Nod factors thin-layer chromatography profiling as a tool to characterize symbiotic specificity of rhizobial strains : application to Sinorhizobium saheli, S. teranga, and Rhizobium sp. strains isolated from Acacia and Sesbania

Rhizobia isolated from #Acacia or #Sesbania belong to several taxonomic groups, including the newly described species #Sinorhizobium saheli, #Sinorhizobium teranga, and the so-called cluster U. A collection of strains belonging to these different groups was analyzed in order to determine whether the host range of a strain could be correlated with various molecular nodulation determinants. Nodulation tests showed that, independently of their taxonomic position, all the strains isolated from the same plant genus exhibited a similar host range, which was different for #Sesbania and #Acacia isolates. The fact that #S. teranga strains nodulate either #Acacia or #Sesbania led us to subdivide this species into biovars #acaciae and #sesbaniae. Thin-layer chromatography (TLC) analysis of the Nod factors synthesized by overproducing strains showed that strains isolated from the same plant genus exhibited similar TLC profiles and profiles of #Acacia and #Sesbania symbionts were easily distinguishable, #Acacia strains producing, in particular, sulfated molecules. In contrast, no correlation could be established between the host range of a strain and its plasmid content, the nature of the nod gene inducers or the presence of DNA sequences homologous to specific nod genes. We thus propose that Nod factor TLC profiling may be used as an easy and powerful tool for the classification of rhizobial strains on the basis of their symbiotic properties. (Résumé d'auteur

Cancer drug-tolerant Persister cells: from biological questions to clinical opportunities

The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, play a prominent role in drug resistance. While long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the last two decades, yet several aspects of their biology remain enigmatic. Here we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumor. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumor microenvironment, including their potential to evade immune surveillance, remain to be discovered. Lastly, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavors in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication

The legend about sailing ship effects – Is it true or false? The example of cleaner propulsion technologies diffusion in the automotive industry

The global automotive industry is faced with major technological change in the field of propulsion systems. Due to low carbon emission regulations and a rising societal demand for sustainability, original equipment manufacturers (OEMs) are forced to innovate either in the conventional technology or in the technological alternatives such as electric drives or fuel cells. However, OEMs are only marginally switching to electromobility so far, but rather incrementally innovating traditional technologies. This behaviour can be described as sailing ship effect which contains the reaction of an old technology to a new technology by fostering innovation in the old technology. Firstly, the present study contributes to the discussion in literature on the sailing ship effect by combining its underlying ideas and consequences with the rationales of path dependence to demonstrate that such a behaviour may be individually economical rational. Based on these considerations, we respond to the call for further empirical investigation of the sailing ship effect. We show patent-based evidence that there has been a temporary sailing ship effect in the automotive industry concerning traditional and emerging propulsion systems and discuss implications for corporate technology strategy and policy

Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

INTRODUCTION: Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. METHODS: BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. RESULTS: We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. CONCLUSION: These improved methods for the detection of micrometastatic cells in patient BM should help clinicians to predict the clinical status of breast cancer patients at the time of surgery or treatment

Transcriptional Profiling of Plasmodium falciparum Parasites from Patients with Severe Malaria Identifies Distinct Low vs. High Parasitemic Clusters

Background: In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking. Methods and Findings: We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system. Conclusions: The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome

High genetic diversity with moderate differentiation in Juniperus excelsa from Lebanon and the eastern Mediterranean region

Juniperus excelsa constitutes a precious woody species of high ecological value able to grow up to Mountain treeline around the Mediterranean. Nuclear microsatellites were used to shed light on genetic diversity and differentiation of different Mediterranean populations. This information is essential in planning conservation strategies and reforestation programs

Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers

BACKGROUND: Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers. METHODS: To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively. RESULTS: We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13(Z )(amplified at ZNF217 only) in 9.9%, and 20q13(Co )(co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13(Z )and 20q13(Co )(1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype. CONCLUSION: Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders