Depletion of Ca2+ from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to stimulate store refilling

Nonmuscle cells have almost ubiquitously evolved a mechanism to detect and prevent Ca(2+) store depletionstore operated calcium entry. No such mechanism has, as yet, been reported in cardiac myocytes. However, it is conceivable that such a mechanism may play an important role in cardiac Ca(2+) homeostasis to ensure the availability of sufficient stored Ca(2+) to maintain normal excitation contraction coupling. We present data that confirms the presence of a mechanism that is able to monitor the Ca(2+) load of the SR and initiate a signaling process to accelerate Ca(2+) uptake by the SR when store depletion is detected. Depletion of SR Ca(2+) activates a protein kinase, the principal SR substrate of which is phospholamban. Phosphorylation of this SR protein promotes Ca(2+) pump activity and therefore store refilling. Furthermore, a protein kinase activity associated with the SR that is inhibited by Ca(2+) ions has been identified. We have measured lumenal [Ca(2+)] by using a fluorescent Ca(2+) indicator and found that by initiating Ca(2+) uptake and increasing Ca(2+) load, we can inhibit the protein kinase activity associated with the SR. This confirms that a protein kinase, that is regulated by lumenal [Ca(2+)], has been identified and represents part of a previously unidentified signalling cascade. This local feedback mechanism would allow the myocyte to detect and prevent SR Ca(2+) load depletio

REFLECTIONS ON RELEVANCE OF PROFESSIONAL JOURNALS

It appears the major private benefit from peer reviewed journals such as the Review of Agricultural Economics (RAE) is certification. To maintain public support for our journals, increased efforts are needed to demonstrate the social benefits from peer reviewed publications. Research cost considerations have led agricultural economists to emphasize applied disciplinary work using secondary data and to ignore the important work of careful data collection and reporting. Moreover, pressures to publish have led to more isolated research efforts ignoring other disciplines. Recommendations to improve the relevance of journal publications include more active efforts by journal editors to make applied journals such as RAE more accessible to the public.Certification, Confirmation studies, Private goods, Public goods, Relevance, Teaching/Communication/Extension/Profession,

The dependence of global super-rotation on planetary rotation rate

An atmosphere may be described as globally super-rotating if its total zonal angular momentum exceeds that associated with solid-body co-rotation with the underlying planet. In this paper, we discuss the dependence of global super-rotation in terrestrial atmospheres on planetary rotation rate. This dependence is revealed through analysis of global super-rotation in idealised General Circulation Model experiments with time-independent axisymmetric forcing, compared with estimates for global super-rotation in Solar System atmospheres. Axisymmetric and three-dimensional experiments are conducted. We find that the degree of global super-rotation in the three-dimensional experiments is closely related to that of the axisymmetric experiments, with some differences in detail. A scaling theory for global super-rotation in an axisymmetric atmosphere is derived from the Held-Hou model. At high rotation rate, our numerical experiments inhabit a regime where global super-rotation scales geostrophically, and we suggest that the Earth and Mars occupy this regime. At low rotation rate, our experiments occupy a regime determined by angular momentum conservation, where global super-rotation is independent of rotation rate. Global super-rotation in our experiments saturates at a value significantly lower than that achieved in the atmospheres of Venus and Titan, which instead occupy a regime where global super-rotation scales cyclostrophically. This regime can only be accessed when eddy induced up-gradient angular momentum transport is sufficiently large, which is not the case in our idealised numerical experiments. We suggest that the 'default' regime for a slowly rotating planet is the angular momentum conserving regime, characterised by mild global (and local) superrotation.Comment: Submitted to Journal of the Atmospheric Sciences. Comments welcome. This manuscript has not yet been peer reviewe

Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence

Objectives  We aimed to evaluate (1) the epidemiological evidence for an association between cannabis use, CUD, and mood disorders; (2) prospective longitudinal, genetic, and neurocognitive evidence of underlying mechanisms; and (3) prognosis and treatment options for individuals with CUD and mood disorders.  Methods  Narrative review of existing literature is identified through PubMed searches, reviews, and meta-analyses. Evidence was reviewed separately for depression, bipolar disorder, and suicide.  Results  Current evidence is limited and mixed but suggestive of a bidirectional relationship between cannabis use, CUD, and the onset of depression. The evidence more consistently points to cannabis use preceding onset of bipolar disorder. Shared neurocognitive mechanisms and underlying genetic and environmental risk factors appear to explain part of the association. However, cannabis use itself may also influence the development of mood disorders, while others may initiate cannabis use to self-medicate symptoms. Comorbid cannabis use and CUD are associated with worse prognosis for depression and bipolar disorder including increased suicidal behaviors. Evidence for targeted treatments is limited.  Conclusions  The current evidence base is limited by the lack of well-controlled prospective longitudinal studies and clinical studies including comorbid individuals. Future studies in humans examining the causal pathways and potential mechanisms of the association between cannabis use, CUD, and mood disorder comorbidity are crucial for optimizing harm reduction and treatment strategies

The Effect of Moxidectin Treatment on the Equine Hind Gut Microbiome, Metabonome and Feed Fermentation Kinetics in Horses with Very Low Parasite Burdens

Seventeen horses, mean 12 ± 3.5 years, kept at pasture, with haylage provided and no concentrates. Faecal Egg Counts were conducted September 2015‐March 2016, no eggs seen, no anthelmintic given. Sampling commenced March 2016, points were 0 (prior), 16, 48 and 168 hours post anthelmintic. Treatments were randomized, nine animals dosed orally with Moxidectin 18.92 mg/g at 0.4 mg/kg bw and eight controls. Three horses from each group were randomly assigned for fermentation kinetics. Sequencing of the 16S rRNA gene was conducted on extracted faecal bacterial DNA, bioinformatics using QIIME assigning operational taxonomic units (OTUs). LEfSe (Segata et al., 2011) was used to identify differentially abundant OTUs. Bacterial metabolic profiles were characterized by 1H NMR spectroscopy (Escalona et al., 2015), from urine, analysed by Principal Components Analysis. Fermentation of hay and oats, separately, were measured by in vitro gas production (Murray et al., 2006), data were analysed by repeated measures ANOVA