A shared antigenic determinant between natural killer cells and nervous tissue

Considerable evidence for shared antigenic determinants between nervous elements and lymphocytes has accumulated. It has also been suggested that this cross-recognition may be involved in the pathogenesis of human neurological diseases such as myasthenia gravis and multiple sclerosis. We report here evidence that a marker for natural killer (NK) cells, anti-Leu-7 (HNK-1), specifically binds to components of human and rodent central nervous tissue as well as peripheral nervous tissue, especially to myelin sheaths. In contrast, another NK-cell marker (VEP13) did not react with nervous tissue. Since NK-cell function is impaired in a population of multiple sclerosis patients, the observed cross-reactivity indicates that autosensitization against myelin may simultaneously cause a defect of NK-cell function. Furthermore, the shared antigenic determinant may help to identify a hitherto undefined nervous tissue antigen and simultaneously increase the knowledge about the nature of NK-cell antigens.     

Conduction,automaticity, and tonus of visceral muscles

Résumé Les muscles lisses des Vertébrés appartiennent à deux catégories: ceux des viscères, lesquels ont une fonction automatique, et ceux qui comme les muscles des vaisseaux sanguins sont innervés par les nerfs moteurs. Les propriétés physiologiques des muscles lisses viscéraux sont très semblables à celles du muscle cardiaque ainsi que l'a montré l'étude de la conduction, du potentiel d'action et des effets du courant électrique. Les particularités des muscles lisses viscéraux tiennent en grande partie à la lenteur de leur réaction et aux fluctuations que présente leur excitabilité. Cette dernière est influencée par des facteurs tels que des hormones, des excitations transmises par les nerfs extrinsèques et, dans le cas de l'intestin, par le système nerveux intrinsèque. Les contractions spontanées débutent par une activité locale qui augmente lentement et se manifeste par un changement du potentiel et un accroissement du «tonus». Le tonus se produit dans les muscles lisses par diverses modifications de l'état physiologique. Rien ne prouve qu'il soit provoqué par un mécanisme essentiellement différent de celui des contractions rapides.     

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.     

"Add-on" domains of<Emphasis Type="Italic"> Drosophila</Emphasis> β1,4-<Emphasis Type="Italic">N</Emphasis>-acetylgalactosaminyltransferase B in the stem region and its pilot protein

The glycolipid specific Drosophila melanogaster β1,4-N-acetylgalactosaminyltransferase B (β4GalNAcTB) depends on a zinc finger DHHC protein family member named GalNAcTB pilot (GABPI) for activity and translocation to the Golgi. The six-membrane spanning protein actually lacks the cysteine in the cytoplasmic DHHC motif, displaying DHHS instead. Here we show that the whole conserved region around the DHHS sequence, which is essential for palmitoylation in DHHC proteins, is not required for GABPI to interact with β4GalNAcTB. In contrast, the two luminal loops between transmembrane domain 3–4 and 5–6 contain conserved amino acids, which are crucial for activity. Besides the dependence on GABPI, β4GalNAcTB requires its exceptional short stem region for activity. A few hydrophobic amino acids positioned close to the transmembrane domain are essential for the interaction with GABPI. Along with its catalytic domain, β4GalNAcTB, thus, requires an area in its own stem region and two small luminal loops of GABPI as "add-on" domains. Moreover, some inactive GABPI mutants could be rescued by fusion with β4GalNAcTB, indicating their importance in direct GABPI-β4GalNAcTB interaction.     

Identification of ten loci associated with height highlights new biological pathways in human growth

Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.     

Effect of moisture on the aging behavior of asphalt binder

The moisture aging effect and mechanism of asphalt binder during the in-service life of pavement were investigated by laboratory simulating tests. Pressure aging vessel (PAV) test simulating the long-term aging of binder during the in-service life of pavement was modified to capture the long-term moisture aging effect of binder. Penetration grade tests including penetration test, soften point test, and ductility test as well as SuperpaveTM performance grade tests including viscosity test, dynamic shear rheometer test, and bending beam rheometer test were conducted to fully evaluate the moisture aging effect of binder. Fourier transform infrared spectroscopy test and Gel-permeation chromatography test were applied to provide a fundamental understanding of the moisture aging mechanism of binder. The results indicate that moisture condition can accelerate the aging of asphalt binder and shorten the service life of asphalt binder. The modified PAV test with moisture condition can well characterize the moisture aging properties of asphalt binder.     

Warming experiments underpredict plant phenological responses to climate change

Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.     

Region of Interest Imaging for a General Trajectory with the Rebinned BPF Algorithm

The back-projection-filtration(BPF) algorithm has been applied to image reconstruction for cone-beam configurations with general source trajectories.The BPF algorithm can reconstruct 3-D region-of-interest(ROI) images from data containing truncations.However,like many other existing algorithms for cone-beam configurations,the BPF algorithm involves a back-projection with a spatially varying weighting factor,which can result in the non-uniform noise levels in reconstructed images and increased computation ti...