Exposure to cumulative stressors affects the laying phenology and incubation behaviour of an Arctic-breeding marine bird.

Wildlife are exposed to multiple stressors across life-history stages, the effects of which can be amplified as human activity surges globally. In Arctic regions, increasing air and ocean temperatures, more severe weather systems, and exposure to environmental contaminants all represent stressors occurring simultaneously. While Arctic vertebrates, including marine birds, are expected to be at risk of adverse effects from these individual stressors, few studies have researched their combined impacts on breeding behaviour and reproductive success. The interactive effects of environmental conditions and mercury (Hg) contamination on laying phenology and incubation behaviour were examined in female common eiders (Somateria mollissima, mitiq, ᒥᑎᖅ áŠá’ªá…ᓕᒡᔪᐊᖅ) nesting at Canada's largest Arctic breeding colony. Conditions with higher pre-breeding air temperatures were linked to females with higher egg Hg concentrations laying earlier than those with lower Hg values. Furthermore, examination of a total of 190 days of incubation behaviour from 61 eiders across two years revealed a negative relationship between wind speed and the frequency of incubation interruptions. Importantly, exposure to higher air temperatures combined with lower Hg concentrations was significantly correlated with increased incubation interruptions. Although previous research has shown that warmer spring temperatures could afford lower quality females more time to improve body condition to successfully lay, results suggest these females may face stronger cumulative fitness costs during incubation in warmer years, potentially in combination with the effects of Hg on physiological stress and hormone secretion. This study highlights how multiple stressors exposure, driven by human-induced environmental changes, can have a complex influence on reproduction.

Clopidogrel attenuates coated-platelet production in patients undergoing elective coronary catheterization.

INTRODUCTION: Coated-platelets are a subclass of highly thrombotic activated platelets with an enhanced ability to generate thrombin. Excessive numbers of coated-platelets are believed to increase thrombotic risk. A previous report demonstrated that P2Y12 inhibition in vitro attenuates coated-platelet formation. The aim of this study was to determine the effect clopidogrel has on coated-platelet formation. METHODS AND RESULTS: We enrolled 27 patients undergoing elective coronary angiography. A total of 3 blood samples were taken from eligible patients: baseline, 24-hour postclopidogrel (preangiography), and 6-hour postangiography. Coated-platelet levels, expressed as percentage of total platelets, were determined with convulxin and thrombin with or without 1.5 or 6 microM adenosine diphosphate (ADP). Baseline levels of coated-platelets were 40.0% +/- 14.3% (mean +/- 1 SD). After clopidogrel exposure, the coated-platelet level was 32.8% +/- 13.6%, representing a significant 7.2% absolute reduction (AR) (17.8% relative reduction (RR); P < 0.0001). Clopidogrel significantly lowered the convulxin, thrombin plus ADP coated-platelet production (11.0% AR; 20.1% RR for 1.5 microM and 11.2% AR; 19.1% RR for 6 microM). CONCLUSIONS: This is the first report on the impact of in vivo administration of a P2Y12 antagonist on coated-platelet formation. The significance of a partial attenuation in coated-platelet potential has yet to be determined, but this could represent a new antithrombotic mechanism of clopidogrel beyond inhibition of ADP-induced aggregation.

A novel mutation in the sterol 27-hydroxylase gene of a Pakistani family with autosomal recessive cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of lipid storage with prominent neurologic features. The disease is associated with mutations in CYP27, which encodes mitochondrial sterol 27-hydroxylase, an enzyme that catalyzes the oxidation of sterol intermediates during bile acid synthesis. The loss of this enzyme results in accumulation of cholestanol in the nervous system and other tissues. Six different mutations have been previously described in CTX. We analyzed a Pakistani family, which included four affected individuals with clinical characteristics of CTX, for mutations in CYP27. The exons of CYP27 in the family DNA were amplified by polymerase chain reaction (PCR) and analyzed for mutations by band shifts (single stranded conformational polymorphism [SSCP]) and DNA sequencing. The PCR product for exon 4 showed an SSCP change in this family. The DNA of affected individuals showed an abnormal mobility pattern interpreted as homozygous for the mutation. One non-affected sibling was homozygous for the normal migrating pattern, whereas the parents and another non-affected sibling were heterozygous. The sequence of exon 4 of affected individuals showed a substitution of C to T in codon 237, thus substituting arginine to a stop codon. This mutation would terminate the translation, which may result in a protein half the size of the wild type rendering it practically inactive.