Pointwise estimates for the Bergman kernel of the weighted Fock space

We prove upper pointwise estimates for the Bergman kernel of the weighted Fock space of entire functions in $L^2(e^{-2\phi})$ where $\phi$ is a subharmonic function with $\Delta \phi$ a doubling measure. We derive estimates for the canonical solution operator to the inhomogeneous Cauchy-Riemann equation and we characterize the compactness of this operator in terms of $\Delta \phi$

Luminescent Bimetallic IrIII /AuI Peptide Bioconjugates as Potential Theranostic Agents

Diverse iridium peptide bioconjugates and the corresponding iridium/gold bimetallic complexes have been synthesized starting from a cyclometallated carboxylic acid substituted IrIII complex [Ir(ppy)2 (Phen-5-COO)] by solid phase peptide synthesis (SPPS). The selected peptide sequences were an enkephalin derivative Tyr-Gly-Gly-Phe-Leu together with the propargyl-substituted species Tyr-Gly-Pgl-Phe-Leu to allow gold coordination (Pgl: propyrgyl-glycine, HC=C-Gly), and a specific short peptide, Ala-Cys-Ala-Phen, containing a cysteine residue. Introduction of the gold center has been achieved via a click reaction with the alkynyl group leading to an organometallic Au-C(triazole) species, or by direct coordination to the sulfur atom of the cysteine. The photophysical properties of these species revealed predominantly an emission originating from the Ir complex, using mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity. The formation of the peptide bioconjugates caused a systematic redshift of the emission profiles. Lysosomal accumulation was observed for all the complexes, in contrast to the expected mitochondrial accumulation triggered by the gold complexes. Only the cysteine-containing Ir/Au bioconjugate displayed cytotoxic activity. The absence of activity may be related to the lack of endosomal/lysosomal escape for the cationic peptide conjugates. Interestingly, the different coordination sphere of the gold atom may play a crucial role, as the Au-S(cysteine) bond may be more readily cleaved in a biological environment than the Au-C(triazole) bond, and thus the Au fragment could be released from or trapped in the lysosomes, respectively. This work represents a starting point in the development of bimetallic peptide bioconjugates as theranostics and in the knowledge of factors that contribute to anti-proliferative activity

Exploring the endocannabinoidome in genetically obese (ob/ob) and diabetic (db/db) mice: Links with inflammation and gut microbiota

Background: Obesity and type 2 diabetes are two interrelated metabolic disorders characterized by insulin resistance and a mild chronic inflammatory state. We previously observed that leptin (ob/ob) and leptin receptor (db/db) knockout mice display a distinct inflammatory tone in the liver and adipose tissue. The present study aimed at investigating whether alterations in these tissues of the molecules belonging to the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system, whose functions are important in the context of metabolic disorders and inflammation, could reflect their different inflammatory phenotypes. Results: The basal eCBome lipid and gene expression profiles, measured by targeted lipidomics and qPCR transcriptomics, respectively, in the liver and subcutaneous or visceral adipose tissues, highlighted a differentially altered eCBome tone, which may explain the impaired hepatic function and more pronounced liver inflammation remarked in the ob/ob mice, as well as the more pronounced inflammatory state observed in the subcutaneous adipose tissue of db/db mice. In particular, the levels of linoleic acid-derived endocannabinoid-like molecules, of one of their 12-lipoxygenase metabolites and of Trpv2 expression, were always altered in tissues exhibiting the highest inflammation. Correlation studies suggested the possible interactions with some gut microbiota bacterial taxa, whose respective absolute abundances were significantly different between ob/ob and the db/db mice. Conclusions: The present findings emphasize the possibility that bioactive lipids and the respective receptors and enzymes belonging to the eCBome may sustain the tissue-dependent inflammatory state that characterizes obesity and diabetes, possibly in relation with gut microbiome alterations

Wnt Signaling Through Nitric Oxide Synthase Promotes the Formation of Multi-Innervated Spines

Structural plasticity of synapses correlates with changes in synaptic strength. Dynamic modifications in dendritic spine number and size are crucial for long-term potentiation (LTP), the cellular correlate of learning and memory. Recent studies have suggested the generation of multi-innervated spines (MIS), in the form of several excitatory presynaptic inputs onto one spine, are crucial for hippocampal memory storage. However, little is known about the molecular mechanisms underlying MIS formation and their contribution to LTP. Using 3D enhanced resolution confocal images, we examined the contribution of Wnt synaptic modulators in MIS formation in the context of LTP. We show that blockage of endogenous Wnts with specific Wnt antagonists supresses the formation of MIS upon chemical LTP induction in cultured hippocampal neurons. Gain- and loss-of-function studies demonstrate that Wnt7a signaling promotes MIS formation through the postsynaptic Wnt scaffold protein Disheveled 1 (Dvl1) by stimulating neuronal nitric oxide (NO) synthase (nNOS). Subsequently, NO activates soluble guanylyl cyclase (sGC) to increase MIS formation. Consistently, we observed an enhanced frequency and amplitude of excitatory postsynaptic currents. Collectively, our findings identify a unique role for Wnt secreted proteins through nNOS/NO/sGC signaling to modulate MIS formation during LTP

Extreme Energy Cosmic Rays (EECR) Observation Capabilities of an "Airwatch from Space'' Mission

The longitudinal development and other characteristics of the EECR induced atmospheric showers can be studied from space by detecting the fluorescence light induced in the atmospheric nitrogen. According to the Airwatch concept a single fast detector can be used for measuring both intensity and time development of the streak of fluorescence light produced by the atmospheric shower induced by an EECR. In the present communication the detection capabilities for the EECR observation from space are discussed.Comment: 3 pages (LaTeX). To appear in the Proceedings of TAUP'9

Classification, characterization and management of radioactive waste in Italy

Radioactive waste produced in Italy belongs to two main categories according to production routes. These are radioactive waste generated from the nuclear fuel cycle and those radioactive waste deriving from non-electronuclear activities, i.e., from nuclear medicine activities, industrial, and scientific research. The latter are responsibility of the Integrated Service for the management of radioactive waste: a group of authorized Operators supervised by ENEA (Italian National Agency for New Technologies, Energy and Sustainable Economic Development). In this paper, the Italian regulatory framework, the classification of radioactive waste and the most used characterization techniques, both destructive and nondestructive, are outlined

Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice

Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice. In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on dopaminergic signaling at the mesolimbic circuit. By confocal and correlative light and electron microscopy (CLEM) morphological studies coupled to molecular, biochemical, and pharmacological approaches, we investigated OX-A-mediated dopaminergic signaling at the LH-VTA-nucleus accumbens (NAc) pathway in obese ob/ob mice compared to wild-type (wt) lean littermates. We found an elevation of OX-A trafficking and release to the VTA of ob/ob mice and consequent orexin receptor-1 (OX1R)-mediated over-activation of dopaminergic (DA) neurons via phospholipase C (PLC)/diacylglycerol lipase (DAGL-α)-induced biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). In fact, by retrograde signaling to cannabinoid receptor type 1 (CB1R) at inhibitory inputs to DA neurons, 2-AG inhibited GABA release thus inducing an increase in DA concentration in the VTA and NAc of ob/ob mice. This effect was prevented by the OX1R antagonist SB-334867 (30 mg/Kg, i.p.), or the CB1R antagonist AM251 (10 mg/Kg, i.p.) and mimicked by OX-A injection (40 μg/Kg, i.p.) in wt lean mice. Enhanced DA signaling to the NAc in ob/ob mice, or in OX-A-injected wt mice, was accompanied by β-arrestin2-mediated desensitization of dopamine D2 receptor (D2R) in a manner prevented by SB-334867 or the D2R antagonist L741 (1.5 mg/Kg, i.p.). These results further support the role of OX-A signaling in the control of neuroadaptive responses, such as compulsive reward-seeking behavior or binge-like consumption of high palatable food, and suggest that aberrant OX-A trafficking to the DA neurons in the VTA of ob/ob mice influences the D2R response at NAc, a main target area of the mesolimbic pathway, via 2-AG/CB1-mediated retrograde signaling