keyword
https://read.qxmd.com/read/38537148/conformation-selection-by-atp-competitive-inhibitors-and-allosteric-communication-in-erk2
#1
JOURNAL ARTICLE
Jake W Anderson, David Vaisar, David N Jones, Laurel M Pegram, Guy P Vigers, Huifen Chen, John G Moffat, Natalie G Ahn
Activation of the extracellular signal-regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named 'L' and 'R,' where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site...
March 27, 2024: ELife
https://read.qxmd.com/read/38536662/natural-killer-group%C3%A2-2d-major-histocompatibility-complex-class%C3%A2-i-polypeptide-related-sequence%C3%A2-a-activation-enhances-natural-killer-cell-mediated-immunity-against-hepatocellular-carcinoma-a-review
#2
REVIEW
Jun Arai, Akinori Okumura, Naoya Kato, Kiyoaki Ito
The recent clinical introduction of immune checkpoint inhibitors has improved therapeutic outcomes in patients with advanced hepatocellular carcinoma. However, these therapies targeting CD8+ T lymphocytes have a response rate of approximately 30%. In addition to CD8+ T lymphocytes, natural killer (NK) cells represent promising therapeutic targets for hepatocellular carcinoma, because they comprise 30%-50% of all lymphocytes in the liver and contribute to antitumor immunity. A recent meta-analysis revealed that the percentage of infiltrating NK cells in hepatocellular carcinoma correlates with a better patient outcome...
March 27, 2024: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://read.qxmd.com/read/38535570/transcriptome-analyses-in-adult-olive-trees-indicate-acetaldehyde-release-and-cyanide-mediated-respiration-traits-as-critical-for-tolerance-against-xylella-fastidiosa-and-suggest-aox-gene-family-as-marker-for-multiple-resilience
#3
JOURNAL ARTICLE
Birgit Arnholdt-Schmitt, Debabrata Sircar, Shahid Aziz, Thais Andrade Germano, Karine Leitão Lima Thiers, Carlos Noceda, Revuru Bharadwaj, Gunasekaran Mohanapriya, José Hélio Costa
Xylella fastidiosa ( Xf ) is a global bacterial threat for a diversity of plants, including olive trees. However, current understanding of host responses upon Xf -infection is limited to allow early disease prediction, diagnosis, and sustainable strategies for breeding on plant tolerance. Recently, we identified a ma jor c omplex t rait for e arly d e novo programming, named CoV-MAC-TED , by comparing early transcriptome data during plant cell survival with SARS-CoV-2-infected human cells. This trait linked ROS/RNS balancing during first hours of stress perception with increased aerobic fermentation connected to alpha-tubulin-based cell restructuration and control of cell cycle progression...
March 5, 2024: Pathogens
https://read.qxmd.com/read/38535201/gut-mycobiome-and-asthma
#4
REVIEW
Amjad N Kanj, Joseph H Skalski
This review explores the 'gut-lung axis' in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community composition alter lung immune function. We comprehensively review available studies that have profiled the composition of the gut mycobiome in adults and children with asthma, and discuss mechanisms of gut-lung interactions that have been described in animal models of asthma. Studies indicate that intestinal fungal dysbiosis, such as an increased abundance of certain fungi like Candida , can elevate the risk of asthma in children and exacerbate it in adults...
March 1, 2024: Journal of Fungi (Basel, Switzerland)
https://read.qxmd.com/read/38535164/examining-the-interplay-between-the-cognitive-and-emotional-aspects-of-gender-differences-in-spatial-processing
#5
JOURNAL ARTICLE
Cynthia M Fioriti, Raeanne N Martell, Richard J Daker, Eleanor P Malone, H Moriah Sokolowski, Adam E Green, Susan C Levine, Erin A Maloney, Gerardo Ramirez, Ian M Lyons
Women reliably perform worse than men on measures of spatial ability, particularly those involving mental rotation. At the same time, females also report higher levels of spatial anxiety than males. What remains unclear, however, is whether and in what ways gender differences in these cognitive and affective aspects of spatial processing may be interrelated. Here, we tested for robust gender differences across six different datasets in spatial ability and spatial anxiety (N = 1257, 830 females). Further, we tested for bidirectional mediation effects...
March 4, 2024: Journal of Intelligence
https://read.qxmd.com/read/38534723/the-role-of-aminopeptidase-erap1-in-human-pathology-a-review
#6
REVIEW
Laura Țiburcă, Dana Carmen Zaha, Maria Claudia Jurca, Emilia Severin, Aurora Jurca, Alexandru Daniel Jurca
Aminopeptidases are a group of enzymatic proteins crucial for protein digestion, catalyzing the cleavage of amino acids at the N-terminus of peptides. Among them are ERAP1 (coding for endoplasmic reticulum aminopeptidase 1), ERAP2 (coding for endoplasmic reticulum aminopeptidase 2), and LNPEP (coding for leucyl and cystinyl aminopeptidase). These genes encoding these enzymes are contiguous and located on the same chromosome (5q21); they share structural homology and functions and are associated with immune-mediated diseases...
February 20, 2024: Current Issues in Molecular Biology
https://read.qxmd.com/read/38534474/engineered-dual-antioxidant-enzyme-complexes-targeting-icam-1-on-brain-endothelium-reduce-brain-injury-associated-neuroinflammation
#7
JOURNAL ARTICLE
Brian M Leonard, Vladimir V Shuvaev, Trent A Bullock, Kalpani N Udeni Galpayage Dona, Vladimir R Muzykantov, Allison M Andrews, Servio H Ramirez
The neuroinflammatory cascade triggered by traumatic brain injury (TBI) represents a clinically important point for therapeutic intervention. Neuroinflammation generates oxidative stress in the form of high-energy reactive oxygen and nitrogen species, which are key mediators of TBI pathology. The role of the blood-brain barrier (BBB) is essential for proper neuronal function and is vulnerable to oxidative stress. Results herein explore the notion that attenuating oxidative stress at the vasculature after TBI may result in improved BBB integrity and neuroprotection...
February 21, 2024: Bioengineering
https://read.qxmd.com/read/38534359/insights-into-disease-progression-of-translational-preclinical-rat-model-of-interstitial-pulmonary-fibrosis-through-endpoint-analysis
#8
JOURNAL ARTICLE
Anil H Kadam, Jan E Schnitzer
Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix (ECM), causing lung distortions and dysfunction. Animal models of human IPF can provide great insight into the mechanistic pathways underlying disease progression and a means for evaluating novel therapeutic approaches. In this study, we describe the effect of bleomycin concentration on disease progression in the classical rat bleomycin model. In a dose-response study (1...
March 15, 2024: Cells
https://read.qxmd.com/read/38534350/inflammatory-skin-diseases-focus-on-the-role-of-suppressors-of-cytokine-signaling-socs-proteins
#9
REVIEW
Antonia Cianciulli, Rosa Calvello, Chiara Porro, Dario Domenico Lofrumento, Maria Antonietta Panaro
Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial...
March 13, 2024: Cells
https://read.qxmd.com/read/38534334/hdac6-enhances-endoglin-expression-through-deacetylation-of-transcription-factor-sp1-potentiating-bmp9-induced-angiogenesis
#10
JOURNAL ARTICLE
Chen Sun, Kuifang Xie, Lejie Yang, Shengyang Cai, Mingjie Wang, Yizhun Zhu, Beibei Tao, Yichun Zhu
Histone deacetylase 6 (HDAC6) plays a crucial role in the acetylation of non-histone proteins and is notably implicated in angiogenesis, though its underlying mechanisms were previously not fully understood. This study conducted transcriptomic and proteomic analyses on vascular endothelial cells with HDAC6 knockdown, identifying endoglin (ENG) as a key downstream protein regulated by HDAC6. This protein is vital for maintaining vascular integrity and plays a complex role in angiogenesis, particularly in its interaction with bone morphogenetic protein 9 (BMP9)...
March 11, 2024: Cells
https://read.qxmd.com/read/38534324/functional-selectivity-of-cannabinoid-type-1-g-protein-coupled-receptor-agonists-in-transactivating-glycosylated-receptors-on-cancer-cells-to-induce-epithelial-mesenchymal-transition-metastatic-phenotype
#11
JOURNAL ARTICLE
David A Bunsick, Jenna Matsukubo, Rashelle Aldbai, Leili Baghaie, Myron R Szewczuk
Understanding the role of biased G protein-coupled receptor (GPCR) agonism in receptor signaling may provide novel insights into the opposing effects mediated by cannabinoids, particularly in cancer and cancer metastasis. GPCRs can have more than one active state, a phenomenon called either 'biased agonism', 'functional selectivity', or 'ligand-directed signaling'. However, there are increasing arrays of cannabinoid allosteric ligands with different degrees of modulation, called 'biased modulation', that can vary dramatically in a probe- and pathway-specific manner, not from simple differences in orthosteric ligand efficacy or stimulus-response coupling...
March 8, 2024: Cells
https://read.qxmd.com/read/38533975/cgmp-dependent-kinase-2-na-h-exchanger-nhe3-and-pdz-adaptor-nherf2-co-assemble-in-apical-membrane-microdomains
#12
JOURNAL ARTICLE
Min Luo, Yongjian Liu, Katerina Nikolovska, Brigitte Riederer, Enrico Patrucco, Franz Hofmann, Ursula Seidler
AIM: Trafficking, membrane retention, and signal-specific regulation of the Na+ /H+ exchanger 3 (NHE3) are modulated by the Na+ /H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adapter proteins. This study explored the assembly of NHE3 and NHERF2 with the cGMP-dependent kinase II (cGKII) within detergent-resistant membrane microdomains (DRMs, "lipid rafts") during in vivo guanylate cycle C receptor (Gucy2c) activation in murine small intestine. METHODS: Small intestinal brush border membranes (siBBMs) were isolated from wild type, NHE3-deficient, cGMP-kinase II-deficient, and NHERF2-deficient mice, after oral application of the heat-stable Escherichia coli toxin (STa) analog linaclotide...
March 27, 2024: Acta Physiologica
https://read.qxmd.com/read/38533876/lymph-node-targeting-mediated-by-albumin-hitchhiking-of-synthetic-tn-glycolipid-leads-to-robust-in-vivo-antibody-production
#13
JOURNAL ARTICLE
Keerthana Thekke Veettil, Narayanaswamy Jayaraman
Tn antigen is a tumor-associated carbohydrate antigen (TACA), which is present prominently on the tumor cell surfaces and attracts an interest in the vaccine development. In this work, we demonstrate that a synthetic Tn antigen carrying glycoconjugate forms complex with circulating albumin, delivers the antigen to lymph nodes and leads to efficient production of antibody against the antigen. Synthetic Tn antigen glycoconjugate, possessing DSPE-PEG2000 linker and lipophilic moieties, undergoes micellization in PBS buffer...
March 27, 2024: Advanced Healthcare Materials
https://read.qxmd.com/read/38533838/compatibility-of-termination-mechanisms-in-bacterial-transcription-with-inference-on-eukaryotic-models
#14
JOURNAL ARTICLE
Eunho Song, Sun Han, Sungchul Hohng, Changwon Kang
Transcription termination has evolved to proceed through diverse mechanisms. For several classes of terminators, multiple models have been debatably proposed. Recent single-molecule studies on bacterial terminators have resolved several long-standing controversies. First, termination mode or outcome is twofold rather than single. RNA is released alone before DNA or together with DNA from RNA polymerase (RNAP), i.e. with RNA release for termination, RNAP retains on or dissociates off DNA, respectively. The concomitant release, described in textbooks, results in one-step decomposition of transcription complexes, and this 'decomposing termination' prevails at ρ factor-dependent terminators...
March 27, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38533662/neural-circuits-underlying-reciprocal-cardiometabolic-crosstalk-2023-arthur-c-corcoran-memorial-lecture
#15
REVIEW
Kamal Rahmouni
The interplay of various body systems, encompassing those that govern cardiovascular and metabolic functions, has evolved alongside the development of multicellular organisms. This evolutionary process is essential for the coordination and maintenance of homeostasis and overall health by facilitating the adaptation of the organism to internal and external cues. Disruption of these complex interactions contributes to the development and progression of pathologies that involve multiple organs. Obesity-associated cardiovascular risks, such as hypertension, highlight the significant influence that metabolic processes exert on the cardiovascular system...
March 27, 2024: Hypertension
https://read.qxmd.com/read/38533452/plant-toll-interleukin-1-receptor-resistance-protein-domains-physically-associate-with-enhanced-disease-susceptibility1-family-proteins-in-immune-signaling
#16
JOURNAL ARTICLE
Jian Chen, Xiaoxiao Zhang, Maud Bernoux, John P Rathjen, Peter N Dodds
Plant Toll/interleukin-1 receptor/resistance protein (TIR) type nucleotide-binding and leucine-rich repeat immune receptors (NLRs) require enhanced disease susceptibility 1 (EDS1) family proteins and the helper NLRs NRG1 and ADR1 for immune activation. We show that the Nb EDS1- Nb SAG101b- Nb NRG1 signaling pathway in N. benthamiana is necessary for cell death signaling by TIR-NLRs from a range of plant species, suggesting a universal requirement for this module in TIR-NLR-mediated cell death in N. benthamiana...
February 16, 2024: IScience
https://read.qxmd.com/read/38533208/lncrna-mediated-cerna-network-reveals-the-mechanism-of-action-of-saorilao-4-decoction-against-pulmonary-fibrosis
#17
JOURNAL ARTICLE
Xinyue Fu, Xinni Song, Shufang Niu, Songli Shi, Hong Chang, Jun Qi, Peng Wang, Wanfu Bai
Introduction: Pulmonary fibrosis (PF), a type of interstitial pneumonia with complex etiology and high mortality, is characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. In this study, we screened for potential biomarkers in PF and clarified the role of the lncRNA-miRNA-mRNA ceRNA network in the inhibitory effect of SRL-4 on PF. Methods: Healthy male SPF SD rats were randomly divided into three groups, namely, CON, MOD, and SRL-4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to determine the biological functions of the target genes...
2024: Frontiers in Genetics
https://read.qxmd.com/read/38533057/lrrc59-promotes-the-progression-of-oral-squamous-cell-carcinoma-by-interacting-with-srp-pathway-components-and-enhancing-the-secretion-of-ckap4-containing-exosomes
#18
JOURNAL ARTICLE
Qijun Sun, Lili Jin, Shunli Dong, Ling Zhang
BACKGROUND: As a ribosome receptor, LRRC59 was thought to regulate mRNA translation on the ER membrane. Evidence suggests that LRRC59 is overexpressed in a number of human malignancies and is associated with poor prognoses, but its primary biological function in the development of oral squamous cell carcinoma (OSCC) remains obscure. OBJECTIVE: The purpose of this study is to investigate at the expression changes and functional role of LRRC59 in OSCC. METHODS: LRRC59 gene expression and correlation with prognosis of OSCC patients were first examined using the data from The Cancer Genome Atlas (TCGA) databases...
March 30, 2024: Heliyon
https://read.qxmd.com/read/38533031/eupatolide-isolated-from-liriodendron-tulipifera-sensitizes-tnf-mediated-dual-modes-of-apoptosis-and-necroptosis-by-disrupting-ripk1-ubiquitination
#19
JOURNAL ARTICLE
Kyeong Ah Park, Chan Seok Jung, Kyung-Cheol Sohn, Eunjin Ju, Sanghee Shin, InWha Park, MinKyun Na, Gang Min Hur
Ubiquitination of RIPK1 plays an essential role in the recruitment of the IKK complex, an upstream component of pro-survival NF-κB. It also limits TNF-induced programmed cell death by inhibiting the spatial transition from TNFR1-associated complex-I to RIPK1-dependent death-inducing complex-II or necrosome. Thus, the targeted disruption of RIPK1 ubiquitination, which induces RIPK1-dependent cell death, has proven to be a useful strategy for improving the therapeutic efficacy of TNF. In this study, we found that eupatolide, isolated from Liriodendron tulipifera, is a potent activator of the cytotoxic potential of RIPK1 by disrupting the ubiquitination of RIPK1 upon TNFR1 ligation...
March 30, 2024: Heliyon
https://read.qxmd.com/read/38532930/targeting-of-lysosomal-bound-protein-meak-7-for-cancer-therapy
#20
REVIEW
Insoon Chang, Yi-Ling Loo, Jay Patel, Joe Truong Nguyen, Jin Koo Kim, Paul H Krebsbach
mEAK-7 (mammalian EAK-7 or MTOR-associated protein, eak-7 homolog), is an evolutionarily conserved lysosomal membrane protein that is highly expressed in several cancer cells. Multiple recent studies have identified mEAK-7 as a positive activator of mTOR (mammalian/mechanistic target of rapamycin) signaling via an alternative mTOR complex, implying that mEAK-7 plays an important role in the promotion of cancer proliferation and migration. In addition, structural analyses investigating interactions between mEAK-7 and V-ATPase, a protein complex responsible for regulating pH homeostasis in cellular compartments, have suggested that mEAK-7 may contribute to V-ATPase-mediated mTORC1 activation...
2024: Frontiers in Oncology
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