Controversy exists regarding the efficacy of lithium for suicide prevention. Except for a recent trial that enrolled over 500 patients, available trials of lithium for suicide prevention have involved small samples. It is challenging to measure suicide in a single randomised controlled trial (RCT). Adding a single large study to existing meta-analyses may provide insights into lithium's anti-suicidal effects. We performed a meta-analysis of RCTs comparing lithium with a control condition for suicide prevention. MEDLINE and other databases were searched up to 30 November 2021. Efficacy was assessed by calculating the summary Peto odds ratio (OR) and incidence rate ratio (IRR) with 95% confidence intervals. Among seven RCTs, the odds of suicide were lower among patients receiving lithium versus control (OR = 0.30, 95% CI 0.09–1.02; IRR = 0.22, 95% CI 0.05–1.05), although the findings were still not statistically significant. The role of lithium in suicide prevention remains uncertain.

Bitter taste is sensed by bitter taste receptors (TAS2Rs) that belong to the G protein-coupled receptor (GPCR) superfamily. In addition to bitter taste perception, TAS2Rs have been reported recently to be expressed in many extraoral tissues and are now known to be involved in health and disease. Despite important roles of TAS2Rs in biological functions and diseases, no crystal structure is available to help understand the signal transduction mechanism or to help develop selective ligands as new therapeutic targets. We report here the three-dimensional structure of the fully activated TAS2R4 human bitter taste receptor predicted using the GEnSeMBLE complete sampling method. This TAS2R4 structure is coupled to the gustducin G protein and to each of several agonists. We find that the G protein couples to TAS2R4 by forming strong salt bridges to each of the three intracellular loops, orienting the activated Gα5 helix of the Gα subunit to interact extensively with the cytoplasmic region of the activated receptor. We find that the TAS2Rs exhibit unique motifs distinct from typical Class A GPCRs, leading to a distinct activation mechanism and a less stable inactive state. This fully activated bitter taste receptor complex structure provides insight into the signal transduction mechanism and into ligand binding to TAS2Rs.

A longstanding issue in the field of nutrition is the potential inaccuracy of methods traditionally used for dietary assessment (i.e. food diaries and food frequency questionnaires). It is possible to overcome the limitations and biases of these techniques by combining them with analytical measurements in human biofluids. Metabolomic technologies are gaining popularity as nutritional tools due to their capacity to measure metabolic responses to external stimuli, such as the ingestion of certain foods. This project performed both LC-MS and 1H-NMR metabolomic profiling on serum samples collected as part of the NICOLA study (Northern Irish Cohort for the Longitudinal Study of Aging) in order to discover novel dietary biomarkers. A dietary validation cohort (NIDAS) was incorporated within NICOLA, involving 45 males and 50 females, aged 50 years and over. Participants provided detailed dietary data (4-day food diary) and blood samples at two time-points, six months apart. Serum samples were processed on two analytical platforms. 1H-NMR spectra were acquired using a Bruker 600 MHz Ascent coupled to a TCI cryoprobe and processed using Bayesil (University of Alberta, Canada). A Waters TQ-S coupled with an Acquity I-class UPLC was used in combination with a targeted commercially available kit (AbsoluteIDQ p180 kit, Biocrates). Mass spectra obtained were processed with MetIDQ and verified using MassLynx (v4.1). Data were tested for normality, and metabolite concentrations were correlated with recorded dietary intake of each food type using SPSS. Additional tests (PCA, PLS-DA, ROC Curves) were performed on MetaboAnalyst 4.0 (University of Alberta, Canada). More than 50 statistically significant (P < 0.05) food-metabolite correlations were detected, 15 of which remained significant after eliminating potential confounding from sex, age and BMI. The strongest correlations were between fruit consumption and acetic acid, and between dairy consumption and certain glycerophospholipids (e.g. LysoPC aa C20:3). Stratifying the cohort by gender yielded further correlations, including PC ae C38:2 (dairy; males), PC aa C34:4 (dairy; females), PC aa C36:4 (dairy; females) and trans-4-Hydroxyproline (meat; males). A number of potential blood-based food biomarkers were detected, many of which are gender-specific, and some are corroborated by previously published studies. However, further validation work is required. For example, biological plausibility needs to be established, and the findings need to be reproduced in other cohorts to demonstrate their applicability in larger and more diverse populations. These results contribute greatly to the ongoing efforts to discover and validate reliable nutritional biomarkers as an objective and unbiased measurement of food intake.

East Africa is a global hot spot for the diversity of ixodid ticks. As ectoparasites and as vectors of pathogens, ticks negatively affect the well-being of humans, livestock and wildlife. To prevent tick infestations, livestock owners and managers typically treat livestock with acaricides that kill ticks when they attempt to feed on livestock hosts. Because of the costs of preventing and mitigating tick parasitism, predicting where and when ticks will be abundant is an important challenge in this region. We used a 7-year monthly record of tick abundance on large experimental plots to assess the effects of rainfall, wildlife and cattle on larvae, nymphs and adults of two common tick species, Rhipicephalus pulchellus and Rhipicephalus praetextatus. Nymphal and adult ticks were more abundant when there had been high cumulative rainfall in the prior months. They were less abundant when cattle were present than when only large wild mammals were. Larval abundance was not affected by the presence of cattle, and larvae did not appear to be sensitive to rainfall in prior months, though they were less abundant in our surveys when rainfall was high in the sampling month. The challenges of managing ticks in this region are being exacerbated rapidly by changes in rainfall patterns wrought by climate change, and by overall increases in livestock, making efforts to predict the impacts of these drivers all the more pressing.

The Darwin–Hatherton Glacial system (DHGS) connects the East Antarctic Ice Sheet (EAIS) with the Ross Ice Shelf and is a key area for understanding past variations in ice thickness of surrounding ice masses. Here we present the first detailed measurements of ice thickness and grounding zone characteristics of the DHGS as well as new measurements of ice velocity. The results illustrate the changes that occur in glacier geometry and ice flux as ice flows from the polar plateau and into the Ross Ice Shelf. The ice discharge and the mean basal ice shelf melt for the first 8.5 km downstream of the grounding line amount to 0.24 ± 0.05 km3 a−1 and 0.3 ± 0.1 m a−1, respectively. As the ice begins to float, ice thickness decreases rapidly and basal terraces develop. Constructed maps of glacier geometry suggest that ice drainage from the EAIS into the Darwin Glacier occurs primarily through a deep subglacial canyon. By contrast, ice thins to <200 m at the head of the much slower flowing Hatherton Glacier. The glaciological field study establishes an improved basis for the interpretation of glacial drift sheets at the link between the EAIS and the Ross Ice Sheet.