Grapevine trunk diseases under thermal and water stresses.

MAIN CONCLUSION: Heat and water stresses, individually or combined, affect both the plant (development, physiology, and production) and the pathogens (growth, morphology, dissemination, distribution, and virulence). The grapevine response to combined abiotic and biotic stresses is complex and cannot be inferred from the response to each single stress. Several factors might impact the response and the recovery of the grapevine, such as the intensity, duration, and timing of the stresses. In the heat/water stress-GTDs-grapevine interaction, the nature of the pathogens, and the host, i.e., the nature of the rootstock, the cultivar and the clone, has a great importance. This review highlights the lack of studies investigating the response to combined stresses, in particular molecular studies, and the misreading of the relationship between rootstock and scion in the relationship GTDs/abiotic stresses. Grapevine trunk diseases (GTDs) are one of the biggest threats to vineyard sustainability in the next 30 years. Although many treatments and practices are used to manage GTDs, there has been an increase in the prevalence of these diseases due to several factors such as vineyard intensification, aging vineyards, or nursery practices. The ban of efficient treatments, i.e., sodium arsenite, carbendazim, and benomyl, in the early 2000s may be partly responsible for the fast spread of these diseases. However, GTD-associated fungi can act as endophytes for several years on, or inside the vine until the appearance of the first symptoms. This prompted several researchers to hypothesise that abiotic conditions, especially thermal and water stresses, were involved in the initiation of GTD symptoms. Unfortunately, the frequency of these abiotic conditions occurring is likely to increase according to the recent consensus scenario of climate change, especially in wine-growing areas. In this article, following a review on the impact of combined thermal and water stresses on grapevine physiology, we will examine (1) how this combination of stresses might influence the lifestyle of GTD pathogens, (2) learnings from grapevine field experiments and modelling aiming at studying biotic and abiotic stresses, and (3) what mechanistic concepts can be used to explain how these stresses might affect the grapevine plant status.

Vitis Methods to Understand and Develop Strategies for Diagnosis and Sustainable Control of Grapevine Trunk Diseases.

Vitis vinifera is affected by many diseases every year, depending on causal agents, susceptibility of cultivars, and climate region. Some are caused by a single agent, such as gray mold caused by Botrytis cinerea or powdery mildew caused by Erysiphe necator. Others result from the actions of a complex of pathogens such as grapevine trunk diseases (GTDs). GTDs are presently among the most devastating diseases in viticulture worldwide because both the economic losses and the long-term sustainability of vineyards are strongly affected. The complexity of GTDs results from the diversity of associated fungi, the undetermined period of latency within the vine (asymptomatic status), the erratic foliar symptom expression from one year to the next, and, probably correlated with all of these points, the lack of efficient strategies to control them. Distinct methods can be beneficial to improve our knowledge of GTDs. In vitro bioassays with cell suspensions, calli, foliar discs, full leaves, or plantlets, and in vivo natural bioassays with cuttings, grafted plants in the greenhouse, or artificially infected ones in the vineyard, can be applied by using progressive integrative levels of in vitro and in vivo, depending on the information searched. In this review, the methods available to understand GTDs are described in terms of experimental procedures, main obtained results, and deliverable prospects. The advantages and disadvantages of each model are also discussed.

Diaporthe diversity and pathogenicity revealed from a broad survey of grapevine diseases in Europe.

Species of Diaporthe are considered important plant pathogens, saprobes, and endophytes on a wide range of plant hosts. Several species are well-known on grapevines, either as agents of pre- or post-harvest infections, including Phomopsis cane and leaf spot, cane bleaching, swelling arm and trunk cankers. In this study we explore the occurrence, diversity and pathogenicity of Diaporthe spp. associated with Vitis vinifera in major grape production areas of Europe and Israel, focusing on nurseries and vineyards. Surveys were conducted in Croatia, Czech Republic, France, Hungary, Israel, Italy, Spain and the UK. A total of 175 Diaporthe strains were isolated from asymptomatic and symptomatic shoots, branches and trunks. A multi-locus phylogeny was established based on five genomic loci (ITS, tef1, cal, his3 and tub2), and the morphological characters of the isolates were determined. Preliminary pathogenicity tests were performed on green grapevine shoots with representative isolates. The most commonly isolated species were D. eres and D. ampelina. Four new Diaporthe species described here as D. bohemiae, D. celeris, D. hispaniae and D. hungariae were found associated with affected vines. Pathogenicity tests revealed D. baccae, D. celeris, D. hispaniae and D. hungariae as pathogens of grapevines. No symptoms were caused by D. bohemiae. This study represents the first report of D. ambigua and D. baccae on grapevines in Europe. The present study improves our understanding of the species associated with several disease symptoms on V. vinifera plants, and provides useful information for effective disease management.

Early events prior to visual symptoms in the apoplectic form of grapevine esca disease.

Plant infection by pathogens generates various forms of symptoms. Most of them have been described as soon as they become visible, whereas preceding, discrete signs during incubation are poorly or not understood. In Vitis vinifera, esca-related pathogenic fungi inhabit living trunk wood and induce the so-called apoplexy, a sudden wilting of leaves within a few days. To further understand the apoplexy expression, the period preceding symptom appearance was investigated by following physiological and molecular markers associated with photosynthetic mechanisms and stress responses. Within the week preceding symptoms, drastic physiological alterations of photosynthesis were registered in pre-apoplectic vines, as revealed by a decrease in gas exchange, changes in chlorophyll fluorescence, and repression of photosynthesis-related genes. In the meantime, expression of defense-related genes was induced and amplified during symptom expression. Water-stress-related genes were specifically investigated because water transport may be impeded by clogging xylem vessels due to esca-causing fungi. Neither of the tested water-stress-related genes was affected in pre-apoplectic grapevine leaves whereas these genes were downregulated in drying leaves. Our results suggest that, during incubation of esca apoplexy, grapevine perceives some signals (likely fungi-originated toxins) and reacts by reducing photosynthesis and triggering defense mechanisms.

Season of birth and not vitamin D receptor promoter polymorphisms is a risk factor for multiple sclerosis.

Both genetic and environmental factors contribute to multiple sclerosis, the most common neurodegenerative disorder with onset in young adults. The objective of the current study is, based on the hypothesis that environmentally predisposed individuals are at risk for multiple sclerosis, to investigate whether they also carry genetic variants within the vitamin D machinery. Using medical files and DNA samples from 583 trios (a patient and both parents) of the French Multiple Sclerosis Genetics Group as well as data from the French Statistics Bureau, we aimed to assess whether: (1) a seasonality of birth was observed in French multiple sclerosis patients; (2) three single nucleotide polymorphisms within the promoter region of the vitamin D receptor were associated with multiple sclerosis susceptibility; and (3) the combination of a high risk month of birth and vitamin D receptor polymorphisms were correlated to multiple sclerosis incidence. We observed a significantly reduced number of individuals born in November who were later diagnosed as multiple sclerosis patients. However, we found no association between the three studied vitamin D receptor polymorphisms and multiple sclerosis. In conclusion, our data suggest that high levels of vitamin D during the third trimester of pregnancy could be a protective factor for multiple sclerosis.

Very- and ultra-long-period seismic signals prior to and during caldera formation on La Réunion Island.

Early detection of the onset of a caldera collapse can provide crucial information to understand their formation and thus to minimize risks for the nearby population and visitors. Here, we analyse the 2007 caldera collapse of Piton de la Fournaise on La Réunion Island recorded by a broadband seismic station. We show that this instrument recorded ultra-long period (ULP) signals with frequencies in the range (0.003-0.01 Hz) accompanied by very-long period (VLP) signals (between 0.02 and 0.50 Hz) prior to and during the caldera formation suggesting it is possible to detect the beginning of the collapse at depth and anticipate its surface formation. Interestingly, VLP wave packets with a similar duration of 20 s are identified prior to and during the caldera formation. We propose that these events could result from repeating piston-like successive collapses occurring through a ring-fault structure surrounding a magma reservoir from the following arguments: the source mechanism from the main collapse, the observations of slow source processes as well as observations from the field and the characteristic ring-fault seismicity.

Ulcerative colitis treatment : an insight into daily clinical practice.

BACKGROUND: The natural history of ulcerative colitis (UC) is unpredictable. Factors associated with the need for different types of step-up therapy in UC patients failing on 5-aminosalicylic acid (5-ASA) or corticosteroids are understudied. AIMS: Describe step-up therapy in patients with UC the first year after failing on 5-ASA or corticosteroids. METHODS: A Belgian, multi-center, prospective, non-interventional observational study comprising adult UC patients failing on 5-ASA or corticosteroids and naïve to immunomodulators/ biologicals. During a 12 months follow-up, patient characteristics, demography, medical therapy, biomarkers, therapy adherence and quality of life (QoL) were assessed. RESULTS: After 1 year, 35% of the patients were on biological therapy. Use of anti-TNF differed depending on baseline treatment: corticosteroid-refractory patients (55.8%), 5-ASA refractory (20.0%), and corticosteroid-dependent (16.0%) patients (p<0.001). The decision to start a line of therapy was based on the Mayo combined severity but not on biomarkers like faecal calprotectin, haemoglobin, CRP, albumin, platelets, and number of extraintestinal manifestations. At year 1, 84.2% of the patients had only mild UC or remission and a significant improvement of fatigue (p=0.004) and IBDQ scores (p<0.001) were observed implying an improved QoL. CONCLUSION: Treatment step-up, based on clinical scores in immunomodulatory and anti-TNF naïve patients with UC, provides good clinical outcomes and QoL.

Sugars and flowering in the grapevine (Vitis vinifera L.).

Sugars play an important role in grapevine flowering. This complex process from inflorescence initiation to fruit maturity takes two growing seasons. Currently, most of the available data concern the involvement of sugars as energy sources during the formation of reproductive structures from initiation of inflorescences during the summer of the first year, until flower opening during the following spring. Sugars devoted to the development of reproductive structures are supplied either by wood reserves or by photosynthesis in leaves or inflorescences, depending on the stage of development. Female meiosis appears to be a key point in the success of flower formation because (i) flowers are vulnerable at this stage and (ii) it corresponds in the whole plant to the transition between reserve mobilization from perennial organs (roots, trunk, and canes) towards efficient leaf photosynthesis. The perturbation of reserve replenishment during the previous year provokes perturbation in the development of inflorescences, whereas altering the photosynthetic sources affects the formation of flowers during the same year. In particular, a lack of sugar availability in flowers at female meiosis caused by various environmental or physiological fluctuations may lead to drastic flower abortion. Apart from energy, sugars also play roles as regulators of gene expression and as signal molecules that may be involved in stress responses. In the future, these two topics should be further investigated in the grapevine considering the sensitivity of flowers to environmental stresses at meiosis.

Thermal convection in three-dimensional fractured porous media.

Thermal convection is numerically computed in three-dimensional (3D) fluid saturated isotropically fractured porous media. Fractures are randomly inserted as two-dimensional (2D) convex polygons. Flow is governed by Darcy's 2D and 3D laws in the fractures and in the porous medium, respectively; exchanges take place between these two structures. Results for unfractured porous media are in agreement with known theoretical predictions. The influence of parameters such as the fracture aperture (or fracture transmissivity) and the fracture density on the heat released by the whole system is studied for Rayleigh numbers up to 150 in cubic boxes with closed-top conditions. Then, fractured media are compared to homogeneous porous media with the same macroscopic properties. Three major results could be derived from this study. The behavior of the system, in terms of heat release, is determined as a function of fracture density and fracture transmissivity. First, the increase in the output flux with fracture density is linear over the range of fracture density tested. Second, the increase in output flux as a function of fracture transmissivity shows the importance of percolation. Third, results show that the effective approach is not always valid, and that the mismatch between the full calculations and the effective medium approach depends on the fracture density in a crucial way.

[Clinical case of the month. Hepatitis B reactivation in an Ag HBs negative patient]. / Le cas clinique du mois. Un cas de réactivation virale B chez un patient Ag HBs négatif.

A 66-year-old man, Ag HBs negative, suffering from glomerulonephritis was treated with prednisone. Hepatitis B reactivation was observed after increasing and regression of corticotherapy. Pathogenesis, efficient therapy and prevention of reactivation of hepatitis B will be reviewed.

Alteration of photosynthesis in grapevines affected by esca.

ABSTRACT To further understand the development of esca disease in grapevine, its physiological impact on plants grown in the vineyard was characterized, focusing mainly on photosynthesis. For this purpose, the state of the photosynthetic apparatus was evaluated in symptomatic and asymptomatic leaves in esca-infected grape plants, and wood carbohydrates stored in annual canes were assayed. In symptomatic leaves, esca greatly affected grapevine physiology. Foliar symptoms were associated with both stomatal closure and alteration of the photosynthetic apparatus as revealed by (i) a decrease in CO(2) assimilation, transpiration, and a significant increase in intercellular CO(2) concentration; (ii) a strong drop in both the maximum fluorescence yield and the effective Photosystem II quantum yield; and (iii) a reduction of total chlorophyll but a stable carotenoid content. On symptomatic canes, all these variables were affected more on leaves with symptoms than without symptoms, suggesting a gradation in photosynthesis disruptions in the plant according to the degree of symptom severity. In addition, canes of symptomatic plants had reduced carbohydrate reserves during the winter rest, whether they exhibit symptoms or not. The following year, the lower pool of reserves may contribute to a significant decrease in plant development, as well as a global loss in plant vigor.

High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.

PURPOSE: The study was designed to assess the toxicity and activity of high-dose ifosfamide (HDI) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas (ASTS) pretreated with doxorubicin and/or a standard-dose ifosfamide (SDI)-containing regimen. PATIENTS AND METHODS: Between January 1991 and November 1993, 40 patients with progressive ASTS were entered onto the study. Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows: SDI-refractory (n = 21), SDI-resistant (n = 2), and indeterminate SDI-sensitive (n = 5). Patients were treated until progression or major toxicity. RESULTS: One hundred forty-seven cycles of HDI were administered. Neutropenia was dose-limiting, with 100% of patients experiencing grade 3 to 4 toxicity and 12 admissions for febrile neutropenia (30% of patients). Neurotoxicity (17% of patients) was significantly associated with acute renal failure (n = 4) (P < .001), grade 4 thrombocytopenia (P < .01) and febrile neutropenia (P = .048). Chronic renal toxicity (n = 4) was significantly associated with retroperitoneal masses and/or prior nephrectomy (P = .008). Partial responses (PRs) were observed in 12 of 36 assessable patients (33%) and eight patients (22%) experienced disease stabilization. All but one response occurred in patients pretreated with SDI, with five PRs among SDI-refractory patients. Leiomyosarcomas appear resistant to HDI. The median response duration was 8 months (range, 6 to 13+) and the median overall survival time was 12 months. CONCLUSION: The activity of HDI in these pretreated ASTS patients and the apparent circumvention of SDI resistance suggest a real dose-response relationship for ifosfamide and deserve further evaluation. Although toxic, this treatment appears feasible and manageable using routine clinical support. Since prophylaxis of ifosfamide-induced renal damage remains unknown, frequent monitoring of renal and tubular functions during therapy is highly recommended.

Toxicity of extracellular proteins from Diplodia seriata and Neofusicoccum parvum involved in grapevine Botryosphaeria dieback.

Botryosphaeria dieback, esca and Eutypa dieback are three economic major grapevine trunk diseases that cause severe yield reduction in vineyards worldwide. The frequency of disease symptoms has increased considerably over the past decade, and no efficient treatment is currently available to control these diseases. The different fungi associated with grapevine trunk diseases mainly induce necrotic wood and characteristic foliar symptoms. In this context, fungi virulence factors and host invasion are not well understood. We hypothesise that extracellular proteins produced by Diplodia seriata and Neofusicoccum parvum, two causal agents associated with Botryosphaeria dieback, are virulence factors responsible for the pathogenicity. In our previous work, we demonstrated that the total extracellular compounds produced by N. parvum induced more necrosis on Chardonnay calli and triggered a different defence gene expression pattern than those produced by D. seriata. Furthermore, this aggressiveness was not clearly correlated with the production of mellein, a characteristic phytotoxin of Botryosphaeriaceae, in our in vitro calli model. To characterise other potential virulence factors and to understand the mechanisms of host invasion by the fungus, we evaluated the profile, quantity and the impact of extracellular proteins produced by these fungi on Vitis vinifera calli necrosis and defence gene expression. Our results reveal that, under the same conditions, N. parvum produces more extracellular proteins and in higher concentrations than D. seriata. With Vitis vinifera cv. Chardonnay cells, we showed that equivalent concentrations of proteins secreted by N. parvum were more aggressive than those of D. seriata in producing necrosis and that they clearly induced more grapevine defence genes.

Identification of two ets related genes in a marine worm, the polychaete annelid Nereis diversicolor.

The ETS family includes a growing number of transcription factors with a highly conserved DNA-binding domain, the ETS domain. We have used PCR amplification with degenerated oligonucleotides to isolate two putative ETS DNA-binding coding domains in a primitive form of coelomate, the polychaete annelid Nereis diversicolor. These sequences are highly related to the ETS and ERG groups of the ets gene family. For the erg sequence an adjacent region encoding for 91 amino acids has been characterized after library screening, and we show an expression in cells isolated from the coelomic cavity of the animal. A phylogenic analysis confirms that the ets-1/ets-2 and the erg/fli dichotomy arose specifically in the vertebrate lineage.

Alternating radiotherapy and chemotherapy in non-metastatic inflammatory breast cancer.

Ninety-nine patients presenting with non-metastatic inflammatory breast cancer were treated with an alternating protocol of radiotherapy and chemotherapy. The alternating schedule consisted of 8 courses of combined chemotherapy, including doxorubicin, vincristine, cyclophosphamide, methotrexate and 5-Fluorouracil, and 3 series of loco-regional radiotherapy delivering a total dose of 65 to 75 Gy to the breast tumor, 65 Gy to the axilla, and 50 Gy to the supraclavicular and internal mammary chain lymph nodes. Radiotherapy was started after the third course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy-five percent of patients were in complete remission at the end of this induction treatment. The 3-year local control was 72% and the 3-year overall survival rate was 70%. An isolated local recurrence was observed in only 4% of patients. Approximately one-half of patients developed distant metastases. These results show that alternating radiotherapy and chemotherapy schedules deserve further investigation in locally advanced breast cancer.

Management of the axilla in conservatively treated breast cancer: 592 patients treated at Institut Gustave-Roussy.

Between June 1970 and April 1982, 592 patients with unilateral T1 and small T2 breast cancers were managed conservatively at the Institut Gustave-Roussy. The treatment policy for the axilla was to perform a lower axillary dissection and to proceed to axillary clearance ( +/- radiotherapy) in patients with axillary invasion by tumor (N+). Some N+ patients had only lower axillary dissection and radiotherapy. Five hundred fifty-eight patients underwent axillary surgery which was a lower axillary dissection in 374 patients (67%) and axillary clearance in 184 patients (33%). There was axillary invasion in 198 cases (36%). Only five patients relapsed in the axilla and the probability of axillary relapse at 5 years was 1.2%. There were no axillary relapses in N+ patients who had had an axillary clearance whether irradiated or not. The incidence of upper limb complications was significantly greater in patients undergoing axillary surgery and radiotherapy compared with axillary surgery alone (p less than 0.0001). It is concluded that a lower axillary dissection accurately identifies N-patients and an axillary clearance in N+ patients ensures good local control and avoids the morbidity associated with axillary irradiation.

Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy.

Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.

Postoperative radiotherapy in the management of adult soft tissue sarcoma of the extremities: results with two different total dose, fractionation, and overall treatment time schedules.

PURPOSE: This retrospective study was performed to evaluate two postoperative radiotherapy schedules in terms of dose, fractionation, and overall treatment time in soft tissue sarcoma (STS) of the extremities. METHODS AND MATERIALS: Between January 1984 and December 1993, 62 patients with newly diagnosed localized STS of the extremities were treated with maximal conservative surgery and postoperative radiotherapy (RT). Forty-five patients received 50 Gy with conventional fractionation plus a boost dose (5 to 20 Gy). Seventeen patients had hyperfractionated accelerated radiotherapy (HFART) up to a dose of 45 Gy in 3 weeks. RESULTS: With a median follow-up of 72 months, the 5-year local failure rate was 25%, the 5-year disease-free and overall survival rates were respectively 42% and 62%. The 3-year local relapse, disease-free, and overall survival rates were respectively 16%, 44%, and 70% in the conventional radiotherapy group, and 36%, 47%, and 82% in the HFART group (NS). No factor significantly influenced local control with a trend, however, in favor of conventional RT (p = 0.10). CONCLUSION: HFART at the dose of 45 Gy does not seem to be superior to the standard RT schedule, neither in terms of local control, survival, nor in terms of long-term side effects. However this dose could be considered too low as well as the power of comparison between the two groups to draw definitive conclusions.

Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma.

UNLABELLED: We assessed the therapeutic benefits of 131I treatment in patients with distant metastases of differentiated thyroid carcinoma. METHODS: Of 2200 patients treated for differentiated thyroid carcinoma at our institution, 394 had lung and/or bone metastases. RESULTS: Two-thirds of the patients had 131I uptake in their metastases, but only 46% achieved a complete response. Prognostic factors for complete response were: younger age, presence of 131I uptake in the metastases and small extent of disease. The survival rate was 33% at 15 yr. As shown by multivariate analysis, favorable prognostic factors for survival were: younger age and time of metastases detection, well-differentiated histologic type of the thyroid tumor, presence of 131I type uptake in the metastases, small extent of the disease and year of discovery of metastases. CONCLUSION: In terms of survival, the benefits of 131I therapy cannot be demonstrated by prospective controlled studies. The present study clearly demonstrates, however, that treatment with 131I is one of the factors which accounts for survival; patients whose metastases concentrated 131I and who could be treated with radioiodine had higher survival rates. Patients who achieved complete response following treatment of distant metastases had a 15-yr survival rate of 89%, while those who did not achieve complete response had a survival rate of only 8%. The survival rate improved with the year of discovery of distant metastases, after 131I total-body imaging and serum thyroglobulin measurements were routinely used.

Cosmetic results following lumpectomy, axillary dissection and radiotherapy for small breast cancers.

Between 1970 and April 1982, 592 women with T(1), small T2, N0, N1, M0 breast cancer were managed by lumpectomy, axillary dissection and radiotherapy at the Institut Gustave-Roussy (IGR). The overall cosmetic result and the degree of asymmetry, fibrosis and telangiectasia of the treated breast were assessed by the radiation oncologist at each follow-up visit. The changes in these cosmetic parameters with time are shown. At 5 years the overall cosmetic result was excellent in 59%, good in 38% and fair or poor in 8%. A multivariate analysis was performed of the factors associated with a cosmetic defect. The most significant factors were tumour size, the presence of defect after surgery and the daily applied dose per fraction to the breast. Surgical and radiotherapy technique (especially alternate day fractionation) can significantly affect the cosmetic result obtained.