Synergistic anion-π interactions in peptidomimetic polyethers.

Anion-π interactions are crucial in various biological processes, such as enzyme catalysis and ion transport. Despite their significance, the exploitation of anion-π interactions in synthetic polymer systems remains underexplored. This study investigates anion-π interactions using chemically well-defined peptidomimetics guided by the composition of mussel foot proteins.

Na-Complexed Dendritic Polyglycerols for Recovery of Frozen Cells and Their Network in Media.

In this study, a novel phenomenon is identified where precise control of topology and generation of polyglycerol induce the retention of Na ions in biological buffer systems, effectively inhibiting ice crystal growth during cryopreservation. Unlike linear and hyperbranched counterparts, densely-packed hydroxyl and ether groups in 4th-generation dendritic polyglycerol interact with the ions, activating the formation of hydrogen bonding at the ice interface. By inhibiting both intra- and extracellular ice growth and recrystallization, this biocompatible dendritic polyglycerol proves highly effective as a cryoprotectant; hence, achieving the cell recovery rates of ≈134-147%, relative to those of 10% dimethyl sulfoxide, which is a conventional cryoprotectant for human tongue squamous carcinoma (HSC-3) cell line and human umbilical vein endothelial (HUVEC) cells.

Synergistic Effect of Polyglycerol and DMSO for Long-Term Cryopreservation of Species.

Herein, we present a significant advancement in long-term cryopreservation techniques for microalgae species using a combination of linear polyglycerol (PG) and dimethyl sulfoxide (DMSO). The technique was tested on three species: , , and , which showed long-term viability and recovery rates superior to those when treated with a traditional cryoprotectant only. While DMSO alone enabled high cell recovery rates for all species after 1 week of cryopreservation, the rates for some of them dropped below 50% after 26 weeks of cryopreservation.

C-H Functionalization of Poly(ethylene oxide) - Embracing Functionality, Degradability, and Molecular Delivery.

This study presents an organocatalytic C-H functionalization approach for postpolymerization modification (PPM) of poly(ethylene oxide) (PEO). Most of PEO PPM is previously processed at the end hydroxy group, but recent advances in C-H functionalization open a way to modify the backbone position. Structurally diverse carboxylic acids are attached to PEO through a cascade process of radical generation by peroxide and oxidation to oxocarbenium by tertiary butylammonium iodide.

Combinatorial clustering of distinct DNA motifs directs synergistic binding of dosage compensation complex to X chromosomes.

Organisms that count X-chromosome number to determine sex utilize dosage compensation mechanisms to balance X-gene expression between sexes. Typically, a regulatory complex is recruited to X chromosomes of one sex to modulate gene expression. A major challenge is to determine the mechanisms that target regulatory complexes specifically to X.

Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in huntingtin (). Given an important role for in development and significant neurodegeneration at the time of clinical manifestation in HD, early treatment of allele-specific drugs represents a promising strategy. The feasibility of an allele-specific antisense oligonucleotide (ASO) targeting single-nucleotide polymorphisms (SNPs) has been demonstrated in models of HD.

Impact of Neonatal Activation of Nuclear Receptor CAR (Nr1i3) on Cyp2 Gene Expression in Adult Mouse Liver.

Perinatal exposure to environmental chemicals is proposed to reprogram development and alter disease susceptibility later in life. Supporting this, neonatal activation of the nuclear receptor constitutive androstane receptor (CAR) (Nr1i3) by TCPOBOP was previously reported to induce persistent expression of mouse hepatic Cyp2 genes into adulthood, and was attributed to long-term epigenetic memory of the early life exposure. Here, we confirm that the same high-dose neonatal TCPOBOP exposure studied previously (3 mg/kg, 15x ED50) does indeed induce prolonged (12 weeks) increases in hepatic Cyp2 expression; however, we show that the persistence of expression can be fully explained by the persistence of residual TCPOBOP in liver tissue.

X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation.

Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-sized topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundaries.

Widespread Epigenetic Changes to the Enhancer Landscape of Mouse Liver Induced by a Specific Xenobiotic Agonist Ligand of the Nuclear Receptor CAR.

Constitutive androstane receptor (CAR) (Nr1i3), a liver nuclear receptor and xenobiotic sensor, induces drug, steroid, and lipid metabolism and dysregulates genes linked to hepatocellular carcinogenesis, but its impact on the liver epigenome is poorly understood. TCPOBOP (1, 4-bis-[2-(3, 5-dichloropyridyloxy)]benzene), a halogenated xenochemical and highly specific CAR agonist ligand, induces localized chromatin opening or closing at several thousand mouse liver genomic regions, discovered as differential DNase-hypersensitive sites (ΔDHS). Active enhancer and promoter histone marks induced by TCPOBOP were enriched at opening DHS and TCPOBOP-inducible genes.

Novel allele-specific quantification methods reveal no effects of adult onset CAG repeats on HTT mRNA and protein levels.

Huntington's disease (HD) reflects dominant consequences of a CAG repeat expansion mutation in HTT. Expanded CAG repeat size is the primary determinant of age at onset and age at death in HD. Although HD pathogenesis is driven by the expanded CAG repeat, whether the mutation influences the expression levels of mRNA and protein from the disease allele is not clear due to the lack of sensitive allele-specific quantification methods and the presence of confounding factors.

The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease.

Huntington disease (HD) is caused by an expanded HTT CAG repeat that leads in a length-dependent, completely dominant manner to onset of a characteristic movement disorder. HD also displays early mortality, so we tested whether the expanded CAG repeat exerts a dominant influence on age at death and on the duration of clinical disease. We found that, as with clinical onset, HD age at death is determined by expanded CAG-repeat length and has no contribution from the normal CAG allele.

Sequence-Level Analysis of the Major European Huntington Disease Haplotype.

Huntington disease (HD) reflects the dominant consequences of a CAG-repeat expansion in HTT. Analysis of common SNP-based haplotypes has revealed that most European HD subjects have distinguishable HTT haplotypes on their normal and disease chromosomes and that ∼50% of the latter share the same major HD haplotype. We reasoned that sequence-level investigation of this founder haplotype could provide significant insights into the history of HD and valuable information for gene-targeting approaches.

HD CAGnome: a search tool for huntingtin CAG repeat length-correlated genes.

Background: The length of the huntingtin (HTT) CAG repeat is strongly correlated with both age at onset of Huntington's disease (HD) symptoms and age at death of HD patients. Dichotomous analysis comparing HD to controls is widely used to study the effects of HTT CAG repeat expansion. However, a potentially more powerful approach is a continuous analysis strategy that takes advantage of all of the different CAG lengths, to capture effects that are expected to be critical to HD pathogenesis.

Esculetin suppresses proliferation of human colon cancer cells by directly targeting β-catenin.

The Wnt pathway is a promising therapeutic and preventive target in various human cancers. The transcriptional complex of β-catenin-T-cell factor (Tcf), a key mediator of canonical Wnt signaling, has been implicated in human colon cancer development. Current treatment of colon cancer depends on traditional cytotoxic agents with limited effects.

Application of hypoiodite-mediated aminyl radical cyclization to synthesis of solasodine acetate.

Solasodine acetate, an anticancer steroidal alkaloid, was synthesized from diosgenin in 8 steps with an overall yield of 23%. A key synthetic step involves the formation of 5/6-oxazaspiroketal moiety via hypoiodite-mediated aminyl radical cyclization of a steroidal primary amine.