Consensus statement on measures to promote equitable authorship in the publication of research from international partnerships.

Despite the acknowledged injustice and widespread existence of parachute research studies conducted in low- or middle-income countries by researchers from institutions in high-income countries, there is currently no pragmatic guidance for how academic journals should evaluate manuscript submissions and challenge this practice. We assembled a multidisciplinary group of editors and researchers with expertise in international health research to develop this consensus statement. We reviewed relevant existing literature and held three workshops to present research data and holistically discuss the concept of equitable authorship and the role of academic journals in the context of international health research partnerships. We subsequently developed statements to guide prospective authors and journal editors as to how they should address this issue. We recommend that for manuscripts that report research conducted in low- or middle-income countries by collaborations including partners from one or more high-income countries, authors should submit accompanying structured reflexivity statements. We provide specific questions that these statements should address and suggest that journals should transparently publish reflexivity statements with accepted manuscripts. We also provide guidance to journal editors about how they should assess the structured statements when making decisions on whether to accept or reject submitted manuscripts. We urge journals across disciplines to adopt these recommendations to accelerate the changes needed to halt the practice of parachute research.

Biased Complement Diversity Selection for Effective Exploration of Chemical Space in Hit-Finding Campaigns.

The success of hit-finding campaigns relies on many factors, including the quality and diversity of the set of compounds that is selected for screening. This paper presents a generalized workflow that guides compound selections from large compound archives with opportunities to bias the selections with available knowledge in order to improve hit quality while still effectively sampling the accessible chemical space. An optional flag in the workflow supports an explicit complement design function where diversity selections complement a given core set of compounds. Results from three project applications as well as a literature case study exemplify the effectiveness of the approach, which is available as a KNIME workflow named Biased Complement Diversity (BCD).

Cancer survivorship issues with radiation and hemorrhagic cystitis in gynecological malignancies.

PURPOSE: Given that more cancers are being diagnosed earlier and that treatment of cancer is improving, health issues of cancer survivors are becoming more common and apparent. Pelvic radiation therapy for the treatment of gynecological cancers can lead to long-term collateral damage to the bladder, a condition termed radiation cystitis (RC). Late sequelae may take many years to develop and include incontinence and pain as well as hematuria. RC is a rare but potentially life-threatening condition for which there are few management and treatment options. METHODS: There are limited data in the literature regarding the effects of radiation on the bladder after gynecological cancer therapy and we hereby review the literature on cancer survivorship issues of pelvic radiation for gynecology literature. RESULTS: Treatment options are available for patients with radiation-induced hemorrhagic cystitis. However, most treatments are risky or only effective for a short timeframe and no therapy is currently available to reverse the disease progress. Furthermore, no standardized guidelines exist describing preferred management options. Common therapies include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Novel developing strategies include Botulinum Toxin injections and liposomal-tacrolimus instillations. These treatments and strategies are discussed. CONCLUSIONS: In this review, we will present current and advanced therapeutic strategies for RC to help cancer survivors deal with long-term bladder health issues.

Highlights of recent progress in plant lipid research.

Raw fossil material reserves are not inexhaustible and as prices continue to raise it is necessary to find new sources of alternative and renewable energy. Oils from oleaginous field crops (sunflower and rape) with properties close to those of fossil fuel could constitute an alternative source of energy for the production of raw materials. This is the context in which the 18th International Symposium on Plant lipids (ISPL) was held in Bordeaux from 20th to 25th July 2008 at "La Cité Mondiale". The 18th ISPL gathered 270 researchers from 33 countries. Sixty nine oral communications and 136 posters were presented during the 12 sessions of the Symposium. The sessions have covered all the different aspects of the Plant Lipid field including: Surface lipids: suberin, cutin and waxes, Fatty acids, Glycerolipids, Plant lipids as renewable sources of energy, Seed oils and bioengineering of metabolic pathways, Lipid catabolism, Models for lipid studies: lower plants, micro-organisms and others, Modifications of proteins by lipids, Sphingolipids, sterols and isoprenoids, Lipid signaling and plant stress responses, Lipid trafficking and membrane dynamics, New methods and technologies: functional lipidomics, fluxome, modelling. During the ISPL 2008 Bordeaux, important and new information was reported in the different fields. A selection of these results is presented here.

Macrocyclic inhibitors for peptide deformylase: a structure-activity relationship study of the ring size.

Peptide deformylase (PDF) catalyzes the removal of the N-terminal formyl group from newly synthesized polypeptides in eubacteria. Its essential role in bacterial cells but not in mammalian cells makes it an attractive target for antibacterial drug design. We have previously reported an N-formylhydroxylamine-based, metal-chelating macrocyclic PDF inhibitor, in which the P(1)' and P(3)' side chains are covalently joined. In this work, we have carried out a structure-activity relationship study on the size of the macrocycle and found that 15-17-membered macrocycles are optimal for binding to the PDF active site. Unlike the acyclic compounds, which are simple competitive inhibitors, the cyclic compounds all act as slow-binding inhibitors. As compared to their acyclic counterparts, the cyclic inhibitors displayed 20-50-fold higher potency against the PDF active site (K(I) as low as 70 pM), improved selectivity toward PDF, and improved the metabolic stability in rat plasma. Some of the macrocyclic inhibitors had potent, broad spectrum antibacterial activity against clinically significant Gram-positive and Gram-negative pathogens. These results suggest that the macrocyclic scaffold provides an excellent lead for the development of a new class of antibiotics.

Glucosylceramide synthases, a gene family responsible for the biosynthesis of glucosphingolipids in animals, plants, and fungi.

Glucosylceramides are membrane lipids in most eukaryotic organisms and in a few bacteria. The physiological functions of these glycolipids have only been documented in mammalian cells, whereas very little information is available of their roles in plants, fungi, and bacteria. In an attempt to establish appropriate experimental systems to study glucosylceramide functions in these organisms, we performed a systematic functional analysis of a glycosyltransferase gene family with members of animal, plant, fungal, and bacterial origin. Deletion of such putative glycosyltransferase genes in Candida albicans and Pichia pastoris resulted in the complete loss of glucosylceramides. When the corresponding knock-out strains were used as host cells for homologous or heterologous expression of candidate glycosyltransferase genes, five novel glucosylceramide synthase (UDP-glucose:ceramide glucosyltransferase) genes were identified from the plant Gossypium arboreum (cotton), the nematode Caenorhabditis elegans, and the fungi Magnaporthe grisea, Candida albicans, and P. pastoris. The glycosyltransferase gene expressions led to the biosynthesis of different molecular species of glucosylceramides that contained either C18 or very long chain fatty acids. The latter are usually channeled exclusively into inositol-containing sphingolipids known from Saccharomyces cerevisiae and other yeasts. Implications for the biosynthesis, transport, and function of sphingolipids will be discussed.

Identification of a novel delta 6-acyl-group desaturase by targeted gene disruption in Physcomitrella patens.

The moss Physcomitrella patens contains high levels of arachidonic acid. For its synthesis from linoleic acid by desaturation and elongation, novel delta 5- and delta 6-desaturases are required. To isolate one of these, PCR-based cloning was used, and resulted in the isolation of a full-length cDNA coding for a putatively new desaturase. The deduced amino acid sequence has three domains: a N-terminal segment of about 100 amino acids, with no similarity to any sequence in the data banks, followed by a cytochrome b5-related region and a C-terminal sequence with low similarity (27% identify) to acyl-lipid desaturases. To elucidate the function of this protein, we disrupted its gene by transforming P. patens with the corresponding linear genomic sequence, into which a positive selection marker had been inserted. The molecular analysis of five transformed lines showed that the selection cartridge had been inserted into the corresponding genomic locus of all five lines. The gene disruption resulted in a dramatic alteration of the fatty acid pattern in the knockout plants. The large increase in linoleic acid and the concomitant disappearance of gamma-linolenic and arachidonic acid in all knockout lines suggested that the new cDNA coded for a delta 6-desaturase. This was confirmed by expression of the cDNA in yeast and analysis of the resultant fatty acids by GC-MS. Only the transformed yeast cells were able to introduce a further double bond into the delta 6-position of unsaturated fatty acids. To our knowledge, this is the first report of a successful gene disruption in a multicellular plant resulting in a specific biochemical phenotype.

Purification and cDNA sequencing of an oleate-selective acyl-ACP:sn-glycerol-3-phosphate acyltransferase from pea chloroplasts.

The soluble acyl-ACP:sn-glycerol-3-phosphate acyltransferase from chloroplasts of chilling-sensitive and -resistant plants differ in their fatty acid selectivity. Enzymes from resistant plants discriminate against non-fluid palmitic acid and select oleic acid whereas the acyltransferase from sensitive plants accepts both fatty acids. To use this difference for improving plant chilling resistance by biotechnology the gene for an oleate-selective enzyme is required. Therefore, the oleate-selective enzyme from pea seedlings was purified to apparent homogeneity. Tryptic peptides of internal origin were sequenced. Polyclonal antibodies raised in rabbits were used for an immunological screening of a pea leaf cDNA expression library in lambda gt11. A positive clone of 1800 bp was selected showing an open reading frame which codes for 457 amino acids. The deduced amino acid sequence coincides perfectly with the tryptic sequences. A tentative assignment of the processing site was made which divides the preprotein into a mature protein of 41 kDa in accordance with experimental findings and a transit peptide of 88 amino acids. At present the comparison between a selective (pea) and an unselective (squash) acyltransferase sequence does not provide a clue for recognizing the structural differences resulting in different selectivities.