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ChemPlusChem Jul 2024We report a synthesis of silver complexes bearing chelating bidentate N-heterocyclic carbene, with various substitutions at the terminal positions of the imidazole...
We report a synthesis of silver complexes bearing chelating bidentate N-heterocyclic carbene, with various substitutions at the terminal positions of the imidazole moiety of the NHC units. The long aliphatic substituents proved to be beneficial in terms of the synthetic efficiency of the complexes, compared to previously reported methyl substitution. The complexes demonstrated excellent suitability for the KA2 coupling reaction, providing quaternary carbon-containing propargylic amines in yields up to 95%, under solvent-free conditions. The method showed high tolerance for a wide range of substrates, including naturally occurring ketones, underscoring its practicality. To our knowledge, this represents the first use of a well-defined silver species in KA2 coupling, marking an advancement in the field.
PubMed: 38958030
DOI: 10.1002/cplu.202400365 -
Journal of Chemical Theory and... Jul 2024Experimental NMR spectroscopy and theoretical molecular dynamics (MD) simulations provide complementary insights into protein conformational dynamics and hence into...
Experimental NMR spectroscopy and theoretical molecular dynamics (MD) simulations provide complementary insights into protein conformational dynamics and hence into biological function. The present work describes an extensive set of backbone NH and side-chain methyl group generalized order parameters for the ribonuclease HI (RNH) enzyme derived from 2-μs microsecond MD simulations using the OPLS4 and AMBER-FF19SB force fields. The simulated generalized order parameters are compared with values derived from NMR N and CHD spin relaxation measurements. The squares of the generalized order parameters, for the N-H bond vector and for the methyl group symmetry axis, characterize the equilibrium distribution of vector orientations in a molecular frame of reference. Optimal agreement between simulated and experimental results was obtained by averaging or calculated by dividing the simulated trajectories into 50 ns blocks (∼five times the rotational diffusion correlation time for RNH). With this procedure, the median absolute deviations (MAD) between experimental and simulated values of and are 0.030 (NH) and 0.061 (CH) for OPLS4 and 0.041 (NH) and 0.078 (CH) for AMBER-FF19SB. The MAD between OPLS4 and AMBER-FF19SB are 0.021 (NH) and 0.072 (CH). The generalized order parameters for the methyl group symmetry axis can be decomposed into contributions from backbone fluctuations, between-rotamer dihedral angle transitions, and within-rotamer dihedral angle fluctuations. Analysis of the simulation trajectories shows that () backbone and side chain conformational fluctuations exhibit little correlation and that () fluctuations within rotamers are limited and highly uniform with values that depend on the number of dihedral angles considered. Low values of , indicative of enhanced side-chain flexibility, result from between-rotamer transitions that can be enhanced by increased local backbone flexibility.
PubMed: 38957960
DOI: 10.1021/acs.jctc.4c00378 -
Epigenomics Jul 2024We investigate the genome-wide DNA methylation (DNAm) patterns of term low birth weight (TLBW) neonates. In the discovery phase, we assayed 32 samples...
We investigate the genome-wide DNA methylation (DNAm) patterns of term low birth weight (TLBW) neonates. In the discovery phase, we assayed 32 samples (TLBW/control:16/16) using the EPIC 850k BeadChip Array. Targeted pyrosequencing of in 60 samples (TLBW/control:28/32) using targeted pyrosequencing during the replication phase. The 850K array identified TLBW-associated 144 differentially methylated positions (DMPs) and 149 DMRs. Nearly 77% DMPs exhibited hypomethylation, located in the opensea and gene body regions. The most significantly enriched pathway in KEGG is sphingolipid metabolism (hsa00600), and the genes and related to this pathway both show hypomethylation. Our analysis provides evidence of genome-wide DNAm alterations in TLBW. Further investigations are needed to elucidate the functional significance of these DNAm changes.
PubMed: 38957889
DOI: 10.1080/17501911.2024.2358744 -
Frontiers in Pediatrics 2024Over the past few decades, the incidence of childhood allergic diseases has increased globally, and their impact on the affected child extends beyond the allergy itself.... (Review)
Review
Over the past few decades, the incidence of childhood allergic diseases has increased globally, and their impact on the affected child extends beyond the allergy itself. There is evidence of an association between childhood allergic diseases and the development of neurological disorders. Several studies have shown a correlation between allergic diseases and tic disorders (TD), and allergic diseases may be an important risk factor for TD. Possible factors influencing the development of these disorders include neurotransmitter imbalance, maternal anxiety or depression, gut microbial disorders, sleep disturbances, maternal allergic status, exposure to tobacco, and environmental factors. Moreover, gut microbial disturbances, altered immunological profiles, and DNA methylation in patients with allergic diseases may be potential mechanisms contributing to the development of TD. An in-depth investigation of the relationship between allergic diseases and TD in children will be important for preventing and treating TD.
PubMed: 38957776
DOI: 10.3389/fped.2024.1360420 -
Frontiers in Microbiology 2024Influenza A virus (IAV) is a negative-sense single-stranded RNA virus that causes acute lung injury and acute respiratory distress syndrome, posing a serious threat to... (Review)
Review
Influenza A virus (IAV) is a negative-sense single-stranded RNA virus that causes acute lung injury and acute respiratory distress syndrome, posing a serious threat to both animal and human health. N6-methyladenosine (mA), a prevalent and abundant post-transcriptional methylation of RNA in eukaryotes, plays a crucial regulatory role in IAV infection by altering viral RNA and cellular transcripts to affect viral infection and the host immune response. This review focuses on the molecular mechanisms underlying mA modification and its regulatory function in the context of IAV infection and the host immune response. This will provide a better understanding of virus-host interactions and offer insights into potential anti-IAV strategies.
PubMed: 38957616
DOI: 10.3389/fmicb.2024.1401997 -
RSC Advances Jun 2024In current trends, an imminent development of self-detoxification filters is highly desirable against exposure to chemical warfare agents (CWAs). Exploiting protective...
In current trends, an imminent development of self-detoxification filters is highly desirable against exposure to chemical warfare agents (CWAs). Exploiting protective materials that can be applicable in day-to-day life for instantaneous detoxification will be of immense importance. The available technologies in the current scenario are susceptible to secondary emission and pose a need for an alternate design strategy for effective degradation. In addition, the choice of active material and successful impregnation on a suitable substrate for developing potential barriers requires complex material design. In this context, the developed self-standing UiO-66 and UiO-66-NH functionalized fabrics (MOFabrics) present an expeditious detoxification performance against CWA simulant, methyl-paraoxon, with a maximum removal percent conversion of 88.9 and 90.68%. It shows a reduced half-life of approximately 10.16 and 11.23 min, in comparison to an unmodified/carboxymethylated fabric of 462 min.
PubMed: 38957585
DOI: 10.1039/d4ra03830d -
Evolutionary Applications Jul 2024The Neolithic transition introduced major diet and lifestyle changes to human populations across continents. Beyond well-documented bioarcheological and genetic effects,...
The Neolithic transition introduced major diet and lifestyle changes to human populations across continents. Beyond well-documented bioarcheological and genetic effects, whether these changes also had molecular-level epigenetic repercussions in past human populations has been an open question. In fact, methylation signatures can be inferred from UDG-treated ancient DNA through postmortem damage patterns, but with low signal-to-noise ratios; it is thus unclear whether published paleogenomes would provide the necessary resolution to discover systematic effects of lifestyle and diet shifts. To address this we compiled UDG-treated shotgun genomes of 13 pre-Neolithic hunter-gatherers (HGs) and 21 Neolithic farmers (NFs) individuals from West and North Eurasia, published by six different laboratories and with coverage c.1×-58× (median = 9×). We used epiPALEOMIX and a Monte Carlo normalization scheme to estimate methylation levels per genome. Our paleomethylome dataset showed expected genome-wide methylation patterns such as CpG island hypomethylation. However, analyzing the data using various approaches did not yield any systematic signals for subsistence type, genetic sex, or tissue effects. Comparing the HG-NF methylation differences in our dataset with methylation differences between hunter-gatherers versus farmers in modern-day Central Africa also did not yield consistent results. Meanwhile, paleomethylome profiles did cluster strongly by their laboratories of origin. Using larger data volumes, minimizing technical noise and/or using alternative protocols may be necessary for capturing subtle environment-related biological signals from paleomethylomes.
PubMed: 38957308
DOI: 10.1111/eva.13743 -
Neuro-oncology Advances 2024Meningiomas are the most common primary brain tumors. While most are benign (WHO grade 1) and have a favorable prognosis, up to one-fourth are classified as...
BACKGROUND
Meningiomas are the most common primary brain tumors. While most are benign (WHO grade 1) and have a favorable prognosis, up to one-fourth are classified as higher-grade, falling into WHO grade 2 or 3 categories. Recently, an integrated risk score (IRS) pertaining to tumor biology was developed and its prognostic relevance was validated in a large, multicenter study. We hypothesized imaging data to be reflective of the IRS. Thus, we assessed the potential of a machine learning classifier for its noninvasive prediction using preoperative magnetic resonance imaging (MRI).
METHODS
In total, 160 WHO grade 2 and 3 meningioma patients from 2 university centers were included in this study. All patients underwent surgery with histopathological workup including methylation analysis. Preoperative MRI scans were automatically segmented, and radiomic parameters were extracted. Using a random forest classifier, 3 machine learning classifiers (1 multiclass classifier for IRS and 2 binary classifiers for low-risk and high-risk prediction, respectively) were developed in a training set (120 patients) and independently tested in a hold-out test set (40 patients).
RESULTS
Multiclass IRS classification had a test set area under the curve (AUC) of 0.7, mostly driven by the difficulties in clearly separating medium-risk from high-risk patients. Consequently, a classifier predicting low-risk IRS versus medium-/high-risk showed a very high test accuracy of 90% (AUC 0.88). In particular, "sphericity" was associated with low-risk IRS classification.
CONCLUSION
The IRS, in particular molecular low-risk, can be predicted from imaging data with high accuracy, making this important prognostic classification accessible by imaging.
PubMed: 38957161
DOI: 10.1093/noajnl/vdae080 -
Critical Reviews in Clinical Laboratory... Jul 2024RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA... (Review)
Review
RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA methylation under diseased conditions have been increasingly unveiled by RNA sequencing technologies with large scale and high resolution. In this review, the fundamental concept of RNA methylation is introduced, and the common types of transcript methylation and their machineries are described. Then, the regulatory roles of RNA methylation, particularly N6-methyladenosine and 5-methylcytosine, in the vascular lesions of ocular and cardiopulmonary diseases are discussed and compared. The ocular diseases include corneal neovascularization, retinopathy of prematurity, diabetic retinopathy, and pathologic myopia; whereas the cardiopulmonary ailments involve atherosclerosis and pulmonary hypertension. This review hopes to shed light on the common regulatory mechanisms underlying the vascular lesions in these ocular and cardiopulmonary diseases, which may be conducive to developing therapeutic strategies in clinical practice.
PubMed: 38957015
DOI: 10.1080/10408363.2024.2370267 -
Organic & Biomolecular Chemistry Jul 2024We describe the synthesis of two tetra-α aryl-extended calix[4]pyrroles (C[4]Ps) 4a-b bearing four terminal carboxylic groups in their -propyl chains defining the lower...
We describe the synthesis of two tetra-α aryl-extended calix[4]pyrroles (C[4]Ps) 4a-b bearing four terminal carboxylic groups in their -propyl chains defining the lower rims. The synthesized C[4]Ps became soluble (1-3 mM) in water at pD = 10. We probed the interaction of 4a towards tetra-methylammonium (G1) chloride in water using H NMR spectroscopy. The C[4]P 4a includes G1 in the shallow aromatic cavity defined by the pyrrole rings in cone conformation forming a 1 : 1 complex G1⊂4a. Pyridine--oxide (PNO) binding in the larger polar aromatic cavity of 4a results in the quantitative self-assembly of the supramolecular receptor PNO@4a featuring the pyrrole rings preorganized in cone conformation. The PNO@4a receptor displays improved binding properties towards G1 than the parent C[4]P 4a. We thermodynamically characterized (H NMR titrations and ITC experiments) the 1 : 1 complexes of PNO@4a with a series of tetra-alkylammonium salts, including biologically relevant examples. The PNO@4a supramolecular receptor displays significant affinity (log = 3-4) but lacks selectivity in water binding of methyl trialkyl ammonium cations. Cation-π and coulombic interactions are the main intermolecular forces stabilizing the complexes. We also performed DFT calculations to gain some insights into the complexes' structures.
PubMed: 38957010
DOI: 10.1039/d4ob00843j