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Plasticity of seven-transmembrane-helix receptor heteromers in human vascular smooth muscle cells.

PLoS One 2021 24;16(6):e0253821. Epub 2021 Jun 24.

Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.

Recently, we reported that the chemokine (C-X-C motif) receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) heteromerize with α1A/B/D-adrenoceptors (ARs) and arginine vasopressin receptor 1A (AVPR1A) in recombinant systems and in rodent and human vascular smooth muscle cells (hVSMCs). In these studies, we observed that heteromerization between two receptor partners may depend on the presence and the expression levels of other partnering receptors. To test this hypothesis and to gain initial insight into the formation of these receptor heteromers in native cells, we utilized proximity ligation assays in hVSMCs to visualize receptor-receptor proximity and systematically studied how manipulation of the expression levels of individual protomers affect heteromerization patterns among other interacting receptor partners. Read More

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[Surgical treatment of true aneurysms of permanent vascular access].

Angiol Sosud Khir 2021 ;27(2):106-113

Department of Vascular Surgery, Republican Clinical Hospital of the Public Health Ministry of the Republic of Tatarstan, Kazan, Russia.

Analyzed herein are the results of surgical treatment of true diffuse aneurysms of the permanent vascular access in 44 patients. Of these, there were 29 men and 15 women, mean age 48.1±2. Read More

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January 2021

A survey of distracted driving and electronic device use among app-based and taxi drivers.

Traffic Inj Prev 2021 Jun 24:1-5. Epub 2021 Jun 24.

Herbert Wertheim School of Public Health and Longevity Science, University of California, San Diego, California.

Objectives: The purpose of this study was to identify, characterize and compare attitudes, beliefs, behaviors and other factors related to electronic device (ED) use and distracted driving (DD) among taxi and app-based drivers.

Methods: A survey among drivers in San Diego and across the United States was used to collect self-reported attitudes and behaviors among taxi and app-based passenger-carrying drivers from October 1, 2016 to January 31, 2017. Chi-square or Fisher's exact test was used to assess the difference between sociodemographics, ED use, ED use attitudes, and citation and crash history by driver type. Read More

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Dehydrocrenatidine extracted from induces the apoptosis of nasopharyngeal carcinoma cells through the JNK and ERK signaling pathways.

Oncol Rep 2021 Aug 24;46(2). Epub 2021 Jun 24.

Post Baccalaureate Medicine, National Chung Hsing University, Taichung 402, Taiwan, R.O.C.

Nasopharyngeal carcinoma (NPC) is an indicator disease in Asia due to its unique geographical and ethnic distribution. Dehydrocrenatidine (DC) is a β‑carboline alkaloid abundantly present in (D. Don) Benn, a deciduous shrub or small tree native to temperate regions of southern Asia, and β‑carboline alkaloids play anti‑inflammatory and antiproliferative roles in various cancers. Read More

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A Robust Multiscale and Multiphasic Structure-Based Modeling Framework for the Intervertebral Disc.

Front Bioeng Biotechnol 2021 7;9:685799. Epub 2021 Jun 7.

Berkeley Biomechanics Laboratory, Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA, United States.

A comprehensive understanding of multiscale and multiphasic intervertebral disc mechanics is crucial for designing advanced tissue engineered structures aiming to recapitulate native tissue behavior. The bovine caudal disc is a commonly used human disc analog due to its availability, large disc height and area, and similarities in biochemical and mechanical properties to the human disc. Because of challenges in directly measuring subtissue-level mechanics, such as fiber mechanics, finite element models have been widely employed in spinal biomechanics research. Read More

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Real-time imaging of nanoscale electrochemical Ni etching under thermal conditions.

Chem Sci 2021 Feb 26;12(14):5259-5268. Epub 2021 Feb 26.

Department of Materials Science and Engineering, Massachusetts Institute of Technology MA 02139 Cambridge USA

The ability to vary the temperature of an electrochemical cell provides opportunities to control reaction rates and pathways and to drive processes that are inaccessible at ambient temperature. Here, we explore the effect of temperature on electrochemical etching of Ni-Pt bimetallic nanoparticles. To observe the process at nanoscale resolution we use liquid cell transmission electron microscopy with a modified liquid cell that enables simultaneous heating and biasing. Read More

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February 2021

Chlorophyll excitation energies and structural stability of the CP47 antenna of photosystem II: a case study in the first-principles simulation of light-harvesting complexes.

Chem Sci 2021 Feb 12;12(12):4463-4476. Epub 2021 Feb 12.

Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 1 45470 Mülheim an der Ruhr Germany.

Natural photosynthesis relies on light harvesting and excitation energy transfer by specialized pigment-protein complexes. Their structure and the electronic properties of the embedded chromophores define the mechanisms of energy transfer. An important example of a pigment-protein complex is CP47, one of the integral antennae of the oxygen-evolving photosystem II (PSII) that is responsible for efficient excitation energy transfer to the PSII reaction center. Read More

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February 2021

CGRP, adrenomedullin and adrenomedullin 2 display endogenous GPCR agonist bias in primary human cardiovascular cells.

Commun Biol 2021 Jun 23;4(1):776. Epub 2021 Jun 23.

Department of Pharmacology, University of Cambridge, Cambridge, UK.

Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist bias with physiological consequences for the calcitonin receptor-like receptor, CLR. Read More

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A new non-classical fold of varroa odorant-binding proteins reveals a wide open internal cavity.

Sci Rep 2021 Jun 23;11(1):13172. Epub 2021 Jun 23.

Biosensor Technologies, Austrian Institute of Technology GmbH, Konrad-Lorenz Straße, 24, 3430, Tulln, Austria.

Odorant-binding proteins (OBPs), as they occur in insects, form a distinct class of proteins that apparently has no closely related representatives in other animals. However, ticks, mites, spiders and millipedes contain genes encoding proteins with sequence similarity to insect OBPs. In this work, we have explored the structure and function of such non-insect OBPs in the mite Varroa destructor, a major pest of honey bee. Read More

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Invasion history shapes host transcriptomic response to a body-snatching parasite.

Mol Ecol 2021 Jun 23. Epub 2021 Jun 23.

Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA, USA.

By shuffling biogeographic distributions, biological invasions can both disrupt long-standing associations between hosts and parasites and establish new ones. This creates natural experiments with which to study the ecology and evolution of host-parasite interactions. In estuaries of the Gulf of Mexico, the white-fingered mud crab (Rhithropanopeus harrisii) is infected by a native parasitic barnacle Loxothylacus panopaei (Rhizocephala), which manipulates host physiology and behavior. Read More

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Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.

Cell Rep 2021 Jun;35(12):109280

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; IRCC International Research Collaboration Center, National Institutes of Natural Sciences, 4-3-13 Toranomon, Minato-ku, Tokyo 105-0001, Japan. Electronic address:

Protein clustering is pervasive in cell signaling, yet how signaling from higher-order assemblies differs from simpler forms of molecular organization is still poorly understood. We present an optogenetic approach to switch between oligomers and heterodimers with a single point mutation. We apply this system to study signaling from the kinase Zap70 and its substrate linker for activation of T cells (LAT), proteins that normally form membrane-localized condensates during T cell activation. Read More

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Molecular Details of a Coupled Binding and Folding Reaction between the Amyloid Precursor Protein and a Folded Domain.

ACS Chem Biol 2021 Jun 23. Epub 2021 Jun 23.

Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Box 582, SE-75123 Uppsala, Sweden.

Intrinsically disordered regions in proteins often function as binding motifs in protein-protein interactions. The mechanistic aspects and molecular details of such coupled binding and folding reactions, which involve formation of multiple noncovalent bonds, have been broadly studied theoretically, but experimental data are scarce. Here, using a combination of protein semisynthesis to incorporate phosphorylated amino acids, backbone amide-to-ester modifications, side chain substitutions, and binding kinetics, we examined the interaction between the intrinsically disordered motif of amyloid precursor protein (APP) and the phosphotyrosine binding (PTB) domain of Mint2. Read More

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Formation of frameshift-stimulating RNA pseudoknots is facilitated by remodeling of their folding intermediates.

Nucleic Acids Res 2021 Jun 23. Epub 2021 Jun 23.

Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.

Programmed -1 ribosomal frameshifting is an essential regulation mechanism of translation in viruses and bacteria. It is stimulated by mRNA structures inside the coding region. As the structure is unfolded repeatedly by consecutive translating ribosomes, whether it can refold properly each time is important in performing its function. Read More

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Exercise physiology in left ventricular assist device patients: insights from hemodynamic simulations.

Ann Cardiothorac Surg 2021 May;10(3):339-352

Department of Cardiovascular Sciences, Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.

Left ventricular assist devices (LVADs) assure longer survival to patients, but exercise capacity is limited compared to normal values. Overall, LVAD patients show high wedge pressure and low cardiac output during maximal exercise, a phenomenon hinting at the need for increased LVAD support. Clinical studies investigating the hemodynamic benefits of an LVAD speed increase during exercise, ended in inhomogeneous and sometimes contradictory results. Read More

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Native mass spectrometry analyses of chaperonin complex TRiC/CCT reveal subunit N-terminal processing and re-association patterns.

Sci Rep 2021 Jun 22;11(1):13084. Epub 2021 Jun 22.

Department of Biology, Stanford University, Stanford, CA, USA.

The eukaryotic chaperonin TRiC/CCT is a large ATP-dependent complex essential for cellular protein folding. Its subunit arrangement into two stacked eight-membered hetero-oligomeric rings is conserved from yeast to man. A recent breakthrough enables production of functional human TRiC (hTRiC) from insect cells. Read More

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Modulation of the effects of Class-Ib antiarrhythmics on cardiac NaV1.5-encoded channels by accessory NaVβ subunits.

JCI Insight 2021 Jun 22. Epub 2021 Jun 22.

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, United States of America.

Native myocardial voltage-gated sodium (NaV) channels function in macromolecular complexes comprising a pore-forming (α) subunit and multiple accessory proteins. Here, we investigated the impact of accessory NaVβ1 and NaVβ3 subunits on the functional effects of two well-known Class-Ib antiarrhythmics, lidocaine and ranolazine, on the predominant NaV channel α subunit, Nav1.5, expressed in mammalian heart. Read More

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Gross morphology, histology, and ultrastructure of the olfactory rosette of a critically endangered indicator species, the Delta Smelt, Hypomesus transpacificus.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2021 Jun 22. Epub 2021 Jun 22.

Integrative Pathobiology Graduate Group and Aquatic Health Program, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, VM3B, 3203, 1089 Veterinary Medicine Dr, Davis, CA, 95616, USA.

The Delta Smelt (Hypomesus transpacificus) is a small, semi-anadromous fish native to the San Francisco Bay-Delta Estuary and has been declared as critically endangered. Their olfactory biology, in particular, is poorly understood and a basic description of their sensory anatomy is needed to advance our understanding of the sensory ecology of species to inform conservation efforts to manage and protect them. We provide a description of the gross morphology, histological, immunohistochemical, and ultrastructural features of the olfactory rosette in this fish and discuss some of the functional implications in relation to olfactory ability. Read More

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Protein-fragment complementation assays for large-scale analysis of protein-protein interactions.

Biochem Soc Trans 2021 Jun 22. Epub 2021 Jun 22.

Univ Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France.

Protein-protein interactions (PPIs) orchestrate nearly all biological processes. They are also considered attractive drug targets for treating many human diseases, including cancers and neurodegenerative disorders. Protein-fragment complementation assays (PCAs) provide a direct and straightforward way to study PPIs in living cells or multicellular organisms. Read More

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Leber's Hereditary Optic Neuropathy Arising From the Synergy Between ND1 3635G>A Mutation and Mitochondrial YARS2 Mutations.

Invest Ophthalmol Vis Sci 2021 Jun;62(7):22

Key Laboratory of Reproductive Genetics, Ministry of Education of PRC, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Purpose: To investigate the mechanism underlying the synergic interaction between Leber's hereditary optic neuropathy (LHON)-associated ND1 and mitochondrial tyrosyl-tRNA synthetase (YARS2) mutations.

Methods: Molecular dynamics simulation and differential scanning fluorimetry were used to evaluate the structure and stability of proteins. The impact of ND1 3635G>A and YARS2 p. Read More

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A metabolomic study of Gomphrena agrestis in Brazilian Cerrado suggests drought-adaptive strategies on metabolism.

Sci Rep 2021 Jun 21;11(1):12933. Epub 2021 Jun 21.

Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå Plant Science Centre, 901 83, Umeå, Sweden.

Drought is the main factor that limits the distribution and productivity of plant species. In the Brazilian Cerrado, the vegetation is adapted to a seasonal climate with long- and short-term periods of drought. To analyze the metabolic strategies under such conditions, a metabolomic approach was used to characterize Gomphrena agrestis Mart. Read More

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Noninvasive assessment of congestive hepatopathy in patients with constrictive pericardial physiology using MR relaxometry.

Int J Cardiol 2021 Jun 18. Epub 2021 Jun 18.

Dept of Imaging and Pathology, KU Leuven and Dept of Radiology, University Hospitals Leuven, Leuven, Belgium.

Background: Constrictive pericarditis represents a treatable cause of mainly right heart failure (RHF), characterized by increased filling pressures and congestive hepatopathy. We hypothesized assessment of T1 and T2 liver relaxation times enables to depict liver congestion, and thus to diagnose RHF.

Methods: Cardiovascular magnetic resonance imaging (CMR) was performed in 45 pericarditis patients i. Read More

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Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines.

Proteins 2021 Jun 21. Epub 2021 Jun 21.

Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

We have shown that water-soluble variants of the human mu opioid receptor (wsMOR) containing a reduced number of hydrophobic residues at the lipid-facing residues of the transmembrane (TM) helices can be expressed in E. coli. In this study we tested the consequences of increasing the number of mutations on the surface of the transmembrane domain on the receptor's aqueous solubility and ligand binding properties, along with mutation of 11 cysteine residues regardless of their solvent exposure value and location in the protein. Read More

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Wild non-eusocial bees learn a colour discrimination task in response to simulated predation events.

Naturwissenschaften 2021 Jun 21;108(4):28. Epub 2021 Jun 21.

Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Burwood, VIC, Australia.

Despite representing the majority of bee species, non-eusocial bees (e.g. solitary, subsocial, semisocial, and quasisocial species) are comparatively understudied in learning, memory, and cognitive-like behaviour compared to eusocial bees, such as honeybees and bumblebees. Read More

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Modeling structural interconversion in Alzheimers' amyloid beta peptide with classical and intrinsically disordered protein force fields.

J Biomol Struct Dyn 2021 Jun 21:1-18. Epub 2021 Jun 21.

Department of Chemistry, University of California, Riverside, CA, USA.

A comprehensive understanding of the aggregation mechanism in amyloid beta 42 (Aβ42) peptide is imperative for developing therapeutic drugs to prevent or treat Alzheimer's disease. Because of the high flexibility and lack of native tertiary structures of Aβ42, molecular dynamics (MD) simulations may help elucidate the peptide's dynamics with atomic details and collectively improve ensembles not seen in experiments. We applied microsecond-timescale MD simulations to investigate the dynamics and conformational changes of Aβ42 by using a newly developed Amber force field ( We compared the and the regular force field by examining the conformational changes of two distinct Aβ42 monomers in explicit solvent. Read More

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Structural Changes in Insulin at a Soft Electrochemical Interface.

Anal Chem 2021 Jun 21. Epub 2021 Jun 21.

Understanding the interaction of proteins at interfaces, which occurs at or within cell membranes and lipoprotein vesicles, is central to our understanding of protein function. Therefore, new experimental approaches to understand how protein structure is influenced by protein-interface interactions are important. Herein we build on our previous work exploring electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) to investigate changes in protein secondary structure that are modulated by protein-interface interactions. Read More

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Chimeric human opsins as optogenetic light sensitisers.

J Exp Biol 2021 Jun 21. Epub 2021 Jun 21.

Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.

Human opsin-based photopigments have great potential as light-sensitisers, but their requirement for phototransduction cascade-specific second messenger proteins may restrict their functionality in non-native cell types. In this study, eight chimeric human opsins were generated consisting of a backbone of either a rhodopsin (RHO) or long-wavelength-sensitive (LWS) opsin and intracellular domains from Gq/11-coupled human melanopsin. Rhodopsin/melanopsin chimeric opsins coupled to both Gi and Gq/11 pathways. Read More

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α-Synuclein Responses in the Laterodorsal Tegmentum, the Pedunculopontine Tegmentum, and the Substantia Nigra: Implications for Early Appearance of Sleep Disorders in Parkinson's Disease.

J Parkinsons Dis 2021 Jun 14. Epub 2021 Jun 14.

Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Background: Parkinson's disease (PD) is a neurodegenerative disorder associated with insoluble pathological aggregates of the protein α-synuclein. While PD is diagnosed by motor symptoms putatively due to aggregated α-synuclein-mediated damage to substantia nigra (SN) neurons, up to a decade before motor symptom appearance, patients exhibit sleep disorders (SDs). Therefore, we hypothesized that α-synuclein, which can be present in monomeric, fibril, and other forms, has deleterious cellular actions on sleep-control nuclei. Read More

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Soluble Amyloid-β Consumption in Alzheimer's Disease.

J Alzheimers Dis 2021 Jun 12. Epub 2021 Jun 12.

Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden.

Brain proteins function in their soluble, native conformation and cease to function when transformed into insoluble aggregates, also known as amyloids. Biophysically, the soluble-to-insoluble phase transformation represents a process of polymerization, similar to crystallization, dependent on such extrinsic factors as concentration, pH, and a nucleation surface. The resulting cross-β conformation of the insoluble amyloid is markedly stable, making it an unlikely source of toxicity. Read More

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Microengineered 3D Collagen Gels with Independently Tunable Fiber Anisotropy and Directionality.

Adv Mater Technol 2021 Apr 10;6(4). Epub 2021 Mar 10.

Microsystems Engineering, Rochester Institute of Technology, Rochester, NY, 14623, USA.

Cellular processes, including differentiation, proliferation, and migration, have been linked to the alignment (anisotropy) and orientation (directionality) of collagen fibers in the native extracellular matrix (ECM). Given the critical role that biophysical cell-matrix interactions play in regulating biological functions, several microfluidic-based methods have been used to establish 3D collagen gels with defined fiber properties; these gels have helped to establish quantitative relationships between structural ECM cues and observed cell responses. Although existing microfluidic fabrication methods provide excellent definition over collagen fiber anisotropy, they have not demonstrated the independent control over fiber anisotropy and directionality necessary to replicate collagen architecture. Read More

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