Grapevines under drought do not express esca leaf symptoms

In the context of climate change, plant mortality is increasing worldwide in both natural and agroecosystems. However, our understanding of the underlying causes is limited by the complex interactions between abiotic and biotic factors and the technical challenges that limit investigations of these interactions. Here, we studied the interaction between two main drivers of mortality, drought and vascular disease (esca), in one of the world’s most economically valuable fruit crops, grapevine. We found that drought totally inhibited esca leaf symptom expression. We disentangled the plant physiological response to the two stresses by quantifying whole-plant water relations (i.e., water potential and stomatal conductance) and carbon balance (i.e., CO₂ assimilation, chlorophyll, and nonstructural carbohydrates). Our results highlight the distinct physiology behind these two stress responses, indicating that esca (and subsequent stomatal conductance decline) does not result from decreases in water potential and generates different gas exchange and nonstructural carbohydrate seasonal dynamics compared to drought.

For many plant pathogens, it is still largely unknown if their interactions with abiotic stresses are synergistic, antagonistic, or neutral. These interactions are particularly crucial in the case of vascular diseases and drought (1–3). Both affect the same plant tissue, the xylem vascular network, which is responsible for the movement of water and nutrients throughout the plant. A strong synergy when combining drought and vascular disease could accelerate plant death (1, 3) and has strong implications in the context of climate change, in which a global increase of drought and associated plant mortality is expected (4).Grapevine, one of the most economically valuable crops in the world (5), is being threatened by future climate change scenarios (6). Since the early 2000s, old-world vineyards have exhibited increasing yield losses, and although the causes are not completely understood, an increased incidence of trunk diseases has been identified as one of the main contributors (7, 8). One of the most prominent of these diseases is esca. Esca is a vascular disease associated with losses in fruit quality and quantity and increased vine mortality, and the mechanisms of esca pathogenesis are still largely misunderstood (9, 10). This latent disease primarily affects perennial organs (i.e., the trunk), causing necrosis of internal tissues. Annual organs (i.e., leaves and clusters) typically begin to display symptoms in mature plants (normally older than 10 y) (11, 12). Recent work by our laboratory quantified the presence of hydraulic failure in the xylem tissue of esca-symptomatic leaves and stems (13, 14), and it is hypothesized that the transpiration stream facilitates the transport of phytotoxic metabolites from the pathogen niche in the trunk to the leaves (8). Therefore, the physiology controlling vine water use likely plays a crucial role during esca pathogenesis. In this context, we hypothesized a strong interaction between esca and drought, which both affect xylem water transport. Drought events cause yield decline, and when severe and/or prolonged, vine mortality (15, 16). Due to their climatic and edaphic environment, most of the world’s wine regions are exposed to a high risk of drought, as irrigation is not a sustainable long-term solution and rainfall is often not sufficient to supply grapevine evapotranspiration [e.g., in the Mediterranean area (17, 18)]. Because both drought and esca are associated with xylem hydraulic failure (13, 14, 19) and, theoretically, with nonstructural carbohydrate (NSC) consumption (1, 3, 8), these stresses could synergize and amplify the current vineyard decline. Therefore, there are real and urgent concerns regarding the outcome of the interaction between drought events and vascular pathogenesis in the grapevine.On some levels, plant responses to vascular disease and drought appear similar and include decreases in leaf gas exchange (20–22), losses of hydraulic conductivity (14, 23, 24), wilting (i.e., decreases in cell turgor), and scorching of leaves (12, 25, 26). Because they induce similar plant responses, it could be assumed that their interactions would be synergistic. However, we lack the detailed whole-plant physiology studies necessary to determine if this is true. This is probably because studying disease–drought interaction can be extremely challenging. Some vascular diseases, including esca, cannot be reproduced through the artificial inoculation of plants. Thus, studies rely on naturally infected field experimentation in which the disease history of specific plants is largely unknown and applying well-controlled water deficits (WD) (as well as controlling other environmental factors) is either difficult or impossible.The main objective of this study was to explore the interaction between esca and drought and to disentangle the whole-plant physiological response to the two stresses. We overcame the technical barriers by transplanting naturally infected plants with known disease histories from the field into pots to precisely manipulate their watering regime and study the combined effect of esca and drought. We maintained half of the plants under a WD at a predawn water potential (Ψ_PD) ∼ −1 MPa during 3 mo in two consecutive seasons, which simulated a moderate to severe level of drought (27). During these periods, we quantified plant–water relations (water potential and whole-plant and leaf-stomatal conductance), carbon balance (CO₂ assimilation, chlorophyll content, and NSC quantification in leaves and stems), and the development of esca symptoms. Our results showed that whole-plant physiological responses to esca or drought are not driven by the same underlying mechanisms; once combined, the two stresses strongly and antagonistically interact, opening perspectives on the plant–pathogen–environment relationships impacting vineyard sustainability.     

Tumor necrosis factor and interleukin-1 activities in free lung cells after single and repeated inhalation of bacterial endotoxin.

Bacterial endotoxins (lipopolysaccharides), important components of many organic dusts, are known to induce macrophages to produce the inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). To investigate the role of these mediators in the early inflammatory responses in the lung, guinea pigs were exposed to an aerosol of bacterial endotoxin. A bronchoalveolar lavage (BAL) was then performed, and TNF-alpha and IL-1 in lysed BAL cells and in the supernatants from BAL cell cultures were studied. The effect of single and repeated LPS inhalation exposures on the activities of TNF and IL-1 was studied, as was the effect of LPS added to the cell culture medium. A single inhalation exposure to LPS caused an increase in the TNF-alpha and IL-1 activities in cell lysate and in the cell culture supernatant. After a second inhalation exposure, cell-associated and extracellular TNF-alpha activity could not be detected, whereas IL-1 activity was markedly enhanced. IL-1 activity was increased when LPS was added to the cell culture medium with or without a prior inhalation exposure. In contrast, TNF-alpha activity was not affected after a second exposure.     

Induction of human interleukin 1 mRNA measured by collagenase- and prostaglandin E2-stimulating activity in rheumatoid synovial cells

Human blood peripheral monocyte/macrophages release in culture a mononuclear cell factor (MCF) which stimulates the production of collagenase and prostaglandin E2 by human rheumatoid synovial cells and dermal fibroblasts. These two products play a role in connective tissue destruction. MCF has an apparent molecular weight of approximately 15 000 and is biologically and biochemically indistinguishable from interleukin 1. MCF therefore belongs to the well-documented nonimmune biological activities attributed to interleukin 1. Studies on the mechanisms of production and action of such monokine(s) have been difficult in view of the minute quantities produced by freshly isolated cells or from human monocytic lines. Starting from lectin-stimulated human blood mononuclear cells, we have isolated poly(A)+ RNA and studied its translation following microinjection into Xenopus laevis oocytes. The mRNA translation products stimulated collagenase and prostaglandin E2 production in human rheumatoid synovial cells and dermal fibroblasts. The size of MCF-mRNA was estimated to be 10 S. The mRNA of a member of the interleukin 1 family can now be studied in a system based on a specific and direct relevant biological assay and eventually compared with those of other monokines.     

Early T cell activation correlates with expression of apoptosis markers in patients with end-stage renal disease.

ABSTRACT. End-stage renal failure (ESRF) and chronic hemodialysis (HD) induce a state of immunodeficiency that involves T cell-mediated responses. A decreased T cell number combined with a reduced T cell lifespan and an increased T cell activation might play a role in the immune impairment associated with ESRF and chronic HD. Increased T cell activation associated with immunodeficiency suggests that activated T cells may be driven to apoptosis. To test this hypothesis, CD3+ T cell activation (CD69) and apoptosis (annexin V, CD95 (Fas), and DNA fragmentation) were analyzed in a case control study after blood draw sampling (ex vivo), in culture conditions, and after phytohemagglutinin or anti-CD3 stimulation. Ex vivo evaluation of T cells showed an increased number of activated CD69+ T cells in chronic HD patients (142 +/- 5 cells/mm3) compared with patients with ESRF (115 +/- 2 cells/mm3, P = 0.04) and controls (74 +/- 2 cells/mm3, P = 0.0006). These data were confirmed in culture conditions and after stimulation. Similarly, annexin V and CD95 (Fas)-positive T cells were more numerous in both patient groups than in controls, irrespective of the experimental conditions (P < or = 0.005 for both markers), and their percentage was always significantly higher in chronic HD patients than in patients with ESRF. The amount of DNA fragmentation was also significantly higher in the cultured resting T cells of chronic HD patients (37 +/- 3%) than in those of patients with ESRF (25 +/- 3%) and controls (20 +/- 2%) (P = 0.01). Percentage of cultured resting T cells expressing both CD69 and annexin V markers was higher in chronic HD patients (17 +/- 4%) than in patients with ESRF (10 +/- 4%) and controls (6 +/- 2%), (P = 0.005). After stimulation (phytohemagglutinin or anti-CD3), CD69+ T cell apoptosis increased by 2.4-fold in chronic HD patients compared with 1.8-fold in patients with ESRF and only 1.2-fold in controls (P = 0.001). T cells from chronic HD patients and patients with ESRF thus showed an aberrant state of early activation that contrasted with an increased proportion of annexin V and CD95 (Fas)-positive T cells engaged in apoptosis, as confirmed by DNA fragmentation. Increased susceptibility to early activated T cell apoptosis is not only associated with uremia, but is also enhanced by HD procedure. This may account for the T lymphopenia, progressive immunodeficiency, and increased infection risk seen in these patients.     

Idiopathic scoliosis: etiological concepts and hypotheses

Scoliosis is diagnosed as idiopathic in 70 % of structural deformities affecting the spine in children and adolescents, probably reflecting our current misunderstanding of this disease. By definition, a structural scoliosis should be the result of some primary disorder. The goal of this article is to give a comprehensive overview of the currently proposed etiological concepts in idiopathic scoliosis regarding genetics, molecular biology, biomechanics, and neurology, with particular emphasis on adolescent idiopathic scoliosis (AIS). Despite the fact that numerous potential etiologies for idiopathic scoliosis have been formulated, the primary etiology of AIS remains unknown. Beyond etiology, identification of prognostic factors of AIS progression would probably be more relevant in our daily practice, with the hope of reducing repetitive exposure to radiation, unnecessary brace treatments, psychological implications, and costs-of-care related to follow-up in low-risk patients.     

A recent history of opioid use in the US: Three decades of change

Background: The opioid epidemic in the United States is a problem that has developed over decades. While clinical, regulatory, and legislative changes have been implemented to combat this issue, changes will not be immediate. Moreover, the changes that have been carried out may have unintended negative consequences such as increased use of illicit opioids (e.g., heroin and synthetics) and challenges in effective and appropriate pain management.

Objectives: This review focuses on the last three decades and presents key changes the United States has seen in the use of opioids. Conclusions/Importance: There have been numerous policy changes and programs aimed at decreasing opioid use and abuse in the United States; however, it will take a major shift in the mindset of clinicians, the general public, and policy makers to alleviate this epidemic.     

Neural correlates of generation and inhibition of verbal association patterns in mood disorders

Objectives: Thought disorders such as rumination or flight of ideas are frequent in patients with mood disorders, and not systematically linked to mood state. These symptoms point to anomalies in cognitive processes mediating the generation and control of thoughts; for example, associative thinking and inhibition. However, their neural substrates are not known. Method: To obtain an ecological measure of neural processes underlying the generation and suppression of spontaneous thoughts, we designed a free word association task during fMRI allowing us to explore verbal associative patterns in patients with mood disorders and matched controls. Participants were presented with emotionally negative, positive or neutral words, and asked to produce two words either related or unrelated to these stimuli. Results: Relative to controls, patients produced a reverse pattern of answer typicality for the related vs unrelated conditions. Controls activated larger semantic and executive control networks, as well as basal ganglia, precuneus and middle frontal gyrus. Unlike controls, patients activated fusiform gyrus, parahippocampal gyrus and medial prefrontal cortex for emotional stimuli. Conclusions: Mood disorder patients are impaired in automated associative processes, but prone to produce more unique/personal associations through activation of memory and self-related areas.