Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Anthrax Toxin Receptor Drives Protective Antigen Oligomerization and Stabilizes the Heptameric and Octameric Oligomer by a Similar Mechanism

Anthrax toxin is comprised of protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins are individually nontoxic; however, when PA assembles with LF and EF, it produces lethal toxin and edema toxin, respectively. Assembly occurs either on cell surfaces or in plasma. In each milieu, PA assembles into a mixture of heptameric and octameric complexes that bind LF and EF. While octameric PA is the predominant form identified in plasma under physiological conditions (pH 7.4, 37°C), heptameric PA is more prevalent on cell surfaces. The difference between these two environments is that the anthrax toxin receptor (ANTXR) binds to PA on cell surfaces. It is known that the extracellular ANTXR domain serves to stabilize toxin complexes containing the PA heptamer by preventing premature PA channel formation--a process that inactivates the toxin. The role of ANTXR in PA oligomerization and in the stabilization of toxin complexes containing octameric PA are not understood.Using a fluorescence assembly assay, we show that the extracellular ANTXR domain drives PA oligomerization. Moreover, a dimeric ANTXR construct increases the extent of and accelerates the rate of PA assembly relative to a monomeric ANTXR construct. Mass spectrometry analysis shows that heptameric and octameric PA oligomers bind a full stoichiometric complement of ANTXR domains. Electron microscopy and circular dichroism studies reveal that the two different PA oligomers are equally stabilized by ANTXR interactions.We propose that PA oligomerization is driven by dimeric ANTXR complexes on cell surfaces. Through their interaction with the ANTXR, toxin complexes containing heptameric and octameric PA oligomers are similarly stabilized. Considering both the relative instability of the PA heptamer and extracellular assembly pathway identified in plasma, we propose a means to regulate the development of toxin gradients around sites of infection during anthrax pathogenesis

Significance analysis of microarray for relative quantitation of LC/MS data in proteomics

<p>Abstract</p> <p>Background</p> <p>Although fold change is a commonly used criterion in quantitative proteomics for differentiating regulated proteins, it does not provide an estimation of false positive and false negative rates that is often desirable in a large-scale quantitative proteomic analysis. We explore the possibility of applying the Significance Analysis of Microarray (SAM) method (PNAS 98:5116-5121) to a differential proteomics problem of two samples with replicates. The quantitative proteomic analysis was carried out with nanoliquid chromatography/linear iron trap-Fourier transform mass spectrometry. The biological sample model included two <it>Mycobacterium smegmatis </it>unlabeled cell cultures grown at pH 5 and pH 7. The objective was to compare the protein relative abundance between the two unlabeled cell cultures, with an emphasis on significance analysis of protein differential expression using the SAM method. Results using the SAM method are compared with those obtained by fold change and the conventional <it>t</it>-test.</p> <p>Results</p> <p>We have applied the SAM method to solve the two-sample significance analysis problem in liquid chromatography/mass spectrometry (LC/MS) based quantitative proteomics. We grew the pH5 and pH7 unlabelled cell cultures in triplicate resulting in 6 biological replicates. Each biological replicate was mixed with a common ¹⁵N-labeled reference culture cells for normalization prior to SDS/PAGE fractionation and LC/MS analysis. For each biological replicate, one center SDS/PAGE gel fraction was selected for triplicate LC/MS analysis. There were 121 proteins quantified in at least 5 of the 6 biological replicates. Of these 121 proteins, 106 were significant in differential expression by the <it>t</it>-test (<it>p </it>< 0.05) based on peptide-level replicates, 54 were significant in differential expression by SAM with Δ = 0.68 cutoff and false positive rate at 5%, and 29 were significant in differential expression by the <it>t</it>-test (<it>p </it>< 0.05) based on protein-level replicates. The results indicate that SAM appears to overcome the false positives one encounters using the peptide-based <it>t</it>-test while allowing for identification of a greater number of differentially expressed proteins than the protein-based <it>t</it>-test.</p> <p>Conclusion</p> <p>We demonstrate that the SAM method can be adapted for effective significance analysis of proteomic data. It provides much richer information about the protein differential expression profiles and is particularly useful in the estimation of false discovery rates and miss rates.</p

TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis

Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. Methodology/Principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.</p> <p>Objectives</p> <p>To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.</p> <p>Methods</p> <p>E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.</p> <p>Results</p> <p>pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (<it>p </it>= 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (<it>p </it>= 0.005) in univariate and multivariate analysis.</p> <p>Conclusion</p> <p>These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx.</p> <p><b>Level of evidence: 2b</b></p

Cognitive and cognitive-motor interventions affecting physical functioning: A systematic review

Background Several types of cognitive or combined cognitive-motor intervention types that might influence physical functions have been proposed in the past: training of dual-tasking abilities, and improving cognitive function through behavioral interventions or the use of computer games. The objective of this systematic review was to examine the literature regarding the use of cognitive and cognitive-motor interventions to improve physical functioning in older adults or people with neurological impairments that are similar to cognitive impairments seen in aging. The aim was to identify potentially promising methods that might be used in future intervention type studies for older adults. Methods A systematic search was conducted for the Medline/Premedline, PsycINFO, CINAHL and EMBASE databases. The search was focused on older adults over the age of 65. To increase the number of articles for review, we also included those discussing adult patients with neurological impairments due to trauma, as these cognitive impairments are similar to those seen in the aging population. The search was restricted to English, German and French language literature without any limitation of publication date or restriction by study design. Cognitive or cognitive-motor interventions were defined as dual-tasking, virtual reality exercise, cognitive exercise, or a combination of these. Results 28 articles met our inclusion criteria. Three articles used an isolated cognitive rehabilitation intervention, seven articles used a dual-task intervention and 19 applied a computerized intervention. There is evidence to suggest that cognitive or motor-cognitive methods positively affects physical functioning, such as postural control, walking abilities and general functions of the upper and lower extremities, respectively. The majority of the included studies resulted in improvements of the assessed functional outcome measures. Conclusions The current evidence on the effectiveness of cognitive or motor-cognitive interventions to improve physical functioning in older adults or people with neurological impairments is limited. The heterogeneity of the studies published so far does not allow defining the training methodology with the greatest effectiveness. This review nevertheless provides important foundational information in order to encourage further development of novel cognitive or cognitive-motor interventions, preferably with a randomized control design. Future research that aims to examine the relation between improvements in cognitive skills and the translation to better performance on selected physical tasks should explicitly take the relation between the cognitive and physical skills into account.ISSN:1471-231

Diverse Effects on Mitochondrial and Nuclear Functions Elicited by Drugs and Genetic Knockdowns in Bloodstream Stage Trypanosoma brucei

The parasite Trypanosoma brucei causes human African trypanosomiasis, which is fatal unless treated. Currently used drugs are toxic, difficult to administer, and often are no longer effective due to drug resistance. The search for new drugs is long and expensive, and determining which compounds are worth pursuing is a key challenge in that process. In this study we sought to determine whether different compounds elicited different responses in the mammalian-infective stage of the parasite. We also examined whether genetic knockdown of parasite molecules led to similar responses. Our results show that, depending on the treatment, the replication of the parasite genomes, proper division of the cell, and mitochondrial function can be affected. Surprisingly, these different responses were not able to predict which compounds affected the long term proliferative potential of T. brucei. We found that some of the compounds had irreversible effects on the parasites within one day, so that even cells that appeared healthy could not proliferate. We suggest that determining which compounds set the parasites on a one-way journey to death may provide a means of identifying those that could lead to drugs with high efficacy