A novel causal mechanism for grey squirrel bark stripping: The Calcium Hypothesis

AbstractGrey squirrels, Sciurus carolinensis, damage trees in the UK by stripping bark and eating the underlying phloem; squirrel motivation for damage is, however, unknown. Damage can result in deterioration of timber quality and a significant economic toll on the forestry industry. Prediction of severe damage followed by targeted killing of squirrels is the current recommended management option. However, the use of warfarin (an anticoagulant poison) is now restricted in the UK and other more humane methods of killing are labour-intensive, so an alternative solution is needed. A better understanding of what motivates grey squirrels to strip bark may enable a preventive approach to be developed. Whilst the bark stripping literature has explored predictive factors affecting the likelihood of damage, causal understanding is lacking. The aim of this review is to introduce the Calcium Hypothesis as a possible explanation for bark stripping, with a view to informing the prevention of damage. The Calcium Hypothesis states that grey squirrels damage trees to ameliorate a calcium deficiency. The main predictive factors of bark stripping behaviour each inform and lend support to the Calcium Hypothesis. Calcium is stored in tree phloem, and damage increases with phloem width, providing squirrels with more calcium per unit area ingested. Calcium levels increase in trees as active growth resumes after winter dormancy, this occurs immediately prior to the main bark stripping season of May–July, and trees growing most vigorously are at increased risk of damage. It is likely grey squirrels also have a requirement for calcium during the bark stripping season. Adult females will be under post-parturition pressures such as lactation, and juveniles will be going through their main period of bone growth, both of which likely represent a requirement for calcium – which supports an observed positive correlation between juvenile abundance and bark stripping. A high autumnal seed crop increases juvenile recruitment the following spring, and could also induce a requirement for calcium to a population due to the high phosphorus to calcium ratio of seeds. To further investigate the hypothesis, the extent to which grey squirrels can utilise calcium oxalate, as calcium occurs in bark, should be determined, and also the extent to which grey squirrels undergo seasonal periods of calcium deficiency. Increasing our causal understanding of bark stripping could inform the future development of preventive measures to aid forest management

Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer

INTRODUCTION: There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer. METHOD: The study population (n = 300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR. RESULTS: The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P = 0.0012) and with progesterone negative tumors (P = 0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P = 0.0053 and P = 0.0199, respectively). CONCLUSION: Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Ageing in general practice (AGP) trial: a cluster randomised trial to examine the effectiveness of peer education on GP diagnostic assessment and management of dementia

Extent: 9p.Background: Dementia is increasing in prevalence as the population ages. An earlier rather than later diagnosis allows persons with dementia and their families to plan ahead and access appropriate management. However, most diagnoses are made by general practitioners (GPs) later in the course of the disease and are associated with management that is poorly adherent to recommended guidelines. This trial examines the effectiveness of a peer led dementia educational intervention for GPs. Methods: The study is a cluster randomised trial, conducted across three states and five sites. All GPs will complete an audit of their consenting patients aged 75 years or more at three time points - baseline, 12 and 24 months. GPs allocated to the intervention group will receive two educational sessions from a peer GP or nurse, and will administer the GPCOG to consenting patients at baseline and 12 months. The first education session will provide information about dementia and the second will provide individualised feedback on audit results. GPs in the waitlist group will receive the RACGP Guidelines by post following the 12 month audit Outcomes: Primary outcomes are carer and consumer quality of life and depression. Secondary outcomes include: rates of GP identification of dementia compared to a more detailed gold standard assessment conducted in the patient’s home; GP identification of differential diagnoses including reversible causes of cognitive impairment; and GP referral to specialists, Alzheimers’ Australia and support services. A “case finding” and a “screening” group will be compared and the psychometrics of the GPCOG will be examined. Sample size: Approximately 2,000 subjects aged 75 years and over will be recruited through approximately 160 GPs, to yield approximately 200 subjects with dementia (reducing to 168 by 24 months). Discussion: The trial outlined in this paper has been peer reviewed and supported by the Australian National Health and Medical Research Council. At the time of submission of this paper 2,034 subjects have been recruited and the intervention delivered to 114 GPs.Constance D Pond, Henry Brodaty, Nigel P Stocks, Jane Gunn, John Marley, Peter Disler, Parker Magin, Nerida Paterson, Graeme Horton, Susan Goode, Bronwen Paine and Karen E Mat

The effectiveness of home versus community-based weight control programmes initiated soon after breast cancer diagnosis: a randomised controlled trial

BackgroundBreast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women.MethodsOverweight or obese (n?=?243) and normal weight (n?=?166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes.ResultsForty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight ?2.3 (?3.5, ?1.0) kg, body fat ?1.6 (?2.6, ?0.7) kg, community vs. control; weight ?2.4 (?3.6, ?1.1) kg, body fat ?1.4 (?2.4, ?0.5) kg (all p?<?0.001). The community group increased physical activity, reduced insulin, cardiovascular disease risk markers, increased QOL and was cost-effective.ConclusionsThe programmes were equally effective for weight control, but the community programme had additional benefits.Clinical trial registrationISRCTN6857614

South African HIV-1 subtype C transmitted variants with a specific V2 motif show higher dependence on α4β7 for replication.

CAPRISA, 2015.Abstract available in pdf

Addressing the climate challenge

In 2021, colleagues from across the University of Birmingham community were invited to write articles about topics relevant to the COP26 climate change summit. In this series of articles, experts from across many different disciplines provide new insight and evidence on how we might all understand and tackle climate change