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Multiple ramp domains are required for generation of amylin receptor phenotype from the calcitonin receptor gene product.

Calcitonin (CT), calcitonin gene-related peptide (CGRP), amylin, and adrenomedullin constitute a family of structurally related peptides that signal via either the calcitonin receptor-like receptor or the CT receptor, with receptor phenotype determined by coexpression of one of the three receptor activity-modifying proteins (RAMPs). The nature of the interaction between the receptor and RAMP was investigated using chimeras between RAMP1 and RAMP2 where the amino-terminal domain of RAMP1 was attached to the transmembrane domain and carboxy terminus of RAMP2 and called RAMP1/2, and vice versa fo…

The Y-chromosomal and autosomal male-determining M factors of Musca domestica are equivalent.

In Musca domestica, male sex is determined by a dominant factor, M, located either on the Y, the X or on an autosome. M prevents the activity of the female-determining gene F. In the absence of M, F becomes active and dictates female development. The various M factors may represent translocated copies of an ancestral Y-chromosomal M. Double mutants and germ line chimeras show that MY, MI, MII, MIII and MV perform equivalent functions. When brought into the female germ line, they predetermine male development of the offspring. This maternal effect is overruled by the dominant female-determining…

Studies on inhibition of mu and delta opioid receptor binding by dithiothreitol and N-ethylmaleimide. His223 is critical for mu opioid receptor binding and inactivation by N-ethylmaleimide.

The sensitivity of mu and delta receptor binding to dithiothreitol and N-ethylmaleimide was examined to probe receptor structure and functio … 0 of N-ethylmaleimide toward both receptor types in a ligand-dependent manner. Analysis of receptor chimeras suggested that the site of N-ethylmaleimide alkylation on the mu receptor was between transmembrane domains 3 and 5. Substitution of cysteines between transmembrane domains 3 and 5 and elsewhere had no effect on receptor binding or sensitivity towa …

Human immunodeficiency virus infection of xenografted SCID-beige mice.

The application of C.B-17 SCID-Beige mice as an experimental animal system for the acceptance of human leukocyte xenografts, the establishme … . These results indicate that SCID-Beige mice are a valuable tool for the generation of human/mouse chimeras and for the establishment of an in vivo HIV infection model. The results are compared with other similar model systems and are discussed in the context of animal models of HIV vaccine studies.

Restoration of the Epstein-Barr virus ZEBRA protein's capacity to disrupt latency by the addition of heterologous activation regions.

The ZEBRA protein has a unique biological function among herpesviral proteins. It is responsible for the disruption of Epstein-Barr virus (E … from the herpes simplex virus VP16 protein or with the activation region of the EBV R protein. Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself. Activation was not target- or cell-type dependent, nor was it dependent on the presence of virus. These activation domains restored ZEBRA's abi …

Successful pancreatic allografts in combination with bone marrow transplantation in mice.

We have established a new method for pancreatic allografts in mice by combining pancreatic transplantation with allogeneic bone marrow trans … nt of both donor (stem cell)-type and host-type MHC determinants. By contrast, the T cells of these chimeras showed a significant responsiveness to third party MHC determinants. These findings suggest that pancreatic allografts combined with bone marrow transplantation may become a viable strategy for the treatment of patients with diabetes or patients wh …

Integrated stress signaling pathways promote adaptive reprogramming for chondrocyte survival in Metaphyseal Chondrodysplasia Type Schmid.

Collagen X, encoded by the Col10a1 gene, is expressed specifically by hypertrophic chondrocytes (HCs) in the cartilage. Mutations of the Col … hypoxia and HIFs pathways are triggered by ER stress or extrinsic factors, we generated WT/GFP-MCDS chimera mice. Our findings showed that the activation of hypoxia and the hypoxic pathway is an intrinsic response to ER stress, which may partly occur through activation of ATF4 in HCs of mice. In parallel, p53 pathway changes and autophagy-associated prote …

A novel matrine derivative B10 exerts its anti-liver cancer activity in vitro and in vivo via targeting FGFR3/PI3K/AKT signaling pathway.

Natural products represent a cornerstone in anticancer drug discovery owing to their structural diversity and unique bioactivities. Among th … ug sorafenib. Critically, to decipher the underlying mechanism, we employed a proteolysis-targeting chimera (PROTAC) strategy, converting B10 into a targeted degrader, K2. This chemical probe enabled us to identify fibroblast growth factor receptor 3 (FGFR3) as a direct target of B10 and to elucidate its role in suppressing the FGFR3/PI3K/AKT signaling pa …

Brown spider venom phospholipase D as a tool to modulate melanoma cell biology.

Phospholipases D (PLDs) from Loxosceles venoms are enzymes that cleave phospholipids triggering biological effects, as uncontrolled inflammatory response. We treated melanoma cell lines B16-F1 and B16-F10 with recombinant PLD from the venom of the spider Loxosceles intermedia. Toxin binding to cell surface and modulating events were evaluated by specific antibodies, or a chimera PLD-GFP and confocal fluorescence microscopy, flow cytometry, inverted microscopy, and scanning electron microscopy. Cytotoxicity was performed using MTT, Trypan Blue, and CellTiterGlo; and intracellular calcium measur…

Concurrent chronic methamphetamine exposure may influence behavioral outcomes following repetitive mild traumatic brain injury.

RATIONALE: Traumatic brain injury (TBI) and substance use disorder (SUD) share several characteristics, including neurological outcomes and … tingent dosing of methamphetamine with the Closed Head Model of Engineered Rotational Acceleration (CHIMERA). Behavioral assays were employed one month after the final TBI to assess short-term effects and were repeated six months following the final TBI for long-term effects. RESULTS: The Loss of Righting Reflex showed that chronic methamphetamine exposu …

In Silico Functional and Structural Analysis of STAT4 Variants of Uncertain Significance.

BACKGROUND: The STAT4 gene plays a key role in immune regulation and is associated with susceptibility to autoimmune diseases such as rheuma … uch as SIFT, PolyPhen, MutPred2, and Align-GVGD, as well as structural modeling platforms including Chimera, ModRefiner, Missense3D, HOPE, and DynaMut2. RESULTS: Eighty missense VUSs were identified; of these, 13 were prioritized based on concordant signals across multiple computational predictors. These variants showed significant alterations in the phy …

Proteasome inhibition enhances lysosome-mediated targeted protein degradation.

Proteasome inhibitor drugs are currently used in the clinic to treat multiple myeloma and mantle cell lymphoma. These inhibitors cause accum … tophagy could instead be leveraged therapeutically. To this end, we designed an autophagy-targeting chimera (AUTAC) compound to selectively degrade the anti-apoptotic protein Mcl1 via the lysosome. Our results show that this lysosome-mediated targeted degradation is significantly amplified in the presence of proteasome inhibition, in a NRF1-dependent mann …

Grass carp reovirus activates fish Ppp1r3g to suppress innate immunity and exacerbate hemorrhage via the 14-3-3ζ/Itgb3 signaling axis.

Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is one of the regulatory subunits of protein phosphatase 1 (PP1). Current research on … that compared with the wild-type controls, ppp1r3g-null rare minnow (Gobiocypris rarus) and ppp1r3g-chimera grass carp (Ctenopharyngodon idella) exhibited significantly enhanced resistance to grass carp reovirus (GCRV), with markedly alleviated hemorrhagic symptoms post-infection. Furthermore, knockdown of ppp1r3g suppressed GCRV replication and upregulat …

Discovery of a potent PROTAC targeting G9a suppresses proliferation of triple-negative breast cancer cells and psoriasis-like keratinocytes.

G9a is a SET domain-containing histone methyltransferase that catalyzes H3K9 methylation to regulate gene transcription. Recent studies have revealed that G9a exerts both catalytic and non-catalytic functions in tumor progression and inflammatory diseases, establishing it as a promising therapeutic target. Herein, we developed L4 by using proteolysis targeting chimera (PROTAC) technology. L4 induces G9a degradation through the ubiquitin-proteasome system (UPS) in both a concentration- and time-dependent manner (DC50 = 1.29 μM), while substantially reducing H3K9me2 expression levels. Through mo…

Pinoresinol as a Potential c-Myc Complex Modulator: An In Silico Study.

The c-Myc oncoprotein is a central regulator of oncogenic transcriptional programs that remains challenging to inhibit directly, necessitati … andard, widely used tools (e.g., AutoDock Vina v1.1.2; visualization and interface analyses in UCSF Chimera/ChimeraX and SeamDock). Molecular docking and binding-interface analyses identified reproducible interactions within defined pockets P0, P1, and P2, with pocket P0 exhibiting the highest Drug Score of 0.82. Binding affinities ranged from -5.0 to -7. …

SARS-CoV-2 proteins show great binding affinity to resin composite monomers and polymerized chains.

BACKGROUND: Due to saliva and salivary glands are reservoir to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), aerosols and sa … dimethacrylate was evaluated. Molecular docking was performed using AutoDock Vina and visualised in Chimera UCSF 1.14. The best ligand-protein model was identified based on the binding energy (ΔG-kcal/moL). RESULTS: Values for the binding energies ranged from -3.6 kcal/moL to -7.3 kcal/moL. The 3-monomer chain had the lowest binding energy (i.e. highest …

Кристальная структура и каталитический механизм дрименоловой синтазы, необычная двухфункциональная терпеновая киклаза-фосфатаза.

Дрименол синтаза из Aquimarina pongiae (ASDMS) — очень необычная химера, интегрирующая two - отдельные, последовательные операции по переработке изопреноидов в рамках единой полипептидной цепи. ASDMS катализирует циклизацию фарнесилового дифосфата (FPP) класса II для образования дрименилового дифосфата, который затем подвергается гидролизу энзим-катализу для получения дрименинола, биоактивного сескитерпенового спирта с антифунгальными и антираковыми свойствами. Здесь мы сообщаем рентгеновские кристаллы ASDMS и его комплекс с сескитерпен тиол. Структура ASDMS имеет дидомаиновую архитектуру, сос

Совпадение в аннотации оригинала
Drimenol synthase from Aquimarina spongiae (AsDMS) is a highly unusual chimera that integrates two distinct, sequential isoprenoid processing activities within a single polypeptide chain. AsDMS catalyzes the class II cyclization of farnesyl diphosphate (FPP) to form drimenyl diphosphate, which then undergoes enzyme-catalyzed hydrolysis to yield drimenol, a b…

Evaluation of chlorogenic acids and melanoidin interactions with salivary proteins and their effect on tooth discoloration.

BACKGROUND: Tooth discoloration is a multifactorial process that is significantly influenced by the interaction between dietary polyphenols … rotein [PRP]). Hex 8.0 was used for molecular docking, whereas Discovery Studio Visualizer and UCSF Chimera were used for molecular dynamics analysis. RESULTS: Molecular docking revealed the strong binding affinity of chlorogenic acid with PRP (-251.66 kJ/mol), histatin (-245.4 kJ/mol), and statherin (-240.5 kJ/mol), stabilized by hydrogen bonds with gly …

Differential Impact of Recruited and Resident Macrophages on Hypoxia-Induced Pulmonary Hypertension.

BACKGROUND: Pulmonary interstitial macrophages can be divided into 2 distinct subsets with different origins: resident macrophages (resMФs) … ulmonary hypertension (PH). Therapeutic approaches included DNA aptamer-based proteolysis-targeting chimera and small interfering RNA-loaded lipid nanoparticle for treating SU5416/hypoxia-exposed rats. RESULTS: Depletion of either resMФs or recMФs using DT treatment significantly reduced SU5416/hypoxia-induced PH in mice. Pulmonary recMФs exhibited a pro …

The p.Ile202Thr Substitution in TUBB2B Can Be Associated with Syndromic Presentation of Congenital Fibrosis of the Extraocular Muscles.

Background: Dominantly acting variants in TUBB2B have primarily been associated with cortical dysplasia complex with other brain malformatio … was performed. The structural impact of the identified substitution was assessed by using the UCSF Chimera (v.1.17.3) software and PyMOL docking plugin DockingPie tool. Results: WGS analysis identified a de novo missense TUBB2B variant (p.Ile202Thr, NM_178012.5), previously associated with isolated CDCBM7. Structural analysis and docking simulations reve …