XH/<Emphasis Type="Italic">π</Emphasis> interactions with the <Emphasis Type="Italic">π</Emphasis> system of porphyrin ring in porphyrin-containing proteins

Searching structures of porphyrin-containing proteins from the Protein Data Bank revealed that the π system of every porphyrin ring is involved in XH/π interactions, with most of the porphyrins having several interactions. Both five-membered pyrrole rings and six-membered chelate rings are involved in XH/π interactions; the number of interactions with five-membered rings is larger than the number of interactions with six-membered rings. We found interactions with C–H and N–H groups as hydrogen-atom donors; however, the number of CH/π interactions is much larger than the number of NH/π interactions. The amino acids involved in the interactions show a high conservation score. Our results that every porphyrin is involved in XH/π interactions and that amino acids involved in these interactions are highly conserved demonstrate that XH/π interactions play an important role in porphyrin–protein stability. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A Quantitative Comparison of Anti-HIV Gene Therapy Delivered to Hematopoietic Stem Cells versus CD4+ T Cells

Gene therapy represents an alternative and promising anti-HIV modality to highly active antiretroviral therapy. It involves the introduction of a protective gene into a cell, thereby conferring protection against HIV. While clinical trials to date have delivered gene therapy to CD4+T cells or to CD34+ hematopoietic stem cells (HSC), the relative benefits of each of these two cellular targets have not been conclusively determined. In the present analysis, we investigated the relative merits of delivering a dual construct (CCR5 entry inhibitor + C46 fusion inhibitor) to either CD4+T cells or to CD34+ HSC. Using mathematical modelling, we determined the impact of each scenario in terms of total CD4+T cell counts over a 10 year period, and also in terms of inhibition of CCR5 and CXCR4 tropic virus. Our modelling determined that therapy delivery to CD34+ HSC generally resulted in better outcomes than delivery to CD4+T cells. An early one-off therapy delivery to CD34+ HSC, assuming that 20% of CD34+ HSC in the bone marrow were gene-modified (G+), resulted in total CD4+T cell counts ≥180 cells/ µL in peripheral blood after 10 years. If the uninfected G+ CD4+T cells (in addition to exhibiting lower likelihood of becoming productively infected) also exhibited reduced levels of bystander apoptosis (92.5% reduction) over non gene-modified (G-) CD4+T cells, then total CD4+T cell counts of ≥350 cells/ µL were observed after 10 years, even if initially only 10% of CD34+ HSC in the bone marrow received the protective gene. Taken together our results indicate that: 1.) therapy delivery to CD34+ HSC will result in better outcomes than delivery to CD4+T cells, and 2.) a greater impact of gene therapy will be observed if G+ CD4+T cells exhibit reduced levels of bystander apoptosis over G- CD4+T cells.     

CHEK2 I157T and endometrial cancer

Endometrial cancer (EC) is the most common malignancy of the female reproductive system in the industrialized world. Similar to other common diseases, gene variations are believed to be able to alter an individual's predisposition to developing the disease. The CHEK2 gene encodes a tumor suppressor that takes part in various cell processes, including cell cycle regulation, DNA repair, and apoptosis. The polymorphic variant Ile157Thr in exon 3 of the gene has been demonstrated to enhance the risk of several types of cancer and at the same time to reduce the risk for developing other cancer types. To study the significance of CHEK2 I157T for EC, we have genotyped 268 patients and 449 female controls. We found carriers of I157T more often among controls than we did among patients (2.45% vs. 1.75%), but the difference was not statistically significant. Case-only analysis revealed that the variant is overrepresented in patients diagnosed at 75 or more years of age (9.09%, p = 0.05) and in those with deep myometrial invasion (3.85%, p = 0.06). The highest frequency was observed in patients with both the aforementioned characteristics (20%, p = 0.01). Tumors of I157T carriers showed endometrioid, clear cell, and mucinous morphology, which suggested that the variant may not be restricted to a certain histotype of the disease and could even be overrepresented in rare ones. This study is the first to explore the association between germline CHEK2 I157T and EC. It suggests the need for further large-scale evaluation of the role this variant plays in endometrial carcinogenesis.     

The parameters of grain filling and yield components in common wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.) and durum wheat (<Emphasis Type="Italic">Triticum turgidum</Emphasis> L. var. <Emphasis Type="Italic">durum</Emphasis>)

Final grain dry weight, a component of yield in wheat, is dependent on the duration and the rate of grain filling. The purpose of the study was to compare the grain filling patterns between common wheat, (Triticum aestivum L.), and durum wheat, (Triticum turgidum L. var. durum), and investigate relationships among grain filling parameters, yield components and the yield itself. The most important variables in differentiating among grain filling curves were final grain dry weight (W) for common wheat genotypes and grain filling rate (R) for durum wheat genotypes; however, in all cases the sets of variables important in differentiating among grain filling curves were extended to either two or all three parameters. Furthermore, in one out of three environmental conditions and for both groups of genotypes, the most important parameter in the set was grain filling duration (T). It indicates significant impact of environmental conditions on dry matter accumulation and the mutual effect of grain filling duration and its rate on the final grain dry weight. The medium early anthesis date could be associated with further grain weight and yield improvements in wheat. Grain filling of earlier genotypes occurs in more temperate environments, which provides enough time for gradual grain fill and avoids the extremes of temperature and the stress of dry conditions.     

Serum gangliosides in patients with brain tumors

In order to determine possible differences in serum gangliosides content and composition before and after surgical removal of tumor, gangliosides isolated from preoperative and postoperative sera of patients with brain tumors were analyzed. Serum samples were collected from patients with glioblastoma, meningioma, acoustic neurinoma, haemangioma, oligodendroglioma and astrocytoma, one week before and one week after surgical removal of the tumor. Serum gangliosides were qualitatively and quantitatively analyzed by high performance thin layer chromatography and laser densitometry. Results showed changes of total gangliosides concentrations in analyzed postoperative sera comparing to preoperative sera. There was not a significant difference in ganglioside pattern of preoperative vs. preoperative sera. However, a postoperative decreased proportion of ganglioside GD3 was observed in sera derived from patients with complete tumor removal. The results of this study indicate that comparative quantitative and compositional analysis of both preoperative and postoperative serum gangliosides may provide useful information concerning tumor progression, surgical success and prognosis.     

Voro3D: 3D Voronoi tessellations applied to protein structures

SUMMARY: Voro3D is an original easy-to-use tool, which provides a brand new point of view on protein structures through the three-dimensional (3D) Voronoi tessellations. To construct the Voronoi cells associated with each amino acid by a number of different tessellation methods, Voro3D uses a protein structure file in the PDB format as an input. After calculation, different structural properties of interest like secondary structures assignment, environment accessibility and exact contact matrices can be derived without any geometrical cut-off. Voro3D provides also a visualization of these tessellations superimposed on the associated protein structure, from which it is possible to model a polygonal protein surface using a model solvent or to quantify, for instance, the contact areas between a protein and a ligand. AVAILABILITY: The software executable file for PC using Windows 98, 2000, NT, XP can be freely downloaded at http://www.lmcp.jussieu.fr/~mornon/voronoi.html CONTACT: franck.dupuis@sanofi-aventis.com; jean-paul-mornon@imcp.jussieu.fr.     

Biomembranes from slaughterhouse blood erythrocytes as prolonged release systems for dexamethasone sodium phosphate

The present study investigated preparation of bovine and porcine erythrocyte membranes from slaughterhouse blood as bio‐derived materials for delivery of dexamethasone‐sodium phosphate (DexP). The obtained biomembranes, i.e., ghosts were characterized in vitro in terms of morphological properties, loading parameters, and release behavior. For the last two, an UHPLC/–HESI–MS/MS based analytical procedure for absolute drug identification and quantification was developed. The results revealed that loading of DexP into both type of ghosts was directly proportional to the increase of drug concentration in the incubation medium, while incubation at 37°C had statistically significant effect on loaded amount of DexP (P < 0.05). The encapsulation efficiency was about fivefold higher in porcine compared to bovine ghosts. Insight into ghosts’ surface morphology by field emission‐scanning electron microscopy and atomic force microscopy confirmed that besides inevitable effects of osmosis, DexP inclusion itself had no observable additional effect on the morphology of the ghosts carriers. DexP release profiles were dependent on erythrocyte ghost type and amount of residual hemoglobin. However, sustained DexP release was achieved and shown over 3 days from porcine ghosts and 5 days from bovine erythrocyte ghosts. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1046–1055, 2016     

Heliophysical activity and incidence variations of skin malignant melanoma in Czechoslovakia: A regional study

Cyclic variations in the incidence of skin malignant melanoma during the years 1964–1985 in East Bohemia (excluding the districts of Pardubice and Svitavy), Czechoslovakia have been studied, as linear correlations with solar activity indexes have been revealed. The following statistical methods were applied: periodogram regression analysis, phase-correlation analysis, sigmamethod and Student'st-test. The discretization of the data is on the basis of 1 year. Different cycles were found in the incidence variations (T=7.5 years,T=11.5 years, etc.), and this has been correlated with the variations of two heliophysical indexes (, W) for the same time period. A few significant statistical relationships have been established with a time difference (lag-period) between the extremes of the data series; the incidence maxima follow the peaks of solar activity and appear about the minima of solar indexes, mainly.This paper was presented in part at the IV National Congress of Medical Geography, 1991, Varna, Bulgaria