Localization of inhibins and activins in normal endocrine cells and endocrine tumors of the gut and pancreas: an immunohistochemical and in situ hybridization study

Activins and inhibins, which belong to the TGF beta family, are composed of different combinations of alpha-, betaA-, and betaB-subunits, resulting in inhibin A (alphabetaA), inhibin B (alphabetaB), activin A (betaAbetaA), activin B (betaBbetaB), and activin AB (betaAbetaB). They regulate several cell functions, acting as paracrine/autocrine factors. Their actions, which depend on binding to specific receptors, are also modulated by follistatin. Gastroenteropancreatic (GEP) endocrine cells and endocrine tumors (ETs) produce several growth factors, but it is not well known whether they express follistatin and the various inhibin/activin subunits. We studied their expression in 65 GEP ETs using immunohistochemistry (IHC) and in situ hybridization (ISH). The alpha-subunit and follistatin were not identified in normal GEP endocrine cells and were poorly expressed in ETs. A betaA-subunit immunoreactivity (IR) was detected in A-, G-, EC-, and GIP-cells, while betaB-chain IR was present only in D-cells. The mRNAs encoding for these molecules were poorly expressed in normal tissues. BetaA- and betaB-subunits were identified in several ETs by both IHC and ISH: betaA-subunit mainly in G-cell and A-cell ETs, and betaB-subunit in D-cell, A-cell, and EC-cell ETs. Our results demonstrate a differential expression of activin/inhibin subunits among different types of GEP endocrine cells and related tumors, suggesting a role in modulation of biological functions of these normal and neoplastic endocrine cell

Types of logistics outsourcing and related impact on the 3PL buying process: empirical evidence

Although logistics outsourcing is recognised as a competitive parameter, so far there has been no adequate research on the types of logistics outsourcing and their implications in terms of the third-party logistics (3PL) buying process. This paper fills the gap by focussing on two key issues, i.e., required competitive advantages and 3PL selection criteria. The aim is to provide a comprehensive investigation of such factors and study if and how they vary depending on the outsourcing type. After a literature review and a focus group, a survey of 482 logistics managers was conducted, and a statistical analysis of results was performed. The findings are of interest to both shippers and 3PL providers because they help the former understand which outsourcing type is the most suitable to achieve the desired competitive advantages, and the latter to evaluate the key factors to focus on depending on the required type of outsourcing

Relationships between crystalline structure and dielectric properties in Sr2Sm(1-x)NdxTi2Nb3O15 ceramics

In this study, tungsten-bronze type materials of Sr2Sm(1-x)NdxTi2Nb3O15 composition (x=0; 0,25; 0,5; 0,75 and 1) were elaborated by classical solid-state reaction. The structural characterization demonstrate that these compounds present tetragonal symmetry, using two space groups P4bm (N°100) and P4/mbm (N°127) respectively. The lattice parameters are a=b≈12,2Ǻ; c≈3,8Ǻ; V≈579,03Ǻ and Z=2. In this compounds, Ti and Nb cations show obvious off-center displacements along the c axis in both the Ti/Nb(1)O6 and the Ti/Nb(2)O6 octahedra. Besides, the unequal Ti/Nb(2)–O bonds length in the equatorial plane of Ti/Nb(2)O6 octahedra indicates the displacement of the Ti/Nb(2) cations in the ab plane, and no displacement of the Ti/Nb(1) cations exists in the ab plane. The results show that this material has two types of octahedral, first octahedron with little deformation around the Ti1/Nb1 and the second octahedron are more distorted around the Ti2/Nb2. The measurements of permittivity and dielectric losses of the ceramic samples performed between 25°C and 700°C (100Hz to 1MHz), high dielectric constants (εr=127 ~ 194) and low dielectric losses (tan(δ) around 10-4 at 1MHz) were found. The maximum value of the dielectric constant is obtained for x=0 (εr=194). The Curie temperature Tc decreases from 332 to 246°C as a function of the substitution of the samarium by neodymium. Detailed microstructural analysis by scanning electron microscope (SEM) and (EDS) for this compounds are also investigated

Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models

SummaryIncreased levels of the mitochondria-shaping protein Opa1 improve respiratory chain efficiency and protect from tissue damage, suggesting that it could be an attractive target to counteract mitochondrial dysfunction. Here we show that Opa1 overexpression ameliorates two mouse models of defective mitochondrial bioenergetics. The offspring from crosses of a constitutive knockout for the structural complex I component Ndufs4 (Ndufs4−/−), and of a muscle-specific conditional knockout for the complex IV assembly factor Cox15 (Cox15sm/sm), with Opa1 transgenic (Opa1tg) mice showed improved motor skills and respiratory chain activities compared to the naive, non-Opa1-overexpressing, models. While the amelioration was modest in Ndufs4−/−::Opa1tg mice, correction of cristae ultrastructure and mitochondrial respiration, improvement of motor performance and prolongation of lifespan were remarkable in Cox15sm/sm::Opa1tg mice. Mechanistically, respiratory chain supercomplexes were increased in Cox15sm/sm::Opa1tg mice, and residual monomeric complex IV was stabilized. In conclusion, cristae shape amelioration by controlled Opa1 overexpression improves two mouse models of mitochondrial disease

Business logistics models in omni-channel: a classification framework and empirical analysis

Purpose – Companies are currently moving from multi-channel strategies to offer their customers an omni-channel (OC) experience. So far, OC research has been mainly tackled from a sales-based view, with numerous operational challenges to be fully investigated yet. The purpose of this paper is to investigate how companies set the logistics variables in their OC management strategy and the business logistics models currently most adopted. Design/methodology/approach – A two-step methodology was adopted. First, a systematic combining approach with scientific literature review and case studies allowed to derive a framework for classifying the key logistics variables and the related options. The framework was then used to conduct a qualitative survey targeting 92 Italian companies operating in food manufacturing, food retailing and non-food retailing. Collected data were analysed by means of cluster analysis. Findings – Implementing an OC management strategy requires to set 11 logistics variables belonging to four strategic areas: delivery service, distribution setting, fulfilment strategy and returns management. A broad empirical investigation showed the choices made by companies when setting the logistics variables to implement an OC management strategy. Lastly, four business logistics models, differing in terms of both business sector and OC maturity, were discussed. Originality/value – The proposed framework extends earlier studies by including additional significant logistics variables. The empirical analysis provides new insights on how to re-structure the business logistics model in OC, suggesting channel integration and the coexistence of multiple configurations as main enablers of an OC proposition

Metachronous hepatic metastases from gastric carcinoma: a multicentric survey

BACKGROUND: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. OBJECTIVE: To survey the clinical approach to the subset of atients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. METHODS: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D >or= 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. RESULTS: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018) of the gastric primary and by the therapeutic approach to the metastases (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p<0.001). CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible

Epitaxial growth and properties of lead-free ferroelectric Na0.5Bi0.5TiO3 thin films grown by pulsed laser deposition on various single crystal substrates

International audienceThe epitaxial growth of lead-free ferroelectric Na0.5Bi0.5TiO3 (NBT) thin films on various single crystal substrates was successfully achieved, using the pulsed laser deposition technique (PLD). The present work is divided in two parts, focused on: (i) the growth of NBT layers on c- and r-sapphire (Al2O3) substrates, with and without introducing a CeO2 buffer layer, and (ii) the growth of NBT layers on bare (001)SrTiO3 substrates, with and without introducing a LaNiO3 layer, that could be used as a bottom electrode. In the first part, it was shown that the introduction of a CeO2 buffer layer completely modifies the out-of-plane growth orientation of the NBT films, as well as their microstructure. Indeed, (001)NBT films epitaxially grow only on r-Al2O3 substrates buffered with epitaxial (001)CeO2 layers, while, growing simply NBT on top of bare c or r-Al2O3 substrates, or on top of CeO2/c-Al2O3 heterostructures leads to polycrystalline or textured films. In the second part, we demonstrate that (001)-oriented NBT layers deposited on either bare (001)SrTiO3 or (001)SrTiO3 substrates (STO) covered with (001)LaNiO3 (LNO) are systematically epitaxially grown. Furthermore, the microstructure of the samples is strongly affected by the introduction of the LaNiO3 layer

Role of neuronal and inducible nitric oxide synthases in the guinea pig ileum myenteric plexus during in vitro ischemia and reperfusion

Background Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. Methods The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Westernimmunoblotting and real time RT-PCR, respectively. NO levels were quantified as nitrite/nitrate. Key Results After in vitro I/R the proportion of nNOSexpressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by Nx-propyl-L-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. Conclusions &amp; Inferences Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more relevant role for this isoform in the alterations occurring in myenteric neurons following I/R