High-Resolution Spectroscopy of Some Very Active Southern Stars

We have obtained high-resolution echelle spectra of 18 solar-type stars that an earlier survey showed to have very high levels of Ca II H and K emission. Most of these stars belong to close binary systems, but 5 remain as probable single stars or well-separated binaries that are younger than the Pleiades on the basis of their lithium abundances and H-alpha emission. Three of these probable single stars also lie more than 1 magnitude above the main sequence in a color-magnitude diagram, and appear to have ages of 10 to 15 Myr. Two of them, HD 202917 and HD 222259, also appear to have a kinematical association with the pre-main sequence multiple system HD 98800.Comment: 25 figures, 3 table

Early-stage [123I]beta-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease

beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. CONCLUSION: [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual case

Joint Evolutionary Trees: A Large-Scale Method To Predict Protein Interfaces Based on Sequence Sampling

The Joint Evolutionary Trees (JET) method detects protein interfaces, the core residues involved in the folding process, and residues susceptible to site-directed mutagenesis and relevant to molecular recognition. The approach, based on the Evolutionary Trace (ET) method, introduces a novel way to treat evolutionary information. Families of homologous sequences are analyzed through a Gibbs-like sampling of distance trees to reduce effects of erroneous multiple alignment and impacts of weakly homologous sequences on distance tree construction. The sampling method makes sequence analysis more sensitive to functional and structural importance of individual residues by avoiding effects of the overrepresentation of highly homologous sequences and improves computational efficiency. A carefully designed clustering method is parametrized on the target structure to detect and extend patches on protein surfaces into predicted interaction sites. Clustering takes into account residues' physical-chemical properties as well as conservation. Large-scale application of JET requires the system to be adjustable for different datasets and to guarantee predictions even if the signal is low. Flexibility was achieved by a careful treatment of the number of retrieved sequences, the amino acid distance between sequences, and the selective thresholds for cluster identification. An iterative version of JET (iJET) that guarantees finding the most likely interface residues is proposed as the appropriate tool for large-scale predictions. Tests are carried out on the Huang database of 62 heterodimer, homodimer, and transient complexes and on 265 interfaces belonging to signal transduction proteins, enzymes, inhibitors, antibodies, antigens, and others. A specific set of proteins chosen for their special functional and structural properties illustrate JET behavior on a large variety of interactions covering proteins, ligands, DNA, and RNA. JET is compared at a large scale to ET and to Consurf, Rate4Site, siteFiNDER|3D, and SCORECONS on specific structures. A significant improvement in performance and computational efficiency is shown

Plasma cholesterol levels and brain development in preterm newborns.

BackgroundTo assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns.MethodsSixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition.ResultsEarly plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.ConclusionsHigher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes

A newcastle disease virus (NDV) expressing a membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent coronavirus disease 2019 (COVID-19) vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine

Destination development in Western Siberia:Tourism governance and evolutionary economic geography

Tourism development has often been identified as a tool for balancing negative effects of economic restructuring, especially in peripheral regions. Tourism-based activities often utilize the availability of abundant nature, but although most English language studies of destination development are presented from western contexts, examples from post-Soviet Russia are rare. Western Siberia is a periphery with access to natural resources and heavy industrialization but remotely located from domestic (Russian) and international markets, where tourism is often considered a saviour, especially for the regional economies. Stakeholders in this Russian resource periphery face challenges in managing governance and cooperation in destinations development due to frequent institutional, economic and social changes. Using evolutionary economic geography and based on primary sources and interview data, tourism development and stakeholder relations are assessed in three Western Siberia regions: Tomsk, Kemerovo and Altai Krai. Findings show that for tourism to make a significant contribution, it must be more central to the economic development agenda in all three regions. However, it is currently only achieving a permanent high-profile in one of them, being crowded out by other (mostly primary) industries in the other two. Although the specific tourism governance set-up varies between the three regions, it is clear that public tourism governance still sits somewhat uneasily between state control and the market economy. Tourism receives substantial public subsidies, especially in large-scale investment projects, which depend on federal support within a governance system where decentralization seems to be somewhat limited and unstable. As a result, the tourism path development in the Siberian periphery is highly dependent on state intervention and success in other sectors.</p

Natural history of ROHHAD syndrome: development of severe insulin resistance and fatty liver disease over time

Absract Background Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare syndrome with unknown etiology. Metabolic abnormalities are not known to be part of the syndrome. We present one of the oldest cases reported in the literature, who developed severe metabolic abnormalities and hepatic disease suggesting that these features may be part of the syndrome. Case presentation A 27-year-old woman, diagnosed with ROHHAD syndrome at age 15, who previously developed diabetes insipidus, growth hormone deficiency, hyperprolactinemia, and hypothyroidism in her first decade of life. This was followed by insulin resistance, NAFLD, liver fibrosis, and splenomegaly before age 14 years. Her regimen included a short course of growth hormone, and cyclic estrogen and progesterone. Her metabolic deterioration continued despite treatment with metformin. Interestingly, she had a favorable response to liraglutide therapy despite having a centrally mediated cause for her obesity. At age 26, a 1.6 cm lesion was found incidentally in her liver. Liver biopsy showed hepatocellular carcinoma which was successfully treated with radiofrequency ablation. Conclusion Metabolic abnormalities, Insulin resistance and fatty liver disease are potentially part of the ROHHAD syndrome that may develop over time. GLP1 agonists were reasonably effective to treat insulin resistance and hyperphagia. Patients with ROHHAD may benefit from close follow up in regards to liver disease.https://deepblue.lib.umich.edu/bitstream/2027.42/152179/1/40842_2019_Article_82.pd

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Prediction of catalytic residues using Support Vector Machine with selected protein sequence and structural properties

BACKGROUND: The number of protein sequences deriving from genome sequencing projects is outpacing our knowledge about the function of these proteins. With the gap between experimentally characterized and uncharacterized proteins continuing to widen, it is necessary to develop new computational methods and tools for functional prediction. Knowledge of catalytic sites provides a valuable insight into protein function. Although many computational methods have been developed to predict catalytic residues and active sites, their accuracy remains low, with a significant number of false positives. In this paper, we present a novel method for the prediction of catalytic sites, using a carefully selected, supervised machine learning algorithm coupled with an optimal discriminative set of protein sequence conservation and structural properties. RESULTS: To determine the best machine learning algorithm, 26 classifiers in the WEKA software package were compared using a benchmarking dataset of 79 enzymes with 254 catalytic residues in a 10-fold cross-validation analysis. Each residue of the dataset was represented by a set of 24 residue properties previously shown to be of functional relevance, as well as a label {+1/-1} to indicate catalytic/non-catalytic residue. The best-performing algorithm was the Sequential Minimal Optimization (SMO) algorithm, which is a Support Vector Machine (SVM). The Wrapper Subset Selection algorithm further selected seven of the 24 attributes as an optimal subset of residue properties, with sequence conservation, catalytic propensities of amino acids, and relative position on protein surface being the most important features. CONCLUSION: The SMO algorithm with 7 selected attributes correctly predicted 228 of the 254 catalytic residues, with an overall predictive accuracy of more than 86%. Missing only 10.2% of the catalytic residues, the method captures the fundamental features of catalytic residues and can be used as a "catalytic residue filter" to facilitate experimental identification of catalytic residues for proteins with known structure but unknown function

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling

Nephrotic syndrome (NS) is divided into steroid-sensitive (SSNS) and -resistant (SRNS) variants. SRNS causes end-stage kidney disease, which cannot be cured. While the disease mechanisms of NS are not well understood, genetic mapping studies suggest a multitude of unknown single-gene causes. We combined homozygosity mapping with whole-exome resequencing and identified an ARHGDIA mutation that causes SRNS. We demonstrated that ARHGDIA is in a complex with RHO GTPases and is prominently expressed in podocytes of rat glomeruli. ARHGDIA mutations (R120X and G173V) from individuals with SRNS abrogated interaction with RHO GTPases and increased active GTP-bound RAC1 and CDC42, but not RHOA, indicating that RAC1 and CDC42 are more relevant to the pathogenesis of this SRNS variant than RHOA. Moreover, the mutations enhanced migration of cultured human podocytes; however, enhanced migration was reversed by treatment with RAC1 inhibitors. The nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish. RAC1 inhibitors were partially effective in ameliorating arhgdia-associated defects. These findings identify a single-gene cause of NS and reveal that RHO GTPase signaling is a pathogenic mediator of SRNS.ope