Mutation rate switch inside Eurasian mitochondrial haplogroups: impact of selection and consequences for dating settlement in Europe

R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America). This lineage played a major role in migration "out of Africa" and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years, as well as several limitations of standard dating methods, likely to lead to false interpretations. These findings highlight the association of a striking under-accumulation of synonymous mutations, an over-accumulation of non-synonymous mutations, and the phenotypic effect on haplogroup J. Consequently, haplogroup J is apparently not a Neolithic group but an older haplogroup (Paleolithic) that was subjected to an underestimated selective force. These findings also indicated an under-accumulation of synonymous and non-synonymous mutations localized on coding and non-coding (HVS1) sequences for haplogroup R0, which contains the major haplogroups H and V. These new dates are likely to impact the present colonization model for Europe and confirm the late glacial resettlement scenario.     

New positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2): identification and synthesis of N-propyl-8-chloro-6-substituted isoquinolones

A series of N-propyl-8-chloro-6-substituted isoquinolones was identified as positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2 PAM) via high throughput screening (HTS). The subsequent synthesis and initial SAR exploration that led to the identification of compound 28 is described.     

Phylogeography of the red coral (<Emphasis Type="Italic">Corallium rubrum</Emphasis>): inferences on the evolutionary history of a temperate gorgonian

The red coral Corallium rubrum (Cnidaria, Octocorallia) is an exploited, long-lived sessile species from the Mediterranean Sea and the adjacent coastline in the Atlantic Ocean. Surveys of genetic variation using microsatellites have shown that populations of C. rubrum are characterized by strong differentiation at the local scale but a study of the phylogeography of this species was still lacking. Here, we used seven polymorphic microsatellite loci, together with sequence data from an intron of the elongation factor 1 (EF1) gene, to investigate the genetic structure of C. rubrum across its geographical range in the western Mediterranean Sea and in the Adriatic Sea. The EF1 sequences were also used to analyse the consequences of demographic fluctuations linked with past environmental change. Clustering analysis with microsatellite loci highlighted three to seven genetic groups with the distinction of North African and Adriatic populations; this distinction appeared significant with AMOVA and differentiation tests. Microsatellite and EF1 data extended the isolation by distance pattern previously observed for this species at the western Mediterranean scale. EF1 sequences confirmed the genetic differentiation observed between most samples with microsatellites. A statistical parsimony network of EF1 haplotypes provided no evidence of high sequence divergence among regions, suggesting no long-term isolation. Selective neutrality tests on microsatellites and EF1 were not significant but should be interpreted with caution in the case of EF1 because of the low sample sizes for this locus. Our results suggest that recent Quaternary environmental fluctuations had a limited impact on the genetic structure of C. rubrum.     

Prospecting sugarcane resistance to Sugarcane yellow leaf virus by genome-wide association

Key message

Using GWAS approaches, we detected independent resistant markers in sugarcane towards a vectored virus disease. Based on comparative genomics, several candidate genes potentially involved in virus/aphid/plant interactions were pinpointed.

Abstract

Yellow leaf of sugarcane is an emerging viral disease whose causal agent is a Polerovirus, the Sugarcane yellow leaf virus (SCYLV) transmitted by aphids. To identify quantitative trait loci controlling resistance to yellow leaf which are of direct relevance for breeding, we undertook a genome-wide association study (GWAS) on a sugarcane cultivar panel (n = 189) representative of current breeding germplasm. This panel was fingerprinted with 3,949 polymorphic markers (DArT and AFLP). The panel was phenotyped for SCYLV infection in leaves and stalks in two trials for two crop cycles, under natural disease pressure prevalent in Guadeloupe. Mixed linear models including co-factors representing population structure fixed effects and pairwise kinship random effects provided an efficient control of the risk of inflated type-I error at a genome-wide level. Six independent markers were significantly detected in association with SCYLV resistance phenotype. These markers explained individually between 9 and 14 % of the disease variation of the cultivar panel. Their frequency in the panel was relatively low (8–20 %). Among them, two markers were detected repeatedly across the GWAS exercises based on the different disease resistance parameters. These two markers could be blasted on Sorghum bicolor genome and candidate genes potentially involved in plant–aphid or plant–virus interactions were localized in the vicinity of sorghum homologs of sugarcane markers. Our results illustrate the potential of GWAS approaches to prospect among sugarcane germplasm for accessions likely bearing resistance alleles of significant effect useful in breeding programs.     

Cell therapy in the heart

Cell therapy is emerging as a new strategy to circumvent the adverse effects of heart disease. Many experimental and clinical studies investigating the transplantation of cells into the injured myocardium have yielded promising results. Moreover, data from these reports show that transplanted stem cells can engraft within the myocardium, differentiate into major cardiac cell types, and improve cardiac function. However, results from clinical trials show conflicting results. These trials demonstrate significant improvements in cardiac function for up to 6 months. However, these improved functions were diminished when examined at 18 months. In this review, we will discuss the current literature available on cell transplantation, covering studies ranging from animal models to clinical trials.     

Transformation of the oilseed crop Camelina sativa by Agrobacterium-mediated floral dip and simple large-scale screening of transformants

Camelina sativa is a promising under-exploited oilseed crop with potential to become a biofuel feedstock. The ability to transform C. sativa would allow for the rapid introduction of novel traits into this emerging crop. We report the development of an Agrobacterium-based floral dip transformation method, requiring no vacuum-infiltration step, with transformation efficiencies up to 0.8%. C. sativa cultivars Ames 26665, ??Calena?? A3U7761, Ames 1043, and ??Celine?? were tested using Agrobacterium tumefaciens strains GV3101, EHA105, and At503. Use of all strains and cultivars resulted in transformed plants; however, GV3101 was the only Agrobacterium strain and Ames 1043 the only C. sativa cultivar to yield transformed plants under all conditions tested. Progeny analysis revealed that in approximately 78% of the transformed plants, the transgene segregated as a single locus. Furthermore, a high-throughput, filter paper-based PCR method was developed to screen marker-free transformed plants. Together, these methods will allow for easier introduction of new genes into this promising oilseed crop.     

AgNOR, p16 and human papillomavirus in low-grade squamous intra-epithelial lesions of the uterine cervix. Preliminary report

It has been shown that infection with high-risk human papillomaviruses (HR-HPV) is related to the development of cervical cancer. The persistence of the virus in intra-epithelial lesions of cervix uteri (SILs) is the basis for the application of HPV testing for screening and management of patients. Most infections by HR-HPVs resolve spontaneously, however, and do not progress to dysplasia or cancer. p16INK4a is a useful biomarker of cervical intra-epithelial neoplasia and could be a marker for the progression of low-grade squamous intra-epithelial lesions (LSILs) to high-grade squamous intra-epithelial lesions (HSILs), because it correlates independently with increasing SIL grade. We conducted a preliminary histological study of 28 patients diagnosed with LSIL, HSIL or nondysplastic epithelium (NDE) from whom 28 biopsies of uterine cervix and 28 endocervical brushed biopsies were taken. Argyrophilic nucleolar organizer region (AgNOR) and p16INK4a assays were performed on the biopsies, and endocervical brushings were used for HPV typing. The high risk HPV group showed that the number of patients with AgNOR areas greater than 3.3 μm(2) and with expression of p16INK4a were statistically greater than the number of lower risk patients. None of the biopsies of LR-HPV carriers expressed p16 and AgNOR areas> 3.3 μm(2) simultaneously. Four LSILs and the NDE of this group expressed neither of the two markers. If the correlation between AgNOR areas and p16INK4a is good, we may be able to develop a low cost simple technology for studying patients infected with HR-HPV and diagnosed with LSIL of uncertain behavior.     

Neurotransmitters as early signals for central nervous system development

During brain ontogenesis, the temporal and spatial generation of the different types of neuronal and glial cells from precursors occurs as a sequence of successive progenitor stages whose proliferation, survival and cell-fate choice are controlled by environmental and cellular regulatory molecules. Neurotransmitters belong to the chemical microenvironment of neural cells, even at the earliest stages of brain development. It is now established that specific neurotransmitter receptors are present on progenitor cells of the developing central nervous system and could play, during neural development, a role that has remained unsuspected until recently. The present review focuses on the occurrence of neurotransmitters and their corresponding ligand-gated ion channel receptors in immature cells, including neural stem cells of specific embryonic and neonatal brain regions. We summarize in vitro and in vivo data arguing that neurotransmitters could regulate morphogenetic events such as proliferation, growth, migration, differentiation and survival of neural precursor cells. The understanding of neurotransmitter function during early neural maturation could lead to the development of pharmacological tools aimed at improving adult brain repair strategies.