopology which is the join of the above topology and the upper Vietoris topology. This uniformly discrete hit-and-miss hypertopology is coarser than the locally finite hypertopology and finer than both Hausdorff metric (uniform) topology and Vietoris topology. In this paper this new hypertopology is studied. Here is a Hasse diagram in which each arrow goes from a coarser topology to a finer one and equality follows UC or TB as indicated. The diagram clearly shows that the new (underlined) topology provides the missing link.

Previously we reported that brief exposure of HL60 cells to a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI) shifts the cells into a state of oxidative stress that induces apoptosis and necrosis. In this study, flow cytometric analysis showed that CMI/MI induces early perturbation of calcium homeostasis, increasing cytosolic and mitochondrial calcium and depleting the intracellular endoplasmic reticulum (ER) stores. The calcium chelator BAPTA-AM reduced necrosis and secondary necrosis, the loss of ΔΨm and S-glutathionylation induced by necrotic doses of CMI/MI, but did not protect against CMI/MI-induced apoptosis, mitochondrial calcium uptake and mitochondrial hyperpolarization. This indicates that increased cytoplasmic calcium does not have a causal role in the induction of apoptosis, while cross-talk between the ER and mitochondria could be responsible for the induction of apoptosis. GSH-OEt pretreatment, which enhances cellular GSH content, reduced S-glutathionylation and cytosolic and mitochondrial calcium levels, thus protecting against both apoptosis and necrosis shifting to apoptosis. Therefore, the degree of GSH depletion, paralleled by the levels of protein S-glutathionylation, may have a causal role in increasing calcium levels. The mitochondrial calcium increase could be responsible for apoptosis, while necrosis is associated with cytoplasmic calcium overload. These findings suggest that S-glutathionylation of specific proteins acts as a molecular linker between calcium and redox signalling.