Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy.

Dominant mutations in glycyl-tRNA synthetase (GlyRS) cause a subtype of Charcot-Marie-Tooth neuropathy (CMT2D). Although previous studies have shown that GlyRS mutants aberrantly interact with Nrp1, giving insight into the disease\u27s specific effects on motor neurons, these cannot explain length-dependent axonal degeneration. Here, we report that GlyRS mutants interact aberrantly with HDAC6 and stimulate its deacetylase activity on α-tubulin. A decrease in α-tubulin acetylation and deficits in axonal transport are observed in mice peripheral nerves prior to disease onset. An HDAC6 inhibitor used to restore α-tubulin acetylation rescues axonal transport deficits and improves motor functions of CMT2D mice. These results link the aberrant GlyRS-HDAC6 interaction to CMT2D pathology and suggest HDAC6 as an effective therapeutic target. Moreover, the HDAC6 interaction differs from Nrp1 interaction among GlyRS mutants and correlates with divergent clinical presentations, indicating the existence of multiple and different mechanisms in CMT2D. Nat Commun 2018 Mar 8; 9(1):1007

Structure−Property Relationships for Two-Photon Absorbing Chromophores: Bis-Donor Diphenylpolyene and Bis(styryl)benzene Derivatives

The two-photon absorption properties of a series of bis dialkylamino- or diarylamino-substituted diphenylpolyenes and bis(styryl)benzenes have been investigated. Two-photon absorption cross sections, δ, as large as 1420 × 10^(-50) cm^4 s/photon-molecule have been observed for molecules with this general bis-donor structure. The effect of the type and length of the conjugated chain and of dialkylamino or diarylamino substitution on the position and magnitude of the peak two-photon absorptivity is reported. The transition dipole moments for the transitions between the ground state and the first excited singlet state (M_(ge)) and between the first and second excited singlet states (M_(ee‘)) have been estimated using experimental data from the one- and two-photon spectra. It was found that increases in chain length result mainly in an increase in M_(ge), whereas the addition of donor end groups or going from diphenylpolyene- to phenylene-vinylene-type bridges leads primarily to an increase in Mee‘. The trends in the energy of the lowest excited singlet states and in the transition moments for the diphenylpolyene series as a function of chain length are in agreement with those calculated by quantum mechanical methods. These results furnish a link between structural features in these classes of molecules and the electronic dipole couplings and state energies that control the strength of the two-photon absorption. In bis(aminophenyl)polyenes containing up to four double bonds (m) the lowest excited singlet state is a B_u state, as opposed to the case of simple polyenes and diphenylpolyenes, for which it is an A_g state for m > 2. The relationship of the state ordering in these systems with the observed values of the radiative and nonradiative decay rates is also discussed

Structure and Photoluminescent Properties of ZnO Encapsulated in Mesoporous Silica SBA-15 Fabricated by Two-Solvent Strategy

The two-solvent method was employed to prepare ZnO encapsulated in mesoporous silica (ZnO/SBA-15). The prepared ZnO/SBA-15 samples have been studied by X-ray diffraction, transmission electron microscope, X-ray photoelectron spectroscopy, nitrogen adsorption–desorption isotherm, and photoluminescence spectroscopy. The ZnO/SBA-15 nanocomposite has the ordered hexagonal mesostructure of SBA-15. ZnO clusters of a high loading are distributed in the channels of SBA-15. Photoluminescence spectra show the UV emission band around 368 nm, the violet emission around 420 nm, and the blue emission around 457 nm. The UV emission is attributed to band-edge emission of ZnO. The violet emission results from the oxygen vacancies on the ZnO–SiO2interface traps. The blue emission is from the oxygen vacancies or interstitial zinc ions of ZnO. The UV emission and blue emission show a blue-shift phenomenon due to quantum-confinement-induced energy gap enhancement of ZnO clusters. The ZnO clusters encapsulated in SBA-15 can be used as light-emitting diodes and ultraviolet nanolasers

Structure and Luminescence Properties of Eu3+-Doped Cubic Mesoporous Silica Thin Films

Eu3+ ions-doped cubic mesoporous silica thin films with a thickness of about 205 nm were prepared on silicon and glass substrates using triblock copolymer as a structure-directing agent using sol–gel spin-coating and calcination processes. X-ray diffraction and transmission electron microscopy analysis show that the mesoporous silica thin films have a highly ordered body-centered cubic mesoporous structure. High Eu3+ ion loading and high temperature calcination do not destroy the ordered cubic mesoporous structure of the mesoporous silica thin films. Photoluminescence spectra show two characteristic emission peaks corresponding to the transitions of5D0-7F1 and 5D0-7F2 of Eu3+ ions located in low symmetry sites in mesoporous silica thin films. With the Eu/Si molar ratio increasing to 3.41%, the luminescence intensity of the Eu3+ ions-doped mesoporous silica thin films increases linearly with increasing Eu3+ concentration

Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

Background: Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Methods: Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. Results: The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 +/- 3.19 vs. 361.29 +/- 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027). Conclusions: High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000285251600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701OncologySCI(E)26ARTICLEnull1

Reduction of Mitoferrin Results in Abnormal Development and Extended Lifespan in Caenorhabditis elegans

Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. Mitoferrin 1 is highly expressed in developing erythrocytes which consume a large amount of iron during hemoglobinization. Mitoferrin 2 is ubiquitously expressed, whose functions are less known. Zebrafish with mitoferrin 1 mutation show profound hypochromic anaemia and erythroid maturation arrests, and yeast with defects in MRS3/4, the counterparts of mitoferrin 1/2, has low mitochondrial iron levels and grows poorly by iron depletion. Mitoferrin 1 expression is up-regulated in yeast and mouse models of Fiedreich's ataxia disease and in human cell culture models of Parkinson disease, suggesting its involvement in the pathogenesis of diseases with mitochondrial iron accumulation. In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages