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In Brazil, zucchini (Cucurbita pepo) is a socioeconomically important vegetable affected by damage caused primarily by zucchini yellow mosaic virus (ZYMV). Although the occurrence of cucumber mosaic virus (CMV) is less frequent, in C. pepo ‘Caserta’ plants it can cause symptoms such as mottle, mosaic, leaf and fruit distortion, as well as reduced plant development. To minimize the damage, the most widely used management technique is the preventive, albeit inefficient, application of insecticides, aimed at controlling aphids, the vectors of this virus. Thus, the search for more effective and less environmentally harmful control methods has been the target of investigations. The purpose of the present study was to assess the action of the extracts of four native Caryophyllales species, as inhibitors of infection by CMV and ZYMV in C. pepo, in addition to evaluating the possible induced resistance in this species. Fresh leaf extracts (LEs) of Guapira opposita, Pisonia ambigua (Nyctaginaceae), Gallesia integrifolia and Seguieria langsdorffii (Phytolaccaceae), previously assessed in the tobacco mosaic virus / Nicotiana glutinosa pathosystem, were submitted to progressive dilutions sprayed on cotyledonary C. pepo leaves 30 min before inoculation with CMV and ZYMV. Leaf extracts of G. integrifolia did not induce inhibition in any of the pathosystems assessed. Guapira opposita LEs inhibited the infection of plants inoculated with ZYMV below 50% but inhibited CMV infection by 70% at a concentration of 1:40. Given that leaf extracts of P. ambigua and S. langsdorffii induced high percentage inhibition, evident in the number of asymptomatic plants and confirmed by serological tests, these species were selected to assess induced resistance in pre-treatment experiments. The LEs were efficient in inhibiting ZYMV and CMV infection in C. pepo when applied up to 48 h before inoculation. The LEs of S. langsdorffii and G. opposita, also tested for this system, were efficient when applied up to 72 h before CMV inoculation. The LEs can be prepared from dry leaves and maintained at -20°C for at least three years, conserving their inhibitory activity. These results expand the possibilities for producers and consumers alike in the sustainable management of the main zucchini viruses, without damaging the environment.

Remote sensing methods are commonly used to monitor the invasive riparian shrub tamarisk (Tamarix spp.) and its response to the northern tamarisk beetle (D. carinulata), a specialized herbivore introduced as a biocontrol agent to control tamarisk in the Southwest USA in 2001. We use a Spectral Angle Mapper (SAM) supervised classification method with WorldView-2 (2 m spatial resolution) multispectral images from May and August of 2019 to map healthy tamarisk, canopy dieback, and defoliated tamarisk over a 48 km segment of the Colorado River in the topographically complex Grand Canyon National Park, where coarse-resolution satellite images are of limited use. The classifications in May and August produced overall accuracies of 80.0% and 83.1%, respectively. Seasonal change detection between May and August 2019 indicated that 47.5% of the healthy tamarisk detected in May 2019 had been defoliated by August 2019 within the WorldView-2 image extent. When compared to a previously published tamarisk map from 2009, derived from multispectral aerial imagery, we found that 29.5% of healthy tamarisk canopy declined between 2009 and 2019. This implies that tamarisk beetle impacts are continuing to accumulate even though land managers have noted the presence of the beetles in this reach of the river for 7 years since 2012.

Timing and spatial dynamics of tamarisk (Tamarix spp. L.) defoliation by the biological control agent Diorhabda carinulata (Desbrochers) were evaluated. Relative abundance of D. carinulata and the phenology of tamarisk along the San Juan and Colorado rivers were recorded in 2011–2012. D. carinulata began reproducing in the spring when temperatures were >15°C. Variation in spring temperature-rise affected the timing of development of larvae of the first summer generation and initial defoliation of tamarisk at each site. Shortening day lengths in mid- to late-summer cued D. carinulata to enter reproductive diapause resulting in cessation of defoliation. The critical day length for inducing reproductive diapause was 33–47 minutes shorter than that of populations of D. carinulata released into North America in 2001. Variation in spring temperature-rise combined with timing of shortening day length resulted in differences in D. carinulata voltinism per site. During the active season, larvae were less likely to establish in areas where defoliation was >70%. Lack of reestablishment of larvae led to temporary loss of D. carinulata from the locations and allowed tamarisks to sprout new canopies. Defoliation of tamarisk was dictated by environmental cues and abundance of D. carinulata, and in turn large amounts of defoliation negatively affected abundance of D. carinulata.

A B S T R A C T Factors regulating excystment of a toxic dinoflagellate in the genus Alexandrium were investigated in cysts from Puget Sound, Washington State, USA. Experiments were carried out in the laboratory using cysts collected from benthic seedbeds to determine if excystment is controlled by internal or environmental factors. The results suggest that the timing of germination is not tightly controlled by an endogenous clock, though there is a suggestion of a cyclical pattern. This was explored using cysts that had been stored under cold (4 8C), anoxic conditions in the dark and then incubated for 6 weeks at constant favorable environmental conditions. Excystment occurred during all months of the year, with variable excystment success ranging from 31–90%. When cysts were isolated directly from freshly collected sediments every month and incubated at the in situ bottom water temperature, a seasonal pattern in excystment was observed that was independent of temperature. This pattern may be consistent with secondary dormancy, an externally modulated pattern that prevents excystment during periods that are not favorable for sustained vegetative growth. However, observation over more annual cycles is required and the duration of the mandatory dormancy period of these cysts must be determined before the seasonality of germination can be fully characterized in Alexandrium from Puget Sound. Both temperature and light were found to be important environmental factors regulating excystment, with the highest rates of excystment observed for the warmest temperature treatment (20 8C) and in the light.

AIMS: The aim of this study was to investigate the associations between recent cannabis use, current symptomatology and age at onset of first manic, depressive and psychotic episodes in a large sample with first-treatment bipolar I disorder (BD I). METHODS: One hundred one patients with first-treatment Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) bipolar I disorder were included as part of the Thematically Organized Psychosis study. The Structural Clinical Interview for DSM-IV was used for DSM-IV diagnosis and identification of episodes of illness. Earlier suicide attempts were recorded. Manic, depressive and psychotic symptoms were rated using the Young Mania Rating Scale, Inventory of Depressive Symptoms and Positive and Negative Syndrome Scale correspondingly. Cannabis use within the six last months was recorded. RESULTS: After controlling for confounders, recent cannabis use was significantly associated with lower age at onset of first manic and psychotic episode, but not with onset of first depressive episode (both P CONCLUSIONS: The present study confirms earlier findings of an association between cannabis use and a lower age at onset. Recent cannabis use was also associated with more lifetime suicide attempts. The current findings suggest that recent cannabis use is associated with a more severe course of illness in the early phase of BD I. Language: en

There is little knowledge about the role of the duration of untreated bipolar (DUB) illness in first-treatment bipolar disorder I (BD I), its association with symptoms at start of first treatment, and development over the first year, and limited knowledge about factors that influence the length of DUB. Substance use has shown to delay identification of primary psychiatric disorders, and while cannabis use is common in BD the role of cannabis in relationship to DUB is unclear. The aim of the present study is to examine the associations between DUB and key clinical outcomes at baseline in BD I, and at one year follow-up, and to evaluate the influence of cannabis use. Patients with first-treatment BD I (N=62) completed comprehensive clinical evaluations, which included both DUB and the number of previous episodes. There were no significant associations between DUB and key clinical outcomes. Longer duration from first manic episode to treatment was associated with risk of starting excessive cannabis use after onset of the bipolar disorder. The main finding is the lack of significant associations between features of previous illness episodes and clinical outcomes. Long duration of untreated mania seems to increase the risk for later cannabis use.

The spread of tamarisk (Tamarix spp., also known as saltcedar) is a significant ecological disturbance in western North America and has long been targeted for control, leading to the importation of the northern tamarisk beetle (Diorhabda carinulata) as a biological control agent. Following its initial release along the Colorado River near Moab, Utah in 2004, the beetle has successfully established and defoliated tamarisk across much of the upper Colorado River Basin. However, the spatial distribution and seasonal timing of defoliation are complex and difficult to quantify over large areas. To address this challenge, we tested and compared two remote sensing approaches to mapping tamarisk defoliation: Disturbance Index (DI) and a decision tree method called Random Forest (RF). Based on multitemporal Landsat 5 TM imagery for 2006-2010, changes in DI and defoliation probability from RF were calculated to detect tamarisk defoliation along the banks of Green, Colorado, Dolores and San Juan rivers within the Co...

Cannabis use seems to play a causal role in the development of psychotic disorders. Recent evidence suggests that it may also precipitate onset in bipolar disorder. We here investigate if there is a dose-response relationship between cannabis use and age at onset in bipolar disorder, and whether there are interactions between cannabis use and illness characteristics (presenting polarity and presence of psychosis). Consecutively recruited patients with a DSM-IV, SCID verified diagnosis of bipolar I, II or NOS disorder (n=324) participated. Two-way ANCOVAS were used to investigate the effect of levels of cannabis use (10 times during one month lifetime,10 times during one month lifetime or a cannabis use disorder) on age at onset, including interaction effects with illness characteristics, while controlling for possible confounders. There was a significant association indicating a dose-response relationship between cannabis use and age at onset, which remained statistically significant after controlling for possible confounders (gender, bipolar subtype, family history of severe mental illness and alcohol or other substance use disorders). There were no interaction effects between cannabis use and presenting polarity or presence of psychosis. Doses of cannabis used may affect the age at onset of bipolar disorder.

Background: The worldwide diversity of dietary intakes of n-6 and n-3 fatty acids influences tissue compositions of n-3 long-chain fatty acids (LCFAs: eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) and risks of cardiovascular and mental illnesses. Objective: We aimed to estimate healthy dietary allowances for n-3 LCFAs that would meet the nutrient requirements of 97-98% of the population. Design: Deficiency in n-3 LCFAs was defined as attributable risk from 13 morbidity and mortality outcomes, including all causes, coronary heart disease, stroke, cardiovascular disease, homicide, bipolar disorder, and major and postpartum depressions. Dietary availability of n-3 LCFAs from commodities for 38 countries and tissue composition data were correlated by best fit to each illness in deficiency risk models. Results: The potential attributable burden of disease ranged from 20.8% (all-cause mortality in men) to 99.9% (bipolar disorder). n-3 LCFA intake for Japan (0.37% of energy, or 750 mg/d) met criteria for uniformly protecting >98% of the populations worldwide. n-3 LCFA intakes needed to meet a tissue target representative of Japan (60% n-3 in LCFA) ranged from 278 mg/d (Philippines, with intakes of 0.8% of energy as linoleate, 0.08% ofenergy as α-linolenate, and 0.06% of energy as arachidonic acid) to 3667 mg/d (United States, with 8.91% of energy as linoleate, 1.06% of energy as α-linolenate, and 0.08% of energy as arachidonic acid). Conclusions: With caveats inherent for ecologic, nutrient disappearance analyses, a healthy dietary allowance for n-3 LCFAs for current US diets was estimated at 3.5 g/d for a 2000-kcal diet. This allowance for n-3 LCFAs can likely be reduced to one-tenth of that amount by consuming fewer n-6 fats.

We previously demonstrated that the selective retinoic acid receptor (RAR) β2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. We hypothesized that by decreasing oxidative stress and consequent fibrogenesis, AC261066 could attenuate the development of contractile dysfunction in post-ischemic heart failure (HF). We tested this hypothesis in vivo using an established murine model of myocardial infarction (MI), obtained by permanent occlusion of the left anterior descending coronary artery. Treating mice with AC261066 in drinking water significantly attenuated the post-MI deterioration of echocardiographic indices of cardiac function, diminished remodeling, and reduced oxidative stress, as evidenced by a decrease in malondialdehyde level and p38 mitogen-activated protein kinase expression in cardiomyocytes. The effects of AC261066 were also associated with a decrease in interstitial fibrosis, as shown by a marked reduction in collagen deposition and α-smooth muscle actin expression. In cardiac murine fibroblasts subjected to hypoxia, AC261066 reversed hypoxia-induced decreases in superoxide dismutase 2 and angiopoietin-like 4 transcriptional levels as well as the increase in NADPH oxidase 2 mRNA, demonstrating that the post-MI cardioprotective effects of AC261066 are associated with an action at the fibroblast level. Thus, AC261066 alleviates post-MI cardiac dysfunction by modulating a set of genes involved in the oxidant/antioxidant balance. These AC261066 responsive genes diminish interstitial fibrogenesis and remodeling. Since MI is a recognized major cause of HF, our data identify RARβ2 as a potential pharmacological target in the treatment of HF. SIGNIFICANCE STATEMENT A previous report showed that the selective retinoic acid receptor (RAR) β2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. This study shows that AC261066 attenuates the development of contractile dysfunction and maladaptive remodeling in post-ischemic heart failure (HF) by modulating a set of genes involved in oxidant/antioxidant balance. Since myocardial infarction is a recognized major cause of HF, these data identify RARβ2 as a potential pharmacological target in the treatment of HF.

In order to assess, in a controlled in vitro model, the differentiation potential of adult bone marrow derived stem cells we have developed a coculture procedure using adult rat cardiomyocytes and mesenchymal stem cells (MSCs) from transgenic GFP positive rats. We investigated in the cocultured MSCs the time course of cellular processes that are difficult to monitor in in vivo experiments. Adult rat cardiomyocytes and adult rat MSCs were cocultured for up to 7 days and analyzed by confocal microscopy. Several markers were studied by immunofluorescence technique. The fluorescent ST-BODIPY-Dihydropyridine was used to label calcium channels in living cells. Intracellular calcium was monitored with the fluorescent probe X-Rhod-1. Immunofluorescence experiments showed the presence of connexin-43 between cardiomyocytes and MSCs and between MSCs, while no sarcomeric structures were observed at any time of the coculture. We looked at the expression of calcium channels and development of voltage-dependent calcium signaling in cocultured MSCs. MSCs showed a time-dependent increase of labeling of ST-BODIPY-Dihydropyridine, reaching a relatively strong level after 72 h of coculture. The treatment with a non-fluorescent DHP, Nifedipine, completely abolished ST-BODIPY labeling. We investigated whether depolarization could modulate intracellular calcium. Depolarization-induced calcium transients increased in MSCs in relation to the coculture time. We conclude that MSCs cocultured with adult cardiomyocytes present preliminary evidence of voltage-dependent calcium modulation uncoupled with the development of nascent or adult myofibrils, thus showing a limited lineage specification and a low plasticity to differentiate in a full cardiomyocyte-like phenotype.

Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110 gamma participates in these processes by sustaining beta-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent mechanism. We have discovered that p110 gamma anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110 gamma to inhibit PIP3 production. This provides local feedback control of PIP3 and cAMP signaling events. In congestive heart failure, p110 gamma is upregulated and escapes PKA-mediated inhibition, contributing to a reduction in beta-adrenergic receptor density. Pharmacological inhibition of p110 gamma normalizes beta-adrenergic receptor density and improves contractility in failing hearts.