Improving effective surgical delivery in humanitarian disasters: lessons from Haiti

Kathryn Chu and colleagues describe the experiences of Médecins sans Frontières after the 2010 Haiti earthquake, and discuss how to improve delivery of surgery in humanitarian disasters.     

Epigenetic heredity in mice: involvement of RNA and miRNas.

By contrast with a wide definition of the 'epigenetic variation', including all changes in gene expression that do not result from alteration of the gene structure, a more restricted class had been defined, initially in plants, under the name 'paramutation'. It corresponds to epigenetic modifications distinct from the regulatory interactions of the cell differentiation pathways, mitotically stable and sexually transmitted with non-Mendelian patterns. This class of epigenetic changes appeared for some time restricted to the plant world, but examples progressively accumulated of epigenetic inheritance in organisms ranging from mice to humans. Occurrence of paramutation in the mouse and possible mechanisms were then established in the paradigmatic case of a mutant phenotype maintained and hereditarily transmitted by wild type homozygotes. Together with recent findings in plants indicative of a necessary step of RNA amplification in the reference maize paramutation, the mouse studies point to a new role of RNA, as an inducer and hereditary determinant of epigenetic variation. Given the known presence of a wide range of RNAs in human spermatozoa, as well as a number of unexplained cases of familial disease predisposition and transgenerational maintenance, speculations can be extended to possible roles of RNA-mediated inheritance in human biology and pathology.La paramutation est une modification épigénétique héréditaire, découverte chez des plantes et récemment, chez la souris. C'est un changement héréditaire du phénotype associé avec un allèle sauvage à la suite de son passage dans une structure hétérozygote avec un allèle mutant (phénomène quelquefois appelé "conversation interchromosomique"). Souvent il est considéré comme une exception à la base de lois de Mendel, "les allèles sont retrouvés inchangés lors des ségrégations au cours des croisements". Au contraire la paramutation observée chez la souris résulte d'une modification de l'allèle sauvage du gène Kit après transmission à partir d'un hétérozygote avec un allèle mutant "insertion". Le phénotype des taches blanches visibles aisément par la couleur du pelage est transmis en absence de l'allèle inducteur sur plusieurs générations. Il est corrélé avec une diminution du niveau d'ARNm de Kit et une accumulation d'ARN de taille variable de Kit dans les spermatozo?des des souris paramutantes. La micro-injection de l'ARN de l'hétérozygote, ou de l'ARN et des microARN spécifiques de Kit dans l'oeuf fécondé induit le phénotype "taches blanches". Le r?le de l'ARN dans l'établissement et le maintien d'un état épigénétique héréditaire est proposé et discuté.     

Variation in HMA4 gene copy number and expression among Noccaea caerulescens populations presenting different levels of Cd tolerance and accumulation

There is huge variability among populations of the hyperaccumulator Noccaea caerulescens (formerly Thlaspi caerulescens) in their capacity to tolerate and accumulate cadmium. To gain new insights into the mechanisms underlying this variability, we estimated cadmium fluxes and further characterized the N. caerulescens heavy metal ATPase 4 (NcHMA4) gene in three populations (two calamine, Saint-Félix-de-Pallières, France and Prayon, Belgium; one serpentine, Puente Basadre, Spain) presenting contrasting levels of tolerance and accumulation. Cadmium uptake and translocation varied among populations in the same way as accumulation; the population with the highest cadmium concentration in shoots (Saint Félix-de-Pallières) presented the highest capacity for uptake and translocation. We demonstrated that the four NcHMA4 copies identified in a previous study are not fixed at the species level, and that the copy truncated in the C-terminal part encodes a functional protein. NcHMA4 expression and gene copy number was lower in the serpentine population, which was the least efficient in cadmium translocation compared to the calamine populations. NcHMA4 expression was associated with the vascular tissue in all organs, with a maximum at the crown. Overall, our results indicate that differences in cadmium translocation ability of the studied populations appear to be controlled, at least partially, by NcHMA4, while the overexpression of NcHMA4 in the two calamine populations may result from convergent evolution.     

Below-ground ectomycorrhizal community in natural Tuber melanosporum truffle grounds and dynamics after canopy opening

The ectomycorrhizal fungus Tuber melanosporum fruits in association with Quercus in natural forests of Spain. Some of these stands are managed to keep an open canopy and meet the habitat requirements of the fungus. However, there are few quantitative studies analysing in these forests the relationship between soil environment and T. melanosporum. Eight forest stands which produce T. melanosporum have been monitored for 6 years in order to characterise the below-ground ectomycorrhizal community and to assess its temporal dynamics after experimental canopy opening. The br?lé, the ground where T. melanosporum fruits, shows a distinct ectomycorrhizal community, characterised by lower density of active ectomycorrhizal tips, lower morphotype richness per soil volume, higher abundance of T. melanosporum and lower abundance of Cenococcum geophilum than soil closest to the trunk of the host Quercus ilex. Opening the canopy has not stimulated an increase in T. melanosporum, suggesting that a shift in the soil environment alone will not trigger the formation of new truffières in the short term. The dry climate of these truffières may be a factor as T. melanosporum abundance appears to be sensitive to annual weather conditions.     

Bohumil Francis Kukachka (1915–1983)

Brittonia - Bohumil Francis Kukachka is remembered for his anatomical studies of the Sapotaceae. He received his Ph.D. from the University of Minnesota in 1942 in wood technology, and in 1945 his...     

Loss of sulfonamide resistance in Neisseria meningitidis

Four strains of Neisseria meningitidis were studied during serial passage. From two strains which originally were sulfonamide resistant, variants developed that had altered susceptibility to sulfonamides. One of the variants became relatively highly sulfonamide-sensitive, the other exhibited merely reduced sulfonamide resistance. There was a difference in the resistance pattern for two sulfonamides (sulfaisodimidine and sulfamethoxazole), and the effect of inoculum size and growth conditions in three different media could be demonstrated. Although the patterns of susceptibility to other antibacterial agents were different for the strains studied, no further susceptibility alterations occurred in parallel to the sulfonamide sensitivity changes. The variants also lost their ability to liberate free endotoxin.     

迷蛱蝶属及相关物种细胞色素b基因序列及其分子系统学研究

迷蛱蝶属Mimathyma隶属于蛱蝶科Nymphalidae闪蛱蝶亚科Apaturinae,该属所包含的种类复杂,其分类学地位存在争议.本文对迷蛱蝶属、闪蛱蝶属Apatura和带蛱蝶属Athyma7个种共19个个体的线粒体DNA细胞色素b基因部分序列进行测定分析,并以花斑螯蛱蝶Charaxes kahruba (Moore)作为外群用PAUP软件构建MP和NJ分子系统树.结果显示迷蛱蝶Mimathyma chevana(Moore)、夜迷蛱蝶Mimathyma nycteis(Ménétriès)、白斑迷蛱蝶Mimathyma schrenckii (Ménétriès)和环带迷蛱蝶Mimathyma ambica Kollar形成1个聚类簇,支持Moore将这4个种由闪蛱蝶属移出并建立迷蛱蝶属的观点.同时,尽管迷蛱蝶在形态上与该属其余3种相似,但研究发现聚类簇Ⅰ中夜迷蛱蝶、白斑迷蛱蝶和环带迷蛱蝶首先相聚,然后再与迷蛱蝶聚在一起,表明迷蛱蝶与这3种亲缘关系较远.此外,本文的研究结果还显示迷蛱蝶属与闪蛱蝶属关系密切,而与带蛱蝶属的关系较远.     

The Lateglacial sequence of the Etelles (northern French Alps): climate instability and vegetation dynamics

A detailed pollen analysis has been conducted in a new sedimentary sequence taken at Les Etelles (700 m), in the hill vegetation belt in the Cha?ne des Hurtières (Northern French Alps). The Lateglacial history of the vegetation has been supported by 10 AMS datings. Variations in relative abundance of main pollen taxa were compared with variations in [symbol: see text] 18O in Swiss lacustrine sediments and with the GRIP ice-core record. Those highlight how the vegetation reacted to minor climatic oscillations. The Lateglacial spread of Quercus, Alnus and Corylus in the region is confirmed, thus allowing a new interpretation of some Lateglacial sedimentary sequences at an adjacent region (Bas-Dauphiné).     

Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on mitochondrial metabolic energy conversion

Obesity is quickly becoming an increasing problem in the developed world. One of the major fundamental causes of obesity and diabetes is mitochondria dysfunction due to faulty metabolic pathways which alter the metabolic substrate flux resulting in the development of these diseases. This paper examines the role of mitochondrial carbonic anhydrase (CA) isozymes in the metabolism of pyruvate, acetate, and succinate when specific isozyme inhibitors are present. Using a sensitive electrochemical approach of wired mitochondria to analytically measure metabolic energy conversion, we determine the resulting metabolic difference after addition of an inhibitory compound. We found that certain sulfonamide analogues displayed broad spectrum inhibition of metabolism, where others only had significant effect on some metabolic pathways. Pyruvate metabolism always displayed the most dramatically affected metabolism by the sulfonamides followed by fatty acid metabolism, and then finally succinate metabolism. This allows for the possibility of using designed sulfonamide analogues to target specific mitochondrial CA isozymes in order to subtly shift metabolism and glucogenesis flux to treat obesity and diabetes.     

Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]

The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time.     

Acyloxymethyl as a drug protecting group. Part 6: N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides as prodrugs of agents containing a secondary sulfonamide group

Tertiary N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides were synthesised and evaluated as novel classes of potential prodrugs of agents containing a secondary sulfonamide group. The chemical and plasma hydrolyses of the title compounds were studied by HPLC. Tertiary N-acyloxymethylsulfonamides are slowly and quantitatively hydrolysed to the parent sulfonamide in pH 7.4 phosphate buffer, with half-lives ranging from 20 h, for 7d, to 30 days, for 7g. Quantitative formation of the parent sulfonamide also occurs in human plasma, the half-lives being within 0.2-2.0 min for some substrates. The rapid rate of hydrolysis can be ascribed to plasma cholinesterase, as indicated by the complete inhibition observed at [eserine] = 0.10 mM. These results suggest that tertiary N-acyloxymethylsulfonamides are potentially useful prodrugs for agents containing a secondary sulfonamide group, especially with pKa < 8, combining a high stability in aqueous media with a high rate of plasma activation. In contrast, N-[(aminocarbonyloxy)methyl]sulfonamides 7h-j do not liberate the parent sulfonamide either in aqueous buffers or in human plasma and thus appear to be unsuitable for development as sulfonamide prodrugs.     

Influence of pore structure on the effectiveness of a biogenic carbonate surface treatment for limestone conservation

A ureolytic biodeposition treatment was applied to five types of limestone in order to investigate the effect of pore structure on the protective performance of a biogenic carbonate surface treatment. Protective performance was assessed by means of transport and degradation processes, and the penetration depth of the treatment was visualized by microtomography. Pore size governs bacterial adsorption and hence the location and amount of carbonate precipitated. This study indicated that in macroporous stone, biogenic carbonate formation occurred to a larger extent and at greater depths than in microporous stone. As a consequence, the biodeposition treatment exhibited the greatest protective performance on macroporous stone. While precipitation was limited to the outer surface of microporous stone, biogenic carbonate formation occurred at depths of greater than 2 mm for Savonnières and Euville. For Savonnières, the presence of biogenic carbonate resulted in a 20-fold decreased rate of water absorption, which resulted in increased resistance to sodium sulfate attack and to freezing and thawing. While untreated samples were completely degraded after 15 cycles of salt attack, no damage was observed in biodeposition-treated Savonnières. From this study, it is clear that biodeposition is very effective and more feasible for macroporous stones than for microporous stones.     

Synthesis and carbonic anhydrase I,II, IV and XII inhibitory properties of N-protected amino acid – sulfonamide conjugates

N-protected amino acids (Gly, Ala and Phe protected with Boc and Z groups) were reacted with sulfonamide derivatives, leading to the corresponding N-protected amino acid–sulfonamide conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Among them, hCA II, IV and XII are antiglaucoma drug targets, being involved in aqueous humor secretion within the eye. Low nanomolar inhibition was measured against all four isoforms with the 20 reported sulfonamides, but no selective inhibitory profiles, except for some CA XII-selective derivatives, were observed. hCA I, II and XII were generally better inhibited by sulfonamides incorporating longer scaffolds and Gly/Ala, whereas the best hCA IV inhibitors were homosulfanilamide derivatives, incorporating Phe moieties. The amino acid–sulfonamide conjugates show good water solubility and effective hCA II, IV and XII inhibition, and may be considered as interesting candidates for antiglaucoma studies.     

IMGT®, the International ImMunoGeneTics Information System® for Immunoinformatics

IMGT, the International ImMunoGeneTics information system ( http://imgt.cines.fr ), was created in 1989 by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM) (Université Montpellier 2 and CNRS) at Montpellier, France, in order to standardize and manage the complexity of immunogenetics data. IMGT is recognized as the international reference in immunogenetics and immunoinformatics. IMGT is a high quality integrated knowledge resource, specialized in (i) the immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates; (ii) proteins that belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF); and (iii) related proteins of the immune systems (RPI) of any species. IMGT provides a common access to standardized data from genome, proteome, genetics, and three-dimensional (3D) structures for the IG, TR, MHC, IgSF, MhcSF, and RPI. IMGT interactive on-line tools are provided for genome, sequence, and 3D structure analysis. IMGT Web resources comprise 10,000 HTML pages of synthesis and knowledge (IMGT Scientific chart, IMGT Repertoire, IMGT Education, etc.) and external links (IMGT Bloc-notes and IMGT other accesses).     

The inhibitor effect of probencid and structural analogues on organic anions and chloride permeabilities in ox erythrocytes.

Probenecid inhibits anion movements (organic anions and chloride) in ox erythrocytes. The I50 is 4. 10(-5) M. Structural analogues such as carinamide, p-carboxybenzene sulfonamide and p-carboxy N,N-diethyl benzene sulfonamide, which are drugs of the sulfonamide class, were also found to inhibit anion transport. These results reinforce the previously discussed view based on structural considerations, that sulfonamides act on the red cell membrane as competitors of anion transport. It is possible that probenecid and carinamide act in a similar way in the kidney.     

Penoxsulam—Structure–activity relationships of triazolopyrimidine sulfonamides

The discovery of the sulfonamide herbicides, which inhibit the enzyme acetolactate synthase (ALS), has resulted in many investigations to exploit their herbicidal activity. One area which proved particularly productive was the N-aryltriazolo[1,5-c]pyrimidine sulfonamides, providing three commercial herbicides, cloransulam-methyl, diclosulam and florasulam. Additional structure–activity investigations by reversing the sulfonamide linkage resulted in the discovery of triazolopyrimidine sulfonamides with cereal crop selectivity and high levels of grass and broadleaf weed control. Research efforts to exploit these high levels of weed activity ultimately led to the discovery of penoxsulam, a new herbicide developed for grass, sedge and broadleaf weed control in rice. Synthetic efforts and structure–activity relationships leading to the discovery of penoxsulam will be discussed.     

Determination of ionization state by resonance Raman spectroscopy Sulfonamide binding to carbonic anhydrase.

Resonance Raman (RR) spectroscopy has been used to study the ionization state of the sulfonamide, 4'-sulfamylphenyl-2-azo-7-acetamido-1-hydroxynaphthalene-3,-6-disulfonate (Neoprontosil), bound to carbonic anhydrase. The correlation of effects of pH and deuteration on the spectra of model compounds with these effects on the Neoprotosil spectrum allows us to assign spectral bands in the 900-1000 and 100-1200 cm-1 regions to the SO2NH2 group. Large shifts in these bands occur upon ionization of the sulfonamide. On the basis of the positions of bands in the enzyme complex, it was determined that the sulfonamide was bound to the enzyme as SO2NH2, rather than as SO2NH-. Rates of association and dissociation and the dissociation equilibrium constant were measured as a function of pH. The rate behavior for Neoprontosil is consistent with that observed for other sulfonamides and kdissoc/kassoc = kdissoc, suggesting a one-step binding mechanism. Since RR spectroscopy establishes that the final ionization state of the sulfonamide in the enzyme complex is SO2NH2, protonated sulfonamide must bind directly to basic form of the enzyme. These conclusions suggest that sulfonamides form "outer-space" complexes with metal at the enzyme active site.     

Shigeo Yamanouchi (1876–1973): A noted Japanese phycologist

Dr Shigeo Yamanouchi was born in Yamagata Prefecture and completed his secondary education at Tokyo Higher Normal School (THNS) where he was also a professor until 1904. In 1905, he went to the University of Chicago in the USA and earned a PhD in Botany in 1907. He is best noted for his excellent research on the cytology and life histories of the marine algae Polysiphonia, Fucus, Cutleria, Aglaozonia and Zanardinia, published between 1906 and 1921 while he was associated with the University of Chicago. He also described the freshwater green alga Hydrodictyon africanum. In 1910, he returned to THNS as a Professor and wrote several botanical textbooks, receiving his DSc degree in 1911 and traveling in England and the USA as an advisor for the Japanese Ministry of Education during 1911–1913. For much of the time between 1920 and 1942 he remained in the USA, returning to Japan following the advent of World War II, During his later life, he was in obscurity, and sadly there is very little recorded of his activities in the post-war years. He died in Tokyo on 2 February 1973 at the age of 96.     

Sulfonamide resistance gene for plant transformation

The sulfonamide resistance gene from plasmid R46 encodes for a mutated dihydropteroate synthase insensitive to inhibition by sulfonamides. Its coding sequence was fused to the pea ribulose bisphosphate carboxylase/oxygenase transit peptide sequence. Incubation of isolated chloroplasts with the fusion protein synthesised in vitro, showed that the bacterial enzyme was transported to the chloroplast stroma and processed into a mature form. Expression of the gene fusion in transgenic plants resulted in a high level of resistance to sulfonamides. Direct selection of transformed shoots on leaf explants was efficient using sulfonamides as sole selective agents. Transformed shoots rooted normally on sulfonamides at concentrations toxic for untransformed ones. Sulfonamide resistance was transmitted to the progeny of transformed plants as a single Mendelian dominant character. These results demonstrate that this chimeric gene can be used as an efficient and versatile selectable marker for plant transformation.