Penaeid and carid community changes in the St Lucia estuarine lake system,South Africa,under low water level,extended closed periods and marine reconnection conditions

Penaeid and carid communities were assessed in St Lucia over a wide range of saline conditions, water level conditions and mouth states, including a six-month marine connection and various connections to the Mfolozi Estuary. Samples were collected biannually in spring and autumn from November 2004 to May 2012 using seine nets. Seven penaeid and seven carid species were recorded, of which Palaemon pacificus, P. peringueyi, Penaeus indicus and Metapenaeus monoceros were the most abundant. The decline from 2004 to 2007 in both species recorded and densities of freshwater, estuarine and marine species during the initial closed period was linked to increased salinity, lack of recruitment and reduced estuarine surface area. Increased wave action and high seas following Cyclone Gamede opened the mouth in March 2007 after a 57-month closed period, resulting in recruitment of marine species, predominantly P. indicus, followed by a decline in densities after reclosure in August 2007. Increases in marine and freshwater species were evident after Mfolozi flood connections during 2008, 2009 and 2010. Highest densities were recorded after breaching in 2007 and after flood connections, highlighting the importance of a marine link to maintain the recruitment of penaeid species.     

Direct simulation of protein-mediated vesicle fusion: lung surfactant protein B

We simulated spontaneous fusion of small unilamellar vesicles mediated by lung surfactant protein B (SP-B) using the MARTINI force field. An SP-B monomer triggers fusion events by anchoring two vesicles and facilitating the formation of a lipid bridge between the proximal leaflets. Once a lipid bridge is formed, fusion proceeds via a previously described stalk - hemifusion diaphragm - pore-opening pathway. In the absence of protein, fusion of vesicles was not observed in either unbiased simulations or upon application of a restraining potential to maintain the vesicles in close proximity. The shape of SP-B appears to enable it to bind to two vesicles at once, forcing their proximity, and to facilitate the initial transfer of lipids to form a high-energy hemifusion intermediate. Our results may provide insight into more general mechanisms of protein-mediated membrane fusion, and a possible role of SP-B in the secretory pathway and transfer of lung surfactant to the gas exchange interface.     

Immune function in a free-living bird varies over the annual cycle, but seasonal patterns differ between years

A central hypothesis of eco-immunology proposes trade-offs between immune defences and competing physiological and behavioural processes, leading to immunological variation within and among annual-cycle stages, as has been revealed for some species. However, few studies have simultaneously investigated patterns of multiple immune indices over the entire annual cycle in free-living birds, and none has investigated the consistency of seasonal patterns across multiple years. We quantified lysis, agglutination, haptoglobin, leukocyte profiles, and body mass in free-living skylarks (Alauda arvensis) through two complete annual cycles and within and between four breeding seasons. The skylarks?? annual cycle is characterised by annually repeated changes in energy and time budgets, social structure and diet. If trade-offs relating to these cyclic changes shape evolution, predictable intra-annual immune patterns may result. Alternatively, intra-annual immune patterns may vary among years if fluctuating environmental changes affect the cost?Cbenefit balances of immune function. We found significant variation in immune indices and body mass across the annual cycle, and these patterns differed between years. Immune parameters differed between four breeding seasons, and in all years, lysis and agglutination increased as the season progressed independent of average levels. Population-level patterns (intra-annual, inter-annual, within breeding season) were consistent with within-individual patterns based on repeated measurements. We found little evidence for sex differences, and only haptoglobin was correlated (negatively) with body mass. We conclude that immune modulation is not simply a pre-programmed phenomenon that reflects predictable ecological changes. Instead, fluctuating environmental conditions that vary among years likely contribute to the immunological variation that we observed.     

Transfer of arginine into lipid bilayers is nonadditive

Computer simulations suggest that the translocation of arginine through the hydrocarbon core of a lipid membrane proceeds by the formation of a water-filled defect that keeps the arginine molecule hydrated even at the center of the bilayer. We show here that adding additional arginine molecules into one of these water defects causes only a small change in free energy. The barrier for transferring multiple arginines through the membrane is approximately the same as for a single arginine and may even be lower depending on the exact geometry of the system. We discuss these results in the context of arginine-rich peptides such as antimicrobial and cell-penetrating peptides.     

Hydrophobicity scales: a thermodynamic looking glass into lipid-protein interactions

The partitioning of amino acid sidechains into the membrane is a key aspect of membrane protein folding. However, lipid bilayers exhibit rapidly changing physicochemical properties over their nanometer-scale thickness, which complicates understanding the thermodynamics and microscopic details of membrane partitioning. Recent data from diverse approaches, including protein insertion by the Sec translocon, folding of a small beta-barrel membrane protein and computer simulations of the exact distribution of a variety of small molecules and peptides, have joined older hydrophobicity scales for membrane protein prediction. We examine the correlations among the scales and find that they are remarkably correlated even though there are large differences in magnitude. We discuss the implications of these scales for understanding membrane protein structure and function.     

Pathogen pressure puts immune defense into perspective

The extent to which organisms can protect themselves from disease depends on both the immune defenses they maintain and the pathogens they face. At the same time, immune systems are shaped by the antigens they encounter, both over ecological and evolutionary time. Ecological immunologists often recognize these interactions, yet ecological immunology currently lacks major efforts to characterize the environmental, host-independent, antigenic pressures to which all animals are exposed. Failure to quantify relevant diseases and pathogens in studies of ecological immunology leads to contradictory hypotheses. In contrast, including measures of environmental and host-derived commensals, pathogens, and other immune-relevant organisms will strengthen the field of ecological immunology. In this article, we examine how pathogens and other organisms shape immune defenses and highlight why such information is essential for a better understanding of the causes of variation in immune defenses. We introduce the concept of "operative protection" for understanding the role of immunologically relevant organisms in shaping immune defense profiles, and demonstrate how the evolutionary implications of immune function are best understood in the context of the pressures that diseases and pathogens bring to bear on their hosts. We illustrate common mistakes in characterizing these immune-selective pressures, and provide suggestions for the use of molecular and other methods for measuring immune-relevant organisms.     

Optimal antithrombotic treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention: triple therapy is too much!

Patients with atrial fibrillation who undergo a coronary intervention are eligible for both anticoagulation and (dual) antiplatelet therapy ((D)APT). An optimal balance has to be found to reduce the thromboembolic risk (i.e. stroke, systemic embolism and myocardial infarction) and to minimise the increased risk of bleeding with concomitant use of an anticoagulant and (D)APT. Owing to a lack of evidence, the guideline recommendations are predominantly based on expert opinion. Current evidence indicates that the combination of a non-vitamin K oral anticoagulant (NOAC) and clopidogrel is safer than vitamin-K oral antagonists plus DAPT, which increases the risk of bleeding, without clear advantages in regard to efficacy. Concerning whether (N)OACs should be combined with single APT rather than DAPT, the findings of the WOEST, PIONEER AF-PCI and RE-DUAL PCI trials seem to favour a combination with clopidogrel only, thus omitting aspirin. Choosing the optimal treatment strategies for individual patients on NOACs and (D)APT will remain a challenge for clinicians, though triple therapy seems to be the less favourable option owing to the increased risk of bleeding.     

Simulation of the coupling between nucleotide binding and transmembrane domains in the ATP binding cassette transporter BtuCD

The nucleotide-induced structural rearrangements in ATP binding cassette (ABC) transporters, leading to substrate translocation, are largely unknown. We have modeled nucleotide binding and release in the vitamin B(12) importer BtuCD using perturbed elastic network calculations and biased molecular dynamics simulations. Both models predict that nucleotide release decreases the tilt between the two transmembrane domains and opens the cytoplasmic gate. Nucleotide binding has the opposite effect. The observed coupling may be relevant for all ABC transporters because of the conservation of nucleotide binding domains and the shared role of ATP in ABC transporters. The rearrangements in the cytoplasmic gate region do not provide enough space for B(12) to diffuse from the transporter pore into the cytoplasm, which could suggest that peristaltic forces are needed to exclude B(12) from the transporter pore.     

Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation

BackgroundCryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI.MethodsWe included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response.ResultsFollowing PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p < 0.001), and to 71.9 ± 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 ± 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 ± 10.6 bpm (pre-ablation), 84.6 ± 9.8 bpm (3 months), 80.1 ± 6.5 bpm (6 months) and 76.3 ± 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation.ConclusionFew patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.