Preferential Gs protein coupling of the galanin Gal1 receptor in the μ-opioid-Gal1 receptor heterotetramer

Recent studies have proposed that heteromers of μ-opioid receptors (MORs) and galanin Gal1 receptors (Gal1Rs) localized in the mesencephalon mediate the dopaminergic effects of opioids. The present study reports converging evidence, using a peptide-interfering approach combined with biophysical and biochemical techniques, including total internal reflection fluorescence microscopy, for a predominant homodimeric structure of MOR and Gal1R when expressed individually, and for their preference to form functional heterotetramers when co-expressed. Results show that a heteromerization-dependent change in the Gal1R homodimeric interface leads to a switch in G-protein coupling from inhibitory Gi to stimulatory Gs proteins. The MOR-Gal1R heterotetramer, which is thus bound to Gs via the Gal1R homodimer and Gi via the MOR homodimer, provides the framework for a canonical Gs-Gi antagonist interaction at the adenylyl cyclase level. These novel results shed light on the intense debate about the oligomeric quaternary structure of G protein-coupled receptors, their predilection for heteromer formation, and the resulting functional significance

Upward spirals of positive emotion and coping: Replication, extension, and initial exploration of neurochemical substrates

The broaden-and-build theory (Fredrickson, 1998, 2001) predicts that positive emotions broaden the scopes of attention and cognition, thereby facilitating the building of personal resources and initiating upward spirals toward increasing emotional well-being. This study attempts to replicate and extend previous empirical support for this model. Using a sample of 185 undergraduates, we assessed whether positive affect and broad-minded coping, interpersonal trust, and social support reciprocally and prospectively predict one another over a two-month period, and whether this upward spiral might be partially based in changes in dopaminergic functioning. As hypothesized, PA and positive coping did mutually build on one another, as did PA and interpersonal trust. Contrary to expectation, PA did not demonstrate an upward spiral relation with social support. Results suggest further study of the relationship between PA and changes in dopamine metabolite levels over time is warranted

Pest categorisation of Saperda tridentata

The EFSA Panel on Plant Health (PLHP) performed a pest categorisation of Saperda tridentata (Coleoptera: Cerambycidae) for the EU. S. tridentata (elm borer) occurs in eastern North America. Ulmus americana and U. rubra are almost exclusively reported as hosts, apart from two 19th century records from the USA of larvae from Acer sp. and Populus sp. The Panel does not exclude the possibility of a post‐entry shift in host range to European Ulmus or Acer and Populus. S. tridentata infests trees that are already weakened, and severe infestations can result in tree death. S. tridentata occurs across a range of climate types in North America that occur also in Europe. Between 2016 and 2019, S. tridentata larvae were intercepted with North American Ulmus logs imported into the EU. In the EU, American Ulmus species are mainly found in arboreta and as ornamental specimen trees. If only North American Ulmus are hosts, establishment is unlikely. However, if European Ulmus, Populus or Acer species become hosts, establishment is much more likely, with impact confined to already weakened trees. The information currently available on geographical distribution, biology, impact and potential entry pathways of S. tridentata has been evaluated against the criteria for it to qualify as potential Union quarantine pest or as Union regulated non‐quarantine pest (RNQP). Since the pest is not reported in EU, it does not meet the criteria assessed by EFSA to qualify as potential Union RNQP. S. tridentata satisfies the criterion for quarantine pest regarding entry into the EU territory. Due to the scarcity of data, the Panel is unable to conclude if S. tridentata meets the post‐entry criteria of establishment, spread and potential impact

Pest categorisation of Phenacoccus solenopsis

info:eu-repo/semantics/publishe

Pest categorisation of Phlyctinus callosus

info:eu-repo/semantics/publishe

Commodity risk assessment of Citrus L. fruits from Israel for Thaumatotibia leucotreta under a systems approach

The European Commission requested EFSA Panel on Plant Health to evaluate a dossier from Israel in which the application of the systems approach to mitigate the risk of entry of Thaumatotibia leucotreta to the EU when trading citrus fruits is described. After collecting additional evidence from the Plant Protection and Inspection Services (PPIS) of Israel, and reviewing the published literature, the Panel performed an assessment on the likelihood of pest freedom for T. leucotreta on citrus fruits at the point of entry in the EU considering the Israelian systems approach. An expert judgement is given on the likelihood of pest freedom following the evaluation of the risk mitigation measures on T. leucotreta, including any uncertainties. The Expert Knowledge Elicitation indicated, with 95% certainty that between 9,863 and 10,000 citrus fruits per 10,000 will be free from this pest. The Panel also evaluated each risk mitigation measure in the systems approach and identified any weaknesses associated with them. Specific actions are identified that could increase the efficacy of the systems approach

Effectiveness of in planta control measures for Xylella fastidiosa

This opinion updates the information included in the previous EFSA Scientific Opinion concerning the in planta control measures for Xylella fastidiosa, with a systematic review and critical analysis of the potential treatment solutions that have been published against this pest so far. The output of this opinion focuses on the application of chemical or biological treatments on living plants. In vitro studies, hot water treatments, use of resistant varieties and vector control are excluded from the review. The use of antibiotics is not considered due to the risk of antimicrobial resistance development. The use of weakly virulent or avirulent strains of X. fastidiosa is covered in this review, although this organism is an EU quarantine plant pest and its introduction in the EU territory is banned. Experiments were recently conducted to assess the effect of application of zinc, copper, and citric acid biocomplex, of N-acetylcysteine, and of ‘diffusible signal factor’ (and of its homologs). Their results showed that these control measures were sometimes able to reduce symptoms caused by X. fastidiosa. Recent experiments also showed that several species of endophytic microorganisms, some bacteriophages and inoculation of weakly virulent/avirulent strains of X. fastidiosa could offer some protection against the Pierce’s disease. However, based on the reviewed results, the Panel concludes that, although several published experiments show some effects in reducing symptoms development, the tested control measures are not able to completely eliminate X. fastidiosa from diseased plants. The Panel confirms as previously stated that there is currently no control measure available to eliminate the bacteria from a diseased plant in open field conditions

CD4(+)CD25(+)FOXP3(+) Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer

BACKGROUND: A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients. METHODOLOGY AND PRINCIPAL FINDINGS: Treg were identified and characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group. CONCLUSIONS/SIGNIFICANCE: Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment