Conformity

The functional effects of an RNA can arise from complex three-dimensional folds known as tertiary structures. However, predicting the tertiary structure of an RNA and whether an RNA adopts distinct tertiary conformations remains challenging. To address this, we developed BASH MaP, a single-molecule dimethyl sulfate (DMS) footprinting method and DAGGER, a computational pipeline, to identify alternative tertiary structures adopted by different molecules of RNA. BASH MaP utilizes potassium borohydride to reveal the chemical accessibility of the N7 position of guanosine, a key mediator of tertiary structures...

Our understanding of the sex-specific role of the non-coding genome in serious mental illness remains largely incomplete. To address this gap, we explored sex differences in 1,393 chromatin accessibility profiles, derived from neuronal and non-neuronal nuclei of two distinct cortical regions from 234 cases with serious mental illness and 235 controls. We identified sex-specific enhancer-promoter interactions and showed that they regulate genes involved in X-chromosome inactivation (XCI). Examining chromosomal conformation allowed us to identify sex-specific cis - and trans -regulatory domains (CRDs and TRDs)...

UNLABELLED: The estrogen receptor-α (ER) is thought to function only as a homodimer, but responds to a variety of environmental, metazoan, and therapeutic estrogens at sub-saturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations -receptor conformational heterodimers-mimicking the binding of two different ligands...

Over the past 15 years, a variety of next-generation sequencing assays have been developed for measuring the 3D conformation of DNA in the nucleus. Each of these assays gives, for a particular cell or tissue type, a distinct picture of 3D chromatin architecture. Accordingly, making sense of the relationship between genome structure and function requires teasing apart two closely related questions: how does chromatin 3D structure change from one cell type to the next, and how do different measurements of that structure differ from one another, even when the two assays are carried out in the same cell type? In this work, we assemble a collection of chromatin 3D datasets-each represented as a 2D contact map- spanning multiple assay types and cell types...

Transparent microelectrodes have received much attention from the biomedical community due to their unique advantages in concurrent crosstalk-free electrical and optical interrogation of cell/tissue activity. Despite recent progress in constructing transparent microelectrodes, a major challenge is to simultaneously achieve desirable mechanical stretchability, optical transparency, electrochemical performance, and chemical stability for high-fidelity, conformal, and stable interfacing with soft tissue/organ systems...

Monoclonal antibodies (mAbs) that target the P-amyloid peptide (Aβ) are important Alzheimer's disease research tools and are now being used as Alzheimer's disease therapies. Conformation-specific mAbs that target oligomeric and fibrillar Aβ assemblies are of particular interest, as these assemblies are associated with Alzheimer's disease pathogenesis and progression. This paper reports the generation of rabbit mAbs against two different triangular trimers derived from Aβ. These antibodies are the first mAbs generated against Aβ oligomer mimics in which the high-resolution structures of the oligomers are known...

Elucidating how damage impacts DNA dynamics is essential for understanding the mechanisms of damage recognition and repair. Many DNA lesions alter their propensities to form low-populated and short-lived conformational states. However, NMR methods to measure these dynamics require isotopic enrichment, which is difficult for damaged nucleotides. Here, we demonstrate the utility of the 1 H chemical exchange saturation transfer (CEST) NMR experiment in measuring the dynamics of oxidatively damaged 8-oxoguanine (8OG) in the mutagenic 8OGsyn ·Aanti mismatch...

This study focuses on the development of regiospecific hydroarylation polyaddition of naphthalene- and carbazole-based monomers with diynes under mild reaction conditions at room temperature. A 1-pyrazole substituent serves as an appropriate directing group for a Co-catalyst to efficiently activate the C-H bonds of generally inactive six-membered aromatic hydrocarbons. The 1-pyrazole groups in 2,6-di(1-pyrazolyl)naphthalene adopt planar conformations and act as directing groups, resulting in a smooth hydroarylation reaction...

In this study, the interaction between human serum albumin (HSA) and the hydroxychloroquine/Silybum marianum (HCQ/SM) mixture was investigated using various techniques. The observed high binding constant (Kb ) and Stern-Volmer quenching constant (KSV ) indicate a strong binding affinity between the HCQ/SM mixture and HSA. The circular dichroism (CD) analysis revealed that HCQ/SM induced conformational changes in the secondary structure of HSA, leading to a decrease in the α-helical content. UV-Vis analysis exhibited a slight redshift, indicating that the HCQ/SM mixture could adapt to the flexible structure of HSA...

Investigations of host-guest interactions at water-oil (w/o) interfaces are limited in single emulsion systems producing simple self-assembled objects with limited uses. Here, within hierarchically ordered water-in-oil-in-water (w/o/w) multiple emulsion droplets, interfacial self-assembly of (polynorbornene-graft-polystyrene)-block-(polynorbornene-graft-polyethylene glycol) (PNPS-b-PNPEG) bottlebrush block copolymers can be precisely controlled through host-guest interactions. α-Cyclodextrin (α-CD) in the aqueous phase can thread onto PEG side chains of the bottlebrush surfactants adsorbed at the w/o interface, leading to dehydration and collapsed chain conformation of the PEG block...

INTRODUCTION: An increase in plan robustness leads to a higher dose to adjacent organs-at-risk (OARs), and an increased chance of post-treatment toxicities. In contrast, more conformal plans lead to sparing of healthy surrounding tissue at the expense of a higher sensitivity to anatomical changes, requiring costly adaptations. In this study, we assess the trade-off and impact of treatment plan robustness on the adaptation rate. METHOD: Treatment planning was performed for 40 lung cancer patients, each having a planning 4DCT and up to eight weekly repeated 4DCTs (reCTs)...

The physical interactions between proteins are largely determined by the structural properties at their binding interfaces. It was found that the binding interfaces in distinctive protein complexes are highly similar. The structural properties underlying different binding interfaces could be further captured by artificial intelligence. In order to test this hypothesis, we broke protein-protein binding interfaces into pairs of interacting fragments. We employed a generative model to encode these interface fragment pairs in a low-dimensional latent space...

Secondary kinase domain mutations in BCR::ABL1 represent the most common cause of resistance to tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia patients. The first five approved BCR::ABL1 TKIs target the ATP-binding pocket. Mutations confer resistance to these ATP-competitive TKIs and those approved for other malignancies by decreasing TKI affinity and/or increasing ATP affinity. Asciminib, the first highly active allosteric TKI approved for any malignancy, targets an allosteric regulatory pocket in the BCR::ABL1 kinase C-lobe...

Skeletonema tropicum is a marine diatom of the genus Skeletonema that also includes many well-known species including S. marinoi. S. tropicum is a high temperature preferring species thriving in tropical ocean regions or temperate ocean regions during summer-autumn. However, mechanisms of ecological adaptation of S. tropicum remain poorly understood due partially to the lack of a high-quality whole genome assembly. Here, we report the first high-quality chromosome-scale genome assembly for S. tropicum, using cutting-edge technologies including PacBio single molecular sequencing and high-throughput chromatin conformation capture...

While 3D chromatin organization in topologically associating domains (TADs) and loops mediating regulatory element-promoter interactions is crucial for tissue-specific gene regulation, the extent of their involvement in human Mendelian disease is largely unknown. Here, we identify 7 families presenting a new cardiac entity associated with a heterozygous deletion of 2 CTCF binding sites on 4q25, inducing TAD fusion and chromatin conformation remodeling. The CTCF binding sites are located in a gene desert at 1 Mb from the Paired-like homeodomain transcription factor 2 gene (PITX2)...

BACKGROUND: Widely documented psychological antecedents of vaccination are confidence in vaccines, complacency, convenience, calculation, collective responsibility (5C model) with the recent addition of confidence in the wider system and social conformism. While the capacity of these seven antecedents (7C) to explain variance in COVID-19 vaccine intentions has been previously documented, we study whether these factors also are associated with vaccine behaviours, beyond intentions. METHODS: From February to June 2022, we recruited a sample of adults in France, including persons with notified recent SARS-CoV-2 infection, along with relatives and randomly selected non-infected persons...

Carbon‑carbon bonds serve as the fundamental structural backbone of organic molecules. As a critical CC bond forming enzyme, α-oxoamine synthase is responsible for the synthesis of α-amino ketones by performing the condensation reaction between amino acids and acyl-CoAs. We previously identified an α-oxoamine synthase, named as Alb29, involved in albogrisin biosynthesis in Streptomyces albogriseolus MGR072. This enzyme belongs to the α-oxoamine synthase (AOS) family, a subfamily under the pyridoxal 5'-phosphate (PLP) dependent enzyme superfamily...

Dominance is usually viewed as a positive male attribute, but this is not typically the case for women. Using a novel dataset of student evaluations of teaching in a school of Business and Economics of a selective university, we construct the face width-to-height ratio (fWHR) as a proxy for perceived dominance to assess whether individuals with a higher ratio obtain better evaluations. Our results show that a higher fWHR is associated with a better evaluation for male faculty, while the opposite is the case for female faculty...

Dose conformity is an essential parameter used in radiotherapy and radiosurgery that measures the correspondence of the dose distribution derived from a Treatment Planning System (TPS) with the actual volume to be treated, the Planning Treatment Volume (PTV). The present work uses a method based on the expansion of dose distributions and PTVs by three-dimensional Zernike polynomials and further comparison of their moments to define a general criterion of dose conformity. To carry on this study, data coming from 20 patients comprising 80 datasets exported from the TPS, which included imaging data (PTVs) and dose distributions corresponding to different treatment modalities: three-dimensional conformal radiotherapy, intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were used...

BACKGROUND: The relationship of cognition and the 24-hour activity cycles (24-HAC), encompassing physical activity, sedentary behaviour, and sleep, in older adults with mild cognitive impairment (MCI) remains uncertain. Distinct combinations of 24-HAC behaviours can characterize unique activity profiles and influence cognition. We aimed to characterize 24-HAC activity profiles in older adults with MCI and assess whether differences in cognition exist across profiles. METHODS: We conducted a cross-sectional analysis utilizing baseline data from three randomized controlled trials involving 253 community-dwelling older adults (55+ years) with MCI (no functional impairment, dementia diagnosis, and Montreal Cognitive Assessment score <26/30)...