Species relationships within the genus Vitis based on molecular and morphological data.

The grape genus Vitis L. includes the domesticated V. vinifera, which is one of the most important fruit crop, and also close relatives recognized as valuable germplasm resources for improving cultivars. To resolve some standing problems in the species relationships within the Vitis genus we analyzed diversity in a set of 90 accessions comprising most of Vitis species and some putative hybrids. We discovered single nucleotide polymorphisms (SNPs) in SANGER sequences of twelve loci and genotyped accessions at a larger number of SNPs using a previously developed SNP array. Our phylogenic analyses consistently identified: three clades in North America, one in East Asia, and one in Europe corresponding to V. vinifera. Using heterozygosity measurement, haplotype reconstruction and chloroplast markers, we identified the hybrids existing within and between clades. The species relationships were better assessed after discarding these hybrids from analyses. We also studied the relationships between phylogeny and morphological traits and found that several traits significantly correlated with the phylogeny. The American clade that includes important species such as V. riparia and V. rupestris showed a major divergence with all other clades based on both DNA polymorphisms and morphological traits.

A novel high-density grapevine (Vitis vinifera L.) integrated linkage map using GBS in a half-diallel population.

KEY MESSAGE: A half-diallel population involving five elite grapevine cultivars was generated and genotyped by GBS, and highly-informative segregation data was used to construct a high-density genetic map for Vitis vinifera L. Grapevine is one of the most relevant fruit crops in the world. Deeper genetic knowledge could assist modern grapevine breeding programs to develop new wine grape varieties able to face climate change effects. To assist in the rapid identification of markers for crop yield components, grape quality traits and adaptation potential, we generated a large Vitis vinifera L. population (N = 624) by crossing five red wine cultivars in a half-diallel scheme, which was subsequently sequenced by an efficient GBS procedure. A high number of fully informative genetic variants was detected using a novel mapping approach capable of reconstructing local haplotypes from adjacent biallelic SNPs, which were subsequently used to construct the densest consensus genetic map available for the cultivated grapevine to date. This 1378.3-cM map integrates 10 bi-parental consensus maps and orders 4437 markers in 3353 unique positions on 19 chromosomes. Markers are well distributed all along the grapevine reference genome, covering up to 98.8% of its genomic sequence. Additionally, a good agreement was observed between genetic and physical orders, adding confidence in the quality of this map. Collectively, our results pave the way for future genetic studies (such as fine QTL mapping) aimed to understand the complex relationship between genotypic and phenotypic variation in the cultivated grapevine. In addition, the method used (which efficiently delivers a high number of fully informative markers) could be of interest to other outbred organisms, notably perennial fruit crops.

Identification of stable QTLs for vegetative and reproductive traits in the microvine (Vitis vinifera L.) using the 18 K Infinium chip.

BACKGROUND: The increasing temperature associated with climate change impacts grapevine phenology and development with critical effects on grape yield and composition. Plant breeding has the potential to deliver new cultivars with stable yield and quality under warmer climate conditions, but this requires the identification of stable genetic determinants. This study tested the potentialities of the microvine to boost genetics in grapevine. A mapping population of 129 microvines derived from Picovine x Ugni Blanc flb, was genotyped with the Illumina® 18 K SNP (Single Nucleotide Polymorphism) chip. Forty-three vegetative and reproductive traits were phenotyped outdoors over four cropping cycles, and a subset of 22 traits over two cropping cycles in growth rooms with two contrasted temperatures, in order to map stable QTLs (Quantitative Trait Loci). RESULTS: Ten stable QTLs for berry development and quality or leaf area were identified on the parental maps. A new major QTL explaining up to 44 % of total variance of berry weight was identified on chromosome 7 in Ugni Blanc flb, and co-localized with QTLs for seed number (up to 76 % total variance), major berry acids at green lag phase (up to 35 %), and other yield components (up to 25 %). In addition, a minor QTL for leaf area was found on chromosome 4 of the same parent. In contrast, only minor QTLs for berry acidity and leaf area could be found as moderately stable in Picovine. None of the transporters recently identified as mutated in low acidity apples or Cucurbits were included in the several hundreds of candidate genes underlying the above berry QTLs, which could be reduced to a few dozen candidate genes when a priori pertinent biological functions and organ specific expression were considered. CONCLUSIONS: This study combining the use of microvine and a high throughput genotyping technology was innovative for grapevine genetics. It allowed the identification of 10 stable QTLs, including the first berry acidity QTLs reported so far in a Vitis vinifera intra-specific cross. Robustness of a set of QTLs was assessed with respect to temperature variation.

New stable QTLs for berry weight do not colocalize with QTLs for seed traits in cultivated grapevine (Vitis vinifera L.).

BACKGROUND: In grapevine, as in other fruit crops, fruit size and seed content are key components of yield and quality; however, very few Quantitative Trait Loci (QTLs) for berry weight and seed content (number, weight, and dry matter percentage) have been discovered so far. To identify new stable QTLs for marker-assisted selection and candidate gene identification, we performed simultaneous QTL detection in four mapping populations (seeded or seedless) with various genetic backgrounds. RESULTS: For berry weight, we identified five new QTLs, on linkage groups (LGs) 1, 8, 11, 17 and 18, in addition to the known major QTL on LG 18. The QTL with the largest effect explained up to 31% of total variance and was found in two genetically distant populations on LG 17, where it colocalized with a published putative domestication locus. For seed traits, besides the major QTLs on LG 18 previously reported, we found four new QTLs explaining up to 51% of total variance, on LGs 4, 5, 12 and 14. The previously published QTL for seed number on LG 2 was found related in fact to sex. We found colocalizations between seed and berry weight QTLs only for the major QTL on LG 18 in a seedless background, and on LGs 1 and 13 in a seeded background. Candidate genes belonging to the cell number regulator CNR or cytochrome P450 families were found under the berry weight QTLs on LGs 1, 8, and 17. The involvement of these gene families in fruit weight was first described in tomato using a QTL-cloning approach. Several other interesting candidate genes related to cell wall modifications, water import, auxin and ethylene signalling, transcription control, or organ identity were also found under berry weight QTLs. CONCLUSION: We discovered a total of nine new QTLs for berry weight or seed traits in grapevine, thereby increasing more than twofold the number of reliable QTLs for these traits available for marker assisted selection or candidate gene studies. The lack of colocalization between berry and seed QTLs suggests that these traits may be partly dissociated.

Cementoplasty for painful bone metastases: a series of 42 cases.

The aim of this study is to assess the interest of cementoplasty in the management of bone metastases, based on a retrospective study involving 42 cementoplasty procedures. The median age of the patients is 59 years, with 24 women (57%) and 18 men, all of them presenting with an advanced disease. The cementoplasty was situated in long bones (ten patients), dorsal or lumbar vertebrae (13) and flat bones (20). The principal indication was pain, sometimes with consolidation. The intensity of pain decreases between the day before and the month following the treatment (P = 0.04) among the 25 patients who had pain assessment before and after the procedure. We note 57% good results (24 patients), 9.5% failures (4 patients), and 31% with partial results (13 patients), that is, a total of 88% with "partial or full" alleviation. 16 patients out of 22 (73%) who were no longer able to walk (because of the pain or risk of fracture) were able to resume walking. We observed in this series 40.5% of complications, all of them benign. Cementoplasty improves the quality of life of patients with bone metastases, by decreasing the pain in 88% of cases and allowing the resumption of walking in almost three-quarters of the patients who had lost the ability to walk.

Comparison of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma.

BACKGROUND: A significant improvement in overall survival (OS) was demonstrated in patients with advanced hepatocellular carcinoma (HCC) who received sorafenib (Sor) in the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, in contrast to a response rate (RR) of 2% assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). Modified RECIST (mRECIST) were developed to assess the response in patients with HCC, based on measurement of viable tumor with arterial enhancement on a computed tomography (CT) scan. In the current study, mRECIST were evaluated and were compared with RECIST in patients who received Sor for advanced HCC. METHODS: The authors retrospectively analyzed 53 patients who received Sor for advanced HCC. Patients must to have undergone a 4-phase CT scan before treatment and repeatedly thereafter. CT scans were analyzed using RECIST 1.1 and mRECIST. RESULTS: The rates of objective response (OR), stable disease (SD), and progressive disease (PD) were 2%, 79%, and 19%, respectively, according to RECIST and 23%, 57%, and 21%, respectively, according to mRECIST (P < .001). Patients who achieved an OR according to mRECIST had a longer OS than nonresponding patients with SD or PD (median OS, 18 months and 8 months, respectively; P = .013). In the 42 patients who achieved SD according to RECIST, OS differed depending on tumor response according to mRECIST, with a median OS of 17 months, 10 months, and 4 months for patients who achieved an OR (n = 11), SD (n = 29), and PD (n = 2), respectively (P = .016). CONCLUSIONS: The current series validated mRECIST in patients who received Sor for advanced HCC. The majority of patients who had SD according to RECIST had a different prognosis according to mRECIST. The results indicated that, for patients with HCC, mRECIST should be used for the standard assessment of treatment efficacy, particularly in patients who are receiving antiangiogenic drugs.

Relapse factors for ileal neuroendocrine tumours after curative surgery: a retrospective French multicentre study.

AIM: To evaluate the characteristics of postoperative relapse, predictive factors and time to relapse after curative surgery for well-differentiated neuroendocrine tumours of the ileum, without hepatic or other distant metastases. METHODS: Clinical data of patients entered into the Groupe d'étude des Tumeurs Endocrines database were collected and analysed retrospectively to identify factors predictive of relapse. RESULTS: Among 100 patients followed for a median of 56.5 (range 1-290) months, 42 relapsed after a median follow-up of 57.5 (range 6-176) months, with liver lesions in 27 (64.3%). Median disease-free survival (Kaplan-Meier) was 88 months (95% confidence interval 72-115). Disease-free survival was shorter for emergency surgery patients (p<0.01), patients with distant mesenteric lymph-node metastases (p<0.01), with fortuitous diagnosis (p=0.02), with tumour diameter >20mm (p=0.02), and those with multiple tumours (p=0.07). Multivariate analysis retained emergency surgery (odds-ratio 4.04 [95% confidence interval 2.01-8.11]), distant mesenteric lymph-node metastases (odds-ratio 2.53 [95% confidence interval 1.22-5.25]), and multiple tumours (odds-ratio 2.14 [95% confidence interval 1.01-4.50]), as being significantly associated with relapse. CONCLUSION: Patients who underwent emergency surgery, with distant mesenteric lymph-node metastases or with multiple ileal tumours relapsed earlier. Closer monitoring for the patients with these risk factors may be required.

Improving attention and preventing reading difficulties among low-income first-graders: a randomized study.

Students' inattention is predictive of reading problems and of non-response to effective reading intervention. In this randomized study, 58 first-grade classrooms located in 30 schools were assigned to a control condition or to one of two intervention conditions. In these last two conditions, peer-tutoring activities were conducted to improve classroom reading instruction. In one of the intervention conditions, the Good Behavior Game was also implemented to maximize students' attention during reading lessons. Both interventions were effective: peer-tutoring activities helped students improve their reading skills and attention was generally higher when the Good Behavior Game was implemented. Contrary to expectations however, students identified as inattentive at pretest did not become better readers when the two interventions were implemented.

Clubbing and hypertrophic osteoarthropathy in two patients taking long-term bevacizumab for metastatic colorectal cancer.

INTRODUCTION: The authors report two cases of young patients who developed clubbing and hypertrophic osteoarthropathy in one case or lung diffusion disorder in the second, after a long-term use of bevacizumab plus chemotherapy in a palliative setting of metastatic colorectal cancer. DISCUSSION: We propose that patients on long-term bevacizumab be examined for clubbing and undergo respiratory function tests and that this would be studied prospectively before beginning trials in evaluating this monoclonal antibody given for 2 years in an adjuvant setting.

Quantitative genetic bases of anthocyanin variation in grape (Vitis vinifera L. ssp. sativa) berry: a quantitative trait locus to quantitative trait nucleotide integrated study.

The combination of QTL mapping studies of synthetic lines and association mapping studies of natural diversity represents an opportunity to throw light on the genetically based variation of quantitative traits. With the positional information provided through quantitative trait locus (QTL) mapping, which often leads to wide intervals encompassing numerous genes, it is now feasible to directly target candidate genes that are likely to be responsible for the observed variation in completely sequenced genomes and to test their effects through association genetics. This approach was performed in grape, a newly sequenced genome, to decipher the genetic architecture of anthocyanin content. Grapes may be either white or colored, ranging from the lightest pink to the darkest purple tones according to the amount of anthocyanin accumulated in the berry skin, which is a crucial trait for both wine quality and human nutrition. Although the determinism of the white phenotype has been fully identified, the genetic bases of the quantitative variation of anthocyanin content in berry skin remain unclear. A single QTL responsible for up to 62% of the variation in the anthocyanin content was mapped on a Syrah x Grenache F(1) pseudo-testcross. Among the 68 unigenes identified in the grape genome within the QTL interval, a cluster of four Myb-type genes was selected on the basis of physiological evidence (VvMybA1, VvMybA2, VvMybA3, and VvMybA4). From a core collection of natural resources (141 individuals), 32 polymorphisms revealed significant association, and extended linkage disequilibrium was observed. Using a multivariate regression method, we demonstrated that five polymorphisms in VvMybA genes except VvMybA4 (one retrotransposon, three single nucleotide polymorphisms and one 2-bp insertion/deletion) accounted for 84% of the observed variation. All these polymorphisms led to either structural changes in the MYB proteins or differences in the VvMybAs promoters. We concluded that the continuous variation in anthocyanin content in grape was explained mainly by a single gene cluster of three VvMybA genes. The use of natural diversity helped to reduce one QTL to a set of five quantitative trait nucleotides and gave a clear picture of how isogenes combined their effects to shape grape color. Such analysis also illustrates how isogenes combine their effect to shape a complex quantitative trait and enables the definition of markers directly targeted for upcoming breeding programs.

ERGs in female carriers of incomplete congenital stationary night blindness (I-CSNB). A family report.

ERG findings in five sisters are reported. By pedigree analysis, four of the five must be obligate carriers for I-CSNB since their sons were affected (impaired night vision, reduced visual acuity, variable ametropia, congenital nystagmus and ERG with both scotopic and photopic b-wave reduced amplitude). The fifth was childless at the time of examination and her ERG analysis was normal. Three of the four obligate carriers showed significant reduction in the sum of the OPs amplitude as previously reported as being an electrophysiological signs in female carriers: two without alteration in other ERG components and the third with association with a flicker ERG amplitude significantly increased. The fourth female carrier showed a normal sum of the OPs amplitude whereas the other b-wave ERG or flicker amplitudes were significantly decreased. These last two ERG results suggest a possible modifications of synaptic transmission at a post-receptoral site (outer plexiform layer or involvement of the bipolar pathways) in these two carriers.