The development of CD-ring modified analogs of 1alpha,25-dihydroxyvitamin D

During a 20-year collaboration the laboratories of UGent and KU Leuven have developed different series of Vitamin D analogs characterized by structural modifications in the central CD-ring system. Modifications have first involved the introduction of substituents at C11 and the epimerization at C14, and subsequently more drastic changes consisting in both ring deletion and enlargement relative to the natural CD-ring system. Lately, the focus has shifted towards the synthesis of analogs featuring a symmetrical CD-ring core. As an illustration two different series are presented.     

Evolution and Development of Ventricular Septation in the Amniote Heart

During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations.     

Digital imaging analysis of size and shape of wheat and pea upon heating under anoxic conditions as a function of the temperature

Three types of experiments were carried out. In the first series of experiments emmer wheat grains (Triticum dicoccum Schübl), var. AR, and peas (Pisum sativum L.), var. RE, were heated at temperatures ranging from 130–700 °C under controlled anoxic conditions for a maximum of 120 min. For each temperature a separate experiment was carried out in a pre-heated tube oven. Image acquisition was carried out on a flat bed scanner with a transparency adapter; for the analysis the image program IMAGE J 1.27 was used. Various size and shape factors are discussed and the definitions of the selected size and shape factors are given. The size and shape were measured and the mean calculated from thirty of the untreated specimens and the charred residues heated at each temperature. The results show a change of size and shape as a function of the temperature. The changes for wheat grains and peas are not identical. It is suggested that the presence of the pericarp enclosing the wheat grains causes this difference. In a second series of experiments it was shown that untreated grains of emmer wheat, bread wheat and macaroni wheat can be separated by measuring the shape, but size varies too much within each species, probably the result of different growing conditions, to be useful for separation purposes. As a result of heating at temperatures higher than 290 °C the shape of the three species becomes identical. This implies that the three species can no longer be separated after being heated, solely on the basis of size and shape. Finally, both emmer wheat grains enclosed by chaff and without chaff were heated under similar conditions. After removal of the chaff from the former, the size and shape of the grains were measured. The results show no significant difference in size and shape between both types.     

Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: Rationale and design of the Sonolysis study

Background

The CONSORT Statement provides recommendations for reporting randomized controlled trials. We assessed the extent to which leading medical journals that publish reports of randomized trials incorporate the CONSORT recommendations into their journal and editorial processes.

Methods

This article reports on two observational studies. Study 1: We examined the online version of 'Instructions to Authors' for 165 high impact factor medical journals and extracted all text mentioning the CONSORT Statement or CONSORT extension papers. Any mention of the International Committee of Medical Journal Editors (ICMJE) or clinical trial registration were also sought and extracted. Study 2: We surveyed the editor-in-chief, or editorial office, for each of the 165 journals about their journal's endorsement of CONSORT recommendations and its incorporation into their editorial and peer-review processes.

Results

Study 1: Thirty-eight percent (62/165) of journals mentioned the CONSORT Statement in their online 'Instructions to Authors'; of these 37% (23/62) stated this was a requirement, 63% (39/62) were less clear in their recommendations. Very few journals mentioned the CONSORT extension papers. Journals that referred to CONSORT were more likely to refer to ICMJE guidelines (RR 2.16; 95% CI 1.51 to 3.08) and clinical trial registration (RR 3.67; 95% CI 2.36 to 5.71) than those journals which did not. Study 2: Thirty-nine percent (64/165) of journals responded to the on-line survey, the majority were journal editors. Eighty-eight percent (50/57) of journals recommended authors comply with the CONSORT Statement; 62% (35/56) said they would require this. Forty-one percent (22/53) reported incorporating CONSORT into their peer-review process and 47% (25/53) into their editorial process. Eighty-one percent (47/58) reported including CONSORT in their 'Instructions to Authors' although there was some inconsistency when cross checking information on the journal's website. Sixty-nine percent (31/45) of journals recommended authors comply with the CONSORT extension for cluster trials, 60% (27/45) for harms and 42% (19/45) for non-inferiority and equivalence trials. Few journals mentioned these extensions in their 'Instructions to Authors'.

Conclusion

Journals should be more explicit in their recommendations and expectations of authors regarding the CONSORT Statement and related CONSORT extensions papers.     

Effects of NaCl salinity on 15N-nitrate fluxes and specific root length in the halophyte Plantago maritima L.

The effect of salinity on nitrate influx, efflux, nitrate net uptake rate and net nitrogen translocation to the shoot was assessed in a ¹⁵N steady state labelling experiment in the halophyte Plantago maritima L. raised for 14 days on solution supplied with 50, 100 and 200 mol m^–3 sodium chloride or without sodium chloride. Additionally, salinity induced changes in root morphology were determined. Specific root length increased upon exposure to elevated sodium chloride concentrations due to variations in biomass allocation and length growth of the tap root. Changes in root morphology, however, had a minor effect on nitrate fluxes when expressed on a root fresh weight basis. The decreased rate of nitrate net uptake in plants grown on elevated levels of sodium chloride was almost entirely due to a decrease in nitrate influx. Expressed as a proportion of influx, nitrate efflux remained unchanged and was even lower at the highest salinity level. At all sodium chloride concentrations applied the initial rate of nitrogen net translocation to the shoot decreased relative to the rate of nitrate net uptake. It is concluded that under steady state conditions the negative effect of sodium chloride on the rate of nitrate net uptake at non growth-limiting salinity levels was due to the interaction between sodium chloride and nitrate transporters in the root plasma membrane and/or processes mediating the translocation of nitrogen compounds, possibly nitrate, to the shoot.     

The Microbial Diversity of Traditional Spontaneously Fermented Lambic Beer

Lambic sour beers are the products of a spontaneous fermentation that lasts for one to three years before bottling. The present study determined the microbiota involved in the fermentation of lambic beers by sampling two fermentation batches during two years in the most traditional lambic brewery of Belgium, using culture-dependent and culture-independent methods. From 14 samples per fermentation, over 2000 bacterial and yeast isolates were obtained and identified. Although minor variations in the microbiota between casks and batches and a considerable species diversity were found, a characteristic microbial succession was identified. This succession started with a dominance of Enterobacteriaceae in the first month, which were replaced at 2 months by Pediococcus damnosus and Saccharomyces spp., the latter being replaced by Dekkera bruxellensis at 6 months fermentation duration.     

NUCLEAR RIBOSOMAL DNA INTERNAL TRANSCRIBED SPACER REGIONS (ITS1 AND ITS2) DEFINE DISCRETE BIOGEOGRAPHIC GROUPS IN CLADOPHORA ALBIDA (CHLOROPHYTA)1

Nucleotide sequences of the nuclear ribosomal DNA internal transcribed spacers (ITS1 and ITS2), the 5.8S, and short stretches of the adjacent 18S and 26S coding regions were determined in isolates from four disjunct Cladophora albida (Huds.) Kütz. populations (NE-America, W-Europe, Japan, and W-Australia). The two Pacific isolates share nearly identical ITS sequences as do the two Atlantic isolates. In contrast, interoceanic comparisons exhibit a 21% sequence difference. Variation within ITS regions is useful for identification of population groups on a regional or oceanic scale. However, both spacers are characterized by numerous repeat motifs as well as point mutations, which result in alignment problems at the interspecific level within Cladophora.     

A novel helper phage that improves phage display selection efficiency by preventing the amplification of phages without recombinant protein

Phage display is a widely used technology for the isolation of peptides and proteins with specific binding properties from large libraries of these molecules. A drawback of the common phagemid/helper phage systems is the high infective background of phages that do not display the protein of interest, but are propagated due to non-specific binding to selection targets. This and the enhanced growth rates of bacteria harboring aberrant phagemids not expressing recombinant proteins leads to a serious decrease in selection efficiency. Here we describe a VCSM13-derived helper phage that circumvents this problem, because it lacks the genetic information for the infectivity domains of phage coat protein pIII. Rescue of a library with this novel CT helper phage yields phages that are only infectious when they contain a phagemid-encoded pIII-fusion protein, since phages without a displayed protein carry truncated pIII only and are lost upon re-infection. Importantly, the CT helper phage can be produced in quantities similar to the VCSM13 helper phage. The superiority of CT over VCSM13 during selection was demonstrated by a higher percentage of positive clones isolated from an antibody library after two selection rounds on a complex cellular target. We conclude that the CT helper phage considerably improves the efficiency of selections using phagemid-based protein libraries.     

The Neuroprotective Antioxidant α-lipoic Acid Induces Detoxication Enzymes in Cultured Astroglial Cells

&#102 -Lipoic acid (LA), an antioxidant with broad neuroprotective capacity, is thought to act by scavenging reactive oxygen species and stimulation of glutathione synthesis. LA shows structural resemblance to dithiolethiones, like anethole dithiolethione (ADT). ADT protects against oxidative damage, primarily by induction of phase II detoxication enzymes, in particular NAD(P)H:quinone oxidoreductase (NQO1) and glutathione- S -transferase (GST). Therefore, we investigated whether LA, like ADT, is capable also of inducing these protective enzymes. Our data show that LA, like ADT, induces a highly significant, time- and concentration dependent, increase in the activity of NQO1 and GST in C6 astroglial cells. The LA or ADT mediated induction of NQO1 was further confirmed by quantitative PCR and western blot analysis. This work for the first time unequivocally demonstrates LA mediated upregulation of phase II detoxication enzymes, which may highly contribute to the compounds' neuroprotective potential. Moreover, the data support the notion of a common mechanism of action of LA and ADT.