Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5.

The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates. This study uses genomic approaches to evaluate genetic diversity in next generation malaria vaccine candidate PfRh5. We used targeted deep amplicon sequencing to identify non-synonymous Single Nucleotide Polymorphisms (SNPs) in PfRh5 (Reticulocyte-Binding Protein Homologue 5) in 189 P. falciparum positive samples from Southern Senegal and identified 74 novel SNPs. We evaluated the population prevalence of these SNPs as well as the frequency in individual samples and found that only a single SNP, C203Y, was present at every site. Many SNPs were unique to the individual sampled, with over 90% of SNPs being found in just one infected individual. In addition to population prevalence, we assessed individual level SNP frequencies which revealed that some SNPs were dominant (frequency of greater than 25% in a polygenomic sample) whereas most were rare, present at 2% or less of total reads mapped to the reference at the given position. Structural modeling uncovered 3 novel SNPs occurring under epitopes bound by inhibitory monoclonal antibodies, potentially impacting immune evasion, while other SNPs were predicted to impact PfRh5 structure or interactions with the receptor or binding partners. Our data demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the caveat that most of the uncovered SNPs are at a low overall frequency in the individual and prevalence in the population. The structural studies reveal that novel SNPs could have functional implications on PfRh5 receptor binding, complex formation, or immune evasion, supporting continued efforts to validate PfRh5 as an effective malaria vaccine target and development of a PfRh5 vaccine.

RACINE2.2: A Software Application for Processing and Mapping Spatial Distribution of Root Length Density and Potential Root Extraction Ratio from Root Counts on Trench Profiles.

A method has been developed to measure root intersection density (RID) on a trench-profile in field conditions. Here we describe how 2D spatial distribution mapping of RID can be processed and converted into root length density (RLD) and root distances (ARD) using a new freeware named RACINE2.2. The software also allows a simple modeling of potential root extraction ratio in the soil (PRER). The software contains models calculating RLD, ARD, and PRER from RID for several crops (maize, sorghum, sugarcane, rice, pearl millet, pineapple, eucalyptus). Models may be changed or added into RACINE2.2. RLD, ARD, and PRER are calculated for each spatial unit and can be used to generate 2D maps using RACINE2.2. Data can be exported to a spreadsheet or a surface mapping software for further analysis. It is also possible to import data into RACINE2.2 from a spreadsheet. This application thus makes studies about root-soil interactions, root growth, and root uptake easier. It opens new avenues to characterize root systems to improve root water and nutrient uptake in field conditions.

Development of a model estimating root length density from root impacts on a soil profile in pearl millet (Pennisetum glaucum (L.) R. Br). Application to measure root system response to water stress in field conditions.

Pearl millet is able to withstand dry and hot conditions and plays an important role for food security in arid and semi-arid areas of Africa and India. However, low soil fertility and drought constrain pearl millet yield. One target to address these constraints through agricultural practices or breeding is root system architecture. In this study, in order to easily phenotype the root system in field conditions, we developed a model to predict root length density (RLD) of pearl millet plants from root intersection densities (RID) counted on a trench profile in field conditions. We identified root orientation as an important parameter to improve the relationship between RID and RLD. Root orientation was notably found to depend on soil depth and to differ between thick roots (more anisotropic with depth) and fine roots (isotropic at all depths). We used our model to study pearl millet root system response to drought and showed that pearl millet reorients its root growth toward deeper soil layers that retain more water in these conditions. Overall, this model opens ways for the characterization of the impact of environmental factors and management practices on pearl millet root system development.

[A no scarring persistent skin lesion for 3 years pyoderma gangrenosum]. / Une lesion cutanée persistante non cicatricielle depuis 3 ans pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare non-infectious neutrophilic dermatosis often unknowed. It usually presents with inflammatory skin ulcer, very painful, with rapid evolution. It is commonly found in a context of malignancy, inflammatory bowel disease, rheumatic and/or haematological disease. Its diagnosis is very often late after multiple therapeutic failures. We report a case of pyoderma gangrenosum whose diagnosis was not obvious. A patient was admitted to our department for a persistent dermatological lesion and adverse evolution despite debridements and the administration of antibiotics. He was followed for prostate cancer, high blood pressure and asthma. Due to observed biological abnormalities such as neutrophil leukocytosis with myelocyte and metamyelocyte myeloma, without blood blastosis and normochromic normocytic anemia, chronic myelogenous leukemia was suspected. It was later overturned by the various inconclusive supplementary examinations. This is how the diagnosis of PG was evoked and confirmed by anatomopathological examination showing a histopathological appearance of granulation tissue consistent with pyoderma gangrenosum and no sign of malignancy. The institution of a corticotherapy treatment resulted in the cure.