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Family with sequence similarity 72 (FAM72) is a protein-coding gene family located on chromosome 1 in humans, uniquely featuring four paralogs: FAM72A, FAM72B, FAM72C, and FAM72D. While FAM72's presence as a gene pair with the SLIT-ROBO Rho GTPase-activating protein 2 (SRGAP2) is intriguing, its functional roles, particularly in neural stem cells, remain incompletely understood. This review explores the distinct characteristics of FAM72, shedding light on its expression patterns, potential roles in cell cycle regulation, stem cell renewal and implications in neurogenesis and tumorigenesis.
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The biogenic synthesis of silver nanoparticles (AgNPs) has a wide range of applications in the pharmaceutical industry. Here, we synthesized AgNPs using the aqueous flower extract of Bauhinia tomentosa Linn. Formation of AgNPs was observed using ultraviolet-visible light spectrophotometry at different time intervals. Maximum absorption was observed after 4 h at 420 nm due to the reduction of Ag+ to Ag0. The stabilizing activity of functional groups was identified by Fourier-transform infrared spectroscopy. Size and surface morphology were also analyzed using scanning electron microscopy. The present study revealed the AgNPs were spherical in form with a diameter of 32 nm. The face-centered cubic structure of AgNPs was indexed using X-ray powder diffraction with peaks at 2θ = 37°, 49°, 63°, and 76° (corresponding to the planes of silver 111, 200, 220, 311), respectively. Energy-dispersive X-ray spectroscopy revealed that pure reduced silver (Ag0) was the major constituent (59.08%). Antimicrobial analyses showed that the biosynthesized AgNPs possess increased antibacterial activity (against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative), with larger zone formation against S. aureus (9.25 mm) compared with that of E. coli (6.75 mm)) and antifungal activity (against Aspergillus flavus and Candida albican (with superior inhibition against A. flavus (zone of inhibition: 7 mm) compared with C. albicans (zone of inhibition: 5.75 mm)). Inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was found to be dose-dependent with half-maximal inhibitory concentration (IC50) values of 56.77 µg/mL and 43.03 µg/mL for AgNPs and ascorbic acid (control), respectively, thus confirming that silver nanoparticles have greater antioxidant activity than ascorbic acid. Molecular docking was used to determine the mode of antimicrobial interaction of our biosynthesized B. tomentosa Linn flower-powder extract-derived AgNPs. The biogenic AgNPs preferred hydrophobic contacts to inhibit bacterial and fungal sustainability with reducing antioxidant properties, suggesting that biogenic AgNPs can serve as effective medicinal agents.
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Family with sequence similarity 72 A (FAM72A) is a pivotal mitosis-promoting factor that is highly expressed in various types of cancer. FAM72A interacts with the uracil-DNA glycosylase UNG2 to prevent mutagenesis by eliminating uracil from DNA molecules through cleaving the N-glycosylic bond and initiating the base excision repair pathway, thus maintaining genome integrity. In the present study, we determined a specific FAM72A-UNG2 heterodimer protein interaction using molecular docking and dynamics. In addition, through in silico screening, we identified withaferin B as a molecule that can specifically prevent the FAM72A-UNG2 interaction by blocking its cell signaling pathways. Our results provide an excellent basis for possible therapeutic approaches in the clinical treatment of cancer.
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Bioactive constituents from natural sources are of great interest as alternatives to synthetic compounds for the treatment of various diseases, including diabetes mellitus. In the present study, phytochemicals present in Leucaena leucocephala (Lam.) De Wit leaves were identified by gas chromatography-mass spectrometry and further examined by qualitative and quantitative methods. α-Amylase enzyme activity assays were performed and revealed that L. leucocephala (Lam.) De Wit leaf extract inhibited enzyme activity in a dose-dependent manner, with efficacy similar to that of the standard α-amylase inhibitor acarbose. To determine which phytochemicals were involved in α-amylase enzyme inhibition, in silico virtual screening of the absorption, distribution, metabolism, excretion, and toxicity properties was performed and pharmacophore dynamics were assessed. We identified hexadecenoic acid and oleic acid ((Z)-octadec-9-enoic acid) as α-amylase inhibitors. The binding stability of α-amylase to those two fatty acids was confirmed in silico by molecular docking and a molecular dynamics simulation performed for 100 ns. Together, our findings indicate that L. leucocephala (Lam.) De Wit-derived hexadecanoic acid and oleic acid are natural product-based antidiabetic compounds that can potentially be used to manage diabetes mellitus.
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Neural stem cells (NSCs) offer great potential for regenerative medicine due to their excellent ability to differentiate into various specialized cell types of the brain. In the central nervous system (CNS), NSC renewal and differentiation are under strict control by the regulation of the pivotal SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2)-Family with sequence similarity 72 (FAM72) master gene (i.e., |-SRGAP2-FAM72-|) via a divergent gene transcription activation mechanism. If the gene transcription control unit (i.e., the intergenic region of the two sub-gene units, SRGAP2 and FAM72) gets out of control, NSCs may transform into cancer stem cells and generate brain tumor cells responsible for brain cancer such as glioblastoma multiforme (GBM). Here, we discuss the surveillance of this |-SRGAP2-FAM72-| master gene and its role in GBM, and also in light of FAM72 for diagnosing various types of cancers outside of the CNS.
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BACKGROUND: Seeding is usually the initial step of high-throughput sequence aligners. Two popular seeding strategies are fixed-size seeding (k-mers, minimizers) and variable-size seeding (MEMs, SMEMs, maximal spanning seeds). The former strategy supports fast seed computation, while the latter one benefits from a high seed uniqueness. Algorithmic bridges between instances of both seeding strategies are of interest for combining their respective advantages. RESULTS: We introduce an efficient strategy for computing MEMs out of fixed-size seeds (k-mers or minimizers). In contrast to previously proposed extend-purge strategies, our merge-extend strategy prevents the creation and filtering of duplicate MEMs. Further, we describe techniques for extracting SMEMs or maximal spanning seeds out of MEMs. A comprehensive benchmarking shows the applicability, strengths, shortcomings and computational requirements of all discussed seeding techniques. Additionally, we report the effects of seed occurrence filters in the context of these techniques. Aside from our novel algorithmic approaches, we analyze hierarchies within fixed-size and variable-size seeding along with a mapping between instances of both seeding strategies. CONCLUSION: Benchmarking shows that our proposed merge-extend strategy for MEM computation outperforms previous extend-purge strategies in the context of PacBio reads. The observed superiority grows with increasing read size and read quality. Further, the presented filters for extracting SMEMs or maximal spanning seeds out of MEMs outperform FMD-index based extension techniques. All code used for benchmarking is available via GitHub at https://github.com/ITBE-Lab/seed-evaluation .
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Alineación de Secuencia/métodos , AlgoritmosRESUMEN
Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in >1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria. Around 300 million clinical cases of malaria occur each year in tropical and subtropical regions of the world, resulting in over one million deaths annually, placing malaria among the most serious infectious diseases. Genomic and proteomic research of the clades of parasites containing Pf is progressing slowly and the functions of most of the â¼5300 genes are still unknown. We applied a 'bottom-up' comparative proteomic atomics analysis across the phylogenetic tree to visualize a protein molecule on its actual basis - i. e., its atomic level. We identified a protruding Pf3D7-specific U5MTase, determined its 3D protein structure, and identified potential inhibitory drug molecules through in silico drug screening that might serve as possible remedies for the treatment of malaria. Besides, this atomic-based proteome map provides a unique approach for the identification of parasite-specific proteins that could be considered as novel therapeutic targets.
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Biología Computacional/métodos , Malaria Falciparum/enzimología , Metiltransferasas/química , Plasmodium falciparum/enzimología , Proteoma/química , Proteoma/metabolismo , Proteínas Protozoarias/química , Secuencia de Aminoácidos , Aminoácidos/química , Carbono/análisis , Simulación por Computador , Bases de Datos Genéticas , Humanos , Hidrógeno/análisis , Ligandos , Malaria Falciparum/tratamiento farmacológico , Metiltransferasas/antagonistas & inhibidores , Metiltransferasas/genética , Metiltransferasas/metabolismo , Modelos Químicos , Nitrógeno/análisis , Oxígeno/análisis , Filogenia , Plasmodium falciparum/química , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Estructura Terciaria de Proteína , Proteómica , Azufre/análisis , Uracilo/metabolismoRESUMEN
With the advent of computational genomics, an intensive search is underway for unique biomarkers for Homo sapiens that could be used to differentiate taxa within the Hominoidea, in particular to distinguish Homo from the apes (Pan, Gorilla, Pongo, and Hylobates) and species or subspecies within the genus Homo (H. sapiens, H. heidelbergensis, H. neanderthalensis, H. erectus, and the Denisovans). Here, we suggest that the |-FAM72-SRGAP2-| (family with sequence similarity 72/SLIT-ROBO Rho GTPase activating protein 2) gene pair is a unique molecular biomarker for the genus Homo that could also help to place Australopithecus at its most appropriate place within the phylogenetic tree and may explain the distinctive higher brain cognitive functions of humans.
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Cognición , Evolución Molecular , Proteínas Activadoras de GTPasa/genética , Hominidae/genética , Animales , Marcadores Genéticos , Hominidae/clasificación , Hominidae/fisiología , Humanos , FilogeniaRESUMEN
FAM72 is a novel neuronal progenitor cell (NPC) self-renewal supporting protein expressed under physiological conditions at low levels in other tissues. Accumulating data indicate the potential pivotal tumourigenic effects of FAM72. Our in silico human genome-wide analysis (GWA) revealed that the FAM72 gene family consists of four human-specific paralogous members, all of which are located on chromosome (chr) 1. Unique asymmetric FAM72 segmental gene duplications are most likely to have occurred in conjunction with the paired genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes have four paralogues in humans but only one vertebra-emerging orthologue in all other species. No species with two or three FAM72/SRGAP2 gene pairs could be identified, and the four exclusively human-defining ohnologues, with different mutation patterns in Homo neanderthalensis and Denisova hominin, may remain under epigenetic control through long non-coding (lnc) RNAs.