411,608 results match your criteria leads


MiR-486-3p promotes osteogenic differentiation of BMSC by targeting CTNNBIP1 and activating the Wnt/╬▓-catenin pathway.

Biochem Biophys Res Commun 2021 Jun 8;566:59-66. Epub 2021 Jun 8.

Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, PR China. Electronic address:

Background: Dysfunction in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) leads to bone loss/osteoporosis. The catenin beta interacting protein 1 (CTNNBIP1) is an inhibitor of Wnt/╬▓-catenin signaling, whose role in osteogenesis remains elusive. This study aimed to reveal the effects of miR-486-3p/CTNNBIP1 in osteogenesis. Read More

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Object expectations alter information use during visual recognition.

Cognition 2021 Jun 9;214:104803. Epub 2021 Jun 9.

Department of Psychology, Universit├ę de Montr├ęal, C.P. 6128, succ. Centre-Ville, Montr├ęal, QC H3C 3J7, Canada.

Prior expectations influence how we perceive and recognize objects. However, how they do so remains unclear, especially in the case of real-world complex objects. Expectations of objects may affect which features are used to recognize them subsequently. Read More

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Memory effects in polymer brushes showing co-nonsolvency effects.

Adv Colloid Interface Sci 2021 May 17;294:102442. Epub 2021 May 17.

Leibniz-Institut f├╝r Polymerforschung Dresden e.V, Hohe Stra├če 6, Dresden 01069, Germany; Max-Planck-Institut f├╝r Polymerforschung, Ackermannweg 10, Mainz 55128, Germany. Electronic address:

Densely packed polymer chains grafted to a substrate, especially polymer brushes, have been studied intensively. Of special interest are systems that react to changes in external conditions or"remember" previous conditions. With this focus, we explore the properties of PNiPAAm brushes and relate published work to own results. Read More

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A homozygous nonsense mutation early in exon 5 of BRCA2 is associated with very severe Fanconi anemia.

Eur J Med Genet 2021 Jun 9:104260. Epub 2021 Jun 9.

Department of Pediatrics III, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; Department of Otorhinolaryngology & Head/Neck Surgery, University Hospital D├╝sseldorf, Heinrich Heine University, 40225 D├╝sseldorf, Germany. Electronic address:

Fanconi anemia (FA) due to biallelic mutations in the BRCA2 gene is very rare and associated with an extremely high risk of early-onset of aggressive childhood malignancies, predominantly brain tumors, leukemia, and nephroblastoma. Here, we present a consanguineous family with three affected children of the D1 subtype of FA and describe the clinical consequences of the earliest known biallelic nonsense/stop-gain germ-line mutation in BRCA2, exon 5 c.469A>T, that leads to a premature stop of translation, p. Read More

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Autoimmunity and COVID-19 - The microbiotal connection.

Autoimmun Rev 2021 Jun 9:102865. Epub 2021 Jun 9.

Department of Medicine C, Wolfson Medical Center, Holon, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background And Aims: The novel SARS-CoV-2 has been rattling the world since its outbreak in December 2019, leading to the COVID-19 pandemic. The learning curve of this new virus has been steep, with a global scientific community desperate to learn how the virus is transmitted, how it replicates, what cause such a wide spectrum of disease manifestations, causing none or few symptoms in some. Others are burdened by an intense immune response that resembles the cytokine storm syndrome (CSS), which leads to severe disease manifestations, often complicated by fatal acute respiratory distress syndrome and death. Read More

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CircRNAs: Decrypting the novel targets of fibrosis and aging.

Ageing Res Rev 2021 Jun 9:101390. Epub 2021 Jun 9.

Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, 710021, China. Electronic address:

Fibrosis is a typical aging-related pathological process involving almost all organs. It is usually initiated by organic injury and leads to the gradual decline of organ function or even loss. Circular RNAs (circRNAs) are being hailed as a newly rediscovered class of covalently closed transcripts without a 5' cap or 3' tail which draw increasing attention. Read More

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Deformation of stylet-driven leads & helix unraveling during acute explant after conduction system pacing.

Indian Pacing Electrophysiol J 2021 Jun 9. Epub 2021 Jun 9.

Stanford Health Care, Palo Alto, CA, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

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Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices.

Am Heart J 2021 Jun 9. Epub 2021 Jun 9.

Department of Medicine, Stanford University School of Medicine, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California. Electronic address:

Background: Kidney function may promote progression of AF.

Objective: We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED).

Methods: We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). Read More

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Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects.

Cell Metab 2021 Jun 8. Epub 2021 Jun 8.

Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp├ęrimentale et Clinique (IREC), UCLouvain, 57 Avenue Hippocrate B1.5704, 1200 Brussels, Belgium. Electronic address:

Tumor acidosis promotes disease progression through a stimulation of fatty acid (FA) metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells, we examined whether excess uptake of specific FAs could lead to antitumor effects. We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively induced ferroptosis in cancer cells under ambient acidosis. Read More

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Chloride channel accessory 1 integrates chloride channel activity and mTORC1 in aging-related kidney injury.

Aging Cell 2021 Jun 12:e13407. Epub 2021 Jun 12.

Department of Medicine, Center for Renal Precision Medicine, University of Texas Health, San Antonio, TX, USA.

The mechanism of kidney injury in aging are not well understood. In order to identify hitherto unknown pathways of aging-related kidney injury, we performed RNA-Seq on kidney extracts of young and aged mice. Expression of chloride (Cl) channel accessory 1 (CLCA1) mRNA and protein was increased in the kidneys of aged mice. Read More

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The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells.

FASEB J 2021 Jul;35(7):e21692

Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

For metastasis formation, individual cells from a primary tumor must migrate toward other tissues. The aim of this study was to determine if mesenchymal stromal cells (MSCs) from human bone marrow are able to emit signals that induce this migratory activity in cancer cells. We separated the supernatant of MSCs derived from human bone marrow by size-exclusion and ion-exchange chromatography and have subsequently studied the migratory behavior of the prostate cancer cell line PC3 and the breast cancer cell line MDA-MB-231 toward the respective fractions in a transwell migration assay. Read More

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Regenerating Critical Size Rat Segmental Bone Defects with a Self-Healing Hybrid Nanocomposite Hydrogel: Effect of Bone Condition and BMP-2 Incorporation.

Macromol Biosci 2021 Jun 12:e2100088. Epub 2021 Jun 12.

Biomaterials, Radboudumc, Philips van Leijdenlaan 25, Nijmegen, Gelderland, 6525 EX, The Netherlands.

The aim of the current study is to assess the biological performance of self-healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP-2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HA -CaP) or hydrogel loaded with BMP-2 in two dosages (HA -CaP-lowBMP2 or HA -CaP-highBMP2). Read More

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Medicinal chemistry of anthranilic acid derivatives: A mini review.

Drug Dev Res 2021 Jun 12. Epub 2021 Jun 12.

Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab, India.

Anthranilic acid and its analogues present a privileged profile as pharmacophores for the rational development of pharmaceuticals deliberated for managing the pathophysiology and pathogenesis of various diseases. The substitution on anthranilic acid scaffold provides large compound libraries, which enable a comprehensive assessment of the structure activity relationship (SAR) analysis for the identification of hits and leads in a typical drug development paradigm. Besides, their widespread applications as anti-inflammatory fenamates, the amide and anilide derivatives of anthranilic acid analogues play a central role in the management of several metabolic disorders. Read More

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Synthesis of Ultrathin and Grid-Structural Carbon Nanosheets Coupled with Mo2C for Electrocatalytic Hydrogen Production.

Chem Asian J 2021 Jun 11. Epub 2021 Jun 11.

Taiyuan University of Technology, Colledge of Chemistry and Chemical Enginering, CHINA.

Molybdenum carbide possessing Pt-like d-band electronic structure is considered as one of potential candidates of electrocatalysts and it shows intrinsic catalytic property. However, high carbonizing temperature easily leads to the coalescence of nanoparticles (NPs). Here, we propose a simple sol-gel route to achieve high dispersity of carbide NPs by designing Mo-involved xerogel. Read More

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Parameterizing elastic network models to capture the dynamics of proteins.

J Comput Chem 2021 Jun 11. Epub 2021 Jun 11.

Unit├ę de Dynamique Structurale des Macromol├ęcules, Institut Pasteur, UMR 3528 du CNRS, Paris, France.

Coarse-grained normal mode analyses of protein dynamics rely on the idea that the geometry of a protein structure contains enough information for computing its fluctuations around its equilibrium conformation. This geometry is captured in the form of an elastic network (EN), namely a network of edges between its residues. The normal modes of a protein are then identified with the normal modes of its EN. Read More

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Argonaute proteins: structures and their endonuclease activity.

Mol Biol Rep 2021 Jun 11. Epub 2021 Jun 11.

Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

Argonaute proteins are highly conserved and widely expressed in almost all organisms. They not only play a critical role in the biogenesis of small RNAs but also defend against invading nucleic acids via small RNA or DNA-mediated gene silencing pathways. One functional mechanism of Argonaute proteins is acting as a nucleic-acid-guided endonuclease, which can cleave targets complementary to DNA or RNA guides. Read More

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Can flowers affect land surface albedo and soil microclimates?

Int J Biometeorol 2021 Jun 12. Epub 2021 Jun 12.

Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark.

The phenology of vegetation, namely leaf-out and senescence, can influence the Earth's climate over regional spatial scales and long time periods (e.g., over 30 years or more), in addition to microclimates over local spatial scales and shorter time periods (weeks to months). Read More

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Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials.

Nat Rev Drug Discov 2021 Jun 11. Epub 2021 Jun 11.

Department of Pathology, Massachusetts General Research Institute, Boston, MA, USA.

Numerous drug treatments that have recently entered the clinic or clinical trials have their genesis in zebrafish. Zebrafish are well established for their contribution to developmental biology and have now emerged as a powerful preclinical model for human disease, as their disease characteristics, aetiology and progression, and molecular mechanisms are clinically relevant and highly conserved. Zebrafish respond to small molecules and drug treatments at physiologically relevant dose ranges and, when combined with cell-specific or tissue-specific reporters and gene editing technologies, drug activity can be studied at single-cell resolution within the complexity of a whole animal, across tissues and over an extended timescale. Read More

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Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain.

Commun Biol 2021 Jun 11;4(1):724. Epub 2021 Jun 11.

Department of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Vic, Australia.

SARS-CoV-2 infection leads to coronavirus disease 2019 (COVID-19), which is associated with severe and life-threatening pneumonia and respiratory failure. However, the molecular basis of these symptoms remains unclear. SARS-CoV-1 E protein interferes with control of cell polarity and cell-cell junction integrity in human epithelial cells by binding to the PALS1 PDZ domain, a key component of the Crumbs polarity complex. Read More

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Antibody-dependent enhancement representing in vitro infective progeny virus titer correlates with the viremia level in dengue patients.

Sci Rep 2021 Jun 11;11(1):12354. Epub 2021 Jun 11.

Mahidol-Osaka Center for Infectious Diseases, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand.

Dengue virus (DENV) causes dengue fever (DF) and dengue hemorrhagic fever in humans. Some DF patients suddenly develop severe symptoms around the defervescent period. Although the pathogenic mechanism of the severe symptoms has not been fully elucidated, the viremia level in the early phase has been shown to correlate with the disease severity. Read More

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Identification of damage development in the core of steel cord belts with the diagnostic system.

Sci Rep 2021 Jun 11;11(1):12349. Epub 2021 Jun 11.

Faculty of Electronics, Wroclaw University of Science and Technology, 27 Wybrzeże Wyspiańskiego st., 50-370, Wrocław, Poland.

Belt conveyors are used for transporting bulk materials over distances. The core of the belt, by transferring the longitudinal stresses and ensuring proper frictional coupling of the belt, enables belt movement and transportation of materials on its surface. As the belt cover and edges are used, the belt becomes abraded, and the core is subject to fatigue. Read More

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Avian extremity reconstruction via osseointegrated leg-prosthesis for intuitive embodiment.

Sci Rep 2021 Jun 11;11(1):12360. Epub 2021 Jun 11.

Clinical Laboratory for Bionic Extremity Reconstruction, Department of Surgery, Medical University of Vienna, Vienna, Austria.

For large avians such as vultures, limb loss leads to loss of ambulation and eventually death from malnutrition. Prosthetic devices may replace the limb, however, conventional prosthetic sockets are not feasible in feathered limbs and the extreme stress and strain of unreflected daily use in animals. Osseointegration is a novel technique, where external prosthetic parts are connected directly to a bone anchor to provide a solid skeletal-attachment. Read More

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E2F6 initiates stable epigenetic silencing of germline genes during embryonic development.

Nat Commun 2021 Jun 11;12(1):3582. Epub 2021 Jun 11.

University of Strasbourg, Strasbourg, France.

In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1. Read More

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K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR.

Cell Death Dis 2021 Jun 11;12(6):608. Epub 2021 Jun 11.

Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Dual specificity tyrosine phosphorylation regulated kinase 1A, DYRK1A, functions in multiple cellular pathways, including signaling, endocytosis, synaptic transmission, and transcription. Alterations in dosage of DYRK1A leads to defects in neurogenesis, cell growth, and differentiation, and may increase the risk of certain cancers. DYRK1A localizes to a number of subcellular structures including vesicles where it is known to phosphorylate a number of proteins and regulate vesicle biology. Read More

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Malus-metasurface-assisted polarization multiplexing.

Light Sci Appl 2020 Jun 12;9(1):101. Epub 2020 Jun 12.

School of Physics & Astronomy, University of Birmingham, Birmingham, B15 2TT, UK.

Polarization optics plays a pivotal role in diffractive, refractive, and emerging flat optics, and has been widely employed in contemporary optical industries and daily life. Advanced polarization manipulation leads to robust control of the polarization direction of light. Nevertheless, polarization control has been studied largely independent of the phase or intensity of light. Read More

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Torsional fracture of viscoelastic liquid bridges.

Proc Natl Acad Sci U S A 2021 Jun;118(24)

Micro/Bio/Nanofluidics Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan;

Short liquid bridges are stable under the action of surface tension. In applications like electronic packaging, food engineering, and additive manufacturing, this poses challenges to the clean and fast dispensing of viscoelastic fluids. Here, we investigate how viscoelastic liquid bridges can be destabilized by torsion. Read More

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Hypertrophic cardiomyopathy ╬▓-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super relaxed state.

Proc Natl Acad Sci U S A 2021 Jun;118(24)

Department of Pediatrics (Cardiology), Stanford University School of Medicine, Palo Alto, CA 94304;

Hypertrophic cardiomyopathy (HCM) is the most common inherited form of heart disease, associated with over 1,000 mutations, many in ╬▓-cardiac myosin (MYH7). Molecular studies of myosin with different HCM mutations have revealed a diversity of effects on ATPase and load-sensitive rate of detachment from actin. It has been difficult to predict how such diverse molecular effects combine to influence forces at the cellular level and further influence cellular phenotypes. Read More

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Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds.

Sci Adv 2021 Jun 11;7(24). Epub 2021 Jun 11.

Department of Medical Neurobiology, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here, we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. Read More

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Experiences and perceptions of trial participants and healthcare professionals in the UK Frozen Shoulder Trial (UK FROST): a nested qualitative study.

BMJ Open 2021 Jun 11;11(6):e040829. Epub 2021 Jun 11.

Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Objectives: To explore the experiences and perceptions of trial participants and healthcare professionals in the UK Frozen Shoulder Trial (UK FROST), a multicentre randomised controlled trial that compared manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR) with a 12-week early structured physiotherapy programme (ESP) in people with unilateral frozen shoulder referred to secondary care.

Design: Nested qualitative study with semistructured interviews. We used constant comparison method to develop our themes. Read More

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A Multicenter Preliminary Study of Cangrelor following Thrombectomy Failure for Refractory Proximal Intracranial Occlusions.

AJNR Am J Neuroradiol 2021 Jun 11. Epub 2021 Jun 11.

Neurology (I.S.), Bordeaux University Hospital, Bordeaux, France.

Background And Purpose: Rescue endovascular and pharmacologic approaches are increasingly being adopted after recanalization failure of acute large-vessel occlusion strokes with mechanical thrombectomy, with encouraging results. The safety and efficacy of glycoprotein IIb/IIIa inhibitors in ischemic stroke have been investigated, though cangrelor, a recent intravenous P2Y12-receptor inhibitor with a rapid onset/offset of action and a short half-life, may be a valuable option. We compared the safety and efficacy of cangrelor with those of glycoprotein IIb/IIIa inhibitors for refractory occlusions. Read More

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