Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration

Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-α (TNF-α) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-α in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration

Understanding the Uniqueness of 2p Elements in Periodic Tables

The Periodic Table, and the unique chemical behavior of the first element in a column (group), were discovered simultaneously one and a half centuries ago. Half a century ago, this unique chemistry of the light homologs was correlated to the then available atomic orbital (AO) radii. The radially nodeless 1s, 2p, 3d, 4f valence AOs are particularly compact. The similarity of r(2s)approximate to r(2p) leads to pronounced sp-hybrid bonding of the light p-block elements, whereas the heavier p elements with n >= 3 exhibit r(ns) MUCH LESS-THAN r(np) of approximately -20 to -30 %. Herein, a comprehensive physical explanation is presented in terms of kinetic radial and angular, as well as potential nuclear-attraction and electron-screening effects. For hydrogen-like atoms and all inner shells of the heavy atoms, r(2s) >> r(2p) by +20 to +30 %, whereas r(3s)greater than or similar to r(3p)greater than or similar to r(3d), since in Coulomb potentials radial motion is more radial orbital expanding than angular motion. However, the screening of nuclear attraction by inner core shells is more efficient for s than for p valence shells. The uniqueness of the 2p AO is explained by this differential shielding. Thereby, the present work paves the way for future physical explanations of the 3d, 4f, and 5g cases.Peer reviewe

Type IIn Supernova SN 2010jl: Optical Observations for Over 500 Days After Explosion

We present extensive optical observations of a Type IIn supernova (SN) 2010jl for the first 1.5 years after the discovery. The UBVRI light curves demonstrated an interesting two-stage evolution during the nebular phase, which almost flatten out after about 90 days from the optical maximum. SN 2010jl has one of the highest intrinsic H_alpha luminosity ever recorded for a SN IIn, especially at late phase, suggesting a strong interaction of SN ejecta with the dense circumstellar material (CSM) ejected by the progenitor. This is also indicated by the remarkably strong Balmer lines persisting in the optical spectra. One interesting spectral evolution about SN 2010jl is the appearance of asymmetry of the Balmer lines. These lines can be well decomposed into a narrow component and an intermediate-width component. The intermediate-width component showed a steady increase in both strength and blueshift with time until t ~ 400 days after maximum, but it became less blueshifted at t ~ 500 days when the line profile appeared relatively symmetric again. Owing to that a pure reddening effect will lead to a sudden decline of the light curves and a progressive blueshift of the spectral lines, we therefore propose that the asymmetric profiles of H lines seen in SN 2010jl is unlikely due to the extinction by newly formed dust inside the ejecta, contrary to the explanation by some early studies. Based on a simple CSM-interaction model, we speculate that the progenitor of SN 2010jl may suffer a gigantic mass loss (~ 30-50 M_sun) in a few decades before explosion. Considering a slow moving stellar wind (e.g., ~ 28 km/s) inferred for the preexisting, dense CSM shell and the extremely high mass-loss rate (1-2 M_sun per yr), we suggest that the progenitor of SN 2010jl might have experienced a red supergiant stage and explode finally as a post-red supergiant star with an initial mass above 30-40 M_sun.Comment: 34 pages, 9 figures, accepted for publication in A

Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer

Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B). We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients

Body silhouette, menstrual function at adolescence and breast cancer risk in the E3N cohort study

We analysed the relation between adult breast cancer risk and adiposity in ages 8–25, and among 90 509 women included in the E3N cohort study, and investigated the potential modification effect of certain factors. Participants completed a questionnaire that included a set of eight silhouettes corresponding to body shape at different ages. During the follow-up (mean=11.4 years), 3491 breast cancer cases were identified. Negative trends in risk of breast cancer with increasing body silhouettes at age 8 and at menarche were observed, irrespective of menopausal status, with relative risks of 0.73 (0.53–0.99) and 0.82 (0.66–1.02) for women who reported a silhouette equal or greater than the fifth silhouette at age 8 and at menarche, respectively. We observed no clear effect modification by age at menarche, delay between age at menarche, regular cycling, regularity of cycles in adult life or body mass index at baseline

SN 2010ay is a Luminous and Broad-lined Type Ic Supernova within a Low-metallicity Host Galaxy

We report on our serendipitous pre-discovery detection and detailed follow-up of the broad-lined Type Ic supernova (SN) 2010ay at z = 0.067 imaged by the Pan-STARRS1 3pi survey just ~4 days after explosion. The SN had a peak luminosity, M_R ~ -20.2 mag, significantly more luminous than known GRB-SNe and one of the most luminous SNe Ib/c ever discovered. The absorption velocity of SN 2010ay is v_Si ~ 19,000 km/s at ~40 days after explosion, 2-5 times higher than other broad-lined SNe and similar to the GRB-SN 2010bh at comparable epochs. Moreover, the velocity declines ~2 times slower than other SNe Ic-BL and GRB-SNe. Assuming that the optical emission is powered by radioactive decay, the peak magnitude implies the synthesis of an unusually large mass of 56 Ni, M_Ni = 0.9 M_solar. Modeling of the light-curve points to a total ejecta mass, M_ej ~ 4.7 M_sol, and total kinetic energy, E_K ~ 11x10^51 ergs. The ratio of M_Ni to M_ej is ~2 times as large for SN 2010ay as typical GRB-SNe and may suggest an additional energy reservoir. The metallicity (log(O/H)_PP04 + 12 = 8.19) of the explosion site within the host galaxy places SN 2010ay in the low-metallicity regime populated by GRB-SNe, and ~0.5(0.2) dex lower than that typically measured for the host environments of normal (broad-lined) Ic supernovae. We constrain any gamma-ray emission with E_gamma < 6x10^{48} erg (25-150 keV) and our deep radio follow-up observations with the Expanded Very Large Array rule out relativistic ejecta with energy, E > 10^48 erg. We therefore rule out the association of a relativistic outflow like those which accompanied SN 1998bw and traditional long-duration GRBs, but place less-stringent constraints on a weak afterglow like that seen from XRF 060218. These observations challenge the importance of progenitor metallicity for the production of a GRB, and suggest that other parameters also play a key role.Comment: 19 pages, 10 figures, V3 has revisions following referee's report; more information at http://www.cfa.harvard.edu/~nsanders/papers/2010ay/summary.htm

Supramolecular electrode assemblies for bioelectrochemistry

For more than three decades, the field of bioelectrochemistry has provided novel insights into the catalytic mechanisms of enzymes, the principles that govern biological electron transfer, and has elucidated the basic principles for bioelectrocatalytic systems. Progress in biochemistry, bionanotechnology, and our ever increasing ability to control the chemistry and structure of electrode surfaces has enabled the study of ever more complex systems with bioelectrochemistry. This feature article highlights developments over the last decade, where supramolecular approaches have been employed to develop electrode assemblies that increase enzyme loading on the electrode or create more biocompatible environments for membrane enzymes. Two approaches are particularly highlighted: the use of layer-by-layer assembly, and the modification of electrodes with planar lipid membranes