Conclusion : what's next ?

This book offered a broad overview of the different business models in the wine industry worldwide. It showed the diversity of this highly fragmented and extremely diverse sector. Above all, the different chapters showed that there is no dominant model and no guarantee of success at national scale in whatever we are talking about Old, New or New World wine countries. In particular, this book refutes the idea, however widespread in the Old World, that the model of the large, vertically integrated industries relying on one or more strong brands sold internationally would be the unique way for success in wine-producing countries. (...

Observational and Physical Classification of Supernovae

This chapter describes the current classification scheme of supernovae (SNe). This scheme has evolved over many decades and now includes numerous SN Types and sub-types. Many of these are universally recognized, while there are controversies regarding the definitions, membership and even the names of some sub-classes; we will try to review here the commonly-used nomenclature, noting the main variants when possible. SN Types are defined according to observational properties; mostly visible-light spectra near maximum light, as well as according to their photometric properties. However, a long-term goal of SN classification is to associate observationally-defined classes with specific physical explosive phenomena. We show here that this aspiration is now finally coming to fruition, and we establish the SN classification scheme upon direct observational evidence connecting SN groups with specific progenitor stars. Observationally, the broad class of Type II SNe contains objects showing strong spectroscopic signatures of hydrogen, while objects lacking such signatures are of Type I, which is further divided to numerous subclasses. Recently a class of super-luminous SNe (SLSNe, typically 10 times more luminous than standard events) has been identified, and it is discussed. We end this chapter by briefly describing a proposed alternative classification scheme that is inspired by the stellar classification system. This system presents our emerging physical understanding of SN explosions, while clearly separating robust observational properties from physical inferences that can be debated. This new system is quantitative, and naturally deals with events distributed along a continuum, rather than being strictly divided into discrete classes. Thus, it may be more suitable to the coming era where SN numbers will quickly expand from a few thousands to millions of events.Comment: Extended final draft of a chapter in the "SN Handbook". Comments most welcom

BLOOD VESSELS IN GANGLIA IN HUMAN ESOPHAGUS MIGHT EXPLAIN THE HIGHER FREQUENCY OF MEGAESOPHAGUS COMPARED WITH MEGACOLON

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon

Seminiferous tubule transfection in vitro to define post-meiotic gene regulation

The electronic version of this article is the complete one and can be found online at: http://www.rbej.com/content/7/1/67Background: Post-meiotically expressed genes in the testis are essential for the proper progression of spermatogenesis, and yet, aside from the construction of individual transgenic mice using specific promoters to drive reporter plasmids, there are only very limited possibilities for relevant and quantitative analysis of gene promoters. This is due to the special nature of post-meiotic haploid cells, which to date are not represented in any appropriate cell-lines. This article reports the development of novel methodology using isolated and cultured rat seminiferous tubules in a multiwell format, into which promoter-reporter constructs can be introduced by a combination of microinjection and electroporation. Methods: Culture conditions were developed which allowed the continued incubation of isolated rat seminiferous tubules for up to 48 h without obvious cell death and loss of post-meiotic cells. Transfection of intact seminiferous tubules by microinjection and electroporation was optimized to achieve high expression efficiencies of control plasmids, using either fluorescent protein or luciferase as reporters, thereby allowing both morphological as well as quantitative assessment. Results: Successful transfection was achieved into all cell types except for mature spermatozoa. However, there appeared to be only limited cell-type specificity for the promoters used, even though these had appeared to be specific when used in transgenic animals. Conclusion: We have devised a methodology which allows relatively high throughput analysis of post-meiotic gene promoters into primary cells of intact seminiferous tubules. An apparent lack of cell-type specificity suggests that the gene fragments used do not contain sufficient targeting information, or that the transient episomal expression of the constructs does not encourage appropriate expression specificity. The results also highlight the doubtful interpretation of many studies using heterologous transfection systems to analyse post-meiotically expressed genes.Sandra Danner, Christiane Kirchhoff and Richard Ivel

Intra-observer and interobserver variability of biventricular function, volumes and mass in patients with congenital heart disease measured by CMR imaging

Cardiovascular magnetic resonance (CMR) imaging provides highly accurate measurements of biventricular volumes and mass and is frequently used in the follow-up of patients with acquired and congenital heart disease (CHD). Data on reproducibility are limited in patients with CHD, while measurements should be reproducible, since CMR imaging has a main contribution to decision making and timing of (re)interventions. The aim of this study was to assess intra-observer and interobserver variability of biventricular function, volumes and mass in a heterogeneous group of patients with CHD using CMR imaging. Thirty-five patients with CHD (7–62 years) were included in this study. A short axis set was acquired using a steady-state free precession pulse sequence. Intra-observer and interobserver variability was assessed for left ventricular (LV) and right ventricular (RV) volumes, function and mass by calculating the coefficient of variability. Intra-observer variability was between 2.9 and 6.8% and interobserver variability was between 3.9 and 10.2%. Overall, variations were smallest for biventricular end-diastolic volume and highest for biventricular end-systolic volume. Intra-observer and interobserver variability of biventricular parameters assessed by CMR imaging is good for a heterogeneous group of patients with CHD. CMR imaging is an accurate and reproducible method and should allow adequate assessment of changes in ventricular size and global ventricular function

Regulation of BMAL1 Protein Stability and Circadian Function by GSK3β-Mediated Phosphorylation

Circadian rhythms govern a large array of physiological and metabolic functions. To achieve plasticity in circadian regulation, proteins constituting the molecular clock machinery undergo various post-translational modifications (PTMs), which influence their activity and intracellular localization. The core clock protein BMAL1 undergoes several PTMs. Here we report that the Akt-GSK3beta signaling pathway regulates BMAL1 protein stability and activity.GSK3beta phosphorylates BMAL1 specifically on Ser 17 and Thr 21 and primes it for ubiquitylation. In the absence of GSK3beta-mediated phosphorylation, BMAL1 becomes stabilized and BMAL1 dependent circadian gene expression is dampened. Dopamine D2 receptor mediated signaling, known to control the Akt-GSK3beta pathway, influences BMAL1 stability and in vivo circadian gene expression in striatal neurons.These findings uncover a previously unknown mechanism of circadian clock control. The GSK3beta kinase phosphorylates BMAL1, an event that controls the stability of the protein and the amplitude of circadian oscillation. BMAL1 phosphorylation appears to be an important regulatory step in maintaining the robustness of the circadian clock

Proteoglycans and osteolysis.

Osteolysis is a complex mechanism resulting from an exacerbated activity of osteoclasts associated or not with a dysregulation of osteoblast metabolism leading to bone loss. This bone defect is not compensated by bone apposition or by apposition of bone matrix with poor mechanical quality. Osteolytic process is regulated by mechanical constraints, by polypeptides including cytokines and hormones, and by extracellular matrix components such as proteoglycans (PGs) and glycosaminoglycans (GAGs). Several studies revealed that GAGs may influence osteoclastogenesis, but data are very controversial: some studies showed a repressive effect of GAGs on osteoclastic differentiation, whereas others described a stimulatory effect. The controversy also affects osteoblasts which appear sometimes inhibited by polysaccharides and sometimes stimulated by these compounds. Furthermore, long-term treatment with heparin leads to the development of osteoporosis fueling the controversy. After a brief description of the principal osteoclastogenesis assays, the present chapter summarizes the main data published on the effect of PGs/GAGs on bone cells and their functional incidence on osteolysis

Semi-automated quantification of left ventricular volumes and ejection fraction by real-time three-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown that real-time three-dimensional (3D) echocardiography (RT3DE) gives more accurate and reproducible left ventricular (LV) volume and ejection fraction (EF) measurements than traditional two-dimensional methods. A new semi-automated tool (4DLVQ) for volume measurements in RT3DE has been developed. We sought to evaluate the accuracy and repeatability of this method compared to a 3D echo standard.</p> <p>Methods</p> <p>LV end-diastolic volumes (EDV), end-systolic volumes (ESV), and EF measured using 4DLVQ were compared with a commercially available semi-automated analysis tool (TomTec 4D LV-Analysis ver. 2.2) in 35 patients. Repeated measurements were performed to investigate inter- and intra-observer variability.</p> <p>Results</p> <p>Average analysis time of the new tool was 141s, significantly shorter than 261s using TomTec (<it>p </it>< 0.001). Bland Altman analysis revealed high agreement of measured EDV, ESV, and EF compared to TomTec (<it>p </it>= <it>NS</it>), with bias and 95% limits of agreement of 2.1 ± 21 ml, -0.88 ± 17 ml, and 1.6 ± 11% for EDV, ESV, and EF respectively. Intra-observer variability of 4DLVQ vs. TomTec was 7.5 ± 6.2 ml vs. 7.7 ± 7.3 ml for EDV, 5.5 ± 5.6 ml vs. 5.0 ± 5.9 ml for ESV, and 3.0 ± 2.7% vs. 2.1 ± 2.0% for EF (<it>p </it>= <it>NS</it>). The inter-observer variability of 4DLVQ vs. TomTec was 9.0 ± 5.9 ml vs. 17 ± 6.3 ml for EDV (<it>p </it>< 0.05), 5.0 ± 3.6 ml vs. 12 ± 7.7 ml for ESV (<it>p </it>< 0.05), and 2.7 ± 2.8% vs. 3.0 ± 2.1% for EF (<it>p </it>= <it>NS</it>).</p> <p>Conclusion</p> <p>In conclusion, the new analysis tool gives rapid and reproducible measurements of LV volumes and EF, with good agreement compared to another RT3DE volume quantification tool.</p

Optical and near-infrared observations of SN 2013dx associated with GRB 130702A

We present optical and near-infrared light curves and optical spectra of SN 2013dx, associated with the nearby (redshift 0.145) gamma-ray burst GRB 130702A. The prompt isotropic gamma-ray energy released from GRB 130702A is measured to be $E_{\gamma,\mathrm{iso}} = 6.4_{-1.0}^{+1.3} \times 10^{50}$erg (1keV to 10MeV in the rest frame), placing it intermediate between low-luminosity GRBs like GRB 980425/SN 1998bw and the broader cosmological population. We compare the observed $g^{\prime}r^{\prime}i^{\prime}z^{\prime}$ light curves of SN 2013dx to a SN 1998bw template, finding that SN 2013dx evolves $\sim20$% faster (steeper rise time), with a comparable peak luminosity. Spectroscopically, SN 2013dx resembles other broad-lined Type Ic supernovae, both associated with (SN 2006aj and SN 1998bw) and lacking (SN 1997ef, SN 2007I, and SN 2010ah) gamma-ray emission, with photospheric velocities around peak of $\sim$21,000 km s$^{-1}$. We construct a quasi-bolometric ($g^{\prime}r^{\prime}i^{\prime}z^{\prime}yJH$) light curve for SN 2013dx, and, together with the photospheric velocity, we derive basic explosion parameters using simple analytic models. We infer a $^{56}$Ni mass of $M_{\mathrm{Ni}} = 0.38\pm 0.01$M$_{\odot}$, an ejecta mass of $M_{\mathrm{ej}} = 3.0 \pm 0.1$ M$_{\odot}$, and a kinetic energy of $E_{\mathrm{K}} = (8.2 \pm 0.40) \times 10^{51}$erg (statistical uncertainties only), consistent with previous GRB-associated SNe. When considering the ensemble population of GRB-associated SNe, we find no correlation between the mass of synthesized $^{56}$Ni and high-energy properties, despite clear predictions from numerical simulations that $M_{\mathrm{Ni}}$ should correlate with the degree of asymmetry. On the other hand, $M_{\mathrm{Ni}}$ clearly correlates with the kinetic energy of the supernova ejecta across a wide range of core-collapse events