Alternative translation initiation in rat brain yields K2P2.1 potassium channels permeable to sodium.

K(2P) channels mediate potassium background currents essential to central nervous system function, controlling excitability by stabilizing membrane potential below firing threshold and expediting repolarization. Here, we show that alternative translation initiation (ATI) regulates function of K(2P)2.1 (TREK-1) via an unexpected strategy. Full-length K(2P)2.1 and an isoform lacking the first 56 residues of the intracellular N terminus (K(2P)2.1Delta1-56) are produced differentially in a regional and developmental manner in the rat central nervous system, the latter passing sodium under physiological conditions leading to membrane depolarization. Control of ion selectivity via ATI is proposed to be a natural, epigenetic mechanism for spatial and temporal regulation of neuronal excitability

How Do You Move? Everyday stories of physical activity

Stories can be a powerful method of exploring complexity, and the factors affecting everyday physical activity within a modern urban setting are nothing if not complex. The first part of our How Do You Move? study focused on the communication of physical activity guidelines to under-served communities. A key finding was that adults especially wanted physical activity messages to come from ‘everyday people, people like us’. This finding also reflects a wider move to use more relatable imagery in health promotion campaigns. Using a portrait vignette approach to create monologues, we set out to explore the experiences of people from diverse backgrounds living in Bristol, all of whom took part in varied leisure time physical activities but would also be considered to lead ‘normal’ lives. We aim to demonstrate that stories of such ‘experts by experience’ can contribute to how physical activity is perceived and elucidate the complex interplay of barriers and enablers in everyday experiences of physical activity

A participatory approach to variety trials for organic systems

A participatory research methodology was used to compare the performance of UK wheat varieties under organic conditions. Plots of three breadmaking winter wheat varieties (Hereward, Solstice and Xi19) and a mixture (1:1:1) of the varieties were grown at 19 UK farms in two seasons (2003/04 and 2004/05). Meas-urements were taken of growth habit, yield and grain quality. Grain yields in both seasons showed significant site by variety interactions, although the variation among sites was greater than among varieties in both instances. Wheat grown at Western sites was significantly shorter and higher-yielding than that grown at Eastern sites in 2003/04 but significantly taller in 2004/05. As with grain yield, greater variation among site than variety was found in the Hagberg Falling Number and protein concentra-tion results in both seasons. The results from the two years of trials illustrate the variability of organic systems and the difficulty in selecting a single variety suitable for organic farms

Early warnings and missed alarms for abrupt monsoon transitions

Journal ArticlePalaeo-records from China demonstrate that the East Asian Summer Monsoon (EASM) is dominated by abrupt and large magnitude monsoon shifts on millennial timescales, switching between periods of high and weak monsoon rains. It has been hypothesized that over these timescales, the EASM exhibits two stable states with bifurcation-Type tipping points between them. Here we test this hypothesis by looking for early warning signals of past bifurcations in speleothem δ18O records from Sanbao Cave and Hulu Cave, China, spanning the penultimate glacial cycle. We find that although there are increases in both autocorrelation and variance preceding some of the monsoon transitions during this period, it is only immediately prior to the abrupt monsoon shift at the penultimate deglaciation (Termination II) that statistically significant increases are detected. To supplement our data analysis, we produce and analyse multiple model simulations that we derive from these data. We find hysteresis behaviour in our model simulations with transitions directly forced by solar insolation. However, signals of critical slowing down, which occur on the approach to a bifurcation, are only detectable in the model simulations when the change in system stability is sufficiently slow to be detected by the sampling resolution of the data set. This raises the possibility that the early warning "alarms" were missed in the speleothem data over the period 224-150 kyr and it was only at the monsoon termination that the change in the system stability was sufficiently slow to detect early warning signals

Recent Accumulation Variability in Northwest Greenland from Ground-Penetrating Radar and Shallow Cores along the Greenland Inland Traverse

Accumulation is a key parameter governing the mass balance of the Greenland ice sheet. Several studies have documented the spatial variability of accumulation over wide spatial scales, primarily using point data, remote sensing or modeling. Direct measurements of spatially extensive, detailed profiles of accumulation in Greenland, however, are rare. We used 400 MHz ground-penetrating radar along the 1009 km route of the Greenland Inland Traverse from Thule to Summit during April and May of 2011, to image continuous internal reflecting horizons. We dated these horizons using ice-core chemistry at each end of the traverse. Using density profiles measured along the traverse, we determined the depth to the horizons and the corresponding water-equivalent accumulation rates. The measured accumulation rates vary from ~0.1 m w.e. a–1 in the interior to ~0.7 m w.e. a–1 near the coast, and correspond broadly with existing published model results, though there are some excursions. Comparison of our recent accumulation rates with those collected along a similar route in the 1950s shows a ~10% increase in accumulation rates over the past 52 years along most of the traverse route. This implies that the increased water vapor capacity of warmer air is increasing accumulation in the interior of Greenland

Mu Opioid Receptor Modulation of Dopamine Neurons in the Periaqueductal Gray/Dorsal Raphe: A Role in Regulation of Pain

The periaqueductal gray (PAG) is a brain region involved in nociception modulation, and an important relay center for the descending nociceptive pathway through the rostral ventral lateral medulla. Given the dense expression of mu opioid receptors and the role of dopamine in pain, the recently characterized dopamine neurons in the ventral PAG (vPAG)/dorsal raphe (DR) region are a potentially critical site for the antinociceptive actions of opioids. The objectives of this study were to (1) evaluate synaptic modulation of the vPAG/DR dopamine neurons by mu opioid receptors and to (2) dissect the anatomy and neurochemistry of these neurons, in order to assess the downstream loci and functions of their activation. Using a mouse line that expresses eGFP under control of the tyrosine hydroxylase (TH) promoter, we found that mu opioid receptor activation led to a decrease in inhibitory inputs onto the vPAG/DR dopamine neurons. Furthermore, combining immunohistochemistry, optogenetics, electrophysiology, and fast-scan cyclic voltammetry in a TH-cre mouse line, we demonstrated that these neurons also express the vesicular glutamate type 2 transporter and co-release dopamine and glutamate in a major downstream projection structure—the bed nucleus of the stria terminalis. Finally, activation of TH-positive neurons in the vPAG/DR using Gq designer receptors exclusively activated by designer drugs displayed a supraspinal, but not spinal, antinociceptive effect. These results indicate that vPAG/DR dopamine neurons likely play a key role in opiate antinociception, potentially via the activation of downstream structures through dopamine and glutamate release

Evolutionary Responses of a Reef-building Coral to Climate Change at the End of the Last Glacial Maximum

Climate change threatens the survival of coral reefs on a global scale, primarily through mass bleaching and mortality as a result of marine heatwaves. While these short-term effects are clear, predicting the fate of coral reefs over the coming century is a major challenge. One way to understand the longer-term effect of rapid climate change is to examine the response of coral populations to past climate shifts. Coastal and shallow-water marine ecosystems such as coral reefs have been reshaped many times by sea-level changes during the Pleistocene, yet few studies have directly linked this with its consequences on population demographics, dispersal, and adaptation. Here we use powerful analytical techniques, afforded by haplotype-phased whole-genomes, to establish such links for the reef-building coral, Acropora digitifera. We show that three genetically distinct populations are present in northwestern Australia, and that their rapid divergence since the last glacial maximum (LGM) can be explained by a combination of founder-effects and restricted gene flow. Signatures of selective sweeps, too strong to be explained by demographic history, are present in all three populations and overlap with genes that show different patterns of functional enrichment between inshore and offshore habitats. In contrast to rapid divergence in the host, we find that photosymbiont communities are largely undifferentiated between corals from all three locations, spanning almost 1000 km, indicating that selection on host genes, and not acquisition of novel symbionts, has been the primary driver of adaptation for this species in northwestern Australia

Neural tube defects in four Shetland sheepdog puppies: clinical characterisation and computed tomography investigation

Case report Here we report on the occurrence of neural tube defects in four related Shetland sheepdog puppies. Neural tube defects present as a range of congenital malformations affecting the spine, skull and associated structures. Despite the severity of these malformations and their relatively high prevalence in humans, the aetiology is not well understood. It is even less well characterised in veterinary medicine. Affected puppies were investigated using computed tomography and then post-mortem examination. Computed tomography identified a range of brain and spine abnormalities in the affected animals, including caudal anencephaly, encephalocele, spina bifida and malformed vertebrae. Other observed abnormalities in these puppies, including cranioschisis, atresia ani and hydrocephalus, may be secondary to, or associated with, the primary neural tube defects identified. Conclusion This case report describes multiple related cases of neural tube defects in an Australian cohort of dogs. This study also highlights the potential of advanced imaging techniques in identifying congenital anomalies in stillborn and neonatal puppies. Further research is required to investigate the aetiology of neural tube defects in this group of affected Shetland sheepdogs

Platelet zinc status regulates prostaglandin-induced signaling, altering thrombus formation

Background: Approximately 17.3% of the global population exhibits an element of zinc (Zn2+) deficiency. One symptom of Zn2+ deficiency is increased bleeding through impaired hemostasis. Platelets are crucial to hemostasis and are inhibited by endothelial-derived prostacyclin (prostaglandin I2 [PGI2]), which signals via adenylyl cyclase (AC) and cyclic adenosine monophosphate signaling. In other cell types, Zn2+ modulates cyclic adenosine monophosphate concentrations by changing AC and/or phosphodiesterase activity. Objectives: To investigate if Zn2+ can modulate platelet PGI2 signaling. Methods: Platelet aggregation, spreading, and western blotting assays with Zn2+ chelators and cyclic nucleotide elevating agents were performed in washed platelets and platelet-rich plasma conditions. In vitro thrombus formation with various Zn2+ chelators and PGI2 was assessed in whole blood. Results: Incubation of whole blood or washed platelets with Zn2+ chelators caused either embolization of preformed thrombi or reversal of platelet spreading, respectively. To understand this effect, we analyzed resting platelets and identified that incubation with Zn2+ chelators elevated pVASPser157, a marker of PGI2 signaling. In agreement that Zn2+ affects PGI2 signaling, addition of the AC inhibitor SQ22536 blocked Zn2+ chelation–induced platelet spreading reversal, while addition of Zn2+ blocked PGI2-mediated platelet reversal. Moreover, Zn2+ specifically blocked forskolin-mediated AC reversal of platelet spreading. Finally, PGI2 inhibition of platelet aggregation and in vitro thrombus formation was potentiated in the presence of low doses of Zn2+ chelators, increasing its effectiveness in inducing platelet inhibition. Conclusion: Zn2+ chelation potentiates platelet PGI2 signaling, elevating PGI2’s ability to prevent effective platelet activation, aggregation, and thrombus formation