The potential clinical impact of the release of two drafts of the human proteome

The authors have carried out an investigation of the two “draft maps of the human proteome” published in 2014 in Nature. The findings include an abundance of poor spectra, low-scoring peptide-spectrum matches and incorrectly identified proteins in both these studies, highlighting clear issues with the application of false discovery rates. This noise means that the claims made by the two papers – the identification of high numbers of protein coding genes, the detection of novel coding regions and the draft tissue maps themselves – should be treated with considerable caution. The authors recommend that clinicians and researchers do not use the unfiltered data from these studies. Despite this these studies will inspire further investigation into tissue-based proteomics. As long as this future work has proper quality controls, it could help produce a consensus map of the human proteome and improve our understanding of the processes that underlie health and disease.     

Downregulation of the Basic Peroxidase Isoenzyme from Zinnia elegans by Gibberellic Acid

Hypocotyl formation during the epigeal germination of seedlings is under strict hormonal regulation. In a 3 d old Zinnia elegans seedling system, gibberellic acid (GA_3) exerts an opposite effect to that exerted by light on hypocotyl photomorphogenesis because GA_3 promotes an etiolated-like growth with an inhibition of radial (secondary) growth. For this reason, the effect of GA_3 on the basic peroxidase isoenzyme from Z. Elegans (ZePrx), an enzyme involved in hypocotyl lignin biosynthesis, was studied. The results showed that GA_3 reduces ZePrx activity, similarly to the way in which it reduces seedling secondary growth. This hormonal response is supported by the analysis of the ZePrx promoter, which contains four types of GA_3-responsive cis-elements: the W Box/O2S; the Pyr Box; the GARE; and the Amy Box. Taken together, these results suggest that ZePrx is directly regulated by GA_3, with this effect matching the inhibitory effect of GA on the hypocotyl secondary growth.     

Endothelial ��-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta

S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide (^•NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and measurement of its activity were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), ^•NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). The role of GGT was assessed by stimulating enzyme activity with cosubstrate glycylglycine, as well as using two independent inhibitors, competitive serine borate complex and non-competitive acivicin. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free ^•NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In vasorelaxation experiments with endothelium-intact aorta, the half maximal effective concentration of GSNO (EC50 = 3.2±0.5.10⁻⁷ M) increased in the presence of the two distinct GGT inhibitors, serine borate complex (1.6±0.2.10⁻⁶ M) and acivicin (8.3±0.6.10⁻⁷ M), while it decreased with glycylglycine (4.7±0.9.10⁻⁸ M). In endothelium-denuded aorta, EC₅₀ for GSNO alone increased to 2.3±0.3.10⁻⁶ M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because therapeutic treatments based on GSNO are presently under development, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective.     

Spontaneous colitis cystica profunda in captive tamarins

Of the 232 tamarins (133 Saguinus mystax and 99 Saguinus labiatus) that died at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru from January 1987 to December 1990, 23 monkeys (9.9%) were diagnosed as having chronic colitis. Typically, the cecal and colonic mucosa was greyish and small yellowish cysts, measuring 1–4 mm, were found randomly distributed bulging the mucosa. Microscopically, colitis cystica profunda was diagnosed additionally in six more animals, giving a total of 29 cases (12.5%). This is the first report to our knowledge that describes colitis cystica profunda in a nonhuman primate.     

13C-N.M.R. characterizations of the sarsasapogenin disaccharides,the filiferins a and b: 2-O-(β-d-xylopyranosyl)- and 2-O(β-d-glucopyranosyl)-β-d-galactopyranosides

Filiferin B is identical to timosaponin A-III, which had previously been shown to be 3-O-[2-O-(β-d-glucopyranosyl)-β-d-galactopyranosyl]sarsasapogenin. A larger-scale isolation of filiferin B from the seeds of Yucca filifera led to the isolation of filiferin A, now shown to be 3-O-[2-O-β-d-xylopyranosyl)-β-d-galactopyranosyl]-sarsasapogenin. The presence of the xylose residue was established by way of hydrolysis. 8-Methoxycarbonyloctyl 2-O-(β-d-glucopyranosyl)-β-d-galactopyranoside was synthesized to serve as a model for interpretation of the ¹³C-n.m.r. spectrum of filiferin B. The information thus gained, together with the ¹³C-n.m.r. spectra of other, simple model-compounds, permitted assignment of the structure for filiferin A. 8-Methoxycarbonyloctyl 2-O-(α-d-glucopyranosyl)-β-d-galactopyranoside was also synthesized.     

A parametrization of the CT number of a substance and its use for stoichiometric calibration

A method to carry out stoichiometric calibrations of CT scanners employed in radiotherapy treatment planning is proposed. The method is based on a simple parametrization of the CT number of a substance, which involves only two variables to describe the substance (electron density and one effective atomic number) and one parameter to describe the beam. The method was tested experimentally on a group of beams. A set of no tissue-like substances of known densities and elemental compositions were employed as calibrators. CT number-to-density curves (RED curves) were calculated with the proposed parametrization and compared to those measured with a commercial density phantom. Differences between the electron densities assigned by the calculated RED curves and the measured ones were in the range 0.009–0.019 (RMS). The proposed method may be employed to carry out accurate stoichiometric calibrations by using only one suitable substance as calibrator, not necessarily tissue-like.     

Endometriosis: New concepts in the pathogenesis

Endometriosis is a gynaecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Though there are several theories, research scientists remain unsure as to the definitive cause(s) of endometriosis. Considering the relevant health problems caused by endometriosis, all new information on the pathogenesis of this disease, may have important clinical implications. Goal of this article is to summarize the latest advances in the pathogenesis of endometriosis, with particular emphasis on the embryological theory, that has been recently re-proposed. The possible clinical implications of these findings will be discussed.