CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations

CBS domains are defined as sequence motifs that occur in several different proteins in all kingdoms of life. Although thought to be regulatory, their exact functions have been unknown. However, their importance was underlined by findings that mutations in conserved residues within them cause a variety of human hereditary diseases, including (with the gene mutated in parentheses): Wolff-Parkinson-White syndrome (γ2 subunit of AMP-activated protein kinase); retinitis pigmentosa (IMP dehydrogenase-1); congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members); and homocystinuria (cystathionine β-synthase). AMP-activated protein kinase is a sensor of cellular energy status that is activated by AMP and inhibited by ATP, but the location of the regulatory nucleotide-binding sites (which are prime targets for drugs to treat obesity and diabetes) was not characterized. We now show that tandem pairs of CBS domains from AMP-activated protein kinase, IMP dehydrogenase-2, the chloride channel CLC2, and cystathionine β-synthase bind AMP, ATP, or S-adenosyl methionine,while mutations that cause hereditary diseases impair this binding. This shows that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a newly identified class of binding domain for adenosine derivatives

Allometric Equations to Estimate Aboveground Biomass in Spotted Gum (Corymbia citriodora Subspecies variegata) Plantations in Queensland

Accurate equations are critical for estimating biomass and carbon accumulation for forest carbon projects, bioenergy, and other inventories. Allometric equations can provide a reliable and accurate method for estimating and predicting biomass and carbon sequestration. Cross-validatory assessments are also essential to evaluate the prediction ability of the selected model with satisfactory accuracy. We destructively sampled and weighed 52 sample trees, ranging from 11.8 to 42.0 cm in diameter at breast height from three plantations in Queensland to determine biomass. Weighted nonlinear models were used to explore the influence of different variables using two datasets: the first dataset (52 trees) included diameter at breast height (D), height (H) and wood density (ρ); and the second dataset (40 trees) also included crown diameter (CD) and crown volume (CV). Cross validation of independent data showed that using D alone proved to be the best performing model, with the lowest values of AIC = 434.4, bias = −2.2% and MAPE = 7.2%. Adding H and ρ improved the adjusted. R2 (Δ adj. R2 from 0.099 to 0.135) but did not improve AIC, bias and MAPE. Using the single variable of CV to estimate aboveground biomass (AGB) was better than CD, with smaller AIC and MAPE less than 2.3%. We demonstrated that the allometric equations developed and validated during this study provide reasonable estimates of Corymbia citriodora subspecies variegata (spotted gum) biomass. This equation could be used to estimate AGB and carbon in similar spotted gum plantations. In the context of global forest AGB estimations and monitoring, the CV variable could allow prediction of aboveground biomass using remote sensing datasets

Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian conditioned stimuli in fMRI when subjects were not intoxicated. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol. Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related. Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations

Species-Specific Allometric Equations for Predicting Belowground Root Biomass in Plantations: Case Study of Spotted Gums (Corymbia citriodora subspecies variegata) in Queensland

Spotted gum (Corymbia citriodora spp. variegata; CCV) has been widely planted, has a wide natural distribution, and is the most important commercially harvested hardwood species in Queensland, Australia. It has a great capacity to sequester carbon, thus reducing the impact of CO2 emissions on climate. Belowground root biomass (BGB) plays an important role as a carbon sink in terrestrial ecosystems. To explore the potential of biomass and carbon accumulation belowground, we developed and validated models for CCV plantations in Queensland. The roots of twenty-three individual trees (size range 11.8–42.0 cm diameter at breast height) from three sites were excavated to a 1-m depth and were weighed to obtain BGB. Weighted nonlinear regression models were most reliable for estimating BGB. To evaluate the candidate models, the data set was cross-validated with 70% of the data used for training and 30% of the data used for testing. The cross-validation process was repeated 23 times and the validation of the models were averaged over 23 iterations. The best model for predicting spotted gum BGB was based on a single parameter, with the diameter at breast height (D) as an independent variable. The best equation BGB = 0.02933 × D2.5805 had an adjusted R2 of 0.854 and a mean absolute percentage error of 0.090%. This equation was tested against published BGB equations; the findings from this are discussed. Our equation is recommended to allow improved estimates of BGB for this species

Species-Specific Allometric Equations for Predicting Belowground Root Biomass in Plantations: Case Study of Spotted Gums (Corymbia citriodora subspecies variegata) in Queensland

Spotted gum (Corymbia citriodora spp. variegata; CCV) has been widely planted, has a wide natural distribution, and is the most important commercially harvested hardwood species in Queensland, Australia. It has a great capacity to sequester carbon, thus reducing the impact of CO2 emissions on climate. Belowground root biomass (BGB) plays an important role as a carbon sink in terrestrial ecosystems. To explore the potential of biomass and carbon accumulation belowground, we developed and validated models for CCV plantations in Queensland. The roots of twenty-three individual trees (size range 11.8–42.0 cm diameter at breast height) from three sites were excavated to a 1-m depth and were weighed to obtain BGB. Weighted nonlinear regression models were most reliable for estimating BGB. To evaluate the candidate models, the data set was cross-validated with 70% of the data used for training and 30% of the data used for testing. The cross-validation process was repeated 23 times and the validation of the models were averaged over 23 iterations. The best model for predicting spotted gum BGB was based on a single parameter, with the diameter at breast height (D) as an independent variable. The best equation BGB = 0.02933 × D2.5805 had an adjusted R2 of 0.854 and a mean absolute percentage error of 0.090%. This equation was tested against published BGB equations; the findings from this are discussed. Our equation is recommended to allow improved estimates of BGB for this species

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 ± 0.3 (mean ± SEM) months later and 53 patients underwent a further assessment 13.1 ± 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 ± 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 ± 0.1 vs. 9.9 ± 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 ± 99 vs. 399 ± 69 µg/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 ± 0.1 vs. 5.4 ± 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 ± 0.04 vs. 1.04 ± 0.06; P < 0.05) and serum triglycerides (2.26 ± 0.14 vs. 1.99 ± 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement. These changes correlated with the increase in Hb (P < 0.001 in each case), and the reduction in ferritin for total cholesterol (P < 0.02), LDL cholesterol (P < 0.03), and to a lesser extent apoprotein B (P < 0.07). No difference was observed in patients using maintenance HD or CAPD, and similar trends were observed in male and female patients. Improvements in the lipid profile occurred independently of the time on dialysis prior to the commencement of EPO. We conclude that EPO treatment is associated with alterations in the lipid profile which may suggest a long-term improvement in the vascular morbidity of chronic renal failure. The causes of the improved lipids are not addressed by this study and may be equally due to a direct or secondary benefit of EPO therapy

Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010-11 Seasons: A Test-negative Observational Study

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons

Optical antennas for wavelength division multiplexing in visible light communications beyond the étendue limit

Funding: UK EPSRC via “Ultra-parallel visible light communications (UP-VLC)” (Programme Grant EP/K00042X/1) and “Super Receivers for Visible Light Communications” (related grants EP/R00689X/1 and EP/R005281/1).This paper presents a novel fluorescent receiver for visible light communications that combines a broad field of view (FoV) with a significant gain, and simultaneously enables wavelength division multiplexing (WDM) for data communications. These characteristics are achieved by creating a receiver that includes a stack of two fluorescent optical antennas, each designed to receive a different part of the spectrum and create two separable communication channels. The device outperforms the theoretical étendue limit in terms of the combination of FoV and gain it can achieve. Furthermore, the demonstrated de‐multiplexing of blue and green spectral components enables the parallel streaming of data by WDM. Since these devices are inexpensive, simple, and compact, they can easily be integrated into portable electronic devices such as phones, tablets, and laptops.PostprintPeer reviewe

Ecological genetics in the North Atlantic: environmental gradients and adaptation at specific loci

The North Atlantic intertidal community provides a rich set of organismal and environmental material for the study of ecological genetics. Clearly defined environmental gradients exist at multiple spatial scales: there are broad latitudinal trends in temperature, meso-scale changes in salinity along estuaries, and smaller scale gradients in desiccation and temperature spanning the intertidal range. The geology and geography of the American and European coasts provide natural replication of these gradients, allowing for population genetic analyses of parallel adaptation to environmental stress and heterogeneity. Statistical methods have been developed that provide genomic neutrality tests of population differentiation and aid in the process of candidate gene identification. In this paper, we review studies of marine organisms that illustrate associations between an environmental gradient and specific genetic markers. Such highly differentiated markers become candidate genes for adaptation to the environmental factors in question, but the functional significance of genetic variants must be comprehensively evaluated. We present a set of predictions about locus-specific selection across latitudinal, estuarine, and intertidal gradients that are likely to exist in the North Atlantic. We further present new data and analyses that support and contradict these simple selection models. Some taxa show pronounced clinal variation at certain loci against a background of mild clinal variation at many loci. These cases illustrate the procedures necessary for distinguishing selection driven by internal genomic vs. external environmental factors. We suggest that the North Atlantic intertidal community provides a model system for identifying genes that matter in ecology due to the clarity of the environmental stresses and an extensive experimental literature on ecological function. While these organisms are typically poor genetic and genomic models, advances in comparative genomics have provided access to molecular tools that can now be applied to taxa with well-defined ecologies. As many of the organisms we discuss have tight physiological limits driven by climatic factors, this synthesis of molecular population genetics with marine ecology could provide a sensitive means of assessing evolutionary responses to climate change