Developmental hypomyelination in Wolfram syndrome: New insights from neuroimaging and gene expression analyses

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration

Enhancement of the mechanical properties of lysine-containing peptide-based supramolecular hydrogels by chemical cross-linking

Exposure of lysine-containing peptide-based gelators to the cross-linking agent glutaraldehyde allows tuning of gel mechanical properties. The effect of cross-linking depends on the position of the lysine residue in the peptide chain, the concentration of gelator and the conditions under which cross-linking takes place. Through control of these factors, cross-linking leads to increased gel strength

The transiting multi-planet system HD3167: a 5.7 MEarth Super-Earth and a 8.3 MEarth mini-Neptune

HD3167 is a bright (V=8.9 mag) K0V star observed by the NASA's K2 space mission during its Campaign 8. It has been recently found to host two small transiting planets, namely, HD3167b, an ultra short period (0.96 d) super-Earth, and HD3167c, a mini-Neptune on a relatively long-period orbit (29.85 d). Here we present an intensive radial velocity follow-up of HD3167 performed with the FIES@NOT, [email protected], and HARPS-N@TNG spectrographs. We revise the system parameters and determine radii, masses, and densities of the two transiting planets by combining the K2 photometry with our spectroscopic data. With a mass of 5.69+/-0.44 MEarth, radius of 1.574+/-0.054 REarth, and mean density of 8.00(+1.0)(-0.98) g/cm^3, HD3167b joins the small group of ultra-short period planets known to have a rocky terrestrial composition. HD3167c has a mass of 8.33 (+1.79)(-1.85) MEarth and a radius of 2.740(+0.106)(-0.100) REarth, yielding a mean density of 2.21(+0.56)(-0.53) g/cm^3, indicative of a planet with a composition comprising a solid core surrounded by a thick atmospheric envelope. The rather large pressure scale height (about 350 km) and the brightness of the host star make HD3167c an ideal target for atmospheric characterization via transmission spectroscopy across a broad range of wavelengths. We found evidence of additional signals in the radial velocity measurements but the currently available data set does not allow us to draw any firm conclusion on the origin of the observed variation.Comment: 18 pages, 11 figures, 5 table

2017-2018 Mostly Music: Ludwig van Beethoven

https://spiral.lynn.edu/conservatory_mostlymusic/1030/thumbnail.jp

Enhancing Quality and Impact of Early Phase Dose-Finding Clinical Trial Protocols:The SPIRIT DoseFinding Extension (SPIRIT-DEFINE) Guidance The SPIRIT-DEFINE Statement

International audienc

Enhancing Reporting Quality and Impact of Early Phase Dose-Finding Clinical Trials:The CONSORT Dose-Finding Extension (CONSORT-DEFINE) Guidance The CONSORT-DEFINE Statement

International audienceThe CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. The CONSORT Dose-finding Extension (DEFINE) extends the guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such trials generally focus on safety, tolerability, activity, and recommending dosing and scheduling regimens for further clinical development. These trials are often inadequately reported, hampering their informativeness and making evidence informed decisions difficult. The CONSORT-DEFINE guidance aims to develop an international, consensus driven guideline for reporting early phase dose-finding trials to promote transparency, completeness, reproducibility, and facilitate the interpretation of the results. The CONSORT-DEFINE guidance provides recommendations for essential items that should be reported in early phase dose-finding trials to promote greater clarity, reproducibility, informativeness, and usefulness of results