Kinetics and Thermodynamics of Membrane Protein Folding

Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparison, advances in the membrane protein folding field lag far behind. Although membrane proteins constitute about a third of the proteins encoded in known genomes, stability studies on membrane proteins have been impaired due to experimental limitations. Furthermore, no systematic experimental strategies are available for folding these biomolecules in vitro. Common denaturing agents such as chaotropes usually do not work on helical membrane proteins, and ionic detergents have been successful denaturants only in few cases. Refolding a membrane protein seems to be a craftsman work, which is relatively straightforward for transmembrane {\beta}-barrel proteins but challenging for {\alpha}-helical membrane proteins. Additional complexities emerge in multidomain membrane proteins, data interpretation being one of the most critical. In this review, we will describe some recent efforts in understanding the folding mechanism of membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. This information will be discussed in the context of current paradigms in the protein folding field

Sclerochronology in the Southern Ocean

This is the final version. Available on open access from Springer via the DOI in this reocrdThis manuscript aims to provide a comprehensive review of the work done by Antarctic sclerochronology research across different taxa (arthropods, bivalves, brachiopods, bryozoans, cephalopods, hard and soft corals, gastropods, echinoderms and teleost fish), provide an analysis of current challenges in the discipline and start a discussion of what sclerochronology can offer for Antarctic research in future. The Southern Ocean ecosystem remains largely unstudied in part for its remoteness, extreme climate and strong seasonality. This lack of knowledge, some of it even on basic biological information, it is especially worrying due to ongoing climate-driven changes that the Southern Ocean ecosystem is experiencing. Lack of long-term in situ instrumental series has also being a detriment to understand long-term feedbacks between the physical environment and the ecosystem. Sclerochronology, the study of periodic accretional patterns in the hard body structures of living organisms, has contributed to a wide range of Antarctic research disciplines (e.g. paleoclimate reconstructions, population structure analysis, environmental proxies). This review highlights a disparity in research focus by taxa with some groups (e.g. bivalves, teleost fish) attracting most of the research attention, whereas other groups (e.g. gastropod) have attracted much little research attention or in some cases it is almost non-existent (e.g. echinoderms). Some of the long-lived species considered in this review have the potential to provide the much-needed high-resolution eco-environmental proxy data and play an important role in blue carbon storage in the Sothern Ocean. Another issue identified was the lack of cross-validation between analytical techniques.Natural Environment Research Council (NERC)CONICY

Gen-2 Hand-Held Optical Imager towards Cancer Imaging: Reflectance and Transillumination Phantom Studies

Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1–5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies

A Multinational Pharmacoeconomic Evaluation of Acute Major Depressive Disorder (MDD): a Comparison of Cost-Effectiveness Between Venlafaxine, SSRIs and TCAs

AbstractMethodsWe conducted a multinational pharmacoeconomic evaluation comparing the immediate release form of a new class of serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine IR to the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) in the treatment of acute major depressive disorder (MDD) in 10 countries (Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States, and Venezuela). We designed a decision analytic model assessing the acute phase of MDD treatment within a 6-month time horizon. Six decision tree models were customized with country-specific estimates from a clinical management analysis, meta-analytic rates from two published meta-analyses, and a resource valuation of treatment costs representing the inpatient and outpatient settings within each country. The meta-analyses provided the clinical rates of success defined as a 50% reduction in depression scores on the Hamilton Depression Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS). Treatment regimen costs were determined from standard lists, fee schedules, and communication with local health economists in each country. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each antidepressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed symptom-free days. A policy analysis was conducted to examine the health system budget impact in each country of increasing the utilization of the most effective antidepressant found in our study.ResultsInitiating treatment of MDD with venlafaxine IR yielded a lower expected cost compared to the SSRIs and TCAs in all countries except Poland in the inpatient setting, and Italy and Poland within the outpatient settings. The weighted average expected cost per patient varied from US$632 (Poland) to US$5647 (US) in the six-month acute phase treatment of MDD. The estimated total budgetary impact for each 1% of venlafaxine utilization, assuming a population of one million MDD patients, ranged from US$1600 (Italy) to US$29,049 (US).ConclusionsWithin the inpatient and outpatient treatment settings, venlafaxine IR was a more cost-effective treatment of MDD compared to the SSRIs and TCAs. Additionally, the results of this investigation indicate that increased utilization of venlafaxine in most settings across Europe and the Americas will have favorable impact on health care payer budgets.ADR, adverse drug reaction; CMA, clinical management analysis; ECT, electroconvulsive therapy; HAM-D, Hamilton Depression Scale; MADRS, Montgomery-Asberg depression rating scale; MDD, major depressive disorder; SFD, symptom-free day; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; WHO, world health organization

Milky Way Demographics with the VVV Survey II. Color Transformations and Near-Infrared Photometry for 136 Million Stars in the Southern Galactic Disk

The new multi-epoch near-infrared VVV survey (VISTA Variables in the Via Lactea) is sampling 562 sq. deg of the Galactic bulge and adjacent regions of the disk. Accurate astrometry established for the region surveyed allows the VVV data to be merged with overlapping surveys (e.g., GLIMPSE, WISE, 2MASS, etc.), thereby enabling the construction of longer baseline spectral energy distributions for astronomical targets. However, in order to maximize use of the VVV data, a set of transformation equations are required to place the VVV JHKs photometry onto the 2MASS system. The impetus for this work is to develop those transformations via a comparison of 2MASS targets in 152 VVV fields sampling the Galactic disk. The transformation coefficients derived exhibit a reliance on variables such as extinction. The transformed data were subsequently employed to establish a mean reddening law of E_{J-H}/E_{H-Ks}=2.13 +/- 0.04, which is the most precise determination to date and merely emphasizes the pertinence of the VVV data for determining such important parameters.Comment: 24 pages, 12 figures, published in A&

Gene flow in the Antarctic bivalve Aequiyoldia eightsii (Jay, 1839) suggests a role for the Antarctic Peninsula Coastal Current in larval dispersal

The Antarctic Circumpolar Current (ACC) dominates the open-ocean circulation of the Southern Ocean, and both isolates and connects the Southern Ocean biodiversity. However, the impact on biological processes of other Southern Ocean currents is less clear. Adjacent to the West Antarctic Peninsula (WAP), the ACC flows offshore in a northeastward direction, whereas the Antarctic Peninsula Coastal Current (APCC) follows a complex circulation pattern along the coast, with topographically influenced deflections depending on the area. Using genomic data, we estimated genetic structure and migration rates between populations of the benthic bivalve Aequiyoldia eightsii from the shallows of southern South America and the WAP to test the role of the ACC and the APCC in its dispersal. We found strong genetic structure across the ACC (between southern South America and Antarctica) and moderate structure between populations of the WAP. Migration rates along the WAP were consistent with the APCC being important for species dispersal. Along with supporting current knowledge about ocean circulation models at the WAP, migration from the tip of the Antarctic Peninsula to the Bellingshausen Sea highlights the complexities of Southern Ocean circulation. This study provides novel biological evidence of a role of the APCC as a driver of species dispersal and highlights the power of genomic data for aiding in the understanding of the influence of complex oceanographic processes in shaping the population structure of marine species

The pre-launch Planck Sky Model: a model of sky emission at submillimetre to centimetre wavelengths

We present the Planck Sky Model (PSM), a parametric model for the generation of all-sky, few arcminute resolution maps of sky emission at submillimetre to centimetre wavelengths, in both intensity and polarisation. Several options are implemented to model the cosmic microwave background, Galactic diffuse emission (synchrotron, free-free, thermal and spinning dust, CO lines), Galactic H-II regions, extragalactic radio sources, dusty galaxies, and thermal and kinetic Sunyaev-Zeldovich signals from clusters of galaxies. Each component is simulated by means of educated interpolations/extrapolations of data sets available at the time of the launch of the Planck mission, complemented by state-of-the-art models of the emission. Distinctive features of the simulations are: spatially varying spectral properties of synchrotron and dust; different spectral parameters for each point source; modeling of the clustering properties of extragalactic sources and of the power spectrum of fluctuations in the cosmic infrared background. The PSM enables the production of random realizations of the sky emission, constrained to match observational data within their uncertainties, and is implemented in a software package that is regularly updated with incoming information from observations. The model is expected to serve as a useful tool for optimizing planned microwave and sub-millimetre surveys and to test data processing and analysis pipelines. It is, in particular, used for the development and validation of data analysis pipelines within the planck collaboration. A version of the software that can be used for simulating the observations for a variety of experiments is made available on a dedicated website.Comment: 35 pages, 31 figure