French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides)

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3–6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12–48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.

     

Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds

Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott–Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks.     

Knocking on Heaven's Door: Are Novel Invaders Necessarily Facing Na?ve Native Species on Islands?

The impact of alien predator species on insular native biota has often been attributed to island prey naïveté (i.e. lack of, or inefficient, anti-predator behavior). Only rarely, however, has the concept of island prey naïveté been tested, and then only a posteriori (i.e. hundreds or thousands of years after alien species introduction). The presence of native or anciently introduced predators or competitors may be crucial for the recognition and development of adaptive behavior toward unknown predators or competitors of the same archetype (i.e. a set of species that occupy a similar ecological niche and show similar morphological and behavioral traits when interacting with other species). Here, we tested whether two squamates endemic to New Caledonia, a skink, Caledoniscincus austrocaledonicus, and a gecko, Bavayia septuiclavis, recognized and responded to the odor of two major invaders introduced into the Pacific islands, but not yet into New Caledonia. We chose one predator, the small Indian mongoose Herpestes javanicus and one competitor, the cane toad Rhinella marina, which belong respectively to the same archetype as the following two species already introduced into New Caledonia in the nineteenth century: the feral cat Felis catus and the golden bell frog Litoria aurea. Our experiment reveals that geckos are naïve with respect to the odors of both an unknown predator and an unknown competitor, as well as to the odors of a predator and a competitor they have lived with for centuries. In contrast, skinks seem to have lost some naïveté regarding the odor of a predator they have lived with for centuries and seem “predisposed” to avoid the odor of an unknown potential competitor. These results indicate that insular species living in contact with invasive alien species for centuries may be, although not systematically, predisposed toward developing adaptive behavior with respect to species belonging to the same archetype and introduced into their native range.     

TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae

Nutrient-sensitive phosphorylation of the S6 protein of the 40S subunit of the eukaryote ribosome is highly conserved. However, despite four decades of research, the functional consequences of this modification remain unknown. Revisiting this enigma in Saccharomyces cerevisiae, we found that the regulation of Rps6 phosphorylation on Ser-232 and Ser-233 is mediated by both TOR complex 1 (TORC1) and TORC2. TORC1 regulates phosphorylation of both sites via the poorly characterized AGC-family kinase Ypk3 and the PP1 phosphatase Glc7, whereas TORC2 regulates phosphorylation of only the N-terminal phosphosite via Ypk1. Cells expressing a nonphosphorylatable variant of Rps6 display a reduced growth rate and a 40S biogenesis defect, but these phenotypes are not observed in cells in which Rps6 kinase activity is compromised. Furthermore, using polysome profiling and ribosome profiling, we failed to uncover a role of Rps6 phosphorylation in either global translation or translation of individual mRNAs. Taking the results together, this work depicts the signaling cascades orchestrating Rps6 phosphorylation in budding yeast, challenges the notion that Rps6 phosphorylation plays a role in translation, and demonstrates that observations made with Rps6 knock-ins must be interpreted cautiously.     

The orientations of cytochrome c in the highly dynamic complex with cytochrome b5 visualized by NMR and docking using HADDOCK

The interaction of bovine microsomal ferricytochrome b5 with yeast iso-1-ferri and ferrocytochrome c has been investigated using heteronuclear NMR techniques. Chemical-shift perturbations for 1H and 15N nuclei of both cytochromes, arising from the interactions with the unlabeled partner proteins, were used for mapping the interacting surfaces on both proteins. The similarity of the binding shifts observed for oxidized and reduced cytochrome c indicates that the complex formation is not influenced by the oxidation state of the cytochrome c. Protein-protein docking simulations have been performed for the binary cytochrome b5-cytochrome c and ternary (cytochrome b5)-(cytochrome c)2 complexes using a novel HADDOCK approach. The docking procedure, which makes use of the experimental data to drive the docking, identified a range of orientations assumed by the proteins in the complex. It is demonstrated that cytochrome c uses a confined surface patch for interaction with a much more extensive surface area of cytochrome b5. Taken together, the experimental data suggest the presence of a dynamic ensemble of conformations assumed by the proteins in the complex.     

Medical sequencing of candidate genes for nonsyndromic cleft lip and palate

Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Étude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.     

Plant microsatellite genotyping with 4-color fluorescent detection using multiple-tailed primers

We extended the concept of fluorescent microsatellite genotyping with a single-universal tailed primer to the simultaneous use of three different tailed primers to allow multiplexed 4-color detection for medium throughput genotyping of plant species. The method was tested on Eucalyptus DNA samples using three forward primer sequences of human microsatellite markers labeled with different fluorescent dyes. The robustness of the method was tested for the simultaneous detection and genetic analysis of microsatellites in a genetic mapping experiment. This method allows reliable and cost-effective genotyping with the same level of multiplexing attained in regular microsatellite fluorescent detection assays. Besides the enhanced quality of the genotypic data provided by the fluorescent detection method when compared to colorimetric ones, the economy brought about by this method becomes greater with an increasing number of microsatellite markers. This method has been particularly useful for genotyping populations of several tropical tree species addressing community-wide population genetics and conservation questions.     

Farmers’ perception of termites in agriculture production and their indigenous utilization in Northwest Benin

Background

Although termites are considered as agricultural pests, they play an important role in maintaining the ecosystem. Therefore, it matters to investigate the farmers’ perception of the impacts of the termites on the agriculture and their indigenous utilization.

Methods

A semi-structured questionnaire was used to interview 94 farmers through 10 villages of Atacora department, in the northwestern region of Benin, to obtain information for the development of successful strategies of termite management and conservation. Their perceptions on the importance and management of termites along with the indigenous nomenclature and utilization of termite mounds were assessed. Termite species identified by farmers were collected and preserved in 80% alcohol for identification.

Results

Eight crops were identified by farmers as susceptible to termites with maize, sorghum, and yam as being the most susceptible. According to farmers, the susceptibility to termites of these crops is due to their high-water content and sweet taste. A total of 27 vernacular names of termites were recorded corresponding to 10 species, Amitermes evuncifer, Macrotermes subhyalinus, and Trinervitermes oeconomus being the most damaging termite species. All the names given to termite species had a meaning. The drought was identified by farmers as the main factor favouring termite attacks. Demolition of termite mounds in the fields was the most commonly reported control method. Salt and other pesticides were commonly used by farmers to protect stored farm products. The lack of effective control methods is the main constraint for termite management. In northwestern Benin, farmers reported different purpose utilizations of termite mounds and termites.

Conclusions

The study has shown that farmers perceived termites as pests of several agricultural crops and apply various indigenous control practices whose efficiency need to be verified. Utilization of termites and termite mound soil as food and medicinal resources underlines the need for a more focused approach to termite control for the conservation of non-pest termite species. The sensitization of farmers on the importance of termites as well as the development of an integrated control method to combat termite pests proved necessary.

     

Interaction of androgens and estrogens in the control of reproduction

Castrated male quail were injected with the synthetic oestrogen, diethylstylbestrol (DES) or the synthetic androgen, methyltrienolone (R 1881) or both compounds simultaneously. Both R 1881 and DES activated male sexual behaviour, inhibited LH and FSH secretion and increased hypothalamic aromatase activity. Additive effects between R 1881 and DES were observed for the induction of brain aromatase and for the inhibition of FSH secretion. As a consequence, mechanisms mediated by androgen and estrogen receptors must be involved in the control of these reproductive characteristics.