Controlling gene expression through five zinc finger domains of ZNF18.

Zinc finger (ZF) proteins are the most abundant transcription factors in vertebrates, and they regulate gene expression through interactions with cis-acting elements. ZF domains selectively recognize specific sequences to accelerate or repress target genes. Zinc finger protein 18 (ZNF18) contains five CXCXHXH-type ZFs at the C-terminus, which are expressed in the brain and other organs of the biological system.

Gaia: An AI-enabled genomic context-aware platform for protein sequence annotation.

Protein sequence similarity search is fundamental to biology research, but current methods are typically not able to consider crucial genomic context information indicative of protein function, especially in microbial systems. Here, we present Gaia (Genomic AI Annotator), a sequence annotation platform that enables rapid, context-aware protein sequence search across genomic datasets. Gaia leverages gLM2, a mixed-modality genomic language model trained on both amino acid sequences and their genomic neighborhoods to generate embeddings that integrate sequence-structure-context information.

Regulation of carcinogenesis through multiple zinc fingers in ZBTB20.

Zinc finger (ZF) proteins regulate transcription by interacting with -acting elements for gene expression in response to stimuli within physiological systems. Bioinformatic studies have proposed that zinc finger and BTB (Broad complex, Tramtrack, Bric-à-brac) domain-containing protein 20 (ZBTB20) acts as a key regulator of crucial genes associated with carcinogenesis. However, biochemical experiments using purified proteins remain unreported.

Biophysical interactions between self-sufficient cytochrome P450 from and ilaprazole.

Proton pump inhibitors (PPIs), metabolized by cytochrome P450 (P450) enzymes, are widely used to inhibit gastric acid secretion. This study investigated CYP116B46, a self-sufficient monooxygenase with a reductase domain, to elucidate its interaction with ilaprazole, a PPI. Binding assays and docking simulations indicate that CYP116B46 serves as a suitable model for studying PPI metabolism.

Genomic language model predicts protein co-regulation and function.

Deciphering the relationship between a gene and its genomic context is fundamental to understanding and engineering biological systems. Machine learning has shown promise in learning latent relationships underlying the sequence-structure-function paradigm from massive protein sequence datasets. However, to date, limited attempts have been made in extending this continuum to include higher order genomic context information.

Decoding the Parkinson's Symphony: PARIS, Maestro of Transcriptional Regulation and Metal Coordination for Dopamine Release.

Parkin interacting substrate (PARIS) is a pivotal transcriptional regulator in the brain that orchestrates the activity of various enzymes through its intricate interactions with biomolecules, including nucleic acids. Notably, the binding of PARIS to insulin response sequences (IRSs) triggers a cascade of events that results in the functional loss in the substantia nigra, which impairs dopamine release and, subsequently, exacerbates the relentless neurodegeneration. Here, we report the details of the interactions of PARIS with IRSs via classical zinc finger (ZF) domains in PARIS, namely, PARIS(ZF2-4).

DW71177: A novel [1,2,4]triazolo[4,3-a]quinoxaline-based potent and BD1-Selective BET inhibitor for the treatment of acute myeloid leukemia.

The bromodomain and extraterminal domain (BET) family proteins recognize acetyl-lysine (K) at the histone tail through two tandem bromodomains, i.e., BD1 and BD2, to regulate gene expression.

Selective interactions of Co-Ca-concanavalin A with high mannose -glycans.

Concanavalin A (ConA) has an intrinsic binding affinity to carbohydrates. Here, we obtained Co-Ca-ConA (2.83 Å, PDB: 8I7Q) X-ray crystallography by substituting native ConA (Mn-Ca); it has binding selectivity for high-mannose -glycan similar to native ConA.

Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways.

Sarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and Bifidobacterium bifidum P61 (Bb), which suppressed muscle RING-finger protein-1 (MuRF1) expression and NF-κB activation in C2C12 cells, and examined their effects on muscle mass loss and dysfunction in aged mice.

Transcriptional regulation of soluble methane monooxygenase via enhancer-binding protein derived from 5.

Methane is a major greenhouse gas, and methanotrophs regulate the methane level in the carbon cycle. Soluble methane monooxygenase (sMMO) is expressed in various methanotroph genera, including and , and catalyzes the hydroxylation of methane to methanol. It has been proposed that MmoR regulates the expression of sMMO as an enhancer-binding protein under copper-limited conditions; however, details on this transcriptional regulation remain limited.

Effect of OK67 in Reducing Body and Visceral Fat in Lifestyle-Modified Overweight Individuals: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Obesity is a global health problem that affects the quality of life. It is a multidimensional chronic risk factor for major medical conditions, such as cardiovascular diseases, diabetes, and cancer. This clinical trial evaluated the efficacy of OK67 (DW2010), a lactic acid bacterium, in reducing body and visceral fat in overweight individuals (body mass index ≥25 kg/m and <30 kg/m), aged 20-60 years.

Viruses interact with hosts that span distantly related microbial domains in dense hydrothermal mats.

Many microbes in nature reside in dense, metabolically interdependent communities. We investigated the nature and extent of microbe-virus interactions in relation to microbial density and syntrophy by examining microbe-virus interactions in a biomass dense, deep-sea hydrothermal mat. Using metagenomic sequencing, we find numerous instances where phylogenetically distant (up to domain level) microbes encode CRISPR-based immunity against the same viruses in the mat.

Differentiated Evolutionary Strategies of Genetic Diversification in Atlantic and Pacific Thaumarchaeal Populations.

Some marine microbes are seemingly "ubiquitous," thriving across a wide range of environmental conditions. While the increased depth in metagenomic sequencing has led to a growing body of research on within-population heterogeneity in environmental microbial populations, there have been fewer systematic comparisons and characterizations of population-level genetic diversity over broader expanses of time and space. Here, we investigated the factors that govern the diversification of ubiquitous microbial taxa found within and between ocean basins.

Electron Transfer to Hydroxylase through Component Interactions in Soluble Methane Monooxygenase.

The hydroxylation of methane (CH) is crucial to the field of environmental microbiology, owing to the heat capacity of methane, which is much higher than that of carbon dioxide (CO). Soluble methane monooxygenase (sMMO), a member of the bacterial multicomponent monooxygenase (BMM) superfamily, is essential for the hydroxylation of specific substrates, including hydroxylase (MMOH), regulatory component (MMOB), and reductase (MMOR). The diiron active site positioned in the MMOH α-subunit is reduced through the interaction of MMOR in the catalytic cycle.

Leave no stone unturned: individually adapted xerotolerant Thaumarchaeota sheltered below the boulders of the Atacama Desert hyperarid core.

Background: The hyperarid core of the Atacama Desert is an extremely harsh environment thought to be colonized by only a few heterotrophic bacterial species. Current concepts for understanding this extreme ecosystem are mainly based on the diversity of these few species, yet a substantial area of the Atacama Desert hyperarid topsoil is covered by expansive boulder accumulations, whose underlying microbiomes have not been investigated so far. With the hypothesis that these sheltered soils harbor uniquely adapted microbiomes, we compared metagenomes and geochemistry between soils below and beside boulders across three distantly located boulder accumulations in the Atacama Desert hyperarid core.

Concanavalin A: coordination diversity to xenobiotic metal ions and biological consequences.

The binding ability of lectins has gained attention owing to the carbohydrate-specific interactions of these proteins. Such interactions can be applied to diverse fields of biotechnology, including the detection, isolation, and concentration of biological target molecules. The physiological aspects of the lectin concanavalin A (ConA) have been intensively studied through structural and functional investigations.

Elucidation of the electron transfer environment in the MMOR FAD-binding domain from 5.

By facilitating electron transfer to the hydroxylase diiron center, MMOR-a reductase-serves as an essential component of the catalytic cycle of soluble methane monooxygenase. Here, the X-ray structure analysis of the FAD-binding domain of MMOR identified crucial residues and its influence on the catalytic cycle.

Microbial Hotspots in Lithic Microhabitats Inferred from DNA Fractionation and Metagenomics in the Atacama Desert.

The existence of microbial activity hotspots in temperate regions of Earth is driven by soil heterogeneities, especially the temporal and spatial availability of nutrients. Here we investigate whether microbial activity hotspots also exist in lithic microhabitats in one of the most arid regions of the world, the Atacama Desert in Chile. While previous studies evaluated the total DNA fraction to elucidate the microbial communities, we here for the first time use a DNA separation approach on lithic microhabitats, together with metagenomics and other analysis methods (i.

Diverse Viruses Carrying Genes for Microbial Extremotolerance in the Atacama Desert Hyperarid Soil.

Viruses play an essential role in shaping microbial community structures and serve as reservoirs for genetic diversity in many ecosystems. In hyperarid desert environments, where life itself becomes scarce and loses diversity, the interactions between viruses and host populations have remained elusive. Here, we resolved host-virus interactions in the soil metagenomes of the Atacama Desert hyperarid core, one of the harshest terrestrial environments on Earth.

Efficacy and Safety of C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Early intervention using dietary supplements may be effective in alleviating cognitive impairment among individuals with mild cognitive impairment (MCI). This study investigated the efficacy and safety of C29-fermented soybean (DW2009) as a nutritional supplement for cognitive enhancement. One hundred individuals with MCI were randomly assigned to take DW2009 (800 mg/day, = 50) or placebo (800 mg/day, = 50) for 12 weeks.

Lactobacillus plantarum C29-Fermented Soybean (DW2009) Alleviates Memory Impairment in 5XFAD Transgenic Mice by Regulating Microglia Activation and Gut Microbiota Composition.

Scope: The study aims to determine whether Lactobacillus plantarum C29-fermented defatted soybean (FDS, DW2009) can attenuate memory impairment in 5XFAD transgenic (Tg) mice.

Methods And Results: Oral administration of FDS or C29 increases cognitive function in Tg mice in passive avoidance, Y-maze, novel object recognition, and Morris water maze tasks. FDS or C29 treatment significantly suppresses amyloid-β, β/γ-secretases, caspase-3 expression, and NF-κB activation, and activates microglia and apoptotic neuron cell populations, and increases BDNF expression in the brain.