Sulfatide promotes the folding of proinsulin, preserves insulin crystals, and mediates its monomerization.

Sulfatide is a glycolipid that has been associated with insulin-dependent diabetes mellitus. It is present in the islets of Langerhans and follows the same intracellular route as insulin. However, the role of sulfatide in the beta cell has been unclear. Here we present evidence suggesting that sulfatide promotes the folding of reduced proinsulin, indicating that sulfatide possesses molecular chaperone activity. Sulfatide associates with insulin by binding to the insulin domain A8--A10 and most likely by interacting with the hydrophobic side chains of the dimer-forming part of the insulin B-chain. Sulfatide has a dual effect on insulin. It substantially reduces deterioration of insulin hexamer crystals at pH 5.5, conferring stability comparable to those in beta cell granules. Sulfatide also mediates the conversion of insulin hexamers to the biological active monomers at neutral pH, the pH at the beta-cell surface. Finally, we report that inhibition of sulfatide synthesis with chloroquine and fumonisine B1 leads to inhibition of insulin granule formation in vivo. Our observations suggest that sulfatide plays a key role in the folding of proinsulin, in the maintenance of insulin structure, and in the monomerization process.     

Local anesthetics and phenothiazine tranquilizers induce parthenogenetic activation of the mouse oocyte

Incubation of recently ovulated mouse oocytes in various concentrations of local anesthetics and phenothiazine tranquilizers initiates the completion of meiosis and the formation of pronuclei. The potency with which these drugs induce oocyte activation is comparable to their relative ability to displace Ca²⁺ from artificial lipid membranes. Oocyte activation induced by these drugs is inhibited by Ca²⁺. Perturbation of the plasma membrane of the oocyte by these drugs may displace Ca²⁺, which is responsible for the integrity of the microtubule-microfilament system that normally maintains the ovulated mammalian oocyte blocked at the Metaphase II of meiosis until sperm penetration.     

Experimental evidence that brighter males sire more extra‐pair young in tree swallows

Across taxa, extra‐pair mating is widespread among socially monogamous species, but few studies have identified male ornamental traits associated with extra‐pair mating success, and even fewer studies have experimentally manipulated male traits to determine whether they are related directly to paternity. As a consequence, there is little experimental evidence to support the widespread hypothesis that females choose more ornamented males as extra‐pair mates. Here, we conducted an experimental study of the relationship between male plumage colour and fertilization success in tree swallows (Tachycineta bicolor), which have one of the highest levels of extra‐pair mating in birds. In this study, we experimentally dulled the bright blue plumage on the back of males (with nontoxic ink markers) early in the breeding season prior to most mating. Compared with control males, dulled males sired fewer extra‐pair young, and, as a result, fewer young overall. Among untreated males, brighter blue males also sired more extra‐pair young, and in paired comparisons, extra‐pair sires had brighter blue plumage than the within‐pair male they cuckolded. These results, together with previous work on tree swallows, suggest that extra‐pair mating behaviour is driven by benefits to both males and females.     

The phenology and clutch size of UK Blue Tits does not differ with woodland composition

The deciduous tree-herbivorous caterpillar-insectivorous bird food chain is a well-studied system for investigating the impacts of climate change across trophic levels. To date, across Europe, most attention has focused on the impacts of increasing spring temperature on changes to phenology in Oak-dominated (Quercus spp.) woodlands. Paridae species and Pied Flycatcher Ficedula hypoleuca are the most studied secondary consumers, all of which demonstrate an advancement in reproductive phenology with increases in spring temperature. Shifts in climate and phenology may also impact on reproductive investment in clutch size, and the effects of climate on phenology and clutch size may vary depending on woodland composition. To date, the effects of among-habitat variation in phenology and reproductive investment have received little attention. Insectivorous birds inhabiting woodlands that differ in tree composition may differ in the timing of breeding, due to local tree leafing phenology acting as a cue for egg-laying date and/or clutch size. Moreover, for most insectivorous birds, woodland composition within a territory is likely to be the main determinant of food availability for both adults and chicks. Consequently, if warming springs affect the temporal patterns of food availability differently across different woodland compositions, this may affect the optimal average local phenology for nesting birds. Here, using data from 34 long-term (mean 15 years) nest monitoring sites across the UK, we investigate the effect of woodland tree composition and temperature on Blue Tit Cyanistes caeruleus first egg date (FED) and clutch size. We supplemented the nest monitoring data by quantifying woodland composition, at a site level, through modified point counts. We predict that birds breeding in woodlands with greater proportions of late-leafing species, such as Oak and Ash Fraxinus excelsior, will breed later than those breeding in woodlands with greater proportions of early-leafing species, such as Birch Betula spp. and Beech Fagus sylvatica. We found no evidence for differences in Blue Tit FED or clutch size in relation to the proportion of any of the tree species investigated, after controlling for temperature and latitude (FED: −3.4 and 2.2, clutch size: −0.4 and − 0.2 eggs for one-unit increase in temperature and latitude, respectively). In recent decades and across all sites, clutch size has decreased as spring temperatures have increased, a strategy which could allow birds flexibly to adjust their breeding phenology such that nestling demand coincides with peak food availability. The lack of an effect of woodland composition on Blue Tit phenology suggests Blue Tits do not fine-tune their reproductive phenology to the local tree composition. Whether this lack of evidence for phenological divergence is due to an absence of divergent selection on breeding phenology and clutch size or to gene flow is not clear.     

Age-dependent diet choice in an avian top predator

Age-dependent breeding performance is arguably one of the best-documented phenomena in ornithology. The existence of age-related trends has major implications for life-history theory, but the proximate reasons for these patterns remain poorly understood. It has been proposed that poor breeding performance of young individuals might reflect lack of foraging skills. We investigated this possibility in a medium-sized, powerful raptor-the northern goshawk Accipiter gentilis. Male goshawks are responsible for providing their females and their offspring with food. We hypothesized that young males may generally show poor breeding performance or even delay breeding, because they lack the experience to hunt efficiently-especially, their principal avian prey, the feral pigeon Columba livia. Our study exploited a rare 'natural experiment', the expansion phase of an urban population, where intraspecific interference was negligible and many young males bred successfully. This enabled us to examine the improvement of foraging skills in a larger sample of young individuals, and in more controlled conditions than usually possible. Using data from individually identified male breeders, we show that, consistent with our hypothesis, the proportion of pigeons in the diet increased significantly with male age, for at least the first three years of life. Other studies have shown a parallel increase in productivity, and a positive effect of a pigeon-rich diet on brood size and nestling condition, stressing the potential fitness relevance of this prey species for goshawks. Our results suggest a causal link between patterns of age-dependence in foraging ecology and reproductive performance. Furthermore, our study is, to our knowledge, the first demonstration that prey choice of breeders, which might reflect individual hunting skills, is age-dependent in a raptor.     

Utility of the Physical Examination in Detecting Pulmonary Hypertension. A Mixed Methods Study

Introduction

Patients with pulmonary hypertension (PH) often present with a variety of physical findings reflecting a volume or pressure overloaded right ventricle (RV). However, there is no consensus regarding the diagnostic utility of the physical examination in PH.

Methods

We conducted a systematic review of publications that evaluated the clinical examination and diagnosis of PH using MEDLINE (1946–2013) and EMBASE (1947–2013). We also prospectively evaluated the diagnostic utility of the physical examination findings. Patients who underwent right cardiac catheterization for any reason were recruited. After informed consent, participants were examined by 6 physicians (3 “specialists” and 3 “generalists”) who were unaware of the results of the patient''s hemodynamics. Each examiner independently assessed patients for the presence of a RV lift, loud P2, jugular venous distension (JVD), tricuspid insufficiency murmur and right-sided 4th heart sound at rest and during a slow inspiration. A global rating (scale of 1–5) of the likelihood that the patient had pulmonary hypertension was provided by each examiner.

Results

31 articles that assessed the physical examination in PH were included in the final analysis. There was heterogeneity amongst the studies and many did not include control data. The sign most associated with PH in the literature was a loud pulmonic component of the second heart sound (P2). In our prospective study physical examination was performed on 52 subjects (25 met criteria for PH; mPAP ≥25 mmHg). The physical sign with the highest likelihood ratio (LR) was a loud P2 on inspiration with a LR +ve 1.9, 95% CrI [1.2, 3.1] when data from all examiners was analyzed together. Results from the specialist examiners had higher diagnostic utility; a loud P2 on inspiration was associated with a positive LR of 3.2, 95% CrI [1.5, 6.2] and a right sided S4 on inspiration had a LR +ve 4.7, 95% CI [1.0, 15.6]. No aspect of the physical exam, could consistently rule out PH (negative LRs 0.7–1.3).

Conclusions

The presence of a loud P2 or audible right-sided 4th heart sound are associated with PH. However the physical examination is unreliable for determining the presence of PH.