Mapping three dimensional interactions between biomolecules and electric fields.

Electroporation is a technique that induces the formation of open pores in cell membranes by the application of an electric field. Electroporation is widely practiced in research and clinical work for transfection of genetic sequences and drug molecule transport through the membrane barrier. However, a full theoretical explanation of the molecular mechanisms and thermodynamics responsible for pore formation, structure, and longevity does not yet exist. Advances in molecular dynamics simulations have enabled theoretical studies of electroporation with previously unobtainable fidelity spanning biologically relevant timescales. All-atom simulations utilizing the recently developed method of computational electrophysiology demonstrate that pore size correlates to the magnitude of the applied electric flux. This insight suggests improvements to electroporation protocols and instrument design to increase treatment efficacy while simultaneously decreasing cell mortality. Data processing, that scales and centers each simulation frame, generates a pore-centric matrix of voxels representing the time-averaged charge density of the simulation volume. This processing enabled the calculation of the first high resolution, three-dimensional maps of the electric fields that act to create and stabilize the pore. Applying this capability to individual moieties gives additional insight to how electrostatic forces between biomolecules and membrane structures give cell membranes their remarkable properties. Complementary processing of atom types, instead of partial charges, produces a similarly scaled, stabilized, and time averaged matrix of moiety number densities. Plotted in three dimensions, these density data reveal additional membrane structure detail that have not previously been reported

Temporal Stability of Surface Roughness Effects on Radar Based Soil Moisture Retrieval During the Corn Growth Cycle

A representative soil surface roughness parameterization needed for the retrieval of soil moisture from active microwave satellite observation is difficult to obtain through either in-situ measurements or remote sensing-based inversion techniques. Typically, for the retrieval of soil moisture, temporal variations in surface roughness are assumed to be negligible. Although previous investigations have suggested that this assumption might be reasonable for natural vegetation covers (Moran et al. 2002, Thoma et al. 2006), insitu measurements over plowed agricultural fields (Callens et al. 2006) have shown that the soil surface roughness can change considerably over time. This paper reports on the temporal stability of surface roughness effects on radar observations and soil moisture retrieved from these radar observations collected once a week during a corn growth cycle (May 10th - October 2002). The data set employed was collected during the Optimizing Production Inputs for Economic and Environmental Enhancement (OPE3) field campaign covering this 2002 corn growth cycle and consists of dual-polarized (HH and VV) L-band (1.6 GHz) acquired at view angles of 15, 35, and 55 degrees. Cross-polarized L baud radar data were also collected as part of this experiment, but are not used in the analysis reported on here. After accounting for vegetation effects on radar observations, time-invariant optimum roughness parameters were determined using the Integral Equation Method (IEM) and radar observations acquired over bare soil and cropped conditions (the complete radar data set includes entire corn growth cycle). The optimum roughness parameters, soil moisture retrieval uncertainty, temporal distribution of retrieval errors and its relationship with the weather conditions (e.g. rainfall and wind speed) have been analyzed. It is shown that over the corn growth cycle, temporal roughness variations due to weathering by rain are responsible for almost 50% of soil moisture retrieval uncertainty depending on the sensing configuration. The effects of surface roughness variations are found to be smallest for observations acquired at a view angle of 55 degrees and HH polarization. A possible explanation for this result is that at 55 degrees and HH polarization the effect of vertical surface height changes on the observed radar response are limited because the microwaves travel parallel to the incident plane and as a result will not interact directly with vertically oriented soil structures

Technical Note: Calibration and validation of geophysical observation models

We present a method to calibrate and validate observational models that interrelate remotely sensed energy fluxes to geophysical variables of land and water surfaces. Coincident sets of remote sensing observation of visible and microwave radiations and geophysical data are assembled and subdivided into calibration (Cal) and validation (Val) data sets. Each Cal/Val pair is used to derive the coefficients (from the Cal set) and the accuracy (from the Val set) of the observation model. Combining the results from all Cal/Val pairs provides probability distributions of the model coefficients and model errors. The method is generic and demonstrated using comprehensive matchup sets from two very different disciplines: soil moisture and water quality. The results demonstrate that the method provides robust model coefficients and quantitative measure of the model uncertainty. This approach can be adopted for the calibration/validation of satellite products of land and water surfaces, and the resulting uncertainty can be used as input to data assimilation schemes

New-Onset Atrial Fibrillation After PCI or CABG for Left Main Disease: The EXCEL Trial

Background: There is limited information on the incidence and prognostic impact of new-onset atrial fibrillation (NOAF) following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD). Objectives: This study sought to determine the incidence of NOAF following PCI and CABG for LMCAD and its effect on 3-year cardiovascular outcomes. Methods: In the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. Outcomes were analyzed according to the development of NOAF during the initial hospitalization following revascularization. Results: Among 1,812 patients without atrial fibrillation on presentation, NOAF developed at a mean of 2.7 ± 2.5 days after revascularization in 162 patients (8.9%), including 161 of 893 (18.0%) CABG-treated patients and 1 of 919 (0.1%) PCI-treated patients (p < 0.0001). Older age, greater body mass index, and reduced left ventricular ejection fraction were independent predictors of NOAF in patients undergoing CABG. Patients with versus without NOAF had a significantly longer duration of hospitalization, were more likely to be discharged on anticoagulant therapy, and had an increased 30-day rate of Thrombolysis In Myocardial Infarction major or minor bleeding (14.2% vs. 5.5%; p < 0.0001). By multivariable analysis, NOAF after CABG was an independent predictor of 3-year stroke (6.6% vs. 2.4%; adjusted hazard ratio [HR]: 4.19; 95% confidence interval [CI]: 1.74 to 10.11; p = 0.001), death (11.4% vs. 4.3%; adjusted HR: 3.02; 95% CI: 1.60 to 5.70; p = 0.0006), and the primary composite endpoint of death, MI, or stroke (22.6% vs. 12.8%; adjusted HR: 2.13; 95% CI: 1.39 to 3.25; p = 0.0004). Conclusions: In patients with LMCAD undergoing revascularization in the EXCEL trial, NOAF was common after CABG but extremely rare after PCI. The development of NOAF was strongly associated with subsequent death and stroke in CABG-treated patients. Further studies are warranted to determine whether prophylactic strategies to prevent or treat atrial fibrillation may improve prognosis in patients with LMCAD who are undergoing CABG. (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularizatio

A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

Nutrition for the ageing brain: towards evidence for an optimal diet

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives