Imbalance of Hsp70 family variants fosters tau accumulation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154405/1/fsb2027004018.pd

Residual Dipolar Couplings in NMR Spectroscopy Using Lanthanide Tags

Nuclear Magnetic Resonance (NMR) spectroscopy is an indispensable technique used in structure determination of small and macromolecules to study their physical properties, elucidation of characteristic interactions, dynamics and thermodynamic processes. Quantum mechanics defines the theoretical description of NMR spectroscopy and treatment of the dynamics of nuclear spin systems. The phenomenon of residual dipolar coupling (RDCs) has become a routine tool for accurate structure determination by providing global orientation information of magnetic dipole-dipole interaction vectors within a common reference frame. This offers accessibility of distance-independent angular information and insights to local relaxation. The measurement of RDCs requires an anisotropic orientation medium for the molecules to partially align along the magnetic field. This can be achieved by introduction of liquid crystals or attaching a paramagnetic center. Although anisotropic paramagnetic tags continue to mark achievements in the biomolecular NMR of large proteins, its application in small organic molecules remains unspread. Here, we propose a strategy for the synthesis of a lanthanide tag and the measurement of RDCs in organic molecules using paramagnetic lanthanide complexes

Structural insights into the binding mechanism of Clr4 methyltransferase to H3K9 methylated nucleosome

Abstract The establishment and maintenance of heterochromatin, a specific chromatin structure essential for genomic stability and regulation, rely on intricate interactions between chromatin-modifying enzymes and nucleosomal histone proteins. However, the precise trigger for these modifications remains unclear, thus highlighting the need for a deeper understanding of how methyltransferases facilitate histone methylation among others. Here, we investigate the molecular mechanisms underlying heterochromatin assembly by studying the interaction between the H3K9 methyltransferase Clr4 and H3K9-methylated nucleosomes. Using a combination of liquid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy, we elucidate the structural basis of Clr4 binding to H3K9-methylated nucleosomes. Our results reveal that Clr4 engages with nucleosomes through its chromodomain and disordered regions to promote de novo methylation. This study provides crucial insights into the molecular mechanisms governing heterochromatin formation by highlighting the significance of chromatin-modifying enzymes in genome regulation and disease pathology

Determination of heavy metals contamination in thyme products by inductively coupled plasma mass spectrometry

Thyme herbs constitute a major part of the Mediterranean diet and are gaining worldwide popularity. However, their chemical contamination with toxic metals may put consumers at a health risk. The objective of this study was to assess the incidence of Arsenic (As), Cadmium (Cd), Lead (Pb) and Mercury (Hg) in thyme-containing products. Composite samples were collected twice at six-month interval. Samples were digested by microwave digestion oven and analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). 11%, 22%, and 86% of samples had unacceptable levels of As, Hg and Pb respectively according to the international standards set by Codex Alimentarius and all the samples had acceptable limits of Cd. This study highlighted the importance of monitoring and enforcing regulatory actions related to the contamination of the food chain with heavy metals.This work was funded by Qatar National Library

Synthesis of lanthanide tag and experimental studies on paramagnetically induced residual dipolar couplings

Abstract Nuclear Magnetic Resonance (NMR) spectroscopy is an indispensable technique for the structure elucidation of molecules and determination of their characteristic interactions. Residual Dipolar Coupling (RDC) is an NMR parameter that provides global orientation information of molecules but necessitates the use of an anisotropic orientation medium for the partial alignment of the target molecule with respect to the magnetic field. Importantly, anisotropic paramagnetic tags have been successful as orienting media in biomolecular NMR applications but their use in small organic molecules remains imperfect due to challenges in designing functional lanthanide complexes with varying degrees of bonding in the Ln(III) inner coordination sphere. In this study, we propose a strategy for the synthesis of the lanthanide tag 4-mercaptomethylpyridine-2,6-dicarboxylic acid, 4-MMDPA and the measurement of RDCs in a target molecule using several paramagnetic lanthanide complexes. Graphical Abstrac

Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity

Heterochromatin is a distinctive chromatin structure that is essential for chromosome segregation, genome stability and regulation of gene expression. H3K9 methylation (H3K9me), a hallmark of heterochromatin, is deposited by the Su(var)3-9 family of proteins; however, the mechanism by which H3K9 methyltransferases bind and methylate the nucleosome is poorly understood. In this work we determined the interaction of Clr4, the fission yeast H3K9 methyltransferase, with nucleosomes using nuclear magnetic resonance, biochemical and genetic assays. Our study shows that the Clr4 chromodomain binds the H3K9me3 tail and that both, the chromodomain and the disordered region connecting the chromodomain and the SET domain, bind the nucleosome core. We show that interaction of the disordered region with the nucleosome core is independent of H3K9me and contributes to H3K9me in vitro and in vivo. Moreover, we show that those interactions with the nucleosome core are contributing to de novo deposition of H3K9me and to establishment of heterochromatin.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Toxic metals in packed rice: Effects of size, type, origin, packing season, and storage duration

The aim of our study was to quantify toxic metals in rice, to determine factors affecting its contamination, and evaluate exposure from its consumption in Lebanon and United Arab Emirates (UAE). For this, a market screening was done and all brands (107 from Lebanon and 129 from UAE) were collected twice and tested using ICP-MS. For As, Cd, Hg and Pb, in UAE, 9%, 1%, 100%, and 69% of samples exceeded the international limits, while in Lebanon, 25%, 73%, 100%, and 69% of samples were above limits, respectively. For As, in Lebanon, brown rice, long grains and brands from developed countries were significantly more contaminated, while in UAE, packing season, country of origin, and collection time had significant effect. For Cd, collection time had significant effect in Lebanon and UAE. Regarding Cr, in Lebanon, country of origin, grain size, rice type, and time between packing and purchasing had significant effect, while in UAE, collection time had significant effect. For Hg, collection time had significant effect in Lebanon and UAE. Alarming exposure levels for Hg and Pb from rice were detected in the UAE. Future studies must assess the effects of handling and cooking to better assess exposure to toxic metals from rice consumption

Snails as Temporal Biomonitors of the Occurrence and Distribution of Pesticides in an Apple Orchard

The intensive use of pesticides in agricultural areas and the resulting effects have created a need to develop monitoring programs for their active assessment at low cost. This research entails a biomonitoring study of the pesticides in an apple orchard, using juvenile Cornu aspersum (O. F. Müller, 1774) snails exposed in field microcosms. The snails were deployed at three different locations in the orchard area and were used to assess the temporal biomonitoring of 100 different semi-volatile and non-volatile pesticides. The study was performed over an 18-week period and targeted the center, the border, and the outside of the orchard. Results showed that greater levels of pesticides were detected at the center of the orchard as compared to the other sites. The type and level of the applied pesticide influenced its environmental dissipation, as significantly greater levels of semi-volatile pesticides were accumulated by the caged snails in comparison to non-volatile pesticides. The presence of semi-volatile pesticides in the snails outside the orchard revealed the usefulness of these species in the biomonitoring of off-site pesticide emissions. The findings of this study showed that C. aspersum can serve as a reliable and effective model organism for the active biomonitoring of pesticide emissions in agricultural sites