5,836 results match your criteria preferential activation

Stereo- and regiodefined DNA-encoded chemical libraries enable efficient tumour-targeting applications.

Nat Chem 2021 Apr 8. Epub 2021 Apr 8.

Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.

The encoding of chemical compounds with amplifiable DNA tags facilitates the discovery of small-molecule ligands for proteins. To investigate the impact of stereo- and regiochemistry on ligand discovery, we synthesized a DNA-encoded library of 670,752 derivatives based on 2-azido-3-iodophenylpropionic acids. The library was selected against multiple proteins and yielded specific ligands. Read More

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Unveiling the Dynamics of KRAS4b on Lipid Model Membranes.

J Membr Biol 2021 Apr 7. Epub 2021 Apr 7.

Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.

Small GTPase proteins are ubiquitous and responsible for regulating several processes related to cell growth and differentiation. Mutations that stabilize their active state can lead to uncontrolled cell proliferation and cancer. Although these proteins are well characterized at the cellular scale, the molecular mechanisms governing their functions are still poorly understood. Read More

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Zinc-dependent multimerization of mutant calreticulin is required for MPL binding and MPN pathogenesis.

Blood Adv 2021 Apr;5(7):1922-1932

School of Molecular and Cellular Biology, Faculty of Biological Sciences, and.

Calreticulin (CALR) is mutated in the majority of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs). Mutant CALR (CALRdel52) exerts its effect by binding to the thrombopoietin receptor MPL to cause constitutive activation of JAK-STAT signaling. In this study, we performed an extensive mutagenesis screen of the CALR globular N-domain and revealed 2 motifs critical for CALRdel52 oncogenic activity: (1) the glycan-binding lectin motif and (2) the zinc-binding domain. Read More

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Effect of Pd Coordination and Isolation on the Catalytic Reduction of O to HO over PdAu Bimetallic Nanoparticles.

J Am Chem Soc 2021 Apr 4. Epub 2021 Apr 4.

Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.

The direct synthesis of hydrogen peroxide (H + O → HO) may enable low-cost HO production and reduce environmental impacts of chemical oxidations. Here, we synthesize a series of PdAu nanoparticles (where 0 ≤ ≤ 220, ∼10 nm) and show that, in pure water solvent, HO selectivity increases with the Au to Pd ratio and approaches 100% for PdAu. Analysis of XAS and FTIR of adsorbed CO and CO show that materials with Au to Pd ratios of ∼40 and greater expose only monomeric Pd species during catalysis and that the average distance between Pd monomers increases with further dilution. Read More

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Expression of Phosphorylated BRD4 Is Markedly Associated with the Activation Status of the PP2A Pathway and Shows a Strong Prognostic Value in Triple Negative Breast Cancer Patients.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Pathology Department, Fundación Jiménez Díaz University Hospital Health Research Institute (IIS-FJD, UAM)-CIBERONC, E-28040 Madrid, Spain.

The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels. Read More

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Tuning Green to Red Color in Erbium Niobate Micro- and Nanoparticles.

Nanomaterials (Basel) 2021 Mar 8;11(3). Epub 2021 Mar 8.

i3N and Physics Department, University of Aveiro, 3810-193 Aveiro, Portugal.

Tetragonal ErNbO and monoclinic ErNbO micro- and nanoparticles were prepared by the citrate sol-gel method and heat-treated at temperatures between 700 and 1600 °C. ErNbO revealed a spherical-shaped crystallite, whose size increased with heat treatment temperatures. To assess their optical properties at room temperature (RT), a thorough spectroscopic study was conducted. Read More

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Microstructural Plasticity in the Hippocampus of Healthy Older Adults after Acute Exercise.

Med Sci Sports Exerc 2021 Mar 25. Epub 2021 Mar 25.

Department of Kinesiology, University of Maryland, College Park, MD Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Program in Neuroscience and Cognitive Science, University of Maryland, College Park, MD Maryland Neuroimaging Center, University of Maryland, College Park, MD.

Introduction: The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural MRI. Read More

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activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis.

PLoS Genet 2021 Mar 29;17(3):e1009466. Epub 2021 Mar 29.

Whitehead Institute for Biomedical Research, Cambridge, MA, United States of America.

Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. Read More

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Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation.

Front Immunol 2021 10;12:625165. Epub 2021 Mar 10.

Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector cells in HSCT and have been associated with post-transplant protection from relapse in clinical studies. Immunocompetent cells from the donor are crucial for patient outcomes and peripheral blood stem cells (PBSC) are being increasingly applied as graft source. Read More

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Hearing Better with the Right Eye? The Lateralization of Multisensory Processing Affects Auditory Learning in Northern Bobwhite Quail () Chicks.

Appl Anim Behav Sci 2021 Mar 23;236. Epub 2021 Feb 23.

Department of Psychology, Florida International University, Miami, FL 33199.

Precocial avian species exhibit a high degree of lateralization of perceptual and motor abilities, including preferential eye use for tasks such as social recognition and predator detection. Such lateralization has been related, in part, to differential experience prior to hatch. That is, due to spatial and resulting postural constraints late in incubation, one eye and hemisphere-generally the right eye / left hemisphere-receive greater amounts of stimulation than the contralateral eye / hemisphere. Read More

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Three-dimensional visualization of bidirectional preferential pathway conduction of premature ventricular contractions originating from the outflow tract.

J Cardiovasc Electrophysiol 2021 Mar 26. Epub 2021 Mar 26.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Introduction: Preferential pathway conduction is mostly detected as fractionated presystolic-potentials preceding the QRS during premature ventricular contractions (PVCs) and late-potentials during sinus rhythm (SR), but the electrophysiologic mechanisms and significance of these potentials have not been fully clarified. We describe a PVC case series in which the preferential pathway conduction was three-dimensionally visualized.

Methods: Five PVCs (two from the left coronary cusp, two from the commissure of the left and right coronary cusps, and one from the pulmonary artery) in four patients for which a fractionated presystolic-potential during the PVCs and late-potential during SR were recorded at the successful ablation site were reviewed, and three-dimensional coherent activation maps with the conduction velocity vector during the PVCs and SR were reconstructed. Read More

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Incidence, prevalence, and trajectories of repetitive conduction patterns in human atrial fibrillation.

Europace 2021 Mar;23(Supplement_1):i123-i132

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

Aims: Repetitive conduction patterns in atrial fibrillation (AF) may reflect anatomical structures harbouring preferential conduction paths and indicate the presence of stationary sources for AF. Recently, we demonstrated a novel technique to detect repetitive patterns in high-density contact mapping of AF. As a first step towards repetitive pattern mapping to guide AF ablation, we determined the incidence, prevalence, and trajectories of repetitive conduction patterns in epicardial contact mapping of paroxysmal and persistent AF patients. Read More

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Heartbeats entrain breathing via baroreceptor-mediated modulation of expiratory activity.

Exp Physiol 2021 Mar 21. Epub 2021 Mar 21.

Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA.

New Findings:   Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat (HB) in expiration. According to the cardiac-trigger hypothesis, the pulse pressure initiates an inspiration via baroreceptor activation. However, the central neural substrate mediating this coupling remains undefined. Read More

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Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.

J Nanobiotechnology 2021 Mar 19;19(1):79. Epub 2021 Mar 19.

Department of Orthopedics, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400014, China.

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Read More

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Design of BET Inhibitor Bottlebrush Prodrugs with Superior Efficacy and Devoid of Systemic Toxicities.

J Am Chem Soc 2021 Mar 19;143(12):4714-4724. Epub 2021 Mar 19.

XTuit Pharmaceuticals, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.

Prodrugs engineered for preferential activation in diseased versus normal tissues offer immense potential to improve the therapeutic indexes (TIs) of preclinical and clinical-stage active pharmaceutical ingredients that either cannot be developed otherwise or whose efficacy or tolerability it is highly desirable to improve. Such approaches, however, often suffer from trial-and-error design, precluding predictive synthesis and optimization. Here, using bromodomain and extra-terminal (BET) protein inhibitors (BETi)-a class of epigenetic regulators with proven anticancer potential but clinical development hindered in large part by narrow TIs-we introduce a macromolecular prodrug platform that overcomes these challenges. Read More

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Highly efficient catalytic properties of Sc and Fe single atoms stabilized on a honeycomb borophene/Al(111) heterostructure via a dual charge transfer effect.

Nanoscale 2021 Mar 16;13(11):5875-5882. Epub 2021 Mar 16.

School of Physics and Microelectronics, Zhengzhou University, Zhengzhou, Henan 450001, China.

Theoretical design and experimental fabrication of highly efficient single-atom catalysts (SACs) containing isolated metal atoms monodispersed on appropriate substrates have surged to the forefront of heterogeneous catalysis in recent years. Nevertheless, the instability of SACs, i.e. Read More

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Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.

Nanomedicine 2021 Mar 13;34:102383. Epub 2021 Mar 13.

Department of Bioengineering, The Pennsylvania State University, University Park, PA; Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA; Department of Pharmacology, Penn State University College of Medicine, Hershey, PA. Electronic address:

Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Read More

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Computational investigation of the impact of deep brain stimulation contact size and shape on neural selectivity.

J Neural Eng 2021 Mar 15. Epub 2021 Mar 15.

Neurology, Univ Utah, 175 North Medical Drive East, Salt Lake City, Utah, 84132, UNITED STATES.

Understanding neural selectivity is essential for optimizing medical applications of deep brain stimulation (DBS). We previously showed that modulation of the DBS waveform can induce changes in orientation-based selectivity, and that lengthening of DBS pulses or directional segmentation can reduce preferential selectivity for large axons. In this work, we sought to investigate a simple, but important question from a generalized perspective: how do the size and shape of the contact influence neural selectivity?We created multicompartment neuron models for several axon diameters and used finite element modeling with standard-sized cylindrical leads to determine the effects on changing contact size and shape on axon activation profiles and volumes of tissue activated. Read More

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Investigation of 2'-Deoxyadenosine-Derived Adducts Specifically Formed in Rat Liver and Lung DNA by '-Nitrosonornicotine Metabolism.

Chem Res Toxicol 2021 Mar 15. Epub 2021 Mar 15.

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States.

The International Agency for Research on Cancer has classified the tobacco-specific nitrosamines '-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as "carcinogenic to humans" (Group 1). To exert its carcinogenicity, NNN requires metabolic activation to form reactive intermediates which alkylate DNA. Previous studies have identified cytochrome P450-catalyzed 2'-hydroxylation and 5'-hydroxylation of NNN as major metabolic pathways, with preferential activation through the 5'-hydroxylation pathway in some cultured human tissues and patas monkeys. Read More

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Metabolic ROS Signaling: To Immunity and Beyond.

Biochemistry (Mosc) 2020 Dec;85(12):1650-1667

Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, NY 10065, USA.

Metabolism is a critical determinant of immune cell functionality. Immunometabolism, by definition, is a multidisciplinary area of immunology research that integrates the knowledge of energy transduction mechanisms and biochemical pathways. An important concept in the field is metabolic switch, a transition of immune cells upon activation to preferential utilization of select catabolic pathways for their energy needs. Read More

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December 2020

5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations.

Acta Cardiol 2021 Mar 8:1-13. Epub 2021 Mar 8.

Third Department of Cardiology, Ιppokratio General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent that can cause cardiotoxicity manifesting, among others, as chest pain. Capecitabine is an oral prodrug of 5-FU, with reported preferential activation in malignant cells that may also cause cardiotoxic reactions. Standard treatment of 5-FU and capecitabine induced chest pain with vasodilators is mostly effective, but there are several cases of patients unresponsive to these agents. Read More

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Quantification of Cytokines in Lip Tissue from Infants Affected by Congenital Cleft Lip and Palate.

Children (Basel) 2021 Feb 12;8(2). Epub 2021 Feb 12.

Department of Biology and Microbiology, Faculty of Medicine, Riga Stradiņš University, Dzirciema Street 16, LV-1007 Riga, Latvia.

Cleft lip and palate are amongst the most common congenital malformations worldwide presenting with variable manifestations. Previous research has been primarily focused on the genetical aspects of its complex and multifactorial etiology. In the present study, we investigated the role of cytokines as mediators of epithelial-mesenchymal crosstalk and local site inflammation in cleft affected infants. Read More

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February 2021

Evidence of Preferential Flow Activation in the Vadose Zone via Geophysical Monitoring.

Sensors (Basel) 2021 Feb 14;21(4). Epub 2021 Feb 14.

Water Research Institute, National Research Council of Italy, 70132 Bari, Italy.

Preferential pathways allow rapid and non-uniform water movement in the subsurface due to strong heterogeneity of texture, composition, and hydraulic properties. Understanding the importance of preferential pathways is crucial, because they have strong impact on flow and transport hydrodynamics in the unsaturated zone. Particularly, improving knowledge of the water dynamics is essential for estimating travel time through soil to quantify hazards for groundwater, assess aquifer recharge rates, improve agricultural water management, and prevent surface stormflow and flooding hazards. Read More

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February 2021

Reproducibility and Concurrent Validity of Manual Palpation with Rehabilitative Ultrasound Imaging for Assessing Deep Abdominal Muscle Activity: Analysis with Preferential Ratios.

Diagnostics (Basel) 2021 Feb 13;11(2). Epub 2021 Feb 13.

Department of Radiology, Rehabilitation and Physiotherapy, Universidad Complutense de Madrid, 28040 Madrid, Spain.

The abdominal drawing-in maneuver (ADIM) is a clinical tool used for identifying preferential activity of deep abdominal muscles. However, concurrent validity and reproducibility of palpation during the ADIM has not been formally investigated. The aims of this study were (1) to assess intra- and interrater reliability of manual palpation during the ADIM, and (2) to determine the concurrent validity of manual palpation during the ADIM by calculating preferential activation ratio cut-off as assessed with ultrasound imaging (RUSI). Read More

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February 2021

Constructing the constitutively active ribosomal protein S6 kinase 2 from Arabidopsis thaliana (AtRPS6K2) and testing its activity in vitro.

Vavilovskii Zhurnal Genet Selektsii 2020 May;24(3):233-238

M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty, Kazakhstan Institute of Plant Biology and Biotechnology, Almaty, Kazakhstan.

Ribosomal protein S6 (RPS6) is the only phosphorylatable protein of the eukaryotic 40S ribosomal subunit. Ribosomes with phosphorylated RPS6 can selectively translate 5'TOP-(5'-terminal oligopyrimidine)-containing mRNAs that encode most proteins of the translation apparatus. The study of translational control of 5'TOP-mRNAs, which are preferentially translated when RPS6 is phosphorylated and cease to be translated when RPS6 is de-phosphorylated, is particularly important. Read More

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Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research.

Front Cell Dev Biol 2021 15;9:629238. Epub 2021 Feb 15.

Department of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czechia.

Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fully comprehended yet, a growing body of evidence indicates their possible interconnection with the acute and chronic activation of an innate immune response. Current progress in insect immuno-metabolic research reveals that the induction of insulin resistance might represent an adaptive mechanism during the acute phase of bacterial infection. Read More

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February 2021

An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens.

Front Immunol 2021 15;12:645426. Epub 2021 Feb 15.

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. The most efficacious vaccine, CVI988/Rispens (CVI988), against MD has been used for several decades. However, the mechanisms leading to protective immunity following vaccination are not fully understood. Read More

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February 2021

Bromodomain protein BRDT directs ΔNp63 function and super-enhancer activity in a subset of esophageal squamous cell carcinomas.

Cell Death Differ 2021 Mar 3. Epub 2021 Mar 3.

Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany.

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer with a particularly high prevalence in certain geographical regions and a poor prognosis with a 5-year survival rate of 15-25%. Despite numerous studies characterizing the genetic and transcriptomic landscape of ESCC, there are currently no effective targeted therapies. In this study, we used an unbiased screening approach to uncover novel molecular precision oncology targets for ESCC and identified the bromodomain and extraterminal (BET) family member bromodomain testis-specific protein (BRDT) to be uniquely expressed in a subgroup of ESCC. Read More

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Effects of NMES pulse width and intensity on muscle mechanical output and oxygen extraction in able-bodied and paraplegic individuals.

Eur J Appl Physiol 2021 Mar 3. Epub 2021 Mar 3.

Department of Medicine, University of Udine, Udine, Italy.

Purpose: Neuromuscular Electrical Stimulation (NMES) is commonly used in neuromuscular rehabilitation protocols, and its parameters selection substantially affects the characteristics of muscle activation. Here, we investigated the effects of short pulse width (200 µs) and higher intensity (short-high) NMES or long pulse width (1000 µs) and lower intensity (long-low) NMES on muscle mechanical output and fractional oxygen extraction. Muscle contractions were elicited with 100 Hz stimulation frequency, and the initial torque output was matched by adjusting stimulation intensity. Read More

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Hepatitis B-induced IL-8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation.

Cancer Res 2021 Mar 2. Epub 2021 Mar 2.

Chinese Academy of Sciences Key Laboratory of Infection and Immunity,IBP, Institute of Biophysics

Hepatitis B-associated hepatocellular carcinoma (HCC) is often accompanied by severe vascular invasion and portal vein tumor thrombus leading to a poor prognosis. However, the underlying mechanism of this disease remains obscure. In this study, we demonstrate that the hepatitis B virus (HBV)-encoded gene HBx induces high IL-8 production through MEK-ERK signal activation, leading to enhanced endothelial permeability to facilitate tumor vascular invasion. Read More

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