149 research outputs found
Verslag van een reis ter bestudering van de rundveehouderij en de varkenshouderij in Denemarken
The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1
First described in 1991, Yin Yang 1 (YY1) is a transcription factor that is ubiquitously
expressed throughout mammalian cells. It regulates both transcriptional activation and
repression, in a seemingly context-dependent manner. YY1 has a well-established role
in the development of the central nervous system, where it is involved in neurogenesis
and maintenance of homeostasis in the developing brain. In neurodevelopmental and
neurodegenerative disease, the crucial role of YY1 in cellular processes in the central
nervous system is further underscored. In this mini-review, we discuss the various
mechanisms leading to the transcriptional activating and repressing roles of YY1,
including its role as a traditional transcription factor, its interactions with cofactors and
chromatin modifiers, the role of YY1 in the non-coding genome and 3D chromatin
organization and the possible implications of the phase-separation mechanism on YY1
function. We provide examples on how these processes can be involved in normal
development and how alterations can lead to various diseases
Shedding a light on the physical stability of suspensions micronised with intensified vibratory milling; A trend observed with decreasing particle size as a function of time
Benzylation of hydroxy groups with tertiary amine as a base
The benzylation of hydroxy groups in the presence of tertiary amines is described. A mixture of an alcohol and a benzyl halide afforded the corresponding benzyl ether in good to excellent yields in the presence of diisopropylethylamine. The importance of solventless conditions was observed. The reaction showed high tolerance to many functional groups including benzoate, even at a reaction temperature of 150 °C. Sodium iodide was found to be an efficient catalyst to accelerate the reaction
Transcriptome analysis reveals tumor microenvironment changes in glioblastoma
A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells
Comparative effectiveness of autologous hematopoietic stem cell transplant vs fingolimod, natalizumab, and ocrelizumab in highly active relapsing-remitting multiple sclerosis
Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).
Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.
Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.
Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab.
Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.
Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).
Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time
Decoding Blockchain for Business: Understand the Tech and Prepare for the Blockchain Future
ChemInform Abstract: Intramolecular 1,3-Diyl Trapping Reactions. A Formal Total Synthesis of (±)-Coriolin.
ChemInform Abstract: A Practical Procedure for the Conversion of Aldehydes to Terminal Alkynes by a One Carbon Homologation.
Make Your Organization a Center of Innovation: Tools and Concepts to Solve Problems and Generate Ideas
- …