Phosphoinositide Signaling in Unicellular Eukaryotes

The review considers the up to date achievements in the role of membrane phosphoinositides and keys enzymes of the lipid branch of the phosphoinositide signal pathway (PI-pathway) in unicellular eukaryotes. Particular attention is paid to mechanisms of phospholipase C (PLC) activation and the PLC interaction both with cell surface receptors and with the effector cytoplasm targets. The role of protein kinase C (PKC) in intracellular signaling and the relationship of the PI-pathway key enzymes with protein tyrosine kinases (PTK)-signaling and cAMP-protein kinase A (PKA) pathway are discussed.     

Recurrent pre‐existing and acquired DNA copy number alterations,including focal TERT gains,in neuroblastoma central nervous system metastases

Stage 4 neuroblastomas have a high rate of local and metastatic relapse and associated disease mortality. The central nervous system (CNS) is currently one of the most common isolated relapse sites, yet the genomic alterations that contribute to these metastases are unknown. This study sought to identify recurrent DNA copy number alterations (CNAs) and target genes relating to neuroblastoma CNS metastases by studying 19 pre‐CNS primary tumors and 27 CNS metastases, including 12 matched pairs. SNP microarray analyses revealed that MYCN amplified (MYCNA) tumors had recurrent CNAs different from non‐MYCNA cohorts. Several CNAs known to be prevalent among primary neuroblastomas occurred more frequently in CNS metastases, including 4p?, 7q+, 12q+, and 19q? in non‐MYCNA metastases, and 9p? and 14q? irrespective of MYCNA status. In addition, novel CNS metastases‐related CNAs included 18q22.1 gains in non‐MYCNA pre‐CNS primaries and 5p15.33 gains and 15q26.1→tel losses in non‐MYCNA CNS metastases. Based on minimal common regions, gene expression, and biological properties, TERT (5p), NR2F2 (15q), ALDH1A3 (15q), CDKN2A (9p), and possibly CDH7 and CDH19 (18q) were candidate genes associated with the CNS metastatic process. Notably, the 5p15 minimal common region contained only TERT, and non‐MYCNA CNS metastases with focal 5p15 gains had increased TERT expression, similar to MYCNA tumors. These findings suggest that a specific genomic lesion (18q22.1 gain) predisposes to CNS metastases and that distinct lesions are recurrently acquired during metastatic progression. Among the acquired lesions, increased TERT copy number and expression appears likely to function in lieu of MYCNA to promote CNS metastasis. © 2013 Wiley Periodicals, Inc.     

Interferon-β Production via Dectin-1-Syk-IRF5 Signaling in Dendritic Cells Is Crucial for Immunity to C. albicans

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Functional tongue and floor of mouth reconstruction with a chimeric flap after total glossectomy

Oral and Maxillofacial Surgery - Presently, the functional reconstruction of the tongue in patients after subtotal or total glossectomy with the removal of the oral floor muscles and spearing of...     

Enzymatic synthesis and electrochemical characterization of sodium 1,2-naphthoquinone-4-sulfonate-doped PEDOT/MWCNT composite

The development of novel materials with improved functional characteristics for supercapacitor electrodes is of current concern and calls for elaboration of innovative approaches. We report on an eco-friendly enzymatic synthesis of a composite based on poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-walled carbon nanotubes (MWCNTs). The redox active compound, sodium 1,2-naphthoquinone-4-sulfonate (NQS), was used as a dopant for the backbone of the polymer. Oxidative polymerization of 3,4-ethylenedioxythiophene (EDOT) was catalyzed by a high redox potential laccase from the fungus Trametes hirsuta. Atmospheric oxygen served as an oxidant. A uniform thin layer of NQS-doped PEDOT formed on the surface of MWCNTs as a result of the enzymatic polymerization. The PEDOT–NQS/MWCNT composite showed a high specific capacitance of ca. 575 F g⁻¹ at a potential scan rate of 5 mV s⁻¹ and an excellent cycling stability within a potential window between −0.5 and 1.0 V, which makes it a promising electrode material for high-performance supercapacitors.

The use of redox active NSQ as a dopant of PEDOT dramatically increases the specific capacitance and cyclic stability of enzymatically synthesized PEDOT–NSQ/MWCNT composite.     

Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia

Little is known about the physiological roles of the M5 muscarinic receptor, the last member of the muscarinic receptor family (M1-M5) to be cloned. In the brain, the M5 receptor subtype is preferentially expressed by dopaminergic neurons of the substantia nigra and the ventral tegmental area. Dopaminergic neurons located in the ventral tegmental area are known to play important roles in mediating both the rewarding effects of opiates and other drugs of abuse and the manifestations of opiate/drug withdrawal symptoms. We therefore speculated that acetylcholine-dependent activation of M5 receptors might modulate the manifestations of opiate reward and withdrawal. This hypothesis was tested in a series of behavioral, biochemical, and neurochemical studies using M5 receptor-deficient mice (M5-/- mice) as novel experimental tools. We found that the rewarding effects of morphine, as measured in the conditioned place preference paradigm, were substantially reduced in M5-/- mice. Furthermore, both the somatic and affective components of naloxone-induced morphine withdrawal symptoms were significantly attenuated in M5-/- mice. In contrast, the analgesic efficacy of morphine and the development of tolerance to the analgesic effects of morphine remained unaltered by the lack of M5 receptors. The finding that M5 receptor activity modulates both morphine reward and withdrawal processes suggests that M5 receptors may represent a novel target for the treatment of opiate addiction.