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Irregular regeneration or inappropriate remodeling of the axons of the primary afferent neurons after peripheral nerve trauma could be associated with the development of neuropathic pain. We analyzed the molecular mechanisms for the neuritogenesis and neurite outgrowth caused by prostaglandin E 2 (PGE 2) in mouse dorsal root ganglion (DRG) neurons, and evaluated their opioid modulation. PGE 2 in combination with IBMX, a phosphodiesterase inhibitor, caused neuritogenesis/neurite outgrowth in DRG cells, an effect abolished by a prostanoid EP 4 , but not EP 2 , receptor antagonist, and inhibitors of adenylyl cyclase or protein kinase A (PKA). Blockers of T-type Ca2+ channels (T-channels), that are responsible for window currents involving the sustained low-level Ca2+ entry at voltages near the resting membrane potentials and can be functionally upregulated by PKA, inhibited the neuritogenesis/neurite outgrowth caused by PGE 2 /IBMX or dibutylyl cyclic AMP, a PKA activator, in DRG neurons, an inhibitory effect mimicked by ZnCl 2 and ascorbic acid that block Ca v 3.2, but not Ca v 3.1 or Ca v 3.3, T-channels. Morphine and DAMGO, μ-opioid receptor (MOR) agonists, suppressed the neuritogenesis and/or neurite outgrowth induced by PGE 2 /IBMX in DRG neurons and also DRG neuron-like ND7/23 cells, an effect reversed by naloxone or β-funaltrexamine, a selective MOR antagonist. Our data suggest that the EP 4 receptor/PKA/Ca v 3.2 pathway is involved in the PGE 2 -induced neuritogenesis/neurite outgrowth in DRG neurons, which can be suppressed by MOR stimulation. We propose that MOR agonists including morphine in the early phase after peripheral nerve trauma might delay the axonal regeneration of the primary afferent neurons but prevent the development of neuropathic pain. [Display omitted] • PGE 2 causes neuritogenesis and neurite outgrowth in mouse DRG neurons. • The effect of PGE 2 is mediated by the EP 4 receptor/PKA/Ca v 3.2 channel pathway. • The effect of PGE 2 is reduced by μ-opioid receptor agonists. • Opioids modulate axonal regeneration or remodeling after sensory nerve trauma. [ABSTRACT FROM AUTHOR]

Abstract: For a nilpotent linear transformation of a vector space V of Jordan type , i.e. the sizes of the Jordan blocks equal to the conjugate of λ, let be the set of f-stable subspaces of dimension d. is partitioned indexed by Littlewood–Richardson tableaux (LR-tableau) T of shapes ''s with , each of which corresponds to the set consisting of such that the dimension of the vector space is equal to the number of cells (squares) in the rth row of T filled with the letter t for all . We define a partial order on the set of LR-tableaux of shapes ''s with by if is contained in the closure of in the Grassmaniann . We give a certain sufficient condition (Corollary C), and a necessary condition (Corollary D) for . For this we introduce the notions of generic vectors, the generic subspace , the rational function field , and the LR-tableau associated to a tableau T, and then show; the map , , where is the subtableau of an LR-tableau T consisting of the cells filled with the letters greater than 1, is a fiber bundle with fiber isomorphic to a union of Schubert cells and is nonsingular (Theorem A); the generic subspace of a tableau T is a generic point of whose function field isomorphic to the rational function field associated to the LR-tableau (Theorem B). [Copyright &y& Elsevier]

Abstract: Adipose differentiation-related protein (ADRP) and TIP47 show sequence similarity, particularly in their N-terminal PAT-1 domain. Under standard culture conditions, ADRP existed in most lipid droplets (LDs), whereas TIP47 was observed only in some LDs and recruited to LDs on treatment with fatty acids. By analyzing deletion mutants, we found that the C-terminal half of TIP47, or more specifically the putative hydrophobic cleft [S.J. Hickenbottom, A.R. Kimmel, C. Londos, J.H. Hurley, Structure of a lipid droplet protein; the PAT family member TIP47, Structure (Camb) 12 (2004) 1199–1207.], was involved in LD targeting and responsiveness to fatty acids. The result contrasted with that observed for ADRP and implied a distinct LD-targeting mechanism for TIP47. Consistent with this, overexpression of Rab18 decreased ADRP, but not TIP47, from LDs, and TIP47 did not displace pre-existing ADRP from LDs. But ADRP may be a factor to control the TIP47 behavior, because TIP47 in LDs increased upon down-regulation of ADRP. The results suggested that the putative hydrophobic cleft is critical for the unique characteristics of TIP47. [Copyright &y& Elsevier]

Background A retrospective study was performed at some high-volume institutions to clarify the prognostic significance of postoperative complications in patients who had undergone hepatectomy for hepatocellular carcinoma (HCC). No published studies have investigated the relationship between postoperative complications of Clavien–Dindo grade III or more and prognosis in patients who have undergone hepatic resection. Methods Patient data were retrospectively collected for 966 consecutive patients who had undergone hepatectomy for HCC with curative intent between January 2004 and December 2012. The patients were assigned to two groups according to the presence of postoperative complications. Clinicopathologic, surgical outcome, and long-term survival data were analyzed. Results Hospital deaths occurred in nine patients (0.9%). Postoperative complications were identified in 165 patients (17.1%). Compared with patients without complications, patients with complications had significantly larger tumors, more advanced-stage tumors, more poorly differentiated tumors, more intrahepatic metastasis, longer operation time, greater blood loss, more blood transfusion, and more anatomic resection and combined resection. The overall 5-y survival rates were 48.6% in patients with postoperative complications and 73.2% in patients without them. The 5-y recurrence-free survival rates were 23.7% in patients with postoperative complications and 36.7% in patients without them. Multivariate analysis revealed that longer operation time and lower serum albumin level of albumin were independent predictive factors for occurrence of postoperative complications. Conclusions In patients with HCC, posthepatectomy complications are predictive of a worse overall survival, even when adjustments have been made for other known predictors. [ABSTRACT FROM AUTHOR]

Abstract: CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily. It is expressed at high levels in adipose tissue and has recently emerged as a novel adipokine. In the present study, we provide the first evidence for a physiological role of the new adipokine, CTRP3, in the reproductive system. CTRP3 was specifically expressed in interstitial Leydig cells, where testosterone is produced, in the adult mouse testis. CTRP3 increased testosterone production by TM3 mouse Leydig cells in a dose-dependent manner. The increased testosterone production was linked to upregulation of steroidogenic proteins expression, such as steroidogenic acute regulatory (StAR) protein and cholesterol side-chain cleavage cytochrome P450 (P450scc). Moreover, increases in intracellular cyclic AMP (cAMP) concentrations and the phosphorylation of cAMP-response element binding protein (CREB) in CTRP3-stimulated TM3 Leydig cells were observed. Inhibition of this signaling pathway by a specific protein kinase A (PKA) inhibitor, H89, blocked testosterone production in CTRP3-stimulated Leydig cells, suggesting that the stimulatory effect of CTRP3 on testosterone production is associated with activation of the cAMP/PKA signaling pathway. Thus, our results demonstrate a physiological role for CTRP3 in testicular steroidogenesis and provide novel insights in the intracellular mechanisms activated by this protein. [Copyright &y& Elsevier]