“Catch me if you can” – improving monitoring and control of vine weevil (Otiorhynchus sulcatus) in soft fruit and ornamental crops.

Vine weevil (Otiorhynchus sulcatus F.; Coleoptera: Curculionidae) is widely considered to be one of the most important soft-fruit and ornamental crop pests worldwide. Management options for vine weevil populations have historically relied on conventional synthetic insecticides. Much progress has been made in developing alternatives to conventional synthetic insecticides for vine weevil control. Research has focused on the use of entomopathogenic nematodes (EPNs) so that standard practice is now to use EPNs, such as Steinernema kraussei or Heterorhabditis bacteriophora, to control vine weevil larvae. However, despite progress in developing sustainable control methods, less progress has been made in developing the other components required to form a holistic integrated pest management (IPM) programme for this pest. The series of experiments presented in this thesis seek, through the development of an improved monitoring tool as well as the application of a biopesticide as an alternative to the use of synthetic insecticides, to offer growers effective tools with which to monitor and control vine weevil. In particular, the influence of visual cues on vine weevil behaviour is investigated to develop an improved monitoring tool of this pest. Similarly, the chemical ecology of this species was studied to identify semiochemicals that can be used as a lure to improve monitoring tool efficacy. To achieve this, host and non-host plants as well as vine weevil produced volatiles were investigated. In addition, a bioinsecticide based on garlic extracts (Pitcher GR®) was evaluated under laboratory and glasshouse conditions in order to determine its potential as a vine weevil control. Finally, the efficacy of EPNs at controlling vine weevil larvae is assessed in six commercially available peat-free growing media. Results showed that visual (monitoring tool shade/colour, height and diameter as well as the effect of monitoring tool density) and olfactory (host plant and apple sauce) cues influence vine weevil monitoring tool efficacy. The garlic-based product was effective against vine weevil eggs and larvae under laboratory conditions, but its efficacy under glasshouse conditions requires further investigation to optimise its use against vine weevil. When the efficacy of EPNs was evaluated in six commercially available peat alternative growing media, EPNS were found to survive in all the growing media types. However, dispersal was affected by growing media, with Coir and John Innes Number 2 having a negative effect on EPNs. In addition, when S. kraussei was tested under glasshouse conditions, the EPN was effective at controlling vine weevil in all growing media tested. This study provides the basis to develop an enhanced monitoring tool that incorporates both visual and olfactory cues, while also promoting the effective use of biopesticides (e.g., garlic-based bioinsecticides) and biological controls (EPNs) for vine weevil control. However, further research is necessary to optimise vine weevil monitoring and management strategies

Bisphenol a deranges the endocannabinoid system of primary sertoli cells with an impact on inhibin b production

Bisphenol A (BPA) is an endocrine disruptor that negatively affects spermatogenesis, a process where Sertoli cells play a central role. Thus, in the present study we sought to ascertain whether BPA could modulate the endocannabinoid (eCB) system in exposed mouse primary Sertoli cells. Under our experimental conditions, BPA turned out to be cytotoxic to Sertoli cells with an half-maximal inhibitory concentration (IC50) of ~6.0 µM. Exposure to a non-cytotoxic dose of BPA (i.e., 0.5 µM for 48 h) increased the expression levels of specific components of the eCB system, namely: type-1 cannabinoid (CB1) receptor and diacylglycerol lipase-α (DAGL-α), at mRNA level, type-2 cannabinoid (CB2) receptor, transient receptor potential vanilloid 1 (TRPV1) receptors, and DAGL-β, at protein level. Interestingly, BPA also increased the production of inhibin B, but not that of transferrin, and blockade of either CB2 receptor or TRPV1 receptor further enhanced the BPA effect. Altogether, our study provides unprecedented evidence that BPA deranges the eCB system of Sertoli cells towards CB2-and TRPV1-dependent signal transduction, both receptors being engaged in modulating BPA effects on inhibin B production. These findings add CB2 and TRPV1 receptors, and hence the eCB signaling, to the other molecular targets of BPA already known in mammalian cells

Optimising Vine Weevil, Otiorhynchus sulcatus F. (Coleoptera: Curculionidae), Monitoring Tool Design.

Vine weevil, Otiorhynchus sulcatus F. (Coleoptera: Curculionidae), is an economically important insect pest of horticultural crops. To identify an effective and reliable monitoring system for adult vine weevil, this study investigated the influence of colour, height and entrance position on the efficacy of a model monitoring tool using modified paper cups as refuges. Vine weevil preferences were determined by the number of individuals recorded within a refuge. When provided with a binary choice between black or white refuges, vine weevil adults showed a preference for black refuges. Vine weevils provided with a range of coloured refuges (blue, green, red and yellow) in addition to black and white refuges showed a preference for black and blue over the other colours and white refuges in group choice experiments. Refuge height and entrance position also influenced vine weevil behaviour with individuals exhibiting a preference for taller refuges and those with entrance openings around the refuge base. These results provide insights into refuge selection by adult vine weevils, which can be exploited to improve monitoring tool design. The importance of developing an effective monitoring tool for vine weevil adults as part of an integrated pest management programme is discussed

Decoding attraction: improving vine weevil monitoring by exploiting key sensory cues

BACKGROUND Monitoring is an integral component of integrated pest management (IPM) programmes used to inform crop management decisions. Vine weevil, Otiorhynchus sulcatus F. (Coleoptera: Curculionidae), continues to cause economically significant losses in horticultural crops due to an inability to reliably detect the presence of this species before crop damage occurs. To improve vine weevil monitoring we investigated the behavioural responses of adult vine weevils to visual (monitoring tool shade/colour, height and diameter as well as the effect of monitoring tool and plant density) and olfactory (host plant and conspecifics) cues under glasshouse conditions. RESULTS Monitoring tool shade, height and diameter all influenced monitoring tool efficacy, with individuals exhibiting a preference for black, tall and wide monitoring tools. The total number of individuals recorded in monitoring tools increased with monitoring tool density. By contrast, plant density did not influence the number of individuals recorded in monitoring tools. Yew-baited monitoring tools retained a larger number of individuals compared to unbaited ones. Similarly, more vine weevils were recorded in monitoring tools baited with yew and conspecifics than in unbaited monitoring tools or those baited with only yew. Baiting monitoring tools with conspecifics alone did not enhance the number of vine weevils recorded in monitoring tools. CONCLUSIONS Our study confirms that visual and olfactory cues influence vine weevil behaviour. This provides information on key factors that influence vine weevil monitoring tool efficacy and can be used to inform the development of a new monitoring tool for this pest

Activation of type-2 cannabinoid receptor inhibits neuroprotective and antiinflammatory actions of glucocorticoid receptor α: when one is better than two.

Endocannabinoids (eCBs) and glucocorticoids (GCs) are two distinct classes of signaling lipids that exert both neuroprotective and immunosuppressive effects; however, the possibility of an actual interaction of their receptors [i.e., type-2 cannabinoid (CB2) and glucocorticoid receptor α (GRα), respectively] remains unexplored. Here, we demonstrate that the concomitant activation of CB2 and GRα abolishes the neuroprotective effects induced by each receptor on central neurons and on glial cells in animal models of remote cell death. We also show that the ability of eCBs and GCs, used individually, to inhibit tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production from activated human T lymphocytes is lost when CB2 and GRα are activated simultaneously. In addition, signal transduction pathways triggered by concomitant activation of both receptors led to increased levels of GRβ, heat-shock proteins-70 and -90, and p-JNK, as well as to reduced levels of p-STAT6. These effects were reversed only by selectively antagonizing CB2, but not GRα. Overall, our study demonstrates for the first time the existence of a CB2-driven negative cross-talk between eCB and GC signaling in both rats and humans, thus paving the way to the possible therapeutic exploitation of CB2 as a new target for chronic inflammatory and neurodegenerative diseases

An apple a day does not keep the weevils away: enhancing vine weevil monitoring with fruit-based volatiles

Vine weevil (Otiorhynchus sulcatus Fabricius; Coleoptera: Curculionidae) is an economically important pest of soft fruit and ornamental crops worldwide. Despite extensive research over three decades, the development of an effective semiochemical lure to improve monitoring for this pest remains a challenge. This study investigated the behavioural and electrophysiological responses of adult vine weevils to apple sauce volatiles under laboratory conditions, using Y-tube olfactometer bioassays and headspace analysis using gas chromatography coupled to mass spectrometry (GC–MS) and GC coupled to electroantennographic detection (GC-EAD). In Y-tube bioassays, more adults selected the olfactometer arm containing apple sauce volatiles compared to the control arm at lower doses (0.1, 1 and 10 g) but not at higher doses (20 g). Thirteen compounds were identified in volatiles collected from apple sauce, with the major components being furfural and sorbic acid. Consistent electrophysiological responses were recorded to (E)-2-heptenal, 1-hexanol, (Z)-3-hexenol and (E)-2-hexenol. The behavioural response of vine weevil adults to refuges baited with semiochemical lures was also tested under glasshouse conditions. In this scenario, a greater proportion of individuals were recorded in refuges baited with apple sauce compared to unbaited refuges. A similar behavioural response was also recorded when refuges were baited with a combination of apple sauce and Fortune's spindle Euonymus fortunei (Turcz.) Hand.-Maz; Celastrales: Celastraceae) compared to those that were unbaited or individually baited with Fortune's spindle or apple sauce. This study indicates that apple sauce positively influences positively vine weevil behaviour and could serve as a basis for developing a novel lure for improved monitoring

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.Acknowledgements: This work was supported by grants from the International Society for Neurochemistry (ISN) and Alexander von Humboldt Foundation (to M.C.D.); Agencia Nacional de Promoción Científica y Tecnológica (PBIT/09 2013, PICT-2015-0285 and PICT-2016-4647 to L.M.; PICT-2014-1537 to M.C.D.); GENMED Labex and JPND PERADES grant; and JPND EADB grant (German Federal Ministry of Education and Research, BMBF: 01ED1619A)

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening