Structural insight into the DNMT1 reaction cycle by cryo-electron microscopy.

DNMT1 is an essential DNA methyltransferase that catalyzes the transfer of methyl groups to CpG islands in DNA and generates a prominent epigenetic mark. The catalytic activity of DNMT1 relies on its conformational plasticity and ability to change conformation from an auto-inhibited to an activated state. Here, we present four cryo-EM reconstructions of apo DNMT1 and DNTM1: non-productive DNA, DNTM1: H3Ub2-peptide, DNTM1: productive DNA complexes.

Short term biodistribution and in vivo toxicity assessment of intravenously injected pristine graphene oxide nanoflakes in SD rats.

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%.

Isolation of Amyloid-like Protein Aggregates (APA) from white bread and their characterisation.

High temperature, acidic pH, and physical agitation are commonly observed during cooking or industrial food processing, which are often considered as favorable conditions, at least for some proteins, to misfold and form amyloid-like protein aggregates (APA). The proteins in various bakery products generally experience high temperatures that might lead to the formation of APA. To test this hypothesis, the presence of APA in white bread was examined in this study.

Mitigating neuroinflammation in Parkinson's disease: Exploring the role of proinflammatory cytokines and the potential of phytochemicals as natural therapeutics.

Parkinson's disease (PD) is one of the most prevalent neuroinflammatory illnesses, characterized by the progressive loss of neurons in the brain. Proinflammatory cytokines play a key role in initiating and perpetuating neuroinflammation, which can lead to the activation of glial cells and the deregulation of inflammatory pathways, ultimately leading to permanent brain damage. Currently, available drugs for PD mostly alleviate symptoms but do not target underlying inflammatory processes.

In-vitro toxicity assessment of a textile dye Eriochrome Black T and its nano-photocatalytic degradation through an innovative approach using Mf-NGr-CNTs-SnO heterostructures.

The present study aimed to assess the in-vitro toxicity of a popular azodye, Eriochrome Black T (EBT) which may be an environmental hazard causing water pollution if released by textile industries as waste effluents to nearby water ponds. We explored the toxic potential of EBT at 200, 400 and 800 μg/ml concentrations, which were selected based on quantification of EBT present in the pond water near carpet industries. We investigated the permeability of EBT across the organ barriers and found it to be 6.

Inhibition of acyl-ACP thioesterase as site of action of the commercial herbicides cumyluron, oxaziclomefone, bromobutide, methyldymron and tebutam.

Background: Understanding the mode and site of action of a herbicide is key for its efficient development, the evaluation of its toxicological risk, efficient weed control and resistance management. Recently, the mode of action (MoA) of the herbicide cinmethylin was identified in lipid biosynthesis with acyl-ACP thioesterase (FAT) as the site of action (SoA). Cinmethylin was registered for selective use in cereal crops for the control of grass weeds in 2020.

Emerging approaches of neural regeneration using physical stimulations solely or coupled with smart piezoelectric nano-biomaterials.

Neural regeneration is a challenging venture as it is limited by various intrinsic physiological parameters such as the presence of biomolecules like Nogo-A, Ephrin-B3 and Neurocan, that inhibit Central nervous system (CNS) regeneration, and the absence of conducive factors such as ATF3, Sox2 and GAP-43, that promote the neuronal differentiation and regeneration. The design of an effective strategy for neuronal repair or regeneration is a daunting task as neural cells are responsive to a very narrow window of the conductive cellular microenvironment. It requires specific inductive signals and chemical cues from neighbouring cells that can trigger the process of regeneration or repair.

Isolation and characterisation of milk-derived amyloid-like protein aggregates (MAPA) from cottage cheese.

Cottage cheese, extensively consumed worldwide, contains coagulated milk protein (casein), produced through boiling and acidification of milk. Casein forms amyloid or amyloid-like structures at high temperatures and low pH. Due to the similarities in the preparation of casein amyloids and cottage cheese, we hypothesized the presence of amyloid or amyloid-like protein aggregates in cottage cheese.

Heat treatment of soluble proteins isolated from human cataract lens leads to the formation of non-fibrillar amyloid-like protein aggregates.

The loss of crystallins solubility with aging and the formation of amyloid-like aggregates is considered the hallmark characteristic of cataract pathology. The present study was carried out to assess the effect of temperature on the soluble lens protein and the formation of protein aggregates with typical amyloid characteristics. The soluble fraction of lens proteins was subjected for heat treatment in the range of 40-60 °C, and the nature of protein aggregates was assessed by using Congo red (CR), thioflavin T (ThT), and 8-anilinonaphthalene-1-sulfonic acid (ANS) binding assays, circular dichroism (CD), Fourier-transform infrared (FT-IR) spectroscopy, and transmission electron microscopy (TEM).

Microglial responses to CSF1 overexpression do not promote the expansion of other glial lineages.

Background: Colony-stimulating factor 1 (CSF1) expression in the central nervous system (CNS) increases in response to a variety of stimuli, and CSF1 is overexpressed in many CNS diseases. In young adult mice, we previously showed that CSF1 overexpression in the CNS caused the proliferation of IBA1 microglia without promoting the expression of M2 polarization markers.

Methods: Immunohistochemical and molecular analyses were performed to further examine the impact of CSF1 overexpression on glia in both young and aged mice.

Molecular Networking Discloses the Chemical Diversity of Flavonoids and Selaginellins in Selaginella convoluta.

is a desiccation tolerant plant native to the Brazilian semiarid region (Caatinga), endowed with an effective drought resistance mechanism. As part of our research efforts to understand the chemical diversity of dehydrated (harvested in their natural habitat in the dry season) and hydrated (plant acclimated in a laboratory after rehydration) specimens were analyzed by HR-LC-ESI-MS/MS followed by a structural annotation on the Global Natural Products Social Molecular Networking Web platform. The molecular networking approach allowed for putative annotation of 39 metabolites, mainly selaginellins and flavonoids.

Exposure of calcium carbide induces apoptosis in mammalian fibroblast L929 cells.

Inspite of various health warnings from Government and health organizations, Calcium carbide (CaC) is still the most commonly and widely used artificial fruit ripener, probably due to its easy availability, low cost and convenience of usage. Assessment of the hazardous effects of the CaC applications for fruit ripening has been a matter of interest since long. Several studies have reported the toxicological outcomes such as histopathological changes in lungs and kidneys, haematological and immunological responses, upon exposure with CaC.

Alternative catalytic residues in the active site of Esco acetyltransferases.

Cohesin is a protein complex whose core subunits, Smc1, Smc3, Scc1, and SA1/SA2 form a ring-like structure encircling the DNA. Cohesins play a key role in the expression, repair, and segregation of eukaryotic genomes. Following a catalytic mechanism that is insufficiently understood, Esco1 and Esco2 acetyltransferases acetylate the cohesin subunit Smc3, thereby inducing stabilization of cohesin on DNA.

Unleashing the Power of ASH1L Methyltransferase.

Trithorax histone methyltransferase Ash1/ASH1L is tightly regulated because it activates developmental gene transcription and counteracts Polycomb silencing. In this issue of Structure, Lee et al. (2019) and Hou et al.

Structural Basis for the Activation of the Deubiquitinase Calypso by the Polycomb Protein ASX.

Ubiquitin C-terminal hydrolase deubiquitinase BAP1 is an essential tumor suppressor involved in cell growth control, DNA damage response, and transcriptional regulation. As part of the Polycomb repression machinery, BAP1 is activated by the deubiquitinase adaptor domain of ASXL1 mediating gene repression by cleaving ubiquitin (Ub) from histone H2A in nucleosomes. The molecular mechanism of BAP1 activation by ASXL1 remains elusive, as no structures are available for either BAP1 or ASXL1.

Coordination of Pharyngeal and Laryngeal Swallowing Events During Single Liquid Swallows After Oral Endotracheal Intubation for Patients with Acute Respiratory Distress Syndrome.

To evaluate timing and duration differences in airway protection and esophageal opening after oral intubation and mechanical ventilation for acute respiratory distress syndrome (ARDS) survivors versus age-matched healthy volunteers. Orally intubated adult (≥ 18 years old) patients receiving mechanical ventilation for ARDS were evaluated for swallowing impairments via a videofluoroscopic swallow study (VFSS) during usual care. Exclusion criteria were tracheostomy, neurological impairment, and head and neck cancer.

Emerging Roles of DHHC-mediated Protein S-palmitoylation in Physiological and Pathophysiological Context.

Protein S-palmitoylation refers to a post-translational modification (PTM) wherein palmitic acid, a 16-carbon long saturated fatty acid gets covalently attached to Cys sidechain of a protein. It has been known to the literature for almost 50 years and in general, this PTM is believed to facilitate membrane attachments of proteins for the obvious hydrophobicity of the palmitoyl group. But after the discovery of the protein palmitoyl acyltransferases (PATs, also known as DHHC-PATs), a major paradigm shift has been observed in the field of protein S-palmitoylation.

The Mitochondrial Unfolded Protein Response: Role in Cellular Homeostasis and Disease.

Mitochondria are the sole semiautonomous organelles of the human cell and play a very important role in not only energy production but also in apoptosis, metabolism and cell signaling. They are also known to be major producers of ROS and RNS free radicals during ATP production. These free radicals in excessive amount may damage the mitochondrial DNA as well as proteome resulting in accumulation of misfolded proteins which may prove deleterious to their functioning and are known to be involved in disease pathology.

CSF1 Overexpression Promotes High-Grade Glioma Formation without Impacting the Polarization Status of Glioma-Associated Microglia and Macrophages.

Current therapies for high-grade gliomas extend survival only modestly. The glioma microenvironment, including glioma-associated microglia/macrophages (GAM), is a potential therapeutic target. The microglia/macrophage cytokine CSF1 and its receptor CSF1R are overexpressed in human high-grade gliomas.

The organization and contribution of helicases to RNA splicing.

Splicing is an essential step of gene expression. It occurs in two consecutive chemical reactions catalyzed by a large protein-RNA complex named the spliceosome. Assembled on the pre-mRNA substrate from five small nuclear proteins, the spliceosome acts as a protein-controlled ribozyme to catalyze the two reactions and finally dissociates into its components, which are re-used for a new round of splicing.

Isolation and characterization of plant synergistic bacteria capable of degrading xenobiotics from oil spillage sites.

Oil spillage sites primarily contain various types of hydrocarbons, such as linear chain, polycyclic, and aromatic compounds, posing several detrimental effects on plants. Results from our previous study showed an alteration of various metabolomic parameters, indirectly resulting in an observable decline of growth in the mung seedlings upon incubation with phenol, toluene, xylene, and hexane. This study evaluates the role of these compounds upon plant growth and focusses to mitigate the effect of the same, using some isolated plant synergistic bacteria.

The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes.

Aquarius is a multifunctional putative RNA helicase that binds precursor-mRNA introns at a defined position. Here we report the crystal structure of human Aquarius, revealing a central RNA helicase core and several unique accessory domains, including an ARM-repeat domain. We show that Aquarius is integrated into spliceosomes as part of a pentameric intron-binding complex (IBC) that, together with the ARM domain, cross-links to U2 snRNP proteins within activated spliceosomes; this suggests that the latter aid in positioning Aquarius on the intron.

PHYTOPLASMAS IN POME FRUIT TREES: UPDATE OF THEIR PRESENCE AND THEIR VECTORS IN BELGIUM.

Among the numerous diseases that can attack pome fruit trees, apple proliferation and pear decline, both caused by a phytoplasma ('Candidatus Phytoplasma mali' (AP) and 'Ca. P. pyri' (PD), respectively), may result into important losses of quality and quantity of the crop.