How calmodulin interacts with the adenosine A(2A) and the dopamine D(2) receptors

Receptor heteromerization is a mechanism used by G protein-coupled receptors to diversify their properties and function. We previously demonstrated that these interactions occur through salt bridge formation between epitopes of the involved receptors. Recent studies claim that calmodulin (CaM) binds to an Arg-rich epitope located in the amino-terminus of the dopamine D(2) receptor third intracellular loop. This is the same epitope involved in adenosine A(2A)-D(2) receptor heteromerization, through Coulombic interaction between the Arg residues and a phosphorylated serine (pS) located in the medial segment of the C-terminus of the A(2A) receptor. Mass spectrometric analysis indicates that an electrostatic interaction involving the D(2) receptor Arg-rich epitope and several CaM acidic epitopes are mainly responsible for the D(2) receptor-CaM binding. CaM could also form multiple noncovalent complexes by means of electrostatic interactions with an epitope localized in the proximal segment of the C-terminus of the A(2A) receptor. Ca(2+) disrupted the binding of CaM to the D(2) but not to the A(2A) receptor epitope, and CaM disrupted the electrostatic interactions between the D(2) receptor epitope and the more distal A(2A) receptor epitope. A model is introduced with the possible functional implications of A(2A)-D(2)-CaM interactions. These in vitro findings imply a possible regulatory role for CaM in receptor heteromers formation.     

Seasonal variations in olfactory sensory neurons--fish sensitivity to sex pheromones explained?

Olfactory sensory neurons of vertebrates regenerate throughout the life of the animal. In fishes, crypt cells are a type of olfactory sensory neurons thought to respond to sex pheromones. Here, we demonstrate that the number of crypt cells in the olfactory epithelium of the crucian carp varies dramatically throughout the year. During winter, few crypt cells are observed at any location within the sensory epithelium. In spring, the majority of crypt cells are located deep in the epithelium not yet exposed to the environment. However, during the summer spawning season, crypt cells are positioned at the epithelial surface. These findings may explain previous studies demonstrating a relationship between circulating androgen and olfactory sensitivity to sex pheromones.     

Impact of simulated moose densities on abundance and richness of vegetation,herbivorous and predatory arthropods along a productivity gradient

Large herbivores can affect vegetation structure and species composition as well as material and energy flows in the ecosystem through their selective feeding, defecation, urination and trampling. These changes have a large potential to indirectly affect other trophic levels, but the mechanisms are poorly known. We studied the impacts of moose Alces alces browsing along a gradient of site productivity by experimentally simulating four different moose densities. Here we show that moose can affect the richness and abundance of three trophic levels in Swedish boreal forests through complex direct and indirect impacts, but in qualitatively different ways depending on how the physical habitat or food resources of a trophic level are affected. Vegetation richness had a hump‐shaped (unimodal) response to increased moose density. Leaf litter production decreased when browsing increased, which in turn depressed the abundance of flying prey for spiders. Consequently, spider abundance and richness declined monotonically. The responses of spider richness to moose density were further conditioned by site productivity: the response was positive at productive and negative at unproductive sites. In contrast, herbivorous Hemiptera were not affected by moose, most likely because the abundance of their food plants was not affected. The highest simulated moose density had an impact on all variables responding to moose even after a few years of treatment and can be considered as overabundance. We also show that the impacts of low or moderate moose density can be positive to some of the organisms negatively affected by high density. The level of herbivore population density that leads to substantial community impacts also depends on site factors, such as productivity.     

The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma

Purpose  We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with stage III–IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the prognosis in stage III–IV malignant melanoma patients. Patients and methods  A cohort of metastatic malignant melanoma patients (n = 91), in stage III (n = 26) or IV (n = 65) were analysed for HLA-A, -B, -Cw and -DRB1 types by PCR/sequence-specific primer method. The frequencies of HLA alleles in the patients were compared to that of healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined by Kaplan–Meier and Cox analysis. Results  The presence of the AHH 62.1 in clinical stage IV patients was significantly and independently associated with the worst survival rate recorded from the appearance of metastasis (HR = 2.14; CI = 1.02–4.4; P = 0.04). In contrast, the period from the primary diagnosis to metastasis was the longest in patients with this haplotype (HR = 0.40; CI = 0.17–0.90; P = 0.02). Conclusions  Melanoma patients in our cohort with 62.1 AHH which is associated with autoimmune diseases have an initial strong anti-tumour control with longer metastasis-free period. These patients have rapid progression after the appearance of metastasis, responding poorly to chemo- or/and immunotherapy. This apparently paradoxical clinical process could be due to the interplay between tumour clones escape and immune surveillance ending up with a rapid disease progression. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Stable oxygen and carbon isotope information on the establishment of a new, opportunistic foraminiferal fauna in a Swedish Skagerrak fjord basin, in 1979/1980

Significant faunal changes reported from recent, coastal environments, which are not directly influenced by urban and industrial impact, are rarely seen. In Gullmar Fjord on the Swedish west coast, a significant foraminiferal fauna change occurred in connection with severe low-oxygen conditions that evolved in the winter of 1979/1980. A foraminiferal fauna marked by common Skagerrak–Kattegat species, which had previously characterised the deep fjord basin, was replaced by the opportunistic, low-oxygen tolerant species Stainforthia fusiformis (Williamsson).To study this phenomenon further we performed stable oxygen and carbon isotope analyses on the indicator species itself, S. fusiformis, both on specimens from sediment cores representing approximately the last 85 years and on living (stained) individuals taken from a transect across the deep fjord basin. Our purpose was to detail how and why S. fusiformis, came to dominate the fauna.The oxygen isotope results suggest that salinities and temperatures in the deep basin have been relatively constant over the last c. 85 years, while the carbon isotopes show a significant change towards more negative values in association with the faunal shift of 1979/1980. The combined results from both the cores and the surface sediments suggest that S. fusiformis did not inhabit the deep basin until 1980. Before then, almost all specimens of S. fusiformis were small sized and their carbon isotope values suggest they were re-deposited shallow-water specimens that had been transported down to the central, deep basin as part of a suspension load. After a major faunal extinction in 1979–1980, S. fusiformis of all sizes suddenly appeared in large numbers and their carbon isotopic values were similar to the signal from registered in the recent, living fauna within the deep basin. This suggests that the opportunistic S. fusiformis established itself in the deep basin as a consequence of the severe low-oxygen event and the faunal crash of the previously dominating Skagerrak–Kattegat fauna.     

What shapes Eurasian lynx distribution in human dominated landscapes: selecting prey or avoiding people?

In the multi-use landscape of southern Norway, the distribution of lynx is likely to be determined both by the abundance of their favoured prey – the roe deer – and the risk associated with the presence of humans because most lynx mortalities are caused by humans (recreational harvest, poaching, vehicle collisions). We described the distribution of the reproductive portion of the lynx population based on snow-track observations of females with dependent kittens collected over 10  yr (1997–2006) in southern Norway. We used the ecological-niche factor analysis to examine how lynx distribution was influenced by roe deer, human activity, habitat type, environmental productivity and elevation. Our first prediction that lynx should be found in areas of relatively high roe deer abundance was supported. However, our second prediction that lynx should avoid human activity was rejected, and lynx instead occupied areas more disturbed in average than those available (with the exception of the most densely occupied areas). Lynx, however, avoided the most disturbed areas and our third prediction of a trade-off between abundance of prey and avoidance of human activity was supported. On the one hand, roe deer in the most disturbed areas benefit to a large extent from current human land use practices, potentially allowing them to escape predation from lynx. On the other hand, the situation is not so favourable for the predators who are restricted in competition refuges with medium to low prey densities. The consequence is that lynx conservation will have to be achieved in a human modifed environment where the potential for a range of conflicts and high human-caused mortality will remain a constant threat.     

Asthma caused by occupational exposures is common – A systematic analysis of estimates of the population-attributable fraction

Background

As more inhaled corticosteroid (ICS) devices become available, there may be pressure for health-care providers to switch patients with asthma to cheaper inhaler devices. Our objective was to evaluate impact on asthma control of inhaler device switching without an accompanying consultation in general practice.

Methods

This 2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation for ≥5 patients within 3 months. Patients 6–65 years of age from these practices whose ICS device was switched were individually matched with patients using the same ICS device who were not switched. Asthma control over 12 months after the switch was assessed using a composite measure including short-acting β-agonist and oral corticosteroid use, hospitalizations, and subsequent changes to therapy.

Results

A total of 824 patients from 55 practices had a device switch and could be matched. Over half (53%) of device switches were from dry powder to metered-dose inhalers. Fewer patients in switched than matched cohort experienced successful treatment based on the composite measure (20% vs. 34%) and more experienced unsuccessful treatment (51% vs. 38%). After adjusting for possible baseline confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29 (95% confidence interval [CI], 0.19 to 0.44; p < 0.001) and for unsuccessful treatment was 1.92 (95% CI, 1.47 to 2.56; p < 0.001).

Conclusion

Switching ICS devices without a consultation was associated with worsened asthma control and is therefore inadvisable.     

Characterization of two Arabidopsis thaliana acyltransferases with preference for lysophosphatidylethanolamine

Background  

Two previously uncharacterized Arabidopsis genes that encode proteins with acyltransferase PlsC regions were selected for study based on their sequence similarity to a recently identified lung lysophosphatidylcholine acyltransferase (LPCAT). To identify their substrate specificity and biochemical properties, the two Arabidopsis acyltransferases, designated AtLPEAT1, (At1g80950), and AtLPEAT2 (At2g45670) were expressed in yeast knockout lines ale1 and slc1 that are deficient in microsomal lysophosphatidyl acyltransferase activities.     

Marine protected areas can be useful but are not a silver bullet for kelp conservation

Kelp forests are among the most valuable ecosystems on Earth, but they are increasingly being degraded and lost due to a range of human-related stressors, leading to recent calls for their improved management and conservation. One of the primary tools to conserve marine species and biodiversity is the establishment of marine protected areas (MPAs). International commitments to protect 30% of the world's ecosystems are gaining momentum, offering a promising avenue to secure kelp forests into the Anthropocene. However, a clear understanding of the efficacy of MPAs for conserving kelp forests in a changing ocean is lacking. In this perspective, we question whether strengthened global protection will create meaningful conservation outcomes for kelp forests. We explore the benefits of MPAs for kelp conservation under a suite of different stressors, focusing on empirical evidence from protected kelp forests. We show that MPAs can be effective against some drivers of kelp loss (e.g., overgrazing, kelp harvesting), particularly when they are maintained in the long-term and enforced as no-take areas. There is also some evidence that MPAs can reduce impacts of climate change through building resilience in multi-stressor situations. However, MPAs also often fail to provide protection against ocean warming, marine heatwaves, coastal darkening, and pollution, which have emerged as dominant drivers of kelp forest loss globally. Although well-enforced MPAs should remain an important tool to protect kelp forests, successful kelp conservation will require implementing an additional suite of management solutions that target these accelerating threats.